gastrins and Helicobacter-Infections

Abetted by widespread usage of acid-suppressing proton pump inhibitors (PPIs), the mitogenic actions of the peptide hormone gastrin are being revisited as a recurring theme in various gastrointestinal (GI) malignancies. While pathological gastrin levels are intricately linked to hyperplasia of enterochromaffin-like cells leading to carcinoid development, the signaling effects exerted by gastrin on distinct cell types of the gastric mucosa are more nuanced. Indeed, mounting evidence suggests dichotomous roles for gastrin in both promoting and suppressing tumorigenesis. Here, we review the major upstream mediators of gastrin gene regulation, including inflammation secondary to

Topics: Gastrins; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Neoplasm Recurrence, Local; Proton Pump Inhibitors

Topics: Animals; Biomarkers; Disease Susceptibility; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Molecular Diagnostic Techniques; Organ Specificity; Proton Pump Inhibitors; Reagent Kits, Diagnostic

Gastric cancer, a disease with a reduced frequency for decades, now appears to be on the rise again in young Americans. The epidemiology of gastric cancer differs between tumors in the cardia and those of the more distal parts of the stomach. The tumors are divided into the intestinal type showing glandular growth pattern and the diffuse type with a different pattern. The latter often expresses neuroendocrine and more specifically ECL-cell markers suggesting that they originate from the ECL cell, the target cell for the antral hormone, gastrin. Helicobacter pylori gastritis is accepted as the major cause of gastric cancer, but only after having induced oxyntic atrophy which reduces gastric acid secretion and thus induces hypoacidity leading to hypergastrinemia. Long-term hypergastrinemia is known to induce malignant neoplasia in the stomach of animals as well as man. Recently treatment with proton pump inhibitor after Helicobacter pylori eradication in patients with gastroesophageal reflux disease, has been reported to predispose to gastric cancer. Since profound acid inhibition is a well-known cause of gastric neoplasia, it is to be expected that Helicobacter pylori infection and profound acid inhibition has an additive or possibly potentiating effect on the development of gastric cancer.

Topics: Animals; Enterochromaffin-like Cells; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Stomach Neoplasms

Gastrin acts physiologically as a gut hormone to stimulate acid secretion after meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin level happens under various conditions including Zollinger-Ellison syndrome, antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As acid suppressive therapy causes hypergastrinemia, the association between acid suppressive therapy and gastric neuroendocrine cell tumor (NET) has been discussed during the past 30 years. In this review article, the definition of hypergastrinemia and the related disorders including acid suppressive therapy and gastric NET are discussed.

Topics: Carcinogenesis; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Neuroendocrine Tumors; Proton Pump Inhibitors; Stomach Neoplasms

Upper-GI diseases are one of the most relevant issue in primary care. Nowadays they are still responsible for about 100 million ambulatory care visits only in the US. The diagnosis of almost every upper-GI condition is still deputed to invasive tests such as upper gastrointestinal endoscopy, gastroesophageal manometry or radiography. The possibility of analysing serum markers like Pepsinogens I and II, produced by gastric mucosa, in order to assess the functional characteristics of the upper GI tract has spread itself since the 80's especially in the diagnosis of peptic ulcer. The discovery of Helicobacter pylori by Marshall and Warren in 1983 and the scientific consecration of its role in the pathogenesis of gastric cancer and peptic ulcer (crystallized in Peleo Correa's Cascade, 1992), led to an increase importance of non-invasive tests, raising the attention towards the assessment of both immunoglobulins anti-H.p. and Gastrin hormone produced by antral G cells, as an implementation of the panel of gastric markers. This narrative review aims to analyze the huge landscape of non-invasive tests for diagnosis of GI diseases, studying the literature of the recent years.

Topics: Antibodies, Bacterial; Biomarkers; Diagnostic Techniques, Digestive System; Dyspepsia; Endoscopy, Gastrointestinal; Esophageal Diseases; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Stomach Diseases

Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for

Topics: Carcinogenesis; Carcinoma; Cell Proliferation; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test is still uncertain.. To assess the diagnostic performance of the serum panel test for the diagnosis of atrophic gastritis.. Medline via PubMed, Embase, Scopus, Cochrane Library databases and abstracts of international conferences proceedings were searched from January 1995 to December 2016 using the primary keywords "pepsinogens," "gastrin," "atrophic gastritis," "gastric precancerous lesions." Studies were included if they assessed the accuracy of the serum panel test for the diagnosis of atrophic gastritis using histology according to the updated Sydney System as reference standard.. Twenty studies with a total of 4241 subjects assessed the performance of serum panel test for the diagnosis of atrophic gastritis regardless of the site in the stomach. The summary sensitivity was 74.7% (95% confidence interval (CI), 62.0-84.3) and the specificity was 95.6% (95%CI, 92.6-97.4). With a prevalence of atrophic gastritis of 27% (median prevalence across the studies), the negative predictive value was 91%. Few studies with small sample size assessed the performance of the test in detecting the site of atrophic gastritis.. The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis. This test may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis; however, a cost-effectiveness analysis is needed.

Topics: Cost-Benefit Analysis; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Hematologic Tests; Humans; Pepsinogen A; Prevalence; Reproducibility of Results; Sensitivity and Specificity; Stomach Neoplasms

The present review summarizes the past year's literature, both clinical and basic science, regarding physiologic and pharmacologic regulation of gastric acid secretion in health and disease.. Gastric acid kills microorganisms, assists digestion, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are the hormone gastrin, released from antral G cells; paracrine agent histamine, released from oxyntic enterochromaffin-like cells; and neuropeptide acetylcholine, released from antral and oxyntic intramural neurons. Gastrin is also a trophic hormone that participates in carcinogenesis. Helicobacter pylori may increase or decrease acid secretion depending upon the acuity and predominant anatomic focus of infection; most patients manifest hypochlorhydria. Despite the fact that proton pump inhibitors (PPIs) are amongst the most widely prescribed drugs, they are underutilized in patients at high risk for UGI bleeding. Although generally considered well tolerated, concerns have been raised regarding associations between PPI use and dementia, kidney disease, myocardial infarction, pneumonia, osteoporosis, dysbiosis, small bowel injury, micronutrient deficiency, and fundic gland polyps.. Our understanding of the physiologic, pathophysiologic, and pharmacologic regulation of gastric secretion continues to advance. Such knowledge is crucial for improved and safe management of acid-peptic disorders.

Topics: Acetylcholine; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Proton Pump Inhibitors

Despite being an overall safe drug, several long-term adverse effects are associated with proton pump inhibitors (PPIs). The link between PPI use and gastric neuroendocrine tumors (NETs), gastric adenocarcinomas and Barrett's esophagus progression gastric cancers has been investigated due to PPI-induced hypergastrinemia.. The pathophysiological mechanisms underlying PPI exposure and gastric NETs, gastric adenocarcinomas and Barrett's esophagus progression are discussed. The quality of randomized control studies, cohort studies and case reports investigating the link between gastric cancers and PPIs are examined. Recommendations for clinicians are provided.. PPIs cause a hypergastrinemic state, increasing enterochromaffin-like cell dysplasia and risk of gastric NET development, increasing gastritis severity in the context of Helicobacter pylori infection, and progression of carcinogenesis in a certain predisposed subset of Barrett's esophagus patients. There are case reports of PPI-induced gastric NETs and adenocarcinomas as consequences of these effects. In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric NET development with chronic PPI use in these patients. Eradication status of H. pylori prior to commencing long-term PPI therapy should be established to reduce the risk of severe atrophic gastritis and development of gastric dysplasia.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Disease Progression; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Neuroendocrine Tumors; Proton Pump Inhibitors; Stomach Neoplasms

Gastric cancer is the third leading cause of cancer-related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late-stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new-targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre-clinical development of new therapeutics.

Topics: Animals; Disease Models, Animal; Gastrins; Helicobacter felis; Helicobacter Infections; Helicobacter pylori; Methylnitrosourea; Mice, Inbred Strains; Mice, Transgenic; Molecular Targeted Therapy; Stomach Neoplasms

Gastric cancer occurs almost exclusively in patients with gastritis. Since Helicobacter pylori (Hp) was proved to cause gastritis, Hp was also expected to play a role in gastric carcinogenesis. Despite extensive studies, the mechanisms by which Hp cause gastric cancer are still poorly understood. However, there is evidence that the anatomical site of Hp infection is of major importance. Infection confined to the antral mucosa protects against gastric cancer but predisposes to duodenal ulcer, whereas Hp infection of the oxyntic mucosa increases the risk of gastric cancer. Hp infection does not predispose to cancers in the gastric cardia. In patients with atrophic gastritis of the oxyntic mucosa, the intragastric pH is elevated and the concentration of microorganisms in the stomach is increased. This does not lead to increased risk of gastric cancer at all anatomical sites. The site specificity of Hp infection in relation to cancer risk indicates that neither Hp nor the changes in gastric microflora due to gastric hypoacidity are carcinogenic per se. However, reduced gastric acidity also leads to hypergastrinemia, which stimulates the function and proliferation of enterochromaffin-like (ECL) cells located in the oxyntic mucosa. The ECL cell may be more important in human gastric carcinogenesis than previously realized, as every condition causing long-term hypergastrinemia in animals results in the development of neoplasia in the oxyntic mucosa. Patients with hypergastrinemia will far more often develop carcinomas in the gastric corpus. In conclusion, hypergastrinemia may explain the carcinogenic effect of Hp.

Topics: Animals; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Risk; Stomach Neoplasms

Helicobacter pylori (H. pylori) have long been associated with a spectrum of disease outcomes in the gastro-duodenal system. Heterogeneity in bacterial virulence factors or strains is not enough to explain the divergent disease phenotypes manifested by the infection. This review focuses on host genetic factors that are involved during infection and eventually are thought to influence the disease phenotype. We have summarized the different host genes that have been investigated for association studies in H. pylori mediated duodenal ulcer or gastric cancer. We discuss that as the bacteria co-evolved with the host; these host gene also show much variation across different ethnic population. We illustrate the allelic distribution of interleukin-1B, across different population which is one of the most popular candidate gene studied with respect to H. pylori infections. Further, we highlight that several polymorphisms in the pathway gene can by itself or collectively affect the acid secretion pathway axis (gastrin: somatostatin) thereby resulting in a spectrum of disease phenotype.

Topics: Animals; Cell Transformation, Neoplastic; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Interleukin-1beta; Molecular Mimicry; Phenotype; Polymorphism, Genetic; Risk Factors; Signal Transduction; Somatostatin; Stomach Neoplasms; Virulence

Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy.. To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology.. A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology.. A total of 16 studies (1920 patients) met the inclusion criteria. During long-term PPI therapy, mean gastrin levels rose to one to three times the upper limit of the normal range (~100 pg/mL), and an increased prevalence of ECL cell hyperplasia was observed (+7.8-52.0%). Helicobacter pylori-positive patients had a significantly increased risk of developing ECL linear/micronodular hyperplasia compared with H. pylori-negative patients [OR: 2.45 (95% CI: 1.47-4.10), P = 0.0006]; however, no evidence of neoplastic changes was found. The risk of corpus atrophy was markedly higher in H. pylori-positive patients than in H. pylori-negative patients [OR: 11.45 (95% CI: 6.25-20.99), P < 0.00001]. Not a single case of gastric adenocarcinoma was found.. Long-term PPI therapy induced moderate hypergastrinaemia in most patients and an increased prevalence of ECL cell hyperplasia. H. pylori-positive patients receiving long-term PPI therapy were exposed to a higher risk of corpus atrophy than H. pylori-negative patients. No neuroendocrine tumours or gastric cancers were found.

Topics: Drug Administration Schedule; Enterochromaffin-like Cells; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Neuroendocrine Tumors; Proton Pump Inhibitors; Risk Factors; Stomach Neoplasms

This review summarizes the past year's literature regarding the neural, paracrine, hormonal, and intracellular regulation of gastric acid secretion.. Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B12, and certain medications. High gastric acidity, in combination with pepsin and lipase, kills ingested microorganisms and may play a role in preventing bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis, community-acquired pneumonia, and infection with Mycobacterium tuberculosis. Stimulants of acid secretion include histamine, gastrin, acetylcholine, and ghrelin. Inhibitors include somatostatin, gastric inhibitory polypeptide, calcitonin gene-related peptide, and adrenomedullin. Helicobacter pylori stimulates or inhibits depending upon the time course of infection and the area of the stomach predominantly infected. Proteins implicated in H-K-ATPase membrane trafficking include myosin IIB, F-actin, ezrin, and Rab GTPases.. Our understanding of the regulation of gastric acid secretion continues to advance. Such knowledge is crucial for the management of acid-peptic disorders and the development of novel medications, such as cholecystokinin-2 receptor antagonists.

Topics: Acetylcholine; Biological Transport; Gastric Acid; Gastric Mucosa; Gastrins; Ghrelin; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Histamine; Histamine H2 Antagonists; Humans; Parietal Cells, Gastric; Stomach

Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

Topics: Animals; Anti-Bacterial Agents; Anticarcinogenic Agents; Cell Transformation, Neoplastic; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; DNA Methylation; Epigenesis, Genetic; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Humans; Risk Factors; Signal Transduction; Stomach; Stomach Neoplasms

Helicobacter pylori (Hp) is one of the most common bacteria infecting humans. Recently, certain extragastric manifestations, linked to Hp infection, have been widely investigated, suggesting that Hp infection might be a 'systemic' disease. Accumulating, yet limited, evidence points to a potential association between Hp infection and lung cancer risk. Epidemiologic studies have shown that odds ratios (estimated relative risks) of lung cancer with Hp infection range from 1.24 to 17.78 compared with the controls, suggesting an increased lung cancer risk in the population exposed to Hp infection although far from supporting a causal relationship between Hp and lung cancer. Many studies have demonstrated the existence of Hp in the mucosa of the upper respiratory tract with no direct evidence of Hp-localization in lung tissue in the published literatures, rendering the possible functional mechanism underlying the association an open question. We followed the classic hypothesis-generating path, where we have thoroughly reviewed the publications on lung cancer and Hp infection from serological association to possible mechanisms as: (i) p130cas activated by Src kinase following Hp-host communication and p130cas-related carcinogenesis as in various malignancies; and (ii) gastroesophageal reflux and inhalation of urease or gastrin, which are Hp-related carcinogenic factors and present in lung tissues. We propose rigorous investigations regarding the Hp-lung cancer association and, if confirmed, the mechanisms of Hp infection leading to lung cancer development and progression. Clarification on Hp-lung cancer association is important for the understanding of lung cancer beyond tobacco-smoking-related carcinogenesis.

Topics: Antigens, Bacterial; Bacterial Proteins; Crk-Associated Substrate Protein; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Lung Neoplasms; Odds Ratio; Stomach; Urease

The review summarizes the past year's literature, basic science and clinical, regarding the neural, paracrine, hormonal, and intracellular regulation of gastric acid secretion.. Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B(12), and certain medications (e.g. thyroxin). It also kills ingested microorganisms and prevents bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis. Stimulants of acid secretion include histamine, gastrin, acetylcholine, and ghrelin. Inhibitors include somatostatin, nefstatin-1, interleukin-11, and calcitonin gene-related peptide. Helicobacter pylori stimulates or inhibits acid secretion depending upon the time course of infection and the area of the stomach predominantly infected. Acute infection activates calcitonin gene-related peptide sensory neurons coupled to inhibition of histamine and acid secretion. Serum chromogranin A, a marker for neuroendocrine tumors, is elevated in patients taking proton pump inhibitors.. Progress continues in our understanding of the regulation of gastric acid secretion in health and disease, as well as the function of gastric neuroendocrine cells. The recognition that gastrin is not only a secretagogue but also a trophic hormone has led to new research into the role of gastrin and its receptor (cholecystokinin-2 receptor) in carcinogenesis and the development of cholecystokinin-2 receptor antagonists.

Topics: Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Neurosecretory Systems; Parietal Cells, Gastric

Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers.. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice.. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria.. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Topics: Achlorhydria; Antibodies, Bacterial; Biomarkers; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Mass Screening; Pepsinogen A; Pepsinogen C; Stomach Neoplasms; Vitamin B 12

Gastric exocrine secretion, both acid and non-acid, is required for micronutrients absorption, such as iron, calcium and vitamin B12, drugs absorption, protein digestion. Clinical presentation of a gastric secretion impairment might be then characterized by the presence of both gastrointestinal and non-gastrointestinal specific symptoms (i.e. anemia) or to a non-response to therapies. The main factor that impairs gastric exocrine secretion homeostasis is mucosal chronic inflammation that principally occurs after colonization by Helicobacter pylori (Hp). The extent and distribution of gastritis ultimately determine the clinical outcome linked to differences in gastric acid secretion status, the involvement of gastric body leading to a decrease in gastric exocrine secretion with possible progression to mucosal atrophy towards cancer. A correct clinical strategy in the management of Hp infected patients should be then to early identify body involvement, a diagnosis generally missed in that body biopsies are not routinely performed. The use of gastric serological markers, gastrin and pepsinogens, are helpful in suspecting the presence of mucosal atrophy but their diagnostic accuracy for non-atrophic chronic gastritis topography is not adequate despite a good specificity due to the low sensitivity, of all the available biomarkers. Gastric serology associated to anemia/iron-deficiency screening might nevertheless been helpful in the framing of patients that undergo endoscopy in order to highlight the need of extensive mucosal biopsies sampling.

Topics: Absorption; Anemia; Biomarkers; Biopsy; Gastric Acid; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Micronutrients; Models, Biological; Parietal Cells, Gastric; Pepsinogens; Secretory Rate; Stomach

Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors [the cholecystokinin (CCK2) receptors] potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation.. We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in gastrointestinal cancers, summarize gastrin's proinflammatory role by inducing the production of cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression.. We discuss trends for future studies directed toward the elucidation of gastrin peptides' role in regulating intercellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer.

Topics: Animals; Cocarcinogenesis; Colorectal Neoplasms; Cytokines; Feedback, Physiological; Gastrins; Gastritis; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation Mediators; Leukocytes; Receptor, Cholecystokinin B

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia, such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.

Topics: Adenocarcinoma; Animals; Cell Movement; Cell Proliferation; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Mice; Mice, Transgenic; Models, Biological; Neoplasm Invasiveness; Neovascularization, Pathologic; Neuroendocrine Tumors; Stomach Neoplasms; Zollinger-Ellison Syndrome

As there is considerable overlap between the fasting serum gastrin concentrations found in Zollinger-Ellison syndrome and various common conditions such as Helicobacter pylori infection and acid suppressing medication use, establishing the cause of hypergastrinaemia in individual cases can sometimes be difficult.. To review the causes of hypergastrinaemia and the role of additional non-invasive investigations in hypergastrinaemic patients.. Review of articles following a Pubmed search.. As gastrinomas may cause serious complications and be potentially life threatening, investigation of hypergastrinaemic patients should particularly focus on confirming or refuting the diagnosis of Zollinger-Ellison syndrome. Establishing the cause of hypergastrinaemia may be difficult when there is only a mild-to-moderate elevation of fasting serum gastrin concentration and concurrent treatment with proton pump inhibitor drugs and the presence of H. pylori infection can both confuse the clinical picture. A variety of provocative tests are therefore useful for establishing whether a hypergastrinaemic patient has a gastrinoma and current evidence suggests that the secretin test should be used first line.. We suggest an algorithm for the investigation of patients found to have an elevated fasting serum gastrin concentration and address the roles of gastrin stimulation tests in current clinical practice.

Topics: Algorithms; Diagnosis, Differential; Gastrinoma; Gastrins; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Secretin; Zollinger-Ellison Syndrome

This review summarizes the last year's literature regarding the regulation and measurement of gastric exocrine and endocrine secretion.. Parietal cells, distributed along much of the length of the oxyntic glands, with highest density in the neck and base, secrete HCl as well as transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor-like growth factor, and sonic hedgehog. Acid facilitates the digestion of protein and absorption of iron, calcium, vitamin B(12) as well as prevents bacterial overgrowth, enteric infection, and possibly food allergy. The major stimulants of acid secretion are gastrin, histamine, and acetylcholine. Ghrelin and orexin also stimulate acid secretion. The main inhibitor of acid secretion is somatostatin. Nitric oxide and dopamine also inhibit acid secretion. Although Helicobacter pylori is associated with duodenal ulcer disease, most patients infected with the organism produce less than normal amount of acid. The cytoskeletal proteins ezrin and moesin participate in parietal cell acid and chief cell pepsinogen secretion, respectively.. Despite our vast knowledge, the understanding of the regulation of gastric acid secretion in health and disease is far from complete. A better understanding of the pathways and mechanisms regulating acid secretion should lead to improved management of patients with acid-induced disorders as well as those who secrete too little acid.

Topics: Acetylcholine; Cytoskeletal Proteins; Gastric Acid; Gastric Mucosa; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Intracellular Signaling Peptides and Proteins; Microfilament Proteins; Neuropeptides; Orexins; Parietal Cells, Gastric; Pepsinogen A

Gastric cancer (GS) remains one of the most common cancers worldwide. It is considered as the second most frequent cause of cancer death worldwide, although much geographical variation in incidence exists. Many studies before linked Helicobacter pylori (Hp) which is now considered as an important pathogen, to the risk of developing noncardia GS. This overview attempts to summarize the recent basic and clinical evidence on the link between H. pylori and gastric cancer, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of Hp and the investigation of their relevance to peptic ulcer disease. It become evident that Hp eradication by antibiotic treatment combined with proton pump inhibitor (PPI) serves as the primary chemoprevention strategy to reduce gastric cancer incidence. Moreover, the eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. Due to understanding the molecular nature of GC which has been nowadays under intense investigation, our review attempts to highlight recent progress in the field of research on Hp-induced GS. We discuss the geographical diversity in Hp infection and cancer incidence and the mechanistic role of gastrin, cyclooxygenase-2 (COX-2), growth factor, nitric oxide (NO)/NO synthase and E-cadherin/beta-cathenin systems, apoptosis and angiogenesis in Hp-induced gastric carcinogenesis. In addition host-related genetic susceptibility and the role of overexpression of a proinflammatory cytokines and their polymorphism is discussed in the relation to the cascade of events such as gastric atrophy, intestinal metaplasia and dysplasia that finally lead to adenocarcinoma.

Topics: Animals; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Prevalence; Stomach Neoplasms; Virulence

Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development in humans. Long-term use of proton pump inhibitors is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication. It is thus recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in patients not infected with H. pylori, but these changes are believed to be reversible and without significant cancer risk.

Topics: Animals; Atrophy; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Precancerous Conditions; Proton Pump Inhibitors

Recent milestones in the understanding of gastric acid secretion and treatment of acid-peptic disorders include the (1) discovery of histamine H(2)-receptors and development of histamine H(2)-receptor antagonists, (2) identification of H(+)K(+)-ATPase as the parietal cell proton pump and development of proton pump inhibitors, and (3) identification of Helicobacter pylori as the major cause of duodenal ulcer and development of effective eradication regimens. This review emphasizes the importance and relevance of gastric acid secretion and its regulation in health and disease. We review the physiology and pathophysiology of acid secretion as well as evidence regarding its inhibition in the management of acid-related clinical conditions.

Topics: Acetylcholine; Animals; Anti-Ulcer Agents; Digestion; Duodenal Ulcer; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Diseases; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Histamine; Histamine H2 Antagonists; Humans; Ion Channels; Paracrine Communication; Proton Pump Inhibitors; Somatostatin; Stomach; Stomach Ulcer

Topics: Biomarkers; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Risk Factors; Stomach Neoplasms

To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Endoscopy, Gastrointestinal; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors

Gastrin is a pro-proliferative, anti-apoptotic hormone with a central role in acid secretion in the gastric mucosa and a long-standing association with malignant progression in transgenic mouse models. However, its exact role in human gastric malignancy requires further validation. Gastrin expression is tightly regulated by two closely associated hormones, somatostatin and gastrin-releasing peptide, and aspects of their interaction may be deregulated during progression to gastric adenocarcinoma. Furthermore, agonists and antagonists of the receptors for all three hormones have shown modest clinical efficacy against gastric adenocarcinoma, which might provide useful information on the future combined use of these agents.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Cancer Vaccines; Cell Differentiation; Cell Movement; Cell Transformation, Neoplastic; Gastrin-Releasing Peptide; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Humans; Mice; Neoplasm Invasiveness; Neoplasms, Experimental; Neovascularization, Pathologic; Precancerous Conditions; Risk Factors; Somatostatin; Stomach Neoplasms

Our understanding of the function and etiology of various gastric diseases has exponentially expanded over the past 40 years. In particular, several animal models had been devised and used for screening of anti-ulcer drugs and elucidation of pathogenesis. This review describes how water-immersion stress ulcer model, Helicobacter pylori ulcer model, and acetic acid ulcer models were established in experimental animals. In recent years, genetically modified mice allowed rapid accumulation of very important findings. H(2)-receptor knockout mice revealed to exhibit Menetrier's disease-like gastric mucosal changes. Gastrin-transgenic mice infected with H. pylori revealed to develop gastric cancer. The hypothesis for the origin of parietal cells was provided.

Topics: Acetates; Animals; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis, Hypertrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immersion; Mice; Mice, Knockout; Mice, Transgenic; Rats; Receptors, Histamine H2; Stomach Ulcer; Stress, Physiological

Classifications of chronic gastritis and neoplastic gastric diseases, developed in recent years (1996 Houston update of 1990 Sidney classification system, 2002 New Orlean classification of atrophic gastritis according to recommendations of International Group for Atrophy Studies; 1998 Padova classification of gastric displasia, and 1998 Vienna classification of gastrointestinal neoplasia) allow to statandardize international research and perform more objective diagnostics of pathological changes in the gastric mucosa. Studies carried out in recent years have established that morphological manifestations of chronic gastritis caused by Helicobacter pylori infection can be reduced after its eradication. Longterm treatment with proton pump inhibitors have been demonstrated not to cause atrophic changes in the gastric mucosa when undertaken after successful eradicational therapy. It has been established that corporal gastritis intensifies in patients treated with proton pump inhibitors. The studies show that measurement of serum levels of Helicobacter pylori antibodies, gastrine, pepsinogen I and II can be used in non-invasive serologic diagnostics of atrophic gastritis. Achievements in diagnostics and treatment of chronic gastritis create the necessary prerequisites for the development of gastric cancer preventing measures.

Topics: Antibodies, Bacterial; Biopsy; Chronic Disease; Dyspepsia; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Pepsinogen C; Proton Pump Inhibitors; Stomach; Stomach Neoplasms; Time Factors

Topics: Biomarkers; Diagnostic Techniques, Endocrine; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hyperparathyroidism; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Zollinger-Ellison Syndrome

Topics: Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Polyps; Stomach Neoplasms

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-8

Topics: DNA Damage; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Hypertrophic; Helicobacter Infections; Helicobacter pylori; Hepatocyte Growth Factor; Humans; Interleukin-1; Risk; Stomach Neoplasms

In 1984, Reg protein was shown to be stimulated during the regeneration of pancreatic islets. Since then, many Reg-related proteins have been identified in humans and other animals. These Reg-related proteins are classified into four subfamilies according to their amino-acid sequences, but they share a similar structure and physiological function. The role of Reg in gastric tissue was investigated, and Reg I was found to be expressed mainly in gastric fundic enterochromaffin-like (ECL) cells. Reg I production in ECL cells is stimulated by gastrin, as well as by the proinflammatory cytokine, cytokine-induced neutrophil chemoattractant (CINC)-2Beta. In patients with chronic hypergastrinemia, Reg production is stimulated, with the increased proliferation of gastric mucosal cells. Patients with Helicobacter pylori infection also showed increased Reg production in the gastric mucosa, partly via increased plasma gastrin concentration and partly via increased proinflammatory cytokine production. Thus, Reg protein induced by H. pylori infection may be partly responsible for the increased proliferation of gastric epithelial cells in H. pylori-infected patients. Reg protein is also produced in many gastric cancer cells, especially in poorly differentiated and advanced cancers. Reg protein stimulates the proliferation of several gastric cancer cell types, and gastric cancers with Reg protein expression tend to show a poorer clinical outcome. In summary, Reg protein may be a growth factor that regulates the proliferation and differentiation of normal and neoplastic gastric epithelial cells.

Topics: Animals; Cell Division; Chronic Disease; Enterochromaffin-like Cells; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; In Situ Hybridization; Stomach Neoplasms

The pathogenesis of cancer in Barrett's esophagus is multifactorial. Gastroesophageal reflux seems to be important in the initiation of Barrett's esophagus, but its role in promoting carcinogenesis has yet to be established. Diet, lifestyle and carcinogens, especially the nitrates, may be important in the development of carcinogenesis, and require further investigation. Inhibition of reflux-stimulated inflammatory changes, for example by inhibiting cyclooxygenase, holds promise for decreasing cancer progression. Similarly, dietary and lifestyle modification used in the management of reflux may also help to prevent the development of esophageal cancer. The molecular changes that are associated with the development of cancer in Barrett's esophagus offer several potential areas of intervention to prevent and manage esophageal cancer. Limiting cell growth, increasing apoptosis of damaged cells, limiting cell invasion and angiogenesis factors could be useful to accomplish this goal. Having a greater understanding of the pathogenesis of this condition can only help to develop more management options in the future.

Topics: Barrett Esophagus; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans

Helicobacter pylori (Hp) infection represents a crucial factor in pathogenesis of gastric cancer (GC). Factors emanating from bacterium as well as from environmental contributions such as salt diet and inadequate supply of antioxidants, affect the risk for GC development.. Atrophic gastritis is considered to be a precursor lesion of intestinal type GC that is accompanied by hypergastrinemia with subsequent induction of cyclooxygenase-2 (COX-2), whose products are responsible for slowing apoptosis and for angiogenesis in GC tumor. The involvement of proinflammatory cytokines (especially IL-1 and IL-8) and reactive oxygen species (ROS) due to NF kappa B activation, increased cell proliferation combined with inhibition of apoptosis as well as upregulation of peroxisome proliferation activated receptor gamma (PPAR gamma) and inducible nitric oxide synthase (iNOS) appear to be major molecular biology alterations in pathogenesis of GC.. These results suggest the therapeutic usefulness of inhibitors of gastrin expression and release such as powerful somatostatin analogs (Sandostatin) or blockers of COX-2 (coxibs) in the control of GC development and progression as chemopreventive agents. Comparative genomic and proteomic is the key in identifying biomarkers in host and bacterium for the prediction of gastric cancer in Hp-infected patients.

Topics: Animals; Apoptosis; Bacterial Proteins; Cyclooxygenase 2; Cytokines; Gastrins; Gastritis, Atrophic; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Humans; Isoenzymes; Membrane Proteins; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Receptors, Cytoplasmic and Nuclear; Stomach Neoplasms; Survival Rate; Transcription Factors

Helicobacter infection is the single most common cause of gastric cancer worldwide. Although infection prevention and eradication of established infection offer the potential for cure, these strategies are neither feasible nor practical for widespread implementation. Patients most at risk need to be identified and targeted for treatment. For disease to occur, bacterial, environmental, and nutritional factors require a genetically susceptible host. Consequently, it is important to understand how the organism interacts with the host to cause disease. Only through an understanding of what places a patient at risk can we hope to identify susceptible patients early enough in disease to have an impact on their outcome. The immune response is the single most important determinant of disease. Single nucleotide polymorphisms within the promoter region of several critical proinflammatory genes dramatically increase the risk of Helicobacter-associated gastric cancer. Additionally, environmental and dietary factors may modulate the immune response or directly influence key apoptotic and proliferative signaling cascades to alter disease presentation. Lastly, concurrent disease states may have a dramatic impact on the host response to Helicobacter infection and influence disease. An understanding of the immune signaling pathways responsible for disease and the ways in which environmental risk factors influence these pathways will allow identification of populations that are most at risk and targeted prevention and treatment strategies.

Topics: Animals; Cadherins; Disease Susceptibility; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Polymorphism, Single Nucleotide; Precancerous Conditions; Stomach Neoplasms

Topics: Anemia; Anti-Bacterial Agents; Anti-Ulcer Agents; Comorbidity; Disease Susceptibility; Drug Therapy, Combination; Duodenal Diseases; Duodenal Ulcer; Enzyme Inhibitors; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Prevalence; Proton Pump Inhibitors; Renal Dialysis; Stomach Diseases; Stomach Ulcer; Urea

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori - antibodies assayed from a blood sample it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The test enables the identification of patients whose risk of gastric cancer, of the consequences of vitamin B12 deficiency (e.g. elevated levels of homocysteine) or of peptic ulcer is considerably increased and who can then undergo gastroscopy. It also facilitates the diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Topics: Finland; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A; Peptic Ulcer; Stomach Neoplasms; Vitamin B 12 Deficiency

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones.

Topics: Animals; Disease Models, Animal; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Somatostatin

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Methylhistamines; Somatostatin; Tumor Necrosis Factor-alpha

Topics: Animals; Cell Division; Chronic Disease; Duodenal Ulcer; Enterochromaffin-like Cells; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Histamine Release; Humans; Somatostatin

Gastric cancer is the second most common cause of cancer-related mortality worldwide and the 14th overall cause of death. Detection of disease usually occurs at an advanced stage and overall survival rates for gastric cancer are poor. Our current model for gastric cancer progression clearly maintains Helicobacter infection as the primary inducer of gastric metaplastic and neoplastic disease. Helicobacter pylori is a ubiquitous organism, infecting more than half the world's population. It has been suggested that this infection directly contributes to the formation of gastric cancer in up to 80% of cases; however, gastric malignancy develops in only a subset (< 1%) of infected patients. Therefore, predisposition to Helicobacter-associated gastric cancer is most likely multifactorial, including the interaction of bacterial, host and environmental components. Our understanding of how the organism interacts with the gastric mucosa and synergizes with dietary and other environmental factors to induce malignant mucosal changes is evolving. Indeed, H. pylori has direct effects on the gastric mucosa, but the major factor in disease progression appears to be a robust host Th1 immune response in the setting of a permissive environment. In combination, these factors predispose to the formation of atrophy, metaplasia and gastric cancer. Understanding the interaction of the bacterium with the host and the environment can potentially identify patients most at risk. Identifying potentially removable factors (in addition to H. pylori infection) in the acquisition and progression of neoplastic disease may provide targets for early intervention and prevention strategies.

Topics: Animals; Cytokines; Diet; Diffusion of Innovation; Gastric Acid; Gastrins; Growth Substances; Helicobacter Infections; Helicobacter pylori; Humans; Mucins; Muscle Proteins; Neuropeptides; Peptides; Sodium Chloride; Stomach Neoplasms; Trefoil Factor-2; Trefoil Factor-3

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment.. Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Costs; Drug Interactions; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Rabeprazole; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Stomach Ulcer; Zollinger-Ellison Syndrome

The decline in duodenal ulcer disease and the established relation of peptic ulcer to Helicobacter pylori have virtually abolished the need for elective ulcer surgery. However, a substantial proportion of the population around retirement age has previously been subjected to partial gastric resection due to peptic ulcer, and the long-term outcome of these patients is of continuing relevance. Patients subjected to elective surgery could represent a selected group of healthy subjects with a lower overall morbidity, but reports indicate that patients operated on for peptic ulcer have more advanced disease associated with excess smoking and a different pattern of social behavior. The surgical procedure induces enterogastric reflux, leading to profound changes in the remnant mucosa and the formation of carcinogens in the gastric juice. In addition, metabolic abnormalities are common, especially fat malabsorption. Evaluation of the impact of these factors on morbidity and mortality is difficult. Increased mortality in gastrointestinal tumors (especially gastric stump carcinoma), respiratory diseases and other smoking-related malignancies, and suicide are found in the long-term follow-up after partial gastric resection due to peptic ulcer. However, these hazards to life are offset by a decreased mortality in cardiovascular disease. Preventive measures against suicide and especially tobacco smoking are recommended to improve th outcome for this cohort.

Topics: Bile Reflux; Cardiovascular Diseases; Female; Gastrectomy; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Nutrition Disorders; Peptic Ulcer; Prognosis; Risk Factors; Sex Factors; Smoking; Stomach Neoplasms; Suicide; Time Factors

Proton pump inhibitors are potent drugs for the treatment of acid-related diseases. The moderate hypergastrinaemia observed during therapy is a physiological response to low intragastric pH and the increase is limited to the first months of therapy with no further changes thereafter. Reports on endocrine cell changes in the antral mucosa under chronic PPI therapy are controversial and lack clinical relevance. In contrast, in the oxyntic mucosa hyperplastic argyrophil cell changes have been reported, dependent on the degree and duration of hypergastrinaemia, the severity of oxyntic mucosal gastritis, especially atrophy, and the presence of H. pylori infection. Current data do not support a progression from hyperplastic to dysplastic argyrophil cell lesions in humans in the absence of additional genetic factors. Data on the progression of oxyntic gastritis under chronic PPI treatment in comparison to untreated controls could not be confirmed in more recent studies including a well-matched control population. The main factor for gastritis progression is the presence of Helicobacter pylori infection. The bacterium not only causes a chronic inflammation of the gastric mucosa, resulting in atrophy and intestinal metaplasia, but also influences endocrine cell populations involved in the regulation of gastric acid secretion. The clinical benefit of H. pylori eradication in reflux esophagitis patients is still a matter of debate. The complex relations in humans between hypergastrinaemia, (oxyntic) gastritis and atrophy, H. pylori infection, argyrophil cell hyperplasia, and the effects of long-term PPI treatment of acid-related diseases do not allow a quantification of the contribution of each single factor for the observed changes.

Topics: Anti-Ulcer Agents; Atrophy; Enzyme Inhibitors; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Proton Pump Inhibitors

Duodenal ulcer patients are characterized by an antrum-predominant, body-sparing, nonatrophic Helicobacter pylori (H. pylori) gastritis, which results in increased gastrin release and increased acid secretion. The increased gastrin release is caused by the infection impairing the acid-mediated inhibitory control of gastrin release. The elevated levels of the gastrin stimulate the healthy uninflamed, non-atrophic acid-secreting region of the stomach to secrete excess amounts of acid. The increased gastrin also exerts trophic effects on the oxyntic mucosa, causing hyperplasia of both the enterochromaffin-like cells and the parietal cells. These trophic changes in the mucosa further enhance its ability to secrete acid. The increased acid secretion results in an increased duodenal acid load, causing gastric metaplasia of the duodenal bulb and eventually the development of ulceration. In H. pylori-infected subjects without duodenal ulceration, a different pattern of gastritis is seen. This includes atrophy of the antrum, which reduces the number of G-cells and thus the degree of hypergastrinaemia induced by the antral infection. There are usually also varying degrees of inflammation and atrophy of the acid-secreting mucosa, which impair its ability to secrete acid in response to gastrin stimulation. The combined effects of the atrophy of the antrum and the inflammation of the antrum of the body mucosa therefore prevent H. pylori-induced acid hypersecretion and may result in varying degrees of hypochlorhydria. The particular pattern of gastritis that a subject develops in response to H. pylori infection and their likelihood of developing a duodenal ulcer is likely to be determinded by host genetic factors plus dietary factors.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Parietal Cells, Gastric

Helicobacter pylori, infecting more than 50% of the world population, results in gastritis, usually located in the antral portion of the stomach, accompanied by hypergastrinemia, the key factor in gastric and colorectal carcinogenesis. Excessive mucosal cell proliferation for many years may eventually result in gastric atrophy, cell mutation and transformation of gastric mucosal cells into gastrin-producing cells, which also express gastrin receptors serving to stimulate cell proliferation and tumor growth. These processes may be completed by the expression of cyclooxygenase-2 (COX-2) as an inflammation enzyme to release excessive amounts of PGE(2), leading to further proliferation, reduction in apoptosis, angiogenesis and tumor growth. H. pylori eradication results in complete regression of MALT lymphoma and subsequent normalisation of excessive gastrin release and COX-2 expression. Reduction of gastrin by active immunisation (gastrimmune), blocking of gastrin receptors with specific blockers and suppression of COX-2 might be helpful in inhibiting tumor growth and invasion.

Topics: Animals; Colorectal Neoplasms; Cyclooxygenase 2; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Isoenzymes; Lymphoma, B-Cell, Marginal Zone; Membrane Proteins; Mice; Prostaglandin-Endoperoxide Synthases; Stomach Neoplasms

Helicobacter pylori infection affects the concentration of regulatory peptides such as gastrin, somatostatin and cholecystokinin and the concentration and activity of glutathione and glutathione S-transferases in the gastric mucosa.. Literature review.. Although some of these peptides have been known since the beginning of this century, their action has changed since the discovery of H. pylori infection in 1983. Chronic infection with H. pylori might lead to an increased risk in developing gastric cancer. Glutathione S-transferases are involved in the cellular detoxification of xenobiotics and other toxic compounds. Since there is a close inverse relationship between the activity of glutathione S-transferase and incidence of malignancies in the gastrointestinal tract, the possible relation between H. pylori infection and activity of glutathione S-transferases in the gastric mucosa is discussed.. The effect of H. pylori infection on regulatory peptides and glutathione/glutathione S-transferases might play a role in the development of neoplastic changes of the H. pylori-infected gastric mucosa.

Topics: Animals; Biomarkers; Cholecystokinin; Chronic Disease; Disease Progression; Gastric Mucosa; Gastrins; Gastritis; Glutathione; Glutathione Transferase; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin; Stomach Neoplasms

Topics: Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Gastroesophageal Reflux; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Stomach Ulcer

Helicobacter pylori (H. pylori) infection leads to profound changes in gastric physiology. Several clinical and animal studies have been performed to clarify the influence of H. pylori on gastric acid secretion. Published data, however, are not consistent throughout. Infection of the gastric antrum, which can be observed mainly in duodenal ulcer patients, increases gastrin release and consecutively acid output. The net effect of corpus and antrum gastritis, such as in patients with gastric cancer, is to decrease acid secretion. Chronic H. pylori infection may finally promote gastric atrophy with irreversibly diminished acid secretion but in earlier stages of this infection eradication of H. pylori normalizes gastric secretory activity.

Topics: Animals; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Somatostatin

An analysis carried out in 1994 by the WHO International Agency for Research on Cancer (IARC) resulted in Helicobacter pylori being designated as a Group 1 carcinogen and thus clearly having an association with the development of gastric cancer. In the case of H. pylori, the evaluation was made solely on the basis of epidemiological results. In Japan, in 1993, only 235,000 of the 60 million people with H. pylori had gastric cancer. This represents only 0.4% of the infected population. Each individual reacts in a unique way to H. pylori infection in terms of the inflammatory response. The probability of developing cancer will be determined by environmental factors such as diet, duration of or age at acquisition of H. pylori infection, the virulence of H. pylori strains, and host factors including genetic make-up.

Topics: Antibodies, Bacterial; Diet; Environment; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Prevalence; Stomach Neoplasms

Helicobacter pylori is the cause of chronic type B gastritis and occurs in almost all patients with duodenal ulcers. Infection with H. pylori is characterized by an increased production of several inflammatory cytokines. Increasing evidence suggests a central role of these cytokines in the pathogenesis of H. pylori-associated gastritis and peptic ulcer disease. Cytokines may be crucial in the recruitment and activation of inflammatory cells and in stimulation of gastrin release. In addition to their proinflammatory properties, cytokines may also inhibit the ulcer occurrence by stimulation of prostaglandins and somatostatin release and by direct impairment of acid secretion. The balance of these factors may determine the clinical outcome of H. pylori infection.

Topics: Animals; Cytokines; Duodenal Ulcer; Gastrins; Gastritis; Genes, MHC Class II; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Intestinal Mucosa; Peptic Ulcer; Somatostatin

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.

Topics: Antibodies, Bacterial; Biomarkers; Enzyme-Linked Immunosorbent Assay; Evaluation Studies as Topic; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Reagent Kits, Diagnostic; Sensitivity and Specificity; Serologic Tests

It is now widely recognized that H. pylori gastritis can produce marked alterations in gastric acid secretion. In subjects with an antral predominant gastritis there is increased release of gastrin and consequently increased acid secretion. Such subjects are at risk of developing duodenal ulcers. In other subjects the infection produces a marked body gastritis and this is associated with marked hyposecretion of acid or complete achlorhydria. These subjects have an increased risk of developing gastric cancer. Between these two ends of the disease spectrum lie the majority of H. pylori-infected subjects who have gastritis of both the antrum and body and no overall change in acid secretion. The reason why the infection exerts these divergent effects on gastric morphology and function remains unclear and is a challenge for ongoing research.

Topics: Cell Count; Duodenal Ulcer; Gastric Acid; Gastric Fundus; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Risk Factors

Helicobacter pylori infected patients have increased gastrin release which shows a marked fall after cure of the infection. Recent studies indicate that inflammatory cells and cytokines play an important role in the pathogenesis of Helicobacter-associated hypergastrinemia. Views differ regarding the impact of gastrin on acid secretion. Current evidence suggests that gastrin is responsible for at least some of the increased acid secretion seen in duodenal ulcer patients.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin

Topics: Animals; Cytokines; Endocrine Glands; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Somatostatin; Stomach; Stomach Ulcer

Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.

Topics: Ascorbic Acid; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

The discovery of H. pylori infection and the recognition of its effects on gastric physiology has significantly advanced our understanding of the pathophysiology of ulcer disease, In DU patients H. pylori gastritis is mainly confined to the antral mucosa. It stimulates increased release of gastrin by the antral mucosa and this is accompanied by high acid output by the oxyntic mucosa. This high acid response to gastrin stimulation by the oxyntic mucosa in DU patients is due to the combination of a high parietal cell mass and the fact that the function of these parietal cells is not impaired by any body gastritis. The increased acid secretion results in an increased duodenal acid load with the development of gastric metaplasia within the duodenal bulb and then actual ulceration. The reason why only some subjects develop this antral predominant pattern of H. pylori gastritis and associated acid hypersecretion is unclear but may be explained by a premorbid high acid output protecting the oxyntic mucosa form H. pylori gastritis.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.

Topics: Animals; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans

Helicobacter pylori is highly adapted to its unusual ecological niche in the human stomach. Urease activity permits H. pylori survival at a pH of <4 in vitro and is required for the organism to colonize in animal models. However, urease does not play an important role in the survival of the organism in a pH range between 4 and 7. Other mechanisms of pH homeostasis remain poorly understood, but preliminary studies indicate that novel proteins are produced when H.pylori cells are shifted from pH 7 to 3, and the gene encoding a P-type adenosine triphosphatase that may catalyze NH4+/H+ exchange across the cytoplasmic membrane has been cloned. Mechanisms of pH homeostasis in other enteric bacteria are reviewed and provide insight into additional pathways that may be used by H. pylori. An important adaptation of H. pylori to the gastric environment may be its ability to alter gastric acid secretion. Acute infection is associated with transient hypochlorhydria, whereas chronic infection is associated with hypergastrinemia and decreased somatostatin levels. Thus, the survival of H. pylori in the gastric environment may be attributed to both the development of specialized intrinsic defenses and the organism's ability to induce physiological alterations in the host environment.

Topics: Acute Disease; Chronic Disease; Cytoplasm; Duodenal Ulcer; Enterococcus faecalis; Escherichia coli; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Salmonella; Somatostatin; Urease

The dictum "no acid-no ulcer" had, in the past, summarized the thinking concerning the pathogenesis of peptic ulcer disease. It is now recognized that infection with Helicobacter pylori is the major causal factor leading to both duodenal and gastric ulceration. Infection is associated with many of the acid secretory abnormalities that have traditionally characterized peptic ulcer disease; indeed, acid secretory physiology returns to normal following bacterial eradication. Since not all individuals infected with H. pylori develop ulcers, host susceptibility, bacterial virulence, and/or specific environmental factors must determine the response to infection and the ultimate clinical outcome. The relative importance of these factors and their complex interactions remain to be determined. H. pylori infection produces tissue damage indirectly because the organism does not directly invade gastroduodenal tissue. A variety of bacterial enzymes, toxins, and inflammatory mediators produced in response to bacterial colonization challenge the integrity of host mucosal defenses. In a susceptible host, breached defenses render epithelium more vulnerable to acid injury and ulcer development. Eradication of H. pylori leads to rapid ulcer healing and reversal of tissue injury, thereby obviating ulcer recurrence.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Stomach Ulcer

Helicobacter pylori is now recognized as the major acquired factor in the pathogenesis of duodenal ulcer disease (DU). There is also an association between H. pylori infection and the subsequent development of gastric cancer. The mechanisms by which such infection predisposes the host to these diseases are incompletely understood, but disorders induced by the bacterium in gastric function play a pivotal role. In most patients, H. pylori infection stimulates acid secretion, leading to a predisposition to DU development. However, in some patients, the infection is associated with a significant decrease in acid secretion, a predisposition to gastric cancer. These divergent effects of H. pylori on gastric acid secretion explain the early conflicting reports on changes in acid secretion associated with the infection. The reason why H. pylori infection produces divergent effects on gastric acid secretion is unclear, but may be related to differences in bacterial strains or genetic, dietary or other environmental factors.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Stomach Neoplasms

Topics: Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Ulcer

Topics: Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Ulcer; Virulence

Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis. Most patients continue through life with a chronic superficial gastritis while some develop either duodenal or gastric ulcer. In a very small proportion the lymphoid reaction to H. pylori infection appears to progress to become a mucosal associated lymphoid tissue (MALT) lymphoma, while in others the evidence suggests that chronic superficial gastritis progresses to atrophy, the loss of gastric acid secretory capacity and the development of gastric cancer. The mechanisms involving H. pylori infection in peptic ulceration are increasingly well understood and H. pylori is now accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 95%. More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those who ulcers have been healed but in whom the infection persists. There is also increasing evidence for the involvement of H. pylori in gastric ulcer, where infection is seen in between 60 and 80%, and there is a similar dramatic reduction in recurrence following cure of H. pylori infection. The progression of H. pylori gastritis from the acute infection to chronic superficial gastritis, predominantly antral gastritis or a pangastritis with increasing atrophy appears to be associated with the differing outcomes seen in this disease. Moreover, there is increasing data on the roles played by bacterial heterogeneity and the virulence of the organism, host factors such as the HLA genotype and immune response, environmental factors and the age of acquisition of infection play in determining these clinical outcomes of the disease.

Topics: Gastric Acid; Gastrins; Gastritis; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Somatostatin; Stomach Neoplasms

Gastrin is a well known endogenous stimulator of gastric acid. In addition, recent studies have revealed that gastrin has a growth promoting effect on gastric ECL cells. Indeed, development of ECL carcinoid tumor occurs almost exclusively in patients with hypergastrinemia such as autoimmune gastritis and Zollinger-Ellison syndrome with MEN type I. We have recently cloned human gastrin receptor gene, and by using it, we found that both gastric carcinoid tumor and endocrine cell carcinoma of the stomach express significant amount of gastrin receptor gene whereas none of gastric cancer tissue shows gastrin receptor gene expression. Thus, it is clear that gastrin plays important roles in the development of gastric carcinoid tumor as well as endocrine cell carcinoma of the stomach.

Topics: Animals; Carcinoid Tumor; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Receptors, Cholecystokinin; Stomach Neoplasms

Before the discovery of Helicobacter pylori, duodenal ulcers were thought to be caused by excessive acid secretion. Duodenal ulcer patients have more parietal cells than controls. In addition, they cannot suppress their acid secretion when the gastric lumen is empty or acidic. These changes, plus an increase in the release of gastrin were attributed to a paucity of the inhibitory peptide somatostatin in the gastric mucosa. It has now been established that the paucity of somatostatin and the failure to suppress acid secretion are actually the result of H. pylori infection. In patients without duodenal ulcers H. pylori infection is often associated with decreased acid secretion. This occurs on first infection and also later because H. pylori gastritis predisposes to gastric atrophy.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Unlike the stimulation of gastric acid secretion, which clearly involves the release of gastrin, the mechanisms of inhibition of this secretory process are poorly defined although recent studies in animals with the use of highly selective cholecystokinin (CCK) antagonists indicate that CCK may play a crucial role in this inhibition. Duodenal ulcer patients (DU) differ from healthy controls by higher total acid secretory rates and diminished inhibition of acid secretion. Several possible pathomechanisms of the abnormal gastric secretory function in DU patients were previously proposed. The deficiency of CCK-induced gastric inhibition in DU patients together with the somatostatin hypothesis appear to be attractive, particularly so the suggestion that a deficiency of somatostatin activity exists in DU patients.

Topics: Animals; Cholecystokinin; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Humans; Reference Values; Somatostatin

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens

Helicobacter pylori is the new-found cause of duodenal ulcers (DU), but acid secretion remains necessary and is elevated in DU patients. My group and others have asked whether H. pylori itself alters gastric physiology. This infection has been found to decrease local expression of the inhibitory peptide somatostatin, and to increase release of the acid-stimulating hormone gastrin. H. pylori infection can alter acid secretion in both directions. Acid disappears temporarily on first infection, and may dwindle later if H. pylori causes gastric atrophy. DU patients have approximately twice the normal parietal cell mass, which increases their maximal secretory capacity, but it is not clear whether or not this is due to H. pylori. However, the infection certainly does change physiological control of acid secretion, as expected from the endocrine changes. Acid secretion is elevated during fasting, during stimulation with an acidic meal and during infusions of gastrin-releasing peptide. The balance between these opposing effects of H. pylori on acid may be crucial in determining the clinical outcome of H. pylori infection. High-acid secretion leads to DUs whilst low acid secretion is found in patients with gastric ulcers and gastric cancer. Inflammatory cytokines released in H. pylori gastritis may cause some of these changes in gastric physiology.

Topics: Animals; Cytokines; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin; Urease

The diagnosis and management of antral gastrin-(G-) cell hyperplasia was a major topic of interest in the 1970s. Following the discovery of Helicobacter pylori in the 1980s, little attention was paid to this condition until it was shown that H. pylori infection was associated with hypergastrinaemia and that eradication of the organism returned the gastrin level to normal. Recent reports have examined the relationship between H. pylori and antral G-cell hyperplasia. H. pylori infection is present in about 50% of cases of antral G-cell hyperplasia and, importantly, eradication of the organism normalizes not only the gastrin level but also the antral G-cell count. Eradication treatment should be the therapy of choice. It is also of interest that H. pylori-negative antral G-cell hyperplasia or hyperfunction does exist. The historical aspects, the relationship between antral G-cell hyperplasia and H. pylori and recent case reports are reviewed.

Topics: Animals; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Pyloric Antrum

Topics: Bacterial Proteins; Breath Tests; Carbon Radioisotopes; Child; Chronic Disease; Gastric Juice; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Predictive Value of Tests; Prevalence; Sensitivity and Specificity; Staining and Labeling; Urease

Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown.. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays.. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.

Topics: Adult; Anti-Bacterial Agents; Cholecystokinin; Dietary Fats; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormones; Humans; Hydrogen-Ion Concentration; Male; Proglumide; Reference Values; Somatostatin

Etiologic role for HP appears to be best established in histologically proven gastritis. The major factors mediating gastritis induced by the colonization of the "gastric type" mucosa with HP are probably cytotoxins, cytokines and free radicals activated by this organisms. The deficiency of negative feedback in somatostatin-gastrin link in antral gastritis may result in an excessive gastrin release and increased gastric acid secretion with increased duodenal acid load under basal state and after meal. Recent NIH consensus 1994 proposes that: (1) ulcer patients with HP require treatment with antimicrobial agents whether on first presentation or on recurrence; (2) the value of treatment of HP infection in non-ulcer dyspepsia remains to be determined and (3) the asymptomatic subjects with HP infection do not require treatment with antimicrobial agents.

Topics: Bacteriological Techniques; Bicarbonates; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer

Helicobacter pylori infection causes inflammation of the gastric and duodenal mucosa, which results in a disturbance of the regulation of gastrin, gastric acid, and pepsin secretion. Acid secretion may be diminished, normal, or increased, depending on the stage of H. pylori infection, although the meal-stimulated gastrin response is invariably elevated. The exact mechanisms involved are not known, but probably involve the release of cytokines in response to bacterial products initiating mucosal inflammation. Helicobacter pylori is suppressed, although not eradicated, by proton pump inhibitors. In various dose combinations with amoxycillin, omeprazole in a twice daily dose of up to 40 mg b.i.d. eradicates the organism in up to 82% of patients. This synergistic effect may be due to the direct effects of omeprazole, the protection of amoxycillin from acid degradation, or the enhancement of host defense mechanisms accompanying acid suppression.

Topics: Amoxicillin; Drug Therapy, Combination; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Omeprazole; Pepsin A; Pepsinogens; Proton Pumps; Stomach Ulcer

Topics: Analgesics; Blood Group Antigens; Diet; Duodenitis; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Peptic Ulcer; Risk Factors; Smoking; Stress, Physiological; Twin Studies as Topic

In summary, it appears that the role of H. pylori in duodenal ulcerogenesis is not directly associated with acid hypersecretion. Similarly, it seems unlikely that H. pylori-induced autoimmune injury is an important mechanism in duodenal ulcerogenesis. An essential question remaining is whether H. pylori infection of areas of gastric metaplasia in the duodenum is essential to ulcer pathogenesis. The low yield of H. pylori in duodenal biopsy studies argues against this mechanism. It is possible that H. pylori gastritis (present in greater than 90% of duodenal ulcer patients) results in the release of inflammatory mediators into the gastric lumen that wash down to the duodenum with gastric emptying. Such a mechanism would explain both the low recovery rate of H. pylori from duodenal biopsies in ulcer patients and the local IgA response seen in the first part of the duodenum in response to H. pylori antigens. This could also explain the high incidence of H. pylori gastritis in patients with duodenal ulcers. Obviously the four theories discussed in this review are not mutually exclusive. Significant interaction may occur between the mechanisms described. In addition, bacterial strain differences may be more important than variations in host response to H. pylori infection. Genetic studies focused on strain differences regarding mediator production and release will help clarify these issues. In the vast majority of patients with duodenal ulcer, H. pylori infection appears to be required but is not sufficient for pathogenesis of the disease. The mechanisms of ulcerogenesis related to H. pylori remain incompletely understood. Several recently identified animal models including the gnotobiotic piglet and the naturally occurring H. mustelae infection in ferrets hold substantial promise for solving the puzzle of H. pylori disease.

Topics: Animals; Antibody Formation; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Models, Biological; Stomach

Topics: Duodenal Diseases; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Models, Biological; Somatostatin; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

There is general agreement that motility, urease activity, and association with gastric mucosal cells are important virulence factors of H. pylori. Urease activity is perhaps the best characterized of these factors. Presumably, urease activity creates a "cloud" of ammonia around the bacterium, thus neutralizing the lethal effects of gastric acid. Motility allows the bacterium to penetrate the mucus layer and promotes specific association of the bacteria with epithelial cells, further allowing evasion of gastric acidity. The association between gastrin levels and H. pylori infection is currently the most thoroughly studied feature relating to pathogenesis in vivo. Prolonged hypergastrinemia associated with H. pylori infection may contribute to increased parietal cell mass and chronically increased secretion of gastric acid; however, long-term studies are needed to validate this hypothesis. The identification of mucosal gamma delta T cells and immunologic cross-reactivity between H. pylori and gastric cells implies that the immune response contributes significantly to the pathogenesis of H. pylori. The role of the immune system in modulating H. pylori infection requires further study. Although many putative pathogenic factors have been identified on the basis of in vitro phenomena alone, their significance in vivo is not known. Ultimately, it will be necessary to evaluate the significance of these factors in animal models by using isogenic strains of H. pylori that differ only in a single genotypic characteristic.

Topics: Bacterial Toxins; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans

Recent studies have been reviewed to establish the possible importance of the interaction between Helicobacter pylori infection and gastric acid secretion. H. pylori infection results in increased gastrin release, but this does not lead to gastric acid hypersecretion and gastrin normalizes after eradication of the infection. An optimal, well-tolerated treatment strategy against H. pylori infection has not yet been clearly defined. One potentially useful approach may be to improve the antibacterial efficacy of antibiotics by effectively regulating gastric acidity. H2-receptor antagonists have no effect against H. pylori infection, while omeprazole (an acid pump inhibitor) appears to have a bacteriostatic action. Combination therapy with omeprazole and amoxycillin has been found to eradicate H. pylori in 50-80% of patients with duodenal ulcer, leading to a significant reduction in ulcer recurrence.

Topics: Amoxicillin; Clinical Trials as Topic; Drug Synergism; Drug Therapy, Combination; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Omeprazole; Peptic Ulcer; Recurrence; Stomach Diseases

Although Helicobacter pylori is now accepted as the major aetiological factor in chronic gastritis in man, many of the factors which determine its pathogenicity are unknown. The organism has adapted to survive in the low-pH environment of the stomach, partly through its ability to buffer hydrogen ion by the hydrolysis of urea and by the presence of lectins on its surface, which bind to gastric mucosa and epithelial cells. After attachment, harmful toxins and enzymes have access to the gastric cells and cellular damage and an immune response ensues. In patients with duodenal ulceration, Helicobacter pylori-related gastritis predominantly affects the gastric antrum and has a high prevalence. Excessive gastrin production has been suggested as a potential aetiological factor linking infection with duodenal ulcer development. Perhaps more important is the association between gastric metaplasia of the duodenal epithelium, which is correlated with acid load and is more extreme in H. pylori positive patients with duodenitis. Organisms may subsequently spread from the gastric antrum into areas of gastric metaplasia in the duodenal bulb, leading to areas of chronic duodenitis and ultimately frank ulceration. It should not be overlooked, however, that other factors such as genetic predisposition, blood group, stress, drugs and smoking all have a role to play in the outcome, given the comparatively small number of patients in the general population infected with H. pylori who develop ulcer disease.

Topics: Duodenal Ulcer; Duodenitis; Duodenum; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa

Topics: Cimetidine; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Ranitidine; Recurrence

Topics: Anti-Inflammatory Agents; Brassica; Cytokines; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-17; Interleukin-18; Interleukin-8; Pepsinogen A; Tumor Necrosis Factor-alpha; Urea

Develop a program to identify, treat, and prevent severe atrophic gastritis to reduce gastric cancer incidence and mortality.. In total, 2,847 people aged > 40 years old underwent serological noninvasive screening for atrophic gastritis by identifying postprandial gastrin-17 and pepsinogen-1 in the fasting state. Anti-H pylori IgG was found in 2,134 patients. Seven years later, 2,220 patientswho had undergone serological noninvasive screening were asked to fill out a questionnaire survey (were interviewed). We could not find any information on 627 of 2,847 patients. Next, 75 patients with multifocal atrophic gastritis who underwent gastroscopy and biopsies (the Updated Sydney System (USS)) were selected. To study gastrin-17 production, morpho-functional correlation was studies in 75 patients with multifocal atrophic gastritis.. During seven years, no reported case of gastric cancer was done among 2,220 persons who underwent serological screening and treatment. In the same population, 4.3 persons who did not receive screening during the same period, developed gastric cancer and died of it. In this study, we can say that 4.3 lives were saved out of 2,220 tested persons. The cost for screening this number of people amounted to €23,750. A comparison of the prevalence rate of the four stages of multifocal atrophic gastritis based on the data of the histopathology tests and noninvasive serologic screening in accordance with OLGA classification showed a strong correlation (the correlation coefficient is 0.812). This finding suggested that using this classification not only for histopathology tests for atrophic gastritis but also for serologic markers of antral mucosa and corpus ventriculi atrophy: gastrin-17 and pepsinogen-1.. Complex pathogenetic treatment of atrophic gastritis significantly reduced gastric cancer risk and incidence for such patients.
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Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Case-Control Studies; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Mass Screening; Pepsinogen A; Precancerous Conditions; Prognosis; Prospective Studies; Stomach Neoplasms

Helicobacter pylori (Hp) infection affects a substantial proportion of the world population and is a major risk factor of gastric cancer (GC). The caveats of common Hp-tests can be evaded by a serological biomarker test (GastroPanel®, Biohit Oyj, Helsinki), the most comprehensive Hp-test on the market. The clinical validation of Helicobacter pylori IgG ELISA of the new-generation GastroPanel® test is reported. The aim of the study is to validate the clinical performance of the Helicobacter pylori IgG ELISA test in diagnosis of biopsy-confirmed Hp-infection in gastroscopy referral patients.. A cohort of 101 patients (mean age=50.1 years) referred for gastroscopy at the outpatient Department of Gastroenterology (SM Clinic, St. Petersburg) were examined by two test versions to validate the new-generation GastroPanel®. All patients were examined by gastroscopy and biopsies, which were stained with Giemsa for specific identification of Hp in the antrum (A) and corpus (C).. Biopsy-confirmed Hp-infection was found in 64% of patients, most often confined to antrum. The overall agreement between Hp IgG ELISA and gastric biopsies in Hp-detection was 91% (95%CI=84.1-95.8%). Hp IgG ELISA diagnosed biopsy-confirmed Hp (A&C) with sensitivity (SE) of 92.3%, specificity (SP) of 88.6%, positive predictive value (PPV) of 93.8% and negative predictive value (NPV) of 86.1%, with AUC=0.904 (95%CI=0.842-0.967). In ROC analysis for Hp detection (A&C), Hp IgG ELISA shows AUC=0.978 (95%CI=0.956-1.000).. The Hp IgG ELISA test successfully concludes the clinical validation process of the new-generation GastroPanel® test, which retains the unrivalled diagnostic performance of all its four biomarkers, extensively documented for the first-generation test in different clinical settings.

Topics: Adolescent; Adult; Antibodies, Bacterial; Biopsy; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Referral and Consultation; Stomach; Stomach Neoplasms; Young Adult

Epidemiological studies found a significant correlation between Helicobacter pylori infection and elevated serum pepsinogen, especially pepsinogen II (PGII), and reduced pepsinogen I (PGI)/PGII ratio. The study aimed to evaluate the association between abnormal gastric function risk and H. pylori infection assessed by H. pylori IgG assay and (14)C-urea breath test (UBT).. A total of 1555 subjects who underwent a health check were enrolled. Serum PGI, serum PGII, PGI/PGII ratio, gastrin 17 (G17), H. pylori IgG antibody titer, and UBT results were collected.. Median PGII and G17 levels were higher, but PGI/PGII ratio was lower in H. pylori-seropositive compared with seronegative participants (P<0.001, respectively). Similar effects were demonstrated by UBT. The consistency between H. pylori IgG assay, and UBT results were 86.9%, 82.29%, and 84.64% in individuals with normal gastric function, but only 73.4%, 67.98%, and 74.6% in those with abnormal gastric function. The correlation coefficients for H. pylori infection and abnormal gastric function diagnosed by PGI/PGII <7 were 0.336 (P<0.001) by H. pylori IgG assay and 0.231 (P<0.001) by UBT, diagnosed by PGII ≥ 8.25 µg/L were 0.594(P<0.001) by H. pylori IgG assay and 0.493 (P<0.001) by UBT, diagnosed by G17 >3 pmol/L was 0.469 (P<0.001) by H. pylori IgG assay and 0.394 (P<0.001) by UBT. The odds ratios (ORs) (95% confidence intervals) of abnormal gastric function were 7.477 (5.278-10.594), 19.204 (14.526-25.387), and 7.921 (6.286-9.982) comparing positive versus negative by H. pylori IgG assay and 4.084 (2.98-5.598), 9.552 (7.494-12.174), and 5.402 (4.335-6.731) comparing positive versus negative by UBT.. H. pylori infection assessments by antibody-based or bacterial component-based detection are both related with abnormal gastric function. Moreover, serum H. pylori IgG assay was stronger associated with abnormal gastric function than UBT assay.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Breath Tests; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Retrospective Studies; Stomach; Urea; Young Adult

Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.. To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266).. Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy.. Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin.. Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Chromogranin A; Enterochromaffin-like Cells; Esomeprazole; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Laparoscopy; Male; Middle Aged; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.

Topics: Adult; Anti-Infective Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastroscopy; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Leptin; Melatonin; Middle Aged; Omeprazole; Stomach Ulcer; Treatment Outcome; Tryptophan; Wound Healing

The aim of this study was to assess the gastric histopathology and serum gastrin-17 and pepsinogens profiles in patients with duodenal ulcer before and after Helicobacter pylori eradication in a population with a very high prevalence of H. pylori. At the same time we assessed the role of H. pylori density on these variables.. Eighty Caucasian patients with H. pylori-associated duodenal ulcer before treatment and 1 year after randomized eradication were studied. Among patients with unsuccessful eradication two groups were distinguished according to the data obtained after treatment: the group with negative rapid urease test and decreased bacterial density according to morphological score (partial elimination group); the group with positive rapid urease test and high bacterial density (failed eradication group).. One year after successful eradication, serum levels of gastrin-17, pepsinogen I and pepsinogen II decreased. Similar changes of serum pepsinogen I and pepsinogen II levels were observed in patients with partial elimination of H. pylori infection. In the group with successful eradication, inflammation, activity, atrophy and number of lymphoid follicles in the antral mucosa fell. In the group with partial elimination, antral mucosa activity and H. pylori score reduced. Other morphological changes were statistically non-significant.. Patients with duodenal ulcer after successful eradication have improvement of morphological and functional characteristics of gastric mucosa.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Biomarkers; Down-Regulation; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Proton Pump Inhibitors; Time Factors; Treatment Failure; Treatment Outcome; Urease; Young Adult

Helicobacter pylori (H. pylori) is an important pathogen in gastritis, peptic ulcer and possibly gastric cancer, but several questions remain unanswered. Particularly how the organism is transmitted and what is the relationship between oral presence of H. pylori and the gastric infection. Accordingly, we aimed to characterize the H. pylori in oral cavity and to evaluate its relationship to gastric H. pylori infection.. Out of total 100 screened for H. pylori infection female subjects (40 to 85 y), 49 patients (pts), who had positive C-urea breath test (UBT) and dyspeptic symptoms, agreed for 1 week regimen of triple anti-H. pylori therapy. The presence of H. pylori in oral cavity was assessed using bacterial culture from saliva and gingival pockets. Gastric H. pylori infection was estimated using capsulated C-urea breath test and plasma anti-H. pylori IgG and saliva IgA antibodies. In addition, plasma gastrin, ghrelin, and pepsinogen I were measured by radioimmunoassay. In selected patients, gastroscopy was additionally performed and gastric biopsy samples were taken for H. pylori random amplification of polymorphic DNA genetic profiling.. The triple therapy resulted in gastric H. pylori eradication in 79% pts, along with significant decrease of plasma gastrin combined with an increase in plasma ghrelin and pepsinogen I (PgI) levels and a marked alleviation of dyspeptic symptoms. In contrast to gastric effects, the eradication therapy failed to cause any changes in the presence of H. pylori in oral cavity. Moreover no relationship was observed between the presence of H. pylori in oral cavity and the gastric H. pylori eradication. In line with these findings, no relationship between gastric and oral H. pylori was found using genetic profiling by random amplification of polymorphic DNA.. H. pylori was detected both in the oral cavity and the stomach but oral H. pylori had no relation to gastric H. pylori and remained unaffected by eradication of gastric H. pylori.

Topics: Adult; Aged; Aged, 80 and over; DNA, Bacterial; Female; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Mouth; Pepsinogen A; Peptide Hormones; Random Amplified Polymorphic DNA Technique; Stomach; Treatment Outcome

The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg.. One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment.. At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment.. The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Enzyme Inhibitors; Esophagitis, Peptic; Female; Gastrins; Helicobacter Infections; Hernia, Hiatal; Humans; Male; Middle Aged; Mixed Function Oxygenases; Pepsinogens; Polymorphism, Genetic; Prospective Studies; Rabeprazole; Wound Healing

Prolonged gastric acid suppression leads to hypergastrinaemia, which promotes hyperplasia of the enterochromaffin-like (ECL) cells of the oxyntic mucosa. The objective was to determine the effects of 5 years of treatment with rabeprazole or omeprazole on the gastric mucosa.. Two hundred and forty-three patients received rabeprazole (20 mg or 10 mg) or omeprazole (20 mg) once daily for up to 5 years, for gastro-oesophageal reflux disease and 51% completed the whole 5 year period. Gastric biopsy specimens were taken and examined for gastritis, Helicobacter pylori infection, and ECL cell status.. H. pylori infection in the gastric corpus was more common than in the antrum, and remained constant, whereas antral H. pylori infection became less common as the study progressed. H. pylori infection was a highly significant predictor of higher gastritis scores, which were similar among the three treatment groups. ECL cell hyperplasia occurred in a minority of patients, and was associated with serum gastrin concentrations. No ECL cell dysplasia or tumours were observed. There were no significant differences among the treatment groups in gastritis or ECL cell hyperplasia grades.. This study has confirmed the link between ECL cell hyperplasia and elevated serum gastrin concentrations, but has found no evidence that this progresses to high grades of hyperplasia during 5 years of treatment with rabeprazole or omeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Biopsy; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Metaplasia; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Severity of Illness Index

To assess long-term effects of Helicobacter pylori (H pylori) eradication on antral G cell morphology and function in patients with and without duodenal ulcer (DU).. Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 H pylori positive patients, 8 had DU (H pylori +DU) and 31 gastritis (H pylori +G). Control groups consisted of 11 uninfected dyspeptic patients (CG1) and 7 healthy volunteers (CG2). Basal plasma gastrin (PGL), antral tissue gastrin concentrations (ATGC), immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy.. We demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy. Elevated PGL were registered in all H pylori+patients (H pylori +DU: 106.78+/-22.72 pg/mL, H pylori +G: 74.95+/-15.63, CG1: 68.59+/-17.97, CG2: 39.24+/-5.59 pg/mL, P<0.01). Successful eradication (e) therapy in H pylori+patients lead to significant decrease in PGL (H pylori+DU: 59.93+/-9.40 and H pylori +Ge: 42.36+/-10.28 pg/mL, P<0.001). ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in H pylori +gastritis, but not in DU patients. In the H pylori +DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups (P<0.01), but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased (P<0.01) in H pylori +Ge group after successful eradication therapy (294+/-32 and 0.31+/-0.02, respectively), in comparison to values before eradication (416+/-40 and 0.48+/-0.09). No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified.. H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function.

Topics: Adult; Anti-Bacterial Agents; Cell Count; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum

To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.. One hundred and seventy-eight consecutive Helicobacter pylori (H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.. There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values.. Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Topics: Atrophy; Biomarkers; Biopsy; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Mass Screening; Pepsinogen A; Precancerous Conditions; Sensitivity and Specificity

Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year.. To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years.. Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease.. One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated.. Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Prospective Studies; Rabeprazole; Recurrence; Treatment Outcome

The eradication of Helicobacter pylori decreases the antisecretory activity of omeprazole and lansoprazole. Rabeprazole is a potent proton pump inhibitor that may not be affected as greatly by H. pylori status.. To compare the effect of H. pylori eradication on intragastric acidity and plasma gastrin during dosing with lansoprazole, omeprazole, rabeprazole and placebo.. Twenty-four healthy H. pylori-infected volunteers were studied on day 7 of dosing with placebo, lansoprazole 30 mg, omeprazole 20 mg and rabeprazole 20 mg, before and at least 5 weeks after H. pylori eradication. On each occasion, the 24-h intragastric acidity was measured by gastric aspiration. Plasma gastrin concentrations were measured hourly from 08.00 to 13.00 h.. Sixteen subjects completed the study. For all three drugs and placebo, H. pylori eradication increased intragastric acidity, particularly nocturnal acidity, and decreased plasma gastrin. There were no differences between the three drugs with respect to 24-h acidity, percentage of time pH > 4 or 5-h plasma gastrin, either before or after H. pylori eradication. Before eradication, the percentage nocturnal time at pH > 3 was significantly greater during rabeprazole than during lanso-prazole dosing.. The increase in intragastric acidity seen after H. pylori eradication during dosing with proton pump inhibitors is a drug-class effect, particularly affecting nocturnal acid control. This is related to increased spontaneous intragastric acidity after H. pylori eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Breath Tests; Cross-Over Studies; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Omeprazole; Rabeprazole; Urea

The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long-term administration.. Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross-over study in which ranitidine and famotidine were administered for 14 days with a 4-week wash-out period. We performed 24-h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days.. The acid-inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH-increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged.. Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.

Topics: Adult; Biomarkers; Cross-Over Studies; Drug Tolerance; Famotidine; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Japan; Male; Middle Aged; Ranitidine; Reference Values; Time Factors; Treatment Outcome

To evaluate the effect of Helicobacter pylori (Hp) eradication therapy on blood gastrin levels in long-term PPI users, since proton pump inhibitors (PPIs) and Helicobacter pylori (Hp) are major causes of hypergastrinaemia.. A prospective study.. Twenty seven Hp (+) patients enrolled in the study. Twenty were given eradication treatment (ET group), and the rest were given symptomatic treatment (ST group). Those who remained Hp (+) after eradication therapy were also added into the ST group. Lansoprazol 30 mg/day was given to both groups for three months thereafter.. Fasting and non-fasting blood gastrin levels (FGL and NFGL) were measured initially and one month and four months after treatment. At the end of fourth month, FGL was significantly higher than both initial and first month level (p < 0.01) in the ST group. NFGL in this group did not change significantly (p > 0.05) after eradication therapy. In the ET group, FGL was significantly higher in the fourth month than the first month (p < 0.001) and than the initial level (p < 0.05). NFGL was higher, but not statistically in the fourth month than in the first month (p > 0.05) and significantly lower than the initial level (p < 0.05) in this group.. We suggest that testing for Hp positivity and treating it if detected would be an appropriate approach to avoid hypergastrinaemia, especially in candidate patients for long term PPI treatment.

Topics: Adult; Anti-Ulcer Agents; Esophagitis; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Prospective Studies; Proton Pump Inhibitors; Time

The aim of this study was to determine the effect of 6-12 months of treatment with esomeprazole on the histopathology of the gastric mucosa.. Two identically designed, randomized, placebo-controlled trials of esomeprazole 40, 20, or 10 mg daily for up to 6 months, as well as a noncomparative, multicenter trial of esomeprazole 40 mg daily for up to 12 months, were conducted in 1326 patients with healed erosive esophagitis (1294 negative for Helicobacter pylori [H. pylori]). Gastric biopsy samples were obtained before treatment and on completion of (or discontinuation from) the trials. Samples were evaluated for the presence of H. pylori, characteristics of acute gastritis or atrophic gastritis, and enterochromaffin-like cell pathology.. During treatment with esomeprazole, the number of patients with an improvement in gastric histological scores was typically greater than or equal to the number who worsened. Gastric histological scores worsened for each corporal or antral characteristic of gastritis in <6.2% of patients. Histological scores with esomeprazole and placebo were similar throughout the 6-month trials. Only one among 1326 patients treated with esomeprazole (H. pylori negative) had evidence of treatment-emergent atrophic gastritis. On final biopsy, 5-12% of patients had abnormal enterochromaffin-like cell scores (simple, linear, or micronodular hyperplasia). There were no instances of enterochromaffin-like cell dysplasia, carcinoids, or neoplasia.. Patients with healed erosive esophagitis receiving esomeprazole for up to 12 months had minor fluctuations in gastric histological scores, similar to those experienced in untreated populations. Use of esomeprazole did not raise any safety concerns with respect to the development of atrophic gastritis, or cause clinically significant changes in enterochromaffin-like cells.

Topics: Adult; Anti-Ulcer Agents; Enterochromaffin-like Cells; Esomeprazole; Esophagitis; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia

To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of alpha-interferon (IFN) treatment on autoimmune gastritis.. We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 12 months), c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies.. APCA positivity and 3-fold gastrin levels were detected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P<0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively, vs baseline; P=not significant vs end of treatment). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity.. In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies, development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.

Topics: Adult; Aged; Antiviral Agents; Autoimmune Diseases; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Organ Specificity; Parietal Cells, Gastric; Prevalence; Prospective Studies; Thyroid Gland; Treatment Outcome

The remnant stomach after surgery for gastric cancer is at high risk for the metachronous development of multiple gastric cancers. Here, we report on eradication therapy of Helicobacter pylori in the remnant stomach, comparing the eradication rate with that in unoperated stomachs. We examined gross and histological changes after treatment.. Forty H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based dual and triple therapies. After eradication, histological changes were classified on the basis of the updated Sydney system.. The eradication rate in the remnant stomach was 70% (14 of 20) after dual therapy and 90% (18 of 20) after triple therapy, using per-protocol analysis, and these rates were comparable to the rates of 70% (186 of 264) and 88% (58 of 66), respectively, in nonsurgery patients. After eradication, three sites in the remnant stomach showed similar histological changes: significant decreases in inflammation and activity scores (P < 0.001) and no significant changes in glandular atrophy and intestinal metaplasia scores.. PPI-based therapy was as effective for H. pylori eradication in the remnant stomach as in the unoperated stomach, and eradication therapy resulted in a significant decrease in inflammatory cell infiltration of the mucosal layer.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abietanes; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Biomarkers; Biopsy; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastrectomy; Gastric Stump; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Lansoprazole; Male; Middle Aged; Omeprazole; Pepsinogen A; Pepsinogen C; Proton Pump Inhibitors; Proton Pumps; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors; Treatment Outcome

: To investigate the effect of the eradication of Helicobacter pylori on histological gastritis.. : Twenty-six patients with moderate to severe atrophy received successful eradication therapy of H.pylori. Four patients dropped out and 22 were followed up prospectively for 5 years. The grades of gastritis were estimated from gastric biopsy specimens. The grade of intestinal metaplasia was also evaluated by dye-endoscopy using methylene blue (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti-parietal cell antibody were also determined.. : The grades of atrophy decreased in patients with successful eradication therapy in the gastric corpus (before vs. 5 years after eradication, 2.09 +/- 0.15 vs. 0.91 +/- 0.17; P < 0.01) and in the antrum (2.14 +/- 0.17 vs. 1.36 +/- 0.17; P < 0.01). The levels of intestinal metaplasia were also decreased in the corpus (0.91 +/- 0.24 vs. 0.50 +/- 0.16; P < 0.05) and in the antrum (1.41 +/- 0.20 vs. 1.00 +/- 0.16; P < 0.05), which was also demonstrated by the methylene blue (methylthioninium chloride) staining method (33.4 +/- 8.2% vs. 23.0 +/- 6.5%; P < 0.05). The improvement of corpus atrophy correlated well with the high serum level of pepsinogen I (P = 0.005), but showed no correlation with the levels of anti-parietal cell antibody.. : These results suggest that gastric atrophy and intestinal metaplasia are reversible events in some patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Biomarkers; Drug Therapy, Combination; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Intestines; Male; Metaplasia; Methylene Blue; Middle Aged; Pepsinogens; Precancerous Conditions; Prognosis; Prospective Studies; Stomach Neoplasms

Helicobacter pylori infection induces atrophic body gastritis, but the long-term effect of its cure on body atrophy is unclear.. To investigate the long-term effects of H. pylori cure on gastric morpho-functional parameters in patients with atrophic body gastritis.. Forty patients with atrophic body gastritis were cured of H. pylori infection. Gastroscopy with biopsies, gastrin and pepsinogen I levels and basal and stimulated acid secretion were evaluated before and 6-12 months after treatment.. At eradication assessment (6-12 months), in eight of the 40 patients, body atrophy was no longer observed, whereas in 32 of the 40 it remained substantially unchanged (2.03 +/- 0.12 vs. 1.83 +/- 0.15). In the eight patients with reversed body atrophy, gastrinaemia decreased significantly with respect to pre-treatment values (265 +/- 59.9 pg/mL vs. 51.8. +/- 6.04 pg/mL), and basal and stimulated acid secretion increased significantly after cure. In the 32 patients still presenting body atrophy, gastrinaemia was similar topre-treatment values (457 +/- 76.04 pg/mL vs. 335.1 +/- 58.8 pg/mL). At follow-up (21-25 and 32-70 months), the eight patients with reversed body atrophy continued with normal gastrinaemia (35.3 +/- 10.1 pg/mL vs. 38.5 +/- 8.8 pg/mL), but in the 19 patients with continued atrophy, both corporal atrophy and intestinal metaplasia remained substantially unchanged.. Following successful treatment in patients with atrophic body gastritis and H. pylori infection, long-term histological investigations are crucial in order to detect reversed body damage or to confirm continued body atrophy.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Prospective Studies

Helicobacter pylori causes gastric adenocarcinoma. We assessed the success of H. pylori eradication therapy in a medically underserved population in Chiapas, Mexico, that is at high risk for gastric cancer risk.. Healthy volunteers with both antibodies to CagA and gastrin levels > or = 25 ng/ml were randomly assigned to receive either a combination of omeprazole, amoxicillin, and clarithromycin or matched placebo for 1 wk. Endoscopy with seven biopsies was performed at baseline, at 6 wk, and 1 yr after treatment. Treatment success was defined as loss of H. pylori by histological analysis. Cure was assessed using change in serology based on the standardized absorbance of a H. pylori ELISA.. H. pylori eradication rates were high (intent-to-treat analysis: 76.3% [95% CI = 68.7-84.0%] after 6 wk and 76.1% [95% CI = 67.7-84.6%] after 1 yr; per protocol analysis: 77.8% [95% CI = 70.1-85.4%] after 6 wk and 75.2% [95% CI = 66.5-84.0%] after 1 yr). Nine subjects on active treatment and one subject on placebo who were without H. pylori at 6 wk were infected at 1 yr (recurrence rates 10.7% and 33.3%, respectively, p = 0.31). Median changes in standardized absorbance at 1 yr were 47% and 1% for successfully and unsuccessfully treated patients, respectively. A 10% decline in standardized absorbance after 1 yr had 84% sensitivity and 100% specificity for H. pylori eradication.. Even with a short course of treatment against H. pylori, a high rate of eradication rate can be achieved in populations at high risk for stomach cancer. Serum antibodies are useful in assessing efficacy of therapy.

Topics: Adenocarcinoma; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Clarithromycin; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Omeprazole; Penicillins; Precancerous Conditions; Recurrence; Risk Factors; ROC Curve; Stomach Neoplasms

This study of patients with Helicobacter pylori infection and low-grade MALT lymphoma aimed to investigate: 1) the effect of H. pylori eradication therapy on the serum gastrin level, 2) whether changes of the serum gastrin level after therapy could predict the prognosis of patients with this tumour, and 3) the relationship between the gastric H. pylori load, the serum gastrin level and the status of MALT lymphoma.. Thirteen patients with documented low-grade MALT lymphoma and H. pylori infection were enrolled and received H. pylori eradication therapy as the sole initial treatment. The presence of H. pylori, the serum gastrin level, the endoscopic findings, the pathologic features of the biopsies and resected specimens, and the endoscopic ultrasonography findings were evaluated before and after therapy. Follow-up was carried out every 3-6 months.. H. pylori eradication was eventually achieved in all 13 patients. The pretreatment fasting serum gastrin level decreased from 177.1 +/- 107.4 pg/ml to 129.2 +/- 78.1, 96.4 +/- 66.6 and 80.1 +/- 42.7 pg/ml after 0-3, 3-6 and 6-9 months, respectively (all P < 0.05). Successful eradication of H. pylori was followed by a decrease of the fasting serum gastrin level and complete regression of initial low-grade MALT lymphoma was observed in all patients. However, two patients subsequently developed recurrent high-grade MALT lymphoma or high-grade lymphoma. In one of them, the serum gastrin level rose again above the pretreatment value. In the other, however, the fasting gastrin level fell throughout the study period. The median fasting serum gastrin level before H. pylori eradication therapy was higher in the patients with tumours of the gastric body (203.4 +/- 108.9 pg/ml) than in those with tumours of the antrum and angulus (89.3 +/- 28.0 pg/ml) (P = 0.06).. Hypergastrinaemia may be associated with an increased risk of gastric MALT lymphoma.

Topics: Adult; Aged; Anti-Bacterial Agents; Biomarkers; Drug Therapy, Combination; Female; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Male; Middle Aged; Probability; Prognosis; Proton Pump Inhibitors; Sensitivity and Specificity; Statistics, Nonparametric; Treatment Outcome

We investigated an antiinflammatory effect of rebamipide [2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid], a gastroprotective agent, in H. pylori-associated gastritis. Eighty-six patients with H. pylori-positive chronic gastritis were enrolled: 53 were treated with rebamipide (300 mg daily for 12 months) and 33 served as controls. Significant decreases in mononuclear cell infiltration into the antrum and corpus were noted in the rebamipide treatment group (before vs after, 1.42 +/- 0.15 vs 1.02 +/- 0.15; P < 0.01 and 1.60 +/- 0.15 vs 1.21 +/- 0.14; P < 0.05, respectively). Levels of infiltrating neutrophil were also decreased in the antrum (before vs after, 0.98 +/- 0.14 vs 0.70 +/- 0.13; P < 0.05) and were associated with a decrease in iNOS production. Sera from patients treated with rebamipide showed a significant decrease in gastrin (276.3 +/- 58.3 pg/ml vs 173.0 +/- 34.2 pg/ml; P < 0.05), whereas no change was observed in the control group. These suggest that long-term rebamipide treatment improved histologic gastritis and decreased serum gastrin levels in H. pylori-associated gastritis.

Topics: Alanine; Anti-Ulcer Agents; Drug Administration Schedule; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pepsinogens; Quinolones; Stomach

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Topics: Adult; Age Distribution; Aged; Biomarkers; Biopsy, Needle; Chronic Disease; Confidence Intervals; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Mass Screening; Mexico; Middle Aged; Pepsinogen A; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Sex Distribution

Body-predominant atrophic gastritis is considered a risk factor for gastric cancer and carcinoid. Timing of follow-up for patients with this disorder has not been defined. This study was undertaken to determine the optimal time for the first endoscopic/histologic follow-up in patients with body-predominant atrophic gastritis.. Forty-two patients with body-predominant atrophic gastritis were randomly assigned to 1 of 2 follow-up intervals: group A (n = 22) at 24 months and group B (n = 20) at 48 months. At baseline and follow-up patients underwent gastroscopy at which biopsies were obtained from the antrum and body for histopathology and evaluation for enterochromaffin-like cells.. In group A patients, 2 antral hyperplastic polyps (9.1%) were present at baseline and 4 antral hyperplastic polyps (18.2%) were found at follow-up. In group B patients, baseline gastroscopy revealed 2 antral hyperplastic polyps (10%) and follow-up 2 antral hyperplastic polyps (10%) and 1 carcinoid tumor (5%) in the body. Atrophy and intestinal metaplasia scores in gastric body and antral mucosa in both groups did not change significantly between baseline and follow-up, except an increase in antral mucosa atrophy in group B patients (p = 0.02) was revealed.. The results of this study indicate that performing the first follow-up in patients with body-predominant atrophic gastritis need not be earlier than at 4 years after diagnosis. This interval is satisfactory for detection of potential neoplastic lesions.

Topics: Adult; Aged; Anemia, Pernicious; Biopsy; Carcinoid Tumor; Enterochromaffin-like Cells; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Polyps; Prospective Studies; Pyloric Antrum; Random Allocation; Stomach Neoplasms; Time Factors

Increased gastric emptying and defective action of endogenous cholecystokinin (CCK), that is known to inhibit this emptying, have been implicated in the pathogenesis of duodenal ulcer (DU). The aim of this double blind study was to assess whether CCK and somatostatin participate in the impairment of gastric motility in active DU patients before and after Helicobacter pylori eradication.. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide, a selective CCK-A receptor antagonist, before and 4 weeks after eradication of H. pylori with 1 week triple therapy that resulted in healing of all DUs tested. The gastric emptying rate after feeding was determined using the 13C-acetate breath test. Before each test, samples of gastric juice were obtained by aspiration using a nasogastric tube for determination of somatostatin using specific radioimmunoassay.. Prior to H. pylori eradication gastric emptying half-time was 31 +/- 6 min in placebo-treated DU patients and this emptying rate was not significantly affected in tests after pretreatment with loxiglumide (10 mg/kg i.v.). Following eradication of H. pylori, in tests with placebo gastric emptying half-time was significantly longer (48 +/- 9 min) compared to that prior to H. pylori eradication. Pretreatment with loxiglumide in H. pylori eradicated DU patients significantly enhanced the gastric emptying rate with an emptying half-time of only 33 +/- 4 min. Eradication of H. pylori resulted in a significant increase in somatostatin concentration in gastric juice and loxiglumide significantly reduced this luminal somatostatin in H. pylori-eradicated subjects compared to values before anti-H. pylori therapy.. 1) H. pylori infection in DU patients is accompanied by enhanced gastric emptying and reduction in luminal release of somatostatin; 2) the failure of loxiglumide to affect gastric emptying in H. pylori-infected DU patients might be attributed, at least in part, to the failure of endogenous CCK to control gastric motility due to deficient release of somatostatin; and 3) H. pylori-infected patients appear to exhibit a deficient somatostatin release by endogenous CCK that can be reversed by the eradication of H. pylori indicating that both CCK and somatostatin may contribute to normalization of gastric emptying following H. pylori eradication in DU patients.

Topics: Adolescent; Adult; Analysis of Variance; Cholecystokinin; Duodenal Ulcer; Follow-Up Studies; Gastric Emptying; Gastric Mucosa; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Hormone Antagonists; Humans; Injections, Intravenous; Male; Postprandial Period; Probability; Proglumide; Reference Values; Sensitivity and Specificity; Somatostatin; Sucralfate; Treatment Outcome

S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism.. To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status.. Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose.. Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups.. The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cross-Over Studies; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Female; Gastric Acidity Determination; Gastrins; Genotype; Helicobacter Infections; Humans; Male; Mixed Function Oxygenases; Omeprazole; Polymorphism, Genetic; Rabeprazole

Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology.. One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis.. This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease.. Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Cell Count; Drug Resistance; Enteroendocrine Cells; Enzyme Inhibitors; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Recurrence; Sulfoxides

The effects of H. pylori eradication on atrophic body gastritis are controversial.. To investigate the effect of triple therapy on atrophic body gastritis in H. pylori-positive patients and its effect on morpho-functional gastric parameters.. Thirty-five consecutive atrophic body gastritis patients with histological/serological evidence of H. pylori infection were treated. Before and 6 and 12 months after H. pylori eradication the patients were evaluated for fasting gastrinemia and pepsinogen I, basal and peak acid output, and detailed histological assessment including the ECL cell proliferative patterns.. Six months after treatment, 25 out of 32 patients were cured (78%). Cure of infection was associated with improvement in both basal (basal acid output mean 0.23 +/- 0.14 mmol/h vs. 1.75 +/- 0.7 mmol/h, P < 0.005) and stimulated acid secretion (peak acid output mean 3.0 +/- 1.06 mmol/h vs. 16.6 +/- 4.1 mmol/h, P=0.0017) as well as with reduction in hypergastrinemia (mean gastrin levels 444.1 +/- 110.7 pg/mL vs. 85.3. +/- 28 pg/mL; P < 0.005). In contrast, the eradication had no effect on body corporal atrophy and intestinal metaplasia, or pepsinogen I levels (mean 16.6 +/- 2.9 ng/mL vs. 14.2 +/- 2.1 ng/mL, N.S.). These results were confirmed at 12 months after eradication. A statistical inverse correlation was obtained (r=-0.3635, P < 0.05) between the corporal chronic infiltrate score and peak acid output values. A total of 53% of atrophic body gastritis patients showed a regression in severity of body ECL cell hyperplastic change.. Cure of H. pylori infection in patients with atrophic gastritis reverses some adverse effects on gastric function and ECL cell hyperplasia. H. pylori infection may be cured in atrophic body gastritis patients with partial reversion of its negative consequences on acid secretion and body ECL cell hyperplasia.

Topics: Adult; Aged; Enterochromaffin Cells; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Middle Aged; Pepsinogen A; Prospective Studies; Treatment Outcome

Gastric atrophy is associated with Helicobacter pylori infection. Conflicting results have been obtained as to whether acid suppressant therapy hastens the development or changes the distribution of atrophy in the stomach. The aim of this study was to investigate whether concomitant proton pump inhibitor (PPI) therapy in H. pylori-infected individuals resulted in an increase or an alteration in atrophy distribution and whether this was reflected by the plasma gastrin.. Multiple gastric biopsy specimens were taken from the antrum and corpus from 46 H. pylori-infected subjects, 18 of whom were taking PPIs, and assessed histologically by the updated Sydney System. The control group was age- and sex-matched to the index group. Fasting gastrin levels were measured.. In the control group there was no significant tendency for either antral or corpus atrophy to predominate (P = 0.44). In the treatment group there was a significant tendency for corpus as opposed to antral atrophy to develop (P < 0.001). There was no significant difference in the overall atrophy score between the treated and untreated groups (P = 0.76). Fasting gastrin levels were significantly higher in the treated group (P < 0.001).. Treatment with PPIs in H. pylori-infected subjects does not lead to an overall increase in gastric atrophy. It does, however, result in an increased prevalence of corpus as opposed to antral atrophy. This is associated with a significantly higher gastrin level.

Topics: Adult; Age Factors; Aged; Atrophy; Biopsy, Needle; Enzyme Inhibitors; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Radioimmunoassay; Reference Values; Statistics, Nonparametric; Stomach

There is accumulating evidence for the role of Helicobacter pylori in the development of gastric cancer as well as of lymphomas that arise in mucosa-associated lymphoid tissue (MALT). We reported recently that gastric cancer patients show high prevalence of cagA-positive H. pylori and express gastrin and gastrin receptors enabling them to stimulate tumour growth in autocrine fashion.. Since the H. pylori infection is considered to be more strongly associated with MALT lymphoma than with gastric cancer, we decided to determine the gastrin and its receptors' mRNA expression and gastrin content in this tumour as well as the release of this hormone both into plasma and gastric lumen. Twenty MALT lymphoma patients were compared with 100 age- and gender-matched controls with similar dyspeptic symptoms.. The overall H. pylori seropositivity in MALT lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%, respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold higher than in controls while gastric luminal gastrin in these patients was over 70 times higher than in controls. Gastrin content in tumour was about 10-fold higher than in antral mucosa. Gastrin and gastrin-receptor (CCKB-receptor) mRNA were detected by reverse transcriptase-polymerase chain reaction in cancer tissue whilst in the fundic and antral mucosa, only enhanced expression of CCKB-receptor mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT lymphoma induced acid secretion that was only about 30% of control value due to atrophic gastritis. This study confirms an important role of CagA-positive H. pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is capable of synthesizing and releasing potent growth promoting gastrin, possibly due to the action on G-cells of H. pylori-originated Nalpha-methyl histamine and cytokines (tumour necrosis factor alpha and interleukin-8).. Gastric MALT lymphoma is closely linked to CagA-positive H. pylori infection. Gastrin and its receptors may be implicated in the pathogenesis of gastric lymphoma.

Topics: Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Cytokines; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Interleukin-8; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged; Radioimmunoassay; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms

Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure.. To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell.. In a randomized, crossover, double-blind study, 24-h intragastric pH was measured in 13 H. pylori-positive subjects before and after a 1-week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured.. In the absence of drug administration, the median 24-h pH values before cure (median 2.0, 90% CI: 1.2-3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3-2.2; P = 0.115). The 24-h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8-6.7 vs. 4.3, 2.6-5.7; P = 0.002) and omeprazole (5.8, 4.0-6.2 vs. 3.6, 2.8-5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24-h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 x 10-4- 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 x 10-3-1.5; P = 0.6).. Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24-h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH-increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.

Topics: Adult; Antacids; Anti-Ulcer Agents; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Imidazoles; Male; Omeprazole; Proton Pump Inhibitors; Pyridines; Stomach

Omeprazole is metabolized by genetically determined S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. This study aimed to determine whether the effect of omeprazole on intragastric pH depends on CYP2C19 genotype status.. CYP2C19 genotype status for 2 mutations associated with the poor metabolizer phenotype was determined by a polymerase chain reaction-restriction fragment length polymorphism method in 16 healthy volunteers. Helicobacterpylori status was determined by serology and the [13C]urea breath test. After a single oral administration of 20 mg omeprazole or a placebo, intragastric pH values were recorded for 24 hours. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured before and 1, 2, 3, 5, 7, 10, and 24 hours after administration.. Fifteen of the 16 subjects were H pylori negative. Five of the 15 subjects were homozygous extensive metabolizers, 4 were heterozygous extensive metabolizers, and 6 were poor metabolizers. After omeprazole administration, significant differences in mean intragastric pH values and plasma levels of gastrin, omeprazole and its metabolites were observed among the 3 groups, whereas no significant differences in these parameters were observed with the placebo administration.. The effect of omeprazole on intragastric pH significantly depends on CYP2C19 genotype status. The genotyping test of CYP2C19 may be useful for an optimal prescription of omeprazole.

Topics: Adult; Anti-Ulcer Agents; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Asian People; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Female; Gastric Mucosa; Gastrins; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Japan; Male; Mixed Function Oxygenases; Omeprazole; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Reference Values; Stomach

A hypothesis suggesting that profound acid inhibition therapy facilitates and hastens the development of gastric glandular atrophy in patients infected with Helicobacter pylori was investigated in this randomized study comparing omeprazole therapy with antireflux surgery (ARS) for chronic gastroesophageal reflux disease (GERD).. Patients with esophagitis and/or chronic GERD were enrolled; 155 patients were randomized to ARS and 155 to long-term omeprazole therapy. Baseline data were obtained and repeated after 3 years in 131 ARS patients and in 139 omeprazole-treated patients. Histopathologic status of the oxyntic mucosa was assessed according to the Sydney system.. Forty omeprazole-treated patients were infected with H. pylori compared with 53 in the ARS group. Basal gastrin levels were significantly higher in H. pylori-infected patients, particularly in the omeprazole group. No further increases in serum gastrin levels were observed during 3 years. Despite 3 years of therapy, only slight changes were found in the prevalence of inflammation in the corpus mucosa of H. pylori-infected subjects. A slow progression of gastric glandular atrophy was observed in these patients irrespective of therapy with no obvious difference between treatment regimens. Intestinal metaplasia (all of type I) was only exceptionally observed with no difference between the treatment arms.. Acid-suppressive therapy in the form of omeprazole maintained for 3 years facilitates neither the development of gastric glandular atrophy of the corpus mucosa nor the occurrence of intestinal metaplasia in H. pylori-infected GERD patients.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Atrophy; Esophagitis; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Prospective Studies

Gastric acid secretion, gastrin release, gastric emptying, and gastroesophageal acid reflux were measured in asymptomatic individuals before and after elimination of Helicobacter pylori gastritis. After basal gastric acid secretion and serum gastrin concentrations were measured, meal-stimulated gastric acid secretion and gastrin release were assessed during in vivo intragastric titration to pH 3. Experiments were repeated 4 wk after treatment with lansoprazole, amoxicillin, and clarithromycin. Esophageal pH was also monitored for 24 h before and after therapy. Basal gastric acidity increased approximately 20 mmol/l in subjects whose infection was eradicated (P < 0.05) but not in those with persistent infection. Basal and meal-stimulated gastric acid secretion did not change after H. pylori eradication, despite a 41% reduction in meal-stimulated gastrin release (P < 0.05). Gastroesophageal acid reflux increased two- to threefold after successful treatment (P < 0. 05) but did not change in subjects with persistent infection. Thus elimination of H. pylori gastritis increases gastric acidity, probably by reducing nonparietal alkaline secretion, and this may facilitate gastroesophageal acid reflux.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Esophagitis; Female; Food; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Monitoring, Physiologic; Omeprazole; Penicillins; Polyethylene Glycols; Postprandial Period; Solvents

Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man.. To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment.. Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment.. In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95).. Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

Topics: Adult; Alginates; Aluminum Hydroxide; Amoxicillin; Antacids; Anti-Ulcer Agents; Drug Combinations; Drug Therapy, Combination; Esophagitis; Female; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Silicic Acid; Sodium Bicarbonate

Rabeprazole, a new proton pump inhibitor, was studied in patients with acid-peptic-related diseases (duodenal ulcer, gastric ulcer, GERD) in three placebo-controlled, double-blind, randomized clinical trials. Men and women over the age of 18 were enrolled if the presence of an active duodenal or gastric ulcer or erosive or ulcerative esophagitis was confirmed on upper gastrointestinal endoscopy. Patients were randomly allocated to either placebo or rabeprazole 20 mg or 40 mg in the duodenal and gastric ulcer protocols or to placebo or rabeprazole 10 mg, 20 mg, or 40 mg in the GERD protocol. All doses of rabeprazole in all three studies were statistically significantly superior to placebo in healing acid-related lesions. There were no treatment differences between the rabeprazole doses in healing active peptic lesions. The incidence of positive [13C]urea breath test for H. pylori was 53% in patients with duodenal or gastric ulcers. H. pylori status was not effected by treatment with rabeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Breath Tests; Dose-Response Relationship, Drug; Double-Blind Method; Duodenal Ulcer; Enzyme Inhibitors; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Proton-Translocating ATPases; Rabeprazole; Stomach Ulcer; Treatment Outcome

To date, it is unclear whether Helicobacter pylori infection is associated with disturbances of gastric emptying or acid secretion in patients with functional dyspepsia (FD). Our aim was to investigate whether, in the long run, cure of H. pylori infection significantly influences gastric emptying of solids, acid secretion, and gastrin and pepsinogen I (PGI) release in patients with FD.. Thirty-eight consecutive H. pylori-positive patients with FD, whose complaints were scored for severity and frequency on the basis of a validated symptom questionnaire, were initially enrolled in the study. They were randomized to receive an eradicating regimen consisting of omeprazole plus clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks. In 33 patients (18 H. pylori-cured and 15 with persistent infection) basal and pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin concentrations, fasting serum PGI levels, and gastric emptying of solids were determined before and 6 months after therapy.. In the 18 H. pylori-cured patients meal-induced gastrin and fasting PGI levels were significantly reduced after 6 months as compared with pretreatment values (peak serum gastrin, 76.0 +/- 23.4 versus 111.9+/-37.4 pg/ml; PGI, 57.1+/-23.4 versus 72.9+/-29.1 ng/ml), whereas they remained virtually unchanged in the 15 patients with persistent infection. In contrast, both basal and stimulated acid secretion and gastric emptying time of solids remained unmodified over time in both groups of patients.. We confirm that also in patients with functional dyspepsia H. pylori eradication in the long run significantly reduces gastrin and PGI release as a result of improvement in the underlying antral gastritis, but this is not accompanied by modifications of gastric emptying of solids or acid secretion.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Drug Therapy, Combination; Dyspepsia; Female; Gastric Acid; Gastric Emptying; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Pepsinogens; Prospective Studies; Ranitidine; Tinidazole; Treatment Outcome

elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD).. A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT).. Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response.. Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

Topics: Aged; Anti-Ulcer Agents; Area Under Curve; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Omeprazole; Pancreatic Polypeptide; Vagus Nerve

A cross sectional study was designed to elucidate the factors influencing the argyrophil cell population in patients with gastroesophageal reflux disease treated with omeprazole (N = 201) or H2-receptor antagonists (N = 118) and in control patients (N = 215). Fasting gastrinemia and Helicobacter pylori serology were determined. Gastritis, Helicobacter pylori infection, and argyrophil cell density and hyperplasia were evaluated in gastric biopsies. The argyrophil cell density was higher in both treatment groups than in controls (P = 0.002 and P = 0.051), whereas argyrophil cell hyperplasia was similar in the three groups. According to multivariate analysis, positive Helicobacter pylori serology was an independent parameter that decreased both density and grade of hyperplasia of argyrophil cells. Female gender and hypergastrinemia were independent factors increasing argyrophil cell density and hyperplasia, whereas antisecretory therapy, age and active gastritis were not. In addition, atrophic gastritis independently increased argyrophil cell hyperplasia. The prevalence of atrophic gastritis was significantly higher in Helicobacter pylori-positive than in negative patients and lower in the patients treated long-term with omeprazole than in the other groups.

Topics: Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Cell Count; Cross-Sectional Studies; Enterochromaffin-like Cells; Esophagitis, Peptic; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hyperplasia; Male; Middle Aged; Multivariate Analysis; Omeprazole; Sex Factors

Helicobacter pylori infection is common in patients with hyperplastic gastric polyps.. To study the effect of eradication of H. pylori on the clinical course of patients with hyperplastic gastric polyps.. Single-blind, randomized, controlled trial.. University-based gastroenterology outpatient clinic.. 35 patients with H. pylori infection and hyperplastic gastric polyps at least 3 mm in diameter.. Patients were randomly assigned to a treatment group (n = 17), which received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium, or to a control group (n = 18), which received no treatment.. Patients underwent endoscopy before enrollment and 12 to 15 months after the end of treatment. Serum gastrin levels and titers of IgG to H. pylori were measured.. In the treatment group, the polyps had disappeared by 3 to 15 months (average, 7.1 +/- 1.2 months) after the end of treatment in 12 of all 17 patients (71%) and in 12 of the 15 patients (80%) in whom H. pylori was eradicated. However, 12 to 15 months after the start of the study, no change in polyps or H. pylori status was seen in any controls (P < 0.001). Histologic findings of inflammation and activity, serum gastrin levels, and titers of IgG to H. pylori showed significant regression in the treatment group compared with the control group (P < 0.01).. Most hyperplastic polyps disappeared after eradication of H. pylori. Thus, eradication should be attempted before endoscopic removal is done in patients with hyperplastic gastric polyps and H. pylori infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abietanes; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Diterpenes; Drug Therapy, Combination; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Immunoglobulin G; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Polyps; Proton Pump Inhibitors; Single-Blind Method; Statistics, Nonparametric; Stomach Neoplasms

Treatment with H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecretion of gastric acid after treatment, and during treatment with H2RAs tolerance develops. In the present study we investigated whether a treatment period with a PPI induced tolerance to an H2RA.. Thirteen patients with esophagitis were given omeprazole for 90 days. Twenty-four-hour pH monitorings without and with ranitidine were performed before and after treatment with omeprazole. Blood samples and biopsy specimens from the oxyntic mucosa were analyzed for gastrin, histamine, and chromogranin A.. An increase in mucosal histamine and a reduction in the effect of ranitidine on gastric pH was found 14 days after discontinuing omeprazole compared with before treatment in Helicobacter pylori-negative but not in H. pylori-positive patients.. Treatment with omeprazole reduces the effect of ranitidine in H. pylori-negative patients. This is caused by an increase in histamine released by the enterochromaffin-like cell secondarily to hypergastrinemia, corresponding to the tolerance towards H2RAs seen in patients with Zollinger-Ellison syndrome.

Topics: Adult; Aged; Chromogranin A; Chromogranins; Drug Tolerance; Esophagitis; Female; Gastric Acid; Gastrins; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Histamine Release; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Ranitidine

We designed this study to follow exocrine, endocrine and microstructural changes in duodenal ulcer patients with H. pylori infection in the course and after quadruple eradication regimen. Quadruple therapy appeared to be highly effective method of both ulcer healing and H. pylori eradication. We observed enhanced regeneration of gastric mucosa in the course of treatment. Almost immediate decrease of plasma gastrin and increase of plasma somatostatin and EGF concentration in gastric juice were noticed.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Somatostatin

Microstructural, endo- and exocrine changes in gastric mucosa of Non-Ulcer Dyspepsia patients with H. pylori infection in the course of eradication has been studied. Before, during and after anti H. pylori therapy plasma gastrin and somatostatin levels, EGF and somatostatin concentration in gastric juice and basal and pentagastrin stimulated gastric acid secretion were measured. Moreover microstructure of gastric mucosa specimens has been studied. Maximal Acid Output initially higher in NUD patients than in healthy volunteers increased slightly in the course of eradication. Plasma gastrin decreased while EGF and somatostatin concentration in gastric juice increased. After treatment the ratio of patients with pronounced features (activity) of gastritis was significantly reduced.

Topics: Amoxicillin; Bismuth; Dyspepsia; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Somatostatin; Stomach Ulcer

Recently, we postulated a new concept of duodenal ulcer pathogenesis suggesting that antral Helicobacter pylori infection blocks inhibitory pathways to the gastrin and parietal cells, resulting in an increased and prolonged postprandial acid secretion. the aim of this study was to examine duodenal acid load and duodenal bulb pH after a meal before and after eradication of H. pylori.. Using a marker-dilution method and a pH electrode in the duodenal bulb, gastric emptying, acid secretion, gastrin release, duodenal acid load, and duodenal bulb pH were studied during 2 hours after peptone meals of pH 7.0 and 2.0 in 8 H. pylori-negative controls and 8 H. pylori-infected subjects before and 6 months after eradication.. The H. pylori-infected subjects had an increased gastric emptying, gastrin release, and acid secretion, higher duodenal acid load, and lower duodenal bulb pH after the meals. These responses were normalized after eradication.. H. pylori-infected subjects have an increased and prolonged postprandial acid secretion, partly caused by an impaired low pH inhibition of acid secretion, gastrin release, and gastric emptying, resulting in an increased duodenal acid load and a prolongation of low pH in the duodenal bulb, as a general prerequisite for the development of duodenal ulcer disease.

Topics: Adult; Duodenum; Eating; Female; Gastric Acid; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged

Helicobacter pylori (Hp) infection may be associated with duodenal ulcer (DU) and accompanied by increased release of gastrin and deficiency of somatostatin (S-S) but the mechanisms of these changes in DU patients after eradication of Hp have been little studied. Cholecystokinin (CCK) has been implicated in the feedback control of gastric acid secretion in healthy subjects but its contribution to secretory disorders in DU patients has been little examined. This study, therefore, investigated whether CCK participates in the impairment of postprandial gastrin release and gastric acid secretion in active DU patients. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide (LOX), a selective CCK-A receptor antagonist, before and 4 wk. after eradication of Hp with triple therapy (omeprazole, amoxycillin and bismuth). In Hp positive DU patients, the postprandial acid secretion (measured by continuous intragastric pH monitoring) was accompanied by a pronounced increment in plasma gastrin with negligible increase of intraluminal release of S-S. The administration of LOX in these patients did not affect significantly the postprandial pH profile and the rise in plasma gastrin. After eradication of Hp the median postprandial intragastric pH increased to about 4.3 (compared to 3.5 before the Hp eradication); the postprandial gastrin concentration was reduced by about 40%, while luminal release of S-S was increased 2 folds. The administration of LOX resulted in significantly greater decrease in median pH (3.1) and higher rise in postprandial plasma gastrin in these patients. Also the postprandial plasma S-S showed a small, but significant decline (by about 25%) as compared to that in placebo treated patients. This study provides evidence that: (1) Hp infection in DU patients is accompanied by enhanced gastrin release and the reduction in luminal release of S-S; (2) The failure of LOX to affect gastric secretion and plasma gastrin DU Hp infected patients could be attributed, at least in part, to the failure of endogenous CCK to control gastric acid secretion via release of S-S; (3) Hp infected patients appear to exhibit a deficiency of S-S release that can be reversed by the eradication of Hp indicating that both peptides may contribute to the acceleration of the ulcer healing following Hp eradication in DU patients; (4) The test with LOX and gastric luminal S-S assay may be useful in identification of Hp po

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormone Antagonists; Humans; Male; Proglumide; Somatostatin

We defined optimal Helicobacter pylori (Hp) treatment as Hp eradication rate about 90%, well-tolerated with few side-effects. Two centers carried out randomized trials including 90 patients (74% men, 26% women, ages ranging from 18 to 65, mean age 42 +/- 8) with active duodenal ulcers (DU). Patients were treated with the combination of Omeprazole (O) 20 mg bd + Clarithromycin (C) 250 mg bd + Tinidazole (T) (500 mg bd) or with Lansoprazole (L) 15 mg bd + Amoxicillin (A) 750 mg bd + Metronidazole (M) 500 mg bd administered for one week. The DU healing rate was evaluated by endoscopy and the Hp status by rapid urease CLO-test and 14C-urea breath test (UBT). The healing rate of the DU in a group treated with the combination of O + C + T was 91% and in group treated with L + A + M was 93%. The eradication of Hp in group O + C + T and L + A + M averaged 91% and 87%, respectively. There was no statistically significant difference in the DU healing rate and the Hp eradication rate between these two groups. Both treatments were accompanied by a marked rise in the basal and postprandial plasma gastrin levels and the rise in the intragastric pH but these alterations returned to the pre-treatment values 4 weeks after the termination of the therapy. Both treatments were well tolerated and the only side effect was the taste disturbance observed in few patents treated with O + C + T. None of patients discontinued the treatment because of the adverse events. We conclude that one week treatment using O + C + T or L + A + M are highly and equally effective in the healing of DU and in the eradication of Hp.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antitrichomonal Agents; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Tinidazole

The aim of the present study was to examine the efficacy and safety of combination therapy with amoxicillin (AMPC), lansoprazole, and plaunotol for the eradication of H. pylori in dialysis patients. The subjects consisted of 15 dialysis patients (10 men and 5 women, mean age of 56 +/- 2.4 years) in whom H. pylori was found in the stomach. H. pylori status was evaluated by histology, culture and rapid urease test with biopsy specimens of the gastric mucosa. The patients were treated with AMPC 500 mg once a day for 3 weeks, lansoprazole 30 mg once a day for 8 weeks and plaunotol 80 mg three times a day for 24 weeks. In addition, the concentrations of serum gastrin and gastric juice ammonia were measured. Fourteen patients completed the treatment schedule, while one discontinued treatment because of nausea and diarrhea. Among the 14 patients, H. pylori was eradicated in 11 without any side effects (eradication rate 78.6%). Concentrations of gastric juice ammonia and serum gastrin were reduced significantly in patients who became H. pylori-negative. The present study indicates that combination therapy with AMPC, lansoprazole and plaunotol is safe and efficient for the eradication of H. pylori in dialysis patients. The results also suggested that elevated concentrations of gastric juice ammonia and serum gastrin in dialysis patients can be attributed, at least in part, to H. pylori infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Ammonia; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Diterpenes; Drug Therapy, Combination; Fatty Alcohols; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Combination therapy with lansoprazole (LPZ) and amoxicillin (AMPC) was administered to eradicate Helicobacter pylori. Changes in eradication rates were monitored and serum antibody titers, levels of pepsinogens I and II (PI and PII), and gastrin were measured. The 40 subjects were divided into two groups: one group received LPZ 30 mg alone, and the other received LPZ 30 mg and AMPC 1,500 mg concomitantly. AMPC was administered for 2 weeks before completion of LPZ treatment. Maintenance therapy was cimetidine 400 mg. The presence of H. pylori was evaluated using the urea breath test (UBT). The clearance rate was 12.5% and the eradication rate was 0% in the LPZ group, and the corresponding rates in the LPZ with AMPC group were 41.6 and 25.0%, respectively. Serum monoclonal H. pylori antibody titers decreased in patients in whom bacterial eradication had been achieved. Serum PI was significantly reduced in those patients in whom eradication had been achieved. Serum PII and gastrin levels also tended to decrease in patients in whom eradication had been achieved, but no such changes were observed in the other patients. Further research into drug treatment and evaluation methods for bacterial eradication is required.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Ulcer Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Breath Tests; Drug Therapy, Combination; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Monitoring, Physiologic; Omeprazole; Penicillins; Pepsinogens; Stomach Ulcer; Urea

Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown.. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays.. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.

Topics: Adult; Anti-Bacterial Agents; Cholecystokinin; Dietary Fats; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormones; Humans; Hydrogen-Ion Concentration; Male; Proglumide; Reference Values; Somatostatin

The role of prostaglandins in peptic ulcer disease and their relation to Helicobacter pylori infection remain controversial. This study sought to compare the effects of oral nizatidine and ranitidine on the gastric mucosal release of prostanoids in duodenal ulcer (DU) patients and to correlate prostanoid concentrations with H. pylori status. Twenty-eight patients with DUs were randomized to receive either nizatidine or ranitidine. Nizatidine 300 mg at night elevated intraluminal PGE2 concentrations; 6-keto-PGF1 alpha concentrations also rose, but did not reach statistical significance. Ranitidine induced non-significant falls in PGE2 and 6-keto-PGE1 alpha concentrations. Patients with H. pylori infection had lower PGE2 and 6-keto-PGF1 alpha concentrations than non-infected patients, but nizatidine was equally effective in increasing prostanoid levels in both groups. These findings may be considered as favourable side effects of nizatidine with uncertain clinical significance. Further studies are needed to elucidate the synergism between prostanoids, eradication of H. pylori and nizatidine in the treatment of DU.

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nizatidine; Pepsinogens; Prostaglandins; Ranitidine

Duodenal and gastric content of mucosal enzymes in duodenal ulcer (DU) patients differs from that of controls. The purpose of this study has been to examine the effect of omeprazole and eradication of Helicobacter pylori on mucosal enzymes in DU patients.. The enzyme activities of seven gastric and duodenal mucosal marker enzymes from the brush border, lysosomes, and mitochondria have been studied. In study I the measurements were made in 29 patients with an active DU before and after 14 days of omeprazole treatment. In study II 22 duodenal ulcer patients were given bismuth subnitrate, oxytetracycline, and metronidazole (triple therapy) for 2 weeks to eradicate H. pylori. Biopsy specimens were taken from the duodenum and the stomach for enzyme measurements and histologic assessment. In study II additional specimens were obtained from the prepyloric region for urease tests and culture of H. pylori.. The ulcer healing rates were more than 90% after both omeprazole and triple therapy. H. pylori was eradicated in 86% after triple therapy. The activities of the brush-border enzymes lactase, neutral-alpha-glucosidase, alkaline phosphatase, leucyl-beta-naphthylamidase, and gamma-glutamyltransferase (gamma-GT) increased significantly in the duodenal bulb and the descending duodenum during treatment with omeprazole. No changes in duodenal enzyme activity were detected after triple therapy, whereas a significant fall in gamma-GT and acid phosphatase activities was seen in the stomach. The mucosal DNA in the gastric antrum decreased both after treatment with omeprazole and after triple therapy.. A similar decrease in mucosal DNA of the gastric antrum was demonstrated after both omeprazole and triple therapy with bismuth subnitrate, oxytetracycline, and metronidazole. Omeprazole also affects the content of duodenal mucosal enzymes, whereas triple therapy particularly affects the gastric mucosal enzyme activity.

Topics: Antacids; Biopsy; Bismuth; DNA; Drug Therapy, Combination; Duodenal Ulcer; Duodenum; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Metronidazole; Middle Aged; Omeprazole; Oxytetracycline; Stomach

Helicobacter pylori (H pylori) raises serum gastrin but it is unclear whether this stimulates increased acid secretion. Gastrin mediated acid secretion and plasma gastrin after the intravenous infusion of gastrin releasing peptide was studied in nine H pylori negative and nine H pylori positive healthy volunteers, and in 11 duodenal ulcer patients. Nine of the last group were re-examined one month after eradication of H pylori. The median acid output (mmol/h) to gastrin releasing peptide (40 pmol/kg/h) in the H pylori positive healthy volunteers was 15.1 (range 3.3-38.3), which was three times that of the H pylori negative healthy volunteers (median = 5.5, range 1.0-9.0) (p < 0.02). The median acid output in the duodenal ulcer patients with H pylori was 37 (range 8.5-57), which was > six times that of the H pylori negative healthy volunteers. Eradication of H pylori in the duodenal ulcer patients lowered their acid secretion by a median of 66% (range 30%-80%) (p < 0.01) and to values equivalent to the H pylori positive healthy volunteers. The pepsin output in response to gastrin releasing peptide followed the same pattern as the acid output. The median plasma gastrin concentrations during gastrin releasing peptide were similar in the H pylori positive duodenal ulcer patients (150 ng/l, range 95-400) and H pylori positive healthy volunteers (129 ng/l, range 23-420) and both were appreciably higher than H pylori negative healthy volunteers (60 ng/l, range 28-135) (p < 0.005 for each). Eradication of H pylori lowered the plasma gastrin in the duodenal ulcer patients to values equivalent to the H pylori negative healthy volunteers. These findings show a threefold increase in acid secretion in H pylori positive healthy volunteers that is explained by H pylori induced hypergastrinaemia and a sixfold increase in acid secretion in the duodenal ulcer patients that is explained by the combination of H pylori induced hypergastrinaemia and an exaggerated acid response to stimulation by gastrin. Eradicating H pylori lowers gastrin mediated acid secretion by 66% in duodenal ulcer patients as a result of the resolution of the hypergastrinaemia. Increased gastrin mediated acid secretion seems to be the key factor in the pathophysiology of duodenal ulceration and explains the role of H pylori infection in the disorder.

Topics: Amoxicillin; Anti-Bacterial Agents; Basal Metabolism; Breath Tests; Carbon Radioisotopes; Duodenal Ulcer; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Infusions, Intravenous; Male; Metronidazole; Organometallic Compounds; Pepsin A; Peptides; Time Factors; Urea

A randomized prospective study on the response of fasting serum gastrin concentrations in peptic ulcer patients was performed in order to test the hypothesis that H. pylori infection in the gastric antrum increases gastrin release, and to examine whether the high fasting serum gastrin concentrations respond to treatment that eradicates H. pylori.. One hundred and twenty-seven patients with gastric or duodenal ulcer were included in this study. Patients were divided into three groups on the basis of antral H. pylori status and therapeutic modalities. The first group, 58 patients infected by H. pylori, was treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and mylanta. The second group, 40 patients also infected by H. Pylori, was treated with ranitidine and mylanta. The third group, 29 patients, free of H. pylori infection, was designed to evaluate the influence of H2-receptor antagonist on the change of gastrin. When ulcers were completely healed, changes of gastrin concentrations and H. pylori status were re-examined.. H. pylori was eradicated in all patients who have received antibacterial therapy in 4 weeks, and serum gastrin concentrations were significantly decreased after eradication of the organism both in gastric and in duodenal ulcer diseases. (Gastric ulcer: 129.3 +/- 47.0 pg/ml before and 63.7 +/- 21.6 pg/ml after treatment. Duodenal ulcer: 108.3 +/- 35.0 pg/ml and 66.5 +/- 21.9 pg/ml, respectively. Total: 112.7 +/- 38.2 pg/ml vs 66.0 +/- 21.6 pg/ml) (p < 0.01). In contrast, H. pylori-positive patients who have not received antibacterial therapy were still infected at the completion of the study, and serum gastrin concentrations increased even though the difference was not significant. (Gastric ulcer: 118.4 +/- 51.2 pg/ml vs 124.0 +/- 56.5 pg/ml. Duodenal ulcer: 85.4 +/- 35.1 pg/ml vs 104.6 +/- 43.5. Total: 99.5 +/- 45.3 vs 112.9 +/- 48.7 pg/ml.) (p > 0.05). None of the patients who were initially H. pylori-negative has been reinfected during the period of the study, and their serum gastrin concentrations were not changed. (Gastric ulcer: 69.8 +/- 38.0 pg/ml. Total: 63.2 +/- 31.1 pg/ml. Duodenal ulcer: 55.1 +/- 17.6 pg/ml vs 55.8 +/- 13.8 pg/ml. Total: 63.2 +/- 31.1 pg/ml vs 63.4 +/- 30.0 pg/ml). Four- to six-week therapy of H2-receptor antagonist and antacid had no influence on serum gastrin concentrations.. On the basis of the above results, we confirmed that the chronic infection of H. pylori of gastric antrum in peptic ulcer patients causes increased release of serum gastrin, and eradication of the organism results in a significant fall in serum gastrin concentrations.

Topics: Adolescent; Adult; Aged; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Prospective Studies; Pyloric Antrum; Stomach Diseases

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (micrograms/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D50) was similar before (0.060 micrograms/kg/h) and after (0.057 micrograms/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/l (range, 22-77) before treatment and fell to 33 ng/l (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Parietal Cells, Gastric; Pentagastrin; Stomach Diseases

Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori-associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1-12.1) to 1.6 (0.4-8) mmol/h, P less than 0.01, whereas peak acid output was unchanged from 41 (21-59) before to 38 (24-55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal-stimulated integrated gastrin response were not altered significantly by sucralfate: 8 (2-17) pmol/L and 732 (188-1045) pmol. min/L pre-treatment and 6 (2-17) pmol/L and 600 (140-1302) pmol. min/L post-treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Sucralfate

Antral G cell hyperfunction (AGCH) is a rare condition, often associated with severe duodenal ulcer disease poorly responsive to medical therapy. Up to now, no studies have been designed to investigate a possible role of medical treatment in the management of this syndrome. In this study we treated 9 AGCH patients with duodenal ulcer, unhealed with the prolonging standard doses of H2 antagonists (300 mg/day ranitidine or 800 mg/day cimetidine), with a nonantacid therapy, tripotassium dicitrato bismuthate (TDB). 6 out of 9 patients showed a complete healing after 8 weeks of treatment. The healing was irrespective to eradication of Campylobacter pylori. After 9 weeks' suspension of H2 blockers basal gastrin levels decreased significantly by 31.5%, whereas peak meal-stimulated levels, although decreased in 6 out 9 patients, were not significantly affected by the withdrawal of the H2 antagonists. Nonantisecretory therapy seems to be an efficacious alternative in the management of AGCH patients.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Bismuth; Cimetidine; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine

Stomach cancer is a leading cause of cancer death. Helicobacter pylori is a bacterial gastric pathogen that is the primary risk factor for carcinogenesis, associated with its induction of inflammation and DNA damage. Dicarbonyl electrophiles are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. 2-hydroxybenzylamine (2-HOBA) is a natural compound derived from buckwheat seeds and acts as a potent scavenger of reactive aldehydes. Our goal was to investigate the effect of 2-HOBA on the pathogenesis of H. pylori infection. We used transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer. First, we found that 2-HOBA is bioavailable in the gastric tissues of these mice after supplementation in the drinking water. Moreover, 2-HOBA reduced the development of gastritis in H. pylori-infected INS-GAS mice without affecting the bacterial colonization level in the stomach. Further, we show that the development of gastric dysplasia and carcinoma was significantly reduced by 2-HOBA. Concomitantly, DNA damage were also inhibited by 2-HOBA treatment in H. pylori-infected mice. In parallel, DNA damage was inhibited by 2-HOBA in H. pylori-infected gastric epithelial cells in vitro. In conclusion, 2-HOBA, which has been shown to be safe in human clinical trials, represents a promising nutritional compound for the chemoprevention of the more severe effects of H. pylori infection.

Topics: Animals; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Stomach Neoplasms

The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting.. The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers.. In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases.. The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.

Topics: Antibodies, Bacterial; Biomarkers; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Stomach Neoplasms

Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

Topics: Esophageal Neoplasms; Esophagectomy; Esophagitis, Peptic; Gastrins; Helicobacter Infections; Humans; Ulcer

Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG)).. To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA).. Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG.. Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis.. Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis.

Topics: Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Prospective Studies

The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis.. Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group.. The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80.. The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Topics: Biomarkers; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A; Reference Values; Retrospective Studies; Stomach Neoplasms

We report here a case of a 62-year-old woman with multiple gastric enterochromaffin-like cell neuroendocrine tumor caused by hypergastrinemia due to parietal cell dysfunction that was successfully treated with somatostatin analogue. Esophagogastroduodenoscopy revealed several G1 neuroendocrine tumors, 10 mm in diameter, in the body of the stomach. No evidence of autoimmune gastritis, Helicobacter pylori infection, neuroendocrine neoplasia type 1, or Zollinger-Ellison syndrome was identified. The pattern of immunohistochemical staining of the background gastric mucosa was suggestive of parietal cell dysfunction. She was treated with long-acting release octreotide acetate. Complete response was confirmed after 9 months and was maintained for 22 months.

Topics: Enterochromaffin-like Cells; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Neuroendocrine Tumors; Somatostatin; Stomach Neoplasms

Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.

Topics: Atrophy; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A

Serum pepsinogen, a useful indicator of gastric acidity, could reflect small intestinal bacterial overgrowth. The aim of this study is to evaluate the relationship between small intestinal bacterial overgrowth and profiles including pepsinogen or gastrin.. We conducted a prospective study with 62 patients with a functional gastrointestinal disorder. All patients underwent glucose breath test for small intestinal bacterial overgrowth, immediately followed by upper endoscopy to survey gastric injury and Campylobacter-like organism test for Helicobacter pylori and serum laboratory tests including gastrin, pepsinogen I and II.. The positivity to small intestinal bacterial overgrowth was 17.7%. Significantly, low total hydrogen concentration during a glucose breath test, low prevalence for gastric injury, and high H. pylori positivity rate were shown in groups with pepsinogen I/II ratio ≤ 3.5 compared to those with pepsinogen I/II ratio > 3.5 or in groups with serum gastrin > 35.4 pg/mL comparing to those with serum ≤ 35.4 pg/mL, respectively. A high gastrin level was independently associated with H. pylori infection. A proportionally correlated tendency between pepsinogen I/II ratio and total hydrogen concentration was shown, whereas that of inverse proportion between H2 and gastrin was observed. Old age was solely independent predicting factor for small intestinal bacterial overgrowth (P = .03) in the multivariate analysis.. Old age was significantly related to the presence of small intestinal bacterial overgrowth in functional gastrointestinal disorder patients. Although pepsinogen and small intestinal bacterial overgrowth seem irrelevant, elevated gastrin level may cautiously indicate a decreased breath hydrogen concentration. Further studies should consider the function of intestinal motility and gastric acidity in patients with hydrogen-producing small intestinal bacterial overgrowth.

Topics: Biomarkers; Gastrins; Glucose; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen; Pepsinogen A; Pepsinogen C; Prospective Studies

Gastric intestinal metaplasia (GIM) is a premalignant lesion, highly associated with Helicobacter pylori infection. Previous studies have shown that H. pylori is able to induce the expression of programmed death ligand 1 (PD-L1), an inhibitory immune modulator, in gastric cells. Our aim was to investigate whether tissues from GIM patients may exploit PD-L1 expression upon H. pylori infection to evade immunosurveillance.. Immunohistochemistry was performed for PD-L1 and enteroendocrine markers somatostatin and gastrin on samples derived from a cohort of patients with known GIM, both before and after H. pylori eradication. To determine the identity of any observed PD-L1-positive cells, we performed multiplex immunofluorescent staining and analysis of single-cell sequencing data.. GIM tissue was rarely positive for PD-L1. In normal glands from GIM patients, PD-L1 was mainly expressed by gastrin-positive G-cells. While the D-cell and G-cell compartments were both diminished 2-fold (p = .015 and p = .01, respectively) during H. pylori infection in the normal antral tissue of GIM patients, they were restored 1 year after eradication. The total number of PD-L1-positive cells was not affected by H. pylori, but the percentage of PD-L1-positive G-cells was 30% higher in infected subjects (p = .011), suggesting that these cells are preferentially rescued from destruction.. Antral G-cells frequently express PD-L1 during homeostasis. G-cells seem to be protected from H. pylori-induced immune destruction by PD-L1 expression. GIM itself does not express PD-L1 and is unlikely to escape immunosurveillance via expression of PD-L1.

Topics: B7-H1 Antigen; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Metaplasia; Precancerous Conditions; Somatostatin; Stomach Neoplasms

In Mongolia, gastric cancer morbidity and mortality are high, and more than 80 percent of cases are diagnosed at an advanced stage. This study aimed to evaluate pepsinogens (PGIs) and gastrin-17 (G-17) levels and to determine the diagnostic performances for gastric cancer and chronic atrophic gastritis among Mongolian individuals. We enrolled a total of 120 subjects, including gastric cancer (40), atrophic gastritis (40), and healthy control (40), matched by age (±2) and sex. Pepsinogen I (PGI), Pepsinogen II (PGII), G-17, and H. pylori IgG levels were measured using GastroPanel ELISA kit (Biohit, Helsinki, Finland). Also, PGI to PGII ratio (PGR) was calculated. For atrophic gastritis, when the optimal cut-off value of PGI was ≤75.07 ng/ml, the sensitivity and specificity were 75% and 50%, respectively; when the optimal cut-off value of PGR was ≤6.25, sensitivity and specificity were 85% and 44.7%, respectively. For gastric cancer, when the optimal cut-off value of PGI was ≤35.25 ng/ml, the sensitivity and specificity were 47.2% and 86.8%, respectively; when the optimal cut-off value of PGR was ≤5.27, sensitivity and specificity were 75% and 60.5%, respectively. Combinations of biomarkers with risk factors could improve diagnostic accuracy (AUC for atrophic gastritis 74.8, 95% CI 64.0-85.7, p<0.001; AUC for gastric cancer 75.5, 95% CI 64.2-86.8, p<0.001). PGI, PGR biomarkers combined with the risk of age, family history of gastric cancer, and previous gastric disease could not be an alternative test for upper endoscopy but might be a supportive method which is identifying individuals at medium- and high risk of gastric cancer and precancerous lesions who may need upper endoscopy.

Topics: Biomarkers; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Pepsinogen A; Pepsinogen C; Stomach Neoplasms

The present study was designed to observe the effect of quadruple therapy combined with probiotics on

Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Motilin; Pectins; Peptic Ulcer; Probiotics; Proton Pump Inhibitors; Somatostatin; Tablets, Enteric-Coated

The clinical spectrum of autoimmune gastritis is silent in the early stages of the disease and no specific symptom is related to this entity. Although gastroscopic findings of this entity are well defined, data regarding colonoscopic findings are limited. The aims of this study were to determine the prevalence of colonoscopic findings and to explore factors that might affect these findings. This is a retrospective chart review of patients with autoimmune gastritis (n=240). Data regarding colonoscopic findings, serum gastrin and chromogranin A (CgA) levels and gastric histopathological results were extracted and compared with 550 patients positive for

Topics: Adult; Aged; Chromogranin A; Colonoscopy; Colorectal Neoplasms; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Precancerous Conditions; Prevalence; Retrospective Studies

Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel. Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing.. The new generation GastroPanel

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers; Biopsy; Enzyme-Linked Immunosorbent Assay; Female; Finland; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Referral and Consultation; Reproducibility of Results; Serologic Tests; Young Adult

PPI use,

Topics: Aged; Amino Acid Sequence; Animals; Arthropod Proteins; Cloning, Molecular; Endoscopy, Digestive System; Fasting; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Invertebrate Hormones; Male; Middle Aged; Nerve Tissue Proteins; Ovary; Penaeidae; Precancerous Conditions; Proton Pump Inhibitors; Stomach Neoplasms; Vitellogenesis; Vitellogenins

Topics: Crohn Disease; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans

Immune checkpoint inhibitors have limited efficacy in many tumors. We investigated mechanisms of tumor resistance to inhibitors of programmed cell death-1 (PDCD1, also called PD-1) in mice with gastric cancer, and the role of its ligand, PD-L1.. Gastrin-deficient mice were given N-methyl-N-nitrosourea (MNU) in drinking water along with Helicobacter felis to induce gastric tumor formation; we also performed studies with H/K-ATPase-hIL1B mice, which develop spontaneous gastric tumors at the antral-corpus junction and have parietal cells that constitutively secrete interleukin 1B. Mice were given injections of an antibody against PD-1 or an isotype control before tumors developed, or anti-PD-1 and 5-fluorouracil and oxaliplatin, or an antibody against lymphocyte antigen 6 complex locus G (also called Gr-1), which depletes myeloid-derived suppressor cells [MDSCs]), after tumors developed. We generated knock-in mice that express PD-L1 specifically in the gastric epithelium or myeloid lineage.. When given to gastrin-deficient mice before tumors grew, anti-PD-1 significantly reduced tumor size and increased tumor infiltration by T cells. However, anti-PD-1 alone did not have significant effects on established tumors in these mice. Neither early nor late anti-PD-1 administration reduced tumor growth in the presence of MDSCs in H/K-ATPase-hIL-1β mice. The combination of 5-fluorouracil and oxaliplatin reduced MDSCs, increased numbers of intra-tumor CD8. In mouse models of gastric cancer, 5-fluorouracil and oxaliplatin reduce numbers of MDSCs to increase the effects of anti-PD-1, which promotes tumor infiltration by CD8

Topics: Administration, Oral; Animals; Carcinogenesis; Gastric Mucosa; Gastrins; Helicobacter felis; Helicobacter Infections; Humans; Immune Checkpoint Inhibitors; Methylnitrosourea; Mice; Mice, Knockout; Myeloid-Derived Suppressor Cells; Neoplasms, Experimental; Programmed Cell Death 1 Receptor; Signal Transduction; Stomach Neoplasms; Tumor Microenvironment

Helicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia. To determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum.. Mouse lines were created to conditionally direct IL1β or IFN-γ to the antrum using the Gastrin-CreERT2 and Tet activator. Primary cilia, which transduces HH signaling, on G cells were disrupted by deleting the ciliary motor protein KIF3a. Phenotypic changes were assessed by histology and western blots. A subclone of GLUTag enteroendocrine cells selected for gastrin expression and the presence of primary cilia was treated with recombinant SHH, IL1β or IFN-γ with or without kif3a siRNA.. IFN-γ increased gastrin and induced antral hyperplasia. However, antral expression of IL1β suppressed tissue and serum gastrin, while also inducing antral hyperplasia. IFN-γ treatment of GLUTAg cells suppressed GLI2 and induced gastrin, without affecting cilia length. By contrast, IL1β treatment doubled primary cilia length, induced GLI2 and suppressed gastrin gene expression. Knocking down kif3a in GLUTAg cells mitigated SHH or IL1β suppression of gastrin.. Overexpression of IL1β in the antrum was sufficient to induce antral hyperplasia coincident with suppression of gastrin via primary cilia. ORCID: #0000-0002-6559-8184.

Topics: Animals; Antiviral Agents; Cilia; Gastrins; Helicobacter Infections; Helicobacter pylori; Hyperplasia; Interferon-gamma; Interleukin-1beta; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pyloric Antrum

Helicobacter pylori and Multiple Endocrine Neoplasia Type 1 (MEN 1) are risk factors for hypergastrinemia. Gastrin-secreting neoplasms of the foregut mucosa are both a source of, and potentially stimulated by, hypergastrinemia.. To determine the relationship between H pylori exposure and the prevalence and severity of hypergastrinemia in patients with MEN 1.. Cross-sectional analysis of patients with a common MEN1 gene mutation managed at a tertiary referral hospital that underwent fasting serum gastrin and H pylori serum IgG measurement.. H pylori IgG and serum gastrin concentration, determined via immunoassay.. The prevalence and severity of hypergastrinemia and its relationship to past H pylori exposure.. Thirty-four of 95 (36%) patients were H pylori IgG seropositive. H pylori seropositive patients were significantly more likely to exhibit hypergastrinemia compared with seronegative patients (relative risk [RR] 1.72, P = .023). H pylori exposure also predicted severe hypergastrinemia (RR 3.52, P = .026 and RR 9.37, P = .031 for patients with gastrin ≥ ×4 and ≥ ×8 the upper limit of normal [ULN], respectively). Gastrin concentrations ≥ ×10 ULN occurred exclusively in H pylori seropositive patients (0/61 vs 6/34, P = .001). Serum gastrin and alpha subunit were positively associated in H pylori-exposed (β = 0.69, P = .001), but not in H pylori-unexposed patients.. Past H pylori exposure was associated with increased prevalence and severity of hypergastrinemia in MEN 1 patients. Past H pylori-related hypergastrinemia may contribute to the pathogenesis of ongoing gastrin hypersecretion by susceptible foregut neuroendocrine tissues.

Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Female; Gastrinoma; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Prevalence; Severity of Illness Index; Tasmania; Young Adult

Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children.. We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded.. The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia.. Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Topics: Adolescent; Anemia, Iron-Deficiency; Autoimmune Diseases; Child; Child, Preschool; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Parietal Cells, Gastric; Retrospective Studies; Stomach; Vitamin B 12 Deficiency

Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence.. In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference.. Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068).. Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Topics: Adult; Aged; Antibodies, Bacterial; Biomarkers; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; France; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Incidence; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Sensitivity and Specificity; Stomach Neoplasms

Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells.. To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection.. Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands.. Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls.. Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

Topics: Case-Control Studies; Enterochromaffin-like Cells; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Proton Pumps; Stomach; Stomach Diseases

Gastrin-17 (G-17) and Helicobacter pylori (H pylori) antibody are widely used in the screening of gastric diseases, especially in gastric cancer. In this study, we aimed to evaluate the value of G-17 and H pylori antibody in gastric disease screening.. Healthy males and females (1368 and 1212, respectively) aged between 21-80 years were recruited for the study. Serum G-17 value was measured using ELISA, and H pylori antibodies were measured using Western blotting. Statistical analyses were performed using the chi-square, Mann-Whitney U, and Kruskal-Wallis H tests.. Serum G-17 level was higher in the H pylori-positive group than in the negative group. Serum G-17 level was higher in the type 1 H pylori-positive group than in the type 2 H pylori-positive group. Further, serum G-17 level was higher in females than in males and showed significant differences among different age-groups, with changes in trend proportional to the age. The positive rate of H pylori infection in all the subjects was 58.29% and did not show a significant difference between males and females. However, it showed significant differences among different age-groups, with the changing trend proportional to the age.. Analysis of serum G-17 level and H pylori antibody typing is valuable in gastric disease screening. Every laboratory should establish its own reference interval for G-17 level.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; China; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Retrospective Studies; Stomach Diseases; Young Adult

Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis.. We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017.. A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET.. This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Biomarkers; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pepsinogen A; Pepsinogen C; Prevalence; Retrospective Studies; ROC Curve; Stomach Neoplasms; Young Adult

 To explore the predictive value of serum gastrin (GAS), epidermal growth factor (EGF) levels in gastric ulcer complicated with acute upper gastrointestinal bleeding.. A descriptive study.. Department of Emergency, Beijing Jiangong Hospital, China, from January 2019 to June 2020.. One hundred and twenty-five patients with gastric ulcer and acute upper gastrointestinal bleeding were selected as Group A. One hundred and twenty-five patients with gastric ulcer and no upper gastrointestinal bleeding were selected as Group B. Logistic regression analysis was used to analyse the risk factors of gastric ulcer complicated with acute upper gastrointestinal bleeding. The value of serum GAS, EGF in early diagnosis of gastric ulcer with upper gastrointestinal bleeding was evaluated by receiver operating characteristic (ROC) curve.. Univariate analysis showed statistically significant differences between Group A and Group B in taking non-steroidal anti-inflammatory drugs (NSAIDs), helicobacter pylori (Hp) infection, serum GAS and EGF (all p <0.001). Logistic regression analysis showed that raised serum GAS and serum EGF were independent risk factors for gastric ulcer and upper gastrointestinal bleeding (both p <0.001). The ROC area of serum EGF to predict gastric ulcer and acute upper gastrointestinal bleeding was 0.810 (95% CI: 0.753-0.867, p <0.001), greater than ROC area of serum GAS. At serum EGF of ≤109.95 pg/mL, had the 84.8%, sensitivity to predict gastric ulcer and acute upper gastrointestinal bleeding with specificity of 68.8%.. The predictive value of serum GAS and EGF is high for gastric ulcer complicated with acute upper gastrointestinal bleeding; the predictive value of serum EGF is greater than that of serum GAS. Key Words: Gastric ulcer, Acute upper gastrointestinal bleeding, Serum, Gastrin (GAS), Epidermal growth factor (EGF), Logistic regression, Receiver operating characteristic (ROC) curve.

Topics: Anti-Inflammatory Agents, Non-Steroidal; China; Epidermal Growth Factor; Gastrins; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Risk Factors; Stomach Ulcer

The aim: To study the gastrin level dynamics in patients with diabetes mellitus (DM) 2 type and chronic gastritis (CG) on the background of antihelicobacter therapy (AHT).. Materials and methods: 60 patients with DM type 2 and HP-associated CG underwent examination. Patients were divided into two groups of 30 patients each: group 1 included patients who received only standard AHT, group 2 - patients who in addition to standard AHT received the drug SB (Normagut, company Mega) 2 capsules 2 times/day.. Results: According to our study results yeast SB, not only increase the HP eradication rate but together with the standard AHT contribute to the serum gastrin reduction, which is a gastric acid stimulator, which in turn leads to an improvement in the CG clinical course.. Conclusions: Patients with DM type 2 and CG associated with HP should include yeast SB to standard AHT as they reduce side effects from this treatment (by an average of 20%), increase the eradication frequency (by 10%), and also lead to significant decrease in serum gastrin (up to 82.15 ± 2.47 pg/ml).A decrease in serum gastrin levels in patients with HP-associated CG and DM type 2 leads to an improvement in the clinical course of the diseases, namely a decrease in nausea, diarrhea, abdominal pain, and discomfort incidence.

Topics: Diabetes Mellitus, Type 2; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans

The goal of this study was to elucidate the most important predictors for elevation of gastrin in patients on long-term PPI therapy through analysis of data from 2 published studies in Icelandic patients with erosive GERD.. Gastrin elevation is a known but variable consequence of proton pump inhibitor (PPI) therapy. Concerns have been raised about the clinical importance of chronic PPI induced gastrin elevation.. This cross-sectional analysis included patients with endoscopically verified erosive esophagitis receiving long-term PPI therapy. PPI exposure in dosage over weight (mg/kg) and dosage over body surface area (mg/m) was compared with fasting gastrin levels in two separate multiple linear regression models. Data was collected on age, gender, weight, H. pylori infection, smoking, PPI duration and type.. Overall data from 157 patients (78 females) were analyzed. Median serum gastrin levels were higher in females than males (92 vs. 60 pg/mL; P=0.001). Simple linear regression showed a correlation between serum gastrin levels and gender (P=0.0008) as well as PPI exposure in mg/kg (P=0.0001) and mg/m (P=0.0001). Multiple linear regression analysis showed that PPI exposure, both in mg/kg (β=0.95 [CI=0.4-1.5]; P=0.001) and mg/m (β=0.02 [CI=0.0-0.0]; P=0.0015) along with female gender (β=0.2 [CI=0.0-0.4]; P=0.02) predicted higher gastrin values.. Dosage and female gender seem to play an important role in the development of gastrin elevation on PPI therapy. A significant correlation was found between fasting serum gastrin and dosage of PPIs over weight and body surface area.

Topics: Aged; Cross-Sectional Studies; Female; Gastrins; Helicobacter Infections; Humans; Iceland; Male; Middle Aged; Proton Pump Inhibitors

Screening and timely treatment of precancerous gastric cancer diseases or of gastric cancer in the early stages has important significance in reducing the incidence and mortality of gastric cancer. Gastroscopy and histopathological biopsy are still the gold standards for the diagnosis of gastric diseases. But the application of astroscopy for the screening and diagnosis of gastric diseases is limited. In recent years, serum pepsinogen (PG), gastrin, and Helicobacter pylori (H. pylori) IgG antibodies have become indicators for "serological biopsy" of the gastric mucosa.. From January 2016 to January 2018, a total of 2,394 patients with digestive tract symptoms underwent gastroscopy. According to the endoscopic examination and pathological diagnosis, there were four case groups: 1,376 cases of chronic non-atrophic gastritis, 708 cases of chronic atrophic gastritis, 265 cases of gastric ulcer, and 45 cases of gastric cancer. Serological gastric biopsies were performed and analyzed.. The serum levels of PGI in the chronic atrophic gastritis group was significantly lower than that in the chronic non-atrophic gastritis group, gastric ulcer group, and gastric cancer group (p < 0.05). The serum levels of PGII and G-17 in the gastric cancer group were significantly higher than those in the chronic non-atrophic Gastritis group, chronic atrophic gastritis group, and gastric ulcer group (p < 0.05). The PGR in the gastric cancer group was significantly lower than that in the chronic non-atrophic gastritis group, chronic atrophic Gastritis group, and gastric ulcer group (p < 0.05). The H. pylori positive rates in the chronic atrophic gastritis group and gastric cancer group were higher than those in the chronic non-atrophic gastritis group and gastric ulcer Group (p < 0.05).. Serological gastric biopsy is closely correlated to gastric mucosal disease and can be used as a Screening tool in gastric disease.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers; Biopsy; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Sensitivity and Specificity; Stomach Neoplasms; Young Adult

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.. La gastrite chronique auto-immune (GAI) est un continuum d’altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d’une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L’association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l’Helicobacter pylori (Hp) peut s’associer avec la GAI, le rôle du microbiote gastrique est mal défini. L’hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L’anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d’anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L’endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l’antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l’ensemble des praticiens.

Topics: Autoimmune Diseases; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans

Trypanosoma cruzi and Helicobacter pylori (HP) are pathogens that cause chronic diseases and have been associated with hypergastrinemia. The aim of this study was to evaluate the fasting gastrin levels in patients with different clinical forms of Chagas disease (CD), coinfected or not by HP. The enrolled individuals were outpatients attending at the university hospital. HP infection was assessed by serology and 13 C-urea breath test. Fasting serum gastrin concentration was measured by chemiluminescence assay. Gastric endoscopic and histological features were also evaluated. Associations between CD and serum gastrin level were evaluated in a logistical model, adjusting for age, gender and HP status. A total of 113 patients were evaluated (45 with Chagas disease and 68 controls). In the multivariate analysis, increasing serum gastrin levels (OR= 1.02; 95% CI= 1.01-1.12), increasing age (OR= 1.05; 95% CI= 1.02 - 1.09) and HP-positive status (OR = 2.88; 95% CI = 1.10 - 7.51) remained independently associated with CD. The serum gastrin levels were significantly higher in the group of patients with the cardiodigestive form ( P = 0.03) as well as with digestive form ( P = <0.001) of Chagas disease than in the controls. In conclusion, patients with cardiodigestive and digestive clinical forms of CD have increased basal serum gastrin levels in comparison with controls. Moreover, we also demonstrated that H. pylori coinfection contributes to the hypergastrinemia shown in CD.

Topics: Case-Control Studies; Chagas Disease; Coinfection; Cross-Sectional Studies; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy.. This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-. The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level,. The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers, Tumor; Diet; Early Detection of Cancer; Female; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Mass Screening; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Random Allocation; Reproducibility of Results; Risk Factors; Secondary Prevention; Stomach Neoplasms

The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps.. Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps.. HPs arise from inflammation caused by

Topics: Adenomatous Polyps; Adult; Aged; Cohort Studies; Endoscopy, Digestive System; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Humans; Male; Middle Aged; Multivariate Analysis; Neutrophil Infiltration; Prospective Studies; Proton Pump Inhibitors; Risk Factors; Stomach Neoplasms

Whether gastric hyperchlorhydria and Helicobacter pylori infection contribute to aspirin-induced gastroduodenal injury still lacks evidence. Because serum pepsinogens (PGs) and gastrin-17 (G17) can reflect gastric acid secretion, this study intended to elucidate whether serum PGs, serum G17, and H. pylori infection are associated with aspirin-induced gastrointestinal injury.. A total of 60 patients taking low-dose aspirin for more than 1 month were enrolled in this study. Serum PG I, PG II, and G17 were determined using ELISA. A 14C-urea breath test was used for the detection of an H. pylori infection. The modified Lanza score was used to evaluate the degree of gastroduodenal injury under endoscopy. The median serum PG I level was significantly higher in the intensive gastroduodenal injury (IGI) group compared to that in the mild gastroduodenal injury group (155.0 vs. 116.6 ng/mL, p = 0.006). The H. pylori infection rate was significantly higher in the IGI group (73 vs. 40%, p = 0.037). Receiver operator characteristic curves analysis revealed that the cutoff value of PG I was 123 ng/mL, with 80% sensitivity and 61.4% specificity. H. pylori infection combined with PG I at >123 ng/mL had an OR (95% CI) of 15.8 (2.4 ± 104.5) for the prediction of aspirin-induced gastroduodenal injury. Key Messages: Serum PG I and H. pylori infection could be used to identify potential high-risk aspirin-induced gastroduodenal injury patients.

Topics: Aged; Area Under Curve; Aspirin; Duodenum; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Multivariate Analysis; Pepsinogen A; Risk Factors; ROC Curve; Stomach

The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs.. Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood.. A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32-8.47), women (OR 2.22; 95% CI 1.33-3.72) and corpus atrophy (OR 1.82; 95% CI 1.14-2.90).. PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.

Topics: Aged; Antibodies, Bacterial; Atrophy; Cross-Sectional Studies; Cytochrome P-450 CYP2C19; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Polymorphism, Genetic; Proton Pump Inhibitors; Sex Factors; Time Factors

Studies have suggested that Helicobacter pylori (Hp) infection is associated with atherosclerotic process, while the relationship between pepsinogens, gastrin and atherosclerosis is unknown.. The aim of the study was to observe association of Hp infection on atherosclerotic parameters and blood pressure, and explore the relationship between atherosclerotic parameters, blood pressure and gastric biomarkers in a healthy population.. 395 subjects were chosen and received physical examinations, carotid artery ultrasound, peripheral atherosclerosis measurement, and testing of serum pepsinogen (PG) I and II, Hp antibody, and gastrin-17 (G-17) levels. Analyses were conducted by Student's t-test, ANOVA, Pearson correlation, multiple linear regression and binary logistic regression.. In Hp-infected subjects, right carotid intima media thickness (R-CIMT) were higher (P = 0.027) and left ankle brachial index were higher in 45-64 years compared to 35-44 years group (P = 0.039, P = 0.016). Hp-IgG, PGI and G-17 respectively positively correlated with CIMT, pulse wave velocity and systolic blood pressure (P = 0.044, P = 0.013, P = 0.021). The unadjusted OR in subjects with elevated CIMT for quartile IV of PGI was 3.542 (95% CI, 1.491-8.411), the adjusted OR was 2.916 (95% CI, 1.035-8.216). The unadjusted OR in subjects with elevated CIMT for quartile III of G-17 was 4.351 (95% CI, 1.670-11.336) and for quartile IV was 3.108 (95% CI, 1.149-8.406), the adjusted OR for quartile III was 4.962 (95% CI, 1.515-16.258).. Hp infection, higher levels of PGI and G-17 may contribute to atherosclerotic process by influencing atherosclerotic parameters and blood pressure in a healthy population, the influence on CIMT was most significant.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; China; Cross-Sectional Studies; Female; Gastrins; Healthy Volunteers; Helicobacter Infections; Helicobacter pylori; Humans; Logistic Models; Male; Middle Aged; Pepsinogens; Pulse Wave Analysis; Risk Factors

Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish smokers.. Totals of 283 incident GNCA, 96 EGJA and 10 gastric carcinoid cases, and 778 matched controls, were included in our analysis. Gastrin and CCK were measured using specific radioimmunoassays. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by multivariable logistic regression with adjustment for all known or suspected confounding factors, including Helicobacter pylori seropositivity.. Those with high gastrin (Q4 vs Q1), had an increased risk of GNCA (fully adjusted OR: 1.92; 95% CI: 1.21, 3.05) and gastric carcinoids, though the small number of carcinoid cases meant the fully adjusted model was unstable (age-adjusted continuous model OR: 4.67; 95% CI: 2.67, 8.15). CCK was associated with risk of GNCA only for those in Q3 relative to Q1 (OR: 0.56; 95% CI: 0.33, 0.96), and no significant trend was observed.. Our data suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear.

Topics: Adenocarcinoma; Case-Control Studies; Cholecystokinin; Esophageal Neoplasms; Finland; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Smokers; Stomach Neoplasms

The aim of this study was to evaluate the correlation between H. pylori infection and global DNA methylation, as well as the methylation levels of the gastrin promoters.. These results indicate that H. pylori/CagA

Topics: Antigens, Bacterial; Bacterial Proteins; Cell Line; Cell Line, Tumor; CpG Islands; DNA; DNA Methylation; Gastric Mucosa; Gastrins; Gene Expression Regulation, Enzymologic; Genomics; Helicobacter Infections; Helicobacter pylori; Humans; Promoter Regions, Genetic; RNA, Messenger; Stomach Neoplasms; Transfection

Topics: Biological Assay; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A

Serum gastrin concentration can help diagnose gastrinomas in dogs if >3-10× the upper reference limit (URL), but antisecretory therapy and other conditions can also cause hypergastrinemia. Effects of antisecretory therapy (famotidine or ranitidine, omeprazole) on serum gastrin concentration in dogs with chronic enteropathy (CE) and its biological variation (BV) are unknown. Aim of the study was to evaluate serum gastrin in acid-suppressant-treated or -naïve CE dogs; test the association between serum gastrin and histopathologic findings in acid-suppressant-naïve CE dogs; and evaluate the BV of serum gastrin in dogs not receiving any gastric acid suppressive therapy. Samples from 231 dogs were used and serum gastrin was measured by chemiluminescence assay. Gastric and duodenal histologic lesions were evaluated and graded. BV of serum gastrin was evaluated in serial samples.. Antisecretory (particularly PPI) treatment leads to hypergastrinemia in CE dogs, but the concentrations seen in this study are unlikely to compromise a diagnosis of gastrinoma. Use of a population-based URL for canine serum gastrin and a URL of ≤27.8 ng/L are appropriate.

Topics: Animals; Biological Variation, Population; Dog Diseases; Dogs; Female; Gastrins; Helicobacter; Helicobacter Infections; Histamine H2 Antagonists; Intestinal Diseases; Male; Proton Pump Inhibitors; Stomach Diseases

Topics: DNA-Binding Proteins; ErbB Receptors; Gastrins; Gene Expression Regulation; Genes, Reporter; Helicobacter Infections; Helicobacter pylori; Heparin-binding EGF-like Growth Factor; Humans; Mitogen-Activated Protein Kinase 1; Mutation; Promoter Regions, Genetic; Proto-Oncogene Proteins c-raf; RNA, Messenger; Signal Transduction; Transcription Factors

We report a case of developing multiple adenocarcinoma foci in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor (PPI) therapy. A 57-year-old man, who was undergoing hemodialysis for chronic renal failure, underwent an upper gastrointestinal endoscopy to elucidate the cause of anemia. Atrophic gastritis with H. pylori infection and multiple adenocarcinoma foci in multiple hyperplastic polyps were found in the endoscopic and histological examinations. Enterochromaffin-like micronests and parietal cell protrusion in the background of the polyps suggested the existence of hypergastrinemia. The serum gastrin level was markedly high-10,206 pg/ml (normal range 37-172 pg/ml). The cause of this marked hypergastrinemia was not autoimmune gastritis and gastrinoma. After discontinuing PPI therapy and successful eradication of H. pylori, the serum gastrin level decreased to normal range. These findings indicate that hypergastrinemia may be caused by long-term PPI therapy in patients with H. pylori infection. This case suggests that hypergastrinemia may mediate gastric carcinogenesis in patients with H. pylori infection.

Topics: Adenocarcinoma; Cocarcinogenesis; Drug Administration Schedule; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Middle Aged; Polyps; Proton Pump Inhibitors; Stomach Neoplasms

A man in his 60s was referred to our institution for the evaluation of a gastric neuroendocrine tumor (G-NET) located in the fornix and that measured 13mm in size. Blood test results revealed hypergastrinemia (up to 3376pg/ml). Additional tests, including esophagogastroduodenoscopy, computed tomography, and intragastric pH monitoring, indicated that hypergastrinemia was not associated with type A autoimmune gastritis or gastrinoma. The patient was positive for the immunoglobulin G antibody against Helicobacter pylori, suggesting type B chronic atrophic gastritis as the cause for the condition. This report describes a rare case of G-NET with hypergastrinemia following type B chronic atrophic gastritis. Evaluation of similar cases is necessary to determine if H. pylori-associated chronic atrophic gastritis is frequently associated with G-NET.

Topics: Chronic Disease; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Neuroendocrine Tumors; Stomach Neoplasms

The ABCD screening method was developed for risk stratification of gastric cancer. It is unclear whether the ABCD method can predict the risk of gastric neoplasms, including gastric adenomas, as observed for gastric cancer. We aimed to devise a modified ABCD method for predicting gastric neoplasms.. We reviewed 562 patients who had undergone upper gastrointestinal tract endoscopy and whose serum IgG anti-Helicobacter pylori antibody, gastrin, and pepsinogen (PG) I and PG II data were available. Patients were classified into the following four groups: H. pylori antibody negative and normal PG level (group A), H. pylori antibody positive and normal PG level (group B), H. pylori antibody positive and low PG level (group C), and H. pylori antibody negative and low PG level (group D).. The PG I/PG II ratio was lower in patients with gastric neoplasms than in patients without these lesions (gastric adenoma vs gastric cancer vs no neoplasm, 3.7 ± 2.0 vs 3.8 ± 1.8 vs 4.9 ± 2.1, P < 0.001). The optimal cutoff values of the PG I/PG II ratio for predicting gastric neoplasms were 3.1 for H. pylori antibody negative patients and 4.1 for H. pylori antibody positive patients. A higher group grade was associated with a significantly higher proportion of gastric neoplasms [odds ratio (95 % confidence interval), group A, reference; group B, 1.783 (1.007-3.156); group C, 3.807 (2.382-6.085); and group D, 5.862 (2.427-14.155)].. The modified ABCD method using two different cutoff values according to the H. pylori antibody status was useful for predicting the presence of gastric neoplasms. This method might be a supplementary screening tool for both gastric adenoma and gastric cancer. However, further studies will be required to provide a definitive conclusion.

Topics: Adenoma; Aged; Antibodies, Bacterial; Endoscopy, Gastrointestinal; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Retrospective Studies; Stomach Neoplasms

To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection.. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology.. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively).. H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Autoimmune Diseases; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Humans; Male; Middle Aged; Pepsinogen A; Prospective Studies; Young Adult

Effectively managing precancerous lesions is crucial to reducing the gastric cancer (GC) burden. We evaluated associations of temporal changes in multiple serological markers (pepsinogen I [PGI], PGII, PGI/II ratio, gastrin-17 and anti-Helicobacter pylori IgG) with risk for progression of gastric precancerous lesions. From 1997 to 2011, repeated esophagogastroduodenoscopies with gastric mucosal biopsies and blood sample collections were conducted on 2,039 participants (5,070 person-visits) in the Zhuanghe Gastric Diseases Screening Program, Liaoning, China. Serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized histologic criteria. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations for correlated binary outcomes. The ORs for progression of gastric conditions comparing those whose serum PGI, PGII, and anti-H. pylori IgG levels increased ≥ 50% relative to those whose decreased ≥ 50% were, respectively 1.67 (CI, 1.22-2.28), 1.80 (CI, 1.40-2.33) and 1.93 (CI, 1.48-2.52). The OR for those whose PGI/II ratio decreased ≥ 50% relative to those whose increased ≥ 50% was 1.40 (CI, 1.08-1.81), and for those whose PGII and anti-H. pylori IgG levels both increased ≥ 50% relative to those whose levels both decreased ≥ 50% the OR was 3.18 (CI, 2.05-4.93). Changes in gastrin-17 were not statistically significantly associated with progression. These findings suggest that temporal changes in serum PGI, PGII, PGI/II ratio, and anti-H. pylori IgG levels (especially PGII and anti-H. pylori IgG combined) may be useful for assessing and managing risk for progression of gastric precancerous lesions.

Topics: Adult; Aged; Biomarkers, Tumor; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Longitudinal Studies; Male; Middle Aged; Neoplasm Staging; Pepsinogen A; Pepsinogen C; Precancerous Conditions; Prognosis; Stomach Neoplasms

The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide over recent decades. A previous study demonstrated that gastric acid secretion, thought to be an important factor in the increase in the rate of GERD, in Japanese individuals increased in the era from the 1970s to the 1990s. The aim of this study was to evaluate whether gastric acid secretion has altered over the past two decades with and without the influence of Helicobacter pylori infection in nonelderly and elderly Japanese.. Gastric acid secretion, the concentrations of serum gastrin, pepsinogen I, and pepsinogen II, and H. pylori infection were determined in 78 healthy Japanese subjects. The findings were compared with data obtained in the 1990s.. Basal acid output (BAO) and maximal acid output (MAO) gradually decreased with age in H. pylori-negative subjects. In addition, those with H. pylori infection tended to show decreased gastric acid secretion as compared with those without infection, particularly in the elderly group. MAO decreased gradually with age in males, whereas it remained unchanged with age in females. MAO in H. pylori-negative subjects has not changed over the past two decades (17.7 mEq/h vs 17.6 mEq/h in nonelderly subjects, and 15.2 mEq/h vs 12.7 mEq/h in elderly subjects).. In contrast to the increased prevalence of GERD, gastric acid secretion has not increased over the past two decades in Japanese. However, secretion has decreased with age in males but not in females, which may partly explain the sex difference in the age-related GERD prevalence.

Topics: Adult; Aged; Aging; Body Mass Index; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Sex Characteristics; Young Adult

The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995-2014) in gastric acid secretion in normal Japanese patients.. A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis.. Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects.. Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.

Topics: Aged; Aging; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Reference Values

Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria.. A total of 223 subjects without organic diseases who underwent esophagogastroduodenoscopy and endoscopic gastrin test (EGT) for estimating gastrin-stimulated gastric acid secretory response between 1999 and 2012 at our institution were retrospectively analyzed. Two blinded expert endoscopists reviewed the images independently and recorded the endoscopic findings.. According to the EGT values, the enrolled subjects were categorized into hyperchlorhydria, normal acid secretion, and hypochlorhydria groups. In all subjects, hematin (odds ratio [95% confidence interval] = 3.32 [1.40-7.84]) and antral erosion(2.88 [1.24-6.70]) were the predictive endoscopic findings for hyperchlorhydria, and swelling of areae gastricae (14.4 [5.74-36.1]) and open-type atrophy (15.1 [7.35-31.1]) were those for hypochlorhydria. In addition, the predictive endoscopic findings for hyperchlorhydria differed according to the H. pylori infection status, hematin in H. pylori-positive subjects and antral erosion in H. pylori-negative subjects, in contrast to those for hypochlorhydria, which were the same irrespective of the H. pylori infection status.. We could predict the acid secretion status based on the endoscopic findings regardless of H. pylori infection status, which would be of some help for evaluating the risk for acid-related diseases.

Topics: Adult; Aged; Aged, 80 and over; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Humans; Male; Middle Aged; Reproducibility of Results; Retrospective Studies; ROC Curve; Young Adult

Epidemiological studies have demonstrated the relationship between Helicobacter pylori infection and gastric and extra-gastric diseases. Therefore, H. pylori infection might be a "systemic" disease.. To investigate the relationship between H. pylori infection status and serum parameter levels responding to multi-organ functions.. A total of 2,044 subjects were selected, including 1,249 males and 795 females with ages ranging from 16 to 86 years. Relevant parameters including blood lipids, complete blood count, tumor markers, indexes of stomach, kidney, liver, thyroid, and immune system function, H.pylori IgG antibody levels, and (14)C-UBT were collected.. Serum pepsinogen (PG)I, PGII, and gastrin (G)17 levels were decreased in chronic long-term, past, and acute short-term infection patients compared with uninfected controls. However, the serum PGI/II ratio increased gradually. Serum white blood cell levels gradually decreased in past, chronic long-term, and acute short-term infection patients compared with uninfected controls. The same trend was also observed for CD4(+) T cell levels. In addition, LDL levels were higher in chronic long-term infection, HDL levels were lower in past infection, and ALP and CEA levels were higher in acute short-term infection compared with the uninfected group.. Helicobacter pylori infection correlated with increased PGI, PGII, G17, WBC, and CD4(+) T cell levels, and decreased PGI/II ratio. In chronic long-term or past infection, H. pylori infection was associated with higher LDL or lower HDL levels. In acute short-term infection, H. pylori infection correlated with higher ALP and CEA levels. H. pylori infection correlated with serum parameter levels responding to multi-organ functions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Breath Tests; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Leukocyte Count; Lipids; Middle Aged; Pepsinogen A

A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori, Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii, JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI.

Topics: Animals; Antibiosis; Disease Models, Animal; Gastric Acid; Gastrins; Gastrointestinal Microbiome; Helicobacter Infections; Helicobacter pylori; Humans; Lactobacillus; Mice; Proton Pump Inhibitors

Secretion of pepsinogen I (PgI), pepsinogen II (PgII), fasting gastrin-17 (fG-17) and stimulated gastrin-17 (sG-17) changes after Helicobacter pylori eradication. Few data are available on the long-term dynamics of gastric biomarkers after H. pylori eradication.The aim of this study was to investigate the dynamics of gastric biomarkers in H. pylori-positive patients after eradication over a 3-year period and to compare the levels with initially H. pylori-negative patients.. Blood samples for the detection of gastric biomarkers were obtained from dyspeptic patients coming for upper gastrointestinal endoscopy. In H. pylori-positive patients, after eradication therapy, three follow-up blood samples were drawn after 12, 24 and 36 months; in H. pylori-negative patients, two samples were taken - at 12 and after 30 months. Median values of biomarkers in follow-up samples were compared with the baseline sample.. The final sample included 110 patients (median age 67 years, M/F ratio 27/83). In patients after H. pylori eradication (n=83) PgI, PgII, fG-17 and sG-17 had decreased significantly during a 36-month period, whereas the PgI/PgII ratio had increased significantly from 5.59 to 11.64.. In H. pylori-positive dyspeptic patients, after eradication therapy, a decrease in PgI, PgII, fG-17 and sG-17 was observed after 36 months whereas an increase in the PgI/II ratio suggested an improvement in gastric atrophy. The median levels of gastric biomarkers in patients after H. pylori eradication therapy may become similar to biomarker levels among initially H. pylori-negative individuals.

Topics: Aged; Aged, 80 and over; Biomarkers; Dyspepsia; Endoscopy, Gastrointestinal; Fasting; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Time Factors

Hypergastrinemia causes carcinoids or carcinomas in the gastric corpus in animal models. Helicobacter pylori (HP) infection in patients causes atrophy, hypergastrinemia and promotes gastric carcinogenesis. Many patients with gastric cancer have hypergastrinemia and it has therefore been hypothesized that hypergastrinemia promotes carcinogenesis. We have examined the associations between serum gastrin, the anatomical localization of gastric cancer, histological classification and patient survival. Patients with non-cardia gastric adenocarcinomas were included prospectively (n = 80). Tumour localization, histological classification according to Laurén and disease stage were recorded. Preoperative fasting serum gastrin was analysed by radioimmunoassay and HP serology by ELISA. Patient survival was determined after a median postoperative follow-up of 16.5 years. Hypergastrinemic patients had carcinomas located in the gastric corpus more often compared to normogastrinemic patients (81.8 vs 36.2%, p = 0.002). Patients with disease stage 2-4 and hypergastrinemia had shorter survival than normogastrinemic patients [5.0 (1.1-8.9) vs 10.0 (6.4-13.6) months (p = 0.04)]. There was no significant difference in serum gastrin or survival between patients with intestinal and diffuse type carcinomas. Hypergastrinemia was associated with adenocarcinomas in the gastric corpus and shorter survival. The findings support the hypothesis that hypergastrinemia promotes carcinogenesis and affects biological behaviour.

Topics: Adenocarcinoma; Aged; Chromogranin A; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Stomach; Stomach Neoplasms; Survival Rate

The antibacterial and anti-inflammatory activities, and protective effects of extracts (flavonoid glycosides) of Polygonum capitatum were investigated to detect the evidence for the utilization of the herb in the clinical therapy of gastritis caused by H. pylori. A mouse gastritis model was established using H. pylori. According to treating methods, model mice were random assigned into a model group (MG group), a triple antibiotics group (TG group, clarithromycin, omeprazole and amoxicillin), low/middle/high concentrations of flavonoid glycosides groups (LF, MF and HF groups) and low/middle/high concentrations of flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups). A group with pathogen-free mice was regarded as a control group (CG group). The eradicate rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels of IFN-gamma and gastrin were higher in a MG group than those from all other groups (P < 0.05). The serum levels of IFN-gamma and gastrin were reduced significantly in LF, MF and HF groups (P < 0.05) while little changes were observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were lower and higher in MG and CG groups compared with other groups (P<0.05). The serum levels of IL-4 were increased significantly in LF, MF and HF groups (P < 0.05) while little changes were found in LFA, MFA and HFA groups. According to pathological scores, flavonoid glycosides therapy showed better protection for gastric injuries than the combination of flavonoid glycoside and amoxicillin (P < 0.05). The results suggested that flavonoid glycoside has repairing functions for gastric injuries. The results suggest that the plant can treat gastritis and protect against gastric injuries. The flavonoid glycosides from Polygonum capitatum should be developed as a potential drug for the therapy of gastritis caused by H. pylori.

Topics: Animals; Anti-Bacterial Agents; Female; Flavonoids; Gastrins; Gastritis; Glycosides; Helicobacter Infections; Helicobacter pylori; Inflammation; Interferon-gamma; Male; Mice; Mice, Inbred C57BL; Phytotherapy; Polygonum

Although serum pepsinogen tests are useful for predicting the presence of atrophic gastritis, the optimal cut-off values have not been fully evaluated.. To determine the optimal serum pepsinogen cut-off value for predicting atrophic gastritis.. Patients scheduled for upper endoscopy at Severance Hospital, Korea, between August 2012 and October 2013, were recruited prospectively. Endoscopic biopsies for atrophic gastritis were obtained and histologically graded, based on the updated Sydney system.. Ninety-five patients were enrolled in the study. The mean age was 57.7±12.1 years, and 44.2% of the patients were male. Serum pepsinogen I/II ratios were lower in patients with atrophic gastritis than in those without it (antrum, 4.2±1.7 vs. 5.2±2.1, P=0.040; corpus, 3.3±1.9 vs. 5.4±1.9, P<0.001). Serum pepsinogen I/II ratios were significantly correlated with histologic atrophic gastritis (antrum, P=0.030; corpus, P<0.001). Using a cut-off value of 4.9, the sensitivity and specificity of the serum pepsinogen I/II ratio for predicting atrophic gastritis in the antrum were 68.2% and 60.3%, respectively.. The optimal serum pepsinogen I/II ratio cut-off values for atrophic gastritis of the antrum and for the corpus were 4.9 and 3.5, respectively. Serum pepsinogen I/II ratios, with these cut-off values, are useful for screening patients for the presence of atrophic gastritis.

Topics: Aged; Area Under Curve; Biomarkers; Biopsy; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Pyloric Antrum; Reference Values; ROC Curve

Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastrins; Gastritis; Gene Frequency; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Polymorphism, Single Nucleotide; Risk Factors; Stomach Neoplasms; Toll-Like Receptor 4; Young Adult

To evaluate the occurrence of gastroesophageal reflux and possible mechanisms in Helicobacter pylori infection.. Symptoms of H. pylori-infected children, their total gastroesophageal reflux episodes, acid exposure percentage, gastrin, ghrelin, and motilin levels were evaluated before and after H. pylori eradication.. Forty-two H. pylori-infected children were eligible for this study. Acid exposure % and total reflux episodes before and after H. pylori eradication were 10.2%±14.8% vs. 7.71%±5.0% and 94.7%±102.1% vs. 64.6%±55.0%, respectively (p=0.28, p=0.082). There was an insignificant change in the serum gastrin (93.4±153.8 pmol/L vs. 1.28±149.4 pmol/L, p=0.67), ghrelin (7.69±197.5 pg/mL vs. 8.36±299.5 pg/mL, p=0.274), and motilin (75.1±81.2 pg/mL vs. 97.2±80.5 pg/mL, p=0.206) levels after eradication. Gastrin and ghrelin levels were negatively correlated after H. pylori eradication (r=-0.38, p=0.031). There was no association between gastroesophageal reflux episodes and gastrin, ghrelin, and motilin levels (r=0.25 and p=0.11; r= 0.24 and p=0.13; r=-0.23 and p=0.14, respectively).. H. pylori infection is neither protective nor harmful in the gastroesophageal reflux. Neither ghrelin nor motilin levels was associated with gastroesophageal reflux. None of gastrin, ghrelin, and motilin levels was affected by H. pylori infection. There is an inverse association between gastrin and ghrelin levels after H. pylori eradication.

Topics: Adolescent; Biomarkers; Child; Female; Follow-Up Studies; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Humans; Incidence; Male; Motilin; Prognosis; Prospective Studies; Turkey

The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease.. Prospective observational study in a single institutional study.. One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured.. One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up.. Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.

Topics: Aged; Autoimmune Diseases; Chromogranin A; Endoscopy; Enterochromaffin-like Cells; Female; Gastrins; Gastritis; Hashimoto Disease; Helicobacter Infections; Humans; Male; Middle Aged; Neuroendocrine Tumors; Phenotype; Prevalence; Prospective Studies; Risk; Stomach Neoplasms; Thyroid Diseases

Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.. The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.. Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1(Cre) mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1(Cre) mice were paired to either an uninfected Vav-1(Cre) littermate or a BL/6 mouse inoculated with Helicobacter pylori.. GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFβ) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGFβ signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression.. Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.

Topics: Animals; Biomarkers; Cell Proliferation; Cell Transformation, Neoplastic; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Hedgehog Proteins; Helicobacter Infections; Helicobacter pylori; Immunoblotting; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Parabiosis; Phenotype; Real-Time Polymerase Chain Reaction; Smad3 Protein; Transforming Growth Factor beta

Dyspepsia develops in healthy volunteers after withdrawal of proton-pump inhibitors. This phenomenon, attributed to rebound acid hypersecretion, is thought to be mediated by reflex hypergastrinemia.. To measure fasting and postprandial gastrin in patients on long-term proton-pump inhibitor treatment and correlate gastrin levels with the duration of treatment and other potential predictors.. In this cross sectional study patients, with erosive esophagitis, on long-term proton-pump inhibitor treatment and healthy controls underwent gastrin measurements at baseline and four times following a meal and Helicobacter pylori status was determined.. A total of 100 patients and 50 controls were studied. Pre- and postprandial gastrin levels were higher in patients (p<0.001). No significant correlation was found between the area under the gastrin-curve and the treatment duration. Female patients had significantly higher gastrin levels than males pre- and postprandial, whereas such differences was not found in the control group. Female gender was the only independent predictor of s-gastrin levels (OR 2.50 compared to males, 95% CI: 1.08-5.76, p=0.032) in the patient group.. Gastrin values were higher in patients compared to controls. There was no correlation between gastrin levels and treatment duration. Female patients had significantly higher gastrin values than males.

Topics: Aged; Case-Control Studies; Chromogranin A; Cross-Sectional Studies; Dyspepsia; Esophagitis, Peptic; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Postprandial Period; Proton Pump Inhibitors; Sex Factors; Substance Withdrawal Syndrome

Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76-4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23-5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14-2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29-3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.

Topics: Aged; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Colon; Colonic Neoplasms; Colonoscopy; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Male; Polyps; Prospective Studies; Risk Factors

Atrophic gastritis (AG), first step in the cascade leading to gastric adenocarcinoma, is related to Helicobacter pylori (H. pylori) infection. Currently, the gold standard for the diagnosis of AG is esophagogastroduodenoscopy (EGD) with histological examination of the biopsy specimens. However, since the latter are taken in random order and the distribution of AG is often patchy, histology is only representative of mucosal status. Considering this limitation, a test named GastroPanel®, that measures the blood concentrations of pepsinogen I and II, gastrin-17 and H. pylori antibodies, has been developed as a potential non-invasive biopsy. Aim of this study has been to assess the accuracy of GastroPanel® in patients with AG.. Forty-seven dyspeptic patients (24 males, mean age 52.2±9.3 years), in follow-up for antral or diffuse AG, were enrolled. All underwent at least two EGDs with random biopsies and blood collection for GastroPanel® parameters examination.. Of the 47 patients, 16 (34.1%) had histological diagnosis of antral and 31 (65.9%) multifocal AG; 17 (36.2%) patients had mild and 30 (63.8%) had moderate-severe AG. H. pylori was detected in 39 (82.9%) and intestinal metaplasia was found in all patients. GastroPanel® showed 82.9% sensitivity for the diagnosis of AG and 53.8% for the diagnosis of H. pylori infection. The prediction of advanced atrophy was not sufficiently accurate, neither in patients with antral nor in those with multifocal AG.. GastroPanel® can be useful for detecting patients with AG. However, it does not reflect the severity of atrophy.

Topics: Adult; Antibodies, Bacterial; Biomarkers; Biopsy; Dyspepsia; Endoscopy, Digestive System; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index

It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies.. To determine the accuracy of GastroPanel for the diagnosis of CAG.. This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist.. Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 μg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios.. GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended.

Topics: Adult; Algorithms; Antibodies, Bacterial; Biomarkers; Biopsy; Chronic Disease; Double-Blind Method; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Prospective Studies; Pyloric Antrum; Stomach

Pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from Helicobacter pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. The aim of our study was to evaluate the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication.. Altogether 42 patients (25 women, 17 men), mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test.. Eradication was successful in 31 patients (74%) and unsuccessful in 11 patients (26%). Pepsinogen II decreased significantly in both the successful (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased significantly in the successful (P=0.025) but not the unsuccessful (P=0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (P=0.0018) but not in the group in which treatment failed (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values.. A decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.

Topics: Adult; Aged; Antibodies, Bacterial; Biomarkers; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Treatment Outcome; Young Adult

Fasting serum gastrin-17 (FsG17) is considered as a noninvasive biomarker reflecting the structure and functional status of gastric mucosa, but its clinical utility remains unclear. This study aimed to evaluate FsG17 comprehensively: establish the ranges and cut-off points of FsG17 levels in different gastric diseases, identify their influencing factors, and investigate the accuracy of FsG17 for identifying diseased stomach.. The study included 4064 participants from Northern China between 2008 and 2013. FsG17 and serum Helicobacter pylori IgG antibody levels were measured by enzyme-linked immunosorbent assay. Diagnostic accuracy was assessed by receiver operator characteristic curves. Multivariate logistic regression analysis was performed to determine the best predictors of gastric histopathological conditions.. Median FsG17 levels in healthy, non-atrophic, atrophic, and cancerous stomachs were 1.8, 4.0, 3.8, and 6.1 pmol/l, respectively. Age, smoking status, alcohol consumption, H. pylori infection, and predominant lesion site were factors that affected FsG17 levels. The optimal cut-off values for FsG17 were 3.0 pmol/l (sensitivity of 59.3% and specificity of 67.3%) for discriminating between healthy stomach and diseased stomach and 10.7 pmol/l (sensitivity of 37% and specificity of 83.7%) for discriminating between cancerous stomach and cancer-free stomach; the screening accuracy was higher (sensitivity of 50.0% and specificity of 83.0%) for gastric cancer in the corpus. Multivariate analysis showed that FsG17, gender, age, and H. pylori infection were independent predictors of cancerous stomach.. With the progression from health stomach to malignancy, FsG17 levels significantly increased and were influenced by other factors. FsG17 combined with age, gender, and H. pylori infection could distinguish between cancerous stomach and cancer-free stomach. The results will enhance our understanding of the potential clinical utility of FsG17.

Topics: Age Factors; Alcohol Drinking; Area Under Curve; Biomarkers; China; Fasting; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Smoking; Stomach Neoplasms

Vagotomy causes inhibition of basal and post-prandial acid secretion in humans, but the knowledge about the trophic effect of the vagal nerves is limited. Vagotomy is known to induce hypergastrinemia and we aimed to study the long-term effects of proximal gastric vagotomy (PGV) on the oxyntic mucosa and the enterochromaffin-like (ECL) cell density in particular.. Eleven patients operated with PGV because of duodenal ulcer and age- and sex-matched controls were examined 26 to 29 years postoperatively by gastroscopy with biopsies from the antrum and oxyntic mucosa. Neuroendocrine cell volume densities were calculated after immunohistochemical labeling of gastrin, the general neuroendocrine cell marker chromogranin A (CgA) and the ECL cell marker vesicular monoamine transporter 2 (VMAT2). Gastritis was graded and Helicobacter pylori (H. pylori) status was determined by polymerase chain reaction of gastric biopsies. Fasting serum gastrin and CgA were measured.. Serum gastrin was higher in the PGV group compared to controls (median 21.0 [interquartile range (IQR) = 22.0] pmol/L vs 13.0 [IQR = 4.0] pmol/L, p = 0.04). However, there was neither a significant difference in serum CgA or in CgA (neuroendocrine) nor VMAT2 (ECL cell) immunoreactive cell volume density in the oxyntic mucosa. There was significantly more inflammation and atrophy in H. pylori-positive patients, but PGV did not influence the grade of gastritis.. Despite higher serum gastrin concentrations, patients operated with PGV did not have higher ECL cell mass or serum CgA. Vagotomy may prevent the development of ECL cell hyperplasia caused by a moderate hypergastrinemia.

Topics: Aged; Biopsy; Chromogranin A; Duodenal Ulcer; Enterochromaffin-like Cells; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Time Factors; Vagotomy, Proximal Gastric; Vesicular Monoamine Transport Proteins

Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients.. Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers.. Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86).. Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas.

Topics: Adult; Antibodies, Bacterial; Case-Control Studies; Cross-Sectional Studies; Early Detection of Cancer; Female; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Male; Middle Aged; Pepsinogen A; Pepsinogen C; ROC Curve; Sensitivity and Specificity; Stomach Neoplasms

In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties.. We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II.. Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did.. The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

Topics: Adult; Aged; China; Feeding Behavior; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Risk Factors; Stomach Neoplasms

The aim of this study was to investigate the value of serum gastric markers to differentiate between patients with precancerous lesions and nonatrophic chronic gastritis.. Serum samples of 128 patients with dyspepsia who were candidates for endoscopic examination were tested for pepsinogen (PG I and PG II), PG I/II ratio, gastrin 17(G-17), anti-Helicobacter pylori (anti-H pylori ) and anti- CagA antibodies. Two sample t-tests, chi-square tests and Pearson's correlation analyses were used for analysis using SPSS (version 20).. PGI, PG I/II ratio values were decreased significantly in the precancerous lesion group (0.05, 0.001 respectively). The frequency of H pylori infection was significantly (p=0.03) different between the two groups ofthe study.. We suggest PGI and the PG I/II ratio as valuable markers for screening of premalignant gastric lesions.

Topics: Aged; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Biomarkers; Chronic Disease; Cross-Sectional Studies; Dyspepsia; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Male; Pepsinogen A; Pepsinogen C; Precancerous Conditions; Prognosis; Stomach Neoplasms

In Japan, the prevalence of Helicobacter pylori infection is decreasing and the number of patients who receive eradication therapy is increasing. Although the serum level of gastrin is affected by H. pylori infection, the normal level has been unchanged for more than 20 years. The aim of this study was to study whether the present normal range for the serum gastrin level is appropriate for Japanese at present or in the near future.. We studied 810 adults (40-80 years old) who participated in a health survey in 2012. We measured H. pylori stool antigen, titer of serum antibody to H. pylori, and serum level of gastrin. The patient's H. pylori status was defined as positive or negative when the results of both stool antigen and serology were concordant. Subjects who were taking proton-pump inhibitor and had a previous history of gastric surgery were excluded.. Mean serum level of gastrin was 66.2±49.6 pg/mL in 281 H. pylori-negative subjects and 69.7±42.2 pg/mL in 115 patients who had H. pylori eradicated at least 2 years ago. The level of gastrin was 134.4±145.6 pg/mL in 224 patients with H. pylori infection and the level was significantly higher when compared with those in uninfected subjects and eradicated patients (P<0.01).. Because the situation of H. pylori infection has changed remarkably in Japan, a new appropriate normal range of gastrin should be established using current Japanese populations.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Biomarkers; Disease Eradication; Duodenal Diseases; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Prevalence; Reference Values; Stomach Diseases

The article is devoted to the problem of diagnostics of atrophic gastritis. The main principles of morphological diagnostics are presented. The endoscopic findings are discussed. The authors had used the mathematical regression model to reveal groups of patients with some specific signs of atrophic gastritis, such as endoscopic sings, morphological and clinical signs. This model can be used to put a diagnosis and to look after the patients with metaplasia, dysplasia and early cancer.

Topics: Biopsy; Decision Trees; Diagnosis, Differential; Endoscopy, Gastrointestinal; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Metaplasia; Models, Biological; Pepsinogens; Prognosis

Helicobacter pylori-infection associated gastritis is known to be a significant risk factor of gastric cancer. Serum levels of Gastrin-17 and Pepsinogen1which are respectively biomarkers of gastric antral and corpus mucosal activity are well known parameters of atrophic gastritis.. To determine the prevalence of Helicobacter pylori and atrophic gastritis amongst dyspeptic patients and to compare the production of PGI and G-17 in the various atrophic stages.. A total of 139 dyspeptic patients aged 46.68±15.50 years [females 106 aged47.23±15.51years, males 33 aged 44.48±14.62] were included during the one year period, March 2008-april 2009 at the district hospital Tombel. The degree of atrophy was determined by the levels of serum pepsinogen1, and gastrin-17 and the presence of Helicobacter pylori antibodies detected by an enzyme immunoassay.. The prevalence of Helicobacter pylori was 79.82% and that for atrophic gastritis was 6.6%. A decrease in mean serum levels of gastin-17 along with increasing antral atrophy was observed; the mean serum levels of pepsinogen1 were reduced during progression of corpus atrophy.. A weak reverse correlation(r =-0.036) was found between Gastrin-17 and Helicobacter pylori antibodies.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Antibodies, Bacterial; Cameroon; Cross-Sectional Studies; Dyspepsia; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pepsinogen A; Prevalence; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Young Adult

Mucosal alterations after Roux-en-Y gastric bypass for morbid obesity have not been clearly evaluated. This study aims to analyze the mucosal alterations (proliferative status (Ki-67); apoptosis (caspase-3 and BCL-2); hormonal function (gastrin)) in the excluded stomach.. Double-balloon enteroscopy was performed in 35 patients who underwent Roux-en-Y gastric bypass longer than 36 months. Multiple biopsies of the proximal pouch and the excluded gastric mucosa were collected. Gastric biopsies from 32 non-operated obese patients were utilized as controls. Endoscopic biopsies were cut from tissue blocks fixed in formalin and embedded in paraffin. Sections 4 μm thick were examined for immunoexpression using the streptavidin-biotin-peroxidase method.. The two groups were comparable for age, gender, gastritis, intestinal metaplasia, and Helicobacter pylori. The mean number of positive gastrin cells was 55.5 (standard deviation (SD) = 11.7) in the control group and 29.6 (SD = 7.9) in the cases, p = 0.0003. Ki-67 proliferative index in cases (body = 24.7%, antrum = 24.9%) was significantly higher compared to controls (body = 15.0% and antrum = 17.7%), p = 0.002 and 0.01, respectively. Caspase-3 immunoexpression was higher in the controls compared to the excluded stomach (46 vs. 31%), p = 0.02. There was no statistical difference between CD3, CD8, and Bcl-2 immunoexpressions in the control and cases.. Cell proliferation is increased and apoptosis is downregulated in the excluded gastric mucosa compared to the non-operated obese controls. Alterations in cell turnover and in hormonal secretions in these conditions may be of relevance in long-term follow-up.

Topics: Adolescent; Adult; Aged; Brazil; Caspase 3; Cell Proliferation; Double-Balloon Enteroscopy; Down-Regulation; Epithelial Cells; Female; Gastric Bypass; Gastric Mucosa; Gastric Stump; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Obesity, Morbid

Health authorities of Kazakhstan are seeking for effective measures to interrupt the untoward trend, projected to increase the current number of gastric cancer (GC) cases (n=3,316) by 50% until the year 2030.. Use of a non-invasive blood test with four stomach-specific biomarkers [Pepsinogen-I (PG-I) and -II (PG-II), amidated gastrin-17 (G-17), and Helicobacter pylori (HP) IgG antibodies], to assess for the prevalence of stomach conditions: Helicobacter pylori (HP) infection and atrophic gastritis (AG), both known to increase GC risk of in Kazakhstan.. A cohort of 835 (symptomatic and asymptomatic) cases (473 women and 362 men)(median age 46.8 years; range 13.6-74.8) was examined with a panel of biomarkers. Results were assigned in five categories: 1) Healthy stomach, 2) HP infection, 3) atrophic gastritis (AG) of the antrum, 4) AG of the corpus, and 5) AG of both antrum and corpus (pangastritis).. The distribution in these five categories was identical in both sexes (p=0.259). Healthy stomach was detected only in 196 (23.5%) subjects, whereas the vast majority, 62.3% (n=519) had HP infection (with no AG). In 118 (14.1%) subjects, results were consistent with AG; in antrum (n=72), corpus (n=42) or pangastritis (n=4). Prevalence of AG increased with patient's age in both sexes. There was no age-related pattern in biomarker levels, and only slight differences between the genders.. While capable of detecting the subjects at risk for GC (HP or AG), GP seems to be a cost-effective means to intervene the current ominous trend in GC incidence in Kazakhstan.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Biomarkers; Dyspepsia; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Kazakhstan; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Phenotype; Prevalence; Sex Distribution; Young Adult

Gastric cancer remains a significant medical and social problem. Familial, hereditary, social, and demographic factors increase the susceptibility of subjects to cancer development, especially those infected with Helicobacter pylori (H. pylori). Apart from genetic studies, there are ongoing biochemical studies of possible practical value in assessment of the risk of gastric cancer development. The GastroPanelBiohit test, that include determination of the levels of gastrin (G-17), pepsinogen I (PGI), pepsinogen II (PGII) and antibodies IgG/IgA against H. pylori in serum, allowed us to determine whether there are any abnormal changes in the gastric mucosa. The aim of the study was to determine whether GastroPanel parameters, identified in patients with dyspeptic symptoms (with or without history of gastric cancer in first degree relatives) before and after successful eradication of H. pylori, have any clinical value, especially in gastric cancer development.. The study comprised 61 patients aged 18-56 years with symptoms of dyspepsia. In all patients, the preliminary urea breath test (UBT) for the presence of H. pylori was performed and the positive result qualified for further study. For final analysis, 42 patients were approved, who were divided into two groups: group I (a control group) - 22 patients with negative family history of gastric cancer among the relatives of first degree, group II - 20 patients with positive history of gastric cancer among the relatives of first degree. All the patients had the gastroscopy with the biopsy of gastric mucosa for the histopathological evaluation. Additionally, the GastroPanel test was performed.. In the blood serum of the patients with H. pylori infection, the concentrations of gastrin (G-17), pepsinogen I (PGI) and pepsinogen II (PGII) did not depend on family history of gastric cancer (p > 0.05). Successful eradication of H. pylori decreases the levels of G-17, PGI and PGII (statistical significance p < 0.05), and this correlates with the histopathological changes of gastric mucosa. The patients with positive family history of gastric cancer had more intense H. pylori colonization of gastric mucosa (IV degree of insensitivity of infection in UBT; group I - 22% vs group II - 69%) as compared to the control group. After effective eradication of H. pylori, statistically significant decreases of IgG H. pylori antibodies and of the level of gastrin (p < 0.05) in blood serum were seen (in a 3 months follow up) only in the control group.. Independently of the history of familial gastric cancer, the GastroPanelBiohit test provides important clinical data useful for diagnosis, for assessment of effectiveness of H. pylori eradication therapy and in evaluation of the degree of the inflammatory changes in gastric mucosa.

Topics: Adolescent; Adult; Biopsy; Breath Tests; Dyspepsia; Female; Gastric Mucosa; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin A; Immunoglobulin G; Male; Medical History Taking; Middle Aged; Pepsinogen A; Pepsinogen C; Stomach Neoplasms; Urea; Young Adult

Gastrin is a growth factor for the gastric epithelial cells. However, it is unknown how gastric receptor (GR) expression is regulated in the gastric mucosa. We studied GR expression using a newly raised antibody and investigated the relationship between GR expression and gastritis.. Gastric receptor expression in 63 human gastric mucosa was studied. Helicobacter pylori infection and histological gastritis status were evaluated in gastric biopsy samples. In gastric ulcer cases, additional biopsy specimens were taken from injured mucosa. Fasting sera were collected and serum gastrin level evaluated. MKN-28 cells were cultured at various pH conditions, and the change in GR expression was determined.. Gastric receptor expression was detected in the foveolar epithelium of the gastric mucosa, and its expression was stronger in patients infected with H. pylori. In particular, higher expression was detected in regenerating injured mucosa. There was no association between gastritis score/serum gastrin level and GR expression in H. pylori-positive cases. In MKN-28 cells, GR protein expression was lower in neutral conditions than in acidic or alkaline conditions.. Gastric mucosal injury with H. pylori infection destroys the pH barrier on the foveolar epithelium and may induce GR expression through pH changes.

Topics: Adenocarcinoma; Aged; Biopsy; Cell Line, Tumor; Female; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Receptor, Cholecystokinin B; Stomach Neoplasms

In a prospective study the risk of subsequent gastric cancer (GC) was assessed in persons aged 45-69 over 5 years after the initial testing with a set of serological tests (pepsinogen I, pepsinogen II, gastrin-17, antibodies to Helicobacter pylori). The presence of gastric atrophy markers was a significant predictor of GC in the forthcoming years. Non-invasive techniques may be used in the formation of high-risk groups, followed by GC active surveillance.

Topics: Aged; Antibodies, Bacterial; Biomarkers; Cohort Studies; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pepsinogens; Retrospective Studies; Serologic Tests; Stomach Neoplasms

Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied, and the mechanisms by which FA exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression, and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers.. Hypergastrinemic mice infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements, and immunohistochemistry with anti-5-methylcytosine. We also profiled gene expression in the same tissues.. We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and immunohistochemistry for lymphocyte markers.. We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to prevent global loss of methylation and suppress inflammation.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Disease Models, Animal; DNA Methylation; Folic Acid; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Profiling; Gene Expression Regulation; Helicobacter felis; Helicobacter Infections; Homocysteine; Immunohistochemistry; Lymphocytes; Male; Mice; Mice, Transgenic; Myofibroblasts; Stomach; Stomach Neoplasms; Stromal Cells; Up-Regulation

One of the most important hormones in the human stomach is the peptide gastrin. It is mainly required for the regulation of gastric pH but is also involved in growth and differentiation of gastric epithelial cells. In Helicobacter pylori infected patients, gastrin secretion can be upregulated by the pathogen, resulting in hypergastrinaemia. H pylori induced hypergastrinaemia is described as being a major risk factor for the development of gastric adenocarcinoma.. In this study, the upstream receptor complex and bacterial factors involved in H pylori induced gastrin gene expression were investigated, utilising gastric epithelial cells which were stably transfected with a human gastrin promoter luciferase reporter construct.. Integrin linked kinase (ILK) and integrin β5, but not integrin β1, played an important role in gastrin promoter activation. Interestingly, a novel CagL/integrin β5/ILK signalling complex was characterised as being important for H pylori induced gastrin expression. On interaction of H pylori with αvβ(5)-integrin and ILK, the epidermal growth factor receptor (EGFR)→Raf→mitogen activated protein kinase kinase (MEK)→extracellular signal regulated kinase (Erk) downstream signalling cascade was identified which plays a central role in H pylori gastrin induction.. The newly discovered recognition receptor complex could be a useful target in treating precancerous conditions triggered by H pylori induced hypergastrinaemia.

Topics: Animals; Bacterial Proteins; Epithelial Cells; Gastric Mucosa; Gastrins; Gene Expression; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Real-Time Polymerase Chain Reaction; Signal Transduction; Stomach Neoplasms

Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia.. Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed.. Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio.. Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.

Topics: Adenocarcinoma; Aged; Antibodies, Bacterial; Antigens, Bacterial; Atrophy; Bacterial Proteins; Biomarkers, Tumor; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Precancerous Conditions; Retrospective Studies; Stomach Neoplasms

Topics: Animals; Bacterial Proteins; Epithelial Cells; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Stomach Neoplasms

Helicobacter pylori (HP) has been associated with neuroendocrine tumors of the stomach and duodenum. Gastric enterochromaffin-like (ECL) cell tumors and duodenal gastrinomas have also been associated with HP gastritis in separate series but have not been reported together. With other possible causes excluded, we present a patient with HP-associated atrophy of the oxyntic mucosa that ultimately resulted in stimulation and reactive hyperplasia of gastrin-producing cells in both the antrum and proximal duodenum, the latter progressing to formation of a gastrin-producing cell nodule (gastrinoma). Both of these sources of gastrin resulted in ECL hyperplasia in the atrophied oxyntic mucosa with progression to microcarcinoids and well-differentiated neuroendocrine tumors, along with hypertrophy of residual proximal gastric parietal cells. As atrophy tends to spread from the antrum proximally, residual oxyntic mucosa was still infected with HP and offers 1 explanation for the apparent paradox of atrophic gastritis with ECL hyperplasia and neoplasia in the distal oxyntic mucosa, with proximal oxyntic mucosa showing mild hypertrophic changes in a background of typical HP gastritis.

Topics: Aged; Atrophy; Chronic Disease; Duodenal Neoplasms; Gastrectomy; Gastrinoma; Gastrins; Gastritis; Helicobacter Infections; Humans; Intestinal Mucosa; Male; Neoplasms, Multiple Primary; Neuroendocrine Tumors; Stomach Neoplasms

We aimed to determine the etiology of patients with duodenal and gastric ulcers.. 140 patients diagnosed with peptic ulcer between April 2002-2009 were enrolled in this prospective study. Two biopsy specimens were collected from the antrum and corpus for histology and one for rapid urease testing, and stool samples were analyzed for Helicobacter pylori antigen. Serum calcium and gastrin levels were also analyzed.. 82 (58%) patients were male, with a median age of 47.70±15.03 years (range: 16-92). The ulcer was located in the duodenum in 96 patients, stomach in 40, and both duodenum and stomach in 4. The rates of patients positive for Helicobacter pylori antigen in stool, positive in urease testing and positive for Helicobacter pylori presence in antral and corpus samples were 48%, 52%, 67%, and 60%, respectively. 107 (76%) patients were positive for Helicobacter pylori in one of the test methods. 64 (46%) patients had a history of nonsteroidal antiinflammatory drug use within the last month. Mean levels of calcium and gastrin were 9.29±0.40 (7.90-10.20) and 73.96±89.88 (12.86-562.50), respectively. Gastrin level was correlated to inflammatory activity (p<0.05). 19 (13.6%) of the patients were negative for Helicobacter pylori, nonsteroidal anti- inflammatory drug use and hypersecretory illness, and were classified as idiopathic.. The most common cause of duodenal and gastric ulcer was Helicobacter pylori, and it was responsible for three-fourths of the cases. About half of the patients had a history of nonsteroidal antiinflammatory drug use, and nonsteroidal antiinflammatory drug and Helicobacter pylori were both responsible for the ulcer in three-fourths of these patients. In about one-tenth of the patients, nonsteroidal antiinflammatory drug use was the cause of ulcer alone, and about one-tenth of the ulcers were classified as idiopathic.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Bacterial; Calcium; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Stomach Ulcer; Urease; Young Adult

Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B(12) deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG.. 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B(12), antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated.. The mean age of the patients was 53.06 ± 12.7 years (range 24-81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B(12) deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA.. In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B(12) deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B(12) deficiency should be investigated for the presence of AIG.

Topics: Adenomatous Polyps; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Autoimmune Diseases; Carcinoid Tumor; Diarrhea; Female; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Iron; Iron Deficiencies; Male; Middle Aged; Parietal Cells, Gastric; Polyps; Sex Factors; Stomach Neoplasms; Vitamin B 12 Deficiency; Young Adult

The aim of the study was to assess the accuracy of some specific biochemical indicators in discriminating between Helicobacter pylori-associated gastritis and H. pylori-associated stomach cancer (serum gastrin level, serum soluble E-cadherin and tissue COX-2 activity, as well as serodiagnostic markers for H. pylori infection) in order to find a simple diagnostic test that can reasonably predict the development of gastric cancer. The study participants comprised 20 patients with gastric carcinoma, 20 patients with positive H. pylori-associated gastritis and 20 individuals as the control group. Standard procedures and quality control measures were followed. Using cut-off values and ROC analysis to assess the diagnostic abilities of the biochemical indicators, E-cadherin showed the highest sensitivity (100%). We suggest that close follow-up together with periodic endoscopic examination for all patients with persistent H. pylori infection and serum soluble E-cadherin level above 5 microg/mL is essential.

Topics: Biomarkers, Tumor; Cadherins; Case-Control Studies; Cyclooxygenase 2; Diagnosis, Differential; Early Diagnosis; Egypt; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Risk Assessment; Sensitivity and Specificity; Stomach Neoplasms

Gastric cancer is one of the most common malignant tumors causing death in Fujian Province, China. However, the mortality of gastric cancer is greatly varied in different areas in Fujian; for example, the mortality in Changle City is 7.4 times higher than that in Fuan City. In this study, we compared the differences in serological parameters, pepsinogen (PG) I, PG II, gastrin-17 (G-17), and Helicobacter pylori (H. pylori) antibody, between the two cities. It has been reported that low serum PG I is correlated with atrophic gastritis, a high-risk condition for developing gastric cancer, while high serum G-17 has been used for serological detection of atrophic corpus gastritis. We recruited 224 healthy subjects in Changle and 229 healthy subjects in Fuan, matched in age and sex. The serum levels of PG II and G-17 were significantly higher in Changle than those in Fuan. Importantly, the frequency of the subjects with low serum PG I (< 25 μg/L) was significantly higher in Changle than in Fuan, although the serum PG I levels were similar between the two cities. Moreover, the percentage of the subjects with high serum G-17 (≥ 2 pmol/L) and the positive rate of serum IgG antibody against H. pylori were significantly higher in Changle than those in Fuan. The detected differences in these serological parameters are consistent with the notion that the prevalence of atrophic gastritis may be higher in Changle than in Fuan, which results in a higher risk condition for developing gastric cancer in Changle.

Topics: Adult; Aged; Antibodies, Bacterial; China; Cities; Female; Gastrins; Geography; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pepsinogens; Residence Characteristics; Stomach Neoplasms

There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model.

Topics: Acute-Phase Proteins; Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 6; Cation Transport Proteins; Gastrins; Gene Expression Regulation; Helicobacter felis; Helicobacter Infections; Hepcidins; Insulin; Iron; Lipocalin-2; Lipocalins; Male; Mice; Mice, Transgenic; Oncogene Proteins; Parietal Cells, Gastric; Receptors, Transferrin; Signal Transduction

To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin.. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency.. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with "borderline" PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases.. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic "serological biopsy."

Topics: Aged; Antibodies; Autoimmune Diseases; Biopsy; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Lymphocytes; Male; Middle Aged; Parietal Cells, Gastric; Serologic Tests

Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice.. We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing.. Germfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P<0.05, compared with germfree controls). Only 2 of 26 female, whereas 8 of 18 male, H pylori-infected INS-GAS mice developed low to high-grade GIN by 11 months postinfection. Stomachs of H pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes.. Gastric lesions take 13 months longer to develop in germfree INS-GAS mice than male SPF INS-GAS mice. H pylori monoassociation accelerated gastritis and GIN but caused less severe gastric lesions and delayed onset of GIN compared with H pylori-infected INS-GAS mice with complex gastric microbiota. Changes in gastric microbiota composition might promote GIN in achlorhydric stomachs of SPF mice.

Topics: Adenocarcinoma; Animals; Bacteroidetes; Female; Gastrins; Gastritis; Gastrointestinal Neoplasms; Germ-Free Life; Helicobacter Infections; Helicobacter pylori; Inflammation Mediators; Insulin; Male; Mice; Mice, Transgenic; Precancerous Conditions; Sex Factors

Gastrin is secreted from a subset of neuroendocrine cells residing in the gastric antrum known as G cells, but low levels are also expressed in fetal pancreas and intestine and in many solid malignancies. Although past studies have suggested that antral gastrin is transcriptionally regulated by inflammation, gastric pH, somatostatin, and neoplastic transformation, the transcriptional regulation of gastrin has not previously been demonstrated in vivo. Here, we describe the creation of an enhanced green fluorescent protein reporter (mGAS-EGFP) mouse using a bacterial artificial chromosome that contains the entire mouse gastrin gene. Three founder lines expressed GFP signals in the gastric antrum and the transitional zone to the corpus. In addition, GFP(+) cells could be detected in the fetal pancreatic islets and small intestinal villi, but not in these organs of the adult mice. The administration of acid-suppressive reagents such as proton pump inhibitor omeprazole and gastrin/CCK-2 receptor antagonist YF476 significantly increased GFP signal intensity and GFP(+) cell numbers in the antrum, whereas these parameters were decreased by overnight fasting, octreotide (long-lasting somatostatin ortholog) infusion, and Helicobacter felis infection. GFP(+) cells were also detected in the anterior lobe of the pituitary gland and importantly in the colonic tumor cells induced by administration with azoxymethane and dextran sulfate sodium salt. This transgenic mouse provides a useful tool to study the regulation of mouse gastrin gene in vivo, thus contributing to our understanding of the mechanisms involved in transcriptional control of the gastrin gene.

Topics: Aging; Animals; Azoxymethane; Carcinogens; Chromosomes, Artificial, Bacterial; Colonic Neoplasms; Dextran Sulfate; Down-Regulation; Fasting; Fetus; Gastric Acid; Gastrin-Secreting Cells; Gastrins; Gene Expression Regulation, Developmental; Genes, Reporter; Green Fluorescent Proteins; Helicobacter felis; Helicobacter Infections; Mice; Mice, Transgenic; Pyloric Antrum; Somatostatin; Tissue Distribution; Transcription, Genetic; Transgenes; Up-Regulation

We investigated whether corpus atrophic gastritis worsens in Mongolian gerbils (MGs) after long-term administration of proton pump inhibitor (PPI). MGs are an excellent model for studying Helicobacter pylori-related gastritis and adenocarcinoma.. MGs were separated into four groups (n =15/group); H pylori (ATCC43504) was inoculated into the OPZ(omeprazole)+Hp (H pylori) and Hp groups, a PPI (OPZ) was administered to the OPZ+Hp and OPZ groups and the control group received no treatment. MGs had access to food containing omeprazole (100 mg/kg body weight/day) for 6 months, after which their stomachs were removed and cut into nine sections (six sections in the fundus and three sections in the antrum). Corpus atrophy was evaluated by the absence of parietal cells in the six sections in the fundus. First, we calculated a percentage of the area devoid of parietal cells in each haematoxylin and eosin-stained section, and then we scored the degree of atrophy by adding the percentages of the six sections. A full score was 600.. Neutrophilic and lymphoid infiltrates were greater in the OPZ+Hp group than in the other groups. The corpus atrophy score in the OPZ+Hp group was significantly higher than that in the Hp group (p < 0.0048, Student t test). Significantly more adenocarcinomas were found in the OPZ+Hp (60%) than in the Hp (7%) group animals.. Long-term PPI administration promotes development of adenocarcinoma, which is associated with the progression of atrophic corpus gastritis in MGs infected with H pylori.

Topics: Adenocarcinoma; Animals; Body Weight; Cocarcinogenesis; Disease Models, Animal; Disease Progression; Drug Administration Schedule; Gastrins; Gastritis, Atrophic; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Metaplasia; Proton Pump Inhibitors; Stomach; Stomach Neoplasms

Epigenetic alterations have been correlated with field cancerization in human patients, but evidence from experimental models that specific epigenetic changes can initiate cancer has been lacking. Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone gastrin exerts a suppressive effect on antral gastric carcinogenesis.. N-methyl-N-nitrosourea (MNU)-dependent gastric cancer was investigated in hypergastrinemic (INS-GAS), gastrin-deficient (GAS(-/-)), Tff1-deficient (Tff1(+/-)), and wild-type (WT) mice. Epigenetic alterations of the trefoil factor 1 (TFF1) tumor suppressor gene were evaluated in vitro and in vivo.. Human intestinal-type gastric cancers in the antrum exhibited progressive TFF1 repression and promoter hypermethylation. Mice treated with MNU exhibited a field defect characterized by widespread Tff1 repression associated with histone H3 lysine 9 methylation and H3 deacetylation at the Tff1 promoter in epithelial cells. In MNU-induced advanced cancers, DNA methylation at the Tff1 promoter was observed. Tumor induction and Tff1 repression were increased in MNU-treated mice by Helicobacter infection. Hypergastrinemia suppressed MNU-dependent tumor initiation and progression in a manner that correlated with gene silencing and epigenetic alterations of Tff1. In contrast, homozygous gastrin-deficient and heterozygous Tff1-deficient mice showed enhanced MNU-dependent field defects and cancer initiation compared with WT mice. In gastric cancer cells, gastrin stimulation partially reversed the epigenetic silencing in the TFF1 promoter.. Initiation of antral gastric cancer is associated with progressive epigenetic silencing of TFF1, which can be suppressed by the hormone gastrin.

Topics: Adult; Aged; Aged, 80 and over; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Chromatin Assembly and Disassembly; Disease Models, Animal; DNA Methylation; Female; Gastrins; Gene Expression Regulation, Neoplastic; Gene Silencing; Helicobacter felis; Helicobacter Infections; Histones; Humans; Male; Methylnitrosourea; Mice; Mice, Knockout; Middle Aged; Neoplastic Stem Cells; Peptides; Promoter Regions, Genetic; RNA, Messenger; Stomach Neoplasms; Time Factors; Transfection; Trefoil Factor-1; Tumor Suppressor Proteins

The effect of Helicobacter pylori treatment on the potential reversal of atrophic body gastritis (ABG) is controversial. Body atrophy reversal was evaluated in a cohort of H. pylori-negative and treated H. pylori-positive ABG patients.. Observational long-term follow-up cohort study including 300 ABG patients with at least one follow-up gastroscopy with three biopsies from the antrum and three from the body performed no earlier than 1 year after diagnosis was included. H. pylori was diagnosed by Giemsa-stain and serology. H. pylori-positive patients (n = 192) were treated with bismuth-based triple regimen.. After a mean follow-up of 5.2 years, body atrophy reversal was observed in 42/300 patients (14%). Body atrophy reversal occurred more frequently in patients treated for H. pylori than in H. pylori-negative ones (21.3% vs 0.9%, p < 0.00001) and was observed between 2 and 8 years after treatment in 52% of cases. Predictive factors for body atrophy reversal at Cox-regression analysis were mild atrophy (HR 2.14; 95% CI 1.12-4.1), moderate-severe inflammation (HR 5.3; 95% CI 1.64-17.3), and absence of intestinal metaplasia (HR 2.4; 95% CI 1.2-4.8).. Body atrophy reversal was observed in about 20% of ABG patients treated for H. pylori infection, and about 50% of reversals occurred during long-term follow-up.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Antibodies; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Intestines; Male; Metaplasia; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Proportional Hazards Models; Pyloric Antrum; Regression Analysis; Retrospective Studies; Young Adult

We investigated whether serum levels of pepsinogen (sPG)I and sPGII, the ratio of sPGI to sPGII, or serum levels of gastrin-17 (sG17), can be used to assess eradication of Helicobacter Pylori 8 weeks after treatment.. We performed a prospective study of 228 consecutive patients with H pylori infections. At the start of the trial (baseline), patients were assessed using the (13)C-urea breath test ((13)C-UBT) and endoscopy, and serum levels of pepsinogens and gastrin levels were measured. Patients were offered a 7-day triple therapy and asked to return 8 weeks after treatment for another (13)C-UBT and measurements of serum levels of sG17, sPGI, and sPGII (175 patients completed the study).. The eradication rate of H pylori was 67%. Percentage variation in levels of sPGI and sPGII, the ratio of sPGI to sPGII, and in levels of sG17 resulted in area under the curve values of 0.858, 0.973, 0.940, and 0.810, respectively, for H pylori eradication. A decrease of 22.7% or greater in the level of sPGII detected H pylori eradication with 100% sensitivity and 96.6% specificity. Spectrum analysis did not identify differences in accuracy.. Percentage variation of sPGII levels 8 weeks after therapy for H pylori infection correlates with eradication. Additional studies are needed to confirm these results.

Topics: Adult; Anti-Bacterial Agents; Drug Monitoring; Drug Therapy; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Prospective Studies; Serum

Topics: Aftercare; Drug Monitoring; Gastrins; Helicobacter Infections; Humans; Pepsinogens; Serum; Treatment Outcome

The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion.. Patients with GERD (n = 123), who were not on acid-suppressive drugs, and had not received anti-H. pylori therapy, underwent gastroduodenoscopy and tests for H. pylori detection. Esophageal manometry, 24-h pH metry, serum pepsinogen-I (PG-I), PG-II and gastrin-17 ELISA were done in all these patients. Univariate and multivariate analyses were performed to assess independent predictors for erosive esophagitis (EE).. Of 123 patients (mean age 40.5 [13.1] years, 85 [69.1%] men), 59 (47.9%) had H. pylori infection. EE was more common in H. pylori non-infected than infected (49 vs. 32, p < 0.001). Among patients older than 40 years, absence of H. pylori was associated with lower esophageal pH and longer reflux (p = 0.02 and p < 0.001, respectively). PG-I/PG-II ratio was lower in H. pylori infected subjects (p < 0.001). In patients with higher LA grade of esophagitis, elevated PG-I levels and PG-I/PG-II ratio were associated with more acidic stomach (p = 0.04 and p = 0.01, respectively). Multivariate analyses showed low gastrin-17 (p = 0.016), higher age (p = 0.013), hiatus hernia (p = 0.004) and absence of H. pylori (p = 0.03) were independent predictors for risk of EE.. H. pylori infection is associated with less acidic stomach and less severe GERD. Low gastrin-17, higher age, hiatus hernia and absence of H. pylori were the best predictors for EE risk.

Topics: Adult; Age Factors; Endoscopy, Digestive System; Esophagitis, Peptic; Esophagus; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Severity of Illness Index; Sex Factors

To investigate plasma ghrelin, gastrin and growth hormone secretagogue receptor (GHS-R) expression in advanced gastric cancer (GC) before and after resection.. Seventy subjects in whom endoscopy of the upper gastrointestinal tract was performed in the Department of General Surgery at Cracow University during the past decade: (1) 25 patients with GC associated with Helicobacter pylori (H. pylori) infection; (2) 10 patients with GC 4-5 years after (total or subtotal) gastrectomy; (3) 25 healthy H. pylori-negative controls, matched by age and BMI to the above two groups; and (4) 10 GC patients 4-5 years after total gastrectomy. Ghrelin and gastrin plasma concentrations were measured by specific radioimmunoassay under fasting conditions and postprandially at 60 and 90 min after ingestion of a mixed meal. GHS-R expression was examined in biopsy samples from intact healthy mucosa and GC tissue using semi-quantitative reverse transcription-polymerase chain reaction.. In healthy controls, fasting plasma ghrelin levels were significantly elevated and declined markedly at 60 and 90 min after a mixed meal. The concomitant enhanced ghrelin, GHS-R and gastrin expression in GC tissue over that recorded in intact mucosa, and the marked rise in plasma gastrin in these subjects under fasting conditions indicate the role of these hormonal factors in GC formation. Fasting plasma levels and postprandial response of ghrelin and gastrin appear to be inversely correlated in healthy subjects. Feeding in the controls resulted in a significant fall in plasma ghrelin with a subsequent rise in plasma gastrin, but in H. pylori-positive GC patients submitted to total or distal gastrectomy, feeding failed to affect significantly the fall in plasma ghrelin that was recorded in these patients before surgery. Fasting ghrelin concentrations were significantly lower in patients 4-5 years after total gastrectomy compared to those in healthy controls and to these in GC patients before surgery.. Elevated plasma gastrin and suppression of fasting ghrelin in patients with GC suggest the existence of a close relationship between these two hormones in gastric carcinogenesis.

Topics: Adult; Aged; Aged, 80 and over; Fasting; Female; Gastrectomy; Gastrins; Ghrelin; Helicobacter Infections; Humans; Male; Middle Aged; Postprandial Period; Radioimmunoassay; Receptors, Ghrelin; Stomach Neoplasms

The neuroendocrine marker, chromogranin A (CgA) increases during medium- or long-term proton-pump inhibitor (PPI) treatment.. To analyze the effect of ultra-short-term and diverse dose of PPI therapy on serum CgA and gastrin levels and evaluate the effect of PPI treatment cessation.. Fasting serum CgA and gastrin were determined in newly diagnosed gastroesophageal reflux disease (GERD) patients (n = 54) treated with diverse doses of PPI during a 28-day period, in patients treated with PPIs for at least 6 months (n = 42), and in subjects where PPI treatment could be stopped (n = 11).. A significant stepwise increase of CgA levels was observed after 5 days during the 28-day period treatment with all PPI doses. Gastrin increased significantly also in the standard and high-dose PPI subgroups. The most prominent increase of CgA was observed in the high-dose PPI subgroup. Serum CgA and gastrin were markedly elevated after 6 months of PPI treatment, and decreased significantly after 5 days of PPI discontinuation.. Serum CgA increases significantly even after ultra-short-term (5 days) PPI therapy. After long-term treatment, 5-day cessation of PPI therapy is sufficient to decrease significantly both CgA and gastrin levels.

Topics: Adult; Aged; Aged, 80 and over; Chromogranin A; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Time Factors; Young Adult

The relative contribution of gastric acid secretion and Helicobacter pylori infection to low-dose aspirin-induced gastropathy remains to be clarified. This is partly because the capability of the infection to modify gastric acid secretion complicates the interaction. The aim of this study was to estimate the association of aspirin-induced mucosal injury, as well as H. pylori infection, with gastric acid output.. A total of 186 male outpatients, comprising 60 aspirin takers, on 100 mg of enteric-coated aspirin daily and 126 non-aspirin takers were prospectively enrolled in this study. Gastrin-stimulated acid output was estimated by the endoscopic gastrin test. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score. Multiple logistic regression analyses were used to adjust for potential confounders.. The gastric acid secretion level, with an odds ratio (OR) (95% confidence interval [CI]) of 10.5 (3.0-36.9) and aspirin administration, with an OR (95% CI) of 7.4 (3.0-18.3) were independently associated with gastric mucosal injury, and the co-existence of both factors greatly elevated the risk of mucosal injury, with an OR (95% CI) of 77.0 (13.5-440.0). H. pylori infection, itself, did not show any significant effect on the aspirin-induced mucosal injury after adjusting for gastric acid secretion.. This study has demonstrated that aspirin-induced gastropathy is directly associated with gastric acid secretion. In addition, it also suggested that the gastric acid secretion level modulates the association between H. pylori infection and aspirin-induced gastropathy.

Topics: Aged; Aspirin; Endoscopy, Gastrointestinal; Fibrinolytic Agents; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Logistic Models; Male; Middle Aged; Prospective Studies; Stomach Diseases

The Operative Link for Gastritis Assessment (OLGA) staging system has been proposed as a histopathological reporting system of gastric atrophy. Noninvasive methods for indirect evaluation of gastric mucosal atrophy by biomarkers are also being introduced.. To analyze gastric mucosal atrophy by biomarkers, pepsinogen I (PgI), pepsinogen II (PgII), PgI/PgII ratio, fasting gastrin-17 (G-17), stimulated gastrin-17 (sG-17), in relation to OLGA gastritis stage.. Gastric biopsies were taken from 269 prospective patients referred for upper endoscopy because of dyspeptic problems and evaluated by two expert pathologists (D.J. and P.S.). Atrophy was assessed according to the OLGA staging system. Pg I, PgII, Pg I/II, G-17, sG-17 were determined in a plasma sample.. The mean levels of PgI and PgI/PgII decreased significantly from 90.8 μg/l and 7.6 in stage 0 gastritis to 64.3 μg/l and 4.3 in high-stage gastritis. The mean values of G-17 and sG-17 were significantly higher among patients with stage II gastritis compared with stage 0 and high-stage gastritis.The proportion of patients with normal mucosa and nonatrophic gastritis according to biomarkers decreased from 78% in stage 0 to 22% in high-stage (III-IV) gastritis. Among the latter no case with normal mucosa, according to biomarkers, was observed.. A significant inverse correlation between the mean levels of PgI, PgI/II ratio and the OLGA stage was observed. Percentage of dyspeptic patients with normal mucosa, by blood biomarkers, decreased with increasing OLGA gastritis stages. OLGA staging system provides a good frame for scientific analysis of gastric mucosal atrophy.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies

Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.. Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.. In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.

Topics: Adenoma; Animals; Base Sequence; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cellular Senescence; Down-Regulation; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Mice, Knockout; MicroRNAs; Molecular Sequence Data; Pyloric Antrum; Signal Transduction; Stomach Neoplasms; Tumor Suppressor Protein p53

Barrett's esophageal cancer is usually included in gastroesophageal (GE) junction adenocarcinoma in Japanese people. No study on the pathogenesis of Barrett's esophageal cancer in comparison with GE junction adenocarcinoma other than Barrett's esophageal cancer has been reported in Japan. The aim of this study was to evaluate the clinical and pathological characteristics and gastric acid secretion of Barrett's esophageal cancer and GE junction adenocarcinoma other than Barrett's esophageal cancer in Japanese subjects.. Twenty-three patients with Barrett's esophageal cancer and 23 patients with GE junction adenocarcinoma other than Barrett's esophageal cancer were enrolled in this study. We evaluated and compared them by assessing the Helicobactor pylori (HP) infection status and gastric acid secretion using the endoscopic gastrin test (EGT).. In the patients with Barrett's esophageal cancer, no significant difference was found in the mean EGT value between HP-positive and -negative patients, but in the patients with GE junction adenocarcinoma other than Barrett's esophageal cancer, the mean EGT value in HP-positive patients was significantly lower than that in HP-negative patients.. Two distinct types of cancer of different origin may be mixed in GE junction adenocarcinomas. One is Barrett's esophageal cancer associated with high gastric acid secretion and reflux of gastric acid into the esophagus, the other is cancer resembling distal gastric cancer associated with gastric atrophy and low gastric acid secretion.

Topics: Adenocarcinoma; Aged; Barrett Esophagus; Case-Control Studies; Endoscopy, Digestive System; Esophageal Neoplasms; Esophagogastric Junction; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Prevalence; Severity of Illness Index

To investigate the association between the gastric emptying rate and the presence of erosive esophagitis in duodenal ulcer (DU) patients among a population with high prevalence of Helicobacter pylori infection.. Cross-sectional survey was performed in a cohort of 60 male patients with either active or healed DU, with or without the presence of erosive esophagitis. Clinical and social-demographic data, blood level of fasting gastrin, pepsinogen I & I/II ratio, and scintigraphic measurement of half emptying time (t(1/2) ) of the solid phase gastric emptying were evaluated.. Patients with active DU and erosive esophagitis tended to have higher plasma level of fasting gastrin than those without erosive esophagitis (75.11±13.74 vs 45.81±5.06pgmL(-1) , P = 0.059). In the absence of H. pylori infection, patients with healed DU and erosive esophagitis had a trend to have longer half-emptying time (t(1/2) : 96.5±6.4 vs 69.1±11.3min, P=0.0572) than those without erosive esophagitis, and statistically significant longer after excluding those diagnosed with hiatal hernia (t(1/2) : 100.8±7.9min vs 69.1±11.3min, P<0.05) from the former group. Among the healed DU patients, those with negative H. pylori infection, hiatal hernia and overweight (body mass index ≥24) had significantly increased risk of severe esophagitis.. Presence of erosive esophagitis in a subset of Taiwanese patients with healed DU and negative H. pylori status was associated with slower solid phase gastric emptying.

Topics: Adult; Cross-Sectional Studies; Duodenal Ulcer; Esophagitis, Peptic; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Taiwan

Proton pump inhibitors (PPIs) are routinely used for control of upper gastrointestinal disorders, often with long-term application. However, there has been some concern about the long-term safety and the possibility of cancer induction and development of neuroendocrine tumors (NET) in the stomach. We therefore analyzed the influence of PPI use on tumor development histologically, immunohistochemically, and serologically in the glandular stomachs of Helicobacter pylori (Hp)-infected and uninfected Mongolian gerbils (MGs). 53 MGs were divided into 6 groups: Hp+25PPI, Hp+5PPI, Hp, 25PPI, 5PPI, and controls. The high-dose Hp+25PPI and 25PPI groups received the PPI (lansoprazole) at 25mg/kg/day, and the low-dose Hp+5PPI and 5PPI groups were given 5mg/kg/day. After 50 or 100 weeks, animals were sacrificed humanely, and the glandular stomach samples were evaluated histologically and phenotypically, using antibodies against chromogranin A (CgA), gastrin and gastric inhibitory polypeptide (GIP). Serum gastrin levels were also examined. NETs occurred in the Hp+25PPI, Hp+5PPI, Hp, and 25PPI groups, but there was no synergistic effect between Hp-infection and high-dose PPI administration. Serum gastrin was increased statistically by Hp infection and high-dose PPI administration, but not influenced by the low-dose. The NETs featured expression of CgA, but not gastrin or GIP. In conclusions, PPI at low dose had no influence on development of carcinomas and NETs in the Hp-infected and uninfected glandular MG stomach, suggesting clinical safety. However, PPI at high dose increased NET development and serum gastrin in the MG model.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Carcinoma; Cell Transformation, Neoplastic; Chromogranin A; Gastric Inhibitory Polypeptide; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lansoprazole; Male; Neoplasms, Glandular and Epithelial; Neuroendocrine Tumors; Proton Pump Inhibitors; Stomach Neoplasms

To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice.. The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylori). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ alone, mice were given a subcutaneous infusion of IFNγ for 7 d. Finally, the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.. H. pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models. Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.. Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression. IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.

Topics: Animals; Cell Line; Female; Gastrins; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Histidine Decarboxylase; Humans; Interferon-gamma; Mice; Mice, Inbred C57BL; Mice, Knockout; Promoter Regions, Genetic; Somatostatin; Stomach

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Gastritis, an inflammation of gastric mucosa, may be due to many pathological factors and infection, such as with Helicobacter pylori. The use of experimental models of gastritis is important to evaluate the biochemical changes and study chemotherapeutic intervention. In a previous study we demonstrated an acute gastritis model induced by iodoacetamide.. Our objective in this study was to evaluate a new gastritis model induced by H. pylori infection in experimental rats in terms of certain biomarkers in serum and mucosal tissues in addition to histopathological examination.. Gastritis was induced in 20 albino Wistar rats by H. pylori isolated from antral biopsy taken from a 49-year-old male patient endoscopically diagnosed as having H. pylori infection. Another ten rats were used as controls. Serum gastrin, pepsinogen I activity, interleukin-6 (IL-6) and gastric mucosal myeloperoxidase (MPO) activity and prostaglandin E(2) (PGE(2)) were measured. Immunostaining for inducible nitric oxide synthase (iNOS), nitrotyrosine and DNA fragmentation were used to further evaluate H. pylori-induced gastritis.. Serum gastrin, IL-6, mucosal MPO activity, and PGE(2) demonstrated significant increases joined with a decreased serum pepsinogen I activity (P < 0.001). Immunohistochemistry demonstrated positive reaction for iNOS, nitrotyrosine and DNA fragmentation.. Helicobacter pylori-induced gastritis models demonstrated massive oxidative stress and pronounced injury in mucosal tissue. Since our model in rats reflected the clinical picture of H. pylori infection, it can be considered as a consistent model to study chemotherapeutic intervention for this type of gastritis.

Topics: Animals; Biomarkers; Biopsy; Dinoprostone; Disease Models, Animal; DNA Fragmentation; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-6; Male; Middle Aged; Nitric Oxide Synthase Type II; Pepsinogen A; Peroxidase; Pyloric Antrum; Rats; Rats, Wistar

Physiology of gastric acid secretion is one of the earliest subjects in medical research and education. Gastric acid secretion has been sometimes inadequately expressed as pH value rather than amount of gastric H(+) secreted per unit time. Gastric acid secretion is regulated by endocrine, paracrine and neurocrine signals via at least three messenger pathways: gastrin-histamine, CCK-somatostatin, and neural network. These pathways have been largely validated and further characterized by phenotyping a series of knockout mouse models. The complexity of gastric acid secretion is illustrated by both expected and unexpected phenotypes of altered acid secretion. For examples, in comparison with wild-type mice, gastrin and CCK double knockout and SSTR(2) knockout mice displayed a shift in the regulation of ECL cells from somatostatin-SSTR(2) pathway to galanin-Gal1 receptor pathway; a shift in the regulation of parietal cells from gastrin-histamine pathway to vagal pathway; and a shift in the CCK(2) receptors on parietal cells from functional silence to activation. The biological function of glycine-extended gastrin in synergizing gastrin-17 has been revealed in gastrin knockout mice. The roles of gastric acid secretion in tumorigenesis and ulceration have not been fully understood. Transgenic hypergastrinemic INS-GAS mice developed a spontaneous gastric cancer, which was associated with an impaired acid secretion. Gastrin knockout mice were still able to produce acid in response to vagal stimulation, especially after H. pylori infection. Taken together, phenotyping of a series of genetically engineered mouse models reveals a high degree of complexity of gastric acid secretion in both physiological and pathophysiological conditions.

Topics: Animals; Cholecystokinin; Gastric Acid; Gastrins; Gene Targeting; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Mice, Knockout; Paracrine Communication; Peptic Ulcer; Receptors, Somatostatin; Stomach Neoplasms

The purpose of this paper is to investigate the relationship between clinical outcome and the intactness of cagPAI in Helicobacter pylori strains from Vietnam. The presence or absence of 30 cagPAI genes was investigated by polymerase chain reaction (PCR) and dot-blotting. H. pylori-induced interleukin-8 secretion and hummingbird phenotype, and H. pylori adhesion to gastric epithelial cells were examined. The serum concentration of pepsinogen 1, pepsinogen 2, and gastrin was also measured in all patients. cagPAI was present in all 103 Vietnamese H. pylori isolates, of which 91 had intact cagPAI and 12 contained only a part of cagPAI. Infection with the partial cagPAI strains was less likely to be associated with peptic ulcer and chronic gastric mucosal inflammation than infection with strains possessing intact cagPAI. The partial cagPAI strains lacked almost all ability to induce interleukin-8 secretion and the hummingbird phenotype in gastric cells. Their adhesion to epithelial cells was significantly decreased in comparison with intact cagPAI strains. Moreover, for the first time, we found an association between cagPAI status and the serum concentration of pepsinogens 1 and 2 in infected patients. H. pylori strains with internal deletion within cagPAI are less virulent and, thus, less likely to be associated with severe clinical outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Adhesion; Bacterial Proteins; DNA, Bacterial; Epithelial Cells; Female; Gastrins; Genomic Islands; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Pepsinogen A; Peptic Ulcer; Polymerase Chain Reaction; Polymorphism, Genetic; Vietnam; Virulence; Virulence Factors; Young Adult

To assess the efficiency of eradication therapy in long-term period using the main signs of functional activity of gastric mucosa (gastrin-17, pepsinogen I, pepsinogen II) and serum antibodies to H. pylori.. 113 patients with chronic gastritis were examihed using clinical, endoscopic and laboratory-based methods of investigation, including GastroPanel Biohit, Finland.. It was observed that after 12 month of successful eradication therapy the titer of IgG to H. pylori did not exceed 60 IU/l, with pepsinogen I and pepsinogen II cut-off values set under 150 microg/l and 15 microg/l respectively.. The decrease of the titer of IgG to H. pylori and concentrations of pepsinogen I and II can be used as criteria of successful eradication therapy in long-term period.

Topics: Adult; Aged; Antibodies, Bacterial; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Time Factors

Helicobacter pylori (H pylori) infection is a major risk factor in the development of distal gastric adenocarcinoma. Development of the invasive phenotype is associated with the phenomenon of epithelial:mesenchymal transition (EMT). Soluble heparin-binding epidermal growth factor (HB-EGF) has been implicated in this process. A study was undertaken to investigate the possibility that matrix metalloproteinase (MMP)-7 is upregulated in H pylori infection as a result of hypergastrinaemia, which may enhance shedding of HB-EGF and contribute towards EMT in gastric adenocarcinoma cell lines.. Three gastric epithelial cell lines (AGS, MGLVA1 and ST16) were co-cultured with the pathogenic H pylori strain 60190 and non-pathogenic strain Tx30a in an in vitro infection model. Gene expression was quantified by real-time PCR, HB-EGF shedding by ELISA and protein expression by immunofluorescence or immunohistochemistry. The INS-GAS mouse, a transgenic mouse model of gastric carcinogenesis which overexpresses amidated gastrin, was used to investigate the in vivo relationship between HB-EGF, MMP-7, gastrin and EMT.. The pathogenic strain of H pylori significantly upregulated EMT-associated genes Snail, Slug and vimentin in all three gastric cell lines to a greater degree than the non-pathogenic strain. Pathogenic H pylori also upregulated HB-EGF shedding, a factor implicated in EMT, which was partially dependent on both gastrin and MMP-7 expression. Gastrin and MMP-7 siRNAs and MMP-7 neutralising antibody significantly reduced upregulation of HB-EGF shedding in H pylori infected gastric cell lines and reduced EMT gene expression. The effect of H pylori on EMT was also reversed by gastrin siRNA. Neutralisation of gastrin in the INS-GAS mouse model reduced expression of MMP-7, HB-EGF and key EMT proteins.. The upregulation of MMP-7 by pathogenic H pylori is partially dependent on gastrin and may have a role in the development of gastric cancer, potentially through EMT, by indirectly increasing levels of soluble HB-EGF.

Topics: Animals; Cell Transformation, Neoplastic; Coculture Techniques; Disease Models, Animal; Epithelial Cells; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinase 7; Mesenchymal Stem Cells; Mice; Mice, Transgenic; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Stomach Neoplasms; Tumor Cells, Cultured; Up-Regulation; Virulence

to find out biomarker as diagnostic tool of H. pylori chronic gastritis.. the design of present study was a diagnostic test and there were 104 subjects with H. pylori chronic gastritis who fulfilled the inclusion and exclusion criteria. The diagnosis of H. pylori chronic gastritis was based on histopathological examination and PCR with ureC primer of the gastric biopsy specimen. In addition, we also performed the examination of serum gastrin, pepsinogen (PG) I and PG (pepsinogen) II level. By using analysis of receiver operating characteristic (ROC), an optimal cut off point of serum gastrin, PGI and PGII level as well as PGI/PGII ratio was determined. Analysis of bivariate logistic regression was used to determine the involved independent variables and possibilities as biomarkers. Significance level was determined by p value <0.05.. we found optimal cut off points on serum gastrin, PGI and PGII level as well as the PGI/PGII ratio at 5.89 pmol/L; 82.5 µg/L; 6.48 µg/L and 13.6 respectively. By using the analysis of bivariate logistic regression, we found gastrin level with p = 0.078 (OR 2.75;95%CI 0.89-8.45) and PGI/PGII ratio with p = 0.000 (OR 14.63;95%CI 3.55-60.63). The opportunity of gastrin level and PGI/PGII ratio as biomarkers was 0.8 with 47% sensitivity, 83% specificity, 74% PPV, 61% NPV, 65% accuracy, LR+ = 2.76 and LR- = 0.64.. gastrin level of >5.89 pmol/L and PGI/PGII ratio ≤13.6 can be utilized as biomarkers of H. pylori chronic gastritis.

Topics: Biopsy; Chronic Disease; Diagnosis, Differential; DNA, Bacterial; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Pepsinogen A; Pepsinogen C; Polymerase Chain Reaction; ROC Curve

Topics: Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Zollinger-Ellison Syndrome

To study the regulatory effect of Helicobacter pylori CagA protein on gastrin promoter and the related signaling pathways as to further elucidate the mechanism of the development and progression of human gastric carcinoma.. After pcDNA3.1ZEO(-)/CagAand PGL/GP were identified by double restriction enzyme digestion, PCR and sequencing, the gastric cancer cell lines AGS and SGC-7901 cells were co-transfected with pcDNA3.1ZEO(-)/CagA and PGL/GP for 48 h. Alternatively, AGS and SGC-7901 cells were transfected by PGL/GP for 36 h later, and infected with Helicobacter pylori for additional 12 h. Meanwhile, the transfected and infected cells were treated using the JAK2 signaling pathway inhibitor AG490 and the ERK signaling pathway inhibitor U0126. The untreated cells and empty-vector-transfected cells were used as the control. Finally, luciferase activity was detected using the luciferase reporter assay system in transfected and infected cells. The levels of gastrin mRNA was determined by TaqMan® real-time quantitative PCR.. After co-transfection with pcDNA3.1ZEO(-)/CagA and PGL/GP, the activities of luciferase were increased by 251.3, 106.1 and 2.4 times in AGS cells and 35.8, 22.7 and 13.4 times in SGC-7901 cells, respectively, as compared with that of the control, pcDNA3.1 ZEO(-)/CagA + PGL3/Basic and pcDNA3.1 ZEO(-) + PGL/GP groups. The activities of luciferase in PGL/GP transfection and HP infection group were also increased by 1673.2, 33.5, 1.4 times in AGS cells and 1180.2, 72.2 and 1.5 times in SGC-7901 cells, respectively, as compared with that of the control, PGL3/Basic + HP and PGL/GP groups. There were statistically significant differences between them (P < 0.05), which suggested that the transcription activity of gastrin promoter increased significantly. But after adding the inhibitor AG490 and U0126, respectively, the activities of luciferase were significantly decreased by 95.7% (U0126) and 33.0% (AG490) in co-transfected AGS cells and 94.8% (U0126) and 86.2% (AG490) in co-transfected SGC-7901 cells with pcDNA3.1ZEO(-)/CagA and PGL/GP (P < 0.05). In the PGL/GP transfection and HP infection group, the activities of luciferase were significantly decreased by 24.6% (U0126) and 25.8% (AG490) in AGS cells and 57.3% (U0126) and 14.1% (AG490) after adding the inhibitor AG490 and U0126, respectively (P < 0.05). The results showed that the gastrin promoter activities were significantly inhibited. The gastrin mRNA levels were 3.0 and 4.5 times higher in HP-infected AGS and SGC-7901 cells, respectively, than that in the control groups. In the cells transfected with pcDNA3.1ZEO(-)/CagA, the gastrin mRNA levels were raised 10.8 and 2.3 times (AGS cells) and 10.9 and 16.2 times (SGC-7901 cells), respectively, as compared with that of control and pcDNA3.1ZEO(-) groups. All of the differences were statistically significant (P < 0.05).. These results suggest that CagA may activate the gastrin promoter and up-regulate the expression of gastrin gene, and CagA is one of the important proteins in regulating gastrin gene expression. The ERK/MAPK and JAK/STAT signaling pathways may be involved in the controlling of gastrin gene expression by CagA.

Topics: Antigens, Bacterial; Antineoplastic Agents; Bacterial Proteins; Butadienes; Cell Line, Tumor; Enzyme Inhibitors; Gastrins; Gene Expression Regulation, Neoplastic; Genetic Vectors; Helicobacter Infections; Helicobacter pylori; Humans; Nitriles; Promoter Regions, Genetic; RNA, Messenger; Stomach Neoplasms; Transfection; Tyrphostins; Up-Regulation

To investigate the effect of a high-protein diet on corpus atrophic gastritis in Helicobacter pylori-infected Mongolian gerbils, H. pylori was administered orally to 5-wk-old Mongolian gerbils; and the animals were then fed a control diet (Group C); a high-fat diet (Group F: 40% fat); a high-protein diet (Group P: 32% protein); or a high-fat, high-protein diet (Group FP: 40% fat, 32% protein) for 50 wk beginning at 7 wk of age. In uninfected animals, the mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). In infected animals, the serum gastrin level was significantly decreased in Group FP and marginally significantly decreased in Group P (P = 0.057) in comparison to Group C. The mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). Mean inflammation and atrophy scores in the corpus were significantly lower in the high-protein groups (Groups P and FP) than in the control groups (Groups C and F; both inflammation and atrophy: P < 0.05). In conclusion, long-term administration of a high-protein diet suppresses corpus atrophic gastritis in H. pylori-infected Mongolian gerbils.

Topics: Animals; Antibodies, Bacterial; Body Weight; Caseins; Dietary Fats; Dietary Proteins; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Metaplasia; Organ Size; Severity of Illness Index; Specific Pathogen-Free Organisms; Stomach; Stomach Neoplasms

Helicobacter pylori (H. pylori) infection has been linked to the development of chronic gastritis, duodenal ulcer disease, and gastric cancer. Helicobacter pylori- infected patients and animal models develop hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis.. To investigate the effect of H. pylori on gastrin gene expression in mice and of human bacterial isolates on gastrin mRNA expressed in a human cell line.. Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were co-cultured with AGS cells to study regulation of human gastrin gene expression. Various MAP kinases were implicated in signal transduction from the bacteria using specific inhibitors. Gastrin reporter constructs and gel shift assays were used to map DNA responsive elements.. In addition to an increase in gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous human gastrin gene through MAP kinase-dependent signaling but not NFκB-dependent signaling. Activation of gastrin through MAPK signaling did not require CagA or VacA virulence factors. Transfection studies demonstrated that a GC-rich motif mediated H. pylori-induction of the gastrin promoter and that the motif inducibly binds Sp1 and Sp3 transcription factors.. Direct contact of live H. pylori bacteria with human cells is sufficient to induce gastrin gene expression.

Topics: Animals; Artificial Gene Fusion; Cell Line, Tumor; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Gastrins; Gene Expression; Gene Expression Profiling; Genes, Reporter; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

to explore whether there is an interaction between Helicobacter pylori (H. pylori), omeprazole and gastrin on the proliferation and apoptosis of gastric epithelial cells.. With omeprazole, H. pylori and gastrin as treatment factors, the in vitro changes of gastric epithelial cells AGS and GES-1 were detected by MTS, Hoechst33342 and flow cytometry.. (1) for a single factor, the gastric mucosal cells (AGS and GES-1) treated by H. pylori or omeprazole show significantly higher apoptosis than that of control group [H. pylori and 104 nmol/L omeprazole group: (17.20 ± 0.90)%, (12.81 ± 0.78)% vs (7.96 ± 1.25)%; (4.60 ± 0.34)%, (6.60 ± 0.76)% vs (3.52 ± 0.16)%; all P < 0.05]. The gastric mucosal cells treated by H. pylori or omeprazole show significantly lower proliferation than that of control group (H. pylori and 104 nmol/L omeprazole group: 13.35 ± 0.55 vs 37.78 ± 1.98, 47.62 ± 2.40 vs 62.44 ± 4.46; 27.15 ± 1.64 vs 32.76 ± 1.57, 29.42 ± 1.44 vs 48.86 ± 4.95; all P < 0.05). The differences were statistically significant and the effects were correlated with the concentration of omeprazole. Gastrin had no direct effect on cellular proliferation and apoptosis (all P > 0.05). (2) For a combinations of factors, the GES-1 cells treated with H. pylori and 500 ng/L gastrin had a significantly higher ratio [(7.25 ± 0.54)% vs (4.60 ± 0.34)%, P < 0.05], while the other groups just showed a rising trend in the proportion of apoptosis cells, but there was no statistical significance. Flow cytometry analysis showed that combinations of H. pylori, omeprazole and gastrin caused lower proliferation than that of H. pylori group, and all changes were statistically significant (AGS: 12.68 ± 0.09, 12.28 ± 0.31 vs 13.35 ± 0.55; GES-1: 22.06 ± 1.61, 18.59 ± 0.09 vs 27.15 ± 1.64; all P < 0.05). And combinations of 104 nmol/L omeprazole and 500 ng/L gastrin caused lower proliferation than that of 104 nmol/L omeprazole group (33.23 ± 5.98 vs 47.62 ± 2.40 and 25.97 ± 0.74 vs 29.42 ± 1.44, both P < 0.05). (3) When comparing the apoptosis and proliferation changes of two cell lines, gastric cancer cells AGS had a more marked changes than immortalized cells GES-1.. gastrin significantly enhances the effects of omeprazole and H. pylori on gastric epithelial cells. It is speculated that the factors of omeprazole, H. pylori and gastrin may have a synergistic effect of decreased proliferation and increased apoptosis of gastric mucosal cells. Thus a long-term proton pump inhibitor treatment of H. pylori patients may carry a higher risk of atrophic gastritis. But it needs to be confirmed by further experiments.

Topics: Apoptosis; Cell Division; Cell Line; Cell Proliferation; Epithelial Cells; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole

Hypergastrinemia and Helicobacter pylori (Hp) infection have been associated with an increased risk for colorectal neoplasia in some studies. However, data from large prospective studies of both associations are lacking. The aim of this study was to evaluate whether serum gastrin levels and/or infection with Hp are associated with the subsequent development of colorectal adenomas.. Subjects (all with a history of adenoma formation) were drawn from 2 previously completed adenoma chemoprevention trials. Participants underwent clearing colonoscopy at baseline with follow-up colonoscopy 1 and 4 years after enrollment. We used commercially available assays on fasting blood specimens to measure serum gastrin levels and Hp serologies 1 year after randomization. Risk ratios for adenoma and advanced adenoma development during the subsequent 3 years were computed by generalized linear regression.. Of the 1794 subjects randomized in the 2 trials, 685 had available serum and were included in the analyses. Gastrin levels were significantly higher in the 239 subjects with Hp titers indicating infection (mean, 88.3 pg/mL) than in those not infected (mean, 73.9 pg/mL; P < .001). In fully adjusted models, gastrin levels were not associated with incident adenoma development (risk ratio [RR], 1.10; 95% confidence interval [CI], 0.78-1.54) or advanced adenoma formation (RR, 0.82; 95% CI, 0.33-2.03). A positive Hp serology was associated with a decreased risk for adenoma formation (RR, 0.76; 95% CI, 0.60-0.96).. Neither hypergastrinemia nor serologic evidence of Hp infection were associated with an increased risk for recurrent adenoma development. These results do not support the notion that gastrin promotes colorectal carcinogenesis, at least at the stage of adenoma development.

Topics: Adenoma; Antibodies, Bacterial; Colorectal Neoplasms; Female; Gastrins; Helicobacter Infections; Humans; Male; Middle Aged; Odds Ratio; Risk Assessment

We have previously developed a rapid, simple endoscopic method for evaluating gastrin-stimulated maximal acid output (the endoscopic gastrin test, EGT). In EGT, gastric fluid newly secreted over 10 min after gastrin stimulation is collected under direct endoscopic visualization. In this study, employing the EGT, we evaluated the effect of rebamipide, a cytoprotective anti-ulcer drug, on gastric mucus secretion. In ten Helicobacter pylori-negative healthy volunteers, gastric juice was collected by EGT prior to and after 4-week administration of rebamipide. The collected gastric juice was subjected to analysis for gastric mucus output. Total gastric mucin output was significantly increased by 53% by rebamipide administration from 3.2 +/- 1.2 mg hexose/10 min to 4.9 +/- 2.2 mg hexose/10 min (P < 0.01). Further analysis by ion-exchange chromatography revealed that rebamipide administration induced a specific increase in acidic mucin rich in sialic acid. Applying EGT, this study demonstrated that rebamipide administration increased gastric mucus secretion in human.

Topics: Adult; Alanine; Anti-Ulcer Agents; Chromatography, Ion Exchange; Endoscopy, Gastrointestinal; Female; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Mucins; Quinolones

The combined evaluation of serum pepsinogens A (PGA) and C (PGC), gastrin-17 (G17) and anti-H. pylori antibodies (anti-H. pylori)(GastroPanel) has recently been proposed as a useful aid for investigating H. pylori-associated gastric mucosal inflammation. Our aim was to evaluate whether GastroPanel can correctly classify children who need or not endoscopy (EGD).. GastroPanel was performed in 554 consecutive children subjected to EGD.. PGC and anti-H. pylori were sensitive (82.5% and 73.1%) and specific (58.1% and 84.0%) indices of H. pylori infection. Antral H. pylori colonization density, inflammation and activity grades were correlated with PGC. PGC and G17 were significantly higher in children with celiac disease (14.9+/-0.88 microg/L and 5.6+/-0.79 pmol/L) than in controls (8.5+/-0.38 microg/L and 2.4+/-0.24 pmol/L). The best cut-offs to distinguish H. pylori infected children from controls were 7.45 microg/L for PGC, 4.2 pmol/L for G17, 18 U for anti-H. pylori and 25 microg/L for PGA. With these cut-offs, GastroPanel had a NPV of 89.6% and a PPV of 66.8%.. A negative GastroPanel result in children with upper abdominal non alarm symptoms, should allow the paediatrician to reasonably rule out the presence of major gastro-duodenal diseases and therefore avoid EGD.

Topics: Adolescent; Antibodies, Bacterial; Celiac Disease; Child; Child, Preschool; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Infant; Logistic Models; Male; Pepsinogen A; Pepsinogen C; Sensitivity and Specificity

Topics: Blood-Brain Barrier; Brain Neoplasms; Breast Neoplasms; Carcinoma; Cytokines; Gastrins; Gastrointestinal Neoplasms; Helicobacter Infections; Humans; Lung Neoplasms; Mast Cells; Neoplasm Metastasis; Stress, Physiological

It has been reported that patients with Barrett's esophagus (BE) may have gastric acid hypersecretion. Serological markers such as serum pepsinogen or gastrin have been used to estimate the gastric secretory function. The aim of this study was to compare the serum pepsinogen and gastrin concentrations in view of Helicobacter pylori infection status between BE patients and the controls.. Thirty-six patients with long-segment BE were enrolled in this study. Three age- and sex-matched controls were assigned to each patient. Serum pepsinogen and gastrin concentrations were measured by radioimmunoassay and H. pylori infection was determined by histology and serum IgG antibodies.. Helicobacter pylori infection was present in 4 of 36 patients (11%) with BE and in 80 of 108 controls (74%), being less prevalent in BE patients than in the controls (P < 0.0001). When examined in the H. pylori-negative subjects, both the serum pepsinogen I and pepsinogen II concentrations in BE patients were significantly higher than those in the controls (mean pepsinogen I:BE 51.0 +/- 14.0 ng/mL vs control 38.9 +/- 13.5 ng/mL, P = 0.0012; mean pepsinogen II:BE 10.8 +/- 4.0 ng/mL vs control 7.9 +/- 2.0 ng/mL, P = 0.0097). There was no significant difference in the serum gastrin levels between BE patients and the controls irrespective of the H. pylori infection status.. Most of the Japanese BE patients are characterized by the absence of H. pylori infection and high levels of serum pepsinogen. Determination of the serum pepsinogen level in combination with the H. pylori infection status could be a useful serological marker for BE screening.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Asian People; Barrett Esophagus; Biomarkers; Case-Control Studies; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Prevalence; Up-Regulation

To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases.. Among 162 Japanese outpatients, pepsinogen I (Pg I) and II (Pg II) were measured using a conventional Japanese technique, and the European GastroPanel examination (Pg I and Pg II, gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori non-atrophic gastritis or atrophic gastritis.. Pg I and Pg II assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg I, but not Pg II, was twice as high with the GastroPanel test as with the Japanese test. The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis. When compared to the endoscopic biopsy findings, the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity.. Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Topics: Adult; Aged; Biopsy; Diagnosis, Differential; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Middle Aged; Outpatients; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Prevalence; Reference Values; Risk Factors; Stomach; Stomach Neoplasms; Young Adult

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Bacterial Proteins; Cytokines; Gastrins; Gastritis; Genomic Islands; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Immunoenzyme Techniques; Precancerous Conditions; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Stomach Neoplasms; Stomach Ulcer

We have previously described a synergistic interaction between hypergastrinemia and Helicobacter felis infection on gastric corpus carcinogenesis in FVB/N mice housed under specific-pathogen-free conditions. However, gastrin-deficient (GAS-KO) mice on a mixed C57BL/6/129Sv genetic background maintained in conventional housing were reported to develop spontaneous gastric antral tumors. Therefore, we investigated the role of gastrin in Helicobacter-associated gastric carcinogenesis in H. felis-infected mice on a uniform C57BL/6 background housed in specific-pathogen-free conditions. Hypergastrinemic transgenic (INS-GAS) mice, GAS-KO mice, and C57BL/6 wild-type mice were infected with H. felis for either 12 or 18 months. At 12 months postinfection, INS-GAS mice had mild corpus dysplasia, while B6 wild-type mice had either severe gastritis or metaplasia, and GAS-KO mice had only mild to moderate gastritis. At 18 months postinfection, both INS-GAS and B6 wild-type mice had both severe atrophic gastritis and corpus dysplasia, while GAS-KO mice had severe gastritis with mild gastric atrophy, but no corpus dysplasia. In contrast, both GAS-KO and B6 wild-type mice had mild to moderate antral dysplasia, while INS-GAS mice did not. H. felis antral colonization remained stable over time among the three groups of mice. These results point to a distinct effect of gastrin on carcinogenesis of both the gastric corpus and antrum, suggesting that gastrin is an essential cofactor for gastric corpus carcinogenesis in C57BL/6 mice.

Topics: Animals; Cytokines; Female; Gastrins; Gastritis; Helicobacter felis; Helicobacter Infections; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Precancerous Conditions; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; T-Lymphocytes, Helper-Inducer

Adenomatous polyps are known risk factor of colon cancer. Gastrin is a peptide hormone involved in the growth of both normal and malignant intestinal tissue, which probably may promote progression through the adenoma-carcinoma sequence.. To assess the association between serum gastrin levels and size, type and localization of colonic adenomas.. The study included 60 patients with adenomatous polyps of the colon and 30 healthy volunteers. Serum gastrin levels and presence of Helicobacter pylori infection were examined in all patients.. We observed higher serum gastrin levels in patients with colonic adenomas compared to control group (59.65 pg/ml vs. 46.89 pg/ml; p < 0.05). There was no association between gastrin levels and size, number, localisation and histologic type of polyps (p > 0.05). No differences between frequency of Helicobacter pylori infection and examined group of patients were observed (p > 0.05).. Despite of elevated serum levels in patients with colonic adenomas we did not observe the association between gastrin levels and size, grade of dysplasia and histologic type of polyps. The exact role of hipergastrinemia in process of colon carcinogenesis remains to be determined.

Topics: Adenomatous Polyps; Case-Control Studies; Causality; Comorbidity; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Middle Aged

Topics: Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Prevalence; Wound Healing

Gastrin and pepsinogens reflect the functional state of the gastric mucosa.. To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD).. In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc).. Kruskal-Wallis test and analysis of variance.. There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean +/- standard deviation 106.2 +/- 51.6 vs. median 114.7, mean +/- standard deviation 130.4 +/- 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298).. Serum gastrin and pepsinogen I and II do not correlate with the different grades of severity of GERD. The non-invasive GastroPanel is not useful for the differentiation of the various forms of GERD.

Topics: Antibodies, Bacterial; Biomarkers; Case-Control Studies; Endoscopy, Gastrointestinal; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Prospective Studies

Cancer of stomach is currently regarded as the final result of a staged multifactor process during which the microenvironment affects cells and causes their changes. One of the main triggering factors is Hp infection. Adenocarcinoma of stomach develops via stages of gastritis, precancerous changes, and cancer. The possibility to prevent cancer ensues from the potential irreversibility of premalignant processes in gastric mucosa, in the first place its atrophy; hence, the importance of its early diagnosis. The state of the endoscopic service in this country is inadequate for mass screening of patients with symptoms of dyspepsia. "GastroPanel", a new serological test for the diagnosis of gastric pathology provides information about histological and functional characteristics of gastric mucosa in the antral and fundal regions of the stomach. The method determines serum gastrin-17, pepsinogen-1, and IgG expressed in response to Hp infection. Our results demonstrate high diagnostic efficiency of "GastroPanel" as a screening technique for atrophic gastritis and assessment of stomach cancer risk.

Topics: Adolescent; Adult; Aged; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Mass Screening; Middle Aged; Neoplasm Staging; Pepsinogen A; Peptide Fragments; Stomach Neoplasms; Young Adult

Our aim was to determine the frequency of peptic ulcer and Helicobacter pylori infection by gastrointestinal evaluations in pretransplantation phase in children with end-stage renal disease (ESRD).. Twenty-four children with ESRD (13 girls and 11 boys) with a mean age of 14.7 +/- 3.4 years on maintenance hemodialysis were included in this study. Upper gastrointestinal endoscopies were performed and 4 gastric, antral, and duodenal biopsy specimens were obtained for urease test and histological study. Serum gastrin levels were measured in all patients, too. A control group was chosen to compare the rate of H pylori infection between children with ESRD and healthy children.. Gastrointestinal symptoms were present in 16 (66.7%) of 24 patients. Seventeen (70.8%) patients had abnormal upper gastrointestinal endoscopic findings. Infection with Helicobacter pylori was detected in 16 patients and 5 healthy children (66.7% versus 20.0%, P < .001). The frequency of dyspeptic symptoms was not different significantly between uremic patients with and without H pylori infection (P = .67). The same results were found regarding the upper gastrointestinal abnormalities found by endoscopy (P = .65). Oral alkalizing supplement was received by 63% of symptomatic and 80% of asymptomatic patients. Serum gastrin levels were significantly higher in infected patients than in noninfected patients with H pylori (P < .001).. We found a significant number of patients with peptic ulcer diseases, H pylori infection, and secondary hypergastrinemia. This study showed that clinical symptoms are not a reliable predictor of gastrointestinal problems and this is more confusing in patients who received alkalizing solutions.

Topics: Adolescent; Biopsy; Case-Control Studies; Child; Dyspepsia; Endoscopy, Gastrointestinal; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Peptic Ulcer; Renal Dialysis; Young Adult

Matrix metalloproteinases (MMPs) have roles in inflammation and other processes relevant to the architectural disturbances seen in the gastric mucosa in response to Helicobacter pylori infection. Upregulation of MMPs has been reported in H pylori infection, but there are no detailed reports regarding altered production of their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs).. To investigate changes in the abundance of TIMPs in human gastric corpus mucosa and murine stomach in Helicobacter infection, and to study cellular sources in man.. Gastric corpus biopsy samples were assessed for abundance of mRNA or protein for TIMP-1 to -4 by real-time quantitative PCR or western blotting, respectively. Antral and corpus biopsies were processed for histology, H pylori status and inflammatory scoring. Cellular sources of TIMP-1, -3 and -4 were examined by indirect immunohistochemistry. Circulating gastrin was measured by radioimmunoassay. Also, abundance of TIMP-1, -3 and -4 mRNA in the stomach of Helicobacter felis infected mice post-infection was compared with that of uninfected control animals.. Compared with uninfected patients, mRNA and protein for TIMP-1, -3 and -4 were significantly more abundant in the gastric corpus of H pylori infected subjects. Gastric TIMP expression did not differ significantly between hyper- and normogastrinaemic subjects within the H pylori negative and positive groups. There was no difference in mRNA abundance for MMP-3 or -8. Immunohistochemistry showed TIMP proteins localised to gastric epithelial, stromal cells and inflammatory cells. Murine H felis infection was associated with upregulation of TIMP-1 and -3 mRNA.. Helicobacter infection is associated with upregulation of specific TIMPs (TIMP-1 and -3) in glandular epithelium and stroma. It is suggested that increased expression of specific protease inhibitors in the corpus mucosa may exert important effects on extracellular matrix remodelling and influence the outcome of H pylori infection.

Topics: Animals; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Tissue Inhibitor of Metalloproteinases; Up-Regulation

Elevated gastrin concentration leading to gastritis is explained as the effect of change in the density of D and G cells. The aim of the study was to determine and compare fasting serum gastrin concentrations, G and D cell densities in gastric antrum mucosa in children with chronic gastritis and in children with no gastritis or Helicobacter pylori infection.. A total of 184 patients aged 6-18 years, with chronic abdominal pain underwent endoscopic examination. We created three groups: I--patients with chronic gastritis and H. pylori infection; II--patients with chronic gastritis but no H. pylori infection; III--patients with neither gastric mucosal abnormalities nor H. pylori infection. G and D cell densities were determined in the biopsy specimens (using Rbalpha H Gastrin & Somatostatin antibodies). Fasting serum gastrin concentrations were measured using a Beckmann gamma-counter and a GASK-PR kit.. The mean serum gastrin concentration in group I was higher when compared with group II (p = 0.04) and group III (p = 0.019). No statistically significant differences were found between groups II and III (p = 0.91). There were no statistically significant differences in G and D cell densities between groups.. The mean G/D cell ratios in groups I and III were almost identical. The mean fasting serum gastrin concentration was higher in children with both chronic gastritis and H. pylori infection compared with patients without infection or without antral inflammation. No difference in the G cell density or D cell density in children was found, regardless of the presence or absence of gastritis or H. pylori infection.

Topics: Adolescent; Cell Count; Child; Child, Preschool; Chronic Disease; Female; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pyloric Antrum; Somatostatin-Secreting Cells

Oxidative stress is linked to gastric carcinogenesis because of its ability to damage DNA. Here we examined antioxidative and anti-inflammatory effects of 4-vinyl-2,6-dimethoxyphenol (canolol), a recently identified potent antioxidative compound obtained from crude canola oil, on Helicobacter (H.) pylori-induced gastritis and gastric carcinogenesis using a Mongolian gerbil model. The animals were allocated to H. pylori-infection alone (12 weeks) or H.pylori + N-methyl-N-nitrosourea (MNU) administration (52 weeks). After oral inoculation of H. pylori, they were fed for 10 and 44 weeks with or without 0.1% canolol. H. pylori-induced gastritis, 5'-bromo-2'-deoxyuridine (BrdU) labeling and scores for cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) immunohistochemistry were attenuated in the canolol-treated groups. Expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), COX-2 and iNOS mRNA in the gastric mucosa, and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), anti-H. pylori IgG and gastrin levels were also significantly lower in canolol-treated groups. Furthermore, the incidence of gastric adenocarcinomas was markedly reduced in the H. pylori + MNU + canolol-treated group [15.0% (6/40)] compared to the control group [39.4% (13/33)] (p < 0.05). These data indicate canolol to be effective for suppressing inflammation, gastric epithelial cell proliferation and gastric carcinogenesis in H. pylori-infected Mongolian gerbils. Interestingly, the viable H. pylori count was not changed by the canolol containing diet. Thus, the data point to the level of inflammation because of H. pylori rather than the existence of the bacteria as the determining factor. Importantly, canolol appears to suppress induction of mRNAs for inflammatory cytokines.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anti-Inflammatory Agents; Antibodies, Bacterial; Antioxidants; Biomarkers; Cell Proliferation; Cell Transformation, Neoplastic; Cyclooxygenase 2; Deoxyguanosine; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunoglobulin G; Immunohistochemistry; Interleukin-1beta; Nitric Oxide Synthase Type II; Oxidative Stress; Phenols; Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Tumor Necrosis Factor-alpha; Vinyl Compounds

To assess serologically diagnosed gastric body atrophy (GBA) by histology in a sample of the general population.. GBA is a precursor lesion in gastric cancer. Data on GBA in a primary health care community in the Netherlands have not been reported.. Thirty-four subjects of 997 consecutive adults from a Dutch family practice had serologic GBA, according to hypergastrinemia (>100 ng/L), hypopepsinogenemia A (<17 microg/L), and a low pepsinogen A/C ratio (<1.6). Two years later, 25 subjects of this group, agreed in serologic retesting and gastroscopy with biopsies for histologic assessment according to the Sydney system.. At serologic retesting, 20 of 25 subjects again fulfilled the serologic criteria of GBA. Histologic examination of the corpus biopsies showed advanced GBA in 18 subjects (75%) of 24 (1 subject had no corpus biopsies) and 17 of 19 (89%) subjects with repeated positive serology. After disclosure of serology results, reexamination of the biopsies revealed GBA also in the 2 patients with initially insufficient evidence of GBA, giving a concordance of 100% (19/19). One subject with normal serum gastrin at retesting had both antral and body atrophy giving a concordance between serologic and histologic GBA of 95% (19/20). No adenomatous polyps, tumors, or dysplastic alterations were found.. Identification by serology of asymptomatic patients with advanced GBA in primary care is adequately possible and useful in selecting for endoscopy.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Atrophy; Autoantibodies; Autoimmune Diseases; Biopsy; Chronic Disease; Cohort Studies; Diagnosis, Differential; Endoscopy; Female; Gastric Fundus; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Netherlands; Pepsinogens; Prevalence; Pyloric Antrum; Serologic Tests

This study was performed to determine whether serum pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in Korea.. Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and gastrin levels were measured in 1006 patients with gastroduodenal diseases including cancer. Follow-up tests were performed 1 year after Helicobacter pylori eradication.. sPGI and sPGII levels increased and PG I/II ratios decreased in line with the severity of activity, chronic inflammation, and the presence of H. pylori (p < .01). In contrast, sPGI levels and PG I/II ratios decreased in proportion with the severity of atrophic gastritis (AG)/intestinal metaplasia (p < .01). Gastrin levels were found to be correlated with chronic inflammation negatively in the antrum but positively in the corpus. H. pylori eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios to the levels of H. pylori-negative patients, and was found to be correlated with reductions in activity and chronic inflammation of gastritis. The sensitivity and specificity of a PG I/II ratio of < or = 3.0 for the detection of dysplasia or cancer were 55.8-62.3% and 61%, respectively. In addition, sPGI and sPGII levels of intestinal-type cancer were significantly lower than those of the diffuse type, respectively (p = .008 and p = .05, respectively). Gastric cancer risk was highest in the H. pylori-positive, low PGI/II ratio (< or = 3.0) group with an odds ratio of 5.52 (confidence interval: 2.83-10.77).. PG I/II ratio (< or = 3.0) was found to be a reliable marker for the detection of dysplasia or gastric cancer, especially of the intestinal type. This detection power of PG I/II ratio (< or = 3.0) significantly increased in the presence of H. pylori, and thus, provides a means of selecting those at high risk of developing gastric cancer in Korea.

Topics: Antigens, Bacterial; Biomarkers; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Korea; Pepsinogens; Sensitivity and Specificity; Stomach Neoplasms

Helicobacter pylori (H. pylori) infection is known as a major cause of atrophic gastritis and is associated with serum gastrin, pepsinogen, and gastric acid secretion. There is still a controversial association between gastroesophageal reflux disease and H. pylori infection. This study was designed to investigate the relationship among serum gastrin, pepsinogen, and H. pylori infection in the erosive reflux esophagitis (ERD) patients.. Patients who were diagnosed as ERD by one gastroenterologist at the Kangnam St. Mary's hospital were prospectively enrolled. The persons without ERD in the control group were matched for age and sex. We examined the gastrin, pepsinogen I (PG I), PG II, PG I/II ratio, and H. pylori infection.. Forty five patients were enrolled in ERD group and 66 persons in control group. The H. pylori infection rate in ERD group was lower than that in the control group (11.1% vs. 43.9%, p<0.001). PG I/II ratio in ERD group was higher than that in the control group (7.0+/-3.1 vs. 5.3+/-2.6, p=0.003). The PG II (p=0.016) and gastrin (p=0.029) in ERD group were lower than those in the control group. BMI in ERD group was higher than that in the control group (24.5 vs. 23.1 kg/m2, p=0.013).. The H. pylori infection rate in ERD group was lower and PG I/II ratio was higher than that in the control group. Reflux esophagitis is thought to be reversely associated with the atrophy of gastric mucosa.

Topics: Adult; Aged; Chi-Square Distribution; Esophagitis, Peptic; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

GastroPanel (Biohit, Helsinki, Finland) is a serum test kit that measures Helicobacter pylori antibodies (HPABs) and pepsinogens I and II and gastrin 17, which reflect the degree of atrophic gastritis. We assessed whether GastroPanel can replace endoscopic biopsies in the diagnostics of H. pylori in children and whether the H. pylori-infected children show markers for atrophic gastritis. Eighty children (median age, 6.8 years; range, 0.6-18.7 years) underwent gastroscopy for H. pylori-related abdominal complaints (n = 40), surveillance after surgery for gastrointestinal tract malformations (n = 20), gastroesophageal reflux (GER) (n = 10), and miscellaneous diseases (n = 10). Gastric biopsies and a serum sample were obtained from all 80 children. HPAB levels of 38 and 15 IU were tested as cutoff values for H. pylori gastritis. The biopsies showed H. pylori-positive gastritis in 30 children, 9 had gastritis not associated with H. pylori, and 41 had normal biopsies. Atrophic gastritis was not found. The sensitivity and specificity of HPAB for H. pylori were 47% and 98% (cutoff, 38 IU), and 73% and 85% (cutoff, 15 IU), respectively. The assays of pepsinogens and gastrin did not improve sensitivity. None of the markers of pepsinogen (PG) I, PGII, and gastrin 17 (G17) indicated atrophic gastritis. GastroPanel is too insensitive for H. pylori screening and does not replace endoscopy. Markers indicative of atrophic gastritis were negative in all children with H. pylori gastritis.

Topics: Adolescent; Antibodies, Bacterial; Child; Child, Preschool; Endoscopy; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Infant; Pepsinogen A; Reagent Kits, Diagnostic

Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases.. To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients.. Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied.. Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication.. Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment.. The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Topics: Aged; Aged, 80 and over; Autoantibodies; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prospective Studies; Vitamin B 12 Deficiency

Helicobacter pylori infects over half the population worldwide and is a leading cause of chronic gastritis and gastric cancer. However, the mechanism by which this organism induces inflammation and carcinogenesis is not fully understood. In the present study we used insulin-gastrin (INS-GAS) transgenic mice that fully develop gastric adenocarcinoma after infection of H. pylori-related Helicobacter felis. Histological examination revealed that more than half of those mice developed invasive adenocarcinoma after 8 months of infection. These carcinomas were stained by NCC-ST-439 and HECA-452 that recognize 6-sulfated and non-sulfated sialyl Lewis X. Lymphocytic infiltration predominantly to submucosa was observed in most H. felis-infected mice, and this was associated with the formation of peripheral lymph node addressin (PNAd) on high endothelial venule (HEV)-like vessels detected by MECA-79. Time-course analysis of gene expression by using gene microarray revealed upregulation of several inflammation-associated genes including chemokines, adhesion molecules, surfactant protein D (SP-D), and CD74 in the infected stomach. Immunohistochemical analysis demonstrated that SP-D is expressed in hyperplasia and adenocarcinoma whereas CD74 is expressed in adenocarcinoma in situ and invasive carcinoma. These results as a whole indicate that H. felis induces HEV-like vessels and inflammation-associated chemokines and chemokine receptors, followed by adenocarcinoma formation.

Topics: Adenocarcinoma; Animals; Antigens, Differentiation, B-Lymphocyte; Female; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Profiling; Glycosyltransferases; Helicobacter felis; Helicobacter Infections; Histocompatibility Antigens Class II; Hyperplasia; Immunohistochemistry; Insulin; Lymphocytes; Male; Mice; Mice, Transgenic; Oligonucleotide Array Sequence Analysis; Oligosaccharides; Pulmonary Surfactant-Associated Protein D; Sialyl Lewis X Antigen; Stomach; Stomach Neoplasms; Up-Regulation

Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrites; Stomach Neoplasms

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; bcl-Associated Death Protein; Cyclooxygenase 2; Disease Progression; Esophageal Neoplasms; Gastrins; Gastroesophageal Reflux; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Models, Biological; Neoplasm Proteins; NF-kappa B; Prevalence; Survivin

Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear.. To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach.. Nested case-control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin.. Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1).. These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer.

Topics: Adenocarcinoma; Adult; Biomarkers; Cardia; Case-Control Studies; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Precancerous Conditions; Risk Factors; Stomach Neoplasms

Clinical features of patients who develop gastric cancer after successful eradication of Helicobacter pylori are still unclear. We attempted to identify host factors associated with the discovery of gastric cancer, including changes in the background gastric mucosa in patients with atrophic gastritis.. We enrolled 101 patients (59 men, 42 women; mean age 56.0 years) who underwent successful eradication therapy. All patients had no neoplastic lesion in the stomach and were diagnosed with corpus atrophic gastritis histologically before the eradication therapy. After successful eradication, these patients were followed up by an annual endoscopic examination (mean follow-up time 63.2 months; range 12-157 months). Fasting sera were obtained before and after eradication therapy and the serum levels of gastrin/pepsinogens were evaluated.. Gastric cancer occurred during follow-up in eight of the 101 patients (7.9%). We compared the host features between the cancer-discovered group (n = 8) and the non-discovered group (n = 93). We found no difference in gender, history of previous treatment of gastric cancer, and serum pepsinogen/gastrin levels at entry between them. The trends in alterations of serum markers did not differ between the two groups. However, gastric cancer was more frequently found in older patients (>54 years at eradication) than in others (P < 0.05).. Improvement of gastric inflammation did not correlate with the discovery of gastric cancer after eradication; however, age at the time of eradication seemed to be important. Strict follow-up after eradication is needed in older patients with atrophic gastritis.

Topics: Aged; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Stomach Neoplasms

The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (Generaltrade mark; Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5-9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA+, VacA+) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score >1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis.

Topics: Animals; Carcinogens; Cotinine; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney; Male; Mice; Mice, Inbred Strains; Mice, Transgenic; Stomach Neoplasms; Sweden; Tobacco, Smokeless

Previously we showed that a probiotic combination with L. rhamnosus GG was beneficial as an adjuvant therapy during H. pylori eradication.. To evaluate whether probiotic combination with LGG adheres to the upper gastrointestinal mucosa and modifies H. pylori colonisation and H. pylori induced inflammation.. Thirteen patients referred for gastroduodenoscopy received a drink consisting of equal doses (2.5x10(9)CFU) of LGG, L. rhamnosus LC705, Propionibacterium freudenreichii JS and Bifidobacterium lactis Bb12 daily. Recovery of probiotics in biopsies (antrum, corpus, duodenum) and faecal samples was evaluated by strain-specific quantitative polymerase chain reaction. H. pylori colonization and gastric inflammation was investigated by urease activity ((13)C-urea breath test), histology and serum pepsinogen I, II and gastrin-17 measurements.. Twelve patients were fully investigated; of these three of the patients had LGG adhering to the biopsies at end of the intervention. Other probiotic strains were not detected, even though the recovery of all individual probiotic strains from the faeces was significantly increased (p<0.01). After the treatment, the level of (13)C-urea breath test (p=0.063) and gastrin-17 (p=0.046) decreased.. The decreases in (13)C-urea breath test and gastrin-17 indicate that the probiotic combination exerts a beneficial effect on gastric mucosa in H. pylori infected patients. LGG showed marginal ability to adhere to the upper gastrointestinal tract mucosa.

Topics: Adult; Aged; Biomarkers; Biopsy; DNA, Bacterial; Feces; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Probiotics

The gastric pathogen Helicobacter pylori accelerates the progression to gastric cancer but the precise mechanisms that mediate carcinogenesis remain unidentified. We now describe how Helicobacter and gastrin stimulate the expression of a putative growth factor, Reg1, in primary gastric epithelial cells. RT-PCR and Western immunoblotting of human gastric corpus and antrum showed significantly increased Reg1alpha in H. pylori-infected patients. Similarly, Reg1 was increased in the stomachs of H. felis-infected INS-GAS mice. To study transcriptional regulation of the Reg1 gene, we transfected primary mouse gastric glands with -2111 bp and -104 bp Reg1 promoter-luciferase reporter constructs. Expression of both constructs was detected in pepsinogen- and VMAT-2-expressing cells, which corresponds to the normal pattern of expression of human and mouse endogenous Reg1. The expression of both constructs was increased in response to gastrin and H. pylori, and there were potentiating interactions between them; in contrast, only the -2111 bp construct responded to H. felis. Mutation of a C-rich putative regulatory element within the -104 bp sequence abolished the response to gastrin but not to H. pylori whereas mutation of the proximal -98 to -93 region of the promoter reduced the response to H. pylori but not to gastrin. Stimulation of Reg1 by H. pylori required the virulence factor CagA. These data indicate that expression of the putative growth factor Reg1 is controlled through separate promoter elements by gastrin and Helicobacter.

Topics: Animals; Epithelial Cells; Gastric Mucosa; Gastrins; Gene Expression; Helicobacter Infections; Helicobacter pylori; Humans; Lithostathine; Male; Mice; Mice, Transgenic; Promoter Regions, Genetic; Pyloric Antrum; Rats

Studies in 45 cryolite production workers (facing chronic gastritis and gastroduodenitis) demonstrated that the diseases in them have moderate inflammatory activity, atrophy of gastric lining contaminated with Helicobacter pylori, hypergastrine mia, hypopancreozymine mia and hyposecretine mia in half of the examinees.

Topics: Adult; Duodenitis; Female; Fluorine Compounds; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Occupational Diseases; Occupational Exposure

To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17 level and to study the diagnostic value of serum gastrin-17 in gastric precancerous lesions and gastric cancer.. Serum gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology.. Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum gastrin-17 level was markedly higher in people>or=60 years old than that in younger age groups. The serum gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group.. In people over 60 years of age, the serum gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum gastrin-17 level, whereas H. pylori infection is usually associated with its increment.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; China; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Precancerous Conditions; Retrospective Studies; Stomach Neoplasms

Helicobacter pylori-induced gastritis is an important factor for gastric carcinogenesis. However, it is still controversial whether it is also applicable for cardiac cancer development. Recently, we reported that H. pylori is an important factor for the induction of cardiac inflammation. We examined the status of H. pylori-induced gastritis in patients with cardiac cancer.. Seventy-five Japanese patients (58 men; mean age, 64.2 years) with cardiac cancer were studied. Cardiac cancer was defined as that mainly located within 2 cm from the squamo-columnar junction (SCJ). Histological gastritis including the cardiac region was evaluated using the biopsy or surgically resected sections. Cardiac inflammation was evaluated at 1 cm distal from SCJ in lesser curvature. Sera were collected and several markers were evaluated. The status of H. pylori infection was evaluated by histology and serum antibodies. Expressions of cytokeratins were examined by immunohistochemical analysis.. Out of 75 patients with cardiac cancer, H. pylori was positive in 71 (95%) patients. The cardiac inflammation was examined in 30 patients (26 with H. pylori and four without H. pylori infection) and we found cardiac inflammation was present in all cases with H. pylori infection. Histologically, H. pylori-related gastritis was also found in the gastric corpus and antrum. Serological data were consistent with the presence of chronic atrophic gastritis. Intestinal metaplasia was found in 18 cases in the cardiac mucosa, and their cytokeratin 7/20 pattern was judged as a gastric pattern in all cases.. H. pylori infection is closely associated with cardiac cancer.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Cardia; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Stomach Neoplasms

To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type IV secretion system.. Mongolian gerbils were infected with wild type (WT) H pylori type I strain B128 or its isogenic mutant B128 deltacagY (defective type IV secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by semi-nested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined.. The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue, but not in the pancreas.. H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type IV secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

Topics: Amylases; Animals; Cytokines; DNA, Bacterial; Female; Gastrins; Gerbillinae; Glucose; Helicobacter Infections; Helicobacter pylori; Hydrogen-Ion Concentration; Lipase; Pancreatitis; Radioimmunoassay; RNA, Messenger

Helicobacter pylori is a major risk factor for atrophic gastritis and gastric cancer. Various extragastric manifestations of H. pylori infection have also recently been suggested. However, the correlation between H. pylori and colorectal cancer (CRC) is controversial. The aim of this study was to examine the correlation between H. pylori, serum gastrin level, and atrophic gastritis with CRC.. Subjects were patients with CRC; controls were participants of a health check-up program that was conducted between October 1998 and March 2002 at four hospitals in Nagano Prefecture. For 121 newly diagnosed CRC cases, two controls matched by age (within 3 years), gender, and residence were randomly selected from the program participants. We conducted questionnaires and obtained blood samples from the cases and their controls. Consequently, the CRC cancer pairs consisted of 113 cases and 226 controls.. Neither H. pylori infection nor gastrin level nor atrophic gastritis showed any association with a risk for CRC. However, serologically determined atrophic gastritis demonstrated significant elevation in odds ratios (ORs) for rectal cancer (OR = 3.15, 95% confidence interval; 1.19-8.35).. Gastric conditions such as chronic H. pylori infection and atrophic gastritis are unlikely to increase the risk for CRC, although atrophic gastritis may increase the risk of rectal cancer.

Topics: Adult; Aged; Case-Control Studies; Colorectal Neoplasms; Confidence Intervals; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Japan; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires

To investigate the associations of serum gastrin-17 (G-17) concentration with helicobacter pylori (Hp) infection.. A (13)C-urea breath and ELISA test to determine the Helicobacter pylori status and to detect the serum gastrin concentration was conducted in 242 villagers in Linqu of Shandong Province, a high gastric cancer prevalence area in China.. Of 242 subjects, 65 of 111 were found Hp-positive in males (58.56%), compared with 65 of 131 in females (49.62%) (chi(2) = 1.932, P = 0.165). The statistical difference was not observed among different age groups (chi(2) = 4.185, P = 0.123). The average level of G-17 among 242 subjects was (24.43 +/- 25.46) pmol/L and it was statistically higher in females (29.87 +/- 28.18) pmol/L than that in males (18.01 +/- 20.11) pmol/L (Z = -3.618, P < 0.001). However, there was no statistical difference found among age groups (chi(2) = 1.948, P = 0.378). The G-17 level in Hp-negative group (35.50 +/- 30.92) pmol/L was observed significantly higher than in Hp-positive group (14.90 +/- 13.79) pmol/L (Z = 5.368, P = 0.0001).. The G-17 concentration was found higher in Hp-negative subjects than in Hp-positive subjects, and higher in female than in male, but no difference was found among age groups.

Topics: Adult; China; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Rural Population; Sampling Studies

Non-invasive methods are advisable for the detection of Helicobacter pylori-related chronic gastritis in pediatric patients. Serum pepsinogens I and II (sPGII and sPGII), gastrin-17 (G-17) and anti-H. pylori antibodies (IgG-Hp) have been proposed as a 'serological gastric biopsy'.. To assess H. pylori infection and to evaluate gastric mucosa status in a pediatric population by means of serological parameters such as sPGI, sPGII, G-17 and IgG-Hp.. 45 consecutively children evaluated for upper gastrointestinal symptoms were analyzed. All children were submitted to upper gastrointestinal endoscopy with biopsies. Serum samples were analyzed for IgG-Hp, sPGII, sPGI and G-17 (Biohit, Helsinki, Finland).. 18 children had H. pylori-related mild or moderate non-atrophic chronic gastritis. They presented significantly higher mean levels of sPGII and of IgG-Hp than negative ones, either under or up to 10 years. sPGI showed significantly increased levels in H. pylori-positive patients only over 10 years. G-17 levels were not different between H. pylori-positive and -negative ones. The best cut-offs of IgG-Hp, sPGII and of product IgG-Hp x sPGII, to identify H. pylori infection, were 30 IU/l, 9 microg/l, and 241 IU/l x microg/l, respectively. The product IgG-Hp x sPGII identified H. pylori infection with a 100% sensitivity, 92% specificity, 90% positive predictive value and 100% negative predictive value. IgG-Hp and IgG-Hp showed a correlation (r = 0.94; p < 0.001).. Combined analysis of sPGII and IgG-Hp antibody levels could be recommended as a non-invasive panel for the assessment of H. pylori-related histological alterations of gastric mucosa in childhood.

Topics: Adolescent; Biomarkers; Biopsy; Child; Child, Preschool; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Pepsinogens

The aim of the present study was to evaluate the effect of Candidatus Helicobacter suis (CHS) and other Helicobacter sp. different from Candidatus Helicobacter suis (non-Candidatus Helicobacter suis, non-CHS) infection on the number of endocrine G and D cells and G/D cells ratio in antral gastric mucosa in swine. Twenty nine stomachs were obtained from clinical healthy pigs about 6 months old and weighing approximately 100-120 kg after slaughter at abattoir located in central Poland. From each stomach samples of the antral gastric mucosa were taken for histopathology, and PCR examination for presence of Helicobacter genus and Candidatus Helicobacter suis. Samples for histopathology and immunohistochemistry were fixed in 10% buffered formalin. To reveal the expression of gastrin- and somatostatin-producing cells specific antibodies were used. Selected endocrine cells were counted in the midzone of pyloric glands, the results were expressed as a mean of the number of immunoreactive cells in one microscopic field, and as the ratio of gastrin to somatostatin cells (G/D). It can be concluded that some species of swine Helicobacter can alter the number of endocrine cells in gastric antral mucosa. Some of these alterations, for example increase the number of G cells, decrease of the D cells and especially increase of ratio G to D cells can be responsible for development of gastroesophageal ulcers in swine.

Topics: Animals; DNA, Bacterial; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Helicobacter; Helicobacter Infections; Immunohistochemistry; Polymerase Chain Reaction; Somatostatin; Somatostatin-Secreting Cells; Swine; Swine Diseases

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pyloric Antrum; Retrospective Studies; Stomach Neoplasms; Stomach Ulcer

The authors describe a current approach to the laboratory diagnosis of chronic gastritis, by using the plates of serological tests: pepsinogen I (PG-I), gastrin 17, and antibodies to Helicobacter pylori (HP). These tests and a questionnaire were used to examine 168 persons aged 45-70 years, who were a random population sample. Almost a fourth of the adult population was observed to have pronounced gastric mucosal atrophic changes, which might be associated with the high prevalence of HP infection. The concentration of PG-I is high in the persons infected with HP, its cytotoxic strains in particular, its elevated level servers as a valid marker of peptic ulcer disease and gastroesophageal reflux.

Topics: Aged; Aged, 80 and over; Antibodies, Bacterial; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Sensitivity and Specificity; Serologic Tests

Family unit is generally accepted as one of the contributors to Helicobacter pylori infection that is most frequently acquired in childhood, so it seems logical to diagnose and treat this infection in childhood. This study was designed to assess H. pylori prevalence in children from shepherd families having contacts with sheep.. This study involved 146 children (58 M/88 F, age 6-17 years; mean: 10.2 years) from families living in Polish Tatra Mountains with contact (group A, n=58) or without contact with sheep (group B, n=88). H. pylori status was determined by (13)C-urea breath test and was compared to 141 age- and gender-matched urban controls (group C). In both groups of mountain children, the anti-H. pylori and anti-CagA IgG were measured by ELISA and serum gastrin, ghrelin and leptin concentrations by RIA.. The H. pylori prevalence in group A was significantly higher (58.6%) than that in group B (21.6%) and urban controls (26%). Serum gastrin concentrations were significantly higher in H. pylori-positive than in H. pylori-negative mountain children (52.2+/-5.8 pmol/L versus 22.7+/-2.1 pmol/L), while serum ghrelin and leptin concentrations were significantly lower in H. pylori-infected (741+/-112 pg/mL and 3.6+/-0.8 ng/mL) than in non-infected children (1323+/-104 pg/mL and 8.6+/-2.4 ng/mL).. Children with sheep contact show about twice higher H. pylori prevalence and higher serum gastrin but lower ghrelin and leptin levels than those without H. pylori infection. Considering almost 100% positive 13C-urea breath test in sheep, it is reasonable to propose that H. pylori infection in shepherd children may originate from sheep and the infection might, therefore, be considered as zoonosis.

Topics: Adolescent; Agricultural Workers' Diseases; Animal Husbandry; Animals; Breath Tests; Child; Female; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Parents; Peptide Hormones; Poland; Prevalence; Seroepidemiologic Studies; Sheep; Urea

Corpus gastritis is a common diagnosis. Studies have shown that about 25% of patients that undergo gastroscopy receive this diagnosis. This study was undertaken to investigate etiological associations in patients with corpus gastritis in our northern Icelandic population.. Patients who had had a histological diagnosis of chronic corpus gastritis between the years of 1994 to 1998 were retrieved from the computer files of the department of pathology. In all 172 patients fulfilled the Sydney pathological criteria. Pathology review was performed by the same pathologist. Blood samples were also taken for variable serology and a urea breath test for Helicobacter pylori (H. pylori) was performed.. Mean age 71 year old (24-99 year). Males were 57%. H. pylori infection was diagnosed in 39%. There appears to be a relationship between active gastritis and H. pylori positivity, especially if there was only chronic gastritis without atrophy or metaplasia. Atrophy was significantly greater if anti-parietal antibody was present. No connections were found between anti-parietal antibody and anti-microsomal antibody. There was significantly higher mean gastrin levels in patients with atrophy or metaplasia compared with only chronic gastritis (p<0.05), present also in patients with chronic gastritis vs active gastritis (p<0.01). There was no difference in mean gastrin levels between H. pylori positive and H. pylori negative patients. Significantly higher mean gastrin levels were seen in patients with anti-parietal antibody (p<0.001). No difference was found in mean gastrin levels between patients with or with out antimicrosomal antibody.. There is a high probability that corpus gastritis and related complications are related to H. pylori infection in a large proportion of our population. Serum gastrin may well be a predictor of the histological grading of the chronic gastritis. We did not see a relationship with antimicrosomal activity.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Biomarkers; Chronic Disease; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Medical Records Systems, Computerized; Middle Aged; Predictive Value of Tests; Retrospective Studies; Stomach

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.

Topics: Adolescent; Adult; Case-Control Studies; Environmental Exposure; Female; Gastric Acid; Gastrins; Helicobacter Infections; Humans; Hygiene; Immunoglobulin A; Immunoglobulin G; Indonesia; Male; Middle Aged; Risk Factors; Salmonella typhi; Typhoid Fever

Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown.. We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot.. The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil.. H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Apoptosis; bcl-2-Associated X Protein; Cyclooxygenase 2; Gastric Acid; Gastric Mucosa; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Omeprazole; Probiotics; Proto-Oncogene Proteins c-bcl-2; Regional Blood Flow; Somatostatin; Stomach; Stomach Neoplasms; Tinidazole

We have previously reported that Helicobacter pylori infection prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including Barrett's adenocarcinoma, has been thought to be a complication of gastroesophageal reflux disease (GERD). However, the relationship between H. pylori infection, gastric acid secretion, and GE junction adenocarcinoma has not yet been investigated in Japan. The aim of this study was to evaluate this relationship in the Japanese population.. A total of 168 Japanese patients (RE alone: 80, short-segment BE (SSBE): 16, long-segment BE (LSBE): 20, GE junction adenocarcinoma: 12, distal early gastric cancer (EGC): 40; male/female = 106/62; mean age 61.5 yr) and 80 Japanese control subjects who had no localized lesions in the upper gastrointestinal tract (male/female = 43/37, mean age 58.1 yr) were enrolled for this study. The prevalence of H. pylori infection was determined by biopsy, the rapid urease test, and measurement of the serum H. pylori IgG antibody. Gastric acid secretion was assessed by the endoscopic gastrin test (EGT). RE was diagnosed according to the Los Angeles classification.. The prevalence of H. pylori infection in the patients with RE alone (30%) was significantly lower than that in control subjects (71.2%). There was also a tendency for the prevalence of H. pylori infection to be lower in patients with BE (SSBE, 18.7%; LSBE, 0%) when compared to that in patients with RE alone. On the other hand, while the prevalence of H. pylori infection in patients with GE junction adenocarcinoma (58.3%) was significantly lower than that in patients with EGC (87.5%), it tended to be higher than that in patients with RE alone or BE. The mean EGT value in patients with RE alone (3.74 mEq/10 min) was significantly higher than that in control subjects (1.83). The mean EGT value in patients with BE (SSBE, 4.74; LSBE, 4.76) tended to be even higher than that in patients with RE alone. The mean EGT value in patients with GE junction adenocarcinoma (3.94) was significantly higher than that in control subjects and patients with EGC (0.67), but it was comparable to that independent of the H. pylori infection status in patients with RE alone or BE.. Preservation of gastric acid secretion may be important for the development of GE junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status.

Topics: Adenocarcinoma; Barrett Esophagus; Esophageal Neoplasms; Esophagitis, Peptic; Esophagogastric Junction; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Stomach Neoplasms

Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection.. To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils.. Thirty-three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 microg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non-ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two-sided p = .05 was considered significant.. Estradiol-treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone-treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high-dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high-dose progesterone group showed a significant reduction in the number of gastrin cells.. Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.

Topics: Animals; Apoptosis; Cell Proliferation; Disease Models, Animal; Estradiol; Female; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; In Situ Nick-End Labeling; Progesterone; Proliferating Cell Nuclear Antigen

We attempted to clarify the pathogenesis of gastric inflammation in the cardia. Eighty Japanese participated in this study. Biopsy specimens of the gastric antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained, and histological gastritis was evaluated. Cardiac inflammation was also evaluated using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal reflux disease (GERD), and habitual smoking and assessed the relations between these factors and cardiac inflammation. The prevalence of H. pylori infection was statistically higher in patients with cardiac inflammation than in those without inflammation (P < 0.05). The relationship was also demonstrated by magnifying gastroscopy. Cardiac inflammation was linked to low acid output but not linked to the BA concentration or habitual smoking. Cardiac inflammation was more pronounced in patients without GERD. These results suggest that H. pylori is a major risk factor for cardiac inflammation in the Japanese.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Cardia; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Risk Factors

To study the expressions of gastrin (GAS) and somatostatin (SS) in gastric antrum tissues of children with chronic gastritis and duodenal ulcer and their role in pathogenic mechanism.. Specimens of gastric antrum mucosa from 83 children were retrospectively analyzed. Expressions of GAS and SS in gastric antrum tissues were assayed by the immunohistochemical En Vision method.. The expressions of GAS in chronic gastritis Hp+ group (group A), chronic gastritis Hp-group (group B), the duodenal ulcer Hp+group (group C), duodenal ulcer Hp-group (group D), and normal control group (group E) were 28.50+4.55, 19.60+2.49, 22.69+2.71, 25.33+4.76, and 18.80+2.36, respectively. The value in groups A-D was higher than that in group E. The difference was not statistically significant. The expressions of SS in groups A-E were 15.47+1.44, 17.29+2.04, 15.30+1.38, 13.11+0.93 and 12.14+1.68, respectively. The value in groups A-D was higher than that in group E. The difference was also not statistically significant.. The expressions of GAS and SS are increased in children with chronic gastritis and duodenal ulcer.

Topics: Child; Chronic Disease; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Retrospective Studies; Somatostatin

To study trends in morphological changes of gastric mucosa (GM) and its functional characteristics (serum gastrin-17, pepsinogens I and II) in eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU).. HP infection was detected with a rapid urease test, morphological study of gastrobiopsies and polymerase chain reaction in 59 patients with DU. The results of HP eradication were assessed two months after the treatment. Morphological study of gastrobiopsies, assays for gastrin-17, pepsinogens I and II in blood serum were made before the treatment and one year after HP eradication.. By the results of eradication two groups were formed: with effective eradication and uneffective eradication of H. pylori. Examination of GM one year after successful H. pylori eradication in DU patients GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM atrophy decreased by 47.8%. In patients with uneffective eradication the above positive changes were not registered. After H. pylori eradication, serum gastrin-17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In uneffective eradication this decrease did not occur.. H. pylori eradication leads to positive changes in morphological and functional indices reflecting GM condition.

Topics: Adult; Anti-Bacterial Agents; Biomarkers; Biopsy; DNA, Bacterial; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Pepsinogen A; Pepsinogen C; Polymerase Chain Reaction; Treatment Outcome

Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion.. To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease.. Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO.. Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R(2) = 0.62).. Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Bacterial; Bacterial Proteins; Biomarkers; Biopsy; Chronic Disease; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pyloric Antrum

Interactions between epithelial and stromal cells are important determinants of mucosal organization, but the signaling mechanisms are understood incompletely. Matrix metalloproteinase (MMP)-7 is produced uniquely in epithelia, may act on growth factors and matrix proteins, and in the stomach is increased with Helicobacter pylori infection. We have studied the role of MMP-7 in signaling between epithelial cells and a key stromal cell type, the myofibroblast.. Immunohistochemistry and Western blotting were applied to gastric corpus biopsy specimens; primary cultures of human gastric glands and myofibroblasts were used to study the role of MMP-7 in regulating proliferation and migration of the latter, and MMP-7 substrates were identified by proteomic methods.. Increased abundance of the myofibroblast marker alpha-smooth muscle actin was identified in H. pylori-positive biopsy specimens. Media from H pylori-infected gastric epithelial cultures stimulated proliferation and migration of primary human gastric myofibroblasts and antisense oligonucleotide treatment indicated a role for MMP-7. Proteomic methods identified insulin-like growth factor binding protein (IGFBP)-5 as a substrate for MMP-7 in medium from gastric myofibroblasts. Knockdown of IGFBP-5 by small interfering RNA or immunoneutralization of IGF-II, abolished myofibroblast responses to MMP-7. Proliferation of gastric epithelial cells also was stimulated by MMP-7-treated myofibroblasts via IGF-II.. MMP-7 acts as an epithelial-derived signal increasing the bioavailability of IGF-II released from myofibroblasts. Because IGF-II acts on both stromal and epithelial cells, the findings suggest that increased MMP-7 expression contributes to redefining the niche occupied by dividing cells and leading to hyperproliferation in H pylori infection.

Topics: Animals; Biopsy, Needle; Blotting, Western; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Fibroblasts; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 7; Mice; Probability; Radioimmunoassay; Sensitivity and Specificity

Topics: Animals; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Helicobacter; Helicobacter Infections; Humans; Inflammatory Bowel Diseases

Both gastrin and Helicobacter pylori have been shown capable of up-regulating gene expression and protein shedding of heparin-binding epidermal growth factor (HB-EGF). Furthermore, the bacteria have previously been shown to induce serum hypergastrinemia in infected individuals. The aim of this work was to assess the extent to which the ability of H. pylori to up-regulate expression of HB-EGF can be attributed to its effect on gastrin. Gastric cells, transfected with either gastrin small interfering RNA or antisense plasmid or the gastrin/cholecystokinin-2 receptor (CCK-2R), were cultured for 24 hours with H. pylori(+/-), a CCK-2R antagonist. Gene expression levels were measured using reverse transcription-PCR, whereas protein changes were measured using ELISA, Western blotting, and immunofluorescence. H. pylori induced significantly higher levels of HB-EGF gene expression and ectodomain shedding in the CCK-2R-transfected cells than the vector control (P < 0.01). Addition of the CCK-2R inhibitor significantly decreased gene and shedding up-regulation. Gastrin down-regulation reduced the effect of the bacteria on HB-EGF gene and protein expression levels. Endogenous gastrin and CCK-2R expression were also found to be significantly up-regulated in all cell lines as a result of exposure to H. pylori (P < 0.02). Gastric mucosal tissue from H. pylori-infected individuals had significantly higher CCK-2R expression levels than noninfected (P < 0.003), and in hypergastrinemic mice, there was an increase in HB-EGF-expressing cells in the gastric mucosa and colocalization of HB-EGF with CCK-2R-positive enterochromaffin-like cells. In conclusion, gastrin and the CCK-2R play significant roles in the induction of HB-EGF gene and protein expression and ectodomain shedding by H. pylori.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Disease Models, Animal; DNA, Antisense; Enterochromaffin Cells; Epidermal Growth Factor; Gastrins; Helicobacter Infections; Helicobacter pylori; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Mice; Plasmids; Receptor, Cholecystokinin B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Stomach Neoplasms; Transfection; Up-Regulation

Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined. We investigated the possible role of gastrin-induced gastric cell apoptosis in the development of gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice after gastrin-17 (G-17) infusion. In addition, we studied the effects of the gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2 (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with or without Helicobacter felis (H. felis) infection. INS-GAS mice had age-associated increases in Bax protein expression and decreases in Bcl-2 protein expression, along with increased glandular and epithelial cell apoptosis. At 8-week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis infection of INS-GAS mice led to increased apoptosis and the development of atrophy, whereas treatment with either YF476 and/or loxtidine strongly inhibited both apoptosis and atrophy. In vitro studies with Fas-expressing RGM1 cells showed that gastrin stimulation alone directly induced apoptosis via gastrin/CCK-2 receptor and synergized with FasL stimulation. These results indicate that gastrin can induce apoptosis in gastric epithelial cells and contribute to the development of gastric carcinogenesis.

Topics: Animals; Apoptosis; Atrophy; Disease Models, Animal; Gastrins; Helicobacter felis; Helicobacter Infections; Male; Mice; Mice, Knockout; Proto-Oncogene Proteins c-bcl-2; Receptor, Cholecystokinin B; Receptors, Histamine H2; Stomach Neoplasms

Intestinal metaplasia has been investigated extensively as a possible premalignant condition for stomach cancer but its pathogenesis is still not fully understood. In the present study, we examined the relationship between endocrine and mucous cell marker expression periodically after Helicobacter pylori infection in the Mongolian gerbil model. The numbers of chromogranin A (CgA)-positive, gastrin-positive and gastric inhibitory polypeptide (GIP)-positive cells in H. pylori-infected groups was increased significantly compared with the non-infected case. However, CgA-positive and gastrin-positive cells then decreased from 50 through 100 experimental weeks after H. pylori infection, whereas GIP-positive cells increased. Coexistence of gastrin-positive and GIP-positive cells was detected in the same gastric and intestinal mixed phenotypic glandular-type glands. In conclusion, the endocrine cell phenotype is in line with that of the mucous counterpart in the glands of H. pylori-infected Mongolian gerbil stomach, supporting the concept that development of intestinal metaplasia is due to the abnormal differentiation of a stem cell.

Topics: Animals; Chromogranin A; Chromogranins; Endocrine Glands; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; Intestines; Metaplasia; Precancerous Conditions; RNA, Messenger; Stomach; Stomach Neoplasms

Gastric mucosal inflammation causes hypergastrinemia, and gastrin receptors have been detected in several leukocyte types. We have analyzed whether gastrin affects the leukocyte-endothelial cell interactions in vivo by monitoring leukocyte rolling, adhesion, and emigration in rat mesenteric venules using intravital microscopy. Mesenteric superfusion with exogenous gastrin increased these processes in a concentration- and time-dependent manner, effects prevented by the cholecystokinin (CCK)-2 receptor antagonists (proglumide, L-365,260) but not by the CCK-1 receptor antagonist devazepide. A similar response was induced by exogenous CCK or endogenously released gastrin. CCK-2 receptors were localized in mesenteric macrophages and polymorphonuclear leukocytes. This effect of gastrin is not modulated by somatostatin and is independent of the endogenous release of histamine. To analyze whether hypergastrinemia elicited by Helicobacter pylori (HP) modulates the inflammation induced by the germ, rats were chronically administered with an extract of a CagA+/VacA+ strain of HP. This protocol increased gastrinemia and induced an inflammatory response in the rat mesentery. Blockade of CCK-2 receptors attenuated this response and induced a qualitative change in the leukocyte infiltrate suggestive of a receding inflammatory process. Our results reveal a new proinflammatory role of gastrin that seems to contribute to the maintenance of the inflammation elicited by HP components.

Topics: Animals; Endothelium, Vascular; Gastrins; Helicobacter Infections; Helicobacter pylori; Inflammation; Leukocytes; Male; Mesenteric Arteries; Mesenteric Veins; Rats; Rats, Sprague-Dawley

Topics: Adenoma; Antigens, Bacterial; Bacterial Proteins; Colorectal Neoplasms; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Helicobacter pylori infection is a recognized cause of hypergastrinemia, but the association of blood gastrin levels with colonic adenomas (CAs) is controversial. The aim of this study is to investigate if hypergastrinemia, H. pylori infection and/or cagA protein are risk factors for CAs.. In this prospective case-control study, fasting serum samples from 78 consecutive patients with CAs and 78 demographically matched colonoscopy-negative controls were assayed for anti-H. pylori immunoglobulin G, cagA protein and serum gastrin levels. Multivariate analysis was performed to identify risk factors for colon adenomas.. Though prevalence of H. pylori antibodies was not significantly different, the prevalence of cagA protein was significantly higher in patients with adenomas (42.3%) as compared with controls (25.6%, p < 0.03). Mediangastrin levels were significantly higher in patients with CAs (55, 20-975 pg/ml) than in controls (45.2, 23-529 pg/ml) (p < 0.001). Hypergastrinemia (>110 pg/ml) was commoner in patients with CAs than in controls (29.5 vs. 11.5%, p = 0.006) and was the only independent risk factor for adenomas (odds ratio 3.2, 95% CI 1.4-7.5) by multivariate analysis, but not H. pylori infection or cagA positivity. There was a significant association of hypergastrinemia and distal distribution of adenomas (p < 0.002).. Our study shows that hypergastrinemia is a risk factor for CAs, especially of the distal colon.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Bacterial Proteins; Case-Control Studies; Colonic Neoplasms; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors

We reviewed the clinicopathologic profile of a series of recently diagnosed sporadic duodenal gastrin-cell (G-cell) tumors. All cases were discovered incidentally and had a unique clinicopathologic profile: all 18 cases were gastrin-positive tumors located in the duodenal bulb, were small in size (mean size 5.4 mm), demonstrated an insular architectural pattern, and were localized to the lamina propria and submucosa. None of the patients had Zollinger-Ellison or carcinoid syndrome. The behavior was indolent and there was no evidence of metastasis at diagnosis or during follow-up. In our sampled population, the presence of Helicobacter pylori gastritis and the use of proton pump inhibitors (PPIs) were significantly associated with the presence of G-cell tumors. Both the presence of H. pylori gastritis and use of PPI remained significant in a logistic regression model adjusted for age, race/ethnicity, and sex with P values of 0.0016 (odds ratio=10.1, 95% confidence interval: 2.3 to 42.4) and 0.008 (odds ratio=8.9, 95% confidence interval: 1.76 to 45.4), respectively. Most patients with tumors showed G-cell hyperplasia in the nontumorous regions of the duodenum. The high incidence of sporadic duodenal G-cell tumors in patients with H. pylori gastritis and long-term PPI use suggests an association that needs to be further explored. Presence of G-cell hyperplasia in the nontumorous duodenal mucosa suggests that these may originate from a proliferative phase, similar to the hyperplasia-dysplasia-neoplasia sequence seen in other endocrine tumors.

Topics: Aged; Aged, 80 and over; Anti-Ulcer Agents; Carcinoid Tumor; Duodenal Neoplasms; Duodenum; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Middle Aged; Proton Pump Inhibitors

Ghrelin and leptin are endogenous peptides that have been implicated in the control of food intake, energy homeostasis and body weight gain. Although the stomach is the major source of circulating ghrelin and partly contributes also to plasma leptin, controversy exists over the influence of gastric Helicobacter pylori (Hp) infection on the ghrelin and leptin release. To resolve this controversy, plasma immunoreactive ghrelin and leptin levels were determined in Hp-positive and Hp negative children (N=60) and in adults (N=120) and daily concentrations of these hormones were measured at 2 h intervals before and after meals. Serum levels of ghrelin and leptin as well as gastrin were measured by RIA. Hp status was assessed using (13)C-urea breath test (UBT) and serology. Children with negative UBT showed significantly higher basal serum levels of ghrelin and lower concentrations of leptin than those with positive UBT. Adults without Hp infection also showed significantly higher fasting serum levels of ghrelin and lower levels of leptin than those in Hp infected subjects. In adults, especially without Hp infection, plasma levels of ghrelin showed a marked rise before the meal and sudden decrease following the food intake, while plasma leptin did not showed significant meal-related alterations, but in general its level was significantly higher in Hp positive than Hp negative subjects. Serum gastrin concentrations were significantly elevated in both Hp positive children and adults and these levels were significantly lower in Hp negative subjects. We conclude that Hp infection in children and adults causes a marked reduction in plasma levels of ghrelin, while increasing plasma levels of leptin and gastrin. These alterations in plasma levels of gastric originated appetite-controlling hormones in Hp infected children and adults may contribute to the alterations of the appetite and dyspeptic symptoms observed in these subjects.

Topics: Adolescent; Adult; Child; Eating; Female; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Leptin; Male; Middle Aged; Tumor Necrosis Factor-alpha

Since application of pediatric gastroscopy in the mid-nineteen nineties, there has been a trend that the prevalence rates of pediatric gastritis and duodenal ulcer (DU) are increasing. The diagnosed rate of pediatric gastritis has accounted for 85% - 95% of the total number of children who received gastroscopy, and the rate of DU accounted for 8% - 22%. Such a high rates of the diseases may influence the development of the children severely. However, the etiology and pathogenesis of pediatric chronic gastritis and DU have not been completely elucidated. The disordered gastrointestinal hormones play a crucial role in the pediatric chronic gastritis and DU. This study focused on the expression of gastrin (GAS), somatostatin (SS) in the mucosa of gastric antrum and PCNA and Fas-L in the sinus ventriculi and their possible roles in the pathogenesis of pediatric chronic gastritis and DU.. The sinus ventriculi mucosal samples of 83 cases were collected via gastroscopic biopsy from the hospital during the recent two years and the cases were divided into five groups: group A, chronic superficial gastritis, Helicobacter pylori (Hp)(+); group B, chronic superficial gastritis, Hp(-); group C, DU, Hp(+); Group D, DU, Hp(-); Group E, normal sinus ventriculi mucosa, Hp(-). Immunohistochemical staining (En Vision) was carried out for GAS, SS, PCNA and Fas-L, and positive cells of each slide were counted (x 400). Statistically significant differences among groups for continuous data were assessed with the software SPSS10.0.. The expressions of GAS and SS in the groups A through E had no significant difference. The expression of PCNA in group A was significantly higher than that in group B (P < 0.05), and no significant differences were found among the other groups. There were no significant differences in expressions of Fas-L among the five groups.. There seems to be an increasing tendency in the expressions of GAS and SS in children with chronic gastritis and duodenal ulcer. Hp infection promotes the multiplication of the sinus ventriculi mucosal epithelium cells in the pediatric chronic gastritis.

Topics: Adolescent; Biopsy; Child; Child, Preschool; Duodenal Ulcer; Fas Ligand Protein; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Proliferating Cell Nuclear Antigen; Pyloric Antrum; Somatostatin

Impaired control of gastric juice secretion is observed in chronic gastritis due to Helicobacter pylori (H. pylori) infection. G cells are stimulated by such cytokines as tumor necrosis factor (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-8 (IL-8). The number of D cells producing somatostatin decreases simultaneously. An increase in gastrin levels could also depend on alkalization in G cell environment caused by bacterial urease. The aim of the study was to evaluate G cell counts in the antrum and gastrin levels in the serum of children with H. pylori infection and after bacterium eradication.. The study was performed in 106 patients. Children were divided into 3 groups with regard to the presence and course of H. pylori infection. Fifty nine children (55.7%) had chronic gastritis in the course of H. pylori infection with a positive titre of antibodies in IgG class against H. pylori; 29 children (27.3%) with past H. pylori infection, without bacterium colonization and gastritis but with a positive titre of antibodies in IgG class against H. pylori; 18 children (17%) with functional disorders of the gastrointestinal tract but without H. pylori infection.. The quantitative analysis of gastrin cells in the antral mucosa of children performed by immunohistochemical method showed the highest gastrin cell count in group I with H. pylori infection (112.1 +/- 58.9 cell/mm2) and in group II with past H. pylori infection (105.3 +/- 73.1 cell/mm2). The serum gastrin level (92.9 +/- 41.6 microU/ml) was the highest in children with H. pylori infection. In controls, it was 70.0 +/- 15.3 microU/ml and could be compared to the results of children with past H. pylori infection.. 1. The H. pylori infection plays a significant role in the stimulation of G cells increase and gastrin release in the blood serum in children. 2. The eradication of H. pylori infection is probably a main factor in gastric secretion down-regulation during gastritis in children.

Topics: Adolescent; Child; Child, Preschool; Female; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male

To determine the concentration of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases.. Concentrations of human neutrophil peptides (HNPs) 1-3, the major forms of alpha-defensins, and human beta-defensin (HBD)-1 and HBD-2 were measured by radioimmunoassay in plasma and gastric juice of 84 subjects, consisting of 54 Helicobacter pylori-infected and 30 uninfected subjects. They included 33 patients with chronic gastritis (CG), 12 with gastric ulcer (GU), 11 with duodenal ulcer (DU), 11 with benign gastric polyp (BGP) and 16 with normal mucosa (N group) on upper endoscopy. Plasma pepsinogen I and II levels, biomarkers for gastric mucosal inflammation and atrophy, were also measured.. Gastric juice HNPs 1-3 levels in patients with CG, GU and BGP were significantly higher than those in patients with DU and N. Gastric juice HBD-2 concentrations in patients with CG and GU were significantly higher than those in the N group, but were significantly lower in DU patients than in GU patients. Gastric juice HBD-1 levels and plasma levels of these peptides were similar in the patient groups. Concentrations of gastric juice HNPs 1-3 and HBD-2 of in H pylori-infected patients were significantly different from those in uninfected subjects. HNPs 1-3 concentrations in gastric juice correlated negatively with plasma pepsinogen I levels and I/II ratios. HBD-2 levels in gastric juice correlated positively and negatively with plasma pepsinogen II concentrations and I/II ratios, respectively.. HNPs 1-3 and HBD-2 levels in gastric juice are diverse among various gastrointestinal diseases, reflecting the inflammatory and atrophic events of the background gastric mucosa affected by H pylori.

Topics: alpha-Defensins; beta-Defensins; Duodenal Diseases; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Stomach Diseases

The conventional view of gastric acid secretion is that a negative feedback mechanism arises in response to high acidity, such that somatostatin keeps G-cells and parietal cells from producing more gastrin and acid, respectively. When the stomach becomes infected, for example with Helicobacter pylori (H. pylori), the feedback mechanism is impaired. In animal models, our laboratory has demonstrated that other types of bacteria besides H. pylori can cause gastritis. For example, under conditions of low acidity, gastritis is secondary to bacterial overgrowth, not production of excessive acid, thus suggesting a new paradigm for the regulation of gastric acid secretion under inflammatory conditions. Cytokines, released during the gastric inflammatory response, including IFN gamma, TNF alpha and IL-1 beta stimulate the G-cell to produce gastrin. Gastrin in turn triggers the release of acid, and hypergastrinemia suppresses somatostatin, the inhibitor of acid. The overall response results in maximal gastric acid output that acts as the stomach's most important anti-microbial agent. The increased acid secretion by the stomach in the presence of H. pylori seems to be part of the innate immune response, in that gastrin and somatostatin are reciprocally regulated by Th1 or Th2 cytokines, respectively. In a mouse model, we showed that octreotide, a somatostatin, analog, is an efficacious treatment for Helicobacter gastritis. In humans, octreotide might accelerate recovery from H. pylori infection, reducing the duration of antibiotic therapy.

Topics: Cytokines; Feedback; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Humans; Stomach Neoplasms

Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori-positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI] 1.6-7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3-52.6) (p < 0.001)). The best cut-off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 >60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow-up is warranted for patients with IM found at the greater curvature of the corpus.

Topics: Aged; Biomarkers; Case-Control Studies; Endoscopy; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Metaplasia; Pepsinogen A; Pepsinogen C; Pyloric Antrum; Stomach Neoplasms

This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years.. Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification.. Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus.. Long-term treatment with pantoprazole is effective and safe.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Cell Count; Enteroendocrine Cells; Female; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Peptic Ulcer; Sulfoxides

It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate.. To investigate the morphological changes in the gastric neoplasm after H. pylori eradication.. We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication.. Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels.. The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate.

Topics: Adenocarcinoma; Adenoma; Aged; Aged, 80 and over; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Pepsinogen A; Stomach Neoplasms

Topics: Anti-Ulcer Agents; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, influences appetite, energy balance, gastric motility and acid secretion. The stomach is the main source of circulating ghrelin. There are inconsistent reports on the influence of Helicobacter pylori (H pylori) infection on circulating ghrelin levels. We sought to elucidate the relationship between ghrelin and various peptides in plasma, with special reference to H pylori.. Plasma ghrelin levels were measured by radioimmunoassay in 89 subjects who were referred for upper gastrointestinal endoscopy, consisting of 42 H pylori infected and 47 uninfected ones. Plasma gastrin, somatostatin, leptin, insulin-like growth hormone 1 (IGF-1) and chromogranin A concentrations were also measured. Twelve patients were treated with anti- H pylori regimen.. Ghrelin circulating levels were greatly decreased in H pylori-positive than negative individuals (194.2+/-90.2 fmol/mL and 250.4+/-84.1 respectively, P<0.05), but did not significantly alter following the cure of infection (176.5+/-79.5 vs 191.3+/-120.4). There was a significant negative correlation between circulating ghrelin and leptin levels, as well as body mass index, for the whole and uninfected population, but not in H pylori-infected patients. Plasma ghrelin concentrations correlated positively with IGF-1 in H pylori-negative group and negatively with chromogranin A in the infected group. There were no significant correlations among circulating levels of ghrelin, gastrin and somatostatin irrespective of H pylori status.. H pylori infection influences plasma ghrelin dynamics and its interaction with diverse bioactive peptides involved in energy balance, growth and neuroendocrine function.

Topics: Adult; Aged; Energy Metabolism; Female; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Neurosecretory Systems; Peptide Hormones

Epidemiological studies suggest that atrophic corpus-dominant gastritis is an increased risk factor for gastric carcinogenesis. The role of the Helicobacter pylori type IV secretion system (T4SS) for pathogenesis in the Mongolian gerbil model was explored.. Mongolian gerbils were infected for 32 weeks either with H. pylori type I strain B128 or with isogenic mutant strain B128delta cytotoxin-associated gene (cagY) or B128delta cagA , defective in T4SS or in the production of its effector protein CagA, respectively. Quantitative H. pylori reisolation was performed from the gastric antrum and corpus separately, cytokines were measured by quantitative reverse-transcription polymerase chain reaction, and gastric pH and hormones were determined.. B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus. All infected animals showed a strong antral inflammation and epithelial cell proliferation. B128-infected, rather than mutant-infected, gerbils presented a severe transmural inflammation with huge lymph aggregates, increased proliferation, significant atrophy, and mucous gland metaplasia in the corpus. Plasma gastrin levels and gastric pH values were significantly increased only in B128-infected gerbils. In all infected animals, the expression of the proinflammatory cytokines interleukin 1beta, interferon gamma, and growth-regulated protein was considerably increased in the antrum, but only in wild type-infected animals was an increase seen in the corpus mucosa.. The presence of an intact T4SS allows H. pylori to colonize the gastric corpus. This results in atrophic corpus-dominant gastritis, a severe precancerous condition, thus highlighting T4SS and CagA as major risk factors for gastric cancer development.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Atrophy; Bacterial Proteins; Cytokines; Female; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Mutation; Precancerous Conditions; Promoter Regions, Genetic; Pyloric Antrum; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Virulence

Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear.. We assessed gastric acidity in 15 patients with follicular gastritis, aged 20-37 years, using a 24-hour intragastric pH-metry, as well as by histologic and serologic evaluations; and compared it with that in other age-matched groups: 18 cases of H. pylori-positive antrum-predominant gastritis, 12 of pangastritis, and 24 H. pylori-negative normals. In eight cases with follicular gastritis, it was re-assessed 6 months after the eradication therapy for H. pylori.. During nighttime, the percentage of time with intragastric pH above 3.0 in follicular gastritis was significantly higher than that in normals (p<.0001), and in antrum-predominant gastritis (p<.001), but was comparable with that in pangastritis. In the daytime period, this parameter in follicular gastritis was significantly higher than that in normal (p<.001), in antrum-predominant gastritis (p<.001), and in pangastritis (p<.05). Marked mononuclear cell and neutrophil infiltration but no apparent glandular atrophy were observed in both the antrum and corpus. Serum pepsinogen I/II ratio was significantly lower in follicular gastritis than that in normals (p<.0001) and in antrum-predominant gastritis (p<.001), whereas serum gastrin was significantly higher than that in normals (p<.0001), in antrum-predominant gastritis (p<.01) and in pangastritis (p<.05). After eradication for H. pylori, all of the parameters in follicular gastritis were altered to the same ranges as those in normals.. In follicular gastritis, gastric acidity is significantly reduced, but can be normalized by eradication of H. pylori. It can thus be speculated that inflammatory cytokines or H. pylori-infection-induced prostaglandins might strongly inhibit gastric acid secretion in follicular gastritis.

Topics: Adult; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Pepsinogens; Pyloric Antrum

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than -negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Female; Gastrins; Gastrointestinal Diseases; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptide Hormones; Upper Gastrointestinal Tract

Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation.. Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test).. The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months.. The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anemia, Iron-Deficiency; Antibodies, Bacterial; Autoantibodies; Autoimmune Diseases; Bacterial Proteins; Breath Tests; Celiac Disease; Child; Clarithromycin; Comorbidity; Drug Therapy, Combination; Female; Ferrous Compounds; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Omeprazole; Parietal Cells, Gastric; Prospective Studies; Urease; Vitamin B 12 Deficiency

Helicobacter pylori-associated atrophic gastritis is known to be a significant risk factor for gastric cancer. Among the well-known parameters of atrophic gastritis are the levels of serum gastrin-17 (G-17) and pepsinogen I (PG1), which are biomarkers of gastric antral and corpus mucosal activity, respectively. The aim of study was to compare the production of G-17 and PG1 in patients with or without stomach mucosal atrophy and to investigate the utility of serum PG1 and/or G-17 concentrations for the objective evaluation of atrophic gastritis.. A total of 178 dyspeptic Helicobacter pylori-positive patients underwent diagnostic upper gastrointestinal endoscopy with biopsy. The degree of histologic gastric mucosal atrophy was compared with the fasting levels of PG1, and to the postprandial levels of G-17 detected by enzyme immunoassay.. A decrease in serum G-17 levels along with worsening of the antral atrophy was observed; the serum levels of PG1 were reduced during progression of the corpus atrophy. In the multifocal atrophic gastritis, values for PG1 and G-17 serum concentrations were significantly lower than the respective cut-off values. Statistical analysis revealed statistically significant differences between the serum levels of PG1 and G-17 measured at different stages of stomach mucosal atrophy.. A strong reverse correlation was found between histologic/ endoscopic antral atrophy and serum G-17 levels, and between corpus atrophy and serum PG1 levels.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers; Biopsy; Endoscopy, Digestive System; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Middle Aged; Pepsinogen A; Pyloric Antrum; Sensitivity and Specificity; Severity of Illness Index

Apart from its importance as an acid secretogogue, the role of histamine as a downstream target of gastrin has not been fully explored. Previous studies have shown that the combination of hypergastrinemia and Helicobacter infection resulted in accelerated gastric cancer in mice. We used this model to examine the role of cholecystokinin 2 (CCK2)/gastrin receptor and histamine H2-receptor signaling in the development of gastric atrophy and cancer.. Male hypergastrinemic mice (INS-GAS mice) were infected with Helicobacter felis and given the CCK2/gastrin receptor antagonist YF476 and/or the histamine H2-receptor antagonist loxtidine for 3 or 6 months. In addition, mice were treated with omeprazole alone or in combination with either YF476 or loxtidine for 3 months.. Mice treated with YF476 or loxtidine alone showed partial suppression of both gastric acid secretion and progression to neoplasia. The combination of YF476 plus loxtidine treatment resulted in nearly complete inhibition of both parameters. YF476 and/or loxtidine treatment did not alter the overall level of H. felis colonization but did result in significant down-regulation of the growth factors regenerating gene I and amphiregulin. Loxtidine treatment, with or without YF476, induced a mild shift in T-helper cell polarization. In contrast, omeprazole treatment resulted in mild progression of gastric hyperplasia/dysplasia, which was ameliorated by the addition of YF476 or loxtidine.. The combination of CCK2/gastrin- and histamine H2-receptor antagonists has synergistic inhibitory effects on development of gastric atrophy and cancer in H. felis/INS-GAS mice, while the proton pump inhibitor showed no such effects. These results support an important role for the gastrin-histamine axis in Helicobacter-induced gastric carcinogenesis.

Topics: Achlorhydria; Animals; Atrophy; Benzodiazepinones; Disease Models, Animal; Gastrins; Helicobacter felis; Helicobacter Infections; Histamine H2 Antagonists; Male; Mice; Mice, Transgenic; Phenylurea Compounds; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Receptors, Histamine H2; Stomach Neoplasms; Triazoles

The role of Helicobacter pylori (H pylori) infection in gastric acid secretion of patients with chronic gastritis remains controversial. This study was designed to elucidate the effect of H pylori on H+/K+-ATPase activities in gastric biopsy specimens.. Eighty-two patients with chronic gastritis who had undergone upper endoscopy were included in this study. H pylori infection was confirmed by rapid urease test and histology. Gastric H+/K+-ATPase activities and serum gastrin concentrations were measured by an enzymatic method and radioimmunoassay, respectively. For those patients who received triple therapy for eradicating H pylori, changes in the activity of gastric H+/K+-ATPase and serum gastrin levels were also measured.. The mean gastric H+/K+-ATPase activity in H pylori-positive group (42 patients) was slightly higher than that in H pylori-negative group (29 patients) (169.65+/-52.9 and 161.38+/-43.85 nmol Pi/(mg.h), respectively, P=0.301). After eradication of H pylori, the gastric H+/K+-ATPase activities slightly decreased compared to prior therapy (165.03+/-59.50 and 158.42+/-38.93 nmol Pi/(mg.h), respectively, P=0.805). The mean basal gastrin concentration was slightly higher in H pylori-positive patients than in H pylori-negative patients (87.92+/-39.65 pg/mL vs 75.04+/-42.57 pg/mL, P=0.228). The gastrin levels fell significantly after the eradication of H pylori. (Before treatment 87.00+/-30.78 pg/mL, after treatment 64.73+/-18.96 pg/mL, P=0.015).. Gastric H+/K+-ATPase activities are not associated with H pylori status in patients with chronic gastritis.

Topics: Chronic Disease; Gastric Mucosa; Gastrins; Gastritis; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Humans; Reference Values

Topics: Antibodies, Bacterial; Dyspepsia; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Needs Assessment; Pepsinogen A; Risk Assessment; Sensitivity and Specificity; Serologic Tests

This study, carried out on 51 patients with multifocal atrophic gastritis (MAG) and 92 age and sex-matched dyspeptic controls, was designed to examine both exocrine (gastric acid) and endocrine (gastrin) gastric secretion before and after therapeutic intervention including Helicobacter pylori eradication and vitamin C treatment.. Fasting and gastrin-releasing peptide-induced gastric acid secretion, serum levels of gastrin and proinflammatory (IL-1beta, IL-8, TNF-alpha) as well as gastric mucosal gene expression of ornithine decarboxylase (ODC), cyclooxygenase 2 (COX-2) and growth factors (epidermal growth factor and transforming growth factor alpha) were determined before and after the eradication of Helicobacter pylori and therapy with large doses (1 g/d) of vitamin C for 3 months.. The H. pylori eradication, assessed by C-urea breath test, and vitamin C therapy failed to reverse the histological atrophy of the gastric mucosa but improved significantly the functional status of the atrophied mucosa, especially its exocrine and endocrine secretory activities, attenuated the expression of premalignant markers such as ODC and COX-2, raised the production of growth factors and diminished the release of proinflammatory cytokines.. These results indicate that MAG may be considered as an environmental disease of the gastric mucosa, whose functional status can be improved by the eradication of H. pylori combined with antioxidant therapy with large doses of vitamin C.

Topics: Adult; Aged; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Case-Control Studies; Cyclooxygenase 2; Cytokines; Epidermal Growth Factor; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Ornithine Decarboxylase; RNA, Messenger; Transforming Growth Factor alpha

Helicobacter pylori (H. pylori) infection induces both gastric (GU) and duodenal ulcers (DU). We examined whether host immunological response to H. pylori determines different disease outcomes.. Thirty-two GU and 28 DU patients infected with H. pylori, and 24 dyspeptic patients without infection were enrolled. The constituents of cellular infiltrates in biopsies from each patient were determined and lymphokines secreted by stimulated T cells were measured. Serum concentrations of IgG subclasses specific to H. pylori were measured.. Low pepsinogen I and high pepsinogen II levels were observed in GU patients, while a high pepsinogen I level was found in DU patients. T cells predominate over other cell types in both GU and DU patients. GU patients had a higher number of T cells (p < 0.01) and lower plasma cells (p < 0.05) than those in DU patients. T cells from GU patients produced greater amounts of IFN-gamma and less IL-4 than those in DU patients (p < 0.01). GU patients had a higher serum level of IgG2 specific to H. pylori than that in DU patients (p < 0.01).. Th response by gastric T cells in GU patient was more polarized to Th1 as compared with that in DU patients, suggesting that a distinct immune response to H. pylori induces different disease outcomes.

Topics: Adult; Cohort Studies; Cytokines; Disease Progression; Duodenal Ulcer; Female; Flow Cytometry; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Intestinal Mucosa; Male; Middle Aged; Pepsinogen A; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Stomach Ulcer; T-Lymphocyte Subsets

To compare the prevalence of chronic atrophic gastritis (CAG) in Japan, China, Tanzania, and the Dominican Republic and to assess the usefulness of Helicobacter pylori infection and serum gastrin level as markers of CAG.. The subjects were volunteers from local communities in Japan (n=859), China (n=1741), Tanzania (n=573), and the Dominican Republic (n=1215). Each individual underwent a health checkup and blood sampling for measurement of serum pepsinogen I and II, pepsinogen I /II ratio, serum gastrin, and H. pylori antibodies, and responded to a questionnaire on upper digestive tract diseases.. The prevalences of H. pylori infection (23.5-96.1%), CAG (5.6-60.4%), and serum gastrin (62.0-136.5 pg/ml) varied by age, sex, and country. Serum gastrin level for men differed in each country according to age. In Tanzanian men, the median gastrin level (101.0 pg/ml) was the highest in the 40 to 49 years age group (p < 0.01) while there was no significant difference among different age groups in Tanzanian women. Serum gastrin level in subjects > or = 70 years was higher than in other age groups in both sexes in the Dominican Republic (males, 92.5, females, 136.5 pg/ml). The prevalence of H. pylori infection increased (p < 0.01) with advancing age in Japan (only for women) and the Dominican Republic but was high in all age groups of both sexes in China and Tanzania. The prevalence of CAG increased (p < 0.01) with age in both sexes in Japan, China (women only), and the Dominican Republic, but not in Tanzania. The odds ratio of CAG in H. pylori infected subjects was 5.3 times that in H. pylori-negative subjects. The odds ratio of CAG increased by 0.6%/1 pg/ml increase in serum gastrin.. Our results indicated that H. pylori infection, serum gastrin, and advancing age are good markers of CAG and that the prevalence of CAG is the highest in Japan.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Asia, Eastern; Dominican Republic; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence

Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease.. To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D cells in gastric antral and corpus biopsies from patients with dyspeptic complaints.. One hundred and twenty two patients with dyspeptic complaints had two antrum and two corpus biopsies taken during upper endoscopy. The severity of inflammation and the density of H pylori were evaluated semiquantitatively. In addition, the density and distribution of neuroendocrine cells, especially G and D cells, were examined using immunohistochemistry. Patients were divided into three groups, those with H pylori positive gastritis, H pylori negative gastritis, and histologically normal gastric mucosa.. The number of immunoreactive G cells was significantly higher and the number of immunoreactive D cells lower in patients with H pylori positive gastritis compared with H pylori negative gastritis or histological normal gastric mucosa. The percentage of G cells as a percentage of mucosal endocrine cells was also raised and that of D cells was decreased.. Helicobacter pylori infection produces alterations in the number of endocrine cells responsible for regulating acid secretion in relation to intragastric pH and feeding. The alterations correlate best with the severity of inflammation and not with H pylori density.

Topics: Adolescent; Adult; Aged; Chromogranins; Dyspepsia; Female; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum; Severity of Illness Index; Somatostatin; Somatostatin-Secreting Cells

Epidemiological studies have shown that Helicobacter pylori infection with associated chronic gastritis is the main risk factor for development of gastric cancer. The aim of this study was to investigate the long-term development of H. pylori-induced gastritis in Mongolian gerbils in terms of morphology, gastrin secretion, epithelial proliferation and gene expression of pro-inflammatory cytokines.. A total of 133 gerbils were inoculated with H. pylori and 62 served as controls. The gerbils were killed at different time-points between 6 and 94 weeks after inoculation. Serum concentrations of anti-H. pylori IgG and gastrin were determined by enzyme-linked immunoabsorbent assay (ELISA) and radioimmunoassay (RIA), respectively. Epithelial proliferation was evaluated immunohistochemically after labeling with 5-bromo-2'-deoxy-uridine. Gene expression of beta-actin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Histological parameters of gastritis were assessed semiquantitatively and expressed as a "gastritis score".. Serum concentrations of anti-H. pylori IgG and gastrin increased over time. Epithelial proliferation in the antrum was increased 6 weeks after inoculation, followed by increased proliferation in the corpus 32 weeks after inoculation. Gene expression of IL-1beta and TNF-alpha were increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for RT-PCR. With time, gastritis expanded from the antrum to the corpus and the gastritis score increased to reach a peak 32 weeks after inoculation. Pseudopyloric metaplasia (loss of specialized cells) was a characteristic feature in the corpus mucosa. Gastric ulcers, but neither dysplasia nor carcinoma, were observed during 94 weeks of infection.. Long-term H. pylori infection in Mongolian gerbils led to progressive gastritis, glandular atrophy, hypergastrinemia, increased epithelial proliferation and elevated gene expression of pro-inflammatory cytokines.

Topics: Actins; Animals; Biomarkers; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation, Bacterial; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunoglobulin G; Immunohistochemistry; Interleukin-1; Male; Pyloric Antrum; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tumor Necrosis Factor-alpha

Determining how Helicobacter pylori promotes gastric cancer and whether H pylori eradication decreases cancer risk would be helped by suitable murine models. Mice lacking the cyclin-dependent kinase inhibitor p27kip1 are susceptible to carcinogen-induced tumors. Furthermore, p27 stimulates gastric epithelial apoptosis and inhibits proliferation, expression is decreased by H pylori, and low levels are associated with a poor prognosis in gastric cancer. We therefore evaluated p27-deficient mice as a model for H pylori-associated gastric cancer.. Wild-type and p27-/- C57BL/6 mice were infected with H pylori mouse-adapted Sydney strain at 6-8 weeks of age and 6-10 mice of each type were euthanized 15, 30, 45, 60, and 75 weeks later.. Uninfected p27-/- mice developed gastric hyperplasia. H pylori-infected p27-/- mice frequently developed intestinal metaplasia (40% at 30 weeks, 67% at 45 weeks), and after 60 weeks 7 of 12 mice developed significant dysplasia and gastric cancer, recapitulating human intestinal-type gastric carcinogenesis. Wild-type mice developed intestinal metaplasia only after 75 weeks of infection; significant gastric dysplasia was observed in 1 animal (P < .05 for each comparison with p27-/- mice). No disease developed in uninfected mice. H pylori infection in p27-/- mice was associated with significantly decreased apoptosis and increased epithelial proliferation, inflammation, and H pylori density compared with infection in wild-type mice.. p27 loss and H pylori colonization cooperate to produce gastric cancer. The p27-deficient mouse affords opportunities to examine the pathogenesis of H pylori in gastric carcinogenesis and to test eradication and chemopreventive strategies.

Topics: Animals; Apoptosis; Cell Division; Cyclin-Dependent Kinase Inhibitor p27; Female; Gastrins; Gastritis; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Hyperplasia; Male; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Stomach Neoplasms

Cell division is brisk in the ulcer margin and many of the new cells will migrate over and cover the ulcer bed. The aim of this study was to determine how agents that promote or delay gastric ulcer healing influence cell proliferation in the gastric epithelium.. Acetic acid ulcers were produced in the rat gastric corpus; non-ulcer rats served as controls. All rats were given a continuous infusion of (3)H-thymidine. Some rats were also given gastrin or indomethacin, or infected with Helicobacter pylori. The rats were killed after 1, 2, 6 or 13 days, and the ulcer margin and undamaged corpus were excised for determination of labeling index (LI) by autoradiography. Antrum, duodenum and colon were also studied. Silver grain counting was carried out in some groups.. LI in the ulcer margin grew exponentially, reaching 84% after 6 days; gastrin increased, and indomethacin decreased LI significantly. In 6-day ulcer rats that were given 3H-thymidine only during the first day LI was 5%, while in those given 3H-thymidine only during the last day LI was 27%. LI and silver grain counting results indicated that during the first 6 days of healing the epithelial cells in the ulcer margin divide twice. In the undamaged epithelium of the 1-day ulcer rats LI was

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Proliferation; Epithelial Cells; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Indomethacin; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Thymidine; Wound Healing

Helicobacter pylori (H. pylori) is an important gastrointestinal pathogen associated with gastritis as well as gastric or duodenal ulcers and gastric cancer. The oral cavity has been considered as a potential reservoir for the gastric infection and reinfection. The objective of our studies was to evaluate the influence of oral H. pylori for the stomach infection and the release of gut hormones affecting food intake such as ghrelin and gastric secretion such as gastrin. Additionally, the contribution of H. pylori in the periodontal disease has been examined. H. pylori infection in stomach was assessed by (13)C- Urease Breath Test and presence of the bacteria in oral cavity by culture. The periodontal status was measured by pockets depth with the periodontal probe. We estimated the serum level of IgG anti-H. pylori, anti-VacA, anti-CagA, ghrelin, gastrin, TNF-alpha and IL-8 in blood and the level of IgA anti-H. pylori in saliva. The presence of H. pylori in oral cavity was detected in 54.1% of examined individuals, whereas the H. pylori gastric infection in tested group was found in 51% cases. However, the correlation analysis between those two groups of patients involving together about 100 subjects showed that within the group of patients with positive gastric H. pylori infection only 45.1% did not show the presence of H. pylori in saliva and 43.1% showed no H. pylori in supragingival plaque. In line of these findings patients who did not have gastric H. pylori infection, 53.2% showed presence of H. pylori in saliva and 42.9% in supragingival plaques. Serum level of ghrelin and gastrin in subjects with oral H. pylori inoculation but without gastric H. pylori infection were not significantly different from those without the presence of this germ in oral cavity. In contrast, gastric H. pylori infection resulted in significant reduction in serum ghrelin levels and significant elevation of gastrin as compared to those who were gastric H. pylori negative. We concluded that oral H. pylori alone does not seem to serve as bacterium sanctuary for gastric H. pylori infection and, unlike gastric infection, it fails to affect serum levels of hormones stimulating appetitive behaviour such as ghrelin and gastric acid secretion such as gastrin.

Topics: Adult; Age Factors; Breath Tests; Dental Plaque; Disease Reservoirs; Dyspepsia; Female; Gastrins; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Mouth; Periodontal Diseases; Prevalence; Saliva; Stomach Diseases

To evaluate serum pepsinogen I (PG I) and gastrin-17 (G-17) levels in patients with Helicobacter pylori (H. pylori)-associated chronic atrophic gastritis, with reference to endoscopical Kimura-Takemoto's staging, chromoendoscopical and histological features.. 267 dyspeptic H. pylori-infected patients were examined by chromoendoscopy with biopsy sampling according to the Sydney System and according to Kimura-Takemoto's scale. Simultaneous assessment of serum pepsinogen I (PG I) and gastrin-17 (G-17) levels by enzyme immunoassay was performed. The serologic and morphologic results were compared with correlation analysis.. There was strong reverse correlation between the stomach mucosal atrophy (antral part or corpus) and the proper serologic markers (respectively, G-17 or PG I) in H. pylori-associated chronic gastritis when gastric biopsies taken according to the Sydney System were assessed. The use of Kimura-Takemoto's scale has revealed the decrease of serum PG I levels only at 0-2 and 0-3 grades of the corpus mucosa atrophy. Probably, these results reflects the development of functional failure of the stomach corpus mucosa at late stages of atrophy when its compensatory capacity becomes insufficient. There were not any advantages in sampling biopsies for the detecting of intestinal metaplasia (IM) by the Sydney System, or by Kimura-Takemoto's scheme. The obvious concordance between histologically proven extent of IM and the number of IM foci detected by chromoendoscopy has been revealed.. The biopsy sampling for the diagnosis of precancerous changes of the stomach mucosa after non-invasive screening of atrophic gastritis (e.g., by means of EIA) should be based preferably on the visual signs acquired via chromoendoscopy than through routine endoscopy, independently of the scheme of examination of stomach mucosa, either according to the Sydney System, or to the Kimura-Takemoto's scale.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Endoscopy; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pepsinogen A

Topics: Aged; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Gene Expression Regulation, Enzymologic; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Ornithine Decarboxylase; Prostaglandin-Endoperoxide Synthases; Stomach Neoplasms

Helicobacter pylori has been established as a major cause of gastritis and peptic ulcer disease in adults and children. H. pylori infection may also have a role in the development of some extra-gastrointestinal diseases, including iron deficiency anemia. The aim of this study is to investigate H. pylori-related changes in gastric physiology and histology and the relationship of these changes to iron deficiency anemia in children.. Fifty-two patients with gastrointestinal complaints were studied. Hematologic parameters, 3-day vitamin C and iron consumption, serum gastrin levels, and gastric juice ascorbic acid levels were compared in patients with and without H. pylori infection. Dietary intake of vitamin C and iron, serum gastrin, gastric juice ascorbic acid content, and gastric histology were compared in patients with H. pylori infection and anemia and in patients with H pylori infection and no anemia. The CagA status of the H. pylori organisms was evaluated.. Twenty-eight of 52 patients had H. pylori. Thirty-one patients had iron deficiency anemia. H. pylori infection was associated with low serum iron levels. H. pylori gastritis was associated with a decrease in the gastric juice ascorbic acid level. Infection with CagA-positive strains was associated with a greater decrease in gastric juice ascorbic acid than infection with CagA-negative strains. However, the gastric juice ascorbic acid levels of patients with H. pylori and anemia were not different from those of non-anemic patients with H. pylori. Among patients with H. pylori infection, pangastritis was twice as common in those with anemia than in those without anemia.. H. pylori infection was associated with a decrease in gastric juice ascorbic acid concentration, and this effect was more pronounced in patients with the CagA-positive strain. Pangastritis was more common in patients whose H. pylori.infection was accompanied by anemia.

Topics: Anemia, Iron-Deficiency; Antigens, Bacterial; Ascorbic Acid; Bacterial Proteins; Child; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Absorption; Iron; Iron, Dietary; Male; Stomach; Virulence

Rebound increased acid secretion has been observed at 2 weeks after discontinuing omeprazole treatment in Helicobacter pylori -negative, but not H. pylori -positive, subjects. It is unknown whether this is a prolonged phenomenon or whether a similar phenomenon appears later in H. pylori positives or is released by eradication therapy. The aims of this study were to answer these 3 questions.. Twelve H. pylori -negative and 20 H. pylori -positive subjects were studied. Each had a basal, submaximal, and maximal pentagastrin-stimulated acid secretion study before, during, and at 7, 14, 28, 42, and 56 days after a 56-day course of omeprazole 40 mg/day. Ten of the H. pylori -positive subjects had their infection eradicated during the last week of treatment.. In the H. pylori -negative subjects, there was rebound secretion of submaximal (P < 0.003) and maximal (P < 0.003) acid output, which persisted until at least 56 days after discontinuing omeprazole. The H. pylori -uneradicated subjects had no rebound increased secretion other than in maximal acid output at 28 (P < 0.01) and at 42 days after treatment (P < 0.02). In those eradicated of H. pylori close to the end of omeprazole, there was rebound increased secretion of submaximal acid output (P < 0.04) lasting until 56 days and of maximal acid output (P < 0.01) lasting until 28 days after treatment.. Rebound increased acid secretion following omeprazole is a prolonged phenomenon in H. pylori -negative subjects. There is little evidence of it in H. pylori -infected subjects, but eradicating the infection releases the phenomenon. The accentuated H. pylori -related oxyntic gastritis induced by omeprazole is likely to protect against the rebound phenomenon.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Fasting; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole

Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients.. Thirty-six children aged 10-17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2-3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication.. H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori-positive patients with duodenal ulcer than in gastritis-only patients or controls [mean +/- standard error (SE): 6.56 +/- 1.4, 3.11 +/- 0.4 and 2.65 +/- 0.2 mEq/10 minutes, respectively; p <.001]. Stimulated acid secretion was higher in H. pylori-positive boys than girls (5.0 +/- 0.8 vs. 2.51 +/- 0.4 mEq/10 minutes, respectively; p <.05). Stimulated acid secretion pre- and post-H. pylori eradication was similar (5.47 +/- 0.8 vs. 4.67 +/- 0.9 mEq/10 minutes, respectively; p =.21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p <.001 and peak from 544 to 133 pg/ml, p <.05).. H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.

Topics: Adolescent; Biopsy; Breath Tests; Child; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Urea; Urease

High levels of inducible nitric oxide synthase and nitrotyrosine in Helicobacter pylori-infected gastric mucosa may contribute to development of gastric cancer. We investigated the relation between expression of inducible nitric oxide synthase and proinflammatory cytokines in gastric mucosa and serum markers of gastritis.. The study included 103 patients with H. pylori infection. We examined levels of interleukin-1beta, interleukin-6 and interleukin-8 by enzyme-linked immunosorbent assay and evaluated expression of inducible nitric oxide synthase and nitrotyrosine by immunohistochemical staining. Furthermore, we assessed serum levels of pepsinogens, gastrin, anti-parietal cell antibody, nitrite and nitrate, as markers of gastritis.. Thirty-seven of 103 (35.6%) gastric mucosa specimens showed simultaneous expression of inducible nitric oxide synthase and nitrotyrosine. In these patients (inducible nitric oxide synthase-positive group), the serum level of gastrin was significantly higher than that of the inducible nitric oxide synthase-negative group (509.5 +/- 141.5 pg/mL vs. 210.0 +/- 227.2 pg/mL; P < 0.01), whereas there were no significant differences in serum levels of pepsinogen, anti-parietal cell antibody, and nitrate and nitrite or in scores of histological gastritis. Interleukin-6 levels were significantly higher in the inducible nitric oxide synthase-positive group than in the inducible nitric oxide synthase-negative group (25.9 +/- 7.0 pg/mg protein vs. 10.6 +/- 4.9 pg/mg protein; P < 0.05).. Inducible nitric oxide synthase-producing gastritis was correlated with high levels of interleukin-6. Patients with hypergastrinaemia should be carefully followed on a long-term basis to ensure that the development of any malignancy is detected early.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-6; Male; Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Tyrosine

The prevalence of duodenal ulcer (DU) in adult patients with portal hypertension is higher than in patients without portal hypertension. This study investigates the prevalence and characteristics of DU in children with portal hypertension.. From January 1997 to December 2001, 80 children with portal hypertension who had undergone upper intestinal endoscopic examinations were enrolled. Possible factors contributing to the development of DU including severity of liver disease, portal hypertension, H. pylori, and serum gastrin level were studied. The control group consisted of 80 age-and sex-matched children with gastrointestinal symptoms but no liver disease and who underwent endoscopic examination during the same period.. The prevalence of DU was significantly higher in children with portal hypertension than in children with digestive symptoms only (22.5%v 8.8%; P =0.017). DU was more common and appeared earlier in children with a history of variceal bleeding. The presence of DU was independent of the severity of liver disease, H. pylori infection and serum gastrin level.. DU occurs commonly in children with portal hypertension, especially in those who have had variceal bleeding. It is mandatory to screen a patient with gastrointestinal bleeding for DU even in the presence of esophageal varices. Elevated portal pressure might be a factor contributing to the development of DU.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Duodenal Ulcer; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hypertension, Portal; Infant; Male; Prevalence

We evaluated the relationship between Helicobacter pylori and various factors associated with gastric cancer in two areas in Japan with different risks for mortality due to gastric cancer.. A total of 250 sera from Niigata and 209 from Okinawa were used. H. pylori antibody and CagA antibody were measured by antigen-specific ELISAs. Serum gastrin and pepsinogen levels were determined by RIA.. Although there was no significant difference in H. pylori prevalence among the persons in Niigata (50%) and Okinawa (42%), CagA prevalence in these populations was significantly different, at 41% and 26%, respectively (OR = 1.98, 95%CI: 1.33-2.95, P < 0.01). Serum gastrin levels in Niigata were significantly lower than those in Okinawa in H. pylori-negative persons (P < 0.01). The serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in H. pylori positive persons (P < 0.01), whereas there was no significant difference in H. pylori-negative persons. Among those positive for H. pylori, serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in CagA-negative persons (P < 0.01), whereas no significant difference was observed in CagA-positive persons.. These results suggest that the difference in the mortality ratio of gastric cancer between Niigata and Okinawa is mainly associated with the difference between areas in the prevalence of cagA-positive strains rather than that of H. pylori itself.

Topics: Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Pepsinogens; Risk Factors; Stomach Neoplasms

A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia.. We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio.. We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System.. In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 +/- 20.8 ng/mL, 9.2 +/- 4.2 ng/mL, 6.0 +/- 1.7 and 53.5 +/- 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 +/- 46.6 ng/mL, 25.9 +/- 17.1 ng/mL, 3.4 +/- 1.3 and 131.9 +/- 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months.. The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Topics: Dyspepsia; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density.. The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer.. We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age-matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA.. Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded-type group than in the depressed-type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases.. Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.

Topics: Aged; Case-Control Studies; Female; Gastric Acid; Gastric Acidity Determination; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Nitrites; Pepsinogens; Prospective Studies; Stomach Neoplasms

Helicobacter pylori infection causes hypergastrinemia. This study aimed to determine the association between serum gastrin and the severity of H. pylori-related gastric histology.. A total of 458 dyspeptic patients were included in this study after the absence of gastric malignancy was confirmed using endoscopy. The gastric specimens of each patient were collected from the antrum and corpus for the analysis of H. pylori-related histology changes by updated Sydney's system. Before endoscopy, the fasting blood samples were collected for gastrin analysis.. The H. pylori-infected patients had higher gastrin levels than those without infection (P = 0.01). Gastrin levels were related to H. pylori density and acute and chronic inflammation scores in the corpus mucosa (P < 0.05), but not in the antral mucosa (P = NS). Gastrin levels were also not related to the presence of gastric atrophy. Multivariate regression showed that the gastrin level was only related to acute corpus inflammation. However, in the patients without infection, the gastrin level was also associated with acute corpus inflammation. Nevertheless, the patients with denser H. pylori infection were more likely to have acute corpus gastritis than those with lighter H. pylori infection, and thus presented with higher gastrin levels (P < 0.05).. The increased level of gastrin of serum after H. pylori infection was associated with acute inflammation in the gastric corpus mucosa, but not in the antral mucosa. Denser H. pylori infection causes more severe corpus gastritis and thus may lead to a higher fasting level of gastrin of serum.

Topics: Adult; Analysis of Variance; Biomarkers; Chi-Square Distribution; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Male; Middle Aged; Regression Analysis

Atrophic gastritis is a precancerous condition that is commonly caused by chronic Helicobacter pylori (H. pylori) infection. This blinded, controlled study was designed to determine if serum gastrin and pepsinogens were reliable markers of atrophy in asymptomatic patients.. One hundred and forty-seven asymptomatic patients underwent endoscopy with multiple gastric biopsies obtained for histology, culture, and rapid urease test. Fasting serum gastrin (total and G-17) and serum pepsinogens (I-II) were determined by standard immunoassays. Gastric atrophy was histologically assessed in accordance with internationally accepted criteria; three main patterns of gastritis were distinguished: (a) nonatrophic gastritis, (b) atrophic antrum-restricted and antrum-predominant gastritis, and (c) corpus-restricted gastritis. Receiving operating characteristic (ROC) analysis was used to determine the best cut-off for each serum test in nonatrophic gastritis versus antrum-restricted/antrum-predominant atrophic gastritis.. No significant differences in serum gastrin and pepsinogens I-II were detected in nonatrophic gastritis versus patients with antrum-restricted/antrum-predominant atrophic gastritis. The positive likelihood ratios for an abnormal serum test to detect antrum-restricted/antrum-predominant atrophy in the gastric body were total serum gastrin 2.13 (95% CI 0.99, 4.6), gastrin-17: 1.55 (95% CI 0.75, 36.17), pepsinogen I: 2.74 (1.4, 5.4), pepsinogen II: 1.74 (1.27, 2.39), and the ratio of pepsinogen I and II: 1.8 (1.2-2.8). Negative likelihood ratios ranged from 0.20 to 0.65.. In an asymptomatic population, serum gastrin (total and G-17) and pepsinogens I-II (and their ratio) do not discriminate nonatrophic versus antrum-restricted/predominant atrophic gastritis.

Topics: Atrophy; Biomarkers; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Multivariate Analysis; Pepsinogen A; Reproducibility of Results; Single-Blind Method; Stomach

In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects.. The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology.. Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects.. In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.

Topics: Adult; Aged; Aging; Antibodies, Bacterial; Endoscopy, Gastrointestinal; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Reference Values; Sex Characteristics; Stomach Neoplasms

Topics: Child; Diagnosis, Differential; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A; Pepsinogen C; Sensitivity and Specificity

To detect the Helicobacter pylori (H. pylori)-induced gastric precancerous lesions leading to cancer formation, and to evaluate the possibility of non-invasive screening of dyspeptic patients to identify those having high risk of gastric cancer.. 178 consecutive H. pylori-positive dyspeptic patients after assessment of serum pepsinogen-1 (PG-1) and gastrin-17 (G-17) levels by enzyme immunoassay were examined with endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.. There was statistically significant reverse dependence between the presence and severity of stomach mucosal atrophy (in antrum or corpus) and the proper serologic markers of stomach functional activity (G-17 or PG-1). On the other hand, the presence and the degree of intestinal metaplasia, dysplasia and gastric cancer did not correspond to the serum levels of G-17 or PG-1. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values. Additionally, we have established the obvious advantage of the chromoendoscopy method in the diagnosis of intestinal metaplasia in the stomach epithelium.. The assays of serum G-17 and PG-1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopic examination with mucosal biopsy to disclose the probable progression of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Precancerous Conditions; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Stomach Neoplasms

The authors investigated whether low vitamin B12 intake, impaired gastric function, infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children.. The plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and and bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests, respectively.. infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin.. The specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Topics: Analysis of Variance; Breath Tests; Child; Diet; Female; Gastrins; Guatemala; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Male; Methylmalonic Acid; Pepsinogen A; Risk Factors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

To determine whether serum vitamin B12 levels in non-vitamin B12 deficient healthy adults correlate with serological evidence of H. pylori infection.. An association between H. pylori infection and vitamin B12 deficiency has been recently reported.. 133 adults, presenting to a community based primary care clinic who met the following exclusion criteria; history of H. pylori eradication or antacid use, liver disease, inflammatory bowel disease, previous gastrointestinal surgery, a vegetarian diet or multivitamin supplementation were studied. Blood was drawn for a complete blood count, serum vitamin B12, gastrin, folic acid and H. pylori IgG antibodies. Subjects with vitamin B12 < or = 145 ng/mL (deficient range) were excluded.. Of 133 subjects 96 (72.2%) were seropositive for H. pylori IgG antibodies (HP+). Age of HP(+) subjects did not differ from that of seronegative subjects (HP-); 52.8 +/- 1.6 mean +/- SE versus 49.2 +/- 2.9 ( = NS). Prevalence of HP seropositivity was significantly higher among subjects with borderline (>145-180 pg/mL) or low normal (>180-250 pg/mL) vitamin B12 levels than among those with vitamin B12 > 250 pg/mL; among 25 subjects with vitamin B12 > 145-180 pg/mL 92% were seropositive and among 47 subjects with vitamin B12 > 180-250 pg/mL 89% were seropositive as compared with 31/61 (51%) of subjects with B12 > 250 pg/mL, Fisher exact test < 0.0001. Vitamin B12 levels did not correlate with age (r = -0.07). Gastrin levels (pg/mL) did not differ significantly between groups; 70.2 +/- 5.8 in HP(+) versus 56.0 +/- 12.4 in HP(-).. The higher prevalence of H. pylori infection among subjects with serum vitamin B12 levels that are within the lower end of the normal range suggests a causal relationship between H pylori infection and vitamin B12 levels in healthy adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Erythrocyte Indices; Female; Folic Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hematocrit; Hemoglobins; Humans; Immunoglobulin G; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Prevalence; Reference Values; Seroepidemiologic Studies; Statistics as Topic; Vitamin B 12

Gastrin stimulates mucosal growth of much of the gastrointestinal tract and has also been implicated in promoting growth of colonic tumors, but its role in colorectal carcinogenesis remains controversial. This study determined fasting serum gastrin levels before and after surgery for colorectal cancer (CRC) and the relationship to the clinical stage of the disease to investigate it possible prognostic role.. Fasting radioimmunoassay gastrin, CA 19-9, and CEA levels were measured before and after surgery for CRC. Helicobacter pylori status was also assessed since it causes significant hypergastrinemia.. Mean fasting plasma gastrin level was significantly higher in CRC patients than in controls before surgery but not 59 days after surgery. Mean CEA and CA 19-9 levels were significantly higher in patients with CRC before surgery than after tumor resection. There was a significant positive correlation between the plasma gastrin, CEA, and CA 19-9 levels and the CRC stage (Dukes' classification).. The significance of gastrin as a marker for diagnosis or prognostic purposes in colorectal cancer needs to be further examined.

Topics: Aged; Aged, 80 and over; Biomarkers; CA-19-9 Antigen; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prognosis; Radioimmunoassay

Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG.. Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA.. Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly.. The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.

Topics: Adult; Aged; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Mass Screening; Middle Aged; Pepsinogen A; Pepsinogen C; Pepsinogens; ROC Curve; Sensitivity and Specificity

The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion.. We undertook 24-hour pH-metry in 12 H. pylori-positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day.. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH >or= 3, as well as increasing the area under the H+ concentration-time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL-1alpha, IL-8, IL-13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H+ concentration-time curve 'without omeprazole' minus 'with omeprazole', when comparing 'after' versus 'before' eradication of H. pylori.. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity 'with' versus 'without' omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.

Topics: Adult; Antacids; Anti-Bacterial Agents; Bile Acids and Salts; Cytokines; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Models, Biological; Omeprazole; Proton Pump Inhibitors

H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 x 20 mg), amoxycillin (2 x 1 g) and clarithromycin (2 x 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic infiltrate) and severity (mononuclear infiltrate) of gastritis was observed. The atrophy score improved in both antrum and corpus after eradication. The expression of COX-2 and ODC was significantly up-regulated in the gastric mucosa of patients with atrophic gastritis and significantly reduced after eradication therapy. In all successfully eradicated patients with atrophic gastritis a significant increase in gastric acid secretion and decrease in serum gastrin were observed. We conclude that: (1) H

Topics: Amoxicillin; Anti-Ulcer Agents; Clarithromycin; Cyclooxygenase 2; Drug Therapy, Combination; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gene Expression; Helicobacter Infections; Helicobacter pylori; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Omeprazole; Ornithine Decarboxylase; Peroxidases; Prostaglandin-Endoperoxide Synthases; RNA, Messenger

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving di

Topics: Amoxicillin; Animals; Anti-Ulcer Agents; Colony Count, Microbial; Drug Therapy, Combination; Gastric Mucosa; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hyperplasia; Microcirculation; Omeprazole; Penicillins; Radioimmunoassay; Somatostatin; Stomach Ulcer; Tinidazole

In the Western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastro-oesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However, there is no plausible biological mechanism of association between H. pylori, obesity, and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake, and body composition, was studied in H. pylori positive asymptomatic subjects.. Plasma ghrelin, leptin, and gastrin were measured for six hours after an overnight fast, before and after cure of H. pylori in 10 subjects. Twenty four hour intragastric acidity was also assessed.. After cure, median (95% confidence intervals) integrated plasma ghrelin increased from 1160.5 (765.5-1451) pg/ml x h to 1910.4 (1675.6-2395.6) pg/ml x h (p=0.002, Wilcoxon's rank sum test), a 75% increase. This was associated with a 14% increase in 24 hour intragastric acidity (p=0.006) and non-significant changes in leptin and gastrin. There was a significant positive correlation between plasma ghrelin and intragastric acidity (r(s) 0.44, p=0.05, Spearman's rank correlation).. After H. pylori cure, plasma ghrelin increased profoundly in asymptomatic subjects. This could lead to increased appetite and weight gain, and contribute to the increasing obesity seen in Western populations where H. pylori prevalence is low. This plausible biological mechanism links H pylori, through increasing obesity and GORD, to the increase in oesophageal adenocarcinoma observed in the West.

Topics: Adenocarcinoma; Adult; Esophageal Neoplasms; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Peptide Hormones; Radioimmunoassay

Helicobacter pylori infection might, in some instances, be considered as zoonosis.. The aim of this study was to assess the H. pylori prevalence in Polish shepherds and in their families as compared to controls. Patients and methods. A total of 42 shepherds from Polish Tatra Mountains with regular contact with sheep, 28 members of their families with incidental contacts and 61 age- and gender-matched farmer controls without such contacts were involved in this study. H. pylori status was determined by 13C-urea breath test. Serology was used to measure anti-H. pylori and anti-CagA IgG. Plasma gastrin, interleukin-8 and tumor necrosis factor-alpha were also determined.. The H. pylori prevalence reached 97.6% in shepherds, 86% in their family members, but significantly less, 65.1%, in controls without contact with sheep. Anti-H. pylori IgG, anti-CagA in contact groups were significantly higher than in controls. Also, plasma gastrin, interleukin-8 and tumor necrosis factor-alpha had significantly higher values as compared to controls.. Shepherds showed almost 100% H. pylori prevalence and higher incidence of CagA seropositivity, plasma gastrin and pro-inflammatory cytokine levels. Considering 100% positive 13C-urea breath test in sheep, it may be reasonable to suggest that H. pylori infection in shepherds and their family members originates from sheep and H. pylori infection might, therefore, be considered as zoonosis.

Topics: Adult; Agricultural Workers' Diseases; Animal Husbandry; Antigens, Bacterial; Bacterial Proteins; Breath Tests; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Poland; Prevalence; Seroepidemiologic Studies

Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils.. Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression.. In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups.. H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.

Topics: Animals; Bacterial Proteins; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Metaplasia; Sterigmatocystin; Tumor Suppressor Protein p53

The aim of this study was to clarify the pathogenesis of Helicobacter pylori-negative duodenal ulcer (DU) by investigating the meal-stimulated serum gastrin (SG) response. The subjects were 9 patients with H. pylori-negative DU, 28 H. pylori-positive DU, 11 H. pylori-positive volunteers, and 30 H. pylori-negative volunteers. Blood samples were taken before and after consumption of a test meal. The integrated 1-hr gastrin response (IGR) was taken to be the area under the SG time curve, calculated by the trapezoid method. H. pylori infection status was determined by histology, serology, and the [13C] urea breath test. The mean basal SG concentration was lower in the H. pylori-negative DU patients than in the H. pylori-positive DU patients, but an exaggerated IGR was observed in three patients (33.3%) with H. pylori-negative DU. In conclusion, our findings indicate that an exaggerated meal-stimulated gastrin response may contribute to the pathogenesis of H. pylori-negative DU.

Topics: Adolescent; Adult; Breath Tests; Duodenal Ulcer; Duodenoscopy; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Postprandial Period; Risk Factors

The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML), 281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.

Topics: Adult; Analysis of Variance; Antigens, Bacterial; Bacterial Proteins; Dyspepsia; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Polymerase Chain Reaction; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Turkey

Helicobacter pylori cag(+) strains and high-expression host interleukin 1beta (IL-1beta) polymorphisms augment the risk for intestinal-type gastric adenocarcinoma, a malignancy that predominates in males. We examined the effects of an H. pylori cancer-associated determinant (cagE), IL-1beta, and host gender in a transgenic hypergastrinemic (INS-GAS) murine model of gastric carcinogenesis.. Male and female INS-GAS mice infected with wild-type H. pylori, an H. pylori cagE(-) mutant, or H. felis were killed 2-24 weeks postchallenge. Gastric injury was scored from 0 to 4, and mucosal IL-1beta levels were quantified by ELISA.. Male INS-GAS mice infected with H. pylori uniformly developed atrophy, intestinal metaplasia, and dysplasia by 6 weeks and carcinoma by 24 weeks. Mucosal IL-1beta concentrations increased 12 weeks following Helicobacter challenge, but levels then decreased by 24 weeks. Inactivation of cagE delayed the progression to carcinoma, but neoplasia ultimately developed in all males infected with the H. pylori mutant. In contrast, none of the H. pylori-infected female mice developed cancer, and injury scores, but not IL-1beta levels, were significantly higher in males compared with females.. H. pylori infection induces gastric adenocarcinoma in an experimental mouse model of disease. Cancer is restricted to males and loss of cagE temporally retards but does not abrogate pathologic progression. Mucosal levels of IL-1beta increase prior to the development of gastric cancer but are not related to gender. The INS-GAS model is effective for investigating discrete host-microbial interactions that culminate in gastric cancer within the context of biologic conditions induced by H. pylori.

Topics: Adenocarcinoma; Animals; Bacterial Proteins; Disease Models, Animal; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Interleukin-1; Male; Mice; Precancerous Conditions; Sex Factors; Stomach; Stomach Neoplasms

Helicobacter pylori infection of Mongolian gerbils is an established model of gastric carcinogenesis, but gastric secretory aspects of this carcinogenesis have not been studied.. The effects of single intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) CFU/ml) or vehicle (saline) were examined at 1, 2, 4, 6, 9, 12 and 30 weeks from inoculation. Gastric morphology, the presence of H. pylori using the rapid urease test, the density of H. pylori and 16S rRNA and the plasma gastrin and somatostatin were determined.. H. pylori was detected in gastric mucosa in all infected animals. Basal gastric acid in gerbils was reduced by about 50% after H. pylori inoculation. Early lesions seen at 4 weeks after H. pylori inoculation consisted of chronic gastritis with thickened mucosal folds, oedema, congestion and mucosal lymphocytic infiltration. Adenomatous hyperplasia with cellular atypia with increased mitotic activity and the formation of apoptotic bodies and visible erosions and ulcerations were observed at 12-30 weeks after inoculation. The atypical gastric glands were situated 'back-to-back', suggesting gastric pre-cancer. The gastric blood flow in H. pylori-infected gerbils was significantly lower than that in the controls. Six- to seven-fold increase in plasma gastrin levels combined with significant fall in gastric somatostatin contents and the intraepithelial neoplasia were noticed in gerbils at all tested periods.. H. pylori-infection in gerbils resulted in gastric pre-cancer associated with functional changes, such as suppression of gastric secretion and impairment of both gastric mucosal microcirculation and the gastrin-somatostatin link.

Topics: Animals; Cell Transformation, Neoplastic; Disease Models, Animal; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Microcirculation; Precancerous Conditions; Somatostatin; Stomach Neoplasms

To study the relationship of Helicobacter pylori, lower esophageal sphincter pressure and gastrin in gastroesophageal reflux disease, to evaluate the effect of Helicobacter pylori on gastroesophageal reflux disease.. 20 patients were underwent 24-hour ambulatory esophageal pH monitoring to confirm the diagnosis of gastroesophageal reflux disease, and their lower esophageal sphincter pressure was measured by esophageal manometry. The patients were diagnosed endoscope negative GERD and endoscope positive GERD by endoscopy, and 3 biopsy specimens obtained from the gastric antrum at the same time were used for Helicobacter pylori culture, rapid urease test and Warthin-Starry stain. Hp infection was affirmed when at least two of the three tests were positive, then the patients were divided into Hp-negative group and Hp-positive group. Fasting serum gastrin concentration was determined by radioimmunoassay in 13 patients.. Hp-positive patients were 8 (male 4, endoscope negative GERD 2, mean age 55 +/- 9), Hp-negative patients were 12 (male 10, endoscope negative GERD 3, mean age 55 +/- 10). 13 of these patients were performed fasting serum gastrin measurement. The mean lower esophageal sphincter pressure, gastrin concentration and 24-hour pH monitoring DeMeester score in Hp-positive patients group were 11.25 mm Hg, 87.437 pg/ml and 72.30 respectively, and those in Hp-negative patients group were 13.75 mm Hg, 88.725 pg/ml and 55.64. Between the two groups, there was no significant difference in LESP, gastrin and DeMeester score (P = 0.193, P = 0.932 and P = 0.479); There was no correlation between LESP and gastrin, while serum gastrin level is associated strongly with DeMeester score (r = 0.902, P < 0.01).. The study showed that Helicobacter pylori had no effect on LESP by gastrin, however serum fasting gastrin concentration and DeMeester score were associated with each other.

Topics: Adult; Aged; Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers.. Prospective, multiple-dose pharmacokinetic and pharmacodynamic study.. University-affiliated medical center in Taiwan.. Twelve healthy volunteers (aged 20-30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six).. Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day.. Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean +/- SD values of area under the concentration-time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 +/- 883 vs 1131 +/- 512 ng x hr/ml and 1703 +/- 432 vs 561 +/- 358 ng x hr/ml, respectively; p<0.001) and on day 4 (5601 +/- 669 vs 1619 +/- 778 ng x hr/ml and 1914 +/- 378 vs 511 +/- 360 ng x hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic-pharmacodynamic relationship of rabeprazole appears to be time dependent.. The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Academic Medical Centers; Adult; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Breath Tests; Cytochrome P-450 CYP2C19; Female; Gastrins; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Inactivation, Metabolic; Male; Mixed Function Oxygenases; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Taiwan; Time Factors

To determine the frequency and significance of pancreatic acinar cells in the gastric oxyntic mucosa.. One hundred gastric oxyntic mucosal biopsy specimens from patients with chronic active gastritis (n = 30), multifocal atrophic gastritis (n = 15), autoimmune gastritis (n = 18), and normal gastric oxyntic mucosa (n = 37) were evaluated for the presence of pancreatic acinar cells. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and those positive for pancreatic acinar cells were immunostained with antibodies against trypsin and pancreatic amylase.. Eleven (11%) of 100 oxyntic mucosal tissue samples contained pancreatic acinar cells. These samples came from 9 of the 18 (50%) specimens of autoimmune gastritis, 1 of the 15 (6.6%) specimens of multifocal atrophic gastritis, and 1 of the 37 (2.7%) specimens of normal oxyntic mucosa. None of the samples with chronic active gastritis contained pancreatic acinar cells.. Pancreatic acinar cells were found in the oxyntic mucosa of patients with autoimmune gastritis significantly more frequently (P <.001) than in individuals with multifocal atrophic gastritis, normal oxyntic mucosa, or chronic active gastritis. Our study supports a metaplastic origin for pancreatic acinar cells in the oxyntic mucosa. Furthermore, detection of pancreatic acinar cells in the oxyntic mucosa of patients with gastritis strongly suggests an autoimmune pathogenesis.

Topics: Autoimmune Diseases; Carrier Proteins; Formaldehyde; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Glycoproteins; Helicobacter Infections; Helicobacter pylori; Humans; Lipase; Metaplasia; Pancreas; Paraffin Embedding; Parietal Cells, Gastric; Tissue Fixation

Gastrin and its precursor, progastrin, are synthesized in the stomach, particularly when infected with Helicobacter pylori, and they are metabolized, at least in part, in the liver. However, little is known about their levels in various hepatic diseases.. This study was carried out on 147 patients including chronic hepatitis B (n = 35), hepatitis C (n = 52) and liver cirrhosis (n = 60) of class A (n = 38), class B (n = 15) and class C (n = 7) (Child-Pugh classification) and age- and sex-matched healthy controls (n = 65). The diagnosis of chronic hepatitis was confirmed by liver biopsy in all patients, whereas the diagnosis of liver cirrhosis was based on clinical and laboratory findings. Liver biopsy was done in 38 out of 60 patients. Blood samples were collected under basal conditions and separated plasma samples were kept frozen at -70 degrees C until radioimmunoassay of progastrin and its products, including bioactive amidated gastrins.. Median (range) plasma concentrations of total progastrin product and amidated gastrin in control subjects were 147.5 (73-345) pM and 33 (15-65), respectively. These concentrations in hepatitis B and C were not significantly different from those in controls. In cirrhosis (classes A, B and C), the concentrations of the progastrin and of gastrin were significantly (P < 0.05) higher than in controls reaching, respectively, 253.5 (135-683 pM) and 47.5 (17-385) pM. Both progastrin and gastrin levels were significantly higher in H. pylori-positive than in negative cirrhotic patients. Antibodies against H. pylori were present in about 50% of controls, 68% of hepatitis B, 57% of hepatitis C and in 83% in cirrhosis patients. The difference in H. pylori prevalence between cirrhosis and controls was statistically significant.. Plasma levels of progastrin and gastrin are significantly increased in cirrhotic patients and this could be attributed to reduced metabolism of these peptides in liver cirrhosis and to their increased release due to H. pylori infection rate in this disease.

Topics: Adolescent; Adult; Aged; Female; Gastrins; Helicobacter Infections; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Male; Middle Aged; Protein Precursors

Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice.. BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated.. Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction.. H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.

Topics: Animals; Antibodies; Autoimmune Diseases; Cytokines; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Hydrogen-Ion Concentration; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Parietal Cells, Gastric; Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

The most common types of benign gastric polyps are fundic gland polyps, hyperplastic polyps, and adenomas. The aim of this study was to determine on which morphological and functional background benign gastric polyps develop. The study includes 85 consecutive patients with gastric polyps and sex- and age-matched controls without polyps selected at random from a general population sample. The type of polyp was hyperplastic in 52 (61%), fundic gland in 18 (21%), adenoma in 10 (12%), carcinoid in 2 (2%), hamartoma in 2 (2%), and inflammatory fibroid in 1 (1%) of the cases. Routine biopsies from the gastric corpus and antrum were examined for presence of gastritis and H. pylori. Blood samples were analyzed for H. pylori antibodies, H+,K+-ATPase antibodies, gastrin, and pepsinogen I. Patients with hyperplastic polyps had increased P-gastrin concentrations and S-H+,K+-ATPase antibody titers and decreased S-pepsinogen I concentrations with a high prevalence of atrophic corpus gastritis or pangastritis. A similar pattern was observed among patients with adenomas, whereas patients with fundic gland polyps had normal serology and a lower prevalence of gastritis and H. pylori infection than controls. In conclusion, hyperplastic polyps and adenomas are generally associated with atrophic gastritis. Patients with fundic gland polyps seem to have a sounder mucosa than controls. Whereas the risk of malignant gastric neoplasia is increased in patients with hyperplastic polyps or adenomas, this does not seem to be the case in patients with fundic gland polyps.

Topics: Adenomatous Polyps; Adult; Aged; Aged, 80 and over; Antibodies; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Male; Middle Aged; Pepsinogen A; Polyps; Prospective Studies; Sodium-Potassium-Exchanging ATPase; Stomach Neoplasms

The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well-defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori.. Mongolian gerbils with or without H. pylori were divided into 10 groups 6 weeks after inoculation and fed diets containing a drug (rebamipide or cimetidine) or control diet. All animals were sacrificed 4 weeks after grouping. Their stomachs were examined for histology, colonization by H. pylori, myeloperoxidase activity (myeloperoxidase), production of neutrophil chemokine (CINC/KC) and tumour necrosis factor-alpha (TNF-alpha), and serum gastrin levels.. H. pylori colonized all of the inoculated animals. Neither rebamipide nor cimetidine decreased myeloperoxidase activity, but each reduced wet stomach weight in H. pylori-infected animals. The amount of increase in CINC/KC and TNF-alpha in gastric tissue caused by H. pylori infection was decreased by treatment with rebamipide or cimetidine. H. pylori infection increased serum gastrin levels, and this increase was significantly enhanced by cimetidine but not rebamipide.. Rebamipide may improve H. pylori-infected chronic gastritis by preventing the production of inflammatory cytokines and chemokines, as does cimetidine, but may be preferable to cimetidine for long-term administration for treatment of H. pylori-infected chronic gastritis due to its effect on serum gastrin levels.

Topics: Alanine; Animals; Anti-Ulcer Agents; Chemokines; Cimetidine; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Neutrophils; Peroxidase; Quinolones; Tumor Necrosis Factor-alpha

Gastrointestinal bleeding caused by peptic ulcer disease is one of the serious complications of living-related liver transplantation (LRLT). The aim of this study was to clarify the factors involved in peptic ulcer formation in adult LRLT recipients. Forty consecutive adult LRLT recipients without a history of peptic ulcer disease were studied. Twenty-five patients (62.5%) tested positive for Helicobacter pylori. After LRLT, duodenal ulcer (DU) developed in six patients, and all of them tested positive for H. pylori. In contrast, none of the H. pylori-negative patients developed DU. Preoperative serum gastrin levels in patients with DU were significantly higher than in those without DU, irrespective of H. pylori infection. Preoperative pepsinogen I levels in patients with DU were significantly higher than in those without DU with H. pylori infection. These data suggest involvement of H. pylori infection in the development of DU after LRLT. Eradication of H. pylori may prevent the development of DU after LRLT particularly in patients with hypergastrinemia and high serum pepsinogen I.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Liver Transplantation; Living Donors; Male; Pepsinogen A

The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF.. Case-control study.. A university hospital.. Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)).. The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h).. In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group.. CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.

Topics: Adult; Aged; Case-Control Studies; Fasting; Female; Gastric Acid; Gastric Acidity Determination; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Quaternary Ammonium Compounds

Helicobacter pylori infection is a causal factor of gastric cancer (which is associated with low gastric acid secretion) or duodenal ulcer (high acid secretion). Parietal cells and ECL cells in the stomach are controlled by gastrin, which plays a crucial role in the regulation of acid secretion. The present study was undertaken to identify a possible role of gastrin in determining the different responses of the parietal cells and ECL cells to chronic H. pylori infection. Wild-type (C57BL/6J) gastrin(+/+) mice and gastrin(-/-) knockout mice, generated through targeted gene disruption and backcrossed eight times to C57BL/6J, were infected with H. pylori for 9 months. The acid output was measured 4 h after pylorus ligation (known to cause vagal excitation). The gastric mucosa was examined by immunocytochemistry with antisera to alpha-subunit of H+/K(+)-ATPase for the parietal cells, and to histamine and vesicle monoamine transporter-2 for the ECL cells, and by quantitative electron microscopy. In infected gastrin(+/+) mice, the acid output and the percentage of secreting parietal cells (freely fed state) were 20-30% of the values in uninfected controls, while the density and ultrastructure of parietal cells were normal. The infected mice had hypergastrinemia and displayed hypertrophy and hyperplasia of ECL cells. Although uninfected gastrin(-/-) mice had lower the acid output than uninfected gastrin(+/+) mice, there was a higher acid output (approximately 3 times) in infected gastrin(-/-) mice than their uninfected homologues. The numbers of parietal cells and ECL cells remained unchanged in infected gastrin(-/-) mice. In conclusion, chronic H. pylori infection results to impaired parietal-cell function (acid hyposecretion), hypergastrinemia and hyperplasia of ECL cells in wild-type mice but leads to vagally induced hypersecretion in gastrin-deficient mice.

Topics: Animals; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Mice; Mice, Knockout; Parietal Cells, Gastric; Photomicrography

Evidence indicates that eradication of Helicobacter pylori leads to the disappearance of hyperplastic polyps in the stomach. However, there are some exceptions. We have compared endoscopic and serologic findings of responder and non-responder cases with hyperplastic polyps to try to identify the cause(s), other than H. pylori infection, of the formation or growth of gastric hyperplastic polyps.. We retrospectively studied 33 patients whose hyperplastic polyps disappeared after eradication of H. pylori and 10 patients whose hyperplastic polyps did not disappear after eradication. The patients were examined both endoscopically and serologically before, 1-3 months after and 12-15 months after the eradication.. The responder and non-responder groups were similar with respect to age, sex, coexisting diseases, and histologic findings. The number and maximum size of polyps tended to be larger before treatment in the non-responder group than in the responder group. The serum gastrin level was higher in the non-responder group than in the responder group before, 1-3 months after and 12-15 months after the eradication (p=0.0096, p>0.2, p=0.0014). On histologic examination, similar reductions in the degree of inflammatory cell infiltration in the gastric mucosa of the antrum and body were seen in both the responder and non-responder groups. In the non-responders, the size and numbers of the polyps regressed in 5 of the 10 patients. The score of glandular atrophy in the antrum and the serum gastrin levels in the non-regressed cases was higher than those in the regressed cases at 1-3 and 12-15 months after eradication.. Persistent high gastrin levels were found in the non-responder cases with gastric hyperplastic polyps.

Topics: Adult; Aged; Anti-Bacterial Agents; Chi-Square Distribution; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Immunoglobulin G; Male; Middle Aged; Penicillins; Pepsinogen A; Polyps; Proton Pump Inhibitors; Retrospective Studies; Statistics, Nonparametric; Stomach Neoplasms

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPARgamma), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPARgamma, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF-alpha values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPARy, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are significantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric car

Topics: Aged; Apoptosis; Case-Control Studies; Caspase 3; Caspases; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytokines; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Inhibitor of Apoptosis Proteins; Isoenzymes; Lactones; Male; Membrane Proteins; Microtubule-Associated Proteins; Middle Aged; Neoplasm Proteins; Prostaglandin-Endoperoxide Synthases; Protein Precursors; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Stomach Neoplasms; Sulfones; Survivin; Transcription Factors

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

Topics: Adult; Aged; Ammonia; Anti-Bacterial Agents; Anti-Ulcer Agents; Bile Acids and Salts; Cytokines; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole

Numerous studies have shown an association between Helicobacter pylori (Hp) infection and gastric cancer (GC).. This study was designed to determine the role of cytotoxin-associated gene A (CagA)-positive Hp infection, serum amidated gastrins and their precursor, progastrin, gastric acidity and serum pepsinogen I (PG-I) levels in gastric cancerogenesis in 74 cancer patients and in 77 age- and gender-matched controls. Serum IgG antibodies to Hp and CagA and levels of IL-8 and PG-I were measured by ELISA, while progastrin and amidated gastrin by specific radioimmunoassay.. The overall Hp and CagA seropositivity in GC patients were significantly higher (82 and 60%) than in matched controls (61 and 27%, respectively). Progastrin and amidated gastrin levels over their cutoff points (122 and 32 pM, respectively) were found in a significantly larger number of GC (59.4 and 44.5%) than in controls (9.0 and 16.8%, respectively). Histologically, all these GCs with increased serum progastrin and amidated gastrins were of intestinal type and showed CagA and Hp seropositivity. Serum IL-8 and gastric pH, above their cutoff points (pH >4.5), and serum PG-I level below its cutoff point (44.2 microg/l) were observed in a significantly higher number of GC patients as compared to controls.. (1) GC patients have higher Hp and CagA seroprevalence than matched controls, confirming that CagA-positive Hp infection is associated with higher risk of GC; (2) serum levels of amidated gastrins and their precursor, progastrin, as well as IL-8 are significantly higher, while serum PG-I levels are reduced in intestinal type GC compared to controls, and (3) determination of high serum progastrin, amidated gastrins and IL-8 combined with low serum PG-I may be useful biomarkers of GC.

Topics: Aged; Aged, 80 and over; Antigens, Bacterial; Bacterial Proteins; Biomarkers, Tumor; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Middle Aged; Pepsinogen A; Protein Precursors; Risk Factors; Seroepidemiologic Studies; Stomach Neoplasms

Although regenerating gene (Reg) protein is reported to have a trophic effect on gastric epithelial cells, its involvement in human gastric diseases is not clear. We have recently shown that both gastrin and gastric mucosal inflammation enhance Reg gene expression in the fundic mucosa in rats. This study was designed to clarify whether Reg protein is involved in Helicobacter pylori-induced gastritis and whether Reg gene expression is linked to serum gastrin levels in this condition. Mongolian gerbils were inoculated with an H. pylori strain isolated from a gastric cancer patient. Four weeks later, some of the gerbils with H. pylori infection were eradicated by lansoprazole, amoxicillin, and clarithromycin. The time courses of changes in Reg gene expression, serum gastrin levels, gastric acidity, and histopathologic factors were examined. Four weeks after H. pylori infection, gastritis started spreading to the fundic mucosa, and gastric acidity started reducing. Serum gastrin levels and Reg mRNA expression in the fundus were significantly increased 6 weeks after infection. Reg mRNA expression in the fundus correlated significantly with both serum gastrin levels and the severity of fundic mucosal inflammation. After H. pylori eradication, serum gastrin levels and fundic mucosal inflammation were normalized, and the increase in Reg mRNA expression was abolished. The Reg gene is associated with hypergastrinemia and fundic mucosal inflammation and may be involved in H. pylori-induced gastritis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Base Sequence; Calcium-Binding Proteins; Cell Division; Disease Models, Animal; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lithostathine; Male; Molecular Sequence Data; Nerve Tissue Proteins; RNA, Messenger; Sequence Alignment; Up-Regulation

Relatives of patients with gastric cancer are at increased risk of developing this disease, especially if they are infected by Helicobacter pylori. Moreover, H. pylori-related atrophic gastritis and hypochlorhydria are well-documented risk factors for noncardia gastric cancer. Serum pepsinogen I (sPGI) and II (sPGII) levels are low in this condition. The aim of our study was to assess by means of a 'Gastropanel' blood test, including sPGI, sPGII, gastrin-17 (G-17) and antibodies anti-H. pylori (IgG-Hp). both functional and morphological features of gastric mucosa in Hp + ve subjects with a family history of gastric cancer.. Twenty-five Hp + ve subjects consecutively referred to our department for gastrointestinal complaints, selected as first-degree relatives of patients suffering from gastric cancer, were enrolled in the study and then matched for sex and age with 25 dyspeptic and Hp + ve subjects with no family history of gastric neoplasia. Blood samples were taken for determination of gastropanel in all patients; in addition, antibodies against CagA were analysed.. No statistically significant differences were detected between the two groups as regards alcohol consumption, coffee intake and smoking habits. Mean sPGI levels in Group A (83.4 +/- 58.4 microg/L) were significantly lower than those in Group B (sPGI 159.5 +/- 80.6 microg/L; P < 0.0001) as well as sPGII (12.5 microg/L = 6.24 versus 20.6 +/- 58 microg/L; P < 0.006). No statistical difference was found between the two groups in relation to G-17 levels, IgG-Hp titres and antibodies against CagA.. First-degree relatives of patients with noncardia gastric cancer affected by H. pylori infection present lower sPGI and sPGII levels, possibly due to the increased frequency of atrophic lesions in these patients.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Biomarkers; Dyspepsia; Family Health; Female; Gastrins; Gastritis, Atrophic; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Stomach Neoplasms

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.

Topics: Adult; Case-Control Studies; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Inflammatory Bowel Diseases; Male; Radioimmunoassay

Helicobacter pylori infection is often diagnosed with non-endoscopic methods, such as serology or breath or antigen stool tests. These tests provide information on the presence or absence of the H. pylori gastritis only. We investigated whether atrophic gastritis can be diagnosed and typed non-endoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G-17) are assayed in connection with H. pylori testing.. The present investigation is an observational case-control study comprising 100 selected dyspeptic outpatients with (cases) or without (controls) advanced (moderate or severe) atrophic gastritis. Before the blood tests, all patients underwent a diagnostic gastroscopy with multiple biopsies. The series of cases includes 56 patients. Eight had an advanced antrum limited atrophic gastritis, 13 had resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and 30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the whole stomach was removed in one patient. Twenty of the 44 controls had a non-atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand) was measured 20 min after a protein-rich drink. The H. pylori antibodies were assayed with a polyclonal EIA method.. A low S-PGI (<25 microg/l; an empirical cut-off with best discrimination) was found in 31 of 37 patients (84%) with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens. A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori-associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but in 3 of 20 control patients (15%) with H. pylori-related non-atrophic gastritis. Median and mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. Among all patients with atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited to antrum or corpus) or resected stomach, 50 of 56 patients (89%; Cl 95%: 81%-97%) had a low S-PGI and/or a low S-G-17prand with positive H. pylori serology. Such low values werc found in 3 of the 44 control patients (7%; CI 95%: 0%-14%).. Low serum levels of G-17prand and PGI are conceivable biomarkers of atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign of the multifocal or antrum-limited atrophic gastritis in patients infected with H. pylori.

Topics: Antibodies, Bacterial; Antibodies, Monoclonal; Biomarkers; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Sensitivity and Specificity

Despite numerous epidemiological studies, the association between Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This study was designed to determine the seropositivity of H. pylori and cytotoxin-associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO) in a large series of GC patients and controls.. 337 GC patients (118 men and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum-amidated gastrin was determined by specific radioimmunoassay and correlated with gastric luminal pH.. The numbers of GC patients and controls involved in the study in various age groups, ranging from 20 to > 70 years, were similar, but overall H. pylori IgG seropositivity in GC patients was significantly higher (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the calculated cut-off value (38.88 pM/L) were found in several-fold larger number in GC patients (48%) than in controls (8.3%) and. similarly, serum IL-8 values over the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH = 4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls, and strong correlation between the serum gastrin and gastric pH was found in GC but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl: 1.61-4.22) for CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have significant influence on GC formation (OR > 1 in logistic regression).. 1. CG patients show significantly higher H. pylori IgG and CagA seropositivity than dyspeptic age- and gender-matched controls, confirming that gastric infection with CagA expressing H. pylori greatly increases the risk of GC. 2. Serum gastrin levels in GC but not in controls are correlated with the rise in intragastric pH, indicating that excessive gastrin release in GC is affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity are significantly increased in the majority of GC patients, and are the only variables in multivariable analysis to have a predominant influence on GC formation, which suggests that both these parameters may be implicated in H. pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce significantly more IL-8 than do non-GC controls, probably reflecting CagA-positive H. pylori-associated gastritis.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Dyspepsia; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Interleukin-8; Male; Middle Aged; Radioimmunoassay; Stomach Neoplasms

Colorectal cancers (CRCs) are one of the most common forms of cancer in Poland and one of the leading causes of death. The tumors have been attributed to genetic, dietary, and other environmental factors, but recently growth factors such as gastrin have also been implicated in the carcinogenesis. The relationship between plasma amidated and nonamidated gastrin in CRCs is controversial. This study was designed (1) to determine the plasma levels of progastrin and amidated gastrin in 50 CRC patients before and 3-6 months after removal of the tumor, (2) to determine the tumor concentrations of these gastrin peptides and the level of expression for gastrin mRNA and gastrin/CCK(B) receptor mRNA, (3) to examine the expression of cyclooxygenase COX-1 and COX-2 mRNA in CRC tissue, and (4) to compare the prevalence of Hp and its cytotoxic protein, CagA, and cytokines (TNFalpha, IL-1beta, and IL-8) in CRCs, before and after removal of tumor. It was found that the CRC, its resection margin, and the plasma contained severalfold higher levels of progastrin than of amidated gastrins and that the removal of the CRC tumor resulted in a marked reduction in plasma progastrin level without a significant alteration in plasma levels of amidated gastrins. Both gastrin and CCK(B)-R mRNA were detected in the cancer tissue and resection margin by RT-PCR, and similarly, COX-1 and COX-2 mRNA were expressed in these tissues of most CRCs. The seroprevalence of Hp, especially that expressing CagA, and levels of IL-1beta, but not other cytokines, were significantly higher in CRC patients than in 100 age-, gender-, and profession-matched controls and did not change significantly about 3-6 months after tumor resection. We conclude that (1) the CRC and its margin contain large amounts of progastrin and show gene expression of gastrin, CCK(B)-R, and COX-2; (2) removal of the CRC markedly reduces the plasma concentrations of progastrin; (3) the Hp infection rate is higher in CRC, and this may contribute to colorectal cancerogenesis via enhancement of progastrin and gastrin release; and (4) plasma progastrin concentrations might serve as a biomarker of CRC.

Topics: Biomarkers, Tumor; Case-Control Studies; Colorectal Neoplasms; Cyclooxygenase 1; Cyclooxygenase 2; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Prostaglandin-Endoperoxide Synthases; Protein Precursors; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Seroepidemiologic Studies

Topics: Acinetobacter Infections; Animals; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Mice; Stomach Neoplasms

Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori-infected stomachs of Mongolian gerbils for a long time.. Five-week-old-male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals.. In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes.. H. pylori infection caused not only gastric carcinomas but also enterochromaffin-like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.

Topics: Adenocarcinoma; Animals; Carcinoid Tumor; Disease Models, Animal; Gastric Mucosa; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Stomach Neoplasms

Our aim was to study the serum pepsinogen levels in gastric cancer patients in our population in relation to histology and the presence of Helicobacter pylori.. Forty-six patients with gastric cancer and 70 controls were studied prospectively in a 1-year period. Serum levels of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin were measured by radioimmunoassay.. The mean PG I levels for cancer patients and controls were 83.5 microg/l and 60.9 microg/l, respectively (P = 0.03), the mean PG II levels were 27.2 microg/l and 12.1 microg/l respectively (P < 0.0001). The PG I/II ratio was significantly lower in cancer patients (P = 0.04) and in those with Helicobacter infection. Serum pepsinogen levels were not affected by any pathological characteristics. Histology showed that the prevalence of chronic gastritis, intestinal metaplasia, and gastric atrophy was 97%, 56%, and 15%, respectively.. The prevalence of gastric atrophy is low in our population, and serum pepsinogen measurement is not useful as a screening tool for gastric cancer in this population.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Stomach Neoplasms

Helicobacter pylori (H. pylori) is now well known to be associated with stomach cancer, with infection during childhood rather than as an adult considered to be more important for carcinogenesis. To evaluate the difference in susceptibility to stomach carcinogenesis in relation to age of acquisition of H. pylori infection, we designed an experiment involving inoculation of H. pylori ATCC43504 followed by N-methyl-N-nitrosourea (MNU) treatment at different ages. Four-week-old male Mongolian gerbils (MGs) were divided into twelve groups. H. pylori was inoculated at 4, 18 and 32 weeks of age, as representatives of early, middle and late infection, respectively. Two weeks later, the animals were treated with MNU. Groups without H. pylori and/or MNU were included as controls. The incidences of adenocarcinomas at 52 weeks after the inoculation in the early (H. pylori+MNU), middle (H. pylori+MNU), and late (H. pylori+MNU) group were 60% (12/20), 18.4% (2/11), and 10% (2/20), respectively. The corresponding figures were 14.8% (4/27), 0% (0/11), and 0% (0/21) in the MNU-alone groups. A higher titer of serum IgG for H. pylori and higher gastrin level were seen in the early-infected compared to the middle and the late groups (P<0.01). The results clearly demonstrated that early acquisition of H. pylori significantly increases gastric chemical carcinogenesis with MNU, as compared to the case with later infection, possibly because of differences in host gastric mucosal factors and immunologic responses.

Topics: Adenocarcinoma; Animals; Antibodies, Bacterial; Gastrins; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunoglobulin G; Male; Methylnitrosourea; Risk; Stomach Neoplasms

H. pylori is a major cause of primary chronic gastritis and peptic ulcer disease in children. The authors give an account of H. pylori infection (cagA+, vacA+) in a 15-year-old girl where the initial clinical features included fatigue, collapses, and anorexia, elevated serum gastrin level (> 1000 mIU/l) raised the suspicion of gastrinoma. H. pylori gastric infection was also associated with iron-deficiency anemia. After treatment for H. pylori infection (omeprazole, clarithromycin, amoxycillin), clinical symptoms improved consistently, the serum gastrin level was repeteadly quite normal and hematologic and iron profiles were within the normal range. There is compelling evidence that H. pylori must be taken into account as a cause of hypergastrinemia other than gastrinoma in childhood.

Topics: Adolescent; Anemia, Iron-Deficiency; Diagnosis, Differential; Female; Gastrinoma; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pancreatic Neoplasms

Helicobacter pylori (H. pylori) infection in patients with chronic renal failure plays an important role in the pathogenesis of upper gastrointestinal tract diseases. In our earlier study we did not find significant relationship between parathormone (PTH) concentration abnormalities and H. pylori infection in hemodialysis patients (HD pts). The aim of our present study was to examine other parameters and interrelationships between them, connected with H. pylori infection in HD pts. The serum concentration of the following substances were measured: gastrin (G), parathormone (PTH), and IgG antibodies against H. pylori. The study was conducted in 65 (36 M, 29 F) stable HD pts: age 49 +/- 12 years, dialysed from 6 to 288 months. The control group (CG) consisted of 15 healthy people, mean age 38 +/- 8 years. The mean concentration of serum PTH serum was significantly higher in HD pts than in CG (538 +/- 520 vs 35 +/- 9.3 pg/ml, p < 0.001). The mean concentration of gastrin in serum was significantly higher in HD pts than in CG (155.37 +/- 235.4 vs 87.97 +/- 9.5 pg/ml, p < 0.01). The mean concentrations of IgG antibodies against IgG H. pylori was similar in HD pts and CG (88.1 +/- 80.0 vs 91.34 +/- 66.8 U/ml). We found significant positive correlation between IgG antibodies against H. pylori infection and gastrin level in serum of HD pts (r = 0.315, p < 0.001). We did not find significant correlation between concentrations: PTH vs G and PTH vs IgG against H. pylori.. Helicobacter pylori infection contributes to hypergastrinaemia in hemodialysed patients. There is no relationships between PTH abnormalities and H. pylori infection.

Topics: Adult; Case-Control Studies; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Risk Factors

Hypergastrinemia and a reduction in tissue somatostatin occur in Helicobacter pylori-infected patients. We investigated whether the D cell may be a direct target of gastric inflammation and hypergastrinemia. D cells were quantified by morphometry and flow cytometry in 16-wk-old wild-type (G+/+) and gastrin-deficient (G-/-) mice. Hypochlorhydric G-/- mice were treated with either antibiotics for 20 days or infused with gastrin (G-17) for 14 days. G+/+ mice were made hypochlorhydric by treating them with omeprazole for 2 mo. G-/- mice showed significant inflammation compared with the G+/+ mice, which resolved after 20 days of antibiotic treatment. D cell numbers were not significantly different between G-/- and G+/+ mice. After G-17 was infused, fundic and antral D cell numbers decreased in the G-/- mice. G+/+ animals made hypergastrinemic with omeprazole exhibited decreased D cell numbers. When omeprazole-treated mice were treated with antibiotics alone, elevated plasma gastrin levels returned to baseline and D cell numbers returned to resting levels despite persistent hypochlorhydria. Hypergastrinemia, induced by inflammation, results in decreased D cell numbers. Thus the stomach responds to the presence of inflammation by reducing somatostatin levels, thereby releasing the inhibition on the G and parietal cells to maximize gastric acid output.

Topics: Animals; Anti-Ulcer Agents; Female; Gastric Acid; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Omeprazole; Parietal Cells, Gastric; Pyloric Antrum; Somatostatin

Reduced gastric acid predisposes the stomach to colonization by bacteria and inflammation. Therefore, we investigated how the chronic gastritis in mice made hypochlorhydric by either gastrin deficiency or omeprazole treatment modulates epithelial cell function.. The gastric pathology of 16-week-old wild-type gastrin-expressing (G+/+) and gastrin-deficient (G-/-) mice maintained in conventional housing was compared. G-/- mice were then treated with antibiotics for 20 days. In a separate experiment, G+/+ mice were treated with omeprazole for 2 months or treated with omeprazole and antibiotics.. Compared with the G+/+ animals, the hypochlorhydric G-/- mice showed significant inflammation that resolved after 20 days of antibiotic treatment and correlated with a decrease in bacterial overgrowth. Elevated G- and parietal-cell numbers in the G-/- mice, quantified by flow cytometry, normalized after antibiotic treatment. G+/+ mice treated with omeprazole had increased bacteria and mucosal lymphocytes that resolved after antibiotic therapy. Quantitation of the gastric cells in these omeprazole-treated mice revealed a significant increase in G- and parietal-cell numbers. On resolution of the gastritis, a decrease in parietal and gastrin-expressing (G) cells was observed despite sustained hypochlorhydria in the presence of omeprazole.. Genetic or chemical hypochlorhydria predisposes the stomach to bacterial overgrowth resulting in inflammation. The specific changes in parietal and G cells correlate with the presence of inflammation and not directly with gastric acid. Thus, the normal stomach responds to inflammation by increasing the number and function of cell types that are able to maximize gastric acid output.

Topics: Achlorhydria; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; B-Lymphocytes; Bacteriological Techniques; Campylobacter; Campylobacter Infections; Female; Flow Cytometry; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Male; Mice; Omeprazole; Parietal Cells, Gastric; T-Lymphocytes

Helicobacter pylori infection may increase or decrease acid secretion and may augment proton pump inhibitor efficacy. Pepsin effects have not been reported. In Zollinger-Ellison syndrome (ZE) specifically, H. pylori has been reported to decrease acid.. To examine H. pylori effects on secretion and dose of medication in hypersecretors (basal acid output > 15 mmol/h) undergoing long-term treatment with individually optimized lansoprazole doses.. Sixty-five patients (47 ZE and 18 non-ZE), treated for > 3 months to 10 years, were tested every 6 months with endoscopy, gastric analysis and serum gastrin.. Forty-three per cent were H. pylori-positive. Acid, pepsin and gastrin were not different between H. pylori-positive and H. pylori-negative patients before or during long-term lansoprazole treatment. Initially, H. pylori-positive patients required less lansoprazole than H. pylori-negative patients (68 +/- 6 vs. 96 +/- 8 mg/day), but after 3 years the doses converged (83 vs. 86 mg/day). The disappearance of H. pylori in 15 patients caused no significant changes in acid, pepsin, gastrin or lansoprazole dose in the following 4 years.. H. pylori had no significant initial or long-term physiological or potential clinical effects on acid or pepsin secretion or gastrin in these acid hypersecretors.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pepsin A; Prospective Studies; Zollinger-Ellison Syndrome

Helicobacter pylori may increase or inhibit gastric acid. We studied acid variations and plasma gastrin in cats harboring Helicobacter felis, harboring H. pylori, or free of gastric pathogens with reference to thioperamide (H(3) receptor antagonist) and SR-27417A (PAF receptor antagonist). In cats harboring H. felis, gastric mucosa were histologically normal. After H. felis eradication, pentagastrin-stimulated acid secretion was increased (40%) compared with the situation before eradication. Thioperamide abolished this inhibitory effect of H. felis, whereas SR-27417A did not. Basal and meal-stimulated plasma gastrin levels were not affected by eradication therapy. Acid secretion was inhibited (-80%) in week 3, increased from weeks 5 to 9, and remained constant for up to 42 weeks after H. pylori infection. SR-27417A had no effect on acid secretion before week 8 but inhibited it thereafter, and thioperamide increased it (20%) only before week 7 in those cats. Helicobacter inhibits gastric acid via an H(3) receptor pathway. Inflammatory mediators are thus involved in adaptation to the inhibitory effects of H. pylori on acid secretion.

Topics: Animals; Anti-Bacterial Agents; Cats; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter; Helicobacter Infections; Helicobacter pylori; Histamine Antagonists; Kinetics; Pentagastrin; Piperidines; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Histamine H3; Thiazoles; Urease

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Carcinoid Tumor; Duodenal Ulcer; Female; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Stomach Neoplasms

The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)-positive patients is almost unknown.. To investigate in HIV-infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV-related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies.. Fifty-nine HIV-positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies.. In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 x 10(6) cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 x 10(6) cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV-positive patients without AIDS or with a CD4+ count of > 100 x 10(6) cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 x 10(6) cells/L than in those with a CD4+ count of > 100 x 10(6) cells/L (62% vs. 26%, P < 0.05).. HIV-positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV-positive patients with overt AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Autoantibodies; CD4 Lymphocyte Count; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen C

In mouse models and humans, Helicobacter pylori is associated with an increase in serum gastrin and gastrin-expressing (G) cells with a concomitant decrease in somatostatin-expressing D cells. Inflammation of the gastric mucosa can progress to metaplastic changes in the stomach and to decreased colonization by H. pylori and increased colonization by non-H. pylori organisms. In addition, about 20% of individuals with chronic gastritis are H. pylori negative, suggesting that other organisms may induce gastritis. Consistent with this hypothesis, we report here that Acinetobacter lwoffii causes the same histologic changes as does H. pylori. Gastric epithelial cells were isolated from the entire stomach by an enzymatic method for quantitation by both flow cytometry and morphometric analysis. Two months after mice were inoculated with H. pylori or A. lwoffii, the mucosal T- and B-cell numbers significantly increased. After 4 months of infection, there was a threefold increase in the number of G cells and a doubling in the number of parietal cells. A threefold decrease in the number of D cells occurred in H. pylori- and A. lwoffii-infected mice. Plasma gastrin levels increased after both H. pylori and A. lwoffii infection. Histology revealed the presence of inflammation in the gastric mucosa with both A. lwoffii and H. pylori infection. A periodic acid-Schiff stain-alcian blue stain revealed mucous gland metaplasia of the corpus. Collectively, the results demonstrate that gastritis and hypergastrinemia are not specific for H. pylori but can be induced by other gram-negative bacteria capable of infecting the mouse stomach.

Topics: Acinetobacter Infections; Animals; DNA, Bacterial; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Ki-67 Antigen; Mice; Mice, Inbred C57BL; T-Lymphocytes

Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I : II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori-associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori-induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori-negative and positive volunteers relative to differences in pepsinogens and gastrin.. Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti-H. pylori antibody, NOx, gastrin and pepsinogens.. In H. pylori antibody-positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori-negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori-positive than negative subjects (p < .001). In subjects with high pepsinogen I : II (6 or higher), serum NOx was higher in H. pylori-positive than in negative subjects.. H. pylori-induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori-negative subjects, serum correlates with serum pepsinogen II.

Topics: Adult; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Nitrates; Nitrites; Pepsinogen A

The association between gastroesophageal reflux disease and end-stage renal disease remains unclear. We aimed to assess the prevalence of gastroesophageal reflux disease and also to identify possible pathogenetic factors in the development of reflux in symptomatic end-stage renal disease patients.. The study involved 42 end-stage renal disease patients with upper GI symptoms (group I) and 46 age- and sex-matched controls who did not have renal disease but had the same symptoms (group II). Endoscopy, endoscopic biopsies, and 24-h esophageal pH studies were used to diagnose gastroesophageal reflux disease. Subjects were also investigated for Helicobacter pylori gastritis and GI amyloidosis.. The prevalences of gastroesophageal reflux disease in the two groups were similar (81% vs 84.8%, p = 0.423). The prevalence of H. pylori infection was significantly lower in group I than in group II (38.1% vs 67.4%, p = 0.01). There were II cases of GI amyloidosis in group I. Multivariate logistic regression analysis in group I showed that GI amyloidosis (OR = 7.28, 95% CI = 1.13-46.93), chronic ambulatory peritoneal dialysis treatment (OR = 5.54, 95% CI = 1.01-30.43), and absence of H. pylori infection (OR = 3.75, 95% CI = 1.01-13.9) were significantly associated with reflux esophagitis.. Upper GI symptoms are important in predicting gastroesophageal reflux disease in end-stage renal disease patients. Chronic ambulatory peritoneal dialysis, GI amyloidosis, and absence of H. pylori infection seem to be risk factors for the development of gastroesophageal reflux disease in end-stage renal disease patients.

Topics: Adult; Amyloidosis; Esophagitis; Esophagus; Female; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Multivariate Analysis; Prevalence; Risk Factors

The relationship between plasma gastrin levels and colorectal cancer is controversial. When confounding factors which increase plasma gastrin levels are taken into account, it has been shown that gastrin levels are not elevated in patients with colorectal cancer. However, these studies only measured amidated gastrin. Total gastrin (which includes unprocessed, partially processed, and mature forms of gastrin) has been shown to be elevated in patients with colorectal cancer.. The aim of this study was to determine whether fasting plasma levels of progastrin, amidated gastrin, or glycine extended gastrin are elevated in patients with colorectal cancer or colorectal polyps compared with controls.. Progastrin, amidated gastrin, and glycine extended gastrin were estimated by radioimmunoassay using the following antibodies: L289, 109-21, and L2. Blood samples were analysed for Helicobacter pylori by an enzyme linked immunosorbent assay.. Median progastrin levels were significantly higher in the cancer group (27.5 pmol/l) than in the polyp (< or =15 pmol/l) or control (< or =15 pmol/l) group (p=0.0001 There was no difference in median levels of amidated gastrin between groups. Median levels of amidated gastrin were significantly higher in H pylori positive patients (19 pmol/l) than in H pylori negative patients (8 pmol/l) (p=0.0022). Median plasma progastrin levels were significantly higher for moderately dysplastic polyps (38 pmol/l) compared with mildly dysplastic (15 pmol/l) and severely dysplastic (15 pmol/l) polyps (p=0.05).. Plasma levels of progastrin, but not amidated gastrin or glycine extended gastrin, are significantly elevated in patients with colorectal cancer compared with those with colorectal polyps or controls, irrespective of their H pylori status. We conclude that measuring plasma progastrin levels in patients with colorectal cancer is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Colonic Polyps; Colorectal Neoplasms; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Protein Precursors

Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Histamine Agonists; Humans; Male; Methylhistamines; Middle Aged; Statistics, Nonparametric

To study the influence of Helicobacter pylori eradication on basal gastrin and pepsinogen I and II levels in patients with gastric ulcer over a 1-year follow-up period, and to assess the usefulness of these values in confirming H. pylori eradication after treatment.. Fifty-six patients with gastric ulcer and H. pylori infection were prospectively studied. At the beginning of the study, endoscopy with biopsies for histologic examination and urease testing was carried out, as were 13C-urea breath test and blood samples for determination of gastrin and pepsinogen I and II values by radioimmunoassay and serology. Histologic study, 13C-urea breath test and laboratory determinations were repeated at months 1, 6 and 12 after completion of eradication treatment.. H. pylori infection was eradicated in 82.1% of patients. In patients with successful H. pylori eradication, the initial mean gastrin value was 75.5 +/- 39.1 pg/ml, while at 1 month after treatment this value decreased to 49.2 +/- 21 pg/ml (p < 0.0001). No further reductions were noted. Initial pepsinogen I and II values were 104 +/- 58 and 15.8 +/- 10 ng/ml, respectively, whereas at month 1 after treatment these values were 77 +/- 42 and 7.3 +/- 4 ng/ml, respectively (p < 0.0001) and were 72 +/- 41 and 6.7 +/- 3 ng/ml respectively at month 6 (p < 0.01); no further variations were observed thereafter. The area under the ROC curve which reveals eradication through reductions in hormonal values was 0.70 for gastrin, 0.78 for pepsinogen I, 0.93 for pepsinogen II and 0.92 for the pepsinogen I/II ratio. At months 6 and 12 after treatment completion, differences in mean gastrin and pepsinogen I and II values between the patients with normal histologic findings and those with chronic gastritis were significant (p < 0.05).. a) H. pylori eradication is associated with an early fall in basal gastrin values and a progressive decrease in basal pepsinogen I and II values. b) In patients with gastric ulcer, determination of the decrease in basal pepsinogen II levels is a useful and early non-invasive method for confirming eradication. c) Determination of gastrin and pepsinogen I and II values may be useful for assessing improvement in gastritis 6 months after treatment completion.

Topics: Area Under Curve; Biomarkers; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Stomach Ulcer

Recently, it has been recognized that Helicobacter pylori (H. pylori) infection is associated with an exaggeration of basal and meal gastrin secretion. We investigate whether there is a relationship between H. pylori-related chronic gastritis and G-cell and D-cell number and granule density index of G and D cells. - The number of antral G cells and D cells and granule density index of D and G cells are compared between thirty two patients with H. pylori-related chronic gastritis and twelve patients without H. pylori and inflammation. Antral mucosal biopsy specimens are examined using light and electron immunohistochemical techniques. - The number of G cells is the same in either infected or uninfected patients (98.40 +/- 11.39, 109.25 +/- 12.76 vs 101.17 +/- 7.72 for infected patients with non atrophic and with mild atrophic chronic gastritis and uninfected controls, respectively) except for the cases with moderate gastric mucosal atrophy, where G cells (58.22 +/- 5.63) decrease in number. The number of D cells is decreased in all patients with H. pylori-related gastritis. G cell granule density index is significantly (p < 0.05) increased in patients with H. pylori-related chronic gastritis than in controls (3.15 +/- 0.43 vs 2.528 +/- 0.01). D cell granule density index is similar between patients with H. pylori chronic gastritis and controls (3.18 +/- 0.05 vs 3.166 +/- 0.12). It is concluded that decreased D cells number in patients with H. pylori-related chronic gastritis might be one of the reasons for the existing hypergastrinaemia.

Topics: Adolescent; Adult; Cytoplasmic Granules; Female; Gastrin-Secreting Cells; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Microscopy, Immunoelectron; Middle Aged; Pyloric Antrum; Somatostatin; Somatostatin-Secreting Cells

Serum pepsinogen (sPG) levels are used in gastric cancer screening programs. However, modification of sPG levels by smoking habit, according to the status of Helicobacter pylori (H. pylori) infection has been little investigated. This study investigated the effects of smoking on serum levels of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin by IgG titer of antibody against H. pylori (Hp-IgG titer) using the data from 356 current-smokers and 262 non-smokers (133 never-smokers and 129 ex-smokers) in a cross-sectional study of 618 men aged 40 to 49 years. PG I, PG II, PG I / PG II ratio and gastrin were significantly associated with Hp-IgG titer in never-smokers [Spearman's correlation coefficient (95% confidence interval): 0.23 (0.07, 0.39), 0.52 (0.41, 0.63), -0.40 (-0.54,-0.27), and 0.25 (0.10, 0.41), respectively]. However, the correlation coefficients of PG I and PG II decreased in current-smokers, 0.02 (-0.1, 0.13) and 0.32 (0.22, 0.42), respectively. In H. pylori seronegative and low titer cases, the mean PG I level was significantly (P < 0.01) higher in current-smokers, compared with non-smokers. However, in high titer cases, the mean PG I level was lower in current-smokers. Mean PG II and gastrin levels, and PG I / PG II ratio did not differ according to smoking habits by Hp-IgG titer. The gastrin level was significantly correlated with PG II, but not PG I. These data indicate that current smoking influences the serum PG I level depending on Hp-IgG titer and the associations between sPGs and Hp-IgG titer. Gastrin is not involved in the modification of PG I levels by smoking.

Topics: Adult; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Smoking; Smoking Cessation

There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.

Topics: Adolescent; Adult; Cholecystokinin; Dyspepsia; Female; Gastric Emptying; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pancreatic Polypeptide

Gastric infection with Helicobacter pylori is associated with hypergastrinemia. Platelet activating factor (PAF) is produced in H. pylori-infected mucosa. The effects of PAF on gastrin release from cultured antral rabbit G cells were examined. Rabbit antral G-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation. After 40 hr in culture, gastrin release in response to PAF was assessed. PAF stimulated gastrin release in a dose-dependent manner. A maximal release of 67% above basal was seen with PAF at 100 nM. PAF also enhanced the gastrin release stimulated by forskolin and bombesin. PAF-stimulated gastrin release was abolished by a PAF-receptor antagonist. Gastrin release stimulated by PAF was abolished by chelation of intra- or extracellular calcium or the L-type calcium channel inhibitor verapamil as well as by the protein kinase C inhibitor chelerythrine. Platelet-activating factor may contribute to the hypergastrinemia of H. pylori infection by stimulating gastrin release from G cells. PAF-stimulated gastrin release involves influx of extracellular calcium via L-type channels and activation of protein kinase C.

Topics: Animals; Bombesin; Calcium Channels, L-Type; Cells, Cultured; Colforsin; Disease Models, Animal; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Platelet Activating Factor; Protein Kinase C; Rabbits

The pathophysiology of hypergastrinemia in H. pylori infection has been largely investigated and different reports clearly show that the infected antrum has a marked inflammatory response with a suggestive local production of cytokines. Notwithstanding, a few data are available on the circulating levels of cytokines and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)-8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)-alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H. pylori negative ones. To this end, thirty healthy volunteers with no digestive symptoms or systemic disease were enrolled and H. pylori infection was identified by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured with a solid-phase ELISA. Fifteen infected people showed significantly higher gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8 levels were significantly higher in the uninfected subjects than in H. pylori positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not affected by H. pylori presence, being not significantly different in the two groups.

Topics: Adult; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Interferon-gamma; Interleukin-10; Interleukin-8; Male; Middle Aged; Radioimmunoassay; Tumor Necrosis Factor-alpha

Topics: Cytokines; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Methylhistamines; Receptors, Histamine H2; Reproducibility of Results

Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection.. Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA-, picB) and 19 Helicobacter-free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-8 and TNF-alpha in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity.. H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori-infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1beta and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output.. The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Cardia; Cat Diseases; Cats; Disease Models, Animal; Female; Gastric Acidity Determination; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Interleukin-1; Interleukin-8; Male; Pyloric Antrum; Reverse Transcriptase Polymerase Chain Reaction; Somatostatin; Tumor Necrosis Factor-alpha

Atrophic gastritis can develop in patients with Helicobacter pylori infection leading to a reduction in basal acid output. Whether the atrophy that develops is reversible is controversial.. To investigate the effect of H. pylori eradication in infected subjects who had developed atrophy of the corpus mucosa.. Ten H. pylori positive patients with corpus atrophy were identified at oesophagogastroduodenoscopy (OGD). They received eradication therapy with amoxicillin, clarithromycin and omeprazole. Repeat OGD with biopsy was performed at least 3 months later. Fasting plasma gastrin was measured at baseline and at re-endoscopy. H. pylori eradication was confirmed by 13C urea breath testing.. Median time to re-endoscopy was 5 months. There was improvement in corpus atrophy in 50% of patients after H. pylori eradication, and a significant reduction in plasma gastrin (P = 0.03). The index patients had a significant diminution of basal acid output compared to controls.. Corpus atrophy as defined by the Sydney System is reversible in some patients after H. pylori eradication. Improvement in atrophy is associated with a fall in fasting plasma gastrin levels. This may have implications in the prevention of gastric carcinoma.

Topics: Adult; Aged; Atrophy; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

The role of Helicobacter pylori (H. pylori) infection in non-ulcer dyspepsia (NUD) remains controversial. This study investigates the clinical, serological and histological differences between patients with H. pylori-positive and -negative NUD.. One hundred and eighty consecutive patients with NUD were enrolled from January to December 1998. The severity of symptoms was evaluated by the Tucci's scoring system. The histological changes of gastric mucosa were assessed according to the Updated Sydney System, and a fasting blood sample was obtained to test the serum gastrin and pepsinogen I levels.. The H. pylori-positive NUD patients were notably older than H. pylori-negative NUD patients (48.2 +/- 15.9 vs 39.8 +/- 15.7 years, P= 0.001). There were no differences in other clinical factors between the two NUD groups. The serum pepsinogen I levels were considerably higher in H. pylori-positive NUD patients than in H. pylori-negative NUD patients (78.9 +/- 42.2 vs 61.5 +/- 43.3 ng/mL, P<0.01). However, no significant differences in serum gastrin levels were discovered between the two groups. The antrum histological scores for chronic inflammation, acute inflammation, gland atrophy and lymphoid follicles were higher in H. pylori-positive NUD patients than in H. pylori-negative NUD patients (2.09 vs 1.01, P<0.001; 1.22 vs 0.36, P<0.001; 0.76 vs 0.36, P<0.01; 0.33 vs 0.13, P<0.01, respectively).. The present study discovered marked differences in age, serum pepsinogen I levels, histological grades of acute inflammation, chronic inflammation, gland atrophy and lymphoid tissue formation between H. pylori-positive and H. pylori-negative NUD patients. Further investigation of the clinical prognosis of the two groups of patients is necessary.

Topics: Adult; Dyspepsia; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A

Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting.. Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique.. Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(-1)h(-1)). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations.. Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Topics: Adult; Autoantibodies; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A

Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1beta (IL-1beta).. (1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1beta mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined.. (1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1beta mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection.. Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1beta induced by H pylori infection.

Topics: Analysis of Variance; Animals; Electrophoresis, Agar Gel; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Interleukin-1; Male; Neutrophil Infiltration; Receptors, Interleukin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sequence Analysis, DNA; Specific Pathogen-Free Organisms; Statistics, Nonparametric

Topics: Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Japan

Examination and long-term follow-up covered 95 patients with duodenal ulcer (DU). Mean age of the patients was 32 +/- 1.67 years. The patients were divided into two groups: with rare DU recurrences (n = 36) and with frequent recurrences (n = 59). Diagnostic criteria for development of rarely recurrent DU were the following: blood group A(II), exacerbations in winter, weak symptoms at DU onset, weak abdominal pains, solitary surface ulcers. For development of frequently recurrent DU, diagnostic criteria include O(I) blood group, spring exacerbations, marked symptoms of the exacerbation, severe abdominal pains, multiple deep ulcers.

Topics: Abdominal Pain; ABO Blood-Group System; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A; Predictive Value of Tests; Prognosis; Recurrence; Risk Factors; Seasons; Severity of Illness Index; Somatostatin; Wound Healing

Gastric cancer is one of the most frequent neoplasms and a leading cause of the death world-wide. In recent years, epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H. pylori. The exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remains unclear. There is evidence that the up-regulation of certain growth factors could play an important role in the promotion of the gastric carcinogenesis.. The present study was designed to determine the gene expression of major known growth factors such as transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and gastrin in the gastric cancer tissue, the surrounding mucosa and, for comparison, in the normal gastric mucosa. Furthermore, the luminal and plasma levels of gastrin in patients with gastric cancer were determined. In addition, the gene and protein expressions of apoptosis-related proteins such as Bax and Bcl-2 were investigated by reverse transcription-polymerase chain reaction and Western blot. Twenty-five gastric cancer patients and 40 age- and gender-matched control subjects hospitalized with non-ulcer dyspepsia were included into this study.. An overall H. pylori-seropositivity among gastric cancer patients was about 72% and was significantly higher than in the controls (56%). The prevalence of CagA-positive strains was also significantly higher among gastric cancer patients than in controls (56% vs. 32%). The gene expression of HGF and TGFalpha was detected more frequently in gastric cancer tissue samples than in normal gastric mucosa (52% vs. 12% for HGF and 48% vs. 24% for TGFalpha). The extent of protein expression in Western blotting analysis for HGF and TGFalpha correlated with the mRNA expression of these factors. Gene expression of gastrin was detected in the antrum of all tested patients and in the majority (84%) of gastric cancer patients. The median plasma and luminal concentrations of gastrin in gastric cancer patients were significantly higher than in controls. The gene expression of bcl-2 was detected in all (100%) and that of proapoptotic bax only in 56% of gastric cancer samples. In comparison to the surrounding non-tumorous tisssue, the gene expression of bax was significantly down-regulated and the gene expression of bcl-2 was up-regulated in gastric cancer tissue. At the protein level, Bax was not detectable and Bcl-2 was seen in 80% of gastric cancer samples.. It is concluded that the patients infected with H. pylori, especially with CagA-positive strains, are at a higher risk of developing a gastric cancer. An increased production and release of gastrin, as well as an over-expression of growth factors such as HGF and TGFalpha, might contribute to the gastric carcinogenesis. In addition, a dysregulation of the Bax/Bcl-2 system with significant up-regulation of Bcl-2 is observed in gastric cancer.

Topics: Adult; Aged; Apoptosis; bcl-2-Associated X Protein; Case-Control Studies; DNA, Neoplasm; Down-Regulation; Female; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Hepatocyte Growth Factor; Humans; Male; Middle Aged; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Transforming Growth Factor alpha; Up-Regulation

Topics: Adult; Antibodies, Monoclonal; Female; Gastrins; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Infliximab; Male; Tumor Necrosis Factor-alpha

Helicobacter pylori (HP) infection is usually accompanied by an increased plasma level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients with colorectal cancers, before and after the removal of tumor, compared with 160 age- and gender-matched controls; (b) the gene expression of gastrin and its receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG, anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2, Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was significantly higher in cancer patients than in controls and did not change 1 week after tumor resection while plasma cytokines were significantly reduced after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa, where only COX-1 was detected. The colorectal cancer tissue contained several folds more immunoreactive gastrin than cancer resection margin and many folds more than the intact colonic mucosa. We conclude that colon adenocarcinoma and its resection margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP infection may contribute to colonic cancerogenesis via overexpression of gastrin and COX-2, which may account for the stimulation of the tumor growth and the reduction in apoptosis as documented by enhanced mRNA expression of anti-apoptotic Bcl2 over proapoptotic Bax proteins.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Bacterial; Apoptosis; Bacterial Proteins; Colorectal Neoplasms; Cyclooxygenase 2; Cytokines; Female; Gastrins; Gene Expression; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-8; Isoenzymes; Male; Membrane Proteins; Middle Aged; Prostaglandin-Endoperoxide Synthases; Tumor Necrosis Factor-alpha

Gastroduodenal ulcerations have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The HP infection is usually accompanied by hypergastrinemia and enhanced generation of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations but no study has been undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the PG production. Since HP infection, usually accompanying peptic ulcerations, results in increased release of gastrin, a potent gastric mitogen that might be capable to induce COX-2 and to generate PG, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric ulcer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of gastric ulcer and in the mucosa of antrum and corpus before and after successful eradication of HP, 3) to assess the plasma levels and gastric luminal contents of gastrin before and after HP eradication and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer margin tissue and gastric antral and fundic mucosa before and after the HP eradication. The trial material included 20 patients with gastric ulcer and 40 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a reference and employing Western blotting for COX-2 expression, while gastrin and PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature within the antral mucosal area. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric ulcers (85%) than in controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer margin and gastrin mRNA was overexpressed in remaining antral mucosa, while CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients. Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum

Topics: Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Poland; Prostaglandin-Endoperoxide Synthases; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach; Stomach Ulcer

There is interest in the development of GERD after Helicobacter pylori eradication. In contrast, the development of duodenal erosions after therapy has received scant attention. Patients were examined after eradication of H pylori infection to determine the frequency of post-therapy duodenal erosions (primary outcome) and whether there was a relation between development of duodenal and esophageal erosions. Additionally, factors were searched for that would identify patients at increased risk for duodenal erosions.. A single-center, endoscopist-blinded, observational study was conducted of 196 patients in whom H pylori was eradicated. The presence of esophageal or duodenal erosions was evaluated 4 weeks and 6 months after eradication. Serum gastrin and pepsinogen I (PG I) and II (PG II) levels were also determined for 83 patients entering the study during its final year.. Multiple small duodenal erosions developed in 8.6% of patients after H pylori eradication and were more common in patients with pre-eradication duodenal ulcer (27.8%) compared with those with gastric ulcer (6.7%) or atrophic gastritis (1.4%) (p < 0.05). Duodenal erosions were associated with high levels of PG I before and after eradication. The frequency of duodenal erosions decreased over time (3.1% by 6 months).. Duodenal erosions occur after H pylori eradication and appear to be related to duodenal ulcer and increased PG I levels, both of which are associated with increased acid secretion. Measurement of PG I may help to identify patients who have duodenal erosions develop after H pylori therapy for studies of the pathogenesis of these lesions.

Topics: Duodenal Ulcer; Duodenum; Endoscopy, Digestive System; Esophagus; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Stomach Ulcer; Time Factors

Serum chromogranin A (CgA), a marker of neuroendocrine neoplasia, increases during profound gastric acid inhibition, possibly reflecting the trophic effect of gastrin on the enterochromaffin-like (ECL) cells.. This study investigated the clinical value of serum CgA as a screening test for gastric fundic enterochromaffin-like (ECL) cell hyperplasia during acid-suppressive therapy.. A consecutive series of 230 dyspeptic patients referred for upper gastrointestinal endoscopy was investigated in a cross-sectional design. They were 154 patients on continuous medium-term (6 weeks to one year) or long-term (longer than one year) acid inhibition with either proton pump inhibitors (PPIs, n = 117) or histamine2-receptor antagonists (H2RAs, n = 37) for gastro-oesophageal reflux disease, and 76 nontreated subjects, with normal endoscopic findings (control group). Fasting blood samples were analysed for gastrin and CgA. Gastric biopsy specimens (oxyntic mucosa) were examined for histological evaluation of gastritis (Sydney classification) and of ECL cell hyperplasia (Solcia classification).. Serum CgA levels correlated positively with serum gastrin, following a quadratic function (r = 0.78, P < 0.0001). Elevated serum CgA values during long-term acid inhibition correlated with the presence and severity of fundic ECL cell hyperplasia. Multivariate analysis identified hypergastrinaemia (P < 0.0001), duration of acid inhibition (P < 0.0001), H. pylori infection (P = 0.008), ECL cell hyperplasia (P = 0.012), and body gland atrophy (P = 0.043) as independent predictors of elevated serum CgA. In subjects on long-term acid inhibition (n = 123), serum CgA was equally sensitive but more specific than serum gastrin for the detection of ECL cell hyperplasia (sensitivity, 91.3% for both; specificity, 73% vs. 43%, P < 0.0001).. During long-term gastric acid inhibition, serum CgA levels reflect the presence and severity of fundic ECL cell hyperplasia. Serum CgA is therefore a useful screening test for gastric ECL cell proliferative changes within this context.

Topics: Adult; Aged; Anti-Ulcer Agents; Chromogranin A; Chromogranins; Cross-Sectional Studies; Enterochromaffin-like Cells; Female; Gastric Acid; Gastric Fundus; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Mass Screening; Middle Aged; Multivariate Analysis; Sensitivity and Specificity

In the accessible literature we did not find data about the connection between Helicobacter pylori (H. pylori) infection and parathyroid hormone (PTH) abnormalities in patients on hemodialysis (HD pts). It is known that hyperparathyroidism is connected with stimulation of gastrin synthesis as well with increased acidity of gastric juice. We speculate that it should be connected with susceptibility to H. pylori infection in HD pts. The aim of our study was the assessment of relationships between PTH abnormalities and parameters of H. pylori infection expressed by concentration of IgG antibodies against H. pylori and histologically performed urease test. The study was conducted in 65 (37 M, 28 F) stable HD pts. They were dialyzed for 6 to 288 months (102.9 +/- 84.5). Simultaneously in 25 HD pts qualified for renal transplantation biopsy specimens taken during gastroscopy were examined by a histological test and urease test (CLO-test). According to the PTH concentration HD pts were divided into 3 groups with PTH < 100 pg/ml; with PTH 100-350 pg/ml and with > 350 pg/ml. Positive IgG H. pylori test > 24 U/ml was found in 60 (92%) HD pts. Mean IgG H. pylori concentration was similar in tree groups of HD pts. (82 vs 91 vs 88 U/ml) and did not differ significantly from control group. We found significant negative correlation between IgG H. pylori concentration and time on dialysis therapy (r = -0.50067, p = < 0.0001). Positive test in biopsy specimen was found in 14 HD pts (56%). PTH level in this group of HD pts not differ significantly from PTH level in pts with negative test (426 vs 398 pg/ml) and IgG H. pylori concentration was significantly higher in positive pts than in negative pts (104 vs 48 U/ml).. We did not find significant relationship between PTH abnormalities and H. pylori infection in HD pts. Longer period of dialysis therapy is connected with decreased ability to produce antibodies againts H. pylori.

Topics: Adult; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperparathyroidism; Immunoglobulin G; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency

Recent studies have reported an association between iron deficiency anaemia and Helicobacter pylori. Helicobacter pylori could cause iron deficiency anaemia by altering iron absorption. We observed that most patients with Helicobacter pylori infection and iron deficiency anaemia present a chronic superficial pangastritis.. To investigate whether Helicobacter pylori-positive patients with iron deficiency anaemia have peculiar histological and functional features when compared with non-anaemic Helicobacter pylori-positive subjects.. Fifty-one patients with iron deficiency anaemia, in whom chronic superficial Helicobacter pylori gastritis was the only gastrointestinal finding, and 103 non-anaemic Helicobacter pylori-positive controls were included in the study. Thirty-seven patients were randomly matched with 37 controls of the same sex and age.. Gastroscopy, with antral (n=3) and body (n=3) biopsies, was performed. Gastrin and pepsinogen I levels and antiparietal cell antibodies were evaluated. Intragastric pH was also measured.. Gastritis involved the corporal mucosa in 90% of patients compared to 42.7% of controls (P < 0.0001). The mean inflammatory score in the gastric body was significantly higher among patients than in controls (2.2 vs. 0.6; P=0.012). Gastrin was significantly higher in patients than in controls (mean 60.2 vs. 29 pg/mL; P=0.0069). Intragastric pH was higher in patients than in controls (median 5.7 vs. 2; P=0.0026).. These data suggest that patients with iron deficiency anaemia and Helicobacter pylori infection have a peculiar pattern of gastritis with corporal involvement and related changes in intragastric pH.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Case-Control Studies; Chronic Disease; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Inflammation; Male; Middle Aged

Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection.. To investigate in a population of patients with ABG the prevalence of H. pylori infection on the basis of histology and serology.. A total of 150 consecutive outpatients with atrophic body gastritis were diagnosed on the basis of a screening system.. All patients had a detailed assessment including measurement of specific anti-H. pylori antibodies, parietal cell antibodies, and fasting gastrin, gastroscopy with biopsies from gastric antrum and body.. 24.6% of patients were histologically and serologically negative (Group A). 52.7% H. pylori was not detected on histology but IgG to H. pylori were in all these patients elevated (Group B). 22.6% of patients were found to be positive at histology in the corpus mucosa; all but one of these patients had elevated circulating IgG to H. pylori (Group C). Mean corporal atrophy score in Group B patients was statistically lower than in Group A patients (2.43 +/- 0.08 vs. 2.75 +/- 0.09; p <.05), but was statistically higher than in Group C patients (1.79 +/- 0.11; p <.001). Thus, in corporal mucosa a gradient of atrophy was shown: Group C < Group B < Group A. A similar gradient was observed for the presence of pernicious anemia being lowest in Group C 11.8% increasing to 45.6% in Group B and being highest in Group C 75.6%. A statistical correlation was obtained (r =.04791, p <.05) between the histological score of corporal atrophy and the titer of antibodies to parietal cells and an inverse correlation was obtained (r = -.2322, p <.0001) between the histological score of corporal atrophy and IgG to H. pylori.. This study shows that two-thirds of ABG patients have evidence of H. pylori infection. This suggests that atrophic gastritis of the corpus is a spectrum of damage where H. pylori is a key agent able to induce gastric atrophic damage and also gastric autoimmunity.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Autoantibodies; Bacterial Proteins; Female; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Parietal Cells, Gastric; Prevalence

Helicobacter pylori infection is associated with complex alterations of the gastric physiology in patients with ulcer disease or functional dyspepsia. We aimed at evaluating whether H. pylori infection is accompanied by changes in interdigestive and postprandial gastrointestinal motility, exocrine pancreatic secretion or hormone release in asymptomatic subjects.. Nineteen healthy men (age range 26-35 years) were studied after 12 h fasting. Motor activity was recorded for a complete motor migrating complex cycle and two postprandial hours. Pancreatic enzyme secretion was evaluated using a standard duodenal perfusion technique. Plasma concentrations of gastrin, PP and motilin were determined at 15-min intervals. H. pylori infection was proved by serology and 13C-urea breath test.. Eight subjects (42%) were H. pylori positive. Interdigestive and postprandial gastrointestinal motility were similar in H. pylori positive and negative subjects. Interdigestive pancreatic secretion was increased in H. pylori positive subjects (P < 0.05). Postprandial pancreatic secretion tended also to be higher in H. pylori positive subjects. H. pylori infection was associated with an increased postprandial release of gastrin (P < 0.05) as well as with a slight increase of interdigestive gastrin release. The release of PP and motilin, as well as the interdigestive coordination between gastrointestinal motility, pancreatic secretion and hormone release, was not altered by H. pylori infection.. H. pylori infection in asymptomatic subjects is associated with changes not only in gastric physiology but also in pancreatic function. This first reported link between H. pylori and the pancreas could have pathophysiological implications in pancreatic diseases and therefore deserves further study.

Topics: Adult; Amylases; Chymotrypsin; Gastrins; Gastrointestinal Motility; Helicobacter Infections; Helicobacter pylori; Humans; Lipase; Male; Motilin; Pancreas; Pancreatic Polypeptide

Leptin, a protein product of obese gene expressed primarily by adipocytes, provides feedback information on the size of energy stores to central OB receptors controlling the food intake, energy expenditure and body weight homeostasis. It has recently been detected in the rat stomach, especially after cholecystokinin (CCK) administration and in human stomach infected with Helicobacter pylori, but its role in gastric secretory functions in humans has not been revealed. This study was designed to determine the involvement of leptin in the control of basal, CCK- and meal-induced gastric H+ secretion and plasma gastrin and CCK levels in humans before and after an eradication of H. pylori.. Two groups (A and B) of subjects were used; group A (n = 7), for comparison of the effects of CCK and leptin on basal gastric H+ and plasma hormone (leptin, gastrin and CCK) levels, and group B (n = 6), for studies on the involvement of leptin in gastric secretory and plasma hormonal responses to vagal stimulation and gastric peptone meal before and after H. pylori eradication.. In H. pylori-positive subjects, CCK (12-200 pmol kg(-1) h(-1)) given i.v. caused a dose-dependent increase of gastric H+ accompanied by a dose-dependent rise in plasma CCK and leptin levels. In contrast, leptin administered i.v. in graded doses (5-80 pmol kg(-1) h(-1)) resulted in a gradual inhibition of basal gastric H+ secretion and in adose-dependent increment in plasma leptin accompanied by an increase in plasma gastrin without alteration of plasma CCK level. Following eradication of H. pylori by 1-week triple therapy in group B patients, the infusion of CCK produced a significantly smaller increase in gastric H+ secretion and significantly smaller rise in plasma leptin as compared to those before the eradication. Cephalic phase stimulation of gastric secretion induced by modified sham-feeding in group B H. pylori-positive subjects increased gastric H+ secretion to about 40% of pentagastrin maximum without affecting plasma leptin, gastrin, or CCK level, while gastric peptone meal resulted in the increase in gastric H+ response reaching about 70% of pentagastrin maximum accompanied by a marked rise in plasma leptin, gastrin and CCK. The treatment with a standard dose of leptin (20 pmol kg(-1) h(-1)) failed to affect sham-feeding-induced gastric H+ secretion but reduced significantly the peptone meal-stimulated H+ secretion, while raising plasma gastrin in response to this meal. Plasma CCK under basal conditions and after sham-feeding was not affected, but plasma CCK response to gastric meal was significantly reduced by leptin infusion. Eradication of H. pylori did not affect basal or sham-feeding-induced H+ secretion but resulted in a significant fall in gastric meal-induced H+ and plasma leptin, gastrin and CCK levels.. 1) The gastric meal and CCK enhance the release of leptin in H. pylori-positive patients and this leptin is capable of inhibiting basal and meal-stimulated gastric H+ secretion, while raising plasma gastrin and reducing the plasma CCK levels, and 2) the eradication of H. pylori reduces the postprandial gastric H+ and plasmagastrin responses as well as the release of leptin in response to CCK and meal.

Topics: Adult; Cholecystokinin; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male

It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed.. To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer.. Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication.. In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value.. The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.

Topics: Adult; Aged; Atrophy; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Stomach Ulcer; Tetragastrin

Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined.. The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice.. INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor alpha. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (< or = 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P < or = 0.05).. These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer.

Topics: Animals; Cell Count; Epidermal Growth Factor; Epithelial Cells; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Heparin; Heparin-binding EGF-like Growth Factor; Hyperplasia; Hypertrophy; Intercellular Signaling Peptides and Proteins; Metaplasia; Mice; Mice, Transgenic; Stomach Neoplasms; Transforming Growth Factor alpha

Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma.. Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay.. Gastric epithelial cell turnover was no different after infection with the wild-type, cagA(-), or vacA(-) strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles.. In H. pylori-infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms.

Topics: Animals; Apoptosis; Cell Division; Epithelial Cells; Gastrins; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Mutation; Statistics, Nonparametric; Stomach; Virulence

The relationship of Helicobacter felis, a bacterium observed in the stomachs of cats, to gastric disease is unclear. The objective of this study was to determine if H. felis infection alters gastric histopathology, proinflammatory cytokine expression, and secretory function and evokes a humoral immune response in cats. Five specific-pathogen-free (SPF) Helicobacter-free cats were studied before and for 1 year after oral inoculation with H. felis (ATCC 49179). Four SPF H. felis-uninfected cats served as controls. The stomachs of all five H. felis-inoculated cats became colonized, as determined by urease activity, histopathology, PCR, culture, and transmission electron microscopy of serial gastric biopsies at 0, 3, 5, 8, and 12 months. Uninoculated cats remained Helicobacter free. Lymphoid follicular hyperplasia, atrophy, and fibrosis were observed primarily in the pylorus of infected cats. Mild mononuclear inflammation was detected in both infected and uninfected cats, but was more extensive in infected cats, with pangastric inflammation, eosinophilic infiltrates, and cardia gastritis observed only in infected cats. No upregulation of antral mucosal interleukin 1alpha (IL-1alpha), IL-1beta, or tumor necrosis factor alpha was detected by reverse transcription-PCR in any cat. The gastric secretory axes, assessed by fasting plasma gastrin, antral mucosal gastrin and somatostatin immunoreactivity, and pentagastrin-stimulated gastric acid secretion, were similar in both infected and uninfected cats. Gradual seroconversion (immunoglobulin G) was observed in four of five infected cats, with enzyme-linked immunosorbent assay values reaching 4x to 12x baseline 12 months postinfection. These findings indicate that H. felis infection in cats induces lymphoid follicular hyperplasia, mild gastritis, and seroconversion, but is associated with normal gastric secretory function.

Topics: Animals; Antibodies, Bacterial; Cats; Cytokines; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Hyperplasia; Immunohistochemistry; Lymphoid Tissue; Male; Polymerase Chain Reaction; Somatostatin; Urease

Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis.. Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs).. H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p <.01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p <.01, corpus; p <. 01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p <.05, PG I/II ratio; p <.01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p <.01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p <.05).. A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area.

Topics: Age Factors; Aged; Case-Control Studies; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Pepsinogens; Prevalence; Pyloric Antrum; Stomach

Atrophic gastritis has been shown to be one of the long term sequelae of Helicobacter pylori infection.. To determine the prevalence of atrophic gastritis in outpatients, to study the accuracy of serological methods for revealing atrophy, and to define the association of H pylori infection with atrophic gastritis in these patients.. A total of 207 consecutive outpatients referred for gastroscopy were included. Biopsy specimens from the antrum and corpus were assessed histologically according to the Sydney system. Serum samples were studied for H pylori IgG and IgA antibodies by enzyme immunoassay, CagA antibodies by immunoblot, pepsinogen I by an immunoenzymometric assay, gastrin by radioimmunoassay, and parietal cell antibodies by indirect immunofluorescence.. Histological examination revealed atrophic gastritis in 52 (25%) of 207 patients. H pylori and CagA antibodies were strongly associated with atrophic antral gastritis but poorly associated with atrophic corpus gastritis. Low serum pepsinogen I was the most sensitive and specific indicator of moderate and severe atrophic corpus gastritis. All six patients with moderate atrophic corpus gastritis had H pylori infection but eight of 10 patients with severe atrophic corpus had increased parietal cell antibodies and nine had no signs of H pylori infection.. Atrophic antral gastritis was strongly associated with CagA positive H pylori infection. Severe atrophic corpus gastritis was not determined by H pylori tests but low serum pepsinogen I, high gastrin, and parietal cell antibodies may be valuable in detecting these changes.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Autoantibodies; Bacterial Proteins; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin A; Immunoglobulin G; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prevalence; Sensitivity and Specificity; Serologic Tests; Stomach

The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years).. Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus.. In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients.. Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Barrett Esophagus; Child; Drug Resistance; Esophagitis; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Hyperplasia; Male; Middle Aged; Omeprazole; Time Factors; Treatment Outcome

Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection.. The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4.. Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age.. In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.

Topics: Adolescent; Adult; Aged; Aging; Antibodies, Bacterial; Biopsy; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Retrospective Studies; Risk Factors

The association between Helicobacter pylori infection and gastric motility abnormalities is still controversial, partly because of the lack of an appropriate animal model. H. heilmannii type 1 (Hh1), a spiral bacterium that infects the stomach of both man and pigs, easily colonises and induces an inflammatory response in the gastric mucosa of rodents. For these reasons, the present study investigated the relationship between gastric motility in rats experimentally infected with Hh1 and correlated the results with serum gastrin and gastric somatostatin concentrations, as these hormones seem to be involved in gastric motility. Ten rats were inoculated with gastric mucus from an Hh1-positive pig and 10 animals with gastric mucus from an Hh1-negative pig (control group). After 56 days, gastric emptying was studied in vivo by scintigraphy. The animals were then killed, blood samples were collected for serum gastrin measurement, strips of the gastric wall were obtained for an in-vitro motor study and fragments of the gastric antrum were obtained for somatostatin content evaluation, Hh1 diagnosis and histological study. There was a significant increase in gastric emptying in the test group compared with the controls as demonstrated by the in-vivo and in-vitro studies. Serum gastrin levels were significantly higher and somatostatin levels were lower in the test group than in the controls. In addition, infected animals showed evidence of gastritis on histological examination. Gastric motility is altered in rats infected with Hh1, a fact possibly related to concurrent abnormalities of gastrin and somatostatin secretion.

Topics: Animals; Female; Gastric Emptying; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Pyloric Antrum; Rats; Rats, Wistar; Somatostatin

Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa.. To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease.. The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9.. H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P = 0.05). A significant correlation was found between CA 19-9 (r = 0.3432, n = 49, P = 0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer.. The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Case-Control Studies; Colorectal Neoplasms; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Israel; Male; Middle Aged; Seroepidemiologic Studies

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.

Topics: Animals; Cell Count; Gastric Mucosa; Gastrins; Helicobacter Infections; Hydrogen-Ion Concentration; Mice; Mice, Inbred C57BL; Organ Size; Parietal Cells, Gastric; Reference Values; RNA, Messenger; Somatostatin; Time Factors

Topics: Anti-Ulcer Agents; Barrett Esophagus; Drug Administration Schedule; Esophageal Neoplasms; Esophagitis, Peptic; Fundoplication; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Proton Pump Inhibitors; Time

Infection with the bacterium Helicobacter pylori is associated with altered gastric acid secretion and gastrointestinal disease. Recent work has suggested that N alpha-methylhistamine, produced by the bacterium and acting on histamine receptors in gastric tissue, might be involved. Gastric juice and tissue biopsies from infected patients have been analysed for the presence of N alpha-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry. N alpha-Methylhistamine was detected in five of seven samples of gastric juice from infected patients (5-180 pmol/ml) but was absent in nine uninfected subjects. The compound was not found in fundic and antral biopsies from both subject groups. Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of N alpha-methylhistamine. Instillation of this compound at 10(-5) mol/l into the gastric lumen produced a significant increase in acid secretion in vivo while plasma gastrin concentration remained unchanged. N alpha-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium. The concentrations found are below those required to affect acid secretion or gastrin production in vivo, although higher local concentrations may exist around a site of infection.

Topics: Gas Chromatography-Mass Spectrometry; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Methylhistamines; Sensitivity and Specificity

Acute Helicobacter pylori (Hp) infection in humans may be associated with markedly reduced gastric acid secretion, but the mechanism of this hypochlorhydria has not been fully explained.. This study was designed to investigate how water extracts (WE) of Hp applied on rat gastric mucosa affect gastric secretion and mucosal histamine concentration as well as the gene expression for histamine decarboxylase (HDC), the key enzyme converting histidine to histamine and for interleukin-1beta (IL-1beta), the important proinflammatory cytokine.. Wistar rats were surgically equipped with small cannulas to form gastric fistulas (GF). Four weeks after formation of GF, rats received either saline (control group) or WE obtained from type I Hp strain expressing CagA/VacA proteins and from type II Hp strain negative for CagA/VacA. Hp-WE was applied intragastrically (i.g.) in a volume of 1 ml at days 0, 2, 4 and 6 (total 4 times). At days 7 and 14, the secretory tests were performed during which basal gastric acid and pepsin secretion was examined and acid and pepsin outputs were measured. After secretory tests, the rats were sacrificed, the stomachs removed and the damage to the gastric mucosa was assessed by measuring the lesion area planimetrically and by histology, the gene expression in gastric mucosa for HDC and interleukin-1beta (IL-1beta) was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot. Additionally, somatostatin concentration in gastric juice, gastric mucosal histamine content and plasma gastrin and IL-1beta levels were determined using radioimmunoassay (RIA).. Administration of Hp-WE failed to induce gross mucosal damage but microscopic examination revealed partial denudation of gastric surface epithelium without causing deep necrosis. In secretory tests, Hp-WE produced marked hypochlorhydria but type I Hp-WE induced significantly stronger inhibition of acid and pepsin secretion than type II Hp-WE, both at days 7 and 14. Both, type I and type II Hp-WE suppressed significantly the gene expression for HDC mRNA and lowered significantly gastric mucosal histamine content as compared to respective values in vehicle-treated control gastric mucosa. Furthermore, Hp-WE, resulted in a significant increase in expression of IL-1beta mRNA and a significant fall in luminal somatostatin concentration as well as a insignificant elevation of plasma gastrin level, the type I Hp-WE being more effective in these alterations than type II Hp-WE.. (1) Ability of Hp-WE to induce superficial damage, the reduction in HDC mRNA and accompanying fall in gastric histamine release, contribute, at least in part, to marked hypochlorhydria observed in the stomach exposed to repeated Hp-WE treatments, and (2) the deleterious effect of Hp-WE on the gastric mucosa involves an impairment of gastrin-somatostatin link possibly resulting from the action of Hp-derived toxins and the induction in mucosal cells of proinflammatory cytokine such as IL-1beta.

Topics: Animals; Gastric Acid; Gastrins; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Histamine; Histidine Decarboxylase; Interleukin-1; Intestinal Mucosa; Male; Rats; Rats, Wistar; Somatostatin; Water

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.

Topics: Adult; Aged; Biopsy; Dyspepsia; Female; Gastric Acidity Determination; Gastric Fundus; Gastric Mucosa; Gastrins; Helicobacter Infections; Humans; Male; Middle Aged; Peptides; Protein Precursors; Pyloric Antrum; Somatostatin

The mechanism by which Helicobacter pylori causes hypergastrinaemia is not completely understood.. To evaluate whether antral lymphocyte density could play a role in this alteration.. A total of 12 patients with active duodenal ulcer and 10 with non-ulcer dyspepsia were enrolled upon detection of Helicobacter pylori infection at endoscopy Enrolled as controls were 7 matched dyspeptic patients without Helicobacter pylori infection. Biopsy specimens were collected for Helicobacter pylori and histological assessments, and for antral lymphocyte density assessment by a histomorphometric method. A blood sample was obtained from each patient to determine basal gastrin levels. All patients were controlled by a further endoscopy 4 weeks after the end of Helicobacter pylori treatment.. Antral lymphocyte density (5,464 +/- 1,328 and 5,635 +/- 1,186 vs 2,267 +/- 557 lymphocytes/mm2; p<0.001 and p<0.001, respectively) and gastrin levels (66.7 +/- 14.1 and 60.4 +/- 21.7 vs 40.7 +/- 7.8 pg/dl; p=0.004 and p=0.02, respectively) were higher in duodenal ulcer and non-ulcer dyspepsia patients than in controls, while no significant differences emerged between duodenal ulcer and non-ulcer dyspepsia patients. There was a significant direct correlation between antral lymphocyte density and gastrin levels both in duodenal ulcer (r=0.77; p=0.003) and in non-ulcer dyspepsia (r=0.75; p=0.03) patients, while no correlation was found in controls [r=0.12; p=0.8). After treatment, this correlation persisted in 10 eradication failure patients (r=0.68; p=0.027), but disappeared in those successfully cured.. These data suggest that lymphocyte density in the antral mucosa could play a role in the impaired gastrin production occurring in patients with Helicobacter pylori infection.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Dyspepsia; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lymphocytes; Male; Middle Aged; Pyloric Antrum

The specificity of colonization by Helicobacter pylori and complex host-bacterium interactions cannot be readily examined in humans. The aim of this study was to perform such analyses in rhesus monkeys.. Four animals that had been cured of natural H. pylori colonization were challenged with a mixture of 7 strains of human origin, and bacteria recovered during periodic videogastroscopy were DNA fingerprinted.. Three animals carried mixtures of several strains for 4 months, after which strain J166 predominated. In the fourth animal, only strain J238 was isolated from the earliest phase of colonization through 7 months, but strain J166 again became predominant by 10 months after the challenge. Gastritis scores and plasma gastrin and anti-H. pylori immunoglobulin G titers reached levels observed in naturally colonized animals by 4 months after the challenge; however, no plasma immunoglobulin A response was observed up to 10 months.. These results show that (1) natural colonization does not elicit protective immunity against subsequent H. pylori challenge; (2) individuals differ in susceptibility to different H. pylori strains during initial stages of colonization; and (3) certain strains are better suited than others for long-term survival in different hosts. These observations show the complexity of H. pylori-host interactions.

Topics: Animals; Antibodies, Bacterial; DNA Fingerprinting; DNA, Bacterial; Fasting; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin A; Immunoglobulin G; Macaca mulatta; Male; Species Specificity; Stomach

The diagnosis of adenocarcinoid (mucinous/goblet cell carcinoid) is usually unexpected by both clinicians and pathologists. We report here the case of a 74-year-old man with gastric lymphoma (B-cell MALToma) diagnosed by endoscopy, who was found on exploratory laparotomy also to have extensive intraabdominal involvement by adenocarcinoid, arising from the ileum and/or appendix. The patient died two years after diagnosis with bladder outlet and small bowel obstruction due to diffuse metastases. In addition to mucin positivity, immunohistochemical stains demonstrated the tumor to be positive for chromogranin, synaptophysin, serotonin, gastrin, and glucagon. Of histogenetic interest, some individual neoplastic cells appeared to be positive for both mucin and chromogranin, and this was confirmed by the electron microscopic finding of microvilli, intracytoplasmic mucin droplets, and neurosecretory granules involving the same neoplastic cells. This also appears to be the first reported case of adenocarcinoid associated with lymphoma and demonstration of histochemical/immunohistochemical and ultrastructural evidence of cellular components with dual mucinous adenocarcinoma and neuroendocrine features, and the second reported case to have prostatic metastases.

Topics: Adenocarcinoma; Aged; Appendiceal Neoplasms; Biomarkers, Tumor; Carcinoembryonic Antigen; Carmine; Chromogranins; Coloring Agents; Gastrins; Glucagon; Helicobacter Infections; Helicobacter pylori; Humans; Ileal Neoplasms; Immunohistochemistry; Laparotomy; Lymphoma, B-Cell, Marginal Zone; Male; Metaplasia; Microscopy, Electron; Neoplasms, Multiple Primary; Prostatic Neoplasms; Serotonin; Stomach Neoplasms; Synaptophysin

Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells.. The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted.. Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p < 0.001). The number of G-cells per gastric gland was similar in infected and uninfected patients (7.1 +/- 3.1 vs 7.3 +/- 3.9, respectively, p > 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001).. These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.

Topics: Case-Control Studies; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin; Somatostatin-Secreting Cells

Omeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production by H pylori has been suggested as a probable mechanism.. To assess the effect of H pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects.. Twenty H pylori positive and 12 H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured.. Prior to omeprazole, measurements were similar in the H pylori positive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia.. The presence of H pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

Topics: Adult; Ammonia; Anti-Ulcer Agents; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Omeprazole

A decrease in gastrin and pepsinogen (PG) levels 1 month after Helicobacter pylori eradication has been described repeatedly, but the long-term progression of such a decrease has been scarcely studied. We therefore studied the effect of H. pylori eradication on basal and stimulated gastrin and PG levels for 1 year. Initially, the usefulness of measuring these parameters for the noninvasive diagnosis of H. pylori eradication was validated. Furthermore, an assessment was made of the association between H. pylori reinfection and a re-increase in gastrin and PG values. Finally, an evaluation was made of the variables influencing gastrin and PG concentration, with particular attention to H. pylori infection and histological lesions of gastric mucosa.. Two-hundred and twenty-two patients with duodenal ulcer were studied prospectively. Exclusion criteria were the administration of antibiotics, H2 antagonists, omeprazole or bismuth prior to endoscopy. In all patients serum basal levels of gastrin, PGI, and PGII were measured before and 1 month after completing eradication therapy. In the successfully eradicated patients, gastrin, PGI, and PGII were also measured at 6 and 12 months. In 80 patients stimulated measurements of gastrin (after ingestion of two beef cubes) and PGI (after injection of pentagastrin) were also performed. H. pylori-negative patients after therapy underwent a urea breath test at 6 and 12 months, and patients who had stimulated gastrin and PG concentration measured had also an endoscopy performed at 6 months.. H. pylori was eradicated in 73% of patients. A histological improvement was observed 1 month after completing H. pylori eradication therapy, both at gastric antrum and body (P < 0.001), while a further improvement at antrum was demonstrated at 6 months (P < 0.01). With regard to the different cut-off points for decreased basal and stimulated measurements for diagnosing H. pylori eradication, the best results were obtained, respectively, with PGII (sensitivity of 90% and specificity of 76%) and PGI 30 min after stimulation (sensitivity and specificity of 82%), with an area under the ROC curve of 0.87 in both cases. In the multiple regressions analysis H. pylori status correlated with gastrin, PGI and PGII after therapy (P < 0.001), while histological lesions correlated only with gastrin levels (P < 0.05). A decrease in basal and stimulated serum parameters was demonstrated immediately after eradication (Wilcoxon test, P < 0.001), and an additional decrease (at 6 months) was observed just in PGI (Friedman test, P < 0.01). However, gastrin and PGII values remained unchanged after the first month post-eradication. Seven patients were reinfected with H. pylori during follow-up. Quantitation of basal and stimulated gastrin and PGI levels was not reliable as a reinfection marker. Regarding basal PGII, the parallelism was strong at 6 months (re-increase in all four reinfected patients), although only in one out of three with reinfection at 1 year did PGII rise at that stage.. (1) Measurement of gastrin and PG levels (especially basal PGII values) is a useful non-invasive method to confirm H. pylori eradication after therapy. (2) H. pylori eradication is associated with a significant decrease in basal and stimulated gastrin levels and in basal PGII levels that is detected immediately (1 month) after finishing treatment, and remains unchanged for 1 year. However, the decrease in basal and stimulated PGI levels occurs progressively for 6 months, although such levels remain also unchanged afterwards. (3) Measurement of gastrin and PGI concentrations has a limited usefulness in the diagnosis of H. pylori reinfections after successful eradication, although PGII determination could be more useful in this situation.

Topics: Breath Tests; Duodenal Ulcer; Eating; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pentagastrin; Pepsinogen A; Pepsinogen C; Prospective Studies; Recurrence; Regression Analysis; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Time Factors; Urea

Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection and gastric pathology are limited due to a deficiency of convenient animal models resembling this infection in humans.. We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic acetic acid-induced ulcers in mouse stomachs. The ulcer area, gastric blood flow, plasma interleukin (IL)-1beta and IL-12, as well as plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA.. Gastric acid and pepsin secretion was reduced by over 50% immediately after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fall in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. The area of ulcers in vehicle-treated controls decreased significantly starting from day 2 after ulcer induction and then continued to decline for a further 14 days to heal almost completely after 28 days. In contrast, the ulcers were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylori infection. The gastric blood flow at the ulcer margin and ulcer crater in vehicle-treated mice gradually increased with decreasing ulcer size, after 14 and 28 days reaching a value which was not significantly different from that in vehicle-administered mice. In contrast, the gastric blood flow in type I H. pylori and, to a lesser extent, in type II H. pylori infected mice was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as oedema or congestion of surface epithelium were found after 7 days whereas mucosal inflammatory infiltration appeared after 14 days with a further increase after 28 days, especially in type I H. pylori and to a lesser extent in type II H. pylori infected mice. Plasma IL-1beta and IL-12 were significantly elevated at all tested days of ulcer healing and their increments were significantly higher in type I than in type II H. pylori infection.. Conventional mice with gastric ulcers can be successfully infected by both toxigenic and nontoxigenic H. pylori strains, and this infection causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the ulcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Colony Count, Microbial; Disease Models, Animal; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Interleukin-1; Interleukin-12; Male; Mice; Mice, Inbred BALB C; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Stomach; Stomach Ulcer

Topics: Anti-Ulcer Agents; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole

Endoscopic esophagitis is less common in the East than in the West. The reason for this is unknown. This study examines prospectively the relationship between endoscopic esophagitis and lower esophageal sphincter pressure, distal esophageal contractility, esophageal peristaltic performance, esophageal acid exposure, gastric acid output, and Helicobacter pylori (H. pylori) status in a consecutive series of Asian patients.. Esophageal manometry and ambulatory pH monitoring were carried out in 48 patients with endoscopic esophagitis and 208 patients with symptoms suspicious of gastroesophageal reflux disease but without esophagitis. Gastric acid output and H. pylori serology were determined in 22 of the esophagitis group and 36 of the nonesophagitis group.. Compared to the nonesophagitis patients, esophagitis patients had a higher prevalence of hypotensive lower esophageal sphincter (49% vs 24%, p < 0.001), impaired esophageal contractility (45% vs 22%, p < 0.005), poor peristaltic performance (23% vs 12%, p < 0.05), and pathological acid reflux (48% vs 27%, p < 0.005). However, there was no difference in the two groups with respect to gastric acid output and H. pylori positivity.. Lower esophageal sphincter competence, esophageal peristaltic contractility, and esophageal acid exposure were important factors in the pathogenesis of reflux esophagitis--results identical to Western studies. Gastric acid output per se and H. pylori infection might not be responsible for susceptibility to esophagitis.

Topics: Adult; Aged; China; Esophagitis, Peptic; Esophagus; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Singapore

The relationship of Helicobacter felis, an organism that is observed in the stomachs of dogs, to gastric disease in dogs is unclear. The objective of this study was to determine if Helicobacter felis infection alters gastric morphology and gastric secretory function in dogs. Five specific-pathogen-free (SPF), Helicobacter-free Beagle dogs were examined before and for 26 weeks after inoculation with H. felis (ATCC 49179). Three SPF uninfected dogs served as controls. All five dogs became colonized by H. felis as determined by urease activity, histopathology, polymerase chain reaction, and transmission electron microscopic examination of serial gastric biopsies. The degree of colonization ranged from < 1 organism/400 x field to > 10 organisms/400 x field. The fundus, body, and cardia were most heavily colonized. Evaluation of gastric biopsies showed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. There was no correlation between the number of organisms observed and the degree of gastric inflammation or number of lymphoid follicles. The gastric secretory axis, assessed by fasting and meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion, was similar in both infected and uninfected dogs. Fasting gastric pH was not a reliable indicator of gastric secretory function. These findings suggest that H. felis may not be a gastric pathogen in dogs. However, the density of colonization and limited duration of infection should be considered when interpreting these findings.

Topics: Animals; Biopsy; Blotting, Southern; DNA Primers; DNA, Bacterial; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastrins; Helicobacter; Helicobacter Infections; Immunohistochemistry; Male; Microscopy, Electron; Polymerase Chain Reaction; Radioimmunoassay; Somatostatin; Specific Pathogen-Free Organisms; Stomach; Stomach Diseases; Urease

Pepsinogen A and C as well as gastrin were measured in the serum of 117 patients with rheumatic diseases. Moreover, the patients were divided up in groups by aids of a semiquantitative, rapid enzyme immunoassay for detection of Helicobacter pylori: 20 patients without H. pylori antibodies (AB) negative, 18 positive + (= weak AB-titre), 21 positive +2 (medium AB-titre), and 58 positive +3 (high AB-titre). The semiquantitative determinations of H. pylori-AB correlated with pepsinogen A, C and gastrin. Patients with H. pylori-AB positive +3 showed significantly higher values of pepsinogen C (p < or = 0.01) as well as pepsinogen A and gastrin (p < or = 0.05) than H. pylori-AB negative patients. Significantly increased levels of pepsinogen A (> 150 ng/ml) and C (> 25 ng/ml) were found to occur in 39% and 100% of patients with high H. pylori-AB titres. The measurement of serum pepsinogen C concentrations may provide additional diagnostic information of the extent of mucosal lesions in patients with positive H. pylori-AB titres treated with antirheumatic drugs. Our findings suggest that the semi-quantitative classification of positive AB-results can be useful in cases determining H. pylori infection and mucosal irritation if other investigations are not available.

Topics: Adult; Aged; Antibodies, Bacterial; Antirheumatic Agents; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Rheumatic Diseases; Sensitivity and Specificity; Stomach Ulcer

A Mongolian gerbil model was used to clarify whether long-term colonization by Helicobacter pylori is an important risk factor for the development of gastric cancer. Fifty-nine gerbils (3 controls and 56 gerbils inoculated with H. pylori) were killed at various times (average, 23 months) more than 12 months after H. pylori inoculation. In the H. pylori-inoculated group, poorly differentiated adenocarcinoma was observed in the pylorus of 1 gerbil, and carcinoid was observed in the fundus of the stomach in 18 gerbils. No lesions were found in the stomachs of the 3 control gerbils. The results imply that long-term colonization by H. pylori is an important risk factor for the development of gastric adenocarcinoma and carcinoid.

Topics: Adenocarcinoma; Animals; Antibodies, Bacterial; Carcinoid Tumor; Disease Models, Animal; Duodenum; Gastrins; Gerbillinae; Helicobacter Infections; Immunoglobulin G; Intestinal Mucosa; Metaplasia; Stomach Neoplasms; Time

Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of DU.. Subjects consisted of 15 patients with H. pylori-positive DU, 10 H. pylori-positive volunteers, and 35 H. pylori-negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1-hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay.. Meal-stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori-positive and -negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper-IGR and normo-IGR. Serum PG I concentration was significantly higher in the hyper-IGR than in the normo-IGR group.. The DU patients differed in some way (other than H. pylori infection) from the H. pylori-positive healthy volunteers. The fact that hyper-IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors.

Topics: Adult; Duodenal Ulcer; Eating; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A

We evaluated the potential value of a change in serum IgG antibodies, fasting or meal-stimulated gastrin levels, and pepsinogen I (PGI) or pepsinogen II (PGII) levels for identifying Helicobacter pylori (H. pylori) status after antibiotic therapy.. A total of 32 men and one woman with peptic ulcer disease and documented H. pylori infection were enrolled. Fasting and 30-min postprandial blood samples were obtained at 0, 2, 7, 11, 17, 23, 27, and 39 wk of the study and were analyzed for the factors evaluated.. Treatment was successful in 25 patients and failed in seven. Serum IgG antibodies, meal-stimulated gastrin, and both fasting and meal-stimulated pepsinogen I and II levels fell throughout the study, and pepsinogen I:II ratios increased in those whose infection was cured. The mean levels at wk 0 versus wk 7 were: fasting gastrin (fmol/ml) 12.4 and 11, meal-stimulated gastrin 26.5 and 15.4, PGI (ng/ml) 83.7 and 59, PGII (ng/ml) 24.5 and 13.6, PGI/PGII 3.5 and 4.7, and enzyme-linked immunosorbent assay value 4.8 and 4.55. The sensitivity, specificity, and positive and negative predictive values for the data analyzed using different percent changes (e.g., 80%, 50%, and 20%) were calculated. The specificity and sensitivity remained <80% at all time points.. Despite a significant fall in serum markers of H. pylori infection in groups of individuals, no marker tested could be used to reliably determine posttherapy H. pylori status for individual patients.

Topics: Adult; Aged; Aged, 80 and over; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Time Factors

The purpose of this study was to investigate whether the densities of antral gastrin and somatostatin-immunoreactive cells in Helicobacter pylori (H. pylori) infection were related to the bacterial expression of cytotoxin-associated gene A (CagA). 32 patients who had underwent diagnostic esophagogastroduodenoscopy were studied. On the histologic examination all patients had antral gastritis. We divided the subjects into three groups. Group I consisted of 6 patients who had chronic superficial gastritis, group II, 9 patients who had H. pylori-associated gastritis but with no expression of CagA, and group III, 17 patients who had H. pylori-associated gastritis with the expression of CagA. In group I and II, serum gastrin levels, and antral G cell and D-cell were measured. In group III, serum gastrin levels, and antral G cell and D-cell were measured, before and after the eradication of H. pylori. The results were as follows. Firstly, serum gastrin concentrations were significantly higher in the patients with H. pylori infection than in the negative controls. Nextly, there was no correlation between the changes in antral G or D-cell density and H. pylori infection. Thirdly, group III had a significant increase in serum gastrin concentrations and a significant decrease in antral D-cell density than group I. Forthly, eradication of H. pylori in group III showed a significantly increased antral D-cell density. Our results suggest that hypergastrinemia in H. pylori-associated gastritis is relevant to the presence of CagA, and the possible mechanism of hypergastrinemia may be related to antral D-cell deficiency, which is caused by H. pylori infection with the expression of CagA.

Topics: Adult; Antigens, Bacterial; Bacterial Proteins; Cell Count; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Osmolar Concentration; Pyloric Antrum

Helicobacter pylori infections are associated with hypochlorhydria in patients with pangastritis. It has previously been shown that eradication of H pylori leads to an increase in acid secretion in H pylori associated enlarged fold gastritis, suggesting that H pylori infection affects parietal cell function in the gastric body. The aim of this study was to evaluate the effects of H pylori infection on parietal cell morphology and function in hypochlorhydric patients.. The presence of H pylori infection, mucosal length, and inflammatory infiltration were investigated in six patients with enlarged fold gastritis and 12 patients without enlarged folds. Parietal cell morphology was examined by immunohistochemistry using an antibody against the alpha subunit of H(+),K(+)-ATPase and electron microscopy. In addition, gastric acid secretion and fasting serum gastrin concentration were determined before and after the eradication of H pylori.. In the H pylori positive patients with enlarged fold gastritis, fold width, foveolar length, and inflammatory infiltration were increased. In addition, the immunostaining pattern of H(+), K(+)-ATPase was less uniform, and the percentage of altered parietal cells showing dilated canaliculi with vacuole-like structures and few short microvilli was greatly increased compared with that in H pylori positive patients without enlarged folds. After eradication, fold width, foveolar length, and inflammatory infiltrates decreased and nearly all parietal cells were restored to normal morphology. On the other hand, altered parietal cells were negligible in H pylori negative patients. In addition, the basal acid output and tetragastrin stimulated maximal acid output increased significantly from 0.5 (0.5) to 4.1 (1.5) mmol/h and from 2.5 (1.2) to 13.8 (0.7) mmol/h (p<0.01), and fasting serum gastrin concentrations decreased significantly from 213.5 (31.6) to 70.2 (7.5) pg/ml (p<0.01) after eradication in patients with enlarged fold gastritis.. The morphological changes in parietal cells associated with H pylori infection may be functionally associated with the inhibition of acid secretion seen in patients with enlarged fold gastritis.

Topics: Adult; Dyspepsia; Female; Gastric Acid; Gastrins; Gastritis; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Parietal Cells, Gastric

Helicobacter pylori infection is associated with increased gastrin release in patients with normal renal function. Hypergastrinaemia is a common finding in haemodialysis patients and, in many cases, may be linked to H. pylori infection. The aim of this study was to examine the effect of H. pylori infection, and its eradication, on elevated gastrin levels in haemodialysis patients.. Eighty-nine dyspeptic patients were included in the study. While 44 patients had normal renal function, the remaining 45 were end-stage renal failure patients. Patients were assigned to one of four groups according to their H. pylori and renal function status. Infected patients were re-evaluated after 2 months following eradication treatment. Serum gastrin levels were measured in these groups both before and after eradication treatment.. Haemodialysis patients with H. pylori infection had higher serum gastrin levels than did H. pylori negative haemodialysis patients (321+/-131 pg/ml vs 154+/-25 pg/ml) (P<0.05). Mean serum gastrin concentration was 152+/-21 pg/ml in the non-uraemic H. pylori-positive group. This value was 58+/-17 pg/ml in the non-uraemic H. pylori-negative group (P<0.05). There were significant decreases in serum gastrin levels from pre- to post-eradication of H. pylori in the infected haemodialysis and non-uraemic patient groups (312+/-131 pg/ml to 179+/-85 pg/ml and 152+/-21 pg/ml to 72+/-2.4 pg/ml respectively, P<0.05). Four patients in group Ib and 5 patients in group IIb who had persistent infection did not have a decrease in serum gastrin level. All patients with successful eradication had a decrease in serum gastrin concentration.. Our findings suggest that H. pylori infection contributes to hypergastrinaemia in haemodialysis patients. More research is needed regarding the clinical consequences of hypergastrinaemia in these individuals.

Topics: Adult; Anti-Bacterial Agents; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

Gastrin levels have been reported to be often increased in patients with primary hyperparathyroidism (PHPT) considered to be caused by hypercalcemia. To determine the prevalence of increased basal gastrin and to investigate its causes, 52 consecutive patients with PHPT were studied prospectively, undergoing a clinical, biochemical, and gastric morphofunctional assessment before any parathyroid surgical procedure. This included evaluation of basal and secretin-stimulated gastrin, basal and pentagastrin-stimulated gastric acid secretion, upper gastrointestinal endoscopy, with histological evaluation for gastritis and Helicobacter pylori infection. Twenty of the 52 PHPT patients (38.5%) had increased fasting gastrin. Further investigation allowed us to clearly demonstrate the causes of hypergastrinemia in 16 of these 20 patients. In 7 of 20 (35%), hypergastrinemia was caused by gastric fundus atrophy; in 3 patients (15%), Zollinger-Ellison syndrome with Multiple Endocrine Neoplasia type I was diagnosed; whereas in another 20% of patients, mild hypergastrinemia was ascribed to Helicobacter pylori gastritis. Finally, in 2 patients, additional clinical history revealed an occasional use of the gastric antisecretory drug omeprazole a few days before the serum gastrin determination. This study shows that the hypercalcemic status per se is not sufficient to produce an increase in fasting gastrin levels. Furthermore, gastric fundus atrophy, and not gastrinoma, is the major cause of relevant (>160 pg/mL) hypergastrinemia.

Topics: Adult; Aged; Atrophy; Female; Gastric Acid; Gastric Fundus; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pentagastrin; Prospective Studies; Secretin

The effects of Helicobacter pylori infection on gastric acid secretion has not been clarified. The aim of this study was to elucidate the effects of H. pylori infection on gastric juice pH in relation to gene expression of interleukin-1beta (IL-1beta), which is reported to inhibit gastric acid secretion. Gastric juice pH and serum gastrin levels were measured in patients with peptic ulcer disease. The amount of IL-1beta mRNA in gastric fundic gland mucosa was also measured by a competitive reverse transcription-polymerase chain reaction method. These parameters were determined before and after treatment with lansoprazole and amoxicillin. Before treatment a significant positive relation was observed between the amount of IL-1beta mRNA in gastric fundic gland mucosa and gastric juice pH. After treatment significant decreases in the amount of IL-1beta mRNA, gastric juice pH, and serum gastrin levels were observed in patients with eradication of H. pylori, whereas no significant changes were observed in patients without eradication. These results suggest that H. pylori infection induces IL-1beta and suppresses acid secretion, resulting in increases in gastric juice pH and serum gastrin levels. Eradication of H. pylori decreases IL-1beta induction, resulting in an increase in gastric juice acidity and normalization of serum gastrin levels.

Topics: Base Sequence; DNA, Complementary; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Interleukin-1; Male; Middle Aged; Molecular Sequence Data; Peptic Ulcer; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Stomach Ulcer

To assess the effect of increasing age on circulating gastrin, we surveyed serum gastrin, Helicobactor pylori seroantibody status and gastric autoimmunity in 366 hospitalized patients aged 15-90 years. Data were subjected to multivariate analysis, using logarithmic transformation to normalize the distribution of gastrin concentrations (presented as geometric means and 95% CIs). The frequency of H. pylori-positive antibody status increased with age from 28% in the second decade to > 70% beyond the fourth decade. Fasting gastrin concentrations rose significantly from 44 ng/l (41-48) in the second decade to 95 ng/l (67-131) by the eighth decade (p = 0.001) in the total group. Twenty-seven patients (6.8% of the total) tested positive for gastric auto-antibodies: 2% of patients in the second decade, rising to 15.9% in the eighth decade. These patients formed a distinct group with respect to circulating gastrin concentrations. Excluding these 27, fasting gastrin concentrations still rose significantly, from 44 ng/l (41-48) in the second decade, to 67 ng/l (50-89) in the eighth decade (p = 0.003) in the remaining 341 patients. Fasting gastrin concentrations were significantly higher in patients who were H. pylori-seropositive (59 ng/l, 54-64 vs. sero-negative 41 ng/l, 37-46) (p = 0.002), and there was no increase in circulating gastrin concentrations with increasing age in either the H. pylori-positive or the H. pylori-negative group. The increase in circulating fasting gastrin observed with increasing age is due to an increased incidence of gastric antibodies associated with auto-immune atrophic gastritis, and an increased incidence of H. pylori infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Anemia, Pernicious; Antibodies, Bacterial; Autoantibodies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Middle Aged; Multivariate Analysis; Parietal Cells, Gastric

The polyamine agmatine is able to increase gastric acid secretion. Therefore, we investigated whether Helicobacter pylori is able to form and release agmatine in vitro and in the human stomach in vivo, and if so, whether a relationship exists among agmatine concentration in gastric juice, H. pylori infection, and gastroduodenal lesions. Agmatine was determined by means of HPLC. In the supernatant of H. pylori cultures, agmatine concentrations up to 1500 ng/ml (approximately 12 microM) were determined, depending on the number of the bacteria in the individual cultures. Agmatine concentration in gastric juice from H. pylori-positive patients was higher than in that from H. pylori-negative patients. Gastrin in blood was elevated in H. pylori-positive patients compared with H. pylori-negative patients. Agmatine concentration in gastric juice and serum gastrin level appeared to be related. In conclusion, H. pylori is able to form and to release agmatine in vitro and in vivo. This may be assumed to be relevant in vivo, since higher amounts of agmatine are present in gastric juice from H. pylori-positive than from H. pylori-negative patients. Accordingly, agmatine produced by H. pylori may be a virulence factor of this bacterium and may be involved in the pathogenesis of gastroduodenal lesions.

Topics: Agmatine; Chromatography, High Pressure Liquid; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Virulence

To study the prevalence of Helicobactor pylori (Hp) infection in rural adult residents of China and its relation to serum levels of pepsinogen I (PG I), pepsinogen II (PG II) and gastrin (GAS).. Serum levels of antibodies against Hp were determined with enzyme-liked immunosorbent assay (ELISA) in 1,504 residents aged over 30 in Zanhuang County of Hebei Province, and their serum levels of PG I, PG II and GAS, as well as PG I/PG II ratio, were analyzed quantitatively, with radioimmunoassay (RIA).. Positivity for serum Hp antibody accounted for 66.4% of the rural adults in Zanhuang County, without significant sex difference. There was no significant difference in positivity for serum Hp antibody between residents in the high and low prevalent areas of gastric cancer. Serum levels of PG I, PG II and GAS were significantly higher in those with positive serum IgG anti-Hp (62.3 micrograms/L, 15.45 micrograms/L and 74.00 pg/ml, respectively) than those negative (42.1 micrograms/L, 6.40 micrograms/L and 66.00 pg/ml, respectively), all with a P-value less than 0.005, and the ratio of serum PG I to PG II levels was significantly lower in the former (4.0) than that in the latter (6.6), with P < 0.005.. More than two thirds of the adult residents in Zanhuang County had infected with Hp, which could affect their serum levels of PG and GAS.

Topics: Adult; Aged; Antibodies, Bacterial; China; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Rural Health; Seroepidemiologic Studies

Numerous epidemiological studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer but the mechanism of the involvement of H. pylori in gastric cancerogenesis remains virtually unknown. This study was designed to determine the seropositivity of H. pylori and cytotoxin associated gene A (CagA), serum gastrin and gastric lumen gastrin levels under basal conditions and following stimulation with histamine in gastric cancer patients and controls. 100 gastric cancer patients aging from 21 to 60 years and 300 gender- and age-adjusted controls hospitalized with non-ulcer dyspepsia (NUD) entered this study. 13C-Urea Breath Test (UBT), serum immunoglobulin (IgG) antibodies to H. pylori and CagA were used to assess the H. pylori infection and serum levels of IL-1beta, IL-8 and TNFalpha were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the degree of gastric inflammation by H. pylori . Gastrin-17 mRNA and gastrin receptors (CCK(B)) mRNA expression in gastric mucosal samples taken by biopsy from the macroscopically intact fundic and antral mucosa as well as from the gastric tumor was determined using RT-PCR. The overall H. pylori seropositivity in gastric cancer patients at age 21-60 years was about 92%, compared, respectively, to 68%, in controls. A summary odds ratio (OR) for gastric cancer in H. pylori infected patients was about 5.0 . The H. pylori CagA seropositivity in gastric cancer patients was about 58.5% compared to 32.4% in controls, giving the summary OR for gastric cancer in CagA positive patients about 8.0. The prevalence of H. pylori- and H. pylori CagA-seropositivity was significantly higher in cancers than in controls, irrespective of the histology of gastric tumor (intestinal, diffuse or mixed type). Median IL-1beta and IL-8 reached significantly higher values in gastric cancer patients (9.31 and 30.8 pg/ml) than in controls (0.21 and 3.12, respectively). In contrast, median serum gastrin in cancers (as total group) was several folds higher (62.6 pM) than in controls (19.3 pM). Also median luminal gastrin concentration in gastric cancer patients was many folds higher (310 pM) than in controls (20 pM). This study shows for the first time that cancer patients are capable of releasing large amounts of gastrin into the gastric lumen to increase luminal hormone concentration to the level that was recently reported to stimulate the growth of H. pylori. There was no any correlation between

Topics: Adult; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Stomach Neoplasms

Helicobacter pylori-induced hypergastrinemia is accompanied by increased acid secretion in patients with duodenal ulcer (DU) but not in infected healthy volunteers. The aim of this study was to investigate the mechanism underlying this difference.. Thirty-four H. pylori-negative and 20 H. pylori-positive healthy volunteers and 15 H. pylori-positive patients with DU were studied. Maximal acid output and sensitivity to gastrin (gastrin concentration required to achieve 50% maximal acid output) were assessed by examining the dose response to gastrin 17. Inhibitory control was tested by comparing the maximal acid response to cholecystokinin octapeptide with that for gastrin 17.. Sensitivity to gastrin was similar in patients with DU (median, 69.5 ng.L-1; range, 26.2-142) and H. pylori-negative healthy volunteers (median, 82.2 ng.L-1; range, 17.7-410); H. pylori-positive healthy volunteers were less sensitive than either (164.5 ng.L-1; range, 44.8 to > 3360 ng.L-1). Patients with DU had higher maximal acid output (51.2 mmol.h-1; range, 30.8-73.7 mmol.h-1) than either infected healthy volunteers (37.8 mmol.h-1; range, 0.0-65.0 mmol.h-1; P < 0.04) or uninfected healthy volunteers (35.3 mmol.h-1; range, 21.3-67.3 mmol.h-1; P < 0.002). The maximal acid output in both groups of healthy subjects was similar. The proportion of maximal acid output to gastrin 17 achieved by cholecystokinin was similar in patients with DU (36.6%; range, 21.5%-58.2%) and H. pylori-negative healthy volunteers (28.7%; range, 5.9%-85.8%).. A combination of decreased sensitivity to gastrin in infected healthy volunteers and increased maximal acid secretory capacity in patients with DU underlies their different acid response to H. pylori-induced hypergastrinemia.

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Epidermal growth (EGF) and transforming growth factor alpha (TGFalpha) are potent gastric secretory inhibitors, mitogens, and mucosal protectors, but the impact of Helicobacter pylori infection on their mucosal expression and luminal release has not been clarified.. In this study, gene and immunoreactive and immunohistochemical expressions of EGF and TGFalpha were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals, in 22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin + omeprazole) and 4 weeks and 2 years later.. Immunohistochemical expression of EGF and TGFalpha in H. pylori-positive DU and NUD was significantly higher than in H. pylori-negative normals, and this increase persisted at 2 and 4 weeks after therapy but normalized 2 years later. EGF mRNA was detected in the gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H. pylori eradication, but it was not found 2 years after the eradication of H. pylori or in gastric mucosa of H. pylori-negative control subjects. TGFalpha mRNA was detected in the gastric mucosa independently of H. pylori status, with the stronger expression observed in the gastric mucosa of H. pylori-positive DU and NUD before eradication than after this procedure. Plasma gastrin, which was significantly increased in H. pylori-positive DU, normalized already after 2 weeks of triple therapy. The eradication rate as determined by histology after triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years after the eradication the H. pylori reinfection rate was 4.5% among DU patients and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in complete ulcer healing.. 1) Chronic H. pylori infection and resulting antral gastritis are associated with increased plasma gastrin and increased mucosal cell proliferation, probably due to enhanced expression of EGF and TGFalpha, and 2) the H. pylori eradication results in a decrease in plasma gastrin, but the increase in gastric TGFalpha and EGF content is sustained, suggesting that they may be involved in ulcer healing.

Topics: Adult; Cell Division; Duodenal Ulcer; Dyspepsia; Epidermal Growth Factor; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Polymerase Chain Reaction; Proliferating Cell Nuclear Antigen; Radioimmunoassay; Transforming Growth Factor alpha

Autoantibodies against epitopes located at the canaliculi of human parietal cells occur in about 30% of Helicobacter pylori-infected patients. This has led to the hypothesis that gastric secretory function could be inhibited by anticanalicular autoantibodies in H. pylori gastritis.. Forty-four H. pylori-infected patients with and without duodenal ulcers were screened for anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin levels and basal and maximal gastric acid output were determined.. Fasting gastrin levels were significantly increased in the group with anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia the presence of anticanalicular autoantibodies was significantly correlated with an impaired basal acid secretion.. Antigastric autoimmunity in H. pylori gastritis seems to be relevant for gastric hyposecretion either directly by inhibiting the proton pump or indirectly through the development of gastric mucosa atrophy.

Topics: Adult; Autoantibodies; Autoimmunity; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Stomach

Elucidation of the significance of various factors in prognosis of duodenal ulcer (DU) severity.. The observational study entered 18 new cases of DU and 13 healthy controls. All the patients were followed up for 7 years with annual esophagogastroduodenoscopy.. 10 patients (group 1) had annual exacerbations of DU, 8 patients had rare exacerbations (group 2). Group 1 was characterized by basal acid hyperproduction, hyperpepsinogenemia, hypergastrinemia, marked contamination with Helicobacter pylori. Patients of group 2 had normal basal and pentagastrin-stimulated acid production, normopepsinogenemia, normogastrinemia, mild Helicobacter pylori infection.. The 7-year follow-up of new DU cases allowed demonstration of functional-morphological prognostic criteria for frequently and rarely recurrent DU courses.

Topics: Biopsy; Duodenal Ulcer; Duodenum; Endoscopy, Digestive System; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Prognosis; Stomach

Serum gastrin and pepsinogen concentrations were measured in 51 children infected with Helicobacter pylori, to investigate the clinical significance and influence of CagA and VacA on serum concentrations of these peptides. CagA+ was 44/51 (86%) and VacA+ was 42/51 (82%). Type I (CagA+/VacA+) included 39/51 (76%), type II (CagA-/VacA-) was 4/51 (8%), and intermediate (CagA-/VacA+, CagA+/VacA-) was 8/51 (16%). There was no significant correlation between endoscopic diagnosis and the state of CagA/VacA. Serum gastrin concentrations were not significantly correlated with the state of CagA/VacA. Serum pepsinogen I and II concentrations were significantly higher in CagA+ than in CagA-, but there was no significant difference between VacA+ and VacA-, Serum pepsinogen I/II ratio was not significantly correlated with the state of CagA/VacA. There was no significant difference between serum concentrations of gastrin, pepsinogen I and H. pylori phenotypes. However, pepsinogen II concentration was significantly higher in type I than type II. Pepsinogen I/II ratio was significantly lower in type I and intermediate than in type II. These findings suggest that CagA positively and phenotype of H. pylori could play a role in the development of upper gastrointestinal diseases in children.

Topics: Adolescent; Antigens, Bacterial; Bacterial Proteins; Child; Child, Preschool; Female; Gastrins; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Male; Osmolar Concentration; Pepsinogens; Phenotype

Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s).. We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g daily). Immediately before the examinations, the severity of gastric mucosal injury was evaluated macroscopically and histologically, and the production of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was determined by immunohistochemistry.. Most subjects had severe gastric injury after aspirin therapy, resulting in a substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or markedly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied.. The disinhibition of acid secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori-related hypergastrinemia apparently has a different background.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cytokines; Female; Gastric Acid; Gastric Dilatation; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Time Factors

How Helicobacter pylori infection affects gastric acid secretion is still unclear.. Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls.. Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed.. These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Ammonia; Amoxicillin; Anti-Ulcer Agents; Case-Control Studies; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Proton Pump Inhibitors; Stomach Ulcer

The aim of this study was to clarify the mechanism of inappropriate hypergastrinemia in Helicobacter pylori (H. pylori)-infected subjects.. We measured fasting serum gastrin (SG) concentrations, and investigated immunohistochemically G and D cell numbers in 47 subjects with normal mucosa, 24 subjects with chronic gastritis, and 24 subjects with duodenal ulcer (DU). The degree of inflammation and atrophy were classified into four categories based on criteria established in the Sydney System: none, mild, moderate, and severe. Avidin-biotin complex methods were used to identify G and D cells, which were counted per unit square (0.25 mm2) in five random fields from each of two well-oriented antral and fundic biopsies. SG concentrations were measured by radioimmunoassay.. The G cell number was not significantly different between 24 subjects with H. pylori-associated gastritis and those with DU. However, the number of antral D cells was significantly lower and the G/D cell ratio was significantly higher in subjects with DU than in those with H. pylori-associated gastritis (p < 0.01), although the degree of inflammation and atrophy in the antrum and H. pylori status were similar between the two groups. The mean fasting SG concentration was higher in subjects with DU than in those with H. pylori-associated gastritis, but the difference was not statistically significant.. Our results demonstrate that a marked decrease in antral D cell number with a high G/D cell ratio may contribute to hypergastrinemia and the pathogenesis of DU.

Topics: Adult; Antibodies, Bacterial; Atrophy; Cell Count; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Inflammation; Male; Somatostatin-Secreting Cells

Infection by viral or bacterial pathogens has been suspected in playing a role in the development of autoimmune thyroid disease. Because Helicobacter pylori might be involved in the development of nongastrointestinal conditions such as rosacea, ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H. pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis (n=21), Hashimoto's thyroiditis (n=18), and Graves' disease (n=20). Twenty patients with nontoxic multinodular goiter served as controls for nonautoimmune thyroid disease, and 11 patients with Addison's disease served as controls for nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were performed. The prevalence of H. pylori infection was markedly increased in the patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls with nontoxic multinodular goiter (40%) and Addison's disease (45.4%). Infection by H. pylori resulted in increased levels of gastrin, pepsinogen I, and pepsinogen II in the H. pylori-positive groups, compared with the H. pylori-negative groups. A positive linear regression was found between the levels of microsomal autoantibodies and those of anti-H. pylori IgG in patients with autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although the overall prevalence of H. pylori infection was not increased, the anti-H. pylori IgG levels and the results from the breath test were higher in the patients with Graves' disease and Hashimoto's thyroiditis patients than in the controls. Clearly, the prevalence of H. pylori infection is increased in autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory function. The strong relation between the levels of anti-H. pylori IgG and the levels of microsomal antibodies suggests that H. pylori antigens might be involved in the development of autoimmune atrophic thyroiditis or that autoimmune function in autoimmune atrophic thyroiditis may increase the likelihood of H. pylori infection.

Topics: Addison Disease; Adult; Antibodies, Bacterial; Cross-Sectional Studies; Female; Gastric Mucosa; Gastrins; Graves Disease; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Pepsinogens; Prevalence; Seroepidemiologic Studies; Thyroiditis, Autoimmune

In order to explore the role of Helicobacter pylori (H. pylori) infection in hypergastrinemia in patients on dialysis, the changes in serum gastrin concentration were examined before and after eradication treatment for H. pylori. Twenty-seven patients on dialysis were treated for the eradication of H. pylori. Fasting serum gastrin concentrations were measured by a radioimmunoassay which detects gastrin 17. Ammonia and pH levels of the gastric juice were also measured. The serum gastrin concentrations were significantly decreased following eradication of H. pylori, and the mean value reached the normal range. The restoration of hypergastrinemia was associated with marked reductions of gastric juice ammonia and pH levels. In contrast, patients in whom H. pylori was not eradicated showed no changes in these parameters. In conclusion, the elevation of the fasting serum gastrin 17 concentration seen in dialysis patients appeared to be attributable to H. pylori infection in the stomach.

Topics: Ammonia; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Male; Metronidazole; Middle Aged; Peptic Ulcer; Renal Dialysis

To date, little is known about a possible relationship between H. pylori-related disturbances of gastric function and the bacterial virulence. The aim of this study was to assess whether certain gastric function indices as well as the pattern of symptoms in nonulcer dyspepsia (NUD) are related to CagA status.. A total of 56 consecutive patients with NUD (38 H. pylori-positive and 18 H. pylori-negative) were studied. Dyspeptic symptoms were categorized according to the predominant complaints and scored for severity and frequency. In all subjects, basal and pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin release, fasting serum pepsinogen I (PG I) levels, and gastric emptying of solids were determined. CagA status was determined by assaying serum CagA IgG antibodies by western blotting.. Eighteen of 38 (47%) H. pylori-positive dyspeptics were CagA seropositive. Type and severity of dyspeptic symptoms did not significantly differ between CagA-positive and CagA-negative dyspeptics nor between H. pylori-positive and negative patients. Among the gastric function indices studied, only meal-stimulated gastrin was significantly influenced by CagA status (peak gastrin 129.9 [44.1] vs 99.1 [48.6] pg/ml in CagA-positive and negative NUD, respectively), but this was not accompanied by any significant modification of basal or stimulated acid secretion or gastric emptying of solids. The activities of both antral and corpus gastritis in NUD harboring CagA-positive strains were significantly higher than those of CagA-negative NUD. Accordingly, serum PG I levels were significantly higher in CagA-positive than CagA-negative or H. pylori-negative dyspeptics.. These findings support a role for CagA status in influencing the activity and perhaps the distribution of gastritis in NUD, as well as the degree of gastrin response to a meal; however, this is not accompanied by disturbances of acid secretion or gastric emptying or by differences in the type and severity of symptoms.

Topics: Adult; Aged; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Blotting, Western; Dyspepsia; Eating; Fasting; Female; Gastric Acid; Gastric Emptying; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pentagastrin; Pepsinogens; Pyloric Antrum; Stomach; Virulence

Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood. We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H. pylori antibody levels, before and after treatment of H. pylori gastritis in 28 men and women. Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline. Elimination of H. pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy). Elimination of H. pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30%. Elimination of H. pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells. Serum gastrin and H. pylori antibody levels declined significantly after elimination of H. pylori. None of these changes was observed in 14 subjects whose H. pylori gastritis was resistant to antimicrobial therapy. In summary, eradication of H. pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Bacterial; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pentagastrin; Pepsin A

There is strong evidence accumulating that chronic infection with Helicobacter pylori (H. pylori) interferes with inhibitory pathways of the regulation of acid secretion. The increase in maximum acid output (MAO), and the increase in the sensitivity of the parietal cell to gastrin commonly observed in patients suffering from duodenal ulcer disease (DU), however, remains largely unexplained. Insufficient evidence is available concerning how these parameters are influenced by H. pylori infection in patients not suffering from peptic ulcer disease (PUD) and how they are related to H. pylori-induced gastritis. The aim of this study was to compare basal gastric acid secretion (BAO), MAO, and the sensitivity of the parietal cell to gastrin in H. pylori-positive and H. pylori-negative patients not suffering from PUD, and to study the relationship with their individual postprandial gastrin release and the degree of gastric antral and corpus gastritis.. H. pylori status was assessed by CLO test and histology (two biopsies each from the antrum and the corpus) in 14 H. pylori-positive and 16 H. pylori-negative nonulcer patients of comparable age, weight and gender. Gastritis score was assessed by a pathologist, who was unaware of the acid secretory data. Following determination of BAO, the relation of pentagastrin and gastric acid secretion was established with a cumulative pentagastrin dose response curve for the dose range 0.03-6.0 microg/kg(-1) h(-1) and MAO (Vmax) and pentagastrin sensitivity (ED50) were determined. Basal and postprandial gastrin release was measured by radioimmunoassay.. There was a significant higher gastritis score in the H. pylori-positive compared with the H. pylori-negative subjects. The dose response curves of the pentagastrin stimulated gastric acid secretion were not different between H. pylori-positive and H. pylori-negative groups. No correlation was seen between the gastritis score, basal acid output (BAO) peak acid output (PAO), maximum acid output (MAO), ED50 values and the plasma gastrin values. There was, however, a considerable larger variation of the PAO and MAO data of the H. pylori-infected subjects and >50% of the respective data was above or below the relatively low range of the respective values of the noninfected subjects.. H. pylori-induced gastritis does not regularly enhance maximum acid output in nonulcer patients, nor does it modify the sensitivity of the parietal cell to gastrin. H. pylori infection is thus unlikely to be directly responsible for an increase of these parameters in DU disease. Our data support, however, the concept that chronic H. pylori infection can either enhance or attenuate maximum acid secretory capacity in certain subgroups of patients.

Topics: Adult; Biopsy; Dose-Response Relationship, Drug; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Postprandial Period; Statistics, Nonparametric; Stimulation, Chemical

Topics: Cytokines; Eye Infections, Bacterial; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Ophthalmology; Rosacea

Although Helicobacter pylori infection increases gastrin secretion, it is unknown whether this is a direct effect or requires activation of the immune system. We developed an H. pylori-infected human primary antral epithelial cell culture model to address this question. This culture protocol favors growth of H. pylori, and infected cultures could be maintained for up to 48 h. These cultures were enriched for gastrin (10-40%), somatostatin (2-5%), and gastric mucin (60-80%) cells but did not contain immunocytes. Bacterial attachment occurred in a random manner within 2 h of infection, although bacterial density was lower than in sections from infected patients. After 24 or 48 h, the bacterial microcolonies were similar in size to those seen in vivo, and at 24 h ultrastructural studies demonstrated well-developed pedestal formation underlying the bacteria. Coculture with H. pylori increased basal but not stimulated gastrin secretion at all time points >2 h. In conclusion, a newly developed cell culture model has been used to characterize the interactions between H. pylori and normal human antral epithelial cells.

Topics: Adult; Bacterial Adhesion; Cells, Cultured; Factor VIII; Female; Fibronectins; Gastric Mucins; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Models, Biological; Nerve Tissue Proteins; Pyloric Antrum; Somatostatin; Thiolester Hydrolases; Ubiquitin Thiolesterase

Topics: Anemia, Pernicious; Autoimmunity; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia

Helicobacter pylori infection in humans has been shown to be associated with changes in gastric physiology, including exaggerated basal and meal-stimulated gastrin levels. This has been suggested to be due to the direct effects of the bacterium through inflammation and its urease enzyme. The gastric bacteria Helicobacter felis and Helicobacter heilmannii colonize the antrum of rats in large numbers and induce no significant inflammatory response. Thus, the direct effect of Helicobacter infection on gastric physiology, independent of gastritis, could be studied. Basal, freely fed and stimulated acid and gastrin levels were recorded from animals infected with H. felis, H. heilmannii or uninfected controls over a 30 week period. No significant difference was found between freely fed gastrin over 7 weeks or fasting gastrin over 24 weeks or basal and stimulated acid over 30 weeks between all three groups. Triple therapy did not alter gastrin or acid output. The antrum of all Helicobacter-infected rats was well colonized; triple therapy cleared H. felis but not H. heilmannii. Very little inflammation was seen in control or Helicobacter-infected animals. In conclusion, Helicobacter-induced effects on gastric physiology are unlikely to be due to direct bacterial effects, but are best explained by other factors (i.e. inflammatory damage).

Topics: Animals; Disease Models, Animal; Female; Gastric Acid; Gastrins; Helicobacter Infections; Inflammation; Rats; Urease

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Animals; Cytokines; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Pentagastrin; Peptides

Helicobacter pylori (Hp) is a major risk factor of peptic ulcer but studies on the relation between Hp infection and gastric pathology are limited due to lack of convenient models resembling Hp infection in humans. We studied the effects of inoculation of conventional BALB/c mice with toxigenic type I Hp (cagA+ and vacA+) and non-toxigenic type II Hp (cagA- and vacA-) vs administration of vehicle on gastric secretion and healing of gastric ulcers. The gastric secretion studies were performed on mice with chronic gastric fistula before and after inoculation with toxigenic or non-toxigenic Hp strain or administration of vehicle (saline). Gastric ulcers were produced in mice inoculated with toxigenic and non-toxigenic Hp strain or vehicle and then sacrificed at day 0 and after 2, 4, 7, 14 and 28 days. Ulcer area and gastric blood flow (GBF), plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy specimens were also taken for the assessment of the presence of viable Hp using rapid urease test, the Hp-culture and the reverse transcriptase--polymerase chain reaction (RT-PCR) analysis of the signal for Hp CagA. Gastric acid output was reduced by over 50% immediately after Hp inoculation and this effect persisted during all time intervals tested, being significantly more pronounced in type I Hp-infected stomach. The area (7 mm2) of ulcers in control mice decreased gradually and then continued to decline during 14 days to disappear almost completely after 28 days. In contrast, the ulcers were present till day 28 in all mice infected with type I or type II Hp strain being significantly larger especially with type I Hp-infection. The GBF in control mice showed gradual rise with decreasing ulcer size being significantly higher at the ulcer margin than the ulcer crater and reached after 14 and 28 days the value not significantly different from that in vehicle-administered mice. In contrast, the GBF in type I Hp-infected mice but to a lesser extent, in type II Hp infected mice was significantly lower than in the vehicle controls, both at the ulcer margin and the crater of ulcers at all tested days. Hp-infection was accompanied by significant increment in plasma gastrin and the fall in gastric somatostatin contents observed at all test days, particularly in mice infected with type I Hp strain. Edema of surface epithelium appeared after 7 days and wak but significant mucosal inflammatory infiltration occurred after 14 days to further incr

Topics: Animals; Bacterial Toxins; Cytotoxins; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Male; Mice; Microcirculation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Stomach; Stomach Ulcer; Wound Healing

To study the effects of the somatostatin analog octreotide on gastric mucosal function and histology during short-term (3 months) preoperative treatment in patients with acromegaly.. Open design clinical study.. 10 patients were studied before treatment with octreotide (pre-tx), on day 1 of 300 microg octreotide/day (d300), after 1 week on 300 (w300), 600 (w600) or 1500 (wl500) microg octreotide/day, and after an additional 2.5 months on 1500 microg octreotide/day (M3). An 8h gastrin profile was obtained and ambulatory intragastric 23h pH-metry carried out at the indicated time points. Gastroscopy was performed at pre-tx and M3 and multiple mucosal biopsy specimens taken.. The mean serum gastrin concentration at first declined during octreotide therapy to a nadir at w1500, then recovered despite ongoing therapy (probably in response to reduced gastric acidity) and was similar to pre-tx values at M3 (mean+/-S.E.: 87+/-26, 50+/-11 and 98+/-46ng/l for pre-tx, w1500 and M3 respectively; P<0.05, pre-tx vs w1500). Gastric acidity had also declined at d300(P<0.05, d300 vs pre-tx), then recovered (despite the increase in the octreotide dose), but declined again at M3 (mean pH (95% confidence interval): 2.4 (1.7-3.2), 3.3 (2.4-4.3), 2.6 (1.8-:3.5, n=8) and 2.9 (1.6-4.2, n=7) at pre-tx, d300, w1500 and M3 respectively). The gastrin concentration at M3, although similar to pre-tx values, remained inadequately low for the reduced gastric acidity. The reduction in gastric acidity was marked during the daytime (0900-2200 h; P<0.01, d300 vs pre-tx and P=0.028, M3 vs pre-tx). However, while the stimulated postprandial gastric acid secretion was reduced at d300 (P<0.01, d300 vs pre-tx) and at M3 (n=7; P=0.027, M3 vs pre-tx), fasting and preprandial acidity was not affected. During the night, gastric acidity was reduced from 2200 to 0300 h, but the reduction was less marked than during the daytime. Paradoxically, the physiological intermittent late nocturnal reduction in acidity ('pH peaks' (0300-0800 h)) was abolished rather than enhanced. No patient acquired new Helicobacter pylori infection. The mean gastritis scores for antrum and body (n=8, Sidney classification) increased marginally from 1.7 to 1.9 (chronicity) and from 0.7 to 0.9 (atrophy), while the activity score was slightly reduced from 1.2 to 1.0.. Three months of preoperative octreotide treatment profoundly and persistently altered gastric mucosal function (gastrin suppression, reduced acidity), but caused only minor variations in the pre-existing gastritis scores.

Topics: Acromegaly; Adult; Aged; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Octreotide; Preoperative Care

To determine the clinical significance of Helicobacter pylori seropositivity and seronegativity in healthy blood donors, we carried out a serological evaluation of Helicobacter pylori status and endoscopy in a healthy blood donors population. In all, 1010 donors were screened for Helicobacter pylori by IgG ELISA and assessed for pepsinogen I and gastrin levels by RIA; 298 IgG seropositive and 61 seronegative subjects underwent endoscopy with biopsies. Of 359, 165 were also tested for CagA by western blotting. Of the 298 IgG seropositives, 274 were shown to be infected on biopsy testing. Endoscopy revealed 70 peptic ulcers, 41 cases of erosive duodenitis, and two gastric cancers. In all 105 seropositive donors were tested for CagA and 69 were CagA positive [34/58 gastritis (58.6%), 24/35 duodenal ulcer (68.6%) and 11/12 gastric ulcer (91.6%)]. Histologically active/chronic gastritis was associated with CagA: 88.4% vs 50% (CagA seropositive vs seronegative). Of the 61 IgG seronegatives, 59 were negative on biopsy testing. At endoscopy three had duodenitis. Of the 60/61 IgG seronegatives tested for CagA, one had a moderate reaction. Duodenal ulcer donors showed higher pepsinogen I levels than donors without duodenal ulcers (97.7 microg/ml vs 80.9 microg/ml respectively). Screening for Helicobacter pylori and anti-CagA seropositivity and pepsinogen I can identify individuals likely to have gastroduodenal pathology even in the absence of symptoms.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Blood Donors; Blotting, Western; Dyspepsia; Endoscopy, Gastrointestinal; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Peptic Ulcer

Tham et al. show that Helicobacter pylori infection lowers the density of immunoreactive somatostatin cells (D-cells) in the antral mucosa and elevates plasma gastrin concentrations. According to current hypothesis, the lack of inhibition by somatostatin allows excessive release of gastrin, which stimulates acid secretion and thus causes duodenal ulcers. The cytokine tumour necrosis factor-alpha which is released in H. pylori gastritis inhibits D-cells in culture and may be responsible. Why do not all infected persons get duodenal ulcers? Recent work shows that more aggressive strains of H. pylori have greater effects on somatostatin/gastrin physiology. Another variable is whether the infection causes corpusitis or not. Inflammation of the gastric corpus diminishes acid secretion, which greatly decreases the likelihood of duodenal ulcers but increases the risk of gastric cancer. Factors which promote corpusitis include diets with high salt content or lacking in antioxidant vitamins. Work in this area is elucidating how H. pylori causes different diseases. Hopefully this will allow us to predict and prevent its serious sequelae.

Topics: Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin; Somatostatin-Secreting Cells; Stomach Diseases

As Helicobacter pylori infection is associated with an elevation in plasma gastrin with normal antral gastrin cell counts, an abnormality in antral somatostatin cells may be associated with the infection. We evaluated the effect of eradication of H. pylori on antral somatostatin cell density in the light of antral gastrin cell density and plasma gastrin levels.. Prospective study.. Of 25 dyspeptic patients with H. pylori infection, nine had H. pylori successfully eradicated and the rest remained infected. Antral biopsies were immunostained for somatostatin cells and plasma gastrin measured before and 4 weeks after H. pylori eradication therapy. Ten other dyspeptic patients without H. pylori infection had their somatostatin cell density evaluated as controls.. Somatostatin cell density in the patients without H. pylori infection at the outset was significantly higher than that in the patients with H. pylori infection at the outset (median 57 [18-83] vs. 37 [6-80] cells/mm) respectively (P <0.05). Somatostatin cell density increased after H. pylori eradication (before treatment, median 50 [15-72]; after treatment 71 [39-107] cells/mm) (P < 0.05) but was unchanged with persistent H. pylori infection. Plasma gastrin decreased after H. pylori eradication (before treatment, median 70 [45-100]; after treatment 30 [10-100] ng/l) (P < 0.05) but was unchanged with persistent H. pylori infection.. Following eradication of H. pylori, there is an increase in somatostatin cell density with a fall in plasma gastrin. This supports the theory that H. pylori infection results in a decrease in somatostatin cell density and, as the latter is an inhibitor of gastrin cells, this results in an increased plasma gastrin.

Topics: Adult; Dyspepsia; Female; Gastrin-Secreting Cells; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Somatostatin-Secreting Cells

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cytokines; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Tumor Necrosis Factor-alpha

Recurrent abdominal pain (RAP) is a significant problem in the pediatric population, and there has been much recent interest in the role that Helicobacter pylori (Hp) might play in this disorder. In this case control study, the authors aimed to determine whether Hp is an agent responsible for RAP, and to assess fasting gastrin concentrations in children with and without RAP in the Hp-positive and -negative groups. The study was conducted in 42 patients with RAP and 50 healthy children attending routine day-case surgery as a control group, aged 3 to 15 years, over a 12-month period. Of the 42 children with RAP, 30 were seropositive (71.4%) for Hp IgG, and of 50 children in the control group, 32 were seropositive (64%) for Hp IgG (P > 0.05). We found that Hp infection was as high in healthy children as in children with RAP. The mean fasting gastrin levels in 62 Hp-seropositive children (60.4 ng/l) were not different from those in 30 Hp-seronegative children (57.3 ng/l) and those in 42 children with RAP (58.2 ng/l) were also not significantly different from those in 50 healthy children (62.9 ng/l). Thus, no association between childhood Hp infection, hypergastrinemia, and RAP was found in our Turkish population.

Topics: Abdominal Pain; Antibodies, Bacterial; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Recurrence; Turkey

The mechanisms causing progression of fundic gastritis and changes in argyrophil cell morphology in patients undergoing long-term treatment with proton pump inhibitors are unknown. The hypothesis of this study was that Helicobacter pylori is a risk factor for both gastritis and argyrophil cell hyperplasia.. Forty-two patients with peptic disorders resistant to H2-blockers were treated with 30-90 mg lansoprazole daily for up to 5 years. Serum gastrin levels, antral gastrin cells, fundic argyrophil cells, parameters of gastritis, and H. pylori infection were evaluated regularly.. In nonantrectomized patients, serum gastrin levels increased from a median of 76 pg/mL to 163 pg/mL within 3 months. Antral gastrin cell density increased from 175 to 267 cells/mm2 (P < 0.001), and fundic argyrophil cell density increased from 83 to 149 cells/mm2 (P < 0.001). Chronic inflammation, activity, and atrophy of the oxyntic mucosa worsened exclusively in patients with H. pylori infection. Linear and/or micronodular argyrophil cell hyperplasia was diagnosed in 2.6% of patients before lansoprazole and in 29.2% after 5 years treatment. These changes were significantly related to serum gastrin levels, H. pylori infection, chronic inflammation, and atrophy of the oxyntic mucosa.. H. pylori represents an important factor for the progression of fundic gastritis and the development of argyrophil cell hyperplasia during long-term treatment with lansoprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Lansoprazole; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Pyloric Antrum; Risk Factors

In order to study the association between gastrin and H. pylori infection the density of antral G cells was evaluated by transcriptional expression of gastrin mRNA using a sensitive cold probe labelled with digoxigenin. the study group included 22 patients with symptomatic H. pylori positive gastritis and/or duodenal ulcer, 12 of whom were re-evaluated after eradication of H. pylori and 6 controls. The number of G cells per high power field in H.pylori positive patients (26.68 +/- 9.51) was significantly higher (P < 0.01) compared to controls (5.83 +/- 3.37). Among the 12 patients re-evaluated after H. pylori eradication, there was a significant decrease (P < 0.001) in the number of G cells (13.5 +/- 5.44) compared to pre-eradication value (26.25 +/- 8.0). The present study suggests that increased transcriptional expression of gastrin is directly related to H. pylori infection.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; RNA, Messenger; Transcription, Genetic

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Peptides

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Parietal Cells, Gastric; Peptides

Helicobacter pylori infection is associated with an exaggeration of gastrin release following meals or bombesin stimulation attributed to a defect of somatostatin secretion of antral D-cells. Nevertheless, these modifications of gastric physiology do not explain the increase of gastric acid secretion which is only observed in duodenal ulcer patients. The inhibitory effect of somatostatin secretion of fundic D-cells on parietal cells is well known. The aim of our prospective study was to compare the number of fundic D-cells and likewise the number of antral G-cells and D-cells between patients with duodenal ulcer and healthy subjects with and without H. pylori infection.. The numbers of D-cells and G-cells were compared between 19 infected patients with duodenal ulcer and 20 healthy subjects, 10 with and 10 without H. pylori infection. Fundic mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of somatostatin, antral mucosal biopsy specimens for the presence of gastrin and somatostatin.. The number of G-cells was significantly lower (P = 0.0012) in duodenal ulcer patients by comparison with infected subjects and controls. The number of antral D-cells was significantly less (P < 0.0001) in duodenal ulcer patients (mean of 10 random fields = 0.45 +/- 0.04) than in either asymptomatic infected patients (0.65 +/- 0.07) or uninfected controls (0.88 +/- 0.10). The number of fundic D-cells was significantly lower (P < 0.0001) in duodenal ulcer patients (mean = 0.20 +/- 0.03) than in either asymptomatic infected subjects (0.29 +/- 0.05) or controls (0.73 +/- 0.09); here the difference between the two groups of infected subjects was not significant. Multivariate analysis showed that the presence of H. pylori infection of the fundic mucosa did not influence the number of fundic D-cells.. Changes in the number of fundic and antral D-cells induced by H. pylori infection did not explain abnormalities of gastric acid secretion usually observed in duodenal ulcer patients; it is suggested that pre-existing abnormalities in the regulation of parietal cell or increase of parietal cell mass are involved.

Topics: Adult; Biopsy; Cell Count; Duodenal Ulcer; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Prospective Studies; Pyloric Antrum; Somatostatin

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and protection but their involvement in Helicobacter pylori associated duodenal ulcer has been little examined.. To assess gastric acid secretion, plasma gastrin concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of these peptides and their receptor (EGFr) as well as salivary and gastric luminal release of EGF under basal conditions and after pentagastrin stimulation in 10 healthy subjects and in 25 H pylori positive patients with duodenal ulcer before and after two weeks of triple anti-H pylori therapy and four weeks after the termination of this therapy.. Pentagastrin stimulation caused a significant increase in salivary and gastric release of EGF both in healthy controls and patients with duodenal ulcers but in the patients, the eradication of H pylori resulted in several fold higher gastric luminal (but not salivary) EGF release than before the anti-H pylori therapy. Mucosal contents of immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and EGFr in H pylori positive patients with duodenal ulcer were significantly higher than those in healthy H pylori negative controls and this increase persisted after eradication of H pylori. Basal plasma gastrin was significantly reduced after two weeks of triple therapy and four weeks after the H pylori eradication all ulcers were completely healed.. (1) H pylori infection in patients with duodenal ulcer was accompanied by enhanced plasma gastrin and increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and enhancement of gastric (but not salivary) luminal release of EGF, particularly after pentagastrin stimulation; and (3) enhanced mucosal content and expression of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute to ulcer healing after eradication of H pylori.

Topics: Duodenal Ulcer; Epidermal Growth Factor; ErbB Receptors; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pentagastrin; Saliva; Transforming Growth Factor alpha

Topics: Cell Count; Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by exocrine gland impairment. Up to now there have been no reports dealing with gastric mucosa involvement in this autoimmune condition, which is frequently associated with Sjögren's syndrome. The aim of this study was to investigate the morphologic, biochemical and immunological features of the gastric mucosa in PBC.. A cross-sectional study with matching was performed. Thirty-three PBC patients (30 F, 3 M, mean age 58 years; 17 with stage II-III, and 16 with stage IV disease) and 33 sex- and age-matched dyspeptic controls were included. Six biopsy specimens from the fundus (2), body (2) and antrum (2) were taken from all patients and controls. A serological assessment was performed for each subject, i.e. pepsinogen A (PGA), pepsinogen C (PGC), gastrin (G), and antibodies against Helicobacter pylori (anti-Hp IgG).. Endoscopic gastritis was found in 22 PBC patients (66.6%). There was no difference between PBC patients and controls regarding the percentage of subjects with mild, moderate, severe or atrophic gastritis (AG). There was no difference in gastric mucosal involvement between PBC subjects with or without secondary Sjögren's syndrome. A discrepancy was observed in the data obtained with respect to Helicobacter pylori (H. pylori) infection. H. pylori colonization was significantly more frequent in controls than in PBC patients (79% vs 49%, p < 0.002), but anti-Hp IgG were detected in the same percentage in the two groups (90% vs 83% respectively). There was no difference between the two groups in the PGA, PGC, PGA/PGC ratio, or gastrin. Eight PBC patients had esophageal varices.. PBC patients are not characterized by chronic atrophic gastritis. Even though they present chronic gastritis with the same prevalence as dyspeptic controls, and show signs of previous H. pylori infection as frequently as dyspeptic patients, they are actually much less frequently infected. The reasons for this observation are unclear.

Topics: Adult; Aged; Antibodies, Bacterial; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Dyspepsia; Female; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Pepsinogens; Sjogren's Syndrome

To investigate the mechanism of the hypergastrinaemia associated with Helicobacter pylori infection by examining the effect of H. pylori infection and the cytokine tumour necrosis factor-alpha (TNF-alpha) on gastrin release from human antral fragments.. In-vitro experimental study.. Human antral biopsy fragments were cultured for 6 h with and without TNF-alpha (20 ng/ml) and the gastrin released over the following 2-h stimulation period measured by radioimmunoassay. The integrity of the paracrine feedback loop inhibiting gastrin release was tested by concurrent administration of cholecystokinin (CCK).. H. pylori-positive fragments were associated with significantly greater bombesin-stimulated gastrin release (increased by 40%, P < 0.05) and less inhibition produced by CCK administration (decreased by 55%, P < 0.05), than H. pylori-negative fragments. TNF-alpha treatment of H. pylori-negative fragments significantly enhanced bombesin-stimulated gastrin release (by 82%, P < 0.01) and diminished inhibitory feedback by CCK (by 53%, P < 0.05).. H. pylori infection is associated with enhanced gastrin release from human antrum and TNF-alpha produces a similar effect. Proinflammatory cytokines generated in the antrum in response to the infection are likely to play a significant role in the hypergastrinaemia of H. pylori infection.

Topics: Bombesin; Cholecystokinin; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Pyloric Antrum; Radioimmunoassay; Tumor Necrosis Factor-alpha

The aims of this study in 50 patients with H. pylori infection and duodenal ulcer were to examine the effect of eradication therapy on the serum levels of gastrin, pepsinogen I, and pepsinogen II and to investigate whether monitoring of the serum changes in these peptides after treatment could predict patient outcome. H. pylori status was assessed at entry and one and six months after therapy by culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath test. Significant decreases were observed in the serum levels of gastrin (-11.4 +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45 patients whose infection was eradicated, but not in the patients without eradication. Serum values of these peptides were unchanged in an additional group of 10 patients that only received omeprazol, none of whom had H. pylori eradicated. The best cutoff point of the percentage of each peptide to predict patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II. A pepsinogen II decrease > 15% resulted in the best marker of H. pylori clearance, accurately identifying patient outcome 86.6% of the time, whereas the diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%, respectively. Significant correlations were found between the bacterial load assessed by histology with the serum concentrations of pepsinogen I and II and with the urease activity as measured by the amount of 14CO2 excreted. In conclusion, eradication of H. pylori infection is followed by a significant drop in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the latter are the most uniform and may be used as an indirect tool to predict treatment outcome.

Topics: Adult; Aged; Breath Tests; Duodenal Ulcer; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

This study was performed to examine the effects of additional enprostil administration on hypergastrinemia and gastric acid suppression induced by omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative patients) before treatment, after two weeks of omeprazole (20 mg/day), and after two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid inhibitory effect of enprostil was evaluated by 24-hr intragastric pH measurements in five healthy Helicobacter pylori-negative volunteers. After omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive patients (3.5-fold of control) was markedly higher than that of Helicobacter pylori-negative patients (1.7-fold of control). Additional treatment with enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recorded during the nonmeal daytime interval increased significantly with additional enprostil. Thus, enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positive patients, and effectively suppresses acid secretion.

Topics: Adult; Aged; Anti-Ulcer Agents; Drug Therapy, Combination; Enprostil; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Peptic Ulcer

We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori-associated enlarged fold gastritis.. To investigate whether locally produced interleukin-1 beta is possibly involved in the inhibition of acid secretion in H. pylori gastritis.. IL-1 beta release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori-positive), five H. pylori-positive and 10 H. pylori-negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1 beta was examined by [14C]-aminopyrine uptake assay using isolated rabbit gastric glands.. IL-1 beta release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori-positive patients (r = -0.591 and r = -0.641, respectively; P < 0.01), and significantly decreased with concomitant increases in acid secretions after eradication of H. pylori. [14C]-aminopyrine uptake was inhibited by IL-1 beta in a dose-dependent manner.. Increased production of IL-1 beta caused by H. pylori infection is possibly involved in the inhibition of acid secretion in enlarged fold gastritis.

Topics: Adult; Aged; Aminopyrine; Animals; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Hypertrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Male; Middle Aged; Rabbits; Stomach

The mechanism by which Helicobacter pylori (Hp) predisposes to duodenal and gastric ulcers remains still unclear. It is possible that Hp infection impaires gastric secretion. Evaluation of gastric acid and mucus secretion before and after Hp eradication would let to estimate the influence of Hp infection on gastric secretion. To evaluate the effect of Hp infection on gastric acid and gastric mucous secretion before and one year after Hp eradication. We examined 28 Hp positive peptic ulcer disease patients (10-gastric ulcer GU, 18-duodenal ulcer DU) before and one year after antibacterial treatment. Gastric acid output was examined basely (BAO) and in response to pentagastrin (6 micrograms/kg) (MAO) using Kay's standard method. Some components of gastric mucus as fucose, galactose, hexosamines and sialic acid were measured using calorimetric methods basaly and after pentagastrin stimulation. Plasma gastrin concentration was measured in 20 patients (6-GU, 14-DU) by radioimmunoassay before and one year after eradication. Hp status was determined by rapid urease test (CLO) and histology (Giemsa stain). One year after Hp successful eradication gastric acid secretion was significantly reduced-BAO: 3,31 vs 1,474 mmol/h; MAO: 19,63 vs 14,85 mmol/h, p < 0.05. Plasma gastrin concentration decreased significantly from 9,783 to 6,017 pmol/I, p < 0.05. In patients with ineffective eradication we did not observe any significant changes in gastric acid secretion. An evident, but not statistically significant, decrease of sialic acid output in eradicated patients was noted. The study has shown the significant influence of Hp infection on gastric acid secretion. Those results support the hypothesis that increased gastric acid secretion may be one of the pathogenic mechanism of Hp infection inducing mucosal damage.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Fucose; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Mucus; N-Acetylneuraminic Acid; Stomach Ulcer; Time Factors

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Transforming Growth Factor alpha

The evolution of gastritis and the behavior of basal and meal-stimulated gastrin release, pepsinogen levels, and gastric emptying of solids were studied in a series of consecutive patients with Helicobacter pylori-positive, uncomplicated, non-NSAID-related type I gastric ulcer over a follow-up period of 3 months after eradication therapy was begun.. Before starting treatment (consisting of omeprazole 40 mg a day for 1 month and amoxycillin 1 g three times daily for 14 days), and for 3 months after ulcer healing, 16 patients had a series of functional examinations, including basal and meal-stimulated serum gastrin concentration, serum pepsinogen I levels, evaluation of gastric emptying of solids by means of serial ultrasonographic measurement of the gastric antrum area, and histological assessment of antral and corpus gastritis.. Double therapy resulted in the successful eradication of H. pylori in eight of 16 evaluable patients. In the group of H. pylori-eradicated patients, the mean scores of gastritis activity and inflammation in the antrum and corpus had fallen, 3 months after eradication. No significant changes in mean gastritis scores were observed in the case and control group with regard to intestinal metaplasia and atrophy in the antrum and corpus. In H. pylori-eradicated patients, the integrated gastrin response to meal, but not fasting gastrin concentration, fell significantly during follow-up, and serum pepsinogen I levels significantly decreased, compared with baseline. In contrast, the fasting and maximal antral area and the gastric emptying of solids remained unchanged over time. In the control group (but not the H. pylori-eradicated group), no significant modifications of any of the above-mentioned parameters were observed during follow-up.. Our findings suggest that in non-NSAID-related type I gastric ulcers, the eradication of H. pylori significantly reduces gastritis activity and inflammatory scores, but not atrophy and intestinal metaplasia, and modifies gastrin and pepsinogen I release in a short follow-up period. In contrast, H.pylori eradication does not significantly affect gastric emptying of solids, at least within a period of 3 months from therapy.

Topics: Amoxicillin; Anti-Ulcer Agents; Drug Therapy, Combination; Female; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Penicillins; Pepsinogens; Stomach; Stomach Ulcer

Gastric acid secretion in Japanese subjects decreases with aging. One of the possible causative mechanisms of this attenuated acid secretion is speculated to be a Helicobacter pylori induced chronic gastritis. The infection rate of this microorganism has decreased recently in Japan.. To investigate whether gastric acid secretion has altered over the past 20 years, and if so, what the influence of H pylori infection might be in the Japanese population.. Gastric acid secretion, serum gastrin and pepsinogen I and II concentrations, and H pylori infection were determined in 110 Japanese subjects in both the 1970s and 1990s.. Basal acid output as well as maximal acid output have greatly increased over the past 20 years, not only in individuals with H pylori infection but also in those without infection. Furthermore, subjects with H pylori infection tended to show decreased gastric acid secretion in comparison with those without infection, particularly in geriatric subjects. There was a positive correlation between gastric acid secretion and serum pepsinogen I concentrations.. In Japan, both basal and stimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in H pylori infection may play an important role in this phenomenon.

Topics: Adult; Aged; Aging; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Pepsinogens; Regression Analysis; Secretory Rate; Statistics, Nonparametric

There are no studies of changes in immunoglobulin G (IgG) titers to Helicobacter pylori, serum pepsinogen, and gastrin in patients with H. pylori-positive gastric ulcers. We investigated the effect of therapy for H. pylori-positive gastric ulcer on IgG titers to H. pylori, serum pepsinogen I and II, and gastrin. Thirty-six patients with H. pylori-positive gastric ulcer were treated with lansorazole and antibiotics for 2 weeks. Serum pepsinogen I and II concentrations, serum gastrin, and IgG titers to H. pylori were measured before treatment and then at 4 and 12 weeks after stopping the treatment. The presence or eradication of H. pylori was determined using the rapid urease test and by histologic H. pylori staining. For 19 patients in whom H. pylori had been successfully eradicated, the pepsinogen I/II ratio increased, pepsinogen II levels decreased, and the anti-H. pylori IgG decreased compared with the results from before therapy and with those from 4 and 12 weeks after therapy. Gastrin levels decreased compared with pretreatment results and those from 4 weeks after the end of treatment. In 17 patients in whom the therapy failed to eradicate H. pylori infection, there were no sequential significant changes in the pepsinogen I/II ratio or in the levels of pepsinogen I, pepsinogen II, anti-H. pylori IgG, and gastrin. A decrease in the serum levels of the IgG antibody to H. pylori and gastrin and also an increase in the pepsinogen I/II ratio could be used as predictors for the eradication of H. pylori infection in gastric ulcer.

Topics: Aged; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogens; Stomach Ulcer

It has recently been shown that humoral antigastric autoreactivities occur in a substantial number of Helicobacter pylori infected patients.. To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course.. Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies.. H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer.. The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Autoantibodies; Chi-Square Distribution; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Statistics, Nonparametric

Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition.. To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole.. Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland.. Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment.. A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Cell Division; Epithelial Cells; Esophagitis, Peptic; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Lansoprazole; Middle Aged; Omeprazole; Proton Pump Inhibitors; Statistics, Nonparametric; Time Factors

Helicobacter pylori infection exerts variable effects on gastric acid secretion. It may increase acid secretion, decrease acid secretion or produce no overall change. The effect of the infection on acid secretion depends upon the relative extent to which the Helicobacter pylori gastritis affects the antral and body mucosa of the stomach. When there is antral predominant, body-sparing gastritis, there is increased gastrin release and this is accompanied by increased acid secretion. When there is a significant body gastritis, acid secretion is reduced and subjects may be completely achlorhydric. The majority of subjects have both antral gastritis and body gastritis and this results in no overall change in gastric acid secretion. There is now increasing evidence that the alteration which Helicobacter pylori infection exerts upon gastric acid secretion is a pivotal factor in determining the clinical outcome of the infection. Subjects in whom the infection produces acid hypersecretion develop duodenal ulcer disease due to the increased duodenal acid load. In subjects in whom the infection induces marked hypochlorhydria, there is an increased risk of gastric cancer. The hypochlorhydria probably plays an important role in the carcinogenic process as high intragastric pH markedly raises intragastric nitrite levels, profoundly lowers gastric juice ascorbic acid and allows colonization by nitrosating bacteria. The reason for the different functional responses to Helicobacter pylori infection is unclear but may be related to the host's pre-morbid acid secretory status.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Stomach Neoplasms

Dyspeptic symptoms frequently recur rapidly after withdrawal of H2 antagonists, and this might be related to rebound acid hypersecretion. We have studied this phenomenon in healthy volunteers with and without Helicobacter pylori infection.. Basal and gastrin-releasing peptide (GRP) (40 pmol/kg/h) stimulated acid output, and gastrin concentration were measured in 18 healthy volunteers (nine were H. pylori positive). Studies were performed before and at 60 h and 10 days after completion of a 60-day course of ranitidine 300 mg nocte.. In the H. pylori-negative healthy volunteers, basal acid output increased by a median of 137% 2 days after stopping ranitidine therapy compared with pretreatment values (p = 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output increased by a median of 108% 2 days post ranitidine (p < 0.01) and remained slightly increased at day 10. In H. pylori-positive healthy volunteers, basal acid output increased by a median of 96% 2 days after ranitidine therapy ceased (p < 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output also increased by a median of 56% 2 days posttreatment and returned to pretreatment values by day 10. The increase in acid output both basal and in response to GRP was not accompanied by any rise in gastrin concentration in either the H. pylori-positive or -negative subjects.. Ranitidine therapy is associated with marked rebound hypersecretion of acid, and this may contribute to rapid resurgence of symptoms after therapy has been discontinued.

Topics: Anti-Ulcer Agents; Bombesin; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Peptides; Ranitidine; Time Factors

The mechanism(s) by which sucralfate heals duodenal ulcers remains unclear. The aim of this study was to determine the effect of sucralfate on Helicobacter pylori infection and on the accompanying hypersecretion of gastric acid the infection induces in patients with duodenal ulcer.. Basal and gastrin-releasing peptide (GRP) stimulated gastrin release and acid secretion. H. pylori density, gastric urease activity, and severity of gastritis were studied in patients with duodenal ulcer who were positive for H. pylori before, during, and after 4 weeks' treatment with sucralfate (2 g twice daily).. The density of H. pylori decreased by 70% during sucralfate treatment and returned to the pretreatment level after discontinuation of therapy. This suppression of H. pylori infection was accompanied by an 80% decrease in gastric urease activity. GRP-stimulated plasma gastrin concentrations, GRP-stimulated acid output, and basal acid output all decreased by approximately 50% during sucralfate therapy and returned to pretreatment levels after treatment was discontinued.. These findings indicate that sucralfate markedly suppresses H. pylori infection and the accompanying hypersecretion of acid the infection induces in patients with duodenal ulcer. These effects are likely to be important mechanisms by which the drug promotes duodenal ulcer healing.

Topics: Adult; Aged; Anti-Ulcer Agents; Breath Tests; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stomach; Sucralfate; Urease

This study aimed to estimate the prevalence and type of chronic gastritis in an asymptomatic working population and to determine whether a combination of serum pepsinogen levels and Helicobacter pylori serology could be used to identify a subgroup with atrophic gastritis at elevated risk of gastric carcinoma. A 10% subsample of 544 male volunteer factory workers aged 18-63 years and participating in a larger study underwent endoscopy and biopsy. Of these men, 29 were seropositive for Helicobacter pylori; all but three (89.7%) had chronic gastritis. Serum pepsinogen A levels increased with progression from a corpus predominant pattern of gastritis through pangastritis to an antral predominant pattern. Nine subjects had corpus atrophy, which was in most cases accompanied by fasting hypochlorhydria and hypergastrinaemia. A combination of pepsinogen A below 80 ng ml-1 and Helicobaceter pylori seropositivity detected corpus atrophy with sensitivity 88.9% and specificity 92.3%. A second screening stage, using a pepsinogen A/C ratio of below 2.5 as a cut-off, resulted in a reduction in numbers requiring further investigation but with some loss of sensitivity (77.8%). Application of this two-stage screening programme to the original sample of 544 workers would have resulted in 11 (2.2%) men being selected for follow-up, excluding 25 (5.1%) false negatives. Our results suggest that a combination of serum pepsinogen levels and Helicobacter pylori serology could be useful as a biomarker strategy for detection of individuals at increased risk of gastric carcinoma and for non-invasive investigation of the natural history of Helicobacter pylori gastritis.

Topics: Adolescent; Adult; Biomarkers; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Occupational Diseases; Pepsinogens; Prevalence; Risk Factors; Stomach Neoplasms

Helicobacter pylori infection and duodenal ulcer disease are firmly correlated. However, the bacteria do mainly colonize the antrum, indicating an indirect pathogenic mechanism. The aim of this study was to test a concept claiming that H. pylori infection of the antrum selectively blocks normal inhibitory reflex pathways to gastrin and parietal cells.. The effect of antral distention was studied on gastric acid secretion stimulated by pentagastrin and on gastrin release stimulated by gastrin-releasing peptide in H. pylori-infected and noninfected patients with and without duodenal ulcer disease, as well as after eradication of the bacteria.. The inhibitory effect on gastric acid secretion induced by antral distention was absent in H. pylori-infected patients irrespective of whether or not they had duodenal ulcer disease. The inhibitory mechanism was restituted in 8 of 10 patients within 9 months after successful eradication of H. pylori infection. Similar results were obtained in studies on gastrin release.. H. pylori infection blocks normal, physiological inhibitory mechanisms from the antrum to both the gastrin cells and to the parietal cell region, resulting in increased gastrin release and impaired inhibition of gastric acid secretion, which will probably lead to an increased duodenal acid load as a general prerequisite for the development of duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Dilatation; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Peptides; Pyloric Antrum; Stomach Diseases

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric

Helicobacter pylori (Hp) infection is known to cause several gastroduodenal diseases. In patients with non-ulcer dyspepsia, we assessed the link between Hp infection and gastric mucosal inflammation, as well as the influence of Hp and inflammation on the serum levels of anti-Hp antibodies (IgG), pepsinogen A (PGA), pepsinogen C (PGC), and gastrin.. Entering the study were 221 patients with non-ulcer dyspepsia, all of whom underwent upper gastrointestinal endoscopy.. Of the 221 patients investigated, 135 (61%) were Hp positive. The higher the bacterial load, the worse the associated gastritis, the gastric antrum and body being considered. All of the serological indices studied were found to be influenced by gastritis. Serum IgG satisfactorily discriminated between Hp-positive and Hp-negative subjects, with a sensitivity of 84% and a specificity of 86%. PGC, PGA, and gastrin were less accurate. Only PGC only found to be correlated with Hp load. The product of IgG and PGC improved the diagnostic accuracy of IgG alone.. Hp infection, frequently found in patients with non-ulcer dyspepsia, is associated with gastric mucosal inflammation; of the indices studied, serum IgG and PGC most accurately indicated Hp infection, and their product may be proposed as an aid in diagnosing Hp infection in dyspeptic patients.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogens; Serologic Tests

To evaluate the association of both Helicobacter pylori (Hp) infection and advancing age with increased prevalence of atrophic gastritis.. Two hundred and thirty-eight subjects who had no esophagitis, peptic ulcers, or malignancies in the upper gastrointestinal tract were divided into three groups according to age: group A, < 30 yr; group B, 30-49 yr; group C, > or = 50 yr. Two biopsy specimens were obtained from the lesser curvature of the antrum and two from the anterior and posterior walls of the fundus to assess the degree of gastritis and histological evidence of Hp infection. Hp infection was evaluated by Giemsa staining and serum IgG antibodies. Serum gastrin (SG) and pepsinogen (PG) were determined by radioimmunoassay.. In all age groups, the prevalence of atrophic gastritis was significantly more common in subjects with evidence of Hp infection. In Hp-positive subjects, the prevalence of atrophic gastritis increased with advancing age. Atrophic gastritis was extremely rare, regardless of age, in Hp-uninfected patients. SG increased, and PG I and the PG I:II ratio decreased with age in Hp-positive subjects. This trend was not apparent in Hp-negative subjects.. Our results suggest that Hp infection is a stronger predictor than advancing age for atrophic gastritis.

Topics: Adult; Aging; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Prevalence; Radioimmunoassay; Risk Factors

To determine whether ferrets naturally infected with Helicobacter mustelae were hypergastrinemic, compared with ferrets that were specific-pathogen-free (SPF) for H mustelae.. Plasma gastrin concentrations in H mustelae-infected and SPF ferrets were measured at 3 time points and compared to determine whether H mustelae was associated with hypergastrinemia.. 21 H mustelae-infected ferrets and 10 SPF ferrets.. The H mustelae status of the ferrets was confirmed prior to commencement of the study. Gastric endoscopy was used to obtain gastric mucosal pinch biopsy specimens that were processed for rapid-urease assay, microaerophilic culturing, and histologic evaluation. Plasma gastrin concentrations were determined at 3 time points: baseline after a 12-hour nonfeeding period, and 30 and 60 minutes after oral administration of a standardized meal. Gastrin was measured by radioimmunoassay.. The results for the H mustelae-infected group (mean +/- SEM pg/ml) were: baseline, 54.4 +/- 2.56; 30 minutes, 94.5 +/- 6.05; and 60 minutes, 82.6 +/- 5.73. The SPF group results were: baseline, 55.8 +/- 7.35; 30 minutes, 80.8 +/- 5.77; and 60 minutes, 59.7 +/- 4.95. There was a significant (P < 0.01) difference at the 60-minute time point between the 2 groups of animals. The H mustelae group had a 17% higher mean gastrin value at 30 minutes.. Helicobacter mustelae is associated with hypergastrinemia in ferrets.. Helicobacter-induced hypergastrinemia may be related to the pathogenesis of peptic ulcer disease in ferrets.

Topics: Animals; Biopsy; Ferrets; Gastric Mucosa; Gastrins; Helicobacter; Helicobacter Infections; Peptic Ulcer; Radioimmunoassay; Specific Pathogen-Free Organisms

To evaluate the clinical usefulness of Pepsinogen A (PGA) and C (PGC), PGA/PGC ratio, gastrin, and specific IgG anti-HP antibodies (anti-HP Ab) in monitoring the effect of cure for Helicobacter pylori (HP) infection in older people.. We studied the changes in serum parameters (PGA, PGC, PGA/PGC ratio, gastrin and anti-HP Ab) in older patients before and 2 months after stopping therapy for the cure of HP infection.. Eighty-eight older patients (M = 43, F = 45, mean age = 73.3, range = 60-89) with chronic gastritis (42), gastric ulcer (14) or duodenal ulcer (32) were found HP-positive by histology of gastric antral and body biopsies and the rapid urease test.. Two different associations of antibiotics and antiulcer drugs (omeprazole, metronidazole, azithromycin, or clarithromycin) for 2-4 weeks.. At the beginning of the study and 2 months after treatment withdrawal, the subjects were studied by upper G.I. endoscopy with at least two antral and two body gastric biopsies (Giemsa stain and rapid urease test for HP); serum PGA (RIA method, microgram/mL), PGC (RIA method, microgram/mL), PGA/PGC ratio, gastrin (RIA method, picogr/mL), and anti-HP Ab (ELISA method, Biolife, MU/mL) were also determined. Statistical analysis was based on either the Wilcoxon test, for paired data, the chi-square test, the Kruskal Wallis test, or the Mann-Whitney test for unpaired data. The choice of the best cut-off value in the different parameters was performed by receiver operating characteristics curves (ROC) and by Youden index. The correlation between HP density in the gastric mucosa and gastritis activity was verified by Spearman rank correlation test.. After therapy, 56/88 patients proved HP-negative (HP-eradicated: M = 30, F = 26, mean age = 73.0, range = 60-87 years), whereas 32/88 were not cured (HP-persistent: M = 13, F = 19, mean age = 73.0, range = 60-89 years). After therapy, in HP-eradicated cases, a statistically significant change was found in anti-HP Ab (75.23 +/- 8.94 vs 47.32 +/- 5.26, P < .001), PGC (21.58 +/- 1.97 vs 14.34 +/- 1.75, P < .001), and PGA/PGC ratio (8.46 +/- 0.68 vs 11.54 +/- 0.89, P < .001), but not in PGA and gastrin. On the other hand, in HP-persistent cases, anti-HP Ab, PGA, PGC, PGA/ PGC ratio and gastrin did not change after therapy. The sensitivity and specificity were, respectively, 0.62 and 0.56 for anti-HP Ab and 0.75 and 0.56 for the PGA/PGC ratio, which demonstrated the best diagnostic accuracy (68%).. The eradication of HP from the stomach of older patients induces a rapid and significant decrease in serum levels of IgG anti-HP antibodies and PGC, with an increase in PGA/PGC ratio but not in gastrin. Unchanged serum levels of IgG anti-HP antibodies, PGC, and PGA/PGC ratio 2 months after completing HP eradication therapy are indicative of ongoing HP infection. The PGA/PGC ratio showed the best diagnostic accuracy among serum measures tested.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Ulcer Agents; Antibodies, Bacterial; Drug Monitoring; Drug Therapy, Combination; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Pepsinogens; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome

Chronic haemodialysis (HD) patients frequently suffer from dyspeptic symptoms and hypergastrinaemia is a common finding in these patients. Helicobacter pylori (H. pylori) infection is associated with dyspepsia and hypergastrinaemia.. The aim of this study was to determine whether H. pylori is frequently found in HD patients and to explore the relationship of H. pylori with dyspeptic symptoms and/or hypergastrinaemia in these patients. Serum H. pylori specific IgG were measured by an in-house enzyme-linked immunosorbent assay (sensitivity and specificity is 97% and 91% respectively) in 103 chronic HD patients. The patients (53 M, 50 F, mean age f60 +/- 13 years) completed a questionnaire exploring the type, frequency and intensity of dyspeptic symptoms. Fasting plasma gastrin levels were also measured. Serum and plasma samples from 103 hospital patients matched for age, sex and dyspepsia were use as controls.. There was no significant difference in terms of serum H. pylori IgG between HD patients and controls (0.977 +/- 0.295 vs 1.046 +/- 0.306 OD respectively). The prevalence of subjects with positive serology was relatively high in both groups, but did not differ between HD patients (73%) and controls (78%). Dyspepsia was reported in 72 (70%) cases. There was no relationship between presence (and grading) of dyspepsia or type of dyspeptic symptoms and H. pylori serology. In the HD group, patients seropositive for H pylori had a significantly higher gastrinaemia than those who were seronegative: 598 +/- 413 ng/ml vs 309 +/- 252 ng/ml (P < 0.0001). The relationship between seropositivity for H. pylori and hypergastrinaemia was significant (P = 0.00038), after adjustment by multiple regression analysis for sex, age, smoking, alcohol, months on dialysis, renal function, drugs, and dyspepsia.. Data of this study suggest that H. pylori may play a role in contributing to hypergastrinaemia of HD patients.

Topics: Dyspepsia; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Regression Analysis; Renal Dialysis

To study basal gastrin levels in duodenal ulcer patients and in those with normal endoscopy, according to Helicobacter pylori infection.. Eighty-four duodenal ulcer patients and 164 with normal endoscopy were studied. Biopsy specimens were taken from gastric antrum and body, and investigated for microbiology (Gram stain and culture) and histology (hematoxilin-eosin stain). Basal gastrin levels were measured (RIA).. In duodenal ulcer patients the percentage of chronic gastritis was higher (p < 0.001) than in patients with normal endoscopy without H. pylori infection, and similar to patients infected by H. pylori. In patients with normal endoscopy (n = 164), those infected with H. pylori (n = 115) had higher (p = 0.02) gastrin levels (mean +/- SD) than non-infected (64 +/- 34 vs 51 +/- 14 pg/ml) and similar to duodenal ulcer patients (62 +/- 20 pg/ml). In the multiple regression model analysis H. pylori infection was the only variable which correlated with gastrin levels (regression coefficient 9.48 [SE = 4.59]; multiple correlation coefficient 0.22 [p = 0.008]). Additional variables (age, sex, duodenal ulcer) were not correlated with gastrin levels. Patients with chronic gastritis had higher gastrin levels (p < 0.01) than those with normal histologic mucosa.. In patients with normal endoscopy, those infected with H. pylori had significantly higher basal gastrin levels than non-infected individuals, and similar to duodenal ulcer patients. Therefore, hypergastrinaemia seems to be associated with H. pylori infection, and is not a distinctive feature of duodenal ulcer disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Chronic Disease; Duodenal Ulcer; Endoscopy; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Regression Analysis; Stomach

Age and close living conditions are known to be risk factors for the acquisition of Helicobacter pylori (HP) infection. It is unknown whether institutionalization of asymptomatic, elderly subjects is an additional risk factor and whether gastric function and nutritional status are affected by the HP infection. The study sample comprised 102 subjects over 65 years of age: 52 living in a nursing home and 50 at home. No subject had symptoms or previous pathology related to the upper digestive tract. In all subjects, serum levels of specific anti-HP antibodies were determined. Gastric function was evaluated by levels of pepsinogen A (PGA), pepsinogen C (PGC) and gastrin. The nutritional status of the subject was evaluated by measuring: albumin, haemoglobin, iron, ferritin, transferrin, vitamin B12, and folic acid in blood, and body mass index and mid-arm muscle area. The prevalence of anti-HP antibodies was 86.5% in institutionalized subjects (men: 100%; women:76.6%, p <0.05) and 82.0% in subjects living at home (men:86.3%; women:76.3%). No differences between the two groups were observed in levels of serum anti-HP antibodies and PGC was identified. In neither group were differences observed between serum positive (HP + ve) and negative (HP - ve) subjects with respect to the biohumoral and anthropometric indices of nutritional status. We conclude: (1) the seroprevalence of the HP infection was high (82-86%) in asymptomatic elderly patients living either at home or in an institution; (2) the presence of specific IgG anti-HP antibodies in asymptomatic elderly individuals, at home or in a nursing home, was not associated with changes in PGA levels in institutionalized subjects; (3) nutritional indices were not influenced by the presence of anti-HP antibodies.

Topics: Aged; Aged, 80 and over; Female; Gastrins; Gastritis; Geriatric Assessment; Helicobacter Infections; Helicobacter pylori; Home Nursing; Homes for the Aged; Humans; Italy; Male; Nursing Homes; Nutritional Status; Pepsinogens; Reference Values

The etiopathogenic relationship of Helicobacter pylori (HP) infection to chronic active antrumgastritis and peptic ulcer disease has been confirmed by a number of studies. The key role in the development of peptic lesions belongs to hypergastrinemia. This is supposed to be related to ammonium synthesis in the antral area influenced (promoted by HP and resulting in interruption) weakening of the negative feedback mechanism maintaining intraluminal acidity.. In our present study we focus our attention to the effectiveness of triple antimicrobial therapy in HP positive patients with chronic active antrumgastritis residing in the lowering of the level of serum gastrin.. There was a group of 15 patients in our current study with HP positivity as well as chronic active antrumgastritis documented by endoscopy, histology, microbiology and serology respectively. Endoscopical and histological findings were classified according to "The Sydney System". The whole group was evaluated on an ambulatory basis, those with active ulcer, endocrinopathy and biliary tract disorders were excluded. The basal level of serum gastrin was evaluated by RIA-test-gastrin before and after successful antimicrobial therapy.. In our group of 15 patients with HP infection in coexistence with chronic active antrumgastritis we have found a significant decrease in the basal level of serum gastrin (p = 0,01) after successful therapy.. The decrease in the basal level of serum gastrin after eradication of HP confirms the importance of HP infection in the pathogenesis of peptic lesions in stomach and duodenum. We consider the antimicrobial therapy in chronic active antrumgastritis in HP positive patients to be a fully indicated therapeutic approach. (Tab. 1, Fig. 1, Ref. 10.).

Topics: Adult; Amoxicillin; Drug Therapy, Combination; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged

The fact that H. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whether H. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients with H. pylori gastritis before and one month after the eradication therapy and also in 15 H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients with H. pylori gastritis before the eradication were significantly (P < 0.05) higher than those in the H. pylori-negative controls. After the eradication of H. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P < 0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P < 0.001). These results suggest that H. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.

Topics: Adult; Blood Glucose; Eating; Female; Gastrins; Gastritis; Glucose Tolerance Test; Helicobacter Infections; Helicobacter pylori; Humans; Insulin; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Biomarkers; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

Helicobacter pylori causes chronic gastritis in all infected individuals and thus may be a risk factor for the ultimate development of trophic gastritis and gastric cancer. The serum levels of pepsinogen A, pepsinogen C and gastrin can be used as markers for both non-atrophic and atrophic gastritis.. We determined the serum levels of gastrin, pepsinogen A and pepsinogen C and the pepsinogen A/C ratio in 150 H. pylori-negative and 186 H. pylori-positive individuals.. The H. pylori infected patients had significantly higher serum levels of pepsinogen A, pepsinogen C and gastrin and a significantly lower pepsinogen A/C ratio. In the non-infected patients, none of the respective serum values changed with increasing age. In contrast, in the infected patients, the pepsinogen A level and pepsinogen A/C ratio decreased significantly with increasing age.. H. pylori infection increases serum levels of pepsinogen A, pepsinogen C and gastrin and decreases the pepsinogen A/C ratio. In infected subjects, levels of pepsinogen A and the pepsinogen A/C ratio decrease with ageing. These findings support the concept of H. pylori as a risk factor for the development of atrophic gastritis.

Topics: Adolescent; Adult; Age Factors; Aged; Biomarkers; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Pepsinogens; Risk Factors

H. pylori infection, both in normal healthy subjects and patients with duodenal ulcer, results in modest elevations of serum gastrin concentrations in the fasting state and quite substantial elevations after a meal or gastrin releasing peptide (GRP) stimulation. Cure of the infection leads to normalization of gastrin homeostasis. Acid secretion in response to a submaximal infusion of GRP is three-fold higher in H. pylori-infected normal subjects and six-fold higher in DU patients than in non-infected controls. These changes also normalize after cure of the infection. H. pylori infection appears to lead to increased basal acid output in some patients with duodenal ulcer while effects on peak acid output to pentagastrin remain under debate. With the possible exception of peak acid output, the abnormalities of gastrin and acid secretion reported for patients with duodenal ulcer are largely a result of infection with H. pylori.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric; Somatostatin

The aim of our study was to demonstrate the effect of Helicobacter pylori eradication on basal and stimulated serum gastrin levels and gastric acid output 5 months after therapy of patients with duodenal ulcer. Thirty-two patients (24 men and eight women with a mean age of 45 years) who had had endoscopy and were diagnosed as having duodenal ulcer entered the study. In all patients three biopsy specimens were taken from the duodenal bulb, gastric antrum, body, and fundus. These specimens were then sent for microbiological and histological examination. Triple therapy consisting of bismuth, metronidazole, and tetracycline was administered. Endoscopy was repeated 1 and 5 months after therapy, and biopsy specimens were again taken from the gastric antrum and body. Before treatment, serum samples were taken to measure basal and stimulated (90 min) gastrin levels after ingestion of two beef cubes, and basal and stimulated acid outputs (after pentagastrin) were studied. Measurements of gastrin and gastric acid output were repeated 5 months after therapy. H. pylori was eradicated in 26 patients (81.3%). Basal gastrin levels (mean +/- SD) at diagnosis and after eradication were 44 +/- 12 and 35.8 +/- 2 pg/ml, respectively (p < 0.05). Similarly, stimulated gastrin levels (integrated values) decreased from 5,303 +/- 1,526 pg/ml/min before therapy to 3,779 +/- 1,204 pg/ml/min after eradication (p < 0.001). However, basal (4.9 +/- 4mEq/h) and stimulated (28.5 +/- 10mEq/h) acid output did not vary after eradication (3.9 +/- 4 mEq/h and 26.2 +/- 12 mEq/h, respectively). We conclude that basal and stimulated gastric acid output are not changed by H. pylori eradication in duodenal ulcer patients 5 months after therapy, in spite of its association with a significant decrease in basal and stimulated gastrin levels.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Time Factors

The eradication of Helicobacter pylori (Hp) is known to reduce the recurrence rate of duodenal ulcer (DU) to similar extent as gastrectomy but it is not clear what is the prevalence of Hp in DU patients after surgical interventions such as gastrectomy or vagotomy. The purpose of this study was to evaluate the influence of gastrectomy or truncal vagotomy with pyloroplasty on the prevalence of Hp in 51 DU patients just before and 6-8 months after these procedures. Using C14-urea breath test (UTB), rapid CLO-test and histology of the biopsy samples of gastric mucosa obtained during gastroscopy, the Hp was detected in all DU subjects submitted to operation. Following distal gastric resection (antrectomy) with Billroth II anastomosis (N = 32) due to an ulcer resistance to conservative therapy, peptic ulceration was not observed during 6-8 months in any of the examined subjects and the Hp was only rarely observed (only in 3 out of 32 operated patients). Histologically, in antral biopsies taken prior to surgery, all DU patients presented chronic active gastritis. After the surgery, the absence of Hp was confirmed also by histology. Histological evaluation of gastrectomy stump biopsies revealed typical chronic gastritis with concomitant foveolar hyperplasia and focal gland dilation. Following selective vagotomy and pyloroplasty (N = 19), the scarring of duodenal bulb (without active ulcer) was seen in 4 out of 19 operated patients but the Hp was detected in all (100%) cases. Gastric biopsies prior and after vagotomy revealed chronic active gastritis associated with Hp infection. Basal plasma gastrin was reduced after gastrectomy by about 30% and basal and maximal pentagastrin-induced acid secretion was decreased by about 60% and 70%, respectively. Vagotomy did not reduce activity of the mucosal inflammation and the incidence of Hp. Basal plasma gastrin level was increased by about 60%, while basal and pentagastrin induced acid secretion was decreased by 25% and 40%, respectively. Because of the high ulcer recurrence rate after vagotomy as opposed to low recurrence after gastrectomy, it is reasonable to conclude that (1) the disappearance of Hp and reduction in plasma gastrin and gastric acid secretion were probably the major factors responsible for the high efficacy of gastrectomy in prevention of ulcer recurrence, (2) in non-complicated DU, gastric surgery should be avoided and replaced by conservative anti-Hp therapy involving both antisecretory or bismuth agen

Topics: Adult; Breath Tests; Duodenal Ulcer; Gastrectomy; Gastric Stump; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Urea; Vagotomy

Gastrin circulates at higher than normal concentrations in patients with end-stage renal failure (ESRF). However, it remains unclear which forms of gastrin are elevated and whether there is also an alteration in the secretory profile after stimulation. In the present study all processed and partially processed forms of circulating gastrin were measured in plasma before and after meal stimulation in ESRF patients and control subjects. Since Helicobacter pylori (HP) infection affects gastrin secretion, HP status was determined. Fasting gastrin-amide (36 +/- 8 pmol/L), gastrin-Gly (55 +/- 16 pmol/L), and total gastrin (218 +/- 32 pmol/L) measured in ESRF/HP-patients were all significantly greater than those in the control group (10 +/- 1, 15 +/- 3, and 17 +/- 2 pmol/L, respectively; P < 0.01). Plasma gastrin-amide (126 +/- 67 pmol/L) and total gastrin (397 +/- 164 pmol/L) were highest in the ESRF/HP+ patients. The proportion of nonamidated gastrin products was 4-fold higher in ESRF patients than in control subjects, suggesting structure-specific changes in gastrin secretion and metabolism, and this was confirmed by chromatography. The meal-stimulated increments in control/HP- and ESRF/HP-groups were similar. However, the ESRF/HP+ group had a markedly potentiated gastrin response. Fasting plasma somatostatin, an inhibitor of gastrin secretion, was also measured and was significantly lower in the ESRF patients than that in the control group. These studies show that the hypergastrinemia associated with renal failure has been underestimated. This is because only amidated products were measured. The potentiated gastrin meal response in ESRF attributed previously to changes in gastrin metabolism are in part explained by the effect of HP infection. The observed diminished somatostatin response suggests that the increase in circulating gastrin in ESRF is the result of loss of inhibition of secretion as well as decreased metabolism. As both amidated and nonamidated gastrin are now considered to have trophic and secretory effects, these findings may explain the gastrointestinal tract hypertrophy often associated with ESRF.

Topics: Adult; Aged; Antibodies, Bacterial; Fasting; Food; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Middle Aged

Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion.. To investigate the role of Helicobacter pylori in AGCH.. Twelve AGCH patients and eight H. pyloripositive non-hypergastrinaemic duodenal ulcer patients were compared.. Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.. Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori-positive duodenal ulcer patients (P < 0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58-192.4, vs. 86.1, range 49-184; P < 0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6-5.6, vs. 3.3, range 1.9-4.3; P < 0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%: P < 0.05) decrease of G cell count and an increase (12%; P < 0.05) of D cell count.. The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.

Topics: Adolescent; Adult; Bombesin; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum

To determine the relationship between Helicobacter pylori infection and parietal cell mass and functional status in 10 patients with duodenal ulcer and 22 patients with functional dyspepsia.. We measured pentagastrin-stimulated acid secretion, determined the activity status of parietal cells on the basis of ultrastructural morphological features, and measured parietal cell mass and canalicular area with computerized densitometric morphometry. The number of antral G cells per square millimeter of mucosa was estimated inmunohistochemically, and basal serum gastrinemia was determined.. In patients with duodenal ulcer, acid secretion, the percentage of activated parietal cells, and canalicular area were increased, but there was no difference between patients and dyspeptic controls in parietal cell mass. Helicobacter pylori infection did not modify these parameters, although it was associated with basal hypergastrinemia.. In patients with duodenal ulcer, parietal cells display functional hyperactivity, which causes hypersecretion of acid; this effect is apparently unrelated to Helicobacter pylori infection.

Topics: Case-Control Studies; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter; Helicobacter Infections; Humans; Male; Microscopy, Electron; Middle Aged; Parietal Cells, Gastric

There is evidence that gastric Helicobacter pylori (Hp) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-alpha) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-alpha pretreatment (100 ng mL-1) of canine G cells significantly increased both basal (by 89%: P < 0.01) and bombesin-stimulated (by 39% P < 0.05) gastrin release. A similar pattern of increase was seen following TNF-alpha (20 ng mL-1) pretreatment of human antral fragments: basal gastrin release was increased by 38% (P < 0.05) and bombesin-stimulated by 26% (P < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-alpha provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.

Topics: Animals; Cells, Cultured; Dogs; Duodenal Ulcer; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Pyloric Antrum; Tumor Necrosis Factor-alpha

To explore the state of the gastric mucosa in individuals with and without peptic ulcer disease from populations with contrasting peptic ulcer risks.. Pepsinogen A, pepsinogen C, gastrin and Helicobacter pylori antibodies are serological markers of gastritis. A decreasing pepsinogen A-C ratio and pepsinogen A level are known to reflect an increasing severity of corpus atrophy, whereas gastrin levels decrease with an increasing severity of antral atrophy when corpus atrophy is present. Helicobacter pylori-positive men, with and without a peptic ulcer history, were the focus of the study.. In 190 Japanese and 425 Dutch male employees, of similar age (mean age 49 years) and level of occupation, fasting serum samples were analysed in the same laboratory for IgG antibodies to H. pylori, pepsinogen A, pepsinogen C and gastrin. Any history of ulcer disease was verified through case notes.. The H. pylori seropositivity rate was higher in the Japanese men (72%) than in the Dutch (33%). There were 23 (12%) Japanese and 18 (4%) Dutch men with a verified duodenal ulcer history, and 14 (7%) Japanese and two (0.5%) Dutch men with a verified gastric ulcer history. H. pylori-positive men with a duodenal ulcer history differed from the H. pylori-positive men without an ulcer history in that they had a significantly higher mean pepsinogen A level (64 and 51 micrograms/l in Japanese men and 71 and 57 micrograms/l in Dutch men) and also a higher mean pepsinogen A-C ratio, whereas pepsinogen C and gastrin levels did not differ. In H. pylori-positive gastric ulcer patients the mean gastrin level was significantly lower than in H. pylori-positive men without ulcer disease (17 and 37 pmol/l in Japanese men), whereas pepsinogen levels were similar.. This study suggests that in H. pylori-positive duodenal ulcer patients there is less mucosal atrophy of the corpus and in H. pylori-positive gastric ulcer patients more atrophy of the antrum than in H. pylori-positive individuals without peptic ulcer disease.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Case-Control Studies; Chi-Square Distribution; Duodenal Ulcer; Employment; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Japan; Male; Middle Aged; Netherlands; Pepsinogens; Prevalence; Stomach Ulcer

Medical treatment for Helicobacter pylori (Hp) infection is now recommended in several types of gastroduodenal disease, and its success is usually monitored by hystology. The end-points of our work were to identify the most suitable serum index of Hp eradication among pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, gastrin, and IgG anti-Hp (IGG). We studied a total of 289 Hp positive (Giemsa staining) patients, who were treated with 40 mg/day omeprazole (140 cases) or with 480 mg/day bismuth subsalicylate (149 cases) for 4 weeks. All the patients also received 1 g/day metronidazole + 2 g/day amoxycillin for the first 2 weeks of treatment. Two months after the end of therapy, the patient underwent a second endoscopy and Hp histological assessment: the infection was eradicated in 192 and still present in the remaining 97 subjects. Gastrin, PGA, PGC, and IGG were measured before and after therapy. All indices significantly decreased after therapy in eradicated patients, while PGA and gastrin significantly decreased after therapy in both eradicated and noneradicated patients, although in the latter group the variations were less pronounced. We calculated the per cent decrease of the studied indices. PGC, with a decrease of more than 25%, was found to be the most accurate biochemical index. Variation in PGC levels before and after treatment were correlated with corresponding variations in Hp bacterial load. In conclusion, between the different biochemical parameters evaluated, PGC showed the highest clinical efficiency.

Topics: Adult; Aged; Anti-Ulcer Agents; Antibodies, Bacterial; Biomarkers; Data Interpretation, Statistical; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Omeprazole; Pepsinogens; Regression Analysis

The effects of acid, infectious (Helicobacter pylori) and neuroendocrine factors on the course and outcome of chronic duodenitis were studied in 57 patients aged 15-35 years. Within 5-year follow-up ulcer emerged in 26% of duodenitis patients. Ulceration occurred as a result of high acid production in the basal and stimulated phases, contamination of pyloric-antral mucosa with Helicobacter pylori, unbalance of serum hormones T4, TTH, FSH, ACTH. In risk of ulcerogenesis there were psychological shifts with appearance of pathological reaction to the disease. Consideration of pathogenetic specificity of different duodenitis forms and basing on objective and subjective criteria allow identification of ulcer risk group and early start of optimal therapy.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Chronic Disease; Duodenal Ulcer; Duodenitis; Follicle Stimulating Hormone; Follow-Up Studies; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Risk Factors; Stomach; Thyroid Hormones; Time Factors

It has been shown previously that antisecretory response of famotidine is altered in patients with renal failure. To evaluate the underlying mechanism(s) of this clinical observation we obtained biopsy specimens of fundic mucosa from 3 groups of patients with variable renal function (group 1 normal renal function (n = 16); group 2 chronic renal failure (n = 16), CLCR > or = 5 < 90 ml/min; group 3 hemodialysis therapy (n = 16)) (matched for age, sex, and Helicobacter pylori (Hp) status. In the homogenized samples adenylate cyclase (AC) activity was assessed and the influence of uremia on this second messenger system involved in gastric acid secretion was tested. AC activity was measured as the formation of cAMP, which was determined by RIA. The mean basal AC activity was 150 in group 1, 190 in group 2, and 120 pmol cAMP/mg protein/20 min in group 3. There was a dose-dependent stimulation by histamine (1 microM-1 mM). Emax of cAMP formation ranged between 230 and 403 pmol cAMP/mg protein/20 min and EC50 between 5.9 and 20.1 microM histamine, dependent on Hp status. Histamine-stimulated AC activation was reduced to about 50% by 0.1 mM famotidine. The sensitivity of AC to histamine seems to decrease in patients undergoing hemodialysis. Similarly, the colonization with Hp may result in decreased maximal response of the AC system towards histamine.

Topics: Adenylyl Cyclases; Anti-Ulcer Agents; Cyclic AMP; Famotidine; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Middle Aged; Sodium Fluoride; Uremia

Omeprazole treatment produces lower intragastric pH values 4 weeks after cure of Helicobacter pylori infection than before. We therefore investigated the effect of healing H. pylori-associated gastritis on intragastric pH in the presence and in the absence of omeprazole therapy.. Before and on day 8 of omeprazole, 20 mg once daily, 24-h intragastric pH-recordings were performed in 14 subjects with H. pylori infection and repeated 4 and 52 weeks after cure of infection. Gastritis severity in corpus and antrum was graded by using a modified Sydney system.. In the absence of omeprazole administration, median 24-h pH values before cure did not differ from those 4 and 52 weeks after cure. On day 8 of omeprazole administration, 24-h pH values were much higher before cure (median, 5.15; 95% confidence interval (CI), 4.3-6.0) than 4 weeks (3.6; 2.1-4.4; P < 0.001) and 52 weeks after cure (3.0; 2.1-4.4; P < 0.001). The activity of corpus and antral gastritis was not associated with the magnitude of H+ change induced by omeprazole.. The increased pH produced by omeprazole during H. pylori infection is likely to be due to neutralizing substances produced by H. pylori and not to H. pylori-induced gastritis.

Topics: Adult; Anti-Ulcer Agents; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Omeprazole; Radioimmunoassay

We have recently shown that antigastric autoantibodies occur in a considerable number of Helicobacter pylori (H. pylori) infected patients. Particularly, autoantibodies to canaliculi within parietal cells of human gastric body mucosa are strongly associated with H. pylori gastritis. In this study we analyzed the implications of this type of autoantibody for histological and for clinical parameters of the disease. 126 patients with upper abdominal complaints were included in our study. Several histological and clinical parameters were evaluated. Presence of anticanalicular autoantibodies is significantly correlated with a higher degree of gastritis in the body mucosa, with atrophic changes in the gastric mucosa, with elevated fasting gastrin levels and a decreased pepsinogen I/pepsinogen II ratio. These data indicate, that the host's autoimmune response to canaliculi of parietal cells is of relevance for the pathogenesis and outcome of H. pylori gastritis.

Topics: Atrophy; Autoantibodies; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens

Patients with the digestive form of chronic Chagas' disease exhibit abnormally increased gastrin release, possibly caused by antral gastrin cell (G cell) hyperfunction. In order to identify the mechanisms underlying this abnormality, we used an immunohistochemical method to assess the population of antral somatostatin-producing cells (D cells) in chagasic patients, since somatostatin is known to be the main inhibitory factor of gastrin secretion. Samples (N = 11) of endoscopic antral biopsies taken from 16 Chagas' disease patients and 13 control subjects were studied. Antral D and G cell populations were determined by an immunohistochemical technique using highly specific antibodies against somatostatin and gastrin. There was no significant difference between Chagas' disease and control groups regarding G cell population (number of cells/mm reported as median (range): 70.0 (23.7-247.0) vs 98.1 (52.7-169.4), P > 0.10). In contrast, the number of antral D cells in Chagas' disease patients was significantly lower than in controls (16.4 (6.9-54.4) vs 59.3 (29.6-113.8), P < 0.05). Chronic superficial gastritis and infection with Helicobacter pylori were more frequent in chagasic patients than in controls, but there was no demonstrable association between these factors and the reduction of the number of antral D cells. These data suggest that reduction in the number of antral somatostatin-producing cells, which should lead to reduced inhibition of gastrin cell activity, may play a role in the increased gastrin secretion observed in Chagas' disease patients.

Topics: Chagas Disease; Chronic Disease; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Somatostatin

The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults.. Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori, serum gastrin, and pepsinogen levels.. The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori-positive adults was significantly greater than in those who were H. pylori-negative (114.3 +/- 11.2 compared to 65.8 +/- 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001).. These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.

Topics: Adult; Aged; Antibodies, Bacterial; Atrophy; Duodenum; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Japan; Male; Metaplasia; Middle Aged; Pepsinogens

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Monitoring, Physiologic; Proglumide; Somatostatin

Among the various themes related to Helicobacter pylori (HP) which is still a subject of discussion, there is the possible influence of this bacterium on gastric secretory physiology. In the present study, an evaluation has been carried out of stimulated gastrinemia, stimulated acid secretion and total peptic activity in gastric juice in the course of a paradigmatic condition, as autonomous chronic gastritis, in order to reveal possible modifications induced by the HP infection. In cases of HP positive chronic superficial antral gastritis associated either with normal body-fundic mucosa or with superficial gastritis, there is a significant increase of stimulated gastrinemia in comparison to HP negative groups and controls. In the course of body-fundic atrophic and preatrophic chronic gastritis associated either with antral superficial chronic gastritis or with antral atrophic gastritis, there are no statistically significant differences between HP positive and HP negative subjects. As regards acid and pepsin secretion no significant differences emerge in any group between HP positive and HP negative subjects. In the HP positive subjects with antral superficial gastritis and higher gastrin values the study of acid and pepsin secretion has yielded no significant variations. From the results of this study it emerges how gastric secretory parameters vary exclusively according to the histologic state of gastric mucosa. Therefore, the lesion action of HP may mainly be attributed to a direct action, rather than to substantial gastric secretory changes.

Topics: Adult; Aged; Biopsy; Chronic Disease; Female; Gastric Fundus; Gastric Juice; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Stomach

Topics: Animals; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Humans; Immunity, Mucosal; Lymphocytes; Mice; Mice, Inbred BALB C; Phenotype

The pathogenic role played by Helicobacter pylori in gastric mucosal defense was investigated in Japanese monkeys infected with H. pylori. Serum gastrin levels and ammonia concentrations in gastric juice were compared in H. pylori-infected (n = 6) and control (n = 7) groups. The gastritis score, the intracellular content of periodic acid-Schiff (PAS)-positive substance and hexosamine, and the bromodeoxyuridine (BrdU) labeling index in the gastric mucosa were compared in the two groups in the antrum and the corpus. The ammonia concentration in the gastric juice was significantly higher in the infected group (P < 0.01). The gastritis scores were significantly higher in the antrum and corpus in the infected group (P < 0.01, and P < 0.05, respectively). The content of PAS-positive substance and hexosamine was significantly decreased in the antrum of the infected group compared with that in the controls (P < 0.01, and P < 0.05, respectively), but there was no significant difference between the two groups in the corpus. The BrdU labeling indices were significantly higher in the antrum and corpus of the infected group (P < 0.01, and P < 0.01, respectively). Colonization by H. pylori injures the gastric mucosa by depressing the gastric mucosal defense factors, and, consequently, the cell kinetics are accelerated.

Topics: Ammonia; Animals; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Hexosamines; Immunity, Innate; Macaca; Periodic Acid-Schiff Reaction; Pyloric Antrum

The risk factors associated with refractory peptic ulcers are still undefined. The purpose of this study was to identify these factors in a multivariate context.. Clinical and endoscopic findings as well as Helicobacter pylori status, gastric secretion analysis, serum gastrin levels, nonsteroidal anti-inflammatory drug (NSAID) use, and objective testing of aspirin use by platelet cyclooxygenase activity were studied in 60 consecutive refractory patients with peptic ulcer and 54 matched nonrefractory controls.. Refractory patients had a longer history of symptomatic ulcer, had an earlier onset, had more frequent relapses, and smoked more during the episode of refractoriness. H. pylori status was similar in both groups, but H. pylori eradication in a subset of refractory patients (23 of 26) was highly effective in healing these ulcers (14 of 23). Globally, NSAID-analgesic abuse (including > 1500 mg/day paracetamol) was present in 40% of refractory patients (P < 0.006). Objective testing showed that 43.7% of NSAID use was surreptitious. Multivariate logistic regression analysis identified only NSAID and analgesic abuse and the number of relapses as individually affecting refractoriness.. NSAID and analgesic abuse is the single most important exogenous factor associated with refractoriness. H. pylori infection emerges as an important intrinsic factor, but almost a quarter of refractory patients cannot be linked to either NSAID use or H. pylori infection.

Topics: Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Platelets; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Prostaglandin-Endoperoxide Synthases; Regression Analysis; Risk Factors; Smoking; Substance-Related Disorders

The relationship between gastrin and the development of colorectal carcinoma (CRC) remains controversial. Problems with previous studies include failure to measure all forms of gastrin, lack of comparison between stored and secreted gastrin, and not controlling for Helicobacter pylori infection (a known cause of hypergastrinemia). The aim of this study was to quantify progastrin and progastrin-derived peptides in the resected tumor and plasma of patients with CRC and in the antrum and plasma of normal subjects.. Four region-specific gastrin antisera were used to measure progastrin, glycine-extended gastrin, amidated gastrin, and total gastrin.. Progastrin, amidated gastrin, total gastrin, and glycine-extended gastrin were detected in 100%, 69%, 56%, and 44% of tumors, respectively (n = 32). When allowing for H. pylori infection, circulating amidated gastrin levels were not significantly elevated in patients with CRC. However, compared with control H. pylori-positive and H. pylori-negative subjects, fasting plasma total gastrin levels were increased in H. pylori-positive (5.2-fold) and H. pylori-negative (2.3-fold) patients with CRC.. Gastrin or its processing intermediates are present in a high proportion of CRCs. Nonamidated gastrin levels are elevated in the circulation of patients with CRC regardless of H. pylori status. We conclude that gastrin should continue to be assessed as a circulating or autocrine growth factor in the development of CRC.

Topics: Aged; Colorectal Neoplasms; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Protein Precursors; Pyloric Antrum

The behaviour of basal and stimulated acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months after eradication with lansoprazole plus amoxicillin and tinidazole (case group), whereas the remainder, with persistent H pylori infection, were studied before and after three and six months from ulcer healing, thus constituting the control group. In the case group, three months after eradication, fasting serum pepsinogen I fell from (mean (SEM)) 91.9 (6.9) (pretreatment) to 72.2 (5.1) ng/l and the integrated gastrin response to a meal reduced from 11,470 (1174) (pretreatment) to 8130 (608) pg/ml/h (p < 0.05). Fasting serum gastrin concentrations and maximal acid output reduced significantly only six months after eradication. In contrast, no significant change of any of these measurements was seen in the control group either at three or six months from healing compared with the pretreatment values. Gastric emptying of liquids did not change over the entire period of follow up in both study groups. In conclusion, eradication of H pylori in duodenal ulcer patients is accompanied by a rapid fall in serum pepsinogen I and plasma gastrin concentrations, whereas a slight but significant reduction of maximal acid secretion takes place later on. In contrast, gastric emptying of liquids does not seem to be influenced by H pylori status.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Helicobacter Infections; Humans; Male; Pepsinogens; Time Factors

Serological markers of gastritis, like pepsinogen A, pepsinogen C, gastrin, and Helicobacter pylori antibodies, can be used to explore the state of the gastric mucosa in populations with contrasting cancer risks. A decreasing pepsinogen A:C ratio and an increasing serum gastrin are known to reflect an increasing severity of atrophic corpus gastritis, which is a precursor of gastric cancer. In 723 subjects (without gastroduodenal surgery) from Japanese (n = 225) and Dutch (n = 498) working populations, which had a similar composition of age (mean 48 years), sex (male to female ratio 6:1), and type of occupation, fasting serum samples were analysed for IgG antibodies to H pylori, pepsinogen A, pepsinogen C, and gastrin in the same laboratory. H pylori infection was significantly more prevalent in the Japanese than in the Dutch (74.7% and 31.3%); as was a very low pepsinogen A, indicative of severe mucosal atrophy (4.4% and 1.6%). Among subjects with and without severe mucosal atrophy the H pylori seropositivity rate was similar. Between the Japanese and the Dutch there were significant differences in mean gastrin (31.8 and 13.4 pmol/l) and pepsinogen A:C ratio (1.7 and 2.9). These intercountry differences were as great for H pylori negative subjects (gastrin: 23.7 and 10.3 pmol/l, pepsinogen A:C ratio: 2.4 and 3.2) as for H pylori positive subjects (gastrin: 34.6 and 20.1 pmol/l, pepsinogen A:C ratio: 1.5 and 2.5). The intercountry difference in gastrin nearly disappeared after stratification into categories of pepsinogen A:C ratio. In conclusion, the intercountry differences in pepsinogen A:C ratio and gastrin reflect a higher prevalence of mild and severe mucosal atrophy of the corpus in the Japanese than in the Dutch, both among H pylori positive and negative subjects. Thus, these findings suggest that in the Japanese the development of atrophic gastritis is in part unrelated to H pylori.

Topics: Adult; Age Distribution; Aged; Antibodies, Bacterial; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Japan; Male; Middle Aged; Netherlands; Pepsinogens; Prevalence; Seroepidemiologic Studies

Recent studies on the role of Helicobacter pylori in the pathogenesis of duodenal ulcers have focused on the mechanism by which H. pylori infections cause exaggerated gastrin release.. We determined meal-stimulated serum gastrin concentrations and antral somatostatin content in 24 asymptomatic volunteers (6 H. pylori-infected, 18 H. pylori-uninfected). Somatostatin content was determined by radioimmunoassay in biopsy specimens obtained from the antrum.. Fasting and integrated 2-h gastrin concentrations were significantly higher in H. pylori-positive volunteers than in H. pylori-negative volunteers (fasting, 111 +/- 16.3 pmol/l versus 53.4 +/- 3.5 pmol/l; p < 0.05; integrated 2-h, 267 +/- 41.2 pmol/l versus 70.1 +/- 2.1 pmol/l; p < 0.01). Antral somatostatin content was 0.764 +/- 0.173 ng/mg and 2.931 +/- 0.414 ng/mg in H. pylori-positive and -negative volunteers, respectively (p < 0.01).. Low antral somatostatin content may cause hypergastrinemia in asymptomatic healthy volunteers, and H. pylori may contribute to the pathogenesis of duodenal ulcer, through this mechanism.

Topics: Adult; Biopsy; Duodenal Ulcer; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pyloric Antrum; Radioimmunoassay; Somatostatin

Many studies have confirmed the close association of Helicobacter pylori with duodenal ulcer (DU) in adults. However, in the subtype of DU known as 'childhood' or 'early onset DU' genetic factors seem to play a prominent role in the pathogenesis. The aim of this study was to investigate the prevalence of H. pylori in teen-age subjects with DU, gastritis, and normal mucosa and to examine the relationship of H. pylori to serum gastrin levels and gastric acid secretion.. Sixty-one teen-age subjects (24 with DU, 14 with gastritis, and 23 normal subjects) were investigated for the presence of H. pylori, antral histology, gastrin levels, basal acid output (BAO), and maximal acid output (MAO).. All 24 patients with DU and 8 of 14 with gastritis were infected with H. pylori; none of the normal subjects were infected. Mean gastritis scores and fasting serum gastrin levels were significantly higher in patients with DU or H. pylori-positive gastritis than in subjects with H. pylori-negative gastritis or normal mucosa (p < 0.05). The difference in serum gastrin levels was also significant when patients with DU were compared with those with H. pylori-positive gastritis (p < 0.05). BAO and MAO were significantly higher in patients with DU than in subjects with H. pylori-positive gastritis or normal mucosa (p < 0.05), but there was no difference between subjects with H. pylori-positive gastritis and those with normal mucosa.. H. pylori infection is associated closely with teen-age DU and gastritis and with hypergastrinemia but does not affect BAO and MAO in most infected teen-age subjects.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Prevalence; Retrospective Studies

The mechanism by which Helicobacter pylori predisposes to duodenal ulcers (DUs) remains unclear. The aim of this study was to investigate the effect of the infection on acid secretion.. Acid output was examined basally and in response to gastrin-releasing peptide (GRP) and gastrin in healthy volunteers with and without H. pylori infection and in patients with DUs before and after eradication of the infection.. Compared with H. pylori-negative healthy volunteers, patients with DUs with H. pylori had the following abnormalities of acid secretion: (1) threefold increase in basal acid output, (2) sixfold increase in acid response to GRP, (3) increased maximal acid response to exogenous gastrin, (4) increased ratio of basal acid output to maximal gastrin-stimulated output, and (5) increased ratio of maximal GRP-stimulated acid output to maximal gastrin-stimulated output. All of these abnormalities resolved fully after H. pylori eradication except for increased maximal acid output to gastrin, which was unchanged. Infected healthy volunteers showed a threefold increase in acid response to GRP that resolved after eradication of H. pylori infection.. These disturbances in acid secretion caused by H. pylori infection are consistent with impaired inhibitory control and are likely to be relevant to the mechanism by which the infection predisposes to DU.

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Metronidazole; Organometallic Compounds; Peptides; Reproducibility of Results

To evaluate the relationship between serum gastrin and Helicobacter pylori status in the antrum and body of gastric mucosa.. Fasting and post-meal serum gastrin levels were studied by radioimmunoassay in 41 patients with dyspepsia. These patients were divided into three groups depending on H pylori status ie H pylori present in both antrum and body; (A + B+; n = 13), present in antrum but not in the body; (A + B-; n = 7) and absent in both antrum and body; (A - B-; n = 21).. There was no difference in fasting or post meal serum gastrin levels between the groups A + B+ and A - B-. Serum gastrin values 20 and 40 minutes post meal were significantly higher (p < 0.05) in the group A + B+ as compared to A + B-.. Post meal serum gastrin levels are higher in patients with dyspepsia in whom Helicobacter pylori is present in the antral and body mucosa as compared to those in whom it is present in the antrum only.

Topics: Adolescent; Adult; Case-Control Studies; Dyspepsia; Fasting; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Radioimmunoassay; Time Factors

Acute Helicobacter pylori associated gastritis causes achlorhydria, a powerful stimulus to gastrin secretion. If H pylori infection is acquired primarily in early childhood, then the degree of hypergastrinaemia in seropositive children should be age dependent. Anti-Helicobacter antibodies and fasting gastrin concentrations were measured in 439 children aged 4 to 13 years attending hospital for routine day case surgery not connected with any gastrointestinal disorder. Thirty per cent were seropositive for H pylori. There was an inverse relationship between the fasting gastrin concentration and age; the mean fasting gastrin in children aged 4-5 years, 155 ng/l, was significantly higher than that seen in children aged 12-13 years, 90 ng/l. The more noticeable hypergastrinaemia seen in young children with H pylori associated gastritis may reflect achlorhydria associated with acute H pylori infection and suggests that this is primarily acquired in early childhood.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Socioeconomic Factors

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric

Topics: Data Interpretation, Statistical; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Regression Analysis

Acid secretion in response to gastrin releasing peptide (GRP) is increased six-fold in Helicobacter pylori positive duodenal ulcer (DU) patients and threefold in H pylori positive healthy volunteers, and this fully resolves after eradication of the infection. This study was undertaken to determine whether a proportion of H pylori positive patients with non-ulcer dyspepsia (NUD) have an acid secretion disturbance similar to DU patients. Basal and GRP stimulated gastrin concentrations and acid output were examined in 25 H pylori positive NUD patients and the results compared with those of 25 H pylori positive healthy volunteers, 25 H pylori negative healthy volunteers, and 25 H pylori positive DU patients. Compared with the H pylori negative healthy volunteers, GRP stimulated gastrin was increased approximately three fold in each of the three infected groups. GRP stimulated acid secretion (median, range) was higher in the H pylori positive NUD patients (29.6 mmol/h (5.2-46.5)) (p < 0.005) than in the H pylori positive healthy volunteers (19.0 (1.0-38.3)) (p < 0.001) or H pylori negative healthy volunteers (6.3 (2.8-20.9)) (p < 0.0001). The H pylori positive NUD patients, however, had lower acid output than the DU patients (39.1 (17.9-64)) (p < 0.005). These findings are consistent with approximately 50% of the NUD patients having a similar disturbance of GRP stimulated acid secretion to DU patients.

Topics: Adolescent; Adult; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stimulation, Chemical

The association between Helicobacter pylori and recurrent abdominal pain (RAP) is controversial. In this cross-sectional study, the authors aim to determine whether hypergastrinaemia causes RAP in children with H pylori gastritis. In 439 children age 4 to 13 years (mean 7.3 years) attending for nongastrointestinal day-case surgery, anti-Helicobacter immunoglobulin G (IgG) was identified in serum by an enzyme-linked immunosorbent assay (ELISA) method validated in children and fasting plasma gastrin was measured. A history of RAP was sought. One hundred twenty-seven children (29%) tested seropositive for H pylori. Fifty-one seronegative children (16.3%) and 22 seropositive children (17.3%) gave a history of RAP. The mean fasting gastrin in seronegative children was 52 ng/L compared with 117 ng/L in seropositive children (P < .001). The mean fasting gastrin in seropositive children with RAP (124 ng/L) was not significantly different from that of seropositive children without RAP (115 ng/L). The high prevalence of H pylori seropositivity in this study is at variance with other reported paediatric data from the developed world. No association between childhood H pylori gastritis, hypergastrinaemia, and RAP was found. In children with H pylori gastritis, the increase in circulating gastrin (mean 140% increase) is greater than that seen in adults (50% increase).

Topics: Abdominal Pain; Case-Control Studies; Child; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Prevalence; Recurrence; Seroepidemiologic Studies

This study was carried out to develop a scoring system for the diagnosis of gastric adenocarcinoma (GAC). A total of 686 subjects, 150 patients with GAC, 182 with gastric ulcer, 127 with duodenal ulcer, and 227 subjects with negative findings, were enrolled. Analysis of the likelihood ratio (LR) showed that patients with advanced age, ulcer in the stomach, low serum levels of pepsinogen I (PGI), low PGI x gastrin values, and low PGI/gastrin ratio were likely to have GAC. Of these indicators, the serum PGI level had the greatest weight, with a LR of 7.59 for the group with a level < 30 ng/ml. A scoring system combining serum PGI level, Helicobacter pylori seropositivity, and gastric ulcer status was derived, using a logistic regression model. This scoring system was found to be better than any one-parameter criterion for diagnosing GAC after evaluation by the area under the receiver operating characteristic curve (0.84; 95% confidence interval, 0.81-0.88) or by specificity-fixed sensitivity (sensitivity 0.82 at specificity 0.72, sensitivity 0.87 at specificity 0.66, sensitivity 0.96 at specificity 0.44). This scoring system may be potentially useful as a new model for the noninvasive diagnosis of GAC in the future.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Radioimmunoassay; Retrospective Studies; Sensitivity and Specificity; Serologic Tests; Stomach Neoplasms

The present report describes two patients with fasting hypergastrinemia, gastric acid hypersecretion, and Helicobacter pylori gastritis. Provocative testing for Zollinger-Ellison syndrome was negative and imaging studies did not demonstrate an intra-abdominal mass. Following eradication of the Helicobacter pylori infection, the fasting hypergastrinemia resolved in both patients and in one patient the gastric acid hypersecretion also resolved. The implications of this case on the differential diagnosis of Zollinger-Ellison syndrome are discussed.

Topics: Adolescent; Adult; Diagnosis, Differential; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Zollinger-Ellison Syndrome

Topics: Air; Endoscopy, Gastrointestinal; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Insufflation; Male; Middle Aged

This study evaluates the effect of eradicating Helicobacter pylori on basal and bombesin-stimulated gastric acid secretion and serum gastrin in non-ulcer dyspepsia.. Before and 1 month after an attempt to eradicate H. pylori basal and bombesin-stimulated gastric acid outputs were measured in 23 patients. H. pylori was eradicated in 15 patients (group A) but not in the other 8 (group B). Incremental gastric acid output was calculated by subtracting basal from bombesin-stimulated values.. Basal acid output increased significantly (p = 0.01) after therapy in group A (delta 1.6 +/- 0.6 mmol/h) but not in group B (delta 0.2 +/- 0.5 mmol/h). Incremental gastric acid output decreased distinctly (delta-3.9 +/- 1.4 mmol/h) after therapy in group A (p = 0.02) but not in group B (delta-2.2 +/- 1.7 mmol/h). Basal serum gastrin decreased significantly (p < 0.005) after therapy in group A (delta-9 +/- 4 pM) but not in group B (delta-1 +/- 2 pM). Integrated serum gastrin responses to bombesin decreased markedly (p < 0.001) after therapy in group A (delta-5.0 +/- 1.6 nM*60 min) but slightly in group B (delta-0.9 +/- 1.3 nM*60 min) (p < 0.05).. In patients with non-ulcer dyspepsia basal serum gastrin concentrations decrease but basal gastric acid outputs increase after eradication of H. pylori. Bombesin-induced increments in gastric acid output, however, decrease in parallel with gastrin release.

Topics: Adult; Bombesin; Dyspepsia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

To evaluate the evolution of fundic argyrophil cell density and hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in patients treated with proton pump inhibitors.. Thirty-two patients treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal ulcer were studied. No patient had a gastric ulcer. The studied parameters were serum gastrin levels, fundic argyrophil cell density, the degree of fundic argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the presence of Helicobacter pylori. The first point of the study was 7 months (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the beginning of the treatment.. Serum gastrin levels significantly increased with treatment. Fundic argyrophil cell density did not change significantly. In 3 patients (9%), serum gastrin levels were twice the normal upper limit. The highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients treated with the highest doses of proton pump inhibitors. Micronodular hyperplasia of the fundic argyrophil cells was observed in 2 patients treated with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years, respectively. Non active superficial chronic gastritis was noted in 2 patients. Serum gastrin levels were significantly correlated with cell densities.. There were minor modifications of fundic argyrophil cell population and of gastrinaemia during the study period. They were not related to chronic atrophic gastritis. However, survey is mandatory in patients treated with high dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when treatment duration is longer than 5 years.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Enzyme Inhibitors; Female; Gastric Fundus; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Time Factors

To evaluate the possible relationship between Helicobacter pylori infection and gastric carcinoma, and its precursor lesion, intestinal metaplasia, in a Japanese population.. H. pylori infection was identified by the presence of anti-H. pylori immunoglobulin (Ig)G. The frequency of H. pylori infection was compared in 109 patients with gastric carcinoma, the same number of patients with atrophic gastritis and asymptomatic controls matched for age, sex and place of birth. To study the relation between H. pylori and intestinal metaplasia, sera and gastric antral and corpus mucosal biopsies were obtained from 58 asymptomatic controls, 92 patients with chronic gastritis and 80 patients with peptic ulcer.. The presence of IgG antibody to H. pylori was significantly more frequent in those with gastric carcinoma than in asymptomatic controls (87.2 versus 74.3%; odds ratio 2.4; 95% confidence interval 1.2-4.8). The positive rates of H. pylori IgG antibody were 80.7% in patients with atrophic gastritis. Mean serum gastrin and pepsinogen II levels in H. pylori-positive patients were higher than those in H. pylori-negative patients. Serum gastrin and pepsinogen I levels were significantly higher in controls than gastric carcinoma patients (P < 0.01 and P < 0.05, respectively). Serum pepsinogen I:II ratios were significantly lower in controls than in gastric carcinoma patients (P < 0.01). Intestinal metaplasia was strongly associated with H. pylori infection, and was only found in patients with IgG antibodies to H. pylori.. These results suggest that H. pylori infection is associated with the development of gastric cancer by providing a suitable environment for carcinogenesis of the gastric mucosa, such as gastric atrophy and intestinal metaplasia.

Topics: Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Intestines; Japan; Male; Metaplasia; Pepsinogens; Stomach Neoplasms

The aim of the present study was to clarify the effects of Helicobacter pylori infection and its eradication on gastric emptying.. Out of a total of 52 patients with non-ulcerative dyspepsia, 34 H.pylori-positive patients were enrolled. Antimicrobial drugs for the eradication of H. pylori were administered to 19 out of the 34 H. pylori-positive patients. Gastric emptying was evaluated according to the acetaminophen method. Inflammatory changes and intracellular periodic acid-Schiff-positive substances in the antral mucosa were examined in biopsy specimens.. Although gastric emptying was significantly prolonged in the patients with non-ulcerative dyspepsia compared with the control group (P < 0.01), there was no difference in gastric emptying between H. pylori-positive and -negative patients, with all patients showing significantly less gastric emptying than the control group. The H. pylori eradication rate was 58% (11 out of 19) and gastric emptying improved significantly in seven patients whose infection was eradicated and whose dyspeptic symptoms disappeared. The ammonia concentration in gastric juice, inflammatory changes in the gastric mucosa and the index of periodic acid-Schiff-positive substances improved significantly when H. pylori was successfully eradicated compared with patients in whom eradication was unsuccessful. As gut hormones may affect gastroduodenal motility associated with H. pylori infection, we also studied the levels of serum gastrin and cholecystokinin. In the patients whose infection was eradicated, serum gastrin decreased significantly, but the cholecystokinin level did not change significantly, although there was a non-significant trend for cholecystokinin to increase.. These results suggest that delayed gastric emptying is partly associated with H. pylori infection and that the infection may contribute to the development of non-ulcerative dyspepsia.

Topics: Adult; Aged; Amoxicillin; Cholecystokinin; Dyspepsia; Female; Gastric Emptying; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Penicillins

The aims were to study gastrin concentrations and gastric mucosal somatostatin and gastrin concentrations in relation to the extent of gastritis in Helicobacter infection.. We measured basal serum gastrin concentrations in antral mucosal biopsy specimens and somatostatin concentrations in corpus biopsy specimens in 88 consecutive dyspeptic subjects undergoing endoscopy. These subjects were divided into three categories on the basis of histology, serology, and culture: H. pylori-positive pangastritis, H. pylori positive antral gastritis with normal body histology, and H. pylori-negative controls. Statistical evaluation was done with the Wilcoxon rank sum test.. Basal serum gastrin concentrations were significantly increased only in subjects with pangastritis and not in those with antral gastritis only, as compared with controls (mean +/- SEM: 72 +/- 7, 46 +/- 10, and 42 +/- 7 ng/l, respectively). Subjects with pangastritis or antral gastritis had significantly lower antral somatostatin concentrations than controls (mean +/- SEM: 0.80 +/- 0.07, 1.03 +/- 0.15, and 2.40 +/- 0.31 micrograms/g(protein), respectively). We also found significantly lower antral gastritis only as compared with controls (mean +/- SEM: 62 +/- 13, 78 +/- 16, and 165 +/- 25 micrograms/g(protein), respectively). In subjects with pangastritis a significantly lower concentration of somatostatin was found in the corpus biopsy specimens than in those with antral gastritis only and controls.. These results suggest that hypergastrinemia in H. pylori gastritis is not caused by antral gastritis and antral somatostatin deficiency alone but that corpus inflammation plays a key role in the origin of hypergastrinemia. Furthermore, in patients with pangastritis a corpus mucosal somatostatin deficiency was found.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin

The aim of this study was to investigate the consequence of Helicobacter pylori eradication on gastric mucosa and antral G and D-cells. Forty children, aged 5-17 years with Helicobacter pylori infection were assessed. Helicobacter pylori was detected by a urease test and identified by serological and microbiological methods. Twenty children were again assessed after the therapy (the combination of colloid bismuth subcitrate, amoxycillin and metronidazole). Gastroscopic examination was performed and at least six bioptic specimens were taken from the antrum, body and fundus. Tissue samples, processed with the paraffin method and stained with hematoxyllin and eosin, were assessed. Monoclonal antiserum Gastrin PAP kit 516 and somatostatin PAP kit 512 (DAKO) in the peroxidase-antiperoxidase technique (PAP) have been used to detect G and D-cells. Helicobacter pylori in the gastric mucosa was demonstrated with the Giemsa method. The results show the coincidence of Helicobacter pylori infection and the count of antral G and D-cells and active chronic gastritis in children. After the treatment Helicobacter pylori was eradicated in 70% of children. In 34% of these cases the eradication was followed by a diminution of activity of gastric antral mucosa inflammation and in 20% of these children the resolution of the inflammatory infiltration in the gastric mucosa was seen. A decrease of the antral G and D-cells count and also a diminution of G/D index in these cases were observed.

Topics: Adolescent; Child; Child, Preschool; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Humans; Immunohistochemistry; Male; Somatostatin

To evaluate the relationship between serum gastrin and Helicobacter pylori status in the antrum and body of gastric mucosa.. Fasting and post-meal serum gastrin level were studied by radioimmunoassay in 41 patients with dyspepsia. These patients were divided into three groups depending on H pylori status ie H pylori present in both antrum and body; (A+B+; n = 13), present in antrum but not in the body; (A+B-; n = 7) and absent in both antrum and body A-B-; n = 21.. There was no difference in fasting or post meal serum gastrin levels between the groups A+B+ and A+B-. Serum gastrin values 20 and 40 minutes post meal were significantly higher (p < 0.05) in the group A+B+ as compared to A+B-.. Post meal serum gastrin levels are higher in patients with dyspepsia in whom Helicobacter pylori is present in the antral and body mucosa as compared to those in whom it is present in the antrum only.

Topics: Adolescent; Adult; Case-Control Studies; Dyspepsia; Fasting; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Radioimmunoassay; Time Factors

Helicobacter pylori infection of the antral mucosa is responsible for an increase in basal and stimulated serum gastrin. In the present study we have investigated whether gastritis induced by H. pylori is responsible for abnormalities in the processing of gastrin in dyspeptic patients.. Basal serum gastrin was measured by radioimmunoassay before, 5 weeks, and 1 year after anti-H. pylori therapy in 73 H. pylori positive functional dyspeptic patients. Three region-specific antisera were used, specific for the biologically active carboxy-terminal part, the biologically inactive amino-terminal part of gastrin 1-17, and for the non-sulphated tyrosyl residue in gastrin 1-17.. Basal serum gastrin levels were markedly (P < 0.01) decreased 5 weeks and 1 year after successful eradication of H. pylori (n = 39) but not in the patients in whom treatment failed (n = 34). A decline of gastrin was observed for each of the three radioimmunoassays.. The decrease of serum gastrin levels in all three radioimmunoassays after a successful eradication of H. pylori does not point to major changes in the processing of gastrin. These results suggest that G-cells in the antral mucosa are not functionally affected by the inflammation.

Topics: Adult; Aged; Chromatography; Dextrans; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Radioimmunoassay; Sensitivity and Specificity; Time Factors

To determine serum concentration of gastrin and pepsinogens (PGs) as markers for the gastric mucosal status and to elucidate the prevalence of serum Helicobacter pylori (H pylori) IgG antibodies and parietal cell autoantibodies (PCAs) in patients with gastric polyps.. The subjects in this study were composed of 36 patients with fundic glandular polyps (FGP), 25 patients with foveolar hyperplastic polyps (FHP), and 27 asymptomatic healthy volunteers (controls). Serum concentrations of gastrin and PGs were determined by radioinmmunoassay. H. pylori IgG antibodies were measured through an enzyme-linked immunosorbent assay. PCAs were detected by an indirect immunofluorescence technique using cryostat sections of rat gastric mucosa.. There were no significant differences between FGP patients and controls in serum concentrations of gastrin, PG I and PG II. FHP patients showed significantly higher serum gastrin, lower PG I, higher PG II levels and, as a consequence, far lower PG I/PG II ratio compared with controls. The prevalence of H pylori infection was much higher in FHP patients (84.0%), whereas lower in FGP patients (19.44%) than that in controls (40.7%) was positive in 24.0% of FHP patients, 2.78% of FGP patients and 4% of controls.. These results suggest that FHP often develops in a gastric mucosa associated with H pylori infection, while FGP does not appear to be related to H pylori infection.

Topics: Antibodies, Bacterial; Autoantibodies; Biomarkers; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogens; Polyps; Stomach Neoplasms

The occurrence of H. pylori infection and the levels of fasting serum gastrin (SEGA) were examined in 97 patients with different morphological types of endoscopically diagnosed gastric polyps. According to the histology of the polyps the series was divided into three groups: inflammatory polyps (43 cases), polyps with foveolar hyperplasia (25 cases), and hyperplastic polyps including adenomas (29 cases). The prevalence of H. pylori infection was significantly lower in patients with hyperplastic polyps (45%) and foveolar hyperplasia (48%) than in the group with inflammatory polyps (81%). SEGA levels were higher in patients with hyperplastic polyps (mean +/- sd: 335 +/- 298 pmol/l) and foveolar hyperplasia (183 +/- 216) than in patients with inflammatory polyps (89 +/- 127). Signs of so-called "autoimmune" gastric, i.e. corpus atrophy and presence of parietal cell antibodies, were commonly found in patients with hyperplastic polyps and foveolar hyperplasia, but rarely in patients with inflammatory polyps. These results suggest that the polyps with hyperplastic changes (hyperplastic polyps and foveolar hyperplasia) are in some of the cases closely related to autoimmune gastritis. The presence of corpus atrophy, hypoacidity and various types of metaplasia, which characterizes autoimmune gastritis, could explain the low prevalence of H. pylori and the high SEGA levels found in these patients.

Topics: Adenoma; Aged; Female; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Middle Aged; Polyps; Stomach Neoplasms

This study examined the effects of eradication of Helicobacter pylori (H pylori) infection on gastric mucosal morphology and acid secretion. Sixteen H pylori positive patients with enlarged gastric body folds were divided into two groups: (a) patients with moderate enlargement (fold width: 6 to 10 mm, n = 8) and (b) patients with severe enlargement (> 10 mm, n = 8). After successful treatment, gastric body fold width was reduced in both groups (p < 0.01) with an associated decrease in inflammatory infiltrates in the body mucosa (p < 0.01 and p < 0.05). Basal acid output and tetragastrin stimulated maximal acid output (mean (SEM)) in all 16 patients significantly increased from 1.1 (0.5) to 2.9 (0.9) mmol/h (p < 0.05) and from 5.4 (1.3) to 18.7 (2.3) mmol/h (p < 0.01), respectively, with a significant decrease in fasting serum gastrin concentrations, from 127.1 (16.1) to 59.6 (3.8) pg/ml (p < 0.01). The increase in acid secretion after eradication of H pylori was more noticeable in the severe group, who had shown lower acid secretion and higher serum gastrin concentrations (p < 0.05) before eradication, than the increase seen in the moderate group. The decreases in ammonia nitrogen content seen after eradication were significant in basal (from 0.91 (0.17) to 0.37 (0.08) mmol/h, p < 0.05) and stimulated gastric secretions (from 1.57 (0.19) to 0.37 (0.13) mmol/h, p < 0.01), although these changes were too small to explain the increases in basal acid output and maximal acid output. These results suggest that inflammation of the gastric body mucosa caused by H pylori infection is associated with enlarged gastric body folds and inhibition of acid secretion in H pylori positive patients with enlarged gastric body folds.

Topics: Adult; Aged; Ammonia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Stomach

Helicobacter pylori infection is associated with abnormalities in serum gastrin concentration, antral gastrin and somatostatin content, and D-cell density in adults. We have studied the effects of H pylori infection in children. We studied 13 children positive for H pylori and 7 negative children. The median antral somatostatin content was significantly lower in the positive than in the negative group (0.69 [range 0.35-0.91] vs 1.31 [0.73-1.67] ng/mg, p = 0.007). Both antral and serum gastrin concentrations were significantly higher in the positive group (30.1 [15.3-83.6] vs 14.8 [13.8-28.8] ng/mg, p = 0.008; and 89.9 [59.4-313.2] vs 29.5 [13.9-71.1] pg/mL, p = 0.006). Treatment to eradicate H pylori was successful in 11 of the 13 positive patients. With eradication antral somatostatin increased to within the normal range (by a median of 0.41 [0.21-0.86] ng/mg to 1.10 [0.81-1.55] ng/mg, p = 0.016). Serum and antral gastrin decreased (by 37.1 [5.5-265.2] pg/mL to 52.8 [21.4-267.5] ng/mg, p = 0.001; and by 8.0 [2.0-47.2] ng/mg to 22.1 [10.9-37.5] ng/mg, p = 0.001). Eradication of H pylori also significantly increased antral D-cell density (8 [5-22] to 15 [9-22] cells per mm, p = 0.031) and decreased G-cell density (138 [89-161] to 88 [33-121] cells per mm, p = 0.016). The hypergastrinaemia in children positive for H pylori may be due to a deficiency of antral somatostatin, which inhibits gastrin synthesis and release.

Topics: Adolescent; Amoxicillin; Cell Count; Child; Drug Therapy, Combination; Female; Furazolidone; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Pyloric Antrum; Somatostatin

Helicobacter pylori infection is associated with increased meal stimulated gastrin secretion, but the reason for this is unknown. Sequence specific radioimmunoassays were used to measure the concentration of alpha-amidated gastrin, the total progastrin product, and somatostatin in biopsy specimens of human antral mucosa. The antral concentrations of alpha-amidated gastrin and of total progastrin products were significantly higher in H pylori infected patients than in those not infected by this organism. In contrast, the antral somatostatin concentration was significantly decreased in infected patients. Progastrin processing, determined by gel chromatography, seemed unaffected by H pylori infection. The results suggest that the finding of increased gastrin secretion from the antral G cells in H pylori infected patients may be a result of reduced inhibition of G-cell secretion by somatostatin.

Topics: Adult; Aged; Aged, 80 and over; Chromatography, Gel; Dyspepsia; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Somatostatin

Antral gastrin cell hyperfunction (AGCH) is a rare syndrome characterized by persistent hypergastrinemia and important peptic symptoms in the absence of a gastrin-producing tumor. The pathogenesis of AGCH is still unknown and debated. Helicobacter pylori (Hp) infection has been reported as a possible cause of sustained hypergastrinemia. To assess the relevance of Hp infection in pediatric AGCH patients, Hp status, G cell function, acid secretion, and antral G and D cell populations were investigated in six children presenting with gastrointestinal bleeding of unknown origin, sideropenic anemia, and variable abdominal symptoms. All patients had moderate high basal gastrinemia with abnormally increased peak values after meals and elevated values of basal acid output (BAO), maximal acid output (MAO), and pentagastrin-stimulated acid output (PAO). Circulating pepsinogen I was also significantly increased. Three children had Hp infection, as assessed by enzyme-linked immunosorbent assay, urease test, and histology. Endoscopy showed duodenal erosions in three children, with ulcer in two Hp-positive cases. At histology, moderate gastritis was observed only in the three Hp-positive cases. In all patients, quantitative assessment of antral gastrin and somatostatin cells gave significantly elevated G cell counts; D cells were at the lower reference limit and the G/D cell ratio was significantly elevated. These data indicated a diagnosis of AGCH, possibly due to the elevated G/D cell ratio, and suggest HP infection as an overlapping factor complicating the clinical picture in some cases.

Topics: Adolescent; Cell Count; Child; Dyspepsia; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Melena; Pyloric Antrum; Somatostatin; Stomach Diseases

We investigated the gene expression of antral gastrin and somatostatin in Helicobacter pylori-infected subjects. Twelve asymptomatic men with normal endoscopic findings participated in this study, four of whom were infected with H. pylori.. Biopsy specimens of the gastric mucosa were obtained after subjects had fasted overnight. Serum gastrin levels, antral gastrin and somatostatin content, and antral G- and D-cell densities also were measured.. Fasting serum gastrin levels were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. There were no differences between groups in antral gastrin content, G-cell density, or gastrin mRNA levels. Antral somatostatin content, D-cell density, somatostatin mRNA levels, and the somatostatin mRNA:D-cell density ratio were significantly decreased in H. pylori-positive subjects.. Our results suggest that in addition to reduced antral D-cell density, a suppression of somatostatin synthesis in D-cells may have contributed to the decrease in antral somatostatin in H. pylori-infected subjects.

Topics: Adult; Blotting, Northern; Cell Count; Gastric Mucosa; Gastrins; Gene Expression; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pyloric Antrum; Radioimmunoassay; RNA, Messenger; Somatostatin

We studied the relationship between Helicobacter pylori (H. pylori) infection and gastric acid secretion, along with fasting serum gastrin levels, in 55 asymptomatic healthy volunteers under 30 years old (29 H. pylori-positive, 26 H. pylori-negative). Mean scores of antral gastritis were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. There was no significant difference in both basal and maximal acid output between H. pylori-positive and H. pylori-negative subjects. Fasting serum gastrin levels were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Sex did not significantly affect gastritis scores, gastric acid secretion, or fasting serum gastrin levels, although maximal acid output was slightly higher in H. pylori-negative men than in H. pylori-positive men. Our results suggest that H. pylori infection has no direct effect on gastric acid secretion in young healthy subjects, although it induces hypergastrinemia.

Topics: Adult; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Retrospective Studies; Sex Factors

To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters.. Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later.. Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H. pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H. pylori-negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin (r = 0.45, p < 0.0001), and pepsinogen A (r = 0.33, p < 0.006) and pepsinogen C (r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted.. These findings suggest that hypergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pepsinogens; Peptic Ulcer; Salicylates

To understand the short-term and long-term effects of the eradication of Helicobacter pylori on serum pepsinogen I, gastrin, and insulin concentration, we studied 53 patients with endoscopically proven duodenal ulceration and H. pylori infection.. All patients received a 2-wk course of colloidal bismuth subcitrate, amoxycillin, and metronidazole, and endoscopy was performed at 1.5, 3, 6, and 12 months after entry. H. pylori status was assessed by a urease test and histology.. Among 43 patients in whom H. pylori was eradicated throughout the follow-up year, the mean basal pepsinogen I was 108 ng/ml at pretreatment, decreasing significantly to 85, 77, 80, and 75 ng/ml at 1.5, 3, 6, and 12 months, respectively, at posttreatment. The basal gastrin was 100 pg/ml at pretreatment and fell significantly to 72, 64, 65, and 59 pg/ml, respectively, posttreatment. Of the four patients in whom the H. pylori was not eradicated, there was no significant change in the median basal pepsinogen I and gastrin concentration. Among the six patients in whom the H. pylori was again detectable within the follow-up year, the fallen serum concentration of pepsinogen I and gastrin returned to the pretreatment level. There was no significant change of basal insulin concentration after triple therapy in either the successfully eradicated or failed group.. We conclude that H. pylori is the leading and direct cause of higher serum concentration of pepsinogen I and gastrin in duodenal ulcer patients.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Insulin; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pepsinogens; Time Factors

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Previous studies have found that colorectal cancer patients have hypergastrinemia, but most have been inadequately controlled. Preoperative fasting and meal-stimulated gastrin levels were measured in patients with colorectal tumors (n = 42) and in carefully matched controls (n = 34). Helicobacter pylori status was assessed because it causes significant hypergastrinemia.. Plasma gastrin levels were measured by radioimmunoassay. Helicobacter status was assessed using the [14C]urea breath test and serology (immunoglobulin G).. Preoperatively, fasting plasma gastrin levels were similar in patients with tumors (median, 55 ng/L; interquartile range, 45-82.5) and controls (77.5 ng/L; 53.7-137.5; P = 0.10). Similarly, peak gastrin levels were not significantly different in tumor patients (200 ng/L; 137.5-312.5) and controls (247.5 ng/L; 147.5-375; P = 0.21). The prevalence of H. pylori infection in patients with tumors (60%) and controls (53%) was similar in both groups. Five (20%) tumor patients who were H. pylori-positive preoperatively were negative postoperatively, and their median peak plasma gastrin level decreased from 200 ng/L to 140 ng/L. After these patients were excluded, fasting and peak plasma gastrin concentrations were similar preoperatively and postoperatively.. When confounding factors are controlled for, plasma gastrin levels are not increased in colorectal cancer and do not decrease after curative resection. Previously noted decreases in gastrin levels after tumor resection may be attributable to loss of H. pylori infection in some patients, as noted here.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Colorectal Neoplasms; Eating; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasm Staging; Parietal Cells, Gastric; Postoperative Period; Radioimmunoassay

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.

Topics: Adult; Aged; Antibodies, Bacterial; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Zollinger-Ellison Syndrome

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.

Topics: Adult; Aged; Cathepsin D; Chymases; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoradiometric Assay; Male; Mast Cells; Middle Aged; Peptic Ulcer; Serine Endopeptidases; Tryptases

Two entities of considerable recent interest, Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody to H. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT < 1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0-1.99%) and 42% of 59 subjects with normal absorption (EYCAT > or = 2.0%) (chi 2 = 9.52, P < 0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03 +/- 1.83% vs 3.11 +/- 2.13%, t = 2.913, P = 0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence of H. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced by H. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.

Topics: Adult; Aged; Antibodies, Bacterial; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Malabsorption Syndromes; Male; Middle Aged; Serologic Tests; Vitamin B 12 Deficiency

The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of antral gastrin and somatostatin were investigated in endoscopic antral biopsy specimens from patients with duodenal ulcer before and after eradication of Helicobacter pylori. After H. pylori eradication both antral somatostatin concentration (p = 0.0002) and antral D-cell density (p = 0.01) increased significantly. Conversely, although the number of G-cells was unchanged, antral (p = 0.0002) and serum (p = 0.001) gastrin contents decreased significantly. The number of oxyntic D-cells did not change significantly. These results strongly suggest that the hypergastrinaemia observed in H. pylori-positive patients may be due to a deficiency in antral somatostatin, which normally inhibits the synthesis and release of gastrin.

Topics: Adult; Biopsy; Cell Count; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pilot Projects; Pyloric Antrum; Somatostatin; Time Factors

Topics: Biopsy; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Somatostatin

The influence of Helicobacter pylori infection on serum levels of pepsinogen I and gastrin in gastric carcinoma was investigated by simultaneous determination of serum pepsinogen I, gastrin, and IgG antibodies against Helicobacter pylori in 100 patients with gastric carcinoma, and in another 100 age- and sex-matched healthy controls. Serum pepsinogen I level was significantly lower in gastric carcinoma than in controls (55.5 +/- 28.1 vs. 76.9 +/- 25.1 ng/ml, p < 0.005), but there was no difference in serum gastrin between them (63.2 +/- 30.2 vs. 57.4 +/- 28.5 pg/ml, p = 0.16). Helicobacter pylori infection caused a significant increase in serum PGI level in advanced, intestinal type, and non-cardia gastric carcinoma. The serum gastrin level was affected by neither Helicobacter pylori infection nor any of the tumor characteristics. It is concluded that pepsinogen I, rather than gastrin, in the serum is greatly influenced by Helicobacter pylori infection and tumor characteristics in gastric carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Stomach Neoplasms

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p < 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p < 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p < 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p<0.02; maximal: 18.9 (4.0); 31.4(1.8); p<0.002; peak: 25.1(5.3); 43.4(2.7); p<0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.

Topics: Adolescent; Adult; Age Factors; Aged; Basal Metabolism; Biopsy; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Severity of Illness Index; Stomach

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Topics: Adult; Bismuth; Female; Food; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Peptic Ulcer; Protein Precursors; Protein Processing, Post-Translational; Salicylates; Tetracycline

To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection.. Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive.. By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations.. Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Topics: Adult; Antibodies, Bacterial; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Protein Precursors

In the past five years 12 patients have been identified presenting with chronic duodenal ulcer (DU) disease and with no evidence of current or recent Helicobacter pylori (H pylori) infection. Four of them were taking regular non-steroidal anti inflammatory agents, one was subsequently found to have Crohn's disease of the duodenum, and one to have the Zollinger-Ellison syndrome. The remaining six patients with idiopathic DU disease were remarkable for their absence of the A1 blood antigen gene. Detailed studies of gastric function were performed in these six patients and compared with H pylori positive patients with DU and with healthy volunteers. The median integrated gastrin response in the patients with idiopathic DU (2810 (range 750-8750) ng/l min) was similar to that of the H pylori positive patients with DU (3355 (550-8725)) and higher than that of the H pylori negative healthy volunteers (560 (225-1125)). The median peak acid output in the patients with idiopathic DU (37 mmol/h, range 17-52) was similar to that of the H pylori positive patients with DU (40 (15-57)) and higher than that of the non-ulcer controls (22 (16-29)). The median percentage of a liquid meal retained in the stomach at 60 minutes was less in the patients with idiopathic DU (23 (15-33)) than in H pylori negative healthy volunteers (34 (30-53) p < 0.01). The median percentage of a solid meal retained at 60 minutes was less in the patients with idiopathic DU (54 (9-83)) than in either H pylori negative healthy volunteers (87 (49-95) p<0.01) or H pylori positive patients with DU (79 (51-100) p<0.01). In conclusion, three abnormalities of gastric function are prevalent in patients with H pylori negative idiopathic DU disease - hypergastrinaemia, increased acid secretion, and the one feature distinguishing them from H pylori positive patients with DU - rapid gastric emptying of both liquids and solids. Each of these abnormalities will increase the exposure of the duodenal mucosa to acid and thus explain its ulceration. The absence of the blood group A1 antigen gene is consistent with a genetic basis for the disturbed gastric function linked to the ABO blood group antigen genes.

Topics: ABO Blood-Group System; Adult; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

The relation between Helicobacter pylori (H pylori) infection and fasting gastrin and pepsinogen-I and -II concentrations was evaluated in 278 volunteers without symptoms and the results were compared with the values obtained in 35 patients with duodenal ulcers. H pylori infection was determined with the 13C-urea breath test in subjects without symptoms and with endoscopy, biopsy (histology and culture), and quick urease test (CLO-test) in patients with duodenal ulcers. Gastrin and pepsinogen-I and -II concentrations were assayed with specific radioimmunoassay systems. The results clearly indicate that fasting gastrin and pepsinogen-I and -II concentrations were significantly higher in H pylori positive compared with H pylori negative subjects. Neither age nor sex affected basal gastrin and pepsinogen concentrations in H pylori negative subjects. Fasting gastrin, pepsinogen-I and -II concentrations in serum samples were similar in H pylori positive persons with no symptoms and those with duodenal ulcers suggesting that similar mechanisms are involved in increasing plasma concentrations of these variables in both populations. Hypergastrinaemia and hyperpepsinogenaemia are therefore probably secondary to active H pylori infection.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Sex Factors

The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive patients with duodenal ulcer before and after antimicrobial therapy and in H. pylori-negative subjects. Determination of serum gastrin was also performed in duodenal ulcer patients before and after H. pylori eradication. The histamine content of the oxyntic mucosa was lower in patients with duodenal ulcer than in H. pylori-negative subjects, but it increased after H. pylori eradication. Conversely, in patients in whom therapy failed to eradicate the microorganism, the histamine content remained unchanged. Serum gastrin levels fell after microorganism eradication, and the percentage of this fall was correlated with the percentage of increase in gastric histamine. In conclusion, our findings suggest that abnormalities of histamine store present in duodenal ulcer patients might be a feature of H. pylori infection.

Topics: Adult; Amoxicillin; Drug Therapy, Combination; Duodenal Ulcer; Female; Furazolidone; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Male; Metronidazole; Time Factors

The effect of ulcer healing with eradication of Helicobacter pylori (H pylori) on gastric function was investigated in nine patients with duodenal ulcer disease. One month after eradication there were significant reductions in both basal plasma gastrin concentration, from a median (range) of 19 (1-22) to 6 (2-15) pmol/l (p < 0.05), and of basal acid secretion from 8.3 (2.4-24) to 2.6 (1.4-8.1) mM H+/h, (p < 0.01). The peak acid secretion rate was unchanged from 37 (16-59) to 37 (21-59) mM H+/h. After treatment there was no change in the parietal cell sensitivity to stepped infusions of gastrin heptadecapeptide: the median concentration of gastrin required for 50% of maximal acid secretion (EC50) was 41 (14.8-126) before and 33 (23-125) pmol/l after eradication of H pylori. The metabolic clearance rate of gastrin was also unaffected by the eradication of H pylori. Thus eradication of H pylori infection from patients with active duodenal ulcers is accompanied by falls in both basal gastrin release and basal acid secretion without a change in the parietal cell sensitivity to gastrin. Cyclical changes in H pylori infection may cause the variations in basal acid secretion that are seen in duodenal ulcer disease.

Topics: Acute Disease; Adult; Aged; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Parietal Cells, Gastric; Tetracycline

H. pylori infection is associated with acid-peptic disease, although its role in the pathogenesis is unclear. The purpose of this study was to determine if chronic infection in asymptomatic subjects impairs the inhibition of meal-stimulated gastrin and acid secretion that is observed normally at low intragastric pH. Presence of infection was determined by both C-14 urea breath test and serology. Acid secretion was measured under basal conditions and in response to peptone meal stimulation and pentagastrin. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and during peptone meal stimulation. Intragastric titration with 1% peptone during the first hour, and 8% peptone during the second hour, was performed at both pH 7.0 and 2.5 on different days to compare the inhibition of gastrin and acid secretion. Compared to noninfected subjects, asymptomatic individuals infected with H. pylori had significantly increased: (1) basal gastrin values (P < 0.005); (2) 8% peptone-stimulated gastrin responses at both pH 7.0 and 2.5 (P < 0.05); and (3) 8% peptone-stimulated acid output at pH 2.5 (P = 0.01). During the second hour of peptone-stimulation, subjects infected with H. pylori had significantly decreased inhibition of gastrin (52% vs 95%) (P = 0.002) and acid (30% vs 81%) (P = 0.01) secretion from pH 7.0 to 2.5. Thus, chronic infection with H. pylori results in impaired inhibition of gastrin and acid secretion at low intragastric pH during the second hour of peptone meal stimulation. These defects may be unrelated to the pathogenesis of acid-peptic disease, since they occur in asymptomatic subjects infected with H. pylori.

Topics: Adult; Aged; Duodenal Ulcer; Feedback; Food; Gastric Acid; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

The prevalence of Helicobacter pylori (H. pylori) was investigated in 164 consecutive patients with different degrees of renal function; group I (normal renal function) n = 84, group II (chronic renal failure, CLCR > or = 5 < 90 ml/min) n = 45, group III (haemodialysis therapy) n = 35, to test the hypothesis that the resulting different concentrations of urea in the gastric juice would have an influence on the colonization of the gastric mucosa by these urea-splitting bacteria. As every individual method for the detection of H. pylori shows disadvantages, the results of the detection methods used (urease test, Warthin-Starry stain, bacterial cultivation, direct examination of the processed sample by phase-contrast microscopy) were combined in a cumulative evaluation. These calculated cumulative indices for the antrum and corpus showed no statistically significant differences between the studied groups. The prevalence of H. pylori ranged from 34 to 54%. The histopathological findings were similar in all groups. In spite of the fact that patients with renal dysfunction had significantly higher levels of serum gastrin (P < 0.05), there was no influence on the gastric juice pH value. The relationship between the cumulative index and ammonia concentration in gastric juice was found to be linear (P < 0.05). The higher urea levels in the blood and gastric juice of patients with renal failure do not seem to be a risk factor for infection with H. pylori.

Topics: Ammonia; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Peptic Ulcer; Stomach Ulcer

Topics: Adenocarcinoma; Carcinoid Tumor; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Stomach Neoplasms

A 60-yr-old man with longstanding duodenal ulcer was found to have hyperchlorhydria, moderate fasting hypergastrinemia, and markedly exaggerated meal-stimulated gastrin release. Antral tissue specimens showed the proliferation of gastrin cells and increased gastrin content, and he was found to have Helicobacter pylori infection in the antral mucosa. His illness was diagnosed as primary gastrin cell hyperplasia with H. pylori infection. Eradication of H. pylori normalized not only gastrin hypersecretion but also gastrin cell hyperplasia. These results indicate that H. pylori infection could be one of the causes of this syndrome.

Topics: Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Metronidazole; Middle Aged; Pyloric Antrum; Tetracycline

Topics: Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans

The effects of chronic drug-induced hypergastrinemia on the exocrine and endocrine stomach are still incompletely understood. Chronic hypergastrinemia in rats and humans is associated with gastric argyrophil cell hyperplasia.. Seventy-four patients with chronic ranitidine-resistant ulcerations were treated chronically with omeprazole (median observation period 48 [6-84] months).. Median fasting serum gastrin levels increased from a pretreatment value of 74-145 pg/mL after 3 months. No further increase was observed thereafter. The finding of atrophic gastritis increased from 1.8% to 20.8% after 5 years. A doubling of the mean argyrophil cell volume density (0.36% vs. 0.74% after 5 years; P < 0.01%) was paralleled by a decrease in the normal endocrine cell growth pattern from 64.3% to 33.3% and an increase in micronodular hyperplasia (8.9% vs. 16.7%). These changes correlated with the severity of corpus gastritis and seemed to be more disease- than drug-related. No statistically significant changes were observed in the antral G- and D-cell volume densities under therapy.. Long-term omeprazole therapy in humans results in moderate hypergastrinemia and a significant argyrophil cell hyperplasia, which are correlated to the grade of corpus gastritis. Because hypergastrinemia and gastritis are closely related, it is difficult to quantitatively assess their respective role in this process.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Division; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Peptic Ulcer; Stomach; Time Factors

It has recently been recognized that Helicobacter pylori infection is associated with abnormalities in the regulation of gastrin secretion. We investigated whether there was a relationship between H. pylori infection and G-cell and D-cell numbers.. The numbers of antral G cells and D cells were compared between 20 patients with duodenal ulcer and 24 volunteers, 12 with and 12 without H. pylori infection. The effect of eradication of H. pylori infection on G-cell number was also evaluated. Antral mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of gastrin and somatostatin.. The number of G cells was significantly (P < 0.02) less in patients with duodenal ulcer than in either infected or uninfected controls (3.7 +/- 0.3 vs. 6.2 +/- 0.6 and 5.3 +/- 0.5 G cells per gland for infected and uninfected controls, respectively). The ratio of G-cells to D-cells was similar in duodenal ulcer patients (2.2) and uninfected controls (2.0). It was found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, it is not associated with a change in the numbers of antral G cells or D cells in patients with duodenal ulcer.. It is concluded that H. pylori infection-associated increase in gastrin secretion appear to be related to local factors regulating G-cell function.

Topics: Cell Count; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum

Hypersecretion of gastric acid, gastrin, and pepsinogen are considered to be causally related to duodenal ulcer diathesis. Until recently, these abnormalities have been considered to be primary and largely genetically determined. However, Helicobacter pylori infection has been shown to be responsible for several of the abnormalities of gastric secretion in duodenal ulcer. H. pylori infection is not only associated with chronic active inflammation but also with a reduction of somatostatin producing D-cells and somatostatin concentrations in the gastric mucosa. The reduced inhibitory action of somatostatin on the secretion of gastric acid, gastrin, and pepsinogen may be responsible for the hypersecretory state of the stomach in duodenal ulcer. These recent findings have drastically changed our understanding of the pathogenesis of duodenal ulcer.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens

Infection of the gastric antrum by Helicobacter pylori is associated with recurrent duodenal ulcer disease but the mechanism of ulcerogenesis is unclear. Since pathways inhibiting gastric secretion are defective in patients with duodenal ulcers, we investigated whether H pylori interferes with the normal gastric inhibition that is mediated by somatostatin. We studied 28 patients with active duodenal ulcers in whom H pylori was eradicated successfully. In 18 patients, we measured the density of antral somatostatin-immunoreactive cells and in a further 10 subjects, the amount of somatostatin mRNA before and after eradication of H pylori was determined. After eradication, the median density of somatostatin-immunoreactive cells increased significantly from 9 (range 3-47) to 19 (6-57) cells per mm muscularis mucosa (p = 0.025). The median somatostatin mRNA/rRNA ratio increased from 50 (25-160) to 95 (40-180) (p = 0.01). The number of gastrin cells and quantity of gastrin mRNA did not change significantly. Our results suggest that in duodenal ulcer disease, gastric secretory function is disinhibited through the suppression of mucosal somatostatin.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Somatostatin

Thirty patients with active duodenal ulcer who were Helicobacter pylori positive (HP+) by HLO test and by histology (Giemsa stain) were given omeprazole (OME) 20 mg/d for a two-week period. Estimation of fasting serum gastrin concentration (RIA) was performed before treatment and 24 hours after the last dosage of OME, and HP was searched for an antral biopsies at the end of the treatment as well. Mean fasting serum gastrin concentration increased significantly after treatment in all patients studied (p less than 0.05). However, the increase remained significant only in those patients who continued to be HP+ while no significant increase was observed in those who became HP-. The results could be considered as further evidence of the 'clearing' effect of Omeprazole on HP.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole

Patients with duodenal ulcers and Helicobacter pylori infection have elevated plasma gastrin concentrations which fall after suppression of the organism. This may be due to H. pylori elevating the pH of the antral mucous layer, therefore preventing luminal acid from inhibiting gastrin release. To test this idea, we measured the plasma gastrin concentrations under basal conditions and in response to 4% peptone when the gastric lumen was maintained at pH 2.5 and at pH 5.5 by gastric perfusion. We studied 11 duodenal ulcer patients before and after suppression of H. pylori. Gastrin concentrations were significantly higher before suppression of H. pylori than after treatment in all three states; basal gastrin (pmol/l) fell from 9.2 (3.7-23, median and range) to 5.1 (1.7-15) after treatment; from 11.3 (3.8-29) to 5.9 (5.7-6.1) at pH 2.5 and from 15.2 (3.9-32) to 7.15 (6.1-14) at pH 5.5. The ratio of peptone-stimulated gastrin at pH 2.5/pH 5.5 was similar before (0.8; 0.5-1.7) and after (0.8; 0.5-1.1) suppression of H. pylori. These results indicate that infection with H. pylori increases basal and peptone-stimulated plasma gastrin concentrations, and that this response is independent of luminal pH.

Topics: Amoxicillin; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds

Studies were performed in patients with and without renal failure to investigate the role of bacterial ammonia production in the pathogenesis of the mucosal abnormalities caused by Helicobacter pylori. The high rate of H pylori ammonia production in uraemic patients should accentuate any ammonia induced effects. The median (range) gastric juice ammonium concentration in the H pylori positive patients with renal failure was 19 mmol/l (II-43) compared with 5 mmol/l (1-11) in the H pylori positive patients without renal failure (p < 0.005). In the H pylori negative patients the values were 3 mmol/l (0.5-11) and 0.7 mmol/l (0.1-1.4) respectively in the patients with and without renal failure (p < 0.01). Despite the much higher ammonia production in the H pylori positive uraemic patients, the nature and severity of their gastritis was the same as that in the H pylori positive non-uraemic patients. The median (range) fasting serum gastrin concentration was raised in the uraemic patients compared with the non-uraemic patients but was similar in the uraemic patients with (95 pmol/l (52-333)) or without (114 pmol/l (47-533)) H pylori infection. The median (range) serum pepsinogen I concentration was also high in the uraemic compared with the non-uraemic patients and was significantly higher in uraemic patients with H pylori (352 ng/ml, range 280-653) than in those without H pylori infection (165 ng/ml, range 86-337) (p < 0.01). These findings indicate that the gastritis and hypergastrinaemia associated with H pylori infection are not the result of mucosal damage induced by the organism's ammonia production.

Topics: Adult; Aged; Ammonia; Gastric Juice; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Pepsinogens; Renal Insufficiency; Stomach Diseases

It has been postulated that Helicobacter pylori-related hypergastrinaemia is due to bacterial ammonia raising antral surface pH and thus preventing acid inhibition of gastrin release. If true, the infection should not alter gastrin release at neutral intragastric pH. To test this, we have studied basal and meal-stimulated gastrin at uncontrolled pH and at pH greater than 6 in duodenal ulcer patients before and after eradication of H. pylori. The median integrated gastrin response to the meal alone was 2525 ng/l.min (range, 550-8725) before and 725 ng/l.min (range, 250-2925) after eradication of H. pylori (p less than 0.01). The corresponding values when intragastric pH was maintained above 6 were 3700 ng/l.min (range, 1900-14,100) and 1400 ng/l.min (range, 400-3400) (p less than 0.01). The median reduction in gastrin after eradication of H. pylori was thus similar when the meal was taken at uncontrolled pH (61%; range, 0-97%) and at pH greater than 6 (69%; range, 36-89%). Likewise, 5 h of gastric alkalinisation did not cause the basal gastrin values when H. pylori was eradicated to increase to those observed when H. pylori was present. These findings indicate that the hypergastrinaemia is not due to elevated antral surface pH.

Topics: Adult; Amoxicillin; Antacids; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pyloric Antrum

Sixty-four consecutive patients which on upper gastrointestinal endoscopy had endoscopic signs of atrophic body gastritis were investigated with standard histology examinations of gastric biopsies, serology and/or culture for Helicobacter pylori and with standard blood chemistry profile. A histologic diagnosis of atrophy could be made in only 27 of the 64 patients (42%). Of these 27 patients, 5 had the pernicious anaemia (PA) type (19%), 22 had not (81%). Past and/or present H. pylori infection was found in 16/22 non-PA patients (73%) but in none of the PA patients (p = 0.00572). The present study thus confirms earlier findings that non-PA type atrophic body gastritis is more common than the PA type and suggests that, as opposed to PA-type atrophy, it is related to H. pylori infection.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Antibodies, Bacterial; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Radioimmunoassay

The rise in serum gastrin and pepsinogen I after 5 days' treatment with the proton pump inhibitor pantoprazole (40 mg/day) was examined in eight duodenal ulcer patients with Helicobacter pylori infection and compared with eight in whom it had been eradicated. Before treatment, the post-prandial serum gastrin concentrations were higher in the H. pylori-positive than -eradicated patients (p less than 0.05). The median rise in pre-prandial serum gastrin concentrations on treatment was similar in the H. pylori-positive (41%) and -eradicated patients (45%). The rise in post-prandial serum gastrin was also similar in the H. pylori-positive (81%) and -eradicated patients (69%), resulting in significantly higher gastrin concentrations during treatment in the former. The median rise in serum pepsinogen I on treatment was greater in the H. pylori-positive (114%) than in the -eradicated patients (8%), resulting in significantly higher concentrations during treatment in the former. These observations indicate that eradication of H. pylori may be a means of moderating the hypergastrinaemia caused by acid-inhibitory therapy. They also indicate that H. pylori-related hypergastrinaemia is not due to an increase of the antral surface pH by the bacterium's urease activity.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Benzimidazoles; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole; Pantoprazole; Pepsinogen A; Pepsinogens; Peptide Fragments; Sulfoxides

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

Helicobacter pylori increases gastrin release in duodenal ulcer patients. This may be through disruption or changes in the mucus layer affecting the access of luminal stimulants to gastrin releasing cells. The effect of suppressing H pylori on gastrin release stimulated by a non-luminal stimulus, gastrin releasing peptide (GRP), was examined. Eleven patients with active duodenal ulcer disease and colonised with H pylori received an intravenous infusion of GRP (2.9 pmol/kg/minute for 30 minutes) and the plasma gastrin response was measured. Basal and peak pentagastrin stimulated acid output were also determined. Patients were treated with tripotassium dicitratobismuthate (De-Nol) and metronidazole to suppress H pylori and the tests were repeated. Suppression of H pylori decreased plasma gastrin concentrations during GRP infusion, but acid output was not affected. Chromatographic analysis of the forms of gastrin in plasma showed a significant fall in gastrin 17, the predominant form found in the gastric antrum. Gastrin 34 did not fall significantly. This study shows that suppression of H pylori decreases the hypergastrinaemia caused by the nonluminal stimulant, GRP, mainly via decreasing gastrin 17.

Topics: Adult; Duodenal Ulcer; Female; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptides; Secretory Rate

Duodenal ulcer patients have increased serum pepsinogen I (PGI) concentrations and an increased prevalence of Helicobacter pylori infection. We have examined the effect of eradicating the infection on PGI. In 12 duodenal ulcer patients in whom H. pylori was successfully eradicated, the median basal PGI was 90 ng/ml (range, 37-252) before treatment and fell to 74 ng/ml (28-197) 1 month after treatment (p less than 0.01). In 12 patients in whom therapy failed to eradicate the infection, the PGI was 87 ng/ml (35-128) before treatment and remained unchanged at 83 ng/ml (36-119) 1 month after treatment. In the group with successful eradication the median basal plasma gastrin was 43 ng/l (15-95) before treatment and fell to 30 ng/l (17-75) 1 month after treatment (p less than 0.003), but there was no change in the corresponding values in the group without eradication (55 ng/l; range, 25-120, and 45 ng/l; range, 5-175; p = 0.9). In conclusion, eradication of H. pylori results in a fall in PGI and plasma gastrin, and these changes are not due merely to the anti-H. pylori drugs themselves or to discontinuation of previous ulcer therapy.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Middle Aged; Pepsinogens; Time Factors

Eradication of Helicobacter pylori is associated with a fall in serum gastrin but the way in which the infection raises the serum gastrin concentration is not clear. It may be related to the ammonia produced by the bacterium's urease stimulating gastrin release by the antral G cells. Alternatively, the antral gastritis induced by the infection may modify the regulation of gastrin release. We have examined serum gastrin in 10 patients before and 24 hours after starting triple anti-H pylori treatment consisting of tripotassium dicitrato bismuthate 120 mg four times daily, metronidazole 400 mg three times daily, and amoxycillin 500 mg three times daily. The urease activity, assessed by the 20 minute value of the 14C-urea breath test, fell from a median of 176 (range 116-504) kg% dose/mmol CO2 x 100 pretreatment to 5 (2-15) at 24 hours (p less than 0.005). The median antral gastritis score was 6 (4-6) pretreatment and fell to 3 (2-5) at 24 hours (p less than 0.02), and this was due to resolution of the polymorphonuclear component. Despite this complete suppression of bacterial urease activity and partial resolution of antral gastritis the median basal gastrin concentration remained unchanged, being 57 ng/l (45-77) pretreatment and 59 ng/l (45-80) at 24 hours and the median integrated gastrin response to a standardised meal was also unaltered, being 4265 ng/l/min (range 1975-8350) and 4272 ng/l/min (range 2075-6495) respectively. These findings do not support a causal association between H pylori urease activity and hypergastrinaemia and show rapid improvement of antral gastritis after starting anti-H pylori treatment.

Topics: Adult; Aged; Drug Therapy, Combination; Eating; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Urease

Helicobacter infection of the gastric antrum is linked to the development of duodenal ulcer. A key element could be the associated hypergastrinemia. This brief commentary seeks answers to the following questions: 1) Does hypergastrinemia occur? 2) How does it occur? and 3) Does it matter?

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Bismuth; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds; Stomach; Time Factors

In a prospective study, eight young healthy subjects (five with an active H. pylori infection in the antral mucosa) were treated with a course of tripotassium dicitrato bismuthate, amoxycillin and metronidazole. The triple therapy eradicated infection when assessed 20-24 weeks later by antral biopsy (urease, histology, and 13C urea breath test [4 out of 5 subjects]). Twenty-four hour intragastric acidity and plasma gastrin concentration were measured before treatment, and 4-6 weeks and 20-24 weeks post-treatment. Treatment did not affect acidity in either the H. pylori-positive or H. pylori-negative groups, nor did it affect the plasma gastrin profile in the H. pylori-negative group. Eradication of H. pylori infection in five subjects caused a drop of the median integrated 24-hour plasma gastrin concentration from 558 pmol.h/L before treatment to 307 and 289 pmol.h/L at 4-6 and 20-24 weeks post-treatment, respectively. It is concluded that H. pylori infection is associated with 24-hour hypergastrinaemia, and that in apparently healthy subjects normal gastric physiology can be restored by eradication of the infection.

Topics: Adult; Amoxicillin; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds

The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.

Topics: Adult; Aged; Aging; Female; Food; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormones; Humans; Male; Middle Aged; Pepsinogens; Regression Analysis

Basal and pentagastrin-stimulated gastric acid secretion and basal serum gastrin level were investigated in 55 active duodenal ulcer patients with antral colonization with Helicobacter pylori (HP) and 17 patients without. Our study shows that basal (BAO) and pentagastrin-stimulated gastric acid secretion (MAO and PAO) were significantly higher in HP positive than in HP negative patients with duodenal ulcer disease. There were also a tendency to increase in basal serum gastrin concentration in HP positive patients. We suggest that antral HP increases antral gastrin release and gastric secretion. Increased acid secretion then causes duodenal ulcers by producing a low intraduodenal pH.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

We studied histologically antral biopsies from 89 consecutive patients with chronic renal failure for Helicobacter pylori (previously Campylobacter pylori). A dose-response gastric secretion test was also performed. The frequency of Helicobacter-positive subjects was low (15/89, 17%), corresponding to figures reported in the literature for young symptomless volunteers. Helicobacter-positive patients had significantly more frequently upper gastrointestinal symptoms than Helicobacter-negative individuals (P less than 0.05). Antral gastritis was more common in the Helicobacter-positive than in the Helicobacter-negative renal patients (P less than 0.01), but the incidence of body gastritis did not differ between them. The Helicobacter-positive patients had lower serum urea levels (P less than 0.01) and higher acid outputs (P less than 0.001) than Helicobacter-negative subjects. All patients had raised fasting serum gastrin levels, which possibly obscured the difference between Helicobacter-positive (283 pg/ml) and -negative (331 pg/ml) patients. We conclude that in chronic renal failure gastric colonization of Helicobacter pylori is not more frequent than usual. It correlates positively with antral gastritis, gastric acid output and upper gastrointestinal symptoms, but negatively with serum urea levels.

Topics: Biopsy; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Pyloric Antrum

Topics: Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer

Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Helicobacter pylori (previously Campylobacter pylori) is almost invariably associated with chronic duodenal ulcer disease. The relationship between H. pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome and also what effect H. pylori infection had on gastric function in patients with Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific serologic (ELISA) assay based on high-molecular-weight cell-associated proteins of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and 5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison syndrome patients had H. pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0 mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5 to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO 44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients, respectively). The difference in BAO was statistically significant (P less than 0.05). The present results indicate that H. pylori is not a major contributing factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The association of a reduced BAO with H. pylori suggests that these findings may be related.

Topics: Adult; Aged; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Recurrence; Zollinger-Ellison Syndrome

Recent studies have shown that the exaggerated meal-stimulated gastrin release in patients with duodenal ulcer abates after eradication of Helicobacter pylori infection. Bombesin-stimulated gastrin release was compared in 11 H. pylori-infected patients with chronic duodenal ulcer and 8 uninfected healthy volunteers both before and after therapy to eradicate H. pylori. Bombesin infusion significantly increased the gastrin release both in control subjects and in patients with duodenal ulcer. Antimicrobial therapy (bismuth, tetracycline, and metronidazole) to eradicate the H. pylori infection was associated with a significant reduction in bombesin-stimulated gastrin release in patients with duodenal ulcer (from 116.9 +/- 19 pg/mL to 69.5 +/- 7 pg/mL following 50 pmol.kg-1.h-1 bombesin; and from 158 +/- 29 to 83.4 +/- 10 following 200 pmol.kg-1.h-1 bombesin: P = 0.01 for each). Antimicrobial therapy had no effect on gastrin release in uninfected volunteers, thus excluding a nonspecific effect of antimicrobial therapy on antral G-cell function. Serum gastrin was also not increased by feeding 500 mg of urea to 5 H. pylori-infected volunteers. This suggests that access of hydrogen ion to the pH-sensitive sites governing gastrin release by mucosal ammonia produced by H. pylori urease is not a critical factor. These data suggest that exaggerated gastrin release present in patients with duodenal ulcer disease is secondary to H. pylori infection.

Topics: Adult; Bombesin; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Urea

Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Infant; Male; Pepsinogens; Prospective Studies; Severity of Illness Index