gastrins and Stomach-Ulcer

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

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

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

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

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

Topics: Betazole; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Humans; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

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

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

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

All vertebrates secrete gastric acid. Acid denatures the proteins in the food and thus makes them more accessible to proteolytic enzymes, and it kills swallowed micro-organisms. Gastric acid plays an important pathogenetic role in peptic ulcer disease and reflux oesophagitis. In these diseases, drugs that inhibit secretion of gastric acid will heal the lesions and suppress the symptoms. However, both reflux oesophagitis and peptic ulcer tend to recur when the acid-inhibitory treatment is stopped. Therefore, these patients often require long-term treatment with acid-inhibitors. In this overview the potential risks of long-term profound inhibition of acid secretion, raising the pH above 4 for a considerable time, resulting in reduced killing of micro-organisms and secondary hypergastrinaemia, are discussed. Gastrin regulates both the function (production and release of histamine) and growth of the enterochromaffin-like (ECL) cell. Hitherto, the role that this cell plays in gastric carcinogenesis appears to have been underestimated.

Topics: Animals; Antacids; Anti-Ulcer Agents; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis, Peptic; Gastric Acid; Gastrins; Histamine; Histamine H2 Antagonists; Humans; Stomach Ulcer

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Duodenal Ulcer; Enprostil; Gastric Juice; Gastrins; Humans; Misoprostol; Omeprazole; Prostaglandins E, Synthetic; Stomach Ulcer

Greatly improved understanding of the cellular basis for gastric acid secretion and gastroduodenal mucosal defense has led to a dramatic improvement in the pharmacologic treatment of peptic ulcer disease. The advances produced by cimetidine and ranitidine are being continued by a new generation of histamine receptor antagonists, as well as by other anti-ulcer agents. These new drugs, when used appropriately, will greatly expand the surgeon's ability to treat patients with peptic ulcer disease. A knowledge of the pathophysiologic characteristics of peptic ulceration and of the inherent limitations of each agent will become increasingly important for surgeons who treat these patients.

Topics: Acetylcholine; Benzimidazoles; Chemical Phenomena; Chemistry; Cimetidine; Disease Susceptibility; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine H2 Antagonists; Humans; Imidazoles; Intestinal Mucosa; Peptic Ulcer; Ranitidine; Receptors, Muscarinic; Stimulation, Chemical; Stomach Ulcer

Topics: Animals; Digestive System; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Liver Circulation; Pepsinogens; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Regional Blood Flow; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

The actions of adrenoceptor agonists and antagonists are by no means agreed even though experiments with adrenal medulla extract date back to the beginning of the century. This review will consider the work of my own group and that of others in an attempt to classify the adrenoceptors which modulate gastric acid secretion. There are a number of factors to consider. Species differences are important and particular attention will be given to results from rat, dog and human. The secretagogue used is also important because the effect of adrenoceptor agonists and antagonists can be modified by the choice of histamine, muscarinic agonist, (penta) gastrin or food. Other factors include the gastric model used and the presence or absence of anaesthesia. The broad conclusions are that both alpha- and beta-adrenoceptors can inhibit gastric acid secretion. Both beta 1- and beta 2-adrenoceptors mediate inhibition of pentagastrin-induced secretion while alpha-adrenoceptors are important in the reduction of histamine-induced gastric acid secretion.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Albuterol; Animals; Atropine; Bethanechol; Bethanechol Compounds; Classification; Deoxyglucose; Dogs; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine Antagonists; Humans; Isoproterenol; Methoxamine; Norepinephrine; Pentagastrin; Propranolol; Rats; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Regional Blood Flow; Stomach Ulcer

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

Topics: Calcium; Diagnosis, Differential; Duodenal Ulcer; False Negative Reactions; False Positive Reactions; Gastrectomy; Gastrins; Humans; Infusions, Parenteral; Injections, Intravenous; Jejunal Diseases; Peptic Ulcer; Secretin; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Duodenal Ulcer; Endoscopy; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Insulin; Intraoperative Period; Male; Middle Aged; Postoperative Complications; Pyloric Antrum; Recurrence; Stomach Ulcer; Time Factors; Vagotomy; Vagotomy, Proximal Gastric

Topics: Acromegaly; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hyperparathyroidism; Ileal Diseases; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease.

Topics: Cimetidine; Cyclic AMP; Duodenal Ulcer; Esophagitis, Peptic; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Metiamide; Pepsin A; Stomach Ulcer

Topics: Adult; Aged; Antacids; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Histamine Antagonists; Humans; Male; Parasympatholytics; Peptic Ulcer; Stomach Ulcer; Zollinger-Ellison Syndrome

Cimetidine is a specific competitive histamine H2-receptor antagonist which effectively inhibits gastric acid secretion and is advocated for the treatment of chronic peptic ulceration, haemorrhage from erosive gastritis, and the control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome. Placebo-controlled trials in outpatients have demonstrated its efficacy in promoting the healing of endoscopically diagnosed duodenal ulceration, during a period of 4 to 6 weeks, but its role in the treatment of gastric ulcer is less clear. Preliminary evidence suggests that maintenance therapy with cimetidine reduces the rate of recurrence of duodenal ulcer, but further studies are required to clarify its role in this situation and in the treatment of oesophagitis and acute gastrointestinal haemorrhage. Cimetidine controls the peptic ulceration of Zollinger-Ellison syndrome in most patients when given continuously for up to 2 years. Side-effects have generally been trivial and have very seldom necessitated withdrawal of therapy except in the rare occurrence of gynaecomastia. The haematological abnormalities particularly agranulocytosis, which lead to the withdrawal from clinical use of metiamide, have not been reported with cimetidine, except for 1 case of transient neutropenia. The safety of long-term cimetidine administration has yet to be determined.

Topics: Acute Disease; Animals; Cimetidine; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Guanidines; Humans; Intrinsic Factor; Recurrence; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycoproteins; Humans; Intestinal Mucosa; Peptic Ulcer; Receptors, Histamine; Secretin; Secretory Rate; Somatostatin; Stomach Ulcer; Vasoactive Intestinal Peptide

The familial aggregation of peptic ulcer disease has been well established, as has its association with such clear-cut genetic factors as blood group O and nonsecretor status. However, the genetics of this disorder, or group of disorders, is still in question. Polygenic inheritance is the prevailing hypothesis that has been proposed for peptic ulcer. This hypothesis was based primarily on the exclusion of a simple mode of inheritance for all ulcer disease. Genetic heterogeneity is an alternative hypothesis that can explain both the familial aggregation of peptic ulcer disease and the lack of a simple Mendelian pattern of inheritance. The evidence for genetic heterogeneity in peptic ulcer disease is reviewed, and studies are proposed to test this hypothesis.

Topics: ABO Blood-Group System; Antigens; Chromosome Aberrations; Chromosome Disorders; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pepsinogens; Peptic Ulcer; Phenotype; Pituitary Neoplasms; Stomach Ulcer; Werner Syndrome

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable elect

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Chromaffin System; Digestive System; Duodenal Ulcer; Endocrine System Diseases; Enterochromaffin Cells; Esophagitis, Peptic; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Intestinal Mucosa; Metabolic Diseases; Serotonin; Somatostatin; Stomach Neoplasms; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Calcium; Dietary Proteins; Duodenal Ulcer; Gastric Juice; Gastrins; Gastritis; Glucagon; Humans; Hyperplasia; Intestine, Small; Kidney Failure, Chronic; Pyloric Antrum; Pyloric Stenosis; Secretin; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Anemia, Pernicious; Duodenal Ulcer; Gastrectomy; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Liver; Molecular Weight; Peptic Ulcer; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

15-Methyl PGE2 and 16,16-dimethyl PGE2 were found (1) to be 40 and 100 times, respectively, more potent than PGE2 after intravenous administration in inhibiting histamine-stimulated gastric secretion in dogs with a denervated (Heidenhain) gastric pouch, (2) to be active orally and intrajejunally, whereas PGE2 was inactive, and (3) to exert antisecretory activity for longer duration than PGE2. 16,16-Dimethyl PGE2 was about 2.5 times more potent than 15-methyl PGE2. Volume, acid concentration, and output, and pepsin output (but not concentration) were reduced in a dose-dependent manner. In the rat, 16,16-dimethyl PGE2 also inhibited gastric secretion and prevented the formation of ulcers produced by various methods: gastric ulcers (Shay, and steroid induced) and duodenal ulcers (secretogogue induced). In this species, 1l816-dimethyl PGE2 was 2 to 50 times more potent than PGE2, depending on the endpoint, and was active orally. These prostaglandins appear to inhibit gastric acid secretion by acting directly on the parietal cells, and making these unresponsive to most stimulants. Vomiting was a side effect of the prostaglandin analogues in the dog, but almost exclusively when these were given orally. After intravenous or intrajejunal administration at doses inhibiting gastric secretion by 80%, vomiting was seen only once. These results suggest that 15-methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer.

Topics: Administration, Oral; Animals; Carbachol; Cyclic AMP; Depression, Chemical; Dogs; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Infusions, Parenteral; Jejunum; Male; Prednisolone; Prostaglandins E; Prostaglandins E, Synthetic; Pylorus; Rats; Stomach; Stomach Ulcer

The patient with gastric ulcer (GU) has abnormal reflux of bile-containing duodenal contents into the stomach. Antral gastritis is prominently associated with GU and is more extensive with severe reflux and with ulcer chronicity and probably when bile salts are accompanied by other constituents of duodenal fluids. Smoking is significantly associated with GU, and it produces reflux in normal subjects and in patients with duodenal ulcer, which in turn is commonly associated with GU. Reflux has not been shown to precede either the gastritis or the gastric ulcer and probably persists despite ulcer healing. The pyloric spincter in the patient with GU probably contracts subnormally to endogenous or exogenous secretin or CCK. This can be explained by associated hypergastrinemia since antral acidification improves the response. Because the pylorus may be usually open, abnormal reflux may be related as much or more to disturbances of other gastroduodenal functions known to control the movement of chyme through what may be a relatively passive pyloric zone. Speculation from animal models implicates bile reflux in aspirin-induced and shock-related gastric ulceration and assigns to bile a possible explanation, in part at least, for the apparent therapeutic efficacy of a carbenoxalone derivative and an antipepsin agent. Similar speculation warrants a search in the patient with GU for abnormalities of gastroduodenal peristalsis-related electric activity and for impaired release of secretin, possibly from antral cells of production. Possible abnormal purinergic inhibition of the gastric fundus and pylorus also warrants further study.

Topics: Animals; Bile; Cholecystokinin; Disease Models, Animal; Duodenum; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Humans; Pyloric Antrum; Pylorus; Secretin; Stomach Ulcer

Advances in the understanding of physiologic control of gastric secretion raise the hope that an effective nonsurgical therapy for peptic ulcer disease will be developed soon. This paper reviews these advances with special emphasis upon those aspects of hormonal control, cyclic nucleotide function, and histamine activity which may have therapeutic applications.

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Models, Biological; Pentagastrin; Receptors, Cholinergic; Secretin; Stomach Ulcer

Topics: Amino Acid Sequence; Animals; Cholecystokinin; Duodenal Ulcer; Gastrins; Gastrointestinal Hormones; Humans; Secretin; Stomach Ulcer

Topics: Animals; Dogs; Duodenal Ulcer; Duodenum; Evaluation Studies as Topic; Follow-Up Studies; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Methods; Stomach Ulcer

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Amino Acid Sequence; Animals; Catecholamines; Dehydration; Diarrhea; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Intestinal Mucosa; Peptic Ulcer; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Absorption; Animals; Cyclic AMP; Depression, Chemical; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Nicotine; Peptic Ulcer; Prostaglandins; Rats; Secretory Rate; Smoking; Stomach Ulcer

Topics: Acetylcholine; Anemia, Pernicious; Atrophy; Calcium; Carcinoma; Catecholamines; Circadian Rhythm; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Hormones, Ectopic; Humans; Ligation; Pancreatic Ducts; Secretin; Stimulation, Chemical; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Antacids; Asphyxia; Esophagitis; Esophagoscopy; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Hernia, Diaphragmatic; Humans; Methods; Parasympatholytics; Radiography; Stomach Ulcer

Topics: Anemia, Hypochromic; Body Weight; Bone Diseases; Chronic Disease; Diarrhea; Dumping Syndrome; Duodenal Obstruction; Duodenal Ulcer; Female; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Insulin; Male; Methods; Pentagastrin; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Postoperative Complications; Recurrence; Stomach Ulcer; Vomiting

Topics: Bile; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Ischemia; Permeability; Stomach Ulcer

Topics: Animals; Cholecystokinin; Dogs; Duodenal Ulcer; Esophagus; Gallbladder; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Pancreatic Juice; Secretin; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Diarrhea; Drainage; Dumping Syndrome; Duodenal Ulcer; Female; Gallbladder; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Gastrointestinal Motility; Humans; Intestine, Small; Male; Pancreas; Peptic Ulcer Perforation; Postoperative Complications; Pyloric Antrum; Pyloric Stenosis; Pylorus; Recurrence; Stomach; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Pepsin A; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Stomach Ulcer; Vagotomy; Vagus Nerve

Topics: Anxiety Disorders; Aspirin; Bile Acids and Salts; Blood Group Antigens; Diet; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Histamine; Humans; Hyperplasia; Male; Pentagastrin; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagotomy

Topics: Adolescent; Adult; Aged; Anemia, Hypochromic; Anemia, Pernicious; Atrophy; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Postgastrectomy Syndromes; Stomach Neoplasms; Stomach Ulcer

Topics: Dietary Proteins; Duodenal Ulcer; Feedback; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adrenal Cortex Hormones; Anemia, Pernicious; Animals; Antibodies; Autoantibodies; Biopsy; Chronic Disease; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Intrinsic Factor; Schilling Test; Stomach; Stomach Neoplasms; Stomach Ulcer; Vitamin B 12

Topics: Biopsy; Diagnosis, Differential; Diffusion; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Hydrogen-Ion Concentration; Male; Radiography; Recurrence; Stomach Ulcer; Vagotomy

Topics: Anemia, Pernicious; Animals; Diabetes Mellitus; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Rats; Secretory Rate; Stomach Ulcer

Topics: Afferent Loop Syndrome; Deglutition Disorders; Diet Therapy; Dumping Syndrome; Gastric Acidity Determination; Gastrins; Gastroenterostomy; Gastroscopy; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pentagastrin; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Stomach; Stomach Ulcer; Sutures; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Age Factors; Body Weight; Diagnosis, Differential; Duodenal Ulcer; Ethnicity; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Male; Methods; Pentagastrin; Sex Factors; Stomach Diseases; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Chlorpromazine; Circadian Rhythm; Cold Temperature; Diabetes Mellitus; Diet; Female; Gastric Juice; Gastrins; Humans; Kidney Diseases; Male; Middle Aged; Stomach Ulcer; Stress, Physiological

Topics: Abdomen; Duodenal Diseases; Duodenal Neoplasms; Duodenal Ulcer; Esophageal Achalasia; Esophageal Diseases; Esophageal Neoplasms; Esophagitis; Esophagoplasty; Esophagus; Female; Gastrins; Gastrointestinal Hemorrhage; Hernia, Diaphragmatic; Humans; Male; Peptic Ulcer; Peptic Ulcer Perforation; Postoperative Complications; Rupture, Spontaneous; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Stress, Psychological; Vagotomy

Topics: Amino Acid Sequence; Duodenal Ulcer; Feedback; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Absorption; Neurosecretory Systems; Pancreas; Peptic Ulcer; Secretin; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Achlorhydria; Adenoma; Anemia, Pernicious; Atrophy; Duodenal Ulcer; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Intrinsic Factor; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Central Nervous System; Cerebral Cortex; Digestion; Duodenal Ulcer; Eating; Emotions; Endopeptidases; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Pepsinogens; Peptic Ulcer; Psychophysiologic Disorders; Stomach; Stomach Ulcer

Topics: Alcohols; Aspirin; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Parasympatholytics; Peptic Ulcer; Peptic Ulcer Perforation; Sex Factors; Steroids; Stomach Ulcer; Stress, Physiological; Stress, Psychological; Time Factors

Topics: Animals; Cats; Ceruletide; Cholecystokinin; Digestive System; Digestive System Physiological Phenomena; Dogs; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon; Guinea Pigs; Humans; Pancreas; Secretin; Stomach Ulcer

Topics: Diagnosis, Differential; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Insulin; Intubation, Gastrointestinal; Methods; Pepsin A; Stomach; Stomach Diseases; Stomach Ulcer; Vagotomy

Topics: Antacids; Blood Circulation; Cryosurgery; Duodenal Ulcer; Electrolytes; Gastric Juice; Gastrins; Gastroenterostomy; Gonadal Steroid Hormones; Humans; Insulin; Pancreas; Pathology; Pepsin A; Peptic Ulcer; Pharmacology; Pylorus; Radiation Effects; Radiotherapy; Research; Stomach Ulcer; Stress, Physiological; Vagotomy; Zollinger-Ellison Syndrome

To evaluate the clinical characteristics, response to treatment and outcome of Zollinger?Ellison syndrome (ZES)-like gastric acid hypersecretors.. Over a 20-year period, patients with gastric acid hypersecretion in the absence of ZES were enrolled in an open label prospective trial evaluating the efficacy of lansoprazole. Following baseline evaluations, patients were treated with escalating doses of lansoprazole based on the results of gastric acid analysis. Following stabilization, patients were followed on a 6 monthly basis with interval history, physical examination, endoscopy with gastric biopsies, gastric acid analysis, and laboratory studies.. The study group represented 21 patients (median age 47 years, 86% male, 91% Caucasian). Historically, complicated ulcer disease was frequent and symptoms had been present for a median of 10 years before study entry. All patients responded to lansoprazole (median dose 90 mg/day) with excellent control of gastric acid hypersecretion. Mucosal relapse was infrequent and no major complications developed while on therapy.. ZES-like gastric acid hypersecretion presents similarly to the classic syndrome. Lansoprazole titrated to gastric acid output is effective in healing mucosal disease and preventing relapse.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Biopsy; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Lansoprazole; Male; Middle Aged; Prospective Studies; Stomach; Stomach Ulcer; Treatment Outcome; Zollinger-Ellison Syndrome

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

Gastric analysis is useful for diagnosing and monitoring the control of hypersecretory conditions and to distinguish appropriate from inappropriate causes of hypergastrinaemia. Pentagastrin, used to measure maximal acid output (MAO), is no longer available in the USA.. We examined the University of Pennsylvania Health System gastric analysis database, which includes demographic data, study indications, gastric analysis, and serum gastrin and secretin testing results according to referral indications, paying specific attention to discordant basal acid output (BAO) and MAO measurements.. One hundred and twenty-four gastric analyses were performed in 103 patients (42 males, mean age 47.5 years, 14 with prior acid-decreasing surgery). Recurrent ulceration or pain unresponsive to antisecretory therapy was the indication in 42 patients. Twelve were hypersecretory, including three each with isolated elevations of BAO or MAO. Hypergastrinaemia was the indication in 35 patients. Five were hypersecretory (four with Zollinger-Ellison syndrome), three had isolated MAO elevations and 16 were hypo- or achlorhydric, indicating appropriate hypergastrinaemia. Of the seven patients with isolated MAO elevations, two had clear benefit from the stimulated portion of the study (four additional patients had equivocal benefit).. Gastrin concentrations cannot be interpreted without knowledge of acid secretory capacity. MAO measurement has a small but significant benefit over measuring BAO alone.

Topics: Achlorhydria; Adolescent; Adult; Aged; Enzyme Inhibitors; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Proton Pump Inhibitors; Recurrence; Retrospective Studies; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

To compare the effects of rabeprazole 10, 20 and 40 mg o.d. on 24-h intragastric acidity and plasma gastrin concentration in a randomized, double-blind placebo-controlled trial.. Twenty-four healthy male volunteers were studied on the 7th day of morning dosing with either placebo or rabeprazole 10, 20 or 40 mg in a crossover fashion. On day 7, hourly intragastric acidity was measured for 24 h from 08.00 hours by gastric aspiration. Plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, and 2-hourly thereafter.. Compared with placebo, rabeprazole 10, 20 and 40 mg produced significant dose-related decreases in intragastric acidity (median 24-h integrated acidity=697, 186, 129 and 82 mmol h/L, respectively). This was associated with significant elevation of plasma gastrin concentration (median 24-h integrated gastrin=141, 1184, 1484 and 1763 pmol.h/L, respectively). Rabeprazole 40 mg resulted in significantly decreased acidity compared with both 10 and 20 mg, and in longer times for which intragastric pH was maintained at > 3 (19. 2 h vs. 17.3 h and 17.5 h) and > 4 (17 h vs. 14.2 h and 15.2 h), but was accompanied by significantly increased plasma gastrin. There was a consistent trend for greater antisecretory activity for 20 mg compared with 10 mg, but these differences did not reach statistical significance. The interindividual variability in antisecretory response was greatest with 10 mg.. Rabeprazole 10, 20 and 40 mg produce significant, profound dose-related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Cross-Over Studies; Double-Blind Method; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Omeprazole; Rabeprazole; Stomach Ulcer; Treatment Outcome

Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30 mg with placebo in preventing recurrence in 49 patients with a history of gastric ulcer. Within one month, 40% of patients receiving placebo experienced ulcer recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30 mg, respectively. All placebo patients became symptomatic, experienced ulcer recurrence or withdrew from the study by month 9. As compared to placebo, a significantly (P < 0.001) higher percentage of patients treated with lansoprazole 15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59% of those treated with lansoprazole 15 mg and 30 mg, respectively, remained asymptomatic at month 12. The incidence of adverse events was comparable among the treatment groups. Lansoprazole safely and effectively reduces ulcer recurrence in patients with a history of gastric ulcer disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Biopsy; Cell Count; Double-Blind Method; Enterochromaffin-like Cells; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Recurrence; Stomach Ulcer; Time Factors

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 compare the effects of long-term lansoprazole and omeprazole treatment (6 months) on serum gastrin levels.. Forty duodenal ulcer patients without previous treatment with proton pump inhibitors were randomized to receive either 20 mg/day or omeprazole or 30 mg/day of lansoprazole. Serum gastrin levels were determined on entry and every 2 months. On finalizing the study antral and fundic biopsies were obtained for immunohistochemical analysis of the enterochromaffin-like cell population.. Before starting the treatment fasting serum gastrin was similar in both groups (108.7 +/- 60.9 pg/mL omeprazole; 102.7 +/- 56.9 pg/mL lansoprazole). The treatment with either omeprazole or lansoprazole increased serum gastrin levels, but the increase was mild, maximal at 2 months and similar between omeprazole and lansoprazole (113.44 +/- 114.9 pg/mL omeprazole vs 166.1 +/- 117.9 pg/mL lansoprazole; p > 0.05). When serum gastrin levels were individually analyzed by patient, most were below 200 pg/mL and only 3 patients (1 omeprazole/2 lansoprazole) had levels near 500 pg/mL which were not correlated with enterochromaffin-like cell hyperplasia.. Long-term treatment with either omeprazole or lansoprazole is safe, at least during 6 months, and results in mild hypergastrinemia. No differences between these two drugs were observed.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Double-Blind Method; Female; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Stomach Ulcer

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

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.

Topics: Adult; Aged; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Peptic Ulcer; Pirenzepine; Radioimmunoassay; Somatostatin; Stomach Ulcer

We studied the effects of lansoprazole with or without amoxicillin on the quality of ulcer healing in relation to eradication of Helicobacter pylori. Ulcer healing rates for lansoprazole 30 mg q.d. alone (group A) were 100% for duodenal ulcers (DU; n = 20) and 92% for gastric ulcers (GU; n = 15). The healing rates for lansoprazole 30 mg plus amoxicillin 1-2 g q.d. (group B) were 100% for both DU (n = 20) and GU (n = 12). Endoscopic findings after treatment showed that the red scar/white scar ratio in group A was 16/4 for DU and 12/1 for GU. The red scar/white scar ratio in group B was 4/16 for DU and 6/6 for GU. The numbers of H. pylori in gastric mucus did not change throughout the course of treatment in group A but decreased significantly, without H. pylori relapse, in group B. Changes in ammonia concentration in gastric juice, as well as serum gastrin and pepsinogen I and II levels, differed between group A and group B. Concomitant treatment with lansoprazole and high-dose amoxicillin eradicated H. pylori and modified gastric secretory function, resulting in high-quality ulcer healing.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Ulcer Agents; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Lansoprazole; Omeprazole; Penicillins; Pepsinogens; Peptic Ulcer; Proton Pump Inhibitors; Stomach Ulcer

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

The effect of lansoprazole, a new benzimidazole proton pump inhibitor, on the relationship between ulcer healing and changes in mucin content was studied in gastric ulcer patients. Twenty-one outpatients with active gastric ulcers received lansoprazole 30 mg once daily given in the morning for 8 weeks. The gastric mucin content was examined by HPLC analysis of hexosamines in gastric biopsy specimens obtained from the lesser curvature of the pylorus and the greater curvature of the upper body. The ulcer healing rate for lansoprazole was 85.7% at 8 weeks. The mucin content of both mucosal regions significantly decreased to approximately 70% (pylorus 70.9%; upper body 74.7%) of the value before drug treatment. The results of this study demonstrate that 30 mg lansoprazole once daily is remarkably effective in healing gastric ulcers because of its potent acid suppression. It appears that acid inhibition is the primary factor in initial treatment. However, maintaining an altered gastric mucosal defense mechanism may have implications for the long-term treatment of gastric ulcers.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Depression, Chemical; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Mucins; Omeprazole; Proton Pump Inhibitors; Stomach Ulcer

Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase.. The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, double-blind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n = 146) or omeprazole 20 mg (n = 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed.. After 4 weeks, complete ulcer healing was seen in 88% of protocol-correct patients given pantoprazole and in 77% given omeprazole (between-group difference P < 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention-to-treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain-free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks.. Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Benzimidazoles; Double-Blind Method; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Pain; Pantoprazole; Proton Pump Inhibitors; Stomach Ulcer; Sulfoxides

A higher incidence of gastric and duodenum ulcer was well recognized in patients with liver cirrhosis, but the mechanism has not been fully identified. In this study, serum gastrin, free portal pressure (FPP) were measured in 24 consecutively admitted cirrhotic portal hypertensive patients, and preoperative basic acid output (BAO) was measured in 13 randomized patients. Among the 24 patients, concomitant duodenal ulcers were found in 3 by both gastroduodenoscopy and barium series, and gastritis was found in all patients. It was found that most patients (71%) with liver cirrhosis have a elevated level in serum gastrin, whereas BAO is lower than normal in all patients, and the higher the FPP, the lower the BAO is. We believe that the congestive gastroduodenal mucosal lesion was underlying the ulceration most often seen in patients with portal hypertension.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Stomach Ulcer

Serum gastrin levels in 44 peptic ulcer patients (26 gastric ulcer patients and 18 duodenal ulcer patients) were determined after they had been treated with omeprazole (OPZ) (20 mg/day) alone or in combination with pirenzepine (PZP) (100 mg/day). Serum gastrin levels were measured before, as well as 2, 4, and 6 weeks after administration, and the changes were compared. The levels were significantly elevated (twofold) at 2 weeks of treatment in both the OPZ and OPZ plus PZP groups. In patients taking OPZ alone, the levels rose up to 6 weeks, while in those taking OPZ plus PZP the levels decreased at 4 and 6 weeks. At 4 weeks, serum gastrin levels in the OPZ plus PZP group were lower (although not significantly) than those in patients taking OPZ alone. In gastric ulcer patients, serum gastrin levels in the OPZ group were significantly elevated, while in the OPZ plus PZP group, these levels were only slightly, but not significantly elevated. There was no significant difference between the two gastric ulcer groups at any time. In duodenal ulcer patients, serum gastrin levels increased significantly at 2 weeks of treatment in both groups. At 4 weeks and thereafter, the serum gastrin levels remained significantly high in patients taking OPZ alone, while they decreased at both 4 and 6 weeks in patients taking OPZ plus PZP. Thus, serum gastrin levels in duodenal ulcer patients were markedly decreased by the addition of PZP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Drug Therapy, Combination; Duodenal Ulcer; Gastrins; Humans; Omeprazole; Peptic Ulcer; Pirenzepine; Stomach Ulcer

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.

Topics: Adolescent; Adult; Aged; Aging; Child; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pepsin A; Pepsinogens; Peptic Ulcer; Retrospective Studies; Stomach Ulcer

Patients (106) with peptic ulceration of the oesophagus, stomach and duodenum, unresponsive to 3 or more months of high-dose treatment with ranitidine, were initially given pantoprazole (40-80 mg, p.o.) daily. In 96.7% of the patients ulcers healed within 2 to 8 weeks, and in 2.3% of patients the ulcers healed within 12 weeks. In just one patient with severe oesophagitis, the lesion took more than 6 months to heal. After ulcer healing, patients (98 to date) were treated with pantoprazole (40 mg/day) as long-term maintenance therapy. Eighty-eight of the 98 patients have been taking pantoprazole for 6 months to 3 years. During maintenance therapy, peptic disease was kept in remission in most patients with 40 mg pantoprazole. Twelve patients with oesophagitis and two patients with gastric ulcers needed higher doses (80-120 mg) to control the disease. One female patient developed peripheral oedema which disappeared quickly after stopping treatment. No further drug-related adverse effects were observed. Seven patients withdrew from the study and two patients died, all for non-drug-related reasons. Routine laboratory tests remained without significant changes in all patients. Mean (+/- S.E.M.) serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (128 +/- 23 pg/ml). Within one year of the start of the pantoprazole treatment, serum gastrin levels rose to 3 times normal values (189 +/- 32 pg/ml). Thereafter, no further increases in serum gastrin were observed for up to 2.5 years. Enterochromaffin-like (ECL) cell density increased very slightly from 0.19% to 0.24% within one year.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis; Female; Gastrins; Humans; Longitudinal Studies; Male; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Ranitidine; Stomach Ulcer; Sulfoxides

Forty-two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high-dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30-60 mg daily. In 40 patients (95.2%) the ulcers healed within 2-12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long-term maintenance treatment with 30-60 mg lansoprazole daily for 1-3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug-related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high-dose ranitidine treatment (125 +/- 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 +/- 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin-like cells has been observed. In conclusion, 30-60 mg lansoprazole daily healed ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with 30-60 mg lansoprazole daily was found to be highly effective and safe over the time observed.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis; Female; Follicle Stimulating Hormone; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Luteinizing Hormone; Male; Omeprazole; Peptic Ulcer; Pyloric Antrum; Ranitidine; Stomach Ulcer; Testosterone

A study was conducted to test the efficacy and safety of a 300 ml silicone-rubber gastric balloon for weight reduction. Eighty-six obese subjects were distributed into four groups: (1) gastric balloon only, (2) gastric balloon and prescribed 1000 kcal/day (239 kJ) diet, (3) 1000 kcal/day diet only, and (4) no treatment. The intervention period was 3 months. The balloon only group lost 3.2 kg +/- 0.9 (s.e.), the balloon and diet group lost 5.1 +/- 1.0 kg, the diet group lost 6.9 +/- 1.4 kg and the control group gained 0.6 +/- 0.5 kg. The three intervention groups each lost significantly more weight than the control group. The diet only group lost significantly more weight than the balloon only group. Body densitometry showed that the treatment groups lost a significant amount of body fat. Gastroscopy revealed three ulcers and two superficial erosions at balloon removal. The gastric balloons were well tolerated despite gastric spasms and nausea which abated after the initial 24-48 hours. Gastric capacity was determined in a subset of 19 subjects from the two balloon groups before the intervention by distending the stomach with a balloon and calculating the volume required to produce an increase in intragastric pressure of 5 cm H2O. Subjects with a smaller gastric capacity lost more weight with the balloon than subjects with a large capacity (r = 0.45, P less than 0.05). These results suggest that for improved efficacy, balloon volume may need to be larger than 300 ml or adjusted to the individual's gastric capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Body Composition; Diet, Reducing; Energy Intake; Female; Follow-Up Studies; Gastric Balloon; Gastrins; Humans; Male; Obesity; Stomach; Stomach Ulcer; Weight Loss

In a double-blind placebo-controlled study, the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in six patients with type I gastric ulcer. Synthetic salmon calcitonin 415 pmol i.v. was given as a bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin suppressed gastric emptying in all patients examined. The mean gastric transit time, MTT90, increased from 38.1 +/- 0.4 min after placebo to 43.1 +/- 0.6 min after calcitonin (P less than 0.001). Calcitonin significantly blunted the postprandial gastrin release: AUC0-90 10,398 +/- 2886 ng. l-1 min (placebo) and 8238 +/- 2573 ng. l-1 min (calcitonin), P less than 0.05, and abolished the postprandial insulin release--AUC0-90 2244 +/- 230 mU.l-1 min (placebo) vs. 638 +/- 198 mU.l-1 min (calcitonin), P less than 0.01. A steady increase in the serum glucose during calcitonin infusion, reaching up to 5.6 +/- 0.31 mmol.l-1 at the end of the infusion, was observed. Calcitonin did not significantly affect serum calcium or phosphorus concentrations. The authors conclude that a delayed gastric emptying is to be expected in patients undergoing calcitonin treatment.

Topics: Adult; Aged; Calcitonin; Double-Blind Method; Eating; Gastric Emptying; Gastrins; Humans; Insulin; Male; Middle Aged; Stomach Ulcer

A total of 143 patients with peptic ulceration of the duodenum, stomach or oesophagus, who did not respond to 3 or more months high-dose treatment with ranitidine (450 mg or more daily), were admitted to oral treatment with omeprazole, 40 mg/day. In 94.4% of the patients, ulcers healed within 2-6 weeks. After healing of their ulcers, 122 patients were admitted to long-term maintenance treatment with omeprazole, 40 mg/day; 91 patients have been on the drug for 1-5.5 years. During maintenance therapy with omeprazole, 40 mg/day, no relapses (verified by endoscopy) have yet occurred and no drug related adverse effects have been observed. There were no significant changes in routine laboratory tests in any patients, including 27 with concomitant liver cirrhosis. Serum gastrin levels were already elevated approximately 2-fold during the initial high-dose ranitidine treatment and rose a further 2-fold at 2-3 months of omeprazole treatment. Thereafter, no further increase of serum gastrin was observed even after 5.5 years of continuous observation. Volume density of G and D cells in the antral mucosa did not change significantly. The volume density of argyrophilic cells in the oxyntic mucosa was 0.73 +/- 0.1% before the start of omeprazole treatment and 0.85 +/- 0.09% after 17-24 months of continuous treatment with omeprazole (ns). In antrectomized patients the volume density was lower (0.23 +/- 0.04%). No clusters of argyrophilic cells were observed in any of the groups. In a control group of patients with gastrinoma the volume density of these cells was higher (1.3 +/- 0.23%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Clinical Trials as Topic; Duodenal Ulcer; Esophagitis, Peptic; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Long-Term Care; Omeprazole; Ranitidine; Stomach Ulcer

Roxatidine acetate is a novel H2-receptor antagonist with a chemical structure different to the earlier drugs of this type. It is a potent inhibitor of histamine-mediated gastric acid secretion and in animal models is 4 to 6 times as potent as cimetidine. In a multicentre double-blind clinical trial of over 700 patients with gastric or duodenal ulcers roxatidine acetate 75 mg twice daily and cimetidine 200mg four times daily produced endoscopically confirmed and subjective and objective healing rates in excess of 90% for both types of ulcer, with no significant difference between the treatments. Roxatidine acetate's efficacy in stomal ulcer (marginal ulcer) and reflux oesophagitis has been confirmed in non-comparative studies of up to 8 weeks' duration. The overall incidence of adverse reactions in 1623 patients treated with roxatidine acetate 75 mg twice daily was 1.7%, with skin rashes and constipation the most frequently reported side effects.

Topics: Adult; Cimetidine; Duodenal Ulcer; Female; Gastrins; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Pepsinogens; Peptic Ulcer; Piperidines; Prolactin; Stomach Ulcer; Time Factors

Fasting plasma levels of immunoreactive gastrin, somatostatin, and pancreatic polypeptide (PP) were determined in 67 patients with an endoscopically proven duodenal, pyloric, or prepyloric ulcer. Pretreatment gastrin (45.6 +/- 53.6 pmol/l, mean +/- S.D.) and somatostatin (54.5 +/- 27.5 pg/ml) did not differ significantly from those in 22 healthy controls (21.8 +/- 20.2 pmol/l and 64.8 +/- 24.7 pg/ml, respectively). The gastrin and somatostatin levels were not changed by 3 weeks of treatment either with propantheline and antacids or with cimetidine and antacids. The mean PP value before treatment was significantly (p less than 0.01) higher in duodenal ulcer patients (0.76 +/- 0.55 ng/ml) than in healthy subjects of similar age (0.36 +/- 0.26 ng/ml). The increased PP level was not lowered significantly by medical treatment even when this resulted in healing of the ulcer.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Propantheline; Radioimmunoassay; Somatostatin; Stomach Ulcer

The influence of Domperidone and Metoclopramide on the Serum Gastrin Level and Gastric Acid Secretion was investigated in a crossed, randomized double blind study in 12 male subjects aged 29 years on the average and presenting a healthy stomach. Neither after Domperidone nor after Metoclopramide could a significant change in Gastrin Level and Acid Secretion be observed. Since both Domperidone and Metoclopramide exert a motility promoting but not secretagogue effect on the upper gastrointestinal tract, both drugs are suitable for the treatment of disordered motility and evacuation related to ulcer disease, as well as for the treatment of postoperative gastroatonia.

Topics: Adult; Antiemetics; Benzimidazoles; Domperidone; Gastric Acid; Gastrins; Gastrointestinal Motility; Humans; Male; Metoclopramide; Piperidines; Postoperative Complications; Stomach Ulcer

In a double-blind trial 16 persons with gastric ulcer and 35 with duodenal ulcer were treated as out-patients with 1200 mg proglumide daily or 1320 mg magnesium tricilicate daily (as an "active placebo") for four weeks. The ulcers were assessed by endoscopy before and after treatment. The gastric ulcers disappeared in 75% of patients receiving proglumide (six of eight subjects) but in only 25% of those on the placebo (two of eight). There was no significant effect of proglumide on duodenal ulcers (17 in the proglumide and 18 in the placebo groups). Proglumide failed to affect either basal or maximally stimulated acid secretion, nor was there any change in the serum gastrin level. There were no side effects during proglumide administration. This underlines its therapeutic value in the treatment of gastric ulcer, in comparison with cimetidine or carbenoxolone.

Topics: Adult; Aged; Ambulatory Care; Double-Blind Method; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Gastroscopy; Glutamine; Humans; Male; Middle Aged; Placebos; Proglumide; Stomach Ulcer

A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.

Topics: Adult; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Glutamine; Guanidines; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proglumide; Stomach Ulcer; Time Factors

The effect of carbenoxolone on the healing of gastric ulcer and erosions was compared with that of placebo. The series consisted of 20 patients with chronic gastric ulcers and 20 patients with superficial erosions of the stomach. The diagnosis as well as the follow-up of the lesions were based on gastroscopic examinations. The ulcers were measured gastroscopically. A double-blind method was used. Besides carbenoxolone 50 mg or placebo three times daily, all the patients received antacids in fixed dosage for six weeks. Subjective symptoms and cardiovascular side-effects were recorded. Maximal acid output and serum gastrin levels were measured before and after the treatment. No difference was seen between carbenoxolone and placebo groups with regard to the healing rate of the ulcers of disappearance of the erosions. The subjective symptoms subsided significantly faster in the treatment groups than in the control groups. No cardiovascular side-effects were evident during the treatment with carbenoxolone. One patient needed potassium supplements. Carbenoxolone had no effect on the pentagastrin-stimulated gastric acid secretion nor on the serum gastrin values.

Topics: Carbenoxolone; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Follow-Up Studies; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Humans; Stomach Ulcer; Triterpenes

The treatment of gastric ulcer by the H2-receptor-antagonist Cimetidine results in an ulcer healing rate of 60 to 80% during a 4 to 6 weeks therapy cure. In most studies Cimetidine is superior to placebo or equipotent to a high dose antacid regimen, the latter being accepted to be of beneficial effect on ulcer healing. In the Zollinger-Ellison-syndrome Cimetidine inhibits largely gastric acid hypersecretion and represents for the first time a true alternative to total gastrectomy.

Topics: Antacids; Carbenoxolone; Cimetidine; Double-Blind Method; Gastric Juice; Gastric Mucosa; Gastrins; Guanidines; Humans; Placebos; Stomach Ulcer; Zollinger-Ellison Syndrome

Parietal cell vagotomy has been in clinical use for 7 years in elective treatment of nonobstructive duodenal ulcer, and for even a shorter period for complicated cases and for gastric ulcer The evolution of the surgical technique has not yet come to an end and the ability to perform the procedure is still improving. It can therefore be questioned, if this operation is yet ripe for a realistic clinical trial, and the great variation in recurrence rate reported in pilot series as well as in prospective randomized clinical trials points to the possibility that we will have to wait several years before the anticipated mean recurrence rate is known. At present it can be stated that even if gastric emptying is not quite undisturbed, the addition of a drainage procedure in nonobstructive cases is unnecessary. The same may be true in some patients with pyloric obstruction. Furthermore, the mortality rate is very low and the incidence of moderate-to-severe dumping and diarrhea is virtually nil.

Topics: Animals; Clinical Trials as Topic; Denmark; Diarrhea; Drainage; Dumping Syndrome; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Motility; Humans; Peptic Ulcer; Pilot Projects; Postoperative Complications; Pyloric Stenosis; Recurrence; Stomach; Stomach Ulcer; Vagotomy

Topics: Blood Glucose; Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Placebos; Propranolol; Stimulation, Chemical; Stomach Ulcer; Vagotomy

Topics: Adolescent; Adult; Aged; Benzamides; Clinical Trials as Topic; Drug Evaluation; Duodenal Ulcer; Female; Gastrins; Gastritis; Gastrointestinal Agents; Glutarates; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

Topics: Absorption; Adult; Dosage Forms; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Mouth Mucosa; Pepsin A; Peptides; Stomach Ulcer

Topics: Adult; Clinical Trials as Topic; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Diseases; Histamine; Humans; Methods; Middle Aged; Stimulation, Chemical; Stomach Ulcer

Topics: Adult; Aged; Anemia, Pernicious; Carcinoma; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Hernia, Diaphragmatic; Histamine; Humans; Male; Middle Aged; Secretory Rate; Stomach; Stomach Neoplasms; Stomach Ulcer

Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear.. This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment.. The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting.. The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01).. The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Topics: Animals; Citrus; Dinoprostone; Gastrins; Gene Expression Regulation; Male; Pepsinogen C; Plant Oils; Pogostemon; Protective Agents; Rats; Rats, Sprague-Dawley; Restraint, Physical; Serotonin; Stomach Ulcer

Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical constitutes, gastroprotective effects, and the active fraction of C. fimbriata, as well as elucidating the underlying mechanisms. Firstly, four in vitro antioxidant tests were applied to determine the oxidation resistance of C. fimbriata methanol extract and its fractions. The gastroprotective effects were evaluated in ethanol-induced gastric ulcer rats, gastric histopathology was visualized by H&E staining, and the acidity of gastric juice was measured by titrating with NaOH solution. The contents of malondialdehyde, catalase, superoxide dismutase, gastrin, and the activity of H

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Methanol; Orchidaceae; Plant Extracts; Rats; Stomach Ulcer

Diagnosis of gastric ulcers by methods other than gastroscopy in dogs has been problematic for many years and biomarkers such as serum gastrin (SG) concentrations have been introduced as a noninvasive way to evaluate gastric diseases.. To determine the time course changes in hematology, SG concentrations, and gastroscopic images of meloxicam-induced gastric ulceration in dogs and identify a relationship between SG and gastroscopic image analysis in a clinical setting.. Fifteen crossbreed dogs.. Two groups: control (n = 5) and meloxicam-treated (n = 10). The meloxicam-treated group received meloxicam 0.2 mg/kg PO for 15 days. Clinical signs, hematology, SG, and image analysis (PI, pixel intensity; ID, integrated density; RA, relative area; and UI, ulcer index) of the gastroscopic examination were evaluated across time (T5, time 5 day; T10, time 10 day; and T15, time 15 day).. Significant changes were observed among 3 time points and between the 2 groups in terms of SG, hematology, and gastroscopic image analysis. In the meloxicam-treated group, decreases in hemoglobin concentration, red blood cell count and packed cell volume at T10 and T15 (P = .0001) were observed, whereas SG, ID, and UI increased over time (P < .0001). The PI decreased significantly (P = .0001) in the meloxicam-treated group compared to controls. Significant correlations were found between SG and PI, and ID and ulcer area (r = -0.89, 0.81, 0.64), respectively.. Gastroscopy is the gold standard for early descriptive diagnosis of gastric ulcerations in dogs, and SG is a good indicator for meloxicam-induced gastric ulcers in dogs and can predict the gastroscopic score of the lesion.

Topics: Animals; Dog Diseases; Dogs; Gastrins; Gastroscopy; Hematology; Meloxicam; Stomach Ulcer; Thiazines; Thiazoles

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Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastrins; Gastrointestinal Hemorrhage; Humans; Stomach Ulcer

 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 antioxidizing properties of curcumin, a highly pleiotropic substance used for centuries in traditional medicine has been confirmed by numerous experimental and clinical studies. Curcumin exhibits anti-inflammatory, antiproliferative and anti-angiogenic actions inhibiting the development and progression of tumors but the efficacy of this compound to influence gastric acid secretion n in the stomach and to affect the gastric mucosal damage induced by non-topical ulcerogenes such as stress has been little studied. We determined the effect of curcumin on basal and pentagastrin- or histamine-stimulated gastric secretion, in rats with surgically implemented gastric fistulas and we assessed the contribution of gastric secretion, endogenous prostaglandin (PG), endogenous nitric oxide (NO), as well as sensory afferent nerves in the mechanisms underlying the potential gastroprotective effects of curcumin against stress-induced gastric mucosal lesions. Rats exposed to water immersion and restraint stress (WRS) for 3.5 h were pretreated either with: 1) vehicle (saline); 2) curcumin (2.5 - 100 mg/kg i.g.) or 3) curcumin (50 mg/kg i.g.) combined with or without indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.) or rofecoxib (10 mg/kg i.g.); 4) curcumin (50 mg/kg i.g.) co-administered with (L-NNA (20 mg/kg i.p.) with or without L-arginine (200 mg/kg i.g.), a substrate for NO-synthase; 5) curcumin (50 mg/kg i.g.) administered in rats with intact or capsaicin-induced functional ablation of sensory nerve fibers, and 6) curcumin (50 mg/kg i.g.) administered with capsazepine (5 mg/kg i.g.), the antagonist of vanilloid TRPV1 receptor. The number of gastric lesions was determined by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique, the plasma gastrin concentrations were measured using the radioimmunoassay (RIA) and the expression of mRNA for tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in gastric mucosa was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Curcumin dose-dependently reduced the WRS-induced gastric lesions, the dose inhibiting these lesions by 50% being about 50 mg/kg. These effects of curcumin were accompanied by an increase in GBF and the reduction in basal and histamine- or pentagastrin-stimulated gastric acid secretion. The protective and hyperemic activities of curcumin (50 mg/kg i.g.) against WRS lesions were significantly attenuated (P < 0.0

Topics: Animals; Anti-Ulcer Agents; Capsaicin; Curcumin; Cyclooxygenase 2; Female; Gastric Acid; Gastric Mucosa; Gastrins; Immersion; Male; Nitric Oxide Synthase Type II; Rats, Wistar; Restraint, Physical; RNA, Messenger; Stomach Ulcer; Stress, Psychological; TRPV Cation Channels; Tumor Necrosis Factor-alpha; Water

The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19 h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56 mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28 mm(2)) compared with model group (26.36 mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers.

Topics: Alkaloids; Animals; Anti-Ulcer Agents; Chromatography, High Pressure Liquid; Gastric Acid; Gastrins; H(+)-K(+)-Exchanging ATPase; Ligation; Mahonia; Male; Mucins; Plant Stems; Rats, Sprague-Dawley; Stomach Ulcer; Tandem Mass Spectrometry

The present study was designed to evaluate the anti-ulcerogenic properties of an alkaloid chromane, rohitukine from Dysoxylum binectariferum. Anti-ulcer potential of rohitukine was assessed in cold restrained, pyloric ligated and ethanol induced ulcers in rats. In addition, rohitukine was tested in vitro for H(+) K(+)-ATPase inhibitory activity in gastric microsomes. Moreover, we studied the role of rohitukine on the cytosolic concentration of Ca(2+) in parietal cell-enriched cell suspension in order to ascertain its mechanism of action. Cytoprotective activity was evaluated through PGE(2) level. Rohitukine significantly attenuated the ulcers in cold restraint ulcer (CRU) model in a dose-related manner. Moreover, it significantly lowered the free acidity and pepsin activity in pyloric ligated rats while improved the depleted level of mucin. Furthermore, rohitukine significantly reversed the cold restrained-induced increase in gastrin level. Our in vitro study revealed that rohitukine moderately inhibited the microsomal H(+) K(+)-ATPase activity with respect to positive control omeprazole. Furthermore, rohitukine potently antagonized the gastrin-elicited increase in cytosolic Ca(2+) level in parietal cell-enriched suspension. In ethanol-induced gastric lesions in rats, rohitukine significantly inhibited the formation of erosions and increased PGE(2) content showing more potency than reference drug sucralfate. Our results thus suggest that rohitukine possess significant anti-ulcer and anti-gastrinic activity in rats. It is likely that gastro-protective influences of rohitukine are dependent partly on its acid-lowering potential and partly on cytoprotective property. The acid-reducing effect of rohitukine might be attributed to its lowering effect on gastrin production and/or antagonism of gastrin-evoked functional responses of parietal cells. Thus, rohitukine represent a useful agent in the treatment of peptic ulcer disease.

Topics: Animals; Anti-Ulcer Agents; Antineoplastic Agents; Calcium; Chromones; Cold Temperature; Disease Models, Animal; Ethanol; Gastrins; H(+)-K(+)-Exchanging ATPase; Ligation; Meliaceae; Microsomes; Piperidines; Plant Bark; Proton Pump Inhibitors; Pylorus; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Nonsteroidal anti-inflammatory drugs (NSAIDs) are valuable agents; however, their use has been limited by their association with mucosal damage in the upper gastrointestinal tract. NSAIDs inhibit cyclooxygenase and consequently block the synthesis of prostaglandins, which have cytoprotective effects in gastric mucosa; these effects on prostaglandins have been thought to be major cause of NSAID-induced ulceration. However, studies indicate that additional NSAID-related mechanisms are involved in formation of gastric lesions. Here, we used a toxicoproteomic approach to understand cellular processes that are affected by NSAIDs in mouse stomach tissue during ulcer formation. We used fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS)-which consists of fluorogenic derivatization, separation and fluorescence detection by LC, and identification by LC-tandem mass spectrometry-in this proteomic analysis of pyrolic stomach from control and diclofenac (Dic)-treated mice. FD-LC-MS/MS results were highly sensitive; 10 differentially expressed proteins were identified, and all 10 were more highly expressed in Dic-treated mice than in control mice. Specifically, expression levels of 78 kDa glucose-regulated protein (GRP78), heat shock protein beta-1 (HSP27), and gastrin were more than 3-fold higher in Dic-treated mice than in control mice. This study represents a first step to ascertain the precise actors of early NSAID-induced ulceration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Cyclooxygenase Inhibitors; Diclofenac; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Fluorescent Dyes; Gastric Mucosa; Gastrins; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Male; Mice; Mice, Inbred C57BL; Proteomics; Stomach Ulcer; Tandem Mass Spectrometry

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

Phytochemical investigation of Annona squamosa twigs, resulted in isolation and identification of twelve known (1-12) compounds among them one 1-(4-β-D-glucopyranosyloxyphenyl)-2-(β-D-glucopyranosyloxy)-ethane (11) is synthetically known but first time isolated from natural sources. Their structures were elucidated using 1D and 2D NMR spectroscopic analysis. The isolated compounds (2-8, 11) were evaluated for H(+) K(+)-ATPase activity. Three of these compounds (+)-O-methylarmepavine (2), N-methylcorydaldine (3), isocorydine (6) showed promising anti-secretory activity. Activity of these compounds, comparable to the standard drug omeprazole is novel to our finding. Moreover, there is no information accessible regarding the pharmacological effect of A. squamosa on the gastrointestinal system. This study is the first of its kind to show the significant anti-ulcer effect of A. squamosa. The present study aimed to evaluate the gastroprotective effect of A. squamosa (AS) and to identify its active constituents. Anti-ulcer activity was evaluated against cold restraint (CRU), pyloric ligation (PL), aspirin (ASP), alcohol (AL) induced gastric ulcer and histamine (HA) induced duodenal ulcer model and further confirmed through in vitro assay of H(+) K(+)-ATPase activity and plasma gastrin level. AS and its chloroform and hexane fraction attenuated ulcer formation in CRU, PL, HA model and displayed anti-secretory activity in vivo through reduced free, total acidity and pepsin in PL, confirmed by in vitro inhibition of H(+) K(+)-ATPase activity with corresponding decrease in plasma gastrin level. Cytoprotection of AS was apparent with protection in AL, ASP models and enhanced mucin level in PL.

Topics: Animals; Annona; Anti-Ulcer Agents; Aporphines; Aspirin; Benzylisoquinolines; Berberine Alkaloids; Cold Temperature; Dinoprostone; Disaccharides; Drug Evaluation, Preclinical; Duodenal Ulcer; Ethanol; Gastric Juice; Gastrins; Guinea Pigs; H(+)-K(+)-Exchanging ATPase; Histamine; Ligation; Omeprazole; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological

RegI (Regenerating islet derived-1) was originally characterized as a growth factor involved in pancreatic islet cell regeneration. It is also considered a gastrointestinal mitogen as its expression is increased during pathologies involving aberrant cell proliferation that can lead to neoplasia. However, the absolute requirement for RegI to directly stimulate gastric mucosal cell proliferation in vivo requires further investigation. We used RegI-deficient mice to determine the requirement for RegI in normal gastric mucosal development, wound healing, hyperplasia and tumourigenesis. We found that epithelial repair of acetic acid ulcers in compound mutant RegI/gastrin-deficient mice was significantly reduced compared to wild type, RegI-deficient or gastrin-deficient mice. In contrast, RegI was dispensable for normal gastric mucosal development, hyperplasia in HKbeta-deficient mice and tumourigenesis in gp130(F/F) mice. Although RegI was not required for proliferation in these pathological models, expression of multiple Reg family members were increased during gp130(F/F) tumourigenesis. Interestingly, loss of RegI in gp130(F/F) mice resulted in decreased expression of other Reg family members. Our results indicate that RegI and gastrin may synergistically regulate gastric mucosal proliferation during certain pathological settings like wound healing while gastric epithelial proliferation in other pathologies may require coordinated expression of multiple Reg genes.

Topics: Animals; Base Sequence; Cell Proliferation; Gastric Mucosa; Gastrins; Hyperplasia; Immunoblotting; Lithostathine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Sequence Alignment; Stomach Neoplasms; Stomach Ulcer; Wound Healing

The effect of the administration of a whey protein isolate (WPI) and collagen hydrolysates on ethanol-induced ulcerative lesions was studied in rats. WPI and bovine or porcine collagen hydrolysate (BCH and PCH, respectively) were given to rats by gavage. In acute experiments, (single-dose) physiological saline (10 mL/kg of body weight) was used as the negative control, and carbenoxolone (200 mg/kg of body weight) was used as a positive control. Ethanol (1 mL per 250-g rat) was also given by gavage. These treatments reduced the ulcerative lesion index (ULI) in a range of 40-77%, depending on the dosage. Some mixtures of WPI with either PCH or BCH provided results that suggested synergisms between WPI and the collagen hydrolysates. For example, WPI/BCH (in the proportion of 375:375 mg/kg of body weight) decreased ULI by 64%. The mechanism for mucosal protection involved a decrease in plasma gastrin (approximately 40%), a significant increase (50-267%) in mucus production, and a reduction in ULI (percentage) when intragastric administrations were performed after in vivo alkylation by N-ethylmaleimide. Results suggest that gastrin, sulfhydryl substances, and some mechanisms related to mucus production are all involved in gastric ulcer protection against ethanol. The collagen hydrolysates (both PCH and BCH) presented a stronger effect on mucus production; on the other hand, the effect of WPI was also dependent on sulfhydryl compounds, resulting in a more protective effect when the two proteins were administered together.

Topics: Alkylation; Animals; Anti-Ulcer Agents; Carbenoxolone; Cattle; Collagen; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Ethanol; Ethylmaleimide; Gastric Mucosa; Gastrins; Hydrolysis; Male; Milk Proteins; Mucus; Rats; Rats, Wistar; Stomach; Stomach Ulcer; Sulfhydryl Compounds; Swine; Whey Proteins

Evidences have suggested that Tectona grandis (TG) attenuates gastric mucosal injury; however its mechanism has not yet been established. The aim of present study was to evaluate the gastroprotective mechanism of ethanolic extract of TG (E-EtOH), butanolic fraction (Fr-Bu) and to identify its active constituents. Anti-ulcer activities were evaluated against cold restraint (CRU) and pyloric ligation (PL) induced gastric ulcer models and further confirmed through H(+) K(+)-ATPase inhibitory activity. Cytoprotective activity was evaluated in alcohol (AL) induced gastric ulcer model and further through PGE(2) level. E-EtOH and Fr-Bu attenuated ulcer formation in CRU. Moreover E-EtOH and Fr-Bu displayed potent anti-secretory activity as evident through reduced free acidity and pepsin activity in PL, confirmed further by in vitro inhibition of H(+) K(+)-ATPase activity. In addition cytoprotective potential of E-EtOH and Fr-Bu were apparent with protection in AL model, increased PGE(2) content and enhanced mucin level in PL. Phytochemical investigations of Fr-Bu yielded terpenoides and a phenolic glycoside, verbascoside. The anti-secretory mechanism of verbascoside mediated apparently through inhibition of H(+) K(+)-ATPase with corresponding decrease in plasma gastrin level, is novel to our finding. Gastroprotection elicited by TG might be through proton pump inhibition and consequent augmentation of the defensive mechanism.

Topics: Animals; Anti-Ulcer Agents; Cold Temperature; Dinoprostone; Disease Models, Animal; Female; Gastric Acid; Gastric Mucosa; Gastrins; Glucosides; Male; Mucins; Pepsin A; Phenols; Phytotherapy; Plant Extracts; Plant Leaves; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Stomach; Stomach Ulcer; Verbenaceae

Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E(2), and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA induced gastric lesions and microbleeding. Gastric mucosal generation of PGE(2) was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.

Topics: Adult; Aspirin; Dinoprostone; Gastric Mucosa; Gastrins; Gastrointestinal Hemorrhage; Humans; Male; Melatonin; Middle Aged; Severity of Illness Index; Statistics, Nonparametric; Stomach Ulcer; Tryptophan

Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this trace element is involved in the integrity of the gastric mucosa. Compounds containing zinc, such as polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and ulcer healing remain unclear. We have determined the efficacy of zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at 3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after ulcer induction (day 0) and at day 3 but then it rose significantly at day 7 after ulcer induction. Treatment with zinc hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric luminal and mucosal levels of Zn(2+), significantly accelerated ulcer healing at day 7 upon ulcer induction. The GBF, which reached a significantly higher value at the ulcer margin than the ulcer bed, was significantly increased in rats treated with zinc hydroaspartate compared with vehicle-controls. The gastric a

Topics: Animals; Aspartic Acid; Carnosine; Drug Evaluation, Preclinical; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Organometallic Compounds; Random Allocation; Rats; Rats, Wistar; Regional Blood Flow; Stomach; Stomach Ulcer; Zinc; Zinc Compounds

We describe the case of an apparently healthy newborn infant who in 7th day of life showed an episode of haematemesis and in 13th day of life presented an episode of apparent life threatening event (ALTE). A fibroscopy of the upper digestive tract showed a great ulcer of the gastric antrum and esophagitis limited to the mucosa. Gastrinemia in the blood showed high values (121 pg/ml). The relationship between ALTE and gastric ulcer may be casual, however in literature a gastroenteric cause is present in about 50% of ALTE in which an etiologic cause is found. We speculate that in the present case the increase of gastrin secretion reduced gastric pH which facilitated the onset of gastric ulcer and esophagitis with ALTE due to pain or reflex.

Topics: Biopsy; Critical Illness; Gastrins; Gestational Age; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Newborn, Diseases; Male; Pyloric Antrum; Stomach Ulcer

Curatella americana L. (Dilleneaceae) is a medicinal plant very frequently cited as acting against gastrointestinal disorders in ethnopharmacological inventories of the Cerrado region of Brazil.. The ethanolic extract (CEB) and infusion (BI) of Curatella americana bark were investigated for their ability to prevent and heal ulceration of the gastric mucosa.. The preventive and healing actions of Curatella americana were evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa.. CEB significantly decreased the severity of gastric damage formation induced by the combination of several gastroprotective models (HCl/ethanol, indomethacin/bethanecol, absolute ethanol, stress and pylorus ligature). But, unlike CEB, the BI did not exert gastroprotective effect. The gastroprotective action of CEB involved antisecretory action, augmentation of gastric mucus (48%) and participation of endogenous sulfhydryl compounds that increase efficacy of barrier mucosa against injurious agents. CEB also presents effective healing action in chronic gastric disease (1.90+/-0.55 vs. 6.86+/-0.46 mm2)in the control) and its action mechanisms consisted of increasing the PGE2 (40%) and somatostatin levels (269%) while decreasing the gastrin level in rat plasma (79%).. The gastroprotective effect and healing action of Curatella americana involved modulation of PGE2, somatostatin and gastrin levels, probably due to the presence of oligomeric and polymeric proanthocyanidins in the bark.

Topics: Animals; Anti-Ulcer Agents; Dilleniaceae; Dinoprostone; Ethylmaleimide; Gastric Mucosa; Gastrins; Hormones; Male; Mice; Mucus; NG-Nitroarginine Methyl Ester; Phytotherapy; Plant Bark; Plant Extracts; Proanthocyanidins; Somatostatin; Stomach Ulcer; Sulfhydryl Compounds

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

Screening of three potential antiulcer preparations containing ultralow doses of antibodies to endogenous regulators of ulcer formation (gastrin, histamine, and H2 histamine receptors) on the model of acetic acid-induced gastric ulcer in rats revealed pronounced antiulcer effect of ultralow doses of antibodies to histamine. The dynamics of regeneration of the ulcer focus by morphological and histological characteristics was similar during treatment with ultralow doses of antibodies to histamine and with famotidine.

Topics: Acetates; Animals; Anti-Ulcer Agents; Antibodies; Famotidine; Gastrins; Histamine; Male; Rats; Rats, Wistar; Receptors, Histamine H2; Stomach Ulcer

Morphofunctional state of gastric mucous tunic and neuroendocrine cells, and clinical indices at various stages of gastric and duodenal ulcer disease was studied. It was shown, that in clinico-endoscopic remission stage of disease intensity of pathogenetic mechanisms of some neuroimmune-endocrine and clinical indices remained.

Topics: Adult; Biomarkers; Disease Progression; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Prognosis; Quality of Life; Serotonin; Severity of Illness Index; Somatostatin; Stomach Ulcer

The gastrin/CCK receptor (CCK2R) mediates the physiological functions of gastrin in the stomach, including stimulation of acid secretion and cellular proliferation and migration, but little is known about the factors that regulate its expression. We identified endogenous CCK2R expression in several cell lines and used luciferase promoter-reporter constructs to define the minimal promoter required for transcription in human gastric adenocarcinoma, AGS, and rat gastric mucosa, RGM1, cells. Consensus binding sites for SP1, C/EBP and GATA were essential for activity. Following serum withdrawal from RGM1 and AR42J cells, endogenous CCK2R mRNA abundance and the activity of a CCK2R promoter-reporter construct were significantly elevated. Transcription of CCK2R was also increased in AGS-G(R) and RGM1 cells by gastrin through mechanisms partly dependent upon protein kinase C (PKC) and mitogen/extracellular signal-regulated kinase (MEK). Gastrin significantly increased endogenous CCK2R expression in RGM1 cells, and CCK2R protein expression was elevated in the stomach of hypergastrinaemic animals. In mice with cryoulcers in the acid-secreting mucosa, CCK2R expression increased progressively in the regenerating mucosa adjacent to the ulcer repair margin, evident at 6 days postinjury and maximal at 13 days. De novo expression of CCK2R was observed in the submucosa beneath the repairing ulcer crater 6-9 days postinjury. Many of the cells in mucosa and submucosa that expressed CCK2R in response to cryoinjury were identified as myofibroblasts, since they coexpressed vimentin and smooth muscle alpha-actin but not desmin. The data suggest that increased CCK2R expression might influence the outcome of epithelial inflammation or injury and that the response may be mediated in part by myofibroblasts.

Topics: Animals; Blotting, Western; Cell Line; Culture Media, Serum-Free; Female; Fibroblasts; Freezing; Gastric Mucosa; Gastrins; Gene Expression Regulation; Genes, Reporter; Humans; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Inbred C57BL; Rats; Receptor, Cholecystokinin B; Reverse Transcriptase Polymerase Chain Reaction; RNA; Stomach Ulcer; Transfection

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

Topics: Animals; Chemokines; Dose-Response Relationship, Drug; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrins; Injections, Intramuscular; Interleukin-1beta; Male; Orchiectomy; Photomicrography; Rats; Rats, Wistar; Regional Blood Flow; Stomach Ulcer; Testosterone; Time Factors; Tongue; Tongue Diseases; Treatment Outcome; Tumor Necrosis Factor-alpha; Wound Healing

The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E(2) (PGE(2)), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX-PG and free radicals, probably mediated by the changes in local gastric melatonin.

Topics: Animals; Circadian Rhythm; Cyclooxygenase 2; Dinoprostone; Free Radicals; Gastrins; Male; Melatonin; Pineal Gland; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Stomach Ulcer; Stress, Physiological

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

Topics: Gastric Antral Vascular Ectasia; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Hyperplasia; Laser Coagulation; Polyps; Postoperative Complications; Stomach Neoplasms; Stomach Ulcer

The hydroethanolic extract of the leaves (HEL) and bark (HEB) obtained from Alchornea castaneaefolia (Euphorbiaceae) were investigated for their ability to prevent ulceration of the gastric mucosa in animal models. HEL (500 and 1000 mg/kg) and HEB (1000 mg/kg) significantly reduced the gastric injuries induced by the combination of HCl/ethanol and lowered the severity of gastric damage formation induced by indomethacin/bethanechol in mice. Further investigation showed that HEL also inhibited formation of ulcers in mice submitted to stress and pylorus ligature, but HEL did not modify gastric juice parameters in Shay mice. HEL was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats. An enriched flavonoidic fraction (EFF at dose of 100mg/kg) obtained from HEL reduced gastric lesions induced by HCl/ethanol and indomethacin/bethanechol in mice. Although EFF did not modify the amount of free mucus production by gastric mucosa, it was able to increase prostaglandin production. When administered to rats submitted to ethanol-induced gastric lesions, EFF increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. Phytochemical investigation on HEL and EFF led to the isolation of flavonoids glycosides as the main compounds, thus suggesting that these substances may be involved in the observed antiulcer activity.

Topics: Animals; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Euphorbiaceae; Gastrins; Male; Mice; Plant Bark; Plant Extracts; Plant Leaves; Prostaglandins; Rats; Rats, Wistar; Somatostatin; Stomach Ulcer

The protective effect of a commercial preparation (STW 5, Iberogast), containing the extracts of bitter candy tuft, lemon balm leaf, chamomile flower, caraway fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and greater celandine herb, against the development of gastric ulcers was previously reported in an earlier publication (Khayyal et al., 2001). All extracts produced a dose dependent anti-ulcerogenic effect associated with a reduced acid output, an increased mucin secretion, an increase in prostaglandin E(2) release and a decrease in leukotrienes. The effect on pepsin content was not uniform and did not seem to bear a relationship with the anti-ulcerogenic activity. The best effects were observed with the combined formulation, STW 5. Furthermore, the effect of the latter in protecting against the development of rebound gastric acidity was examined experimentally in rats and compared with the effect of some commercial antacid preparations (Rennie, Talcid and Maaloxan). A model of testing rebound acidity was developed by inducing a marginal increase in gastric acidity through the administration of indomethacin, in such a way that it could be easily neutralized, allowing any eventual secondary increase in acidity to be measured within a few hours of administration. In addition, the serum gastrin level was measured after drug treatment to establish any correlation between it and any rebound acidity. The results obtained demonstrated that STW 5 did not only lower the gastric acidity as effectively as the commercial antacid, but it was more effective in inhibiting the secondary hyperacidity. Moreover, STW 5 was capable of inhibiting the serum gastrin level in rats, an effect which ran parallel to its lowering effect on gastric acid production.

Topics: Animals; Gastric Acidity Determination; Gastric Juice; Gastrins; Indomethacin; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer

Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.

Topics: Animals; Capsaicin; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Ghrelin; Injections, Intraperitoneal; Injections, Intraventricular; Ischemia; Male; Neurons, Afferent; Protective Agents; Rats; Rats, Wistar; Recombinant Proteins; Stomach; Stomach Ulcer; Vagus Nerve

The present work aimed at testing, in a rat model of ethanol-induced gastric ulceration, a local folk medicinal claim that dates are beneficial in gastric ulcers in humans. Aqueous and ethanolic undialyzed and dialyzed extracts from date fruit and pits were given orally to rats at a dose of 4 ml/kg for 14 consecutive days. On the last day of treatment, rats were fasted for 24 h, and were then given ethanol, 80% (1 ml/rat) by gastric intubation to induce gastric ulcer. Rats were killed after 1 h of ethanol exposure, and the incidence and severity of the ulceration were estimated, as well as the concentrations of gastrin in plasma, and histamine and mucus in the gastric mucosa. A single group of rats that were fasted for 24 h, was administered orally with lansoprazole (30 mg/kg), and was given 80% ethanol as above, 8 h thereafter, served as a positive control. The results indicated that the aqueous and ethanolic extracts of the date fruit and, to a lesser extent, date pits, were effective in ameliorating the severity of gastric ulceration and mitigating the ethanol-induced increase in histamine and gastrin concentrations, and the decrease in mucin gastric levels. The ethanolic undialyzed extract was more effective than the rest of the other extracts used. It is postulated that the basis of the gastroprotective action of date extracts may be multi-factorial, and may include an anti-oxidant action.

Topics: Animals; Ethanol; Fruit; Gastrins; Histamine; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer

The gastric mucosa is most susceptible to stress that has been shown to induce mucosal damage in humans and animals. This study aims to explore the underlying mechanisms of partial sleep deprivation, as a source of psychophysiological stress, on gastric functions and its effect on mucosal integrity. Sprague-Dawley rats were partially sleep deprived (PSD) for 7 or 14 days by housing inside slowly rotating drums. Gastric tissues and plasma were sampled at the end of the sleep deprivation periods and mucosal lesion scores were evaluated. Morphological examination was performed after Hematoxylin and Eosin staining. Plasma levels of noradrenaline, adrenaline, gastrin, histamine and somatostatin were determined with enzyme immunoassays. Gastric acidity was measured with acid-base titration in pylorus ligated rats. Gastric mucosal blood flow was evaluated with Laser Doppler Flowmetry. It was found that gastric lesions were induced in about 30%-50% of the PSD rats. Gastric acidity as well as plasma levels of noradrenaline, gastrin and histamine were elevated. Gastric mucosal blood flow and plasma somatostatin level were on the contrary reduced, especially in rats with PSD for 14 days. It is concluded that partial sleep deprivation compromises gastric mucosal integrity by increasing gastric acidity, plasma levels of noradrenaline, gastrin, histamine, and decreasing gastric mucosal blood flow. These results provided experimental evidence on the gastric damaging effects of PSD and it could be one of the risk factors contributing to gastric ulcer formation.

Topics: Animals; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Male; Norepinephrine; Rats; Rats, Sprague-Dawley; Sleep Deprivation; Stomach Ulcer; Stress, Psychological

Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa.. Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels.. 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Biopsy; Blood Flow Velocity; Candida albicans; Chronic Disease; Colony Count, Microbial; Cytokines; Disease Models, Animal; Electrophoresis, Agar Gel; Gastric Juice; Gastric Mucosa; Gastrins; Gene Expression Regulation; Lactobacillus acidophilus; Male; Microcirculation; Probiotics; Ranitidine; Rats; Rats, Wistar; RNA, Messenger; Stomach Ulcer

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

Melatonin attenuates acute gastric lesions induced by topical strong irritants because of scavenging of free radicals, but its role in the pathogenesis of stress-induced gastric lesions has been sparingly investigated. In this study we compared the effects of intragastric (i.g.) or intracerebroventricular (i.c.v.) administration of melatonin and its precursor, L-tryptophan, with or without concurrent treatment with luzindole, a selective antagonist of melatonin MT2 receptors, on gastric lesions induced by water immersion and restraint stress (WRS). The involvement of pineal gland, endogenous prostaglandins (PG) and sensory nerves in gastroprotective action of melatonin and L-tryptophan against WRS was studied in intact or pinealectomized rats or those treated with indomethacin or rofecoxib to suppress cyclooxygenase (COX)-1 and COX-2, respectively, and with capsaicin to induce functional ablation of the sensory nerves. In addition, the influence of i.c.v. and i.g. melatonin on gastric secretion was tested in a separate group of rats equipped with gastric fistulas. At 3.5 hr after the end of WRS, the number of gastric lesions was counted, the gastric blood flow (GBF) was determined by H2-gas clearance technique and plasma melatonin and gastrin levels were measured by specific radioimmunoassay (RIA). Biopsy mucosal samples were taken for determination of expression of mRNA for COX-1 and COX-2 by reverse transcriptase-polymerase chain reaction (RT-PCR) and of the mucosal generation of prostaglandin E2 (PGE2) by RIA. Melatonin applied i.g. (1.25-10 mg/kg) or i.c.v. (1.25-10 microg/kg) dose-dependently inhibited gastric acid secretion and significantly attenuated the WRS-induced gastric damage. This protective effect of melatonin was accompanied by a significant rise in the GBF and plasma melatonin and gastrin levels and in mucosal generation of PGE2. Pinealectomy, which suppressed plasma melatonin levels, aggravated the gastric lesions induced by WRS and these effects were counteracted by i.g. or i.c.v. application of melatonin. Luzindole abolished completely the gastroprotective effects of melatonin and L-tryptophan and attenuated significantly the rise in GBF evoked by the indoleamine and its precursor. Indomethacin and rofecoxib, which diminished PGE2 biosynthesis by c. 90 and 75% or capsaicin denervation, attenuated significantly melatonin- and L-tryptophan-induced protection and the rise in the GBF. Both the protection and the hyperemia were restored by

Topics: Administration, Topical; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Cerebral Ventricles; Cyclooxygenase 1; Cyclooxygenase 2; Gastrins; Immersion; Indomethacin; Melatonin; Neurons, Afferent; Pineal Gland; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Regional Blood Flow; Restraint, Physical; Stomach; Stomach Ulcer; Stress, Psychological; Tryptophan

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

The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Aspirin; Benzimidazoles; Cysteamine; Duodenal Ulcer; Epirizole; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Immersion; Indomethacin; Male; Pepsin A; Pylorus; Pyridines; Rats; Stomach Ulcer; Thiazoles

We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis. The PA extract demonstrated significantly activity in both, acute and chronic gastric ulcers on rats. The effects of PA extract were dose dependent. The mechanisms implicated on this activity were evaluated by determination of gastrin plasma levels in rats subjected to the acute treatment with PA extract and by expression of mRNA of Epidermal Growth Factor (EGF) after chronic treatment with this extract. The results showed that the PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF.

Topics: Animals; Dose-Response Relationship, Drug; Epidermal Growth Factor; Gastrins; Male; Mice; Plant Extracts; Pyrrolizidine Alkaloids; Rats; Senecio; Stomach Ulcer

To study the effect of environmental hyperthermia on gastrin, somatostatin and motilin in rat ulcerated antral mucosa.. Forty-two Wistar rats were equally divided into six groups, according to the room temperature (high and normal) and the treatment (acetic acid, normal saline and no treatment). Levels of gastrin, somatostatin and motilin in rat ulcerated antral mucosa were measured with a radioimmunoassay method.. The average temperature and humidity were 32.5 degrees and 66.7% for the high temperature group, and 21.1 degrees and 49.3% for the normal temperature group, respectively. Gastric ulcer model was successfully induced in rat injected with 0.05 mL acetic acid into the antrum. In rats with gastric ulcers, the levels of gastrin and motilin increased, whereas the somatostatin level declined in antral mucosa, compared with those in rats treated with normal saline and the controls. However, the change extent in the levels of gastrin, motilin and somatostatin in antral mucosa was less in the high temperature group than in the normal temperature group.. The levels of gastrin, somatostatin and motilin in rat ulcerated antral mucosal tissue remain relatively stable in a high temperature environment, which may relate to the equilibration of the dynamic system.

Topics: Adaptation, Physiological; Animals; Environment; Fever; Gastric Mucosa; Gastrins; Hot Temperature; Male; Motilin; Pyloric Antrum; Rats; Rats, Wistar; Somatostatin; Stomach Ulcer

Ghrelin, the endogenous ligand for GH secretagogue receptors, has been reported to influence acid gastric secretion and motility, but its potential gastroprotective effect is unknown. The aims of this study were 1) to examine the effects of central and peripheral administration of ghrelin on ethanol-induced gastric ulcers in conscious rats, and 2) to investigate the possible roles of nitric oxide (NO), vagal nerve, and sensory fibers in the gastric effects of ghrelin. Ghrelin was administered either intracerebroventricularly or sc 30 min before ethanol, and mucosal lesions were examined macroscopically. Additionally, rats were either treated with the inhibitor of NO synthesis N(omega)-nitro-L-arginine methyl ester (L-NAME) or underwent bilateral cervical vagotomy or capsaicin-induced sensory denervation. Conventional histology and immunohistochemistry for ghrelin, gastrin, and somatostatin were performed on gastric specimens from representative rats. Central ghrelin (4-4,000 ng/rat) dose-dependently reduced ethanol-induced gastric ulcers by 39-77%. Subcutaneous ghrelin administration (80 micro g/kg) reduced ulcer depth only. L-NAME and capsaicin, but not vagotomy, prevented the gastroprotective effect of central ghrelin (4000 ng/rat). This is the first evidence that ghrelin exerts a potent central gastroprotective activity against ethanol-induced lesions. The gastroprotective effect of ghrelin is mediated by endogenous NO release and requires the integrity of sensory nerve fibers.

Topics: Animals; Capsaicin; Denervation; Enzyme Inhibitors; Ethanol; Gastric Mucosa; Gastrins; Ghrelin; Immunohistochemistry; Injections, Intraventricular; Injections, Subcutaneous; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Peptide Hormones; Rats; Rats, Sprague-Dawley; Somatostatin; Stomach Ulcer; Vagotomy

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

To investigate the changes of gastrin, somatostatin and motilin production in the gastric antral mucosa of rats with experimental gastric ulcer.. Rat models of gastric ulcer model were induced successfully by injection of acetic acid into the gastric antral wall of 2 groups of Wistar rats (7 in each group) that were subjected to environment of either high or normal temperature. Another 2 groups of rats (n=7) receiving normal saline injection in the same manner, along with still another 2 groups (n=7) without any treatment, all of which were kept under conditions with different temperatures accordingly, constituted the control groups. The levels of gastrin, somatostatin and motilin in the gastric antral mucosa of the rats were measured with radioimmunoassay.. In rats with gastric ulcer, the levels of gastrin and motilin in the antral mucosa increased, but in a lesser scale in rats with ulcer kept in high temperature than in normal temperature group, while that of somatostatin was reduced. The level of somatostatin declined less in the high temperature group with ulcer than in the normal temperature group with ulcer.. High temperature can affect gastrin, somatostatin and motilin production in the gastric antral mucosa of rats with gastric ulcer.

Topics: Animals; Disease Models, Animal; Gastric Mucosa; Gastrins; Male; Motilin; Pyloric Antrum; Rats; Rats, Wistar; Somatostatin; Stomach Ulcer; Temperature

Gastrin, PGs, and growth factors have important roles in maintaining gastrointestinal mucosal integrity. Cyclooxygenases (COX-1 and COX-2) are the key enzymes involved in PG synthesis. This study aimed to clarify the mechanisms of gastric mucosal protection by gastrin. Fasted rats were administered subcutaneous gastrin 17 with or without gastrin receptor antagonist YM022 pretreatment. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and COX-2 expression were examined using Western blot analysis. Another series of experiments investigated 1) PGE(2) levels in gastric mucosa, 2) the protective action of gastrin against gastric damage by acidified ethanol, 3) the effects of a specific HB-EGF-neutralizing antibody on gastrin-induced COX-2 expression, and 4) the effects of a specific COX-2 inhibitor NS-398 on PGE(2) synthesis and the mucosal protection afforded by gastrin. Gastrin dose-dependently increased HB-EGF, COX-2 expression, and PGE(2) levels and reduced gastric damage. However, pretreatment with YM022 dose-dependently abolished such effects of gastrin. A specific HB-EGF- neutralizing antibody and an EGF receptor inhibitor decreased gastrin-induced COX-2 expression. NS-398 blocked gastrin-induced PGE(2) synthesis and mucosal protection. In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE(2) upregulation in rats.

Topics: Animals; Antibodies; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Epidermal Growth Factor; Ethanol; Gastric Mucosa; Gastrins; Heparin-binding EGF-like Growth Factor; Hepatocyte Growth Factor; Hydrogen-Ion Concentration; Immunoenzyme Techniques; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Isoenzymes; Male; Membrane Proteins; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Sulfonamides

We investigated the pattern of changes in serum gastrin level produced by three H2-receptor antagonists (H2RA) in patients with gastric and duodenal ulcers between 1990 and 1999. The subjects were 51 patients (cimetidine: 18 patients; famotidine: 16 patients; ranitidine: 17 patients). The gastrin test (in the fasting and meal-stimulated states) was conducted during drug administration and on the fourth day after drug cessation. After cessation of the drug therapy, the fasting serum gastrin level was significantly lower than that during the drug therapy with the three H2RAs. Gastrin level in the fasting test was significantly higher during famotidine therapy than during cimetidine therapy (p = 0.0123). In the meal-stimulated gastrin test, the AUC of gastrin during treatment with H2RA treatment was significantly higher with famotidine than with cimetidine (p = 0.0024). The results indicate different patterns of change in the serum gastrin level in the fasting and meal-stimulated test according to the H2RA administered. Gastrin level was highest in patients administered famotidine and lowest among those administered cimetidine. The pattern of gastrin change in patients administered ranitidine was intermediate between famotidine and cimetidine.

Topics: Adult; Anti-Ulcer Agents; Area Under Curve; Cimetidine; Duodenal Ulcer; Famotidine; Female; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Multivariate Analysis; Ranitidine; Receptors, Histamine H2; Statistics, Nonparametric; Stomach Ulcer

To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats.. Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system.. In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process.. In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction.

Topics: Animals; Disease Models, Animal; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Male; Rats; Rats, Wistar; Somatostatin; Somatostatin-Secreting Cells; Stomach Ulcer

In this study, we compared the effects of cimetidine and omeprazole on the healing of acetic acid-induced gastric ulcers in 8-, 48-, and 96-week-old rats. The repeated oral administration of cimetidine or omeprazole for 14 consecutive days markedly accelerated the ulcer healing in 8- and 48-week-old rats. However, both drugs were ineffective in 96-week-old rats. The basal gastric acid secretion of 8-, 48-, and 96-week-old rats decreased with aging. A single oral administration of cimetidine or omeprazole strongly decreased basal gastric acid secretion in the three different ages of rats. Cimetidine and omeprazole produced a potent and sustained serum gastrin-elevating action in 8- and 48-week-old rats. However, the gastrin-elevating actions of both drugs in 96-week-old rats were much weaker than in the 8- and 48-week-old rats. These results indicate that cimetidine and omeprazole have potent gastric ulcer healing actions in 8- and 48-week-old rats, as well as potent serum gastrin-elevating actions, but both drugs are ineffective in 96-week-old rats, which have lost their gastrin-elevating actions.

Topics: Aging; Animals; Cimetidine; Gastrins; Male; Omeprazole; Rats; Rats, Wistar; Stomach Ulcer

Melatonin, a major hormone of pineal gland, was recently shown to attenuate acute gastric lesions induced by strong irritants because of the scavenging of free radicals but its role in ulcer healing has been little investigated. In this study we compared the effects of intragastric (i.g.) administration of melatonin and its precursor, L-tryptophan, with or without concurrent treatment with luzindole, a selective antagonist of melatonin MT2 receptors, on healing of chronic gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2). The involvement of endogenous prostaglandins (PG), nitric oxide (NO) and sensory nerves in ulcer healing action of melatonin and L-tryptophan was studied in rats treated with indomethacin and NG-nitro-L-arginine (L-NNA) to suppress, respectively, cyclo-oxygenases (COX) and NO synthases or in those with functionally deactivated sensory nerves with capsaicin. The influence of melatonin on gastric secretion during ulcer healing was tested in separate group of rats with gastric ulcer equipped with gastric fistulas (GF). At day 8 and 15 upon the ulcer induction, the area of gastric ulcers was measured by planimetry, the mucosal blood flow (GBF) was determined by H2-gas clearance technique and gastric luminal NO2-/NO3- levels was assessed by Griess reaction. Plasma melatonin and gastrin levels were measured by specific radioimmunoassay (RIA). Biopsy mucosal samples were taken for expression of constitutive NO-synthase (cNOS) and inducible NOS (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). Melatonin (2.5-20 mg/kg-d i.g.) and L-tryptophan (25-100 mg/kg-d i.g.) dose-dependently accelerated ulcer healing, the dose inhibiting by 50% (ED50) of ulcer area being 10 and 115 mg/kg, respectively. This inhibitory effect of melatonin (10 mg/kg-d i.g.) and L-tryptophan (100 mg/kg-d i.g.) on ulcer healing was accompanied by a significant rise in the GBF at ulcer margin and an increase of plasma melatonin. luminal NO2-/NO3- and plasma gastrin levels. Gastric acid and pepsin outputs were significantly inhibited during the ulcer healing in melatonin-treated gastric mucosa as compared with those in vehicle-treated animals. Luzindole abolished completely the healing effects of melatonin and L-tryptophan and attenuated significantly the rise in plasma gastrin evoked by the hormone and its precursor. Indomethacin (5 mg/kg-d i.p). that blocked PG biosynthesis by 90% or L-NAME (20 mg/kg i.v), inhibitor of NOS. that

Topics: Actins; Animals; Capsaicin; Dinoprostone; Enzyme Inhibitors; Gastric Mucosa; Gastrins; Male; Melatonin; Neurons, Afferent; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Prostaglandins; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Melatonin; Regional Blood Flow; Stomach Ulcer; Tryptamines; Tryptophan

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

Prostaglandins (PG) derived from COX-1 are essential for the maintenance of mucosal integrity but COX-2 isoform synthesizes PG at a site of inflammation. Recently, COX-2 mRNA expression was demonstrated at the ulcer edge during healing of chronic gastric ulcers but the role for expression of COX-2 and its products such as PGE(2) and cytokines including interleukin (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in ulcer healing remains unknown. In this study, Wistar rats with gastric ulcers produced by serosal application of acetic acid (ulcer area 28 mm(2)) received daily treatment either with: (1) vehicle (saline); (2) NS-398 (10 mg/kg-d i.g.) and Vioxx (5 mg/kg-d i.g.), both, highly specific COX-2 inhibitors; (3) meloxicam (5 mg/kg-d i.g.), a preferential inhibitor of COX-2; (4) resveratrol (10 mg/kg-d i.g.), a specific COX-1 inhibitor; (5) indomethacin (5 mg/kg-d i.g); and (6) aspirin (ASA; 50 mg/kg-d i.g.), non-selective inhibitors of both COX-1 and COX-2. At day 3, 7, and 14 after ulcer induction, the animals were sacrificed and the area of gastric ulcers was determined by planimetry and histology, gastric blood flow (GBF) at ulcer base and margin was measured by H(2) clearance technique, and blood was withdrawn for measurement of plasma IL-1beta and TNFalpha levels. The mucosal biopsy samples were taken for the determination of PGE(2) generation by RIA and expression of COX-1, COX-2, IL-1beta, and TNFalpha mRNA by RT-PCR. In vehicle-treated rats, gastric ulcers healed progressively and at day 14 the healing was completed, accompanied by a significant rise in the GBF at ulcer margin. The IL-1beta, TNFalpha, and COX-1 mRNA were detected in intact and ulcerated gastric mucosa, whereas COX-2 mRNA were upregulated only in ulcerated mucosa with peak observed at day 3 after ulcer induction. The plasma IL-1beta level was significantly increased at day 3 and 7 but then declined at day 14 to that measured in vehicle-controls. Indomethacin and ASA, which suppressed PGE(2) generation both in the non-ulcerated and ulcerated gastric mucosa, significantly delayed the rate of ulcer healing and this was accompanied by the fall in GBF at ulcer margin and further elevation of plasma IL-1beta and TNFalpha levels, which was sustained up to the end of the study. Treatment with NS-398 and Vioxx, which caused only a moderate decrease in the PGE(2) generation in the non-ulcerated gastric mucosa, delayed ulcer healing and attenuated significantly the GBF at ulcer marg

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chronic Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Gastric Mucosa; Gastrins; Indomethacin; Interleukin-1; Isoenzymes; Lactones; Male; Meloxicam; Membrane Proteins; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Radioimmunoassay; Rats; Rats, Wistar; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stilbenes; Stomach Ulcer; Sulfonamides; Sulfones; Thiazines; Thiazoles; 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

Ulcer healing involves expression of various growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) at the ulcer margin, but the influence of EGF, HGF and bFGF applied locally with or without neutralizing anti-EGF, HGF and bFGF antibodies or cyclooxygenase (COX)-1 and COX-2 inhibitors on ulcer healing and the expression of COX-1 and COX-2 during ulcer healing have only been studied a little.. Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2 received a submucosal injection of either (1) vehicle (saline), (2) EGF, (3) HGF, and (4) bFGF with or without antibodies against EGF, HGF and bFGF or indomethacin (2 mg/kg/day i.p.), a nonspecific inhibitor of COX, or NS-398 (10 mg/kg/day i.g.) and Vioxx (5 mg/kg/day i.g.), both highly specific COX-2 inhibitors. A separate group of animals with chronic gastric fistulas was also used to assess gastric secretion during ulcer healing with and without growth factors. Each growth factor and specific antibody against EGF, HGF and bFGF (100 ng/100 microl each) were injected just around the ulcer immediately after ulcer induction and this local injection was repeated on day 2 following anesthesia and laparotomy. On days 13 and 21, the ulcer area was determined by planimetry, gastric blood flow (GBF) at the ulcer margin was examined by the H2-gas clearance technique, and mucosal generation of PGE2 and the gene expression of COX-1 and COX-2 in the non-ulcerated and ulcerated gastric mucosa were assessed. Gastric ulcers healed progressively within 21 days after induction and this effect was accompanied by a significant increase in GBF at the ulcer margin and in the expression of COX-2 in the ulcer area. Local treatment with EGF, HGF and bFGF produced a significant decrease in gastric acid secretion and significantly accelerated the rate of ulcer healing and raised GBF at the ulcer margin causing further significant upregulation of COX-2 but not COX-1 expression in the ulcerated mucosa. The acceleration of ulcer healing and hyperemia at the ulcer margin exhibited by locally applied EGF, HGF and bFGF were similar to those obtained with systemic administration of these growth factors. HGF applied submucosally, upregulated COX-2 expression and this was significantly attenuated by concurrent treatment with antibody against this peptide. Anti-EGF and anti-bFGF antibodies completely abolished the acceleration of the ulcer healing and hyperemia at the ulcer margin induced by these growth factors. Indomethacin and both COX-2 inhibitors significantly prolonged ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and GBF at the ulcer margin. The acceleration of ulcer healing by EGF, HGF and bFGF and the accompanying rise in GBF at the ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vio. (1) Growth factors accelerate ulcer healing due to enhancement in the microcirculation around the ulcer and these effects are specific because they can be abolished by neutralization with antibodies; (2) COX-2-derived prostaglandins and suppression of gastric secretion may play an important role in the acceleration of ulcer healing by various growth factors, and (3) the local effects of EGF, HGF and bFGF on ulcer healing can be reproduced by their systemic application indicating the high efficacy of growth factors to accelerate this healing.

Topics: Animals; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Gastric Mucosa; Gastrins; Growth Substances; Isoenzymes; Male; Membrane Proteins; Models, Animal; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; RNA, Messenger; Stomach Ulcer; Wound Healing

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

Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased formation of histamine leading to an increase in gastric acid secretion is accompanied with gastroprotection and acceleration of gastric ulcer healing.. Of this study was to examine the effect of histamine on stress induced gastric ulcers in rats.. Male Wistar rats were exposed to water immersion and restrain stress (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole.. WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or omeprazole caused an additional reduction in ulcer area. Gastroprotective effect of histamine was accompanied with the increase in gastric blood flow (GBF). Administration of omeprazole or ranitidine alone was without significant effect on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1beta was significantly reduced after administration of omeprazole, ranitidine, or histamine, however, the effect of histamine was less pronounced. DNA synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in combination with ranitidine or omeprazole caused an additional increase in DNA synthesis.. Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induced gastric lesions. This effect of histamine seems to be independent on gastric acid secretion but related to the increase in gastric blood flow and the reduction in activation of cytokine cascade.

Topics: Animals; DNA; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Hydrogen-Ion Concentration; Interleukin-1; Male; Protective Agents; Rats; Rats, Wistar; Regional Blood Flow; Stomach Ulcer; Stress, Physiological

The present study was designed to evaluate the usefulness of plasma gastrin determinations as a diagnostic aid and to review the clinical and haematological findings in cattle with bleeding abomasal ulcers. Twenty-nine cows with bleeding abomasal ulcers and six healthy cows were used. Clinical and laboratory examinations, including plasma gastrin levels, were performed. Anorexia, depression, dark-coloured to black faeces, pale mucous membranes, abdominal pain, moderate tachycardia and tachypnoca were the most pronounced clinical symptoms in the cattle with bleeding abomasal ulcers. Plasma gastrin concentration was significantly higher (P < 0.05) in the cattle with bleeding abomasal ulcers than in healthy cows. The mean plasma gastrin concentration in healthy cattle was 103.2 pg/ml, while the mean plasma gastrin concentrations in cattle with bleeding abomasal ulcers were found to be 213.6 pg/ml. Haemoglobin levels, packed cell volume, total white blood cell count and mean corpuscular volume were significantly lower (P < 0.05) in the cows with bleeding abomasal ulcer than in the healthy cattle. The results of this study show that measurement of plasma gastrin can be useful in the diagnosis of bleeding abomasal ulcers in cattle.

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Diagnosis, Differential; Female; Gastrins; Peptic Ulcer Hemorrhage; Stomach Ulcer

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

Ischemia followed by reperfusion is known to produce gastric lesions due to oxidative stress, but the role of gastric H(+) secretion in the formation of this mucosal injury remains unknown. We studied alterations in gastric acid secretion and gastric histamine content, as well as the expression of histidine-decarboxylase and interleukin-1beta during the mucosal recovery from ischemia-reperfusion erosions. Gastric secretion was studied in rats (series A) with gastric fistula before, during and after the ischemia induced by clamping of celiac artery for 0.5 h followed by reperfusion in animals pretreated with vehicle (saline), omeprazole, a proton pump inhibitor, or ranitidine, a histamine (H(2)) receptor antagonist. In series B, the animals were submitted to 0.5 h of ischemia followed by 1 h of reperfusion and then anesthetized at 0, 3, 12 and 24 h or 3, 5, 10 or 15 days after the end of ischemia-reperfusion to determine gastric blood flow by H(2)-gas clearance technique, area of gastric lesions, plasma gastrin and interleukin-1beta levels, histamine content by radioimmunoassay (RIA) and expression of histidine-decarboxylase and interleukin-1beta mRNA by reverse transcription polymerase chain reaction. Clamping of celiac artery caused cessation of gastric blood flow and almost complete suppression of basal gastric acid secretion (series A) that returned gradually to the control value at day 3 after ischemia-reperfusion, accompanied by the rise in plasma gastrin levels, pronounced expression of histidine-decarboxylase mRNA and increased mucosal histamine content. Ischemia, followed by 1 h of reperfusion, produced gastric erosions (series B) that reached maximum at 12 h, but then declined at 24 h. These erosions progressed at day 3 into deeper ulcers whose area declined progressively within the next 5-15 days. The gastric blood ceased to flow (series B) during 30 min of clamping and was reduced throughout the period of healing of acute erosions, being accompanied by a gradual rise in mucosal interleukin-1beta mRNA content and in plasma interleukin-1beta levels. Treatment with omeprazole or ranitidine, which completely suppressed gastric acid secretion and significantly raised plasma gastrin level, greatly reduced the formation of erosive lesions preventing the progression of these lesions to chronic gastric ulcers, and this was accompanied by the rise in gastric blood flow and plasma gastrin levels and the significant attenuation of plasma interleukin-1beta

Topics: Acute Disease; Animals; Anti-Ulcer Agents; Blood Flow Velocity; Disease Progression; Gastric Acid; Gastric Mucosa; Gastrins; Gene Expression Regulation; Histamine; Histidine Decarboxylase; Interleukin-1; Male; Omeprazole; Polymerase Chain Reaction; Ranitidine; Rats; Rats, Wistar; Reperfusion Injury; RNA, Messenger; Stomach; Stomach Diseases; Stomach Ulcer; Time Factors

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy.

Topics: Acetamides; Animals; Disease Models, Animal; Endoscopy, Gastrointestinal; Famotidine; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Male; Outcome Assessment, Health Care; Piperidines; Pyridines; Rats; Rats, Wistar; Secondary Prevention; Stomach Ulcer

Although physiological functions of the CCK-B/gastrin receptor are well explored, little is known about its role during healing. Here, we evaluated the role of this receptor in the rat oxyntic mucosa following the introduction of a cryoulcer. In this model, we located and quantified CCK-B/gastrin receptors by reverse transcriptase PCR and receptor autoradiography. Rats with cryoulcers were treated with placebo, omeprazole, the CCK-B/gastrin receptor antagonist YF-476, omeprazole plus YF-476, gastrin-17, and gastrin 17 plus YF-476. During wound healing, CCK-B/gastrin receptors were specifically expressed and localized to the regenerative mucosal ulcer margin. This high expression was limited in time, and the pattern of expression of CCK-B/gastrin receptors correlated closely with the proliferative activity of the regenerative mucosa. Functionally, omeprazole and gastrin-17 caused profound hypergastrinemia, increased cell proliferation in the mucosal ulcer margin and accelerated the late ulcer healing phase. These effects were completely reversed by cotherapy with YF-476. These in vivo and vitro data suggest that CCK-B/gastrin receptors in regenerative rat gastric oxyntic mucosa enhance trophic effects during wound healing.

Topics: Animals; Benzodiazepinones; Female; Freezing; Gastric Mucosa; Gastrins; Omeprazole; Parietal Cells, Gastric; Phenylurea Compounds; Rats; Rats, Wistar; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Regeneration; Stomach Ulcer; Wound Healing

Regenerating (Reg) protein has a trophic effect on gastric mucosal cells. We have shown that Reg gene expression is increased in enterochromaffin-like (ECL) cells during the healing of damaged gastric mucosa around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage.. Time course changes of the expression of genes for various proinflammatory cytokines and Reg were investigated after induction of gastric mucosal lesions in rats. The direct effect of proinflammatory cytokines on Reg gene expression and Reg protein production were investigated in vitro using counterflow elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain reaction. Reg gene expression was also investigated in rats treated by the neutralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 beta).. During healing, the gene expression of several proinflammatory cytokines and Reg was markedly augmented. Among the proinflammatory cytokines, CINC-2 beta is the only cytokine in which augmented expression preceded the increase of Reg gene expression. In rats treated with CINC-2 beta neutralizing antibody, the augmentation of Reg gene expression was significantly inhibited. When ECL cells were incubated with these proinflammatory cytokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg protein in ECL cells. CXCR-2 was identified in isolated ECL cells.. CINC-2 beta, expressed in damaged gastric mucosa, stimulates the production of Reg protein in ECL cells via CXCR-2 and may be involved in the accelerated healing of injured gastric mucosa.

Topics: Animals; Antibodies; Calcium-Binding Proteins; Chemokines, CXC; Chemotactic Factors; Cytokines; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gene Expression; Growth Substances; Immersion; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-1; Lithostathine; Male; Nerve Tissue Proteins; Osmolar Concentration; Rats; Rats, Wistar; Restraint, Physical; Stomach Ulcer; Stress, Physiological; Tumor Necrosis Factor-alpha

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

The antigastrinic, antisecretory and antiulcer activities of CR 2945, (R)-1-naphthalenepropanoic acid,beta-[2-[[2-(8-azaspiro[4.5]dec-8-yl-carbonyl)-4,6-dimethylph enyl] amino]-2-oxoethyl], were investigated in vitro and in vivo in rats and cats. Its activities were compared with those of two gastrin/CCK(B) receptor antagonists, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)-N'-(3-methylphenyl)urea and CAM-1028 (4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[1,7,7-trimethylbicyclo [2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino -4-oxo-[1S-1alpha,2beta[S'(S')4alpha]]-butanoate -N-methyl-D-glucamine), of the histamine H2 receptor antagonist, ranitidine, and the proton pump inhibitor, omeprazole. Cytosolic Ca2+ elevation in rabbit parietal cells induced by gastrin (50 nM) was blocked by CR 2945 with an IC50 value of 5.9 nM. CAM-1028 and L-365,260 showed similar activity. CR 2945 antagonized pentagastrin-stimulated gastric acid secretion in rats (ED50 = 1.3 mg kg(-1) i.v. and 2.7 mg kg(-1) i.d.) and cats (1.6 mg kg(-1) i.v.). CR 2945 was slightly less potent than the reference compounds after i.v. administration, whereas after intraduodenal (i.d.) administration, it was more potent than both ranitidine and omeprazole. In the rat, the gastrin antagonism exhibited by CR 2945 was reversible and competitive, with a pA2 value of 7.33. CR 2945 had specific antigastrin activity, as it was unable to antagonize the gastric acid secretion stimulated by histamine or carbachol in rats up to the dose of 30 mg kg(-1). CR 2945 was about as efficacious as ranitidine against the indomethacin- and ethanol-induced gastric ulcers and the cysteamine-induced duodenal ulcer in rats. On the contrary, L-365,260 was only slightly effective. These results suggest that CR 2945 might be a promising compound for the therapy of acid-related disorders, and that its clinical use could help clarify the therapeutic potential of gastrin/CCK(B) receptor antagonists in the gut.

Topics: Animals; Anti-Anxiety Agents; Anti-Ulcer Agents; Benzodiazepines; Benzodiazepinones; Calcium; Cats; Chronic Disease; Cysteamine; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Indomethacin; Male; Omeprazole; Parietal Cells, Gastric; Pentagastrin; Perfusion; Phenylurea Compounds; Rabbits; Ranitidine; Rats; Receptors, Cholecystokinin; Stomach; Stomach Ulcer

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

CCK exhibits a potent cytoprotective activity against acute gastric lesions, but its role in ulcer healing has been little examined. In this study we determined whether exogenous CCK or endogenously released CCK by camostate, an inhibitor of luminal proteases, or by the diversion of pancreatico-biliary secretion from the duodenum, could affect ulcer healing. In addition, the effects of antagonism of CCK-A receptors (by loxiglumide, LOX) or CCK-B receptors (by L-365,260), an inhibition of NO-synthase by N(G)-nitro-L-arginine (L-NNA), or sensory denervation by large neurotoxic dose of capsaicin on CCK-induced ulcer healing were examined. Gastric ulcers were produced by serosal application of acetic acid and animals were sacrificed 9 days after ulcer induction. The area of ulcers and blood flow at the ulcer area were determined. Plasma levels of gastrin and CCK and luminal somatostatin were measured by RIA and mucosal biopsy samples were taken for histological evaluation and measurement of DNA synthesis. CCK given s.c. reduced dose dependently the ulcer area; the threshold dose of CCK being 1 nmol/kg and the dose inhibiting this area by 50% being 5 nmol/kg. This healing effect of CCK was accompanied by a significant increase in the GBF at ulcer margin and the rise in luminal NO production, plasma gastrin level and DNA synthesis. Concurrent treatment with LOX, completely abolished the CCK-8-induced acceleration of the ulcer healing and the rise in the GBF at the ulcer margin, whereas L-365,260 remained without any influence. Treatment with camostate or diversion of pancreatic juice that raised plasma CCK level to that observed with administration of CCK-8, also accelerated ulcer healing and this effect was also attenuated by LOX but not by L-365,260. Inhibition of NO-synthase by L-NNA significantly delayed ulcer healing and reversed the CCK-8 induced acceleration of ulcer healing, hyperemia at the ulcer margin and luminal NO release, and these effects were restored by the addition to L-NNA of L-arginine but not D-arginine. Capsaicin denervation attenuated CCK-induced ulcer healing, and the accompanying rise in the GBF at the ulcer margin and decreased plasma gastrin and luminal release of somatostatin when compared to those in rats with intact sensory nerves. Detectable signals for CCK-A and B receptor mRNAs as well as for cNOS mRNA expression were recorded by RT-PCR in the vehicle control gastric mucosa. The expression of CCK-A receptor mRNA and cNOS mRNA wa

Topics: Animals; Cholecystokinin; DNA Replication; Dopamine Agents; Esters; Gabexate; Gastric Mucosa; Gastrins; Guanidines; Hormone Antagonists; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Pancreatin; Proglumide; Protease Inhibitors; Rats; Rats, Wistar; Receptors, Cholecystokinin; Regional Blood Flow; RNA, Messenger; Sensory Receptor Cells; Sincalide; Somatostatin; Stomach; Stomach Ulcer

We have investigated the involvement of human apolipoprotein A-IV (apoA-IV) in gastric acid secretion and ulcer formation in recently generated apoA-IV transgenic mice. Compared to control littermates, transgenic animals showed a gastric acid secretion decreased by 43-77% whereas only slight variations were observed in the different cell population densities within the gastric mucosa. In addition, no variation in gastrin levels was observed. Transgenics were protected against indomethacin-induced ulcer formation, with lesions diminishing by 45 to 64% compared to controls. These results indicate that endogenous apoA-IV expression can regulate gastric acid secretion and ulcer development.

Topics: Age Factors; Animals; Apolipoproteins A; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Indomethacin; Mice; Mice, Transgenic; Stomach Ulcer

In this study, ischemia-reperfusion produced in rats by clamping the celiac artery for 0.5 h followed by 1 h of reperfusion was used to develop a new model of superficial gastric erosions progressing to deeper ulcers. Ischemia alone resulted in an immediate fall in gastric blood flow but no gross mucosal lesions were observed. When ischemia was followed by reperfusion, gastric erosive lesions occurred, reached a maximum at 12 h and then declined after 24 h. These acute erosions progressed into deeper lesions 24 h after ischemia-reperfusion and reached a peak after 3 days. Gastric blood flow and the mucosal generation of prostaglandin E(2) were significantly suppressed immediately following ischemia-reperfusion, but with the healing of deeper gastric ulcers, both gastric blood flow and prostaglandin E(2) generation were gradually restored. Cyclooxygenase-1 mRNA was detected by reverse transcription-polymerase chain reaction in intact gastric mucosa and throughout the recovery of the mucosa from acute ischemia-reperfusion lesions, whereas cyclooxygenase-2 mRNA, was recorded only after ischemia-reperfusion. NS-398 and rofecoxib, selective inhibitors of cyclooxyganase-2, failed to affect prostaglandin E(2) generation in the non-ulcerated gastric mucosa but inhibited it significantly in the ulcer area. The two cyclooxygenase-2 inhibitors as well as resveratrol, a specific cyclooxygenase-1 inhibitor and indomethacin and meloxicam, non-specific inhibitors of cyclooxygenase, augmented acute gastric erosions induced by ischemia-reperfusion and delayed significantly the progression of these lesions into deeper ulcers at each time interval after ischemia-reperfusion. We conclude that prostaglandins generated by both cyclooxygenase-1 and cyclooxygenase-2 contribute to the healing of gastric lesions induced by ischemia-reperfusion.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Disease Models, Animal; Gastric Mucosa; Gastrins; Gene Expression Regulation, Enzymologic; Indomethacin; Interleukin-1; Isoenzymes; Lactones; Meloxicam; Membrane Proteins; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Regional Blood Flow; Reperfusion Injury; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stilbenes; Stomach Ulcer; Sulfonamides; Sulfones; Thiazines; Thiazoles; Time Factors

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

During recent years, gastric ECL cells have attracted much attention, mainly due to the fact that mice and rats were found to develop gastric carcinoids following lifelong treatment with blockers of acid secretion. We present the structure and functions of ECL cells and their influence on physiology and pathology of stomach and duodenum. We describe interactions of enzymes and hormones in histamine-stimulated gastric output.

Topics: Animals; Anti-Ulcer Agents; Chromogranin A; Duodenal Neoplasms; Duodenal Ulcer; Enterochromaffin-like Cells; Gastrins; Histamine; Mice; Pancreatic Hormones; Rats; Stomach Neoplasms; Stomach Ulcer

A follow-up of argyrophil cell hyperplasia in Helicobacter pylori-positive corpus gastritis in gastric ulcer patients during the natural course of ulcer disease.. Endoscopic biopsies (4 specimens) were obtained step-wise from the posterior wall of the corpus mucosa in 55 gastric ulcer (GU) patients. The natural course of GU was followed up in 38 patients during more than 10 years (maximum 19 years), and altogether 115 endoscopic examinations were made: 20 patients were re-examined once, 14 twice, and 4 three times. A total of 364 biopsies from 307 biopsy sites were stained by Grimelius' silver, hematoxylin-eosin, and Giemsa method for the analysis of the argyrophil endocrine cells, chronic gastritis, and H. pylori colonization, respectively, according to the Sydney System.. Of 307 biopsy sites, 153 (50%) showed some grade of ACH. Focal (linear/micronodular) hyperplasia was found in 118 (77%) of biopsy sites; it was detected in 78 (66%) cases of atrophic corpus mucosa, but was present in only 14 (12%) cases of gastritis without atrophy or in the normal mucosa. In the follow-up patients, ACH evolved in 17 and progressed in 6 cases, and a simultaneous development of atrophic corpus gastritis was found in 20 cases.. This study demonstrates that ACH evolves during the natural course of GU, alongside the development of chronic atrophic gastritis.

Topics: Adult; Aged; Antacids; Enteroendocrine Cells; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter pylori; Humans; Hyperplasia; Male; Middle Aged; Stomach Ulcer

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

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

Growth factors such as epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) have been shown to share common receptor (EGFR) and to accelerate ulcer healing due to stimulation of cell proliferation, but the time sequence of expression of EGF and TGF alpha during ulcer healing has not been investigated. In this study the rate of cell proliferation and the gastric secretion and gene expression of mRNA for EGF and TGF alpha were determined during ulcer healing.. Gastric ulcers were induced in 150 Wistar rats by serosal application of 100% acetic acid (ulcer area, 14 mm2). Some of these animals were also equipped with a gastric fistula for the assessment of gastric secretion during ulcer healing. The animals were killed 0, 2, 4, 6, or 8 days after ulcer induction, and the ulcer area was determined. The mucosal sections with gastric ulcer were immunostained for proliferating cell nuclear antigen (PCNA) and for immunoexpression of EGF, TGF alpha, and EGFR. The expression of mRNA EGF and mRNA TGF alpha was also determined in the ulcer margin by reverse transcriptase (RT) polymerase chain reaction (PCR) using specific primers.. Two, 4, 6, and 8 days after ulcer induction the gastric ulcer area was gradually reduced from the initial size (day 0) by 47%, 70%, 80%, and 87%, respectively, and this was accompanied by an increase in PCNA with its maximum on day 4. The gastric acid and pepsin secretion was significantly reduced by 75% and 79%, respectively, on day 2 after ulcer induction but then the secretion tended to return to normal value by day 8. The expression of EGF, TGF alpha, and EGFR was negligible on day 0 but increased significantly during the healing, reaching maximum on day 4. Expression of EGF mRNA was detected on days 2, 4, and 6, and that of TGF alpha mRNA on days 2, 4, 6, and 8 after ulcer induction, with the most intense signals for both transcripts observed on day 2.. 1) The enhancement in cell proliferation during ulcer healing may be mediated by increased release of EGF and TGF alpha; 2) the expression of EGF and TGF alpha mRNA precedes the overexpression of these growth factors at the ulcer margin during ulcer healing; and 3) the overexpression of growth factors coincides with the inhibition of gastric secretion and increased blood flow at the ulcer margin, indicating that these factors affect gastric secretion and blood flow in the course of ulcer healing.

Topics: Animals; Cell Division; Epidermal Growth Factor; ErbB Receptors; Female; Gastric Acid; Gastrins; Gene Expression; Immunohistochemistry; Male; Rats; Rats, Wistar; Regional Blood Flow; RNA, Messenger; Stomach; Stomach Ulcer; Time Factors; Transforming Growth Factor alpha; Wound Healing

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer

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

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

Melatonin, a pineal hormone, synthesized from L-tryptophan, is known to exist in the gut and to scavenge oxygen free radicals but its role in gastroprotection against acute lesions induced by various strong irritants has been little studied. In this study, we determined the effects of melatonin and L-tryptophan on gastric secretion and the formation of acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), stress, and ischemia-reperfusion (I/R). Area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using a H2-gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentration by specific radioimmunoassay. Intragastric (i.g.) administration of melatonin (2.5-10 mg/kg) or L-tryptophan (25-200 mg/kg) failed to affect gastric lesions by ethanol and ASA but dose-dependently reduced the lesions provoked by stress and I/R; this protective effect was accompanied by a significant rise in plasma melatonin level, GBF, and DNA synthesis and by a marked fall in blood free radicals. L-tryptophan, which significantly elevated the plasma melatonin by about 3-5-fold, also reduced the stress and I/R-induced lesions and blood levels of free radicals, while increasing the GBF, DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE2 by indomethacin abolished the protection and the rise of GBF afforded by melatonin and L-tryptophan, whereas pretreatment with N(G)-nitro-L-arginine (L-NNA), to suppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L-tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hyperemia probably mediated by endogenous prostaglandin but not NO.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; DNA; Dose-Response Relationship, Drug; Ethanol; Female; Free Radical Scavengers; Gastric Mucosa; Gastrins; Male; Melatonin; Radioimmunoassay; Rats; Rats, Wistar; Reperfusion Injury; Solvents; Stomach; Stomach Ulcer; Stress, Physiological; Tryptophan

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

We investigated if hypergastrinemia exerted any influence on the proliferation of gastroduodenal epithelium during the healing of ulcers in rats. A mucosal ulcer was induced in the corpus region of the stomach in three groups of rats, which were then given vehicle, omeprazole (400 mumol/kg/day), or gastrin-17 (60 nmol/kg/day) for three or six days. A fourth group of unoperated rats served as controls. One hour before killing, [3H]thymidine was injected. The ulcer margin and corresponding control tissues were excised and processed for light microscopic determination of epithelial labeling index (LI), mitotic index, and apoptotic index. LI was also determined in other parts of the gastroduodenal mucosa. Three and six days after the ulcer operation, the LI in the vehicle-treated ulcer rats was significantly increased in the ulcer margin and in the duodenum, in comparison with the intact controls. In the ulcer margin, the mitotic index was significantly increased, in parallel with the LI; the apoptotic index remained at the control level. The LI in the ulcer margin was increased further after administration of omeprazole or gastrin-17, which elevated the plasma gastrin levels by 5-15 times. It is concluded that hypergastrinemia may increase cell proliferation in the ulcer margin, which may accelerate the rate of healing.

Topics: Animals; Anti-Ulcer Agents; Apoptosis; Autoradiography; Cell Count; Cell Division; Duodenum; Epithelium; Female; Gastric Mucosa; Gastrins; Hormones; Immunohistochemistry; Intestinal Mucosa; Mitotic Index; Omeprazole; Rats; Rats, Sprague-Dawley; Stomach Ulcer

To determine the clinical efficacy of once-daily treatment with omeprazole in refractory acid-related diseases in children.. Endoscopic healing and 24-hour intragastric pH values were assessed in 13 patients with refractory reflux esophagitis (n = 5), refractory and/or giant duodenal ulcer (n = 6), or giant gastric ulcer (n = 2). The mean dose of omeprazole was 0.6 mg/kg per day (range, 0.3 to 0.7 mg/kg per day). Pharmacokinetic studies of omeprazole were performed in seven patients.. The cumulative healing rates at 2, 4, 6, and 8 weeks of treatment were 46%, 85%, 92%, and 92%, respectively. Esophagitis in one patient did not heal despite increases in doses of up to 1.6 mg/kg per day (40 mg/day). The mean intragastric pH of omeprazole-treated patients was 5.2 (range, 3.0 to 6.6) and mean hydrogenion activity was 1.78 mmol/L (range, 0.01 to 10.42 mmol/L). There was wide interindividual variation in the reduction of gastric acid production. Mean intragastric H+ activity in omeprazole-treated patients was significantly lower than that of control subjects (p < 0.005) and that of patients treated with histamine type 2(H2)-receptor antagonists (p < 0.05). Mean intragastric H+ activity was not significantly correlated to the area under the concentration-time curve of omeprazole. No severe adverse effects were reported during treatment or at follow-up.. Omeprazole has a potent antisecretory effect and is a suitable alternative for short-term treatment of refractory acid-related diseases; a relatively low dose (0.6 mg/kg per day) appears to be optimal in most patients. Unhealed esophagitis at 8 weeks of treatment was considered to be refractory to omeprazole.

Topics: Anti-Ulcer Agents; Case-Control Studies; Child; Dose-Response Relationship, Drug; Duodenal Ulcer; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Follow-Up Studies; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Omeprazole; Stomach Ulcer; Time Factors

This study was conducted to investigate the influence of cimetidine on the Helicobacter [correction of Helilcobacter] pylori(HP) colonization and serum acidic markers in gastric ulcer patients.. Forty-eight patients with gastric ulcer confirmed by endoscopy were consecutively enrolled. HP colonization was confirmed by either urease test or histological examination. Fasting serum gastrin and pepsinogen I (PGI) levels were measured before and after 8 weeks of cimetidine treatment.. Healing of ulcer at the end of treatment was 75%. Initially, the infection rate of HP was 87.5% (42/48). After 8 weeks of treatment, HP clearance rate was only 7.1% (3/42). A significant elevation of serum gastrin level was seen in HP positive subjects after treatment (86.3 +/- 22.2 pg/ml vs. 103.1 +/- 44.36 pg/ml, p <0.05) while HP negative patients did not show the effect. There was no significant change in the mean serum PGI concentration before and after cimetidine treatment (91.5 +/- 36.6 ng/ml vs. 95.6 +/- 43.8 ng/ml, NS).. Cimetidine is not able to clear HP despite its good efficacy in healing gastric ulcers. HP should play an important role in the elevation of serum gastrin levels during cimetidine therapy while serum PGI levels are not influenced by the antisecretory ability of cimetidine.

Topics: Aged; Anti-Ulcer Agents; Cimetidine; Female; Gastrins; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Middle Aged; Stomach Ulcer

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

The present study was designed to determine the relationship between changes in gastric function caused by aging and the healing of gastric ulcers. Male Fischer-344 rats (young, 2 months; aged, 24-26 months) were used. Gastric ulcers were induced by luminal application of an acetic acid solution (60%, 0.2 ml, 45 sec). The basal and histamine-stimulated gastric acid secretions in aged animals were significantly lower than those in young animals. However, the serum gastrin levels were almost the same in the two groups. Gastric mucosal blood flow and mucosal cell proliferation were also decreased in aged animals. Gastric contractile activity induced by electrical vagal stimulation was almost the same in the two groups, while the gastric relaxative response was significantly reduced in aged animals. The development and healing rate of gastric ulcers in aged animals were almost the same as those in young animals. Histologically, regeneration of the ulcerated mucosa was significantly reduced and tissue contraction occurred in aged animals, as compared to in young animals. We concluded that aging had little or no influence on the development and healing rate of gastric ulcers in rats, but the quality of ulcer healing was quite different between young and aged animals, probably resulting from various gastric dysfunctions related to ulcer healing.

Topics: Acetates; Acetic Acid; Aging; Animals; Cell Division; Gastric Acid; Gastrins; Gastrointestinal Motility; Male; Rats; Rats, Inbred F344; Remission, Spontaneous; Stomach; Stomach Ulcer

Indomethacin delays healing of experimental gastric ulcers. We investigated whether inhibition of gastric acid secretion by omeprazole or stimulation of angiogenesis by basic fibroblast growth factor (bFGF) may reverse this delay. Rats with gastric ulcers induced by cryoprobe were treated subcutaneously with either placebo, indomethacin (2 x 0.5 mg/kg), bFGF (2 x 100 micrograms/kg), omeprazole (1 x 40 mumol/kg), indomethacin plus omeprazole, or indomethacin plus bFGF given daily for 8, 10, 15, and 22 days. Ulcer size, epithelial cell proliferation, angiogenesis, and maturation of granulation tissue were sequentially quantified. Omeprazole significantly accelerated ulcer healing in an early phase (days 3-8). In contrast, bFGF accelerated healing in a late phase (days 10-15). Indomethacin significantly delayed ulcer healing in late phase and decreased prostaglandin generation, cell proliferation, angiogenesis, and maturation of granulation tissue. Despite stimulation of angiogenesis, bFGF did not reverse indomethacin-induced delay in ulcer healing. In contrast, omeprazole reversed indomethacin-induced effects on angiogenesis, cell proliferation, maturation of granulation tissue, and ulcer healing rate.

Topics: Animals; Bromodeoxyuridine; Drug Combinations; Female; Fibroblast Growth Factor 2; Gastric Acid; Gastric Mucosa; Gastrins; Gastroscopy; Indomethacin; Kinetics; Neovascularization, Pathologic; Omeprazole; Prostaglandins; Rats; Rats, Wistar; Stomach Ulcer; Wound Healing

To evaluate endogenous and exogenous factors affecting the quality of ulcer healing produced by proton pump inhibitors, gastric acid pH, serum gastrin, and serum pepsinogen (PG) I and II were measured in peptic ulcer patients before and after treatment with lansoprazole 30 mg once daily. Lansoprazole achieved more rapid scarring in duodenal ulcer (n = 34), with a healing rate of 97.1% after 6 weeks, than in gastric ulcer (n = 56), with a healing rate of 92.8% after 8 weeks. Scarring was the most rapid in gastroduodenal ulcer (n = 8), with a healing rate of 100% after 8 weeks, but the rate of complete scarring was the lowest (37.5%). Lower gastric acidity and lower PG I:II ratio were associated with poor quality ulcer scarring in patients with gastric ulcers, but the opposite was true for those with duodenal and gastroduodenal ulcers. For gastric ulcers, not only ulcer size but also mucosal atrophy was an important factor in ulcer healing. Smoking and alcohol consumption had little effect on the quality of ulcer healing during treatment. These results suggest that there are a number of differences between gastric ulcers and duodenal ulcers in terms of the quality of ulcer healing after lansoprazole treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Age Factors; Alcohol Drinking; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pepsinogens; Peptic Ulcer; Proton Pump Inhibitors; Sex Factors; Smoking; Stomach Ulcer

Primary endocrine neoplasms of intra- and extrahepatic biliary ducts are very rare. We describe the first case of a primary endocrine tumor of the common bile duct producing gastrin. A 53-year-old woman had a 3-year history of recurrent duodenal and gastric ulcers as well as obstructive jaundice. A small neoplasm was found in the lower third of the common bile duct, which showed diffuse gastrin production and focal synthesis of serotonin and pancreatic polypeptide by immunohistochemistry and electron microscopy. Although serum gastrin was within normal levels (90 ng/ml), symptoms of peptic acid disease could have been related to hypergastrinemia, since gastric and duodenal ulcers healed after surgical removal of the tumor. She has remained asymptomatic for 8 months.

Topics: Cholestasis; Common Bile Duct Neoplasms; Duodenal Ulcer; Female; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Middle Aged; Stomach Ulcer

This study was designed to determine the efficacy of L-arginine in healing of gastric ulcers induced by acetic acid and to assess the role of nitric oxide (NO), prostaglandins, gastrin and polyamines in the healing process. Intragastric administration of L-arginine (32.5-300 mg/kg/day) enhanced the healing rate of these ulcers in a dose-dependent manner, while D-arginine (300 mg/kg/day) was not effective. The acceleration of healing by L-arginine was accompanied by a marked increase in gastric blood flow (GBF) at the ulcer margin, and an enhancement of serum gastrin level, mucosal DNA synthesis, and DNA and RNA contents and angiogenesis in the granulation tissue in the ulcer bed. A similar increase in ulcer healing associated with hyperemia at the ulcer margin and enhanced angiogenesis but without alteration in serum gastrin were observed after treatment with glyceryl trinitrate, an NO exogenous supplier. Treatment with NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, delayed ulcer healing and this was accompanied by a reduction of GBF at the ulcer margin and in angiogenesis in granulation tissue and by a decrease in serum gastrin level and mucosal growth. Addition of L-arginine to L-NNA restored ulcer healing, hyperemia at the ulcer margin and angiogenesis and prevented the fall in serum gastrin and mucosal growth caused by L-NNA. Pretreatment with indomethacin also delayed ulcer healing and this was reversed by the coadministration of L-arginine. Inhibition of polyamine biosynthesis by difluoro-methyl-ornithine completely abolished the acceleration of the healing and the increase in mucosal growth induced by L-arginine. Our findings indicate that L-arginine accelerates ulcer healing due to its hyperemic, angiogenic and growth-promoting actions, possibly involving NO, gastrin and polyamines.

Topics: Animals; Arginine; Chronic Disease; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Eflornithine; Gastrins; Indomethacin; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Nitroglycerin; Polyamines; Prostaglandins; Rats; Rats, Wistar; Regional Blood Flow; Stomach; Stomach Ulcer; Vasodilator Agents

The experimental Wistar rats were divided into two groups, the acupuncture group and the control group. Stress-induced gastric ulcer models were established by immersion of restrained rats in water. The electroacupuncture was able to protect stress rat from stress induced peptic ulcer. The results indicated that electroacupuncture protecting rat from stress ulceration was relevant to enhancing gastric mucosal barrier, stabilizing gastric mast cell and inhibiting the gastrin levels in gastric mucous.

Topics: Animals; Cell Degranulation; Electroacupuncture; Female; Gastric Mucosa; Gastrins; Male; Mast Cells; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological

Male young adult Wistar rats were treated parenterally with cortisol and cortisol combined with salmon calcitonin for 28 and 56 days and the stomach was investigated histologically as well as the G cells using immunohistochemistry. After 28 days of cortisol administration desquamation of the superficial layers of gastric mucosa was found and after 56 days ulcer-like changes developed and increased gastrin immunoreactivity was observed. Administration of high doses of salmon calcitonin together with cortisol resulted in a significant hypoplasia of G cells and prevented the pathological changes in the gastric mucosa.

Topics: Animals; Calcitonin; Disease Models, Animal; Drug Interactions; Gastric Mucosa; Gastrins; Hydrocortisone; Immunohistochemistry; Injections, Intraperitoneal; Male; Rats; Rats, Wistar; Stomach Ulcer

We examined the effect of a liquid diet or a combined diet of liquid plus cellulose on the healing of gastric ulcers induced in rats in comparison with that of solid chow. Ulcers were induced in the fundus of the stomach by luminal application of an acetic acid solution. The healing of ulcers could be divided into two phases based on the healing rate: early phase (days 1 to 10) and late phase (days 10 to 20). The liquid diet, but not the combined one, administered for 10 days significantly accelerated ulcer healing in both the early and late phases. The length of the ruptured muscularis mucosa decreased only in the liquid diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet group was observed only in the late phase, it being markedly inhibited in the liquid diet group. The serum gastrin level significantly decreased in the liquid and combined diet groups in contrast to that in the chow group. The liquid and combined diets significantly reduced gastric mucosal DNA synthesis. We conclude that 1) the healing in this gastric ulcer model comprises two phases, and 2) tissue contraction is a major factor for the healing of gastric ulcers in the early phase, while both tissue contraction and regeneration of the ulcerated mucosa are involved in the healing in the late phase.

Topics: Acetates; Acetic Acid; Animal Feed; Animals; Body Weight; Cell Division; Cellulose; Food, Formulated; Gastric Emptying; Gastric Mucosa; Gastrins; Male; Muscle Contraction; Muscle, Smooth; Rats; Stomach Ulcer

The effects of cimetidine, omeprazole and atropine sulfate on the healing of acetic acid-induced gastric ulcers in rats with limited food intake time (9:00-10:00 a.m. and 5:00-6:00 p.m.) were evaluated 15 days after the acid injection. Oral repeated administration of cimetidine (25-100 mg/kg twice daily) or omeprazole (10-50 mg/kg once daily) dose dependently accelerated ulcer healing. Atropine sulfate (10 mg/kg twice daily, p.o.) was ineffective. A single oral administration of omeprazole (50 mg/kg) or cimetidine (100 mg/kg) resulted in potent and long-lasting anti-acid secretory and gastrin-releasing actions. The degree and duration of anti-acid secretion by atropine sulfate were equal to those of cimetidine, but the elevation of gastrin release by atropine sulfate was weak and temporary. These results indicate that the gastric ulcers of rats with a limited food intake time are useful for evaluating the healing effects of cimetidine and omeprazole on gastric ulcers. In addition, the effects of both drugs may be related to the increased gastrin release rather than to the reduced acid secretion.

Topics: Acetates; Acetic Acid; Administration, Oral; Analysis of Variance; Animals; Atropine; Cimetidine; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Gastric Acid; Gastrins; Hydrogen-Ion Concentration; Male; Omeprazole; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Wound Healing

Daily oral administration of cimetidine or omeprazole markedly accelerated the healing of acetic acid-induced gastric ulcers in rats with a limited food intake time. The increased gastric acid secretion induced by daily treatment with histamine affected neither the spontaneous healing of the ulcers nor the healing-promoting actions of both agents. Pretreatment of rats with ulcers with 6-hydroxydopamine significantly inhibited the increase in the antrum gastrin cells, serum gastrin levels and corpus mucosal thickness elicited by repeated administration of cimetidine or omeprazole. Pretreatment with 6-hydroxydopamine did not affect the inhibitory actions of cimetidine and omeprazole on acid secretion, but completely abolished the ulcer healing-promoting actions of both drugs. Daily intraperitoneal administration of pentagastrin accelerated ulcer healing. These results suggest that cimetidine and omeprazole mainly accelerate the healing of gastric ulcers by the trophic action of gastrin via the increase in gastrin secretion, while the inhibition of acid secretion may play a minor role in ulcer healing.

Topics: Analysis of Variance; Animals; Cimetidine; Disease Models, Animal; Drug Interactions; Drug Synergism; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Male; Omeprazole; Oxidopamine; Pentagastrin; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Wound Healing

Unilateral vagotomy causes atrophy of the denervated fundic mucosa in rat stomachs. We examined whether or not unilateral vagotomy delays healing of gastric ulcers induced on the denervated mucosa. Kissing ulcers were induced in the fundus of rat stomachs by intraluminal application of an acetic acid solution. Anterior unilateral vagotomy was performed subdiaphragmatically at the time of ulceration. The healing of gastric ulcers induced on the denervated side was significantly enhanced, whereas that on the vagally intact side was not affected. In unilaterally denervated animals, the total gastric acid secretion (both basal and 2-deoxy-D-glucose stimulated) was inhibited, and the pH around the ulcers was increased only in the anterior side. Repeatedly administered histamine failed to affect the enhanced ulcer healing in unilaterally denervated animals. Gastric emptying and mucosal cell proliferation stimulated by food or pentagastrin were unaffected. Serum gastrin significantly increased 19 days after vagotomy. Gastric relaxation on refeeding was inhibited on the denervated side, but this inhibition of relaxation was reversed by hexamethonium treatment. A liquid diet significantly enhanced the healing of ulcers on both the denervated and vagally intact sides. The mechanism by which unilateral vagotomy accelerates the healing of ulcers on the denervated side appears to relate to the inhibition of both gastric acid secretion and gastric relaxation.

Topics: Animals; Cell Division; Deoxyglucose; Diet; Food; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Hexamethonium; Histamine; Male; Muscle Relaxation; Rats; Stomach Ulcer; Vagotomy

Gastroendoscopic surveys have shown that horses in race training have a greater prevalence of gastric ulceration than sedentary horses. To determine if exercise affects gastric endocrine function the following experiment was performed. Four horses were fed total mixed ration of ground corn and chopped hay at 2% of their body weight, divided into 2 equal portions, daily. Horses were fasted overnight, and serum gastrin concentration was determined just before and 2 hours after feeding. The horses were then sprint trained on a high speed treadmill for 6 weeks. The response of serum gastrin to feeding was then repeated as before. Serum gastrin increased following feeding both before and after training, however the postfeeding gastrin value was higher [p = 0.035] after training (68.1 +/- 6.9 pg/ml [mean +/- 1 SEM]) than before (42.7 +/- 3.8 pg/ml). These data show that treadmill exercise has an effect upon the gastric hormonal response to a meal in the horse. The relationship of this finding to the development of gastric ulcer disease is unknown at present, but warrants further investigation.

Topics: Animals; Eating; Gastrins; Horse Diseases; Horses; Physical Conditioning, Animal; Stomach Ulcer; Stress, Physiological

The role of the autonomic nervous system in cell proliferation of the gastric mucosa during restraint water immersion stress was investigated utilizing the spontaneously hypertensive rat (SHR) and its progenitor, the Wistar-Kyoto rat (WKY). Three hours of water-immersion restraint induced gastric lesions more frequently in WKY than in SHR, although there were few visual lesions in either strain in two hours of stress. The number of 5-bromo-2'-deoxyuridine (BrdU) positive cells in the corpus ventriculi mucosa markedly decreased in the WKY, but did not change in the SHR after two hours of water-immersion restraint stress. The acetylcholine content in the mucosa significantly decreased and the density of acetylcholinesterase (ACh-E) containing fiber of mucosa remarkably increased in only WKY after two hours stress exposure. On the other hand, there was no significant difference in either the responsiveness or the content of norepinephrine and epinephrine, which indicates sympathetic nervous function, after stress exposure in WKY and SHR. Similarly, the response of serum gastrin was not significantly different between the two strains. These results strongly suggest that the parasympathetic nerve plays an essential role in cell proliferation of the gastric mucosa in the pathogenesis of stress ulcer.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Autonomic Nervous System; Bromodeoxyuridine; Cell Division; Corticosterone; Epinephrine; Gastric Mucosa; Gastrins; Histocytochemistry; Male; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stomach Ulcer; Stress, Psychological

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

Previous studies demonstrated that epidermal growth factor (EGF) and polyamines (PA) are capable of protecting gastric mucosa against topical irritants. This study was designed to examine whether EGF, PA, and PG affect the healing of acute gastric lesions induced by water immersion and restraint stress. It was found that the healing process of stress lesions in sham-operated rats was significant after 6 hr after stress, and after 24 hr the number of stress lesions was reduced by about 75%. In sham-operated rats, the healing of ulcerations observed at 6, 12, and 24 hr after the stress was accompanied by gradual restoration of DNA synthesis, and both these processes were significantly reduced by administration of DFMO (an inhibitor of ornithine decarboxylase activity) or indomethacin (an inhibitor of cyclooxygenase). In salivectomized rats, the healing was significantly delayed and the DNA was lowered at all time intervals after the stress. Administration of EGF, spermine, aminoguanidine (an inhibitor of degradation of PA), or 16,16-dmPGE2 after stress promoted significantly the healing and DNA synthesis, but pretreatment with DFMO abolished the effect of EGF but not that of spermine. We conclude that EGF, PA, and PG are implicated in healing of stress lesions and that EGF acts, at least in part, by the stimulation of PA formation in the gastric mucosa.

Topics: Acute Disease; Animals; DNA; Drug Therapy, Combination; Epidermal Growth Factor; Gastric Mucosa; Gastrins; Polyamines; Prostaglandins; Rats; Rats, Wistar; Salivary Glands; Stomach; Stomach Ulcer; Stress, Psychological; Time Factors; Wound Healing

Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.

Topics: Animals; Capillary Permeability; Epidermal Growth Factor; Ethanol; Gastrins; Hydrochloric Acid; Indomethacin; Male; Rats; Rats, Wistar; Salivary Glands; Stomach; Stomach Ulcer

The postoperative results of pylorus-preserving gastrectomy (PPG) for gastric ulcer performed in 134 patients during the past 25 years (mean postoperative period, 16.6 years) were studied. The incidence of postoperative complications was low. Dumping syndrome occurred in only 4.4% and 0% of cases as assessed by questionnaire and interview, respectively. Four (5.4%) of 74 patients available for this study had ulcer recurrence. In one of these four patients concurrent gastroduodenal ulcer was suspected from preoperative gastric analysis. The site of recurrence was found in all cases to be the remnant antral gland area along the greater curvature between the proper gastric gland area and the duodenum. Basal and maximal acid outputs at the time of relapse were significantly higher in patients with recurrence than in patients without recurrence. The fasting and postprandial serum gastrin levels were high in one patient with recurrence, whose antrum was preserved as long as 3 cm proximal to the pyloric ring; this was longer than that described in our original method of PPG. In two other recurrent cases the serum gastrin levels were not different from those in nonrecurrent cases. Immunohistochemical examination of the residual antrum showed no increase in the G-cell density in patients either with or without recurrence. These results suggest that the long-term quality of life of patients treated with PPG remains favorable. Recurrence rate can be further reduced if PPG is strictly indicated for gastric ulcer only and carried out by meticulous surgical techniques. In the pathogenesis of the ulcer recurrence the role of gastrin release from the residual antral mucosa seems to be limited.

Topics: Adult; Female; Follow-Up Studies; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Postgastrectomy Syndromes; Postoperative Period; Pylorus; Radiography; Recurrence; Stomach Ulcer

Pronounced inhibition of acid secretion appears to induce an intragastric environment suitable for N-nitrosamine formation, hyper-gastrinemia, ECL cell hyperplasia and carcinoid tumor formation. Development of gastric cancer, however, has not been obvious in clinical and experimental studies, but oncongenicity studies indicate an increased risk of gastric cancer with long-term use of proton pump inhibitors in subjects with hyperplastic or other, changes in the gastric mucosa. The findings suggest that proton pump inhibitors should be used only for short term treatment.

Topics: Adenosine Triphosphatases; Animals; Depression, Chemical; Gastric Acid; Gastrins; H(+)-K(+)-Exchanging ATPase; Humans; Nitrosamines; Omeprazole; Stomach; Stomach Neoplasms; Stomach Ulcer; Time Factors

Topics: Aged; Carcinoma, Small Cell; Gastrins; Humans; Lung Neoplasms; Male; Paraneoplastic Endocrine Syndromes; Stomach Ulcer; Zollinger-Ellison Syndrome

Ebrotidine is a novel H2-receptor antagonist that exhibits both gastroprotective and ulcer-healing properties. Gastroprotection afforded by ebrotidine against ethanol damage was observed only after intragastric, but not parenteral administration, and it was accompanied by an increase in the mucosal blood flow. Ranitidine given at the same dose (100 mg/kg i.g. or s.c.) did not show any protective activity. When administered twice daily at various doses (1-100 mg/kg) for 10 days, ebrotidine reduced dose dependently the area of chronic gastric ulcers, and it was accompanied by significantly higher contents of epidermal growth factor (EGF) in the ulcer bed than in the intact mucosa. Administration of ranitidine resulted in a similar rate of ulcer healing and in a similar accumulation of EGF in the ulcer area to that observed after ebrotidine, but the increments in plasma gastrin levels in rats treated with ranitidine were observed at lower doses than in tests with ebrotidine. Concurrent administration of indomethacin delayed ulcer healing and reduced the accumulation of EGF in the ulcer area, but did not affect the ulcer healing by ebrotidine or ranitidine. We conclude that ebrotidine but not ranitidine shows gastroprotective activity, but it enhances the healing of chronic ulcerations in a similar manner to ranitidine.

Topics: Acetates; Acetic Acid; Animals; Benzenesulfonates; Epidermal Growth Factor; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Male; Ranitidine; Rats; Rats, Inbred Strains; Regional Blood Flow; Stomach Ulcer; Thiazoles

Ninety patients suffering from peptic ulcer and 25 healthy subjects were examined for the content of gastrin, bombesin and somatostatin in blood and gastric juice. Among patients with duodenal ulcer, 2 groups were distinguished: group I included patients in whom peptic ulcer occurred before 30 years; the majority of the patients manifested blood hypergastrinemia, a decrease of bombesin concentration and normal somatostatin concentration; gastric juice was characterized by a lowering of somatostatin concentration and unchanged gastrin concentration; group II was made up of patients who developed peptic ulcer after 30: in the majority of the patients, gastrin concentration was reduced under basal conditions, after loading it was unchanged; in part of the patients, blood somatostatin concentration was elevated, in 16 in exacerbation and in 19 in remission; in the remainder, it was unchanged. The concentration of bombesin in blood remained unchanged. In gastric juice, gastrin concentration was increased only after histamine administration, somatostatin concentration was unchanged whatever the disease stage. In patients with gastric ulcer, gastrin concentration in blood was elevated only under basal conditions, being unchanged in gastric juice irrespective of the disease stage. Meanwhile, the concentration of bombesin was lowered both under basal conditions and after insulin administration, the concentration of somatostatin was decreased both in blood and gastric juice whatever the disease stage.

Topics: Adult; Bombesin; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Somatostatin; Stomach Ulcer

Fasting serum gastrin levels greater than 1000 pg/ml are said to establish the diagnosis of gastrinoma in a patient with peptic ulcer disease. The authors observed a patient with recurrent peptic ulcer disease, diarrhea, and a fasting serum gastrin of 1044 pg/ml who had a gastrocolic fistula, not the Zollinger-Ellison syndrome. The provocative tests of gastrin secretion, including secretin infusion and standard meal test, were helpful in ruling out a gastrinoma. This is the first reported association of gastrocolic fistula and hypergastrinemia. The patient demonstrates that the differential diagnosis of markedly elevated serum gastrin should be expanded to include gastrocolic fistula.

Topics: Adult; Colonic Diseases; Diagnosis, Differential; Female; Gastric Fistula; Gastrins; Humans; Intestinal Fistula; Stomach Ulcer; Zollinger-Ellison Syndrome

The connection between the character of gastrin and acid reactions and visible morphological changes of gastric mucosa in immobilising-cold stress was studied in the experiments on mongrel rats. It is established that in the rats the fundal gastric mucosa is resistant to the disturbing action of the immobilising-cold stress. The post-stress gastrin contents in the antrum and duodenum mucosa is higher and in the serum lower than in rats with ulceration. The rats with the stress erosions have the intermediate position. The acid factor didn't play the significant role in the ulcerogenesis because its value didn't overstep the limits established in the extradigestive period.

Topics: Animals; Cold Temperature; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Immobilization; Male; Rats; Stomach Ulcer; Stress, Physiological

The gastric and antiulcer effects of UP 5145-52, a new naphthyridinone derivative (1-phenyl-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl)-4-acetoxy butane, were studied in rats. UP 5145-52 dose dependently prevented the formation of gastric lesions induced by a necrotizing agent such as absolute ethanol, indomethacin or stress (ED50 values were 0.065, 1.26 and 0.72 mg/kg p.o., respectively). A beneficial action was also observed against indomethacin-induced intestinal lesions. UP 5145-52 inhibited total acid output in the pylorus-ligated rat (ED50 on total acid output was 0.16 mg/kg p.o.) and in the rat chronic gastric fistula model. The mechanism of antisecretory activity currently remains unknown as UP 5145-52 fails to bind to receptors involved in gastric secretion (H2 or muscarinic) and to inhibit H+/K+ adenosine triphosphatase. The ability of UP 5145-52 (1 mg/kg p.o.) to restore synthesis of gastric acid glycoproteins depressed by previous administration of absolute ethanol suggests that cytoprotection could play a role in the antiulcer efficacy of the drug.

Topics: Adenosine Triphosphatases; Administration, Oral; Animals; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Guinea Pigs; Indomethacin; Male; Naphthyridines; Pain; Rabbits; Rats; Rats, Inbred Strains; Receptors, Opioid; Stomach Ulcer

Being pepsinogen A (PGA) levels generally reduced and pepsinogen C (PGC) increased in gastric cancer patients, PGA/PGC ratio has been proposed as a useful marker of the tumour. We tested PGA, PGC and Gastrin (G) levels in patients with gastric cancer (39) and, as a control, in patients with epithelial dysplasia (21), chronic atrophic gastritis (57), gastric ulcer (11) or subjects lacking major or minor endoscopic and microscopic changes at gastroscopy (48). PGA and PGA/PGC levels were significantly reduced in gastric cancer patients (p less than 0.005 and p less than 0.0001 respectively with analysis of variance). Gastrin levels were also reduced in the same patients (p less than 0.005). We therefore adopted an index number (PGA x Gastrin) which was also dramatically reduced in gastric cancer (p less than 0.005); using an arbitrarily chosen cut-off, the "marker" showed very high sensitivity (76%), specificity (96%) and overall accuracy (74%, by Youden J test). We therefore suggest the use of the index number PGA x G in the diagnosis of gastric cancer, as the most useful gastrin presently available, to our knowledge.

Topics: Biomarkers, Tumor; Chronic Disease; Gastrins; Gastritis, Atrophic; Humans; Mathematics; Pepsinogens; Sensitivity and Specificity; Stomach Neoplasms; Stomach Ulcer

The effects of antrectomy and proximal gastric vagotomy on the metabolism of histamine in the human gastric mucosa were studied in the basal state and during pentagastrin stimulation in patients with duodenal or gastric ulcer disease. Mucosal biopsy specimens were taken from the antral and oxyntic gland areas, whereafter histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Vagotomy was followed by a decrease in the acid secretory capacity and an increase in basal serum gastrin levels. Histamine content of the oxyntic mucosa increased after vagotomy, but the ability of pentagastrin to form new amounts of the amine was impaired. Antrectomy caused a decrease in acid secretion and a fall in gastrin concentrations. Basal histamine content and rate of amine formation in the remaining oxyntic mucosa were unaffected by antrectomy. Antrectomy impaired the ability of pentagastrin to release histamine. Histamine methyltransferase was not affected by pentagastrin, vagotomy, or antrectomy. In conclusion, both antral gastrin and the vagus nerve seem to exert a regulatory influence on the metabolism of histamine in the human oxyntic mucosa. The withdrawal of these factors either causes impaired ability of pentagastrin to release histamine from its storage site or counteracts the ability of pentagastrin to accelerate histamine synthesis.

Topics: Analysis of Variance; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Middle Aged; Pentagastrin; Pyloric Antrum; Stomach Ulcer; Vagotomy

A different pathophysiological mechanism is widely accepted for gastric and duodenal ulcer. In particular, the exact role of gastrin in the determinism of non hormono-dependent peptic ulcer disease is not completely clarified. Therefore, the aim of present study was to analyse fasting and post-prandial serum gastrin levels in 99 duodenal ulcer patients, 17 gastric ulcer patients and 11 subjects presenting an association of gastric and duodenal ulcer. The possible correlation between post-prandial gastrin concentrations and basal and maximal acid output in the 3 fasting serum gastrin levels appear not different among the 3 classes of patients, while post-prandial gastrin concentrations are statistically higher at 15 minutes in duodenal ulcer patients and in subjects with the association of gastric and duodenal ulcer as compared to gastric ulcer patients. Mean fasting and stimulated gastrin levels are higher in gastric ulcer females than in males during the entire test and with statistically difference at 30 minutes. The concentrations of the hormone are not different in males of the 3 groups of patients at basal time, while are statistically lower at 15 and 30 minutes in gastric ulcer males compared to the males with duodenal ulcer and the association of the localization. Finally, positive correlation has been observed between BAO and MAO and post-prandial gastric concentrations in the 3 groups of patients, while there is an inverse correlation between the previous parameters as regards sex, both in gastric and duodenal ulcer.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Feeding Behavior; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Sex Characteristics; Stomach Ulcer; Time Factors

It was found that in patients with gastroduodenal hemorrhage the number of serotonin-, histamine-, and melatonin-producing apudocytes in the gastric mucosa increases while the number of cells producing gastrin, adrenaline, and noradrenaline reduces. In timely arrest of hemorrhage, the primarily increased number of melatonin-producing apudocytes diminishes with time from the onset of bleeding and reaches normal values gradually. The essential differences in the content of melatonin- and noradrenaline- producing apudocytes in patients with and without hemorrhage allow this morphological sign to be used as diagnostic and prognostic criteria in gastroduodenal hemorrhages.

Topics: Adult; Aged; APUD Cells; Catecholamines; Cell Count; Duodenal Ulcer; Female; Gastrins; Hormones, Ectopic; Humans; Male; Melatonin; Middle Aged; Peptic Ulcer Hemorrhage; Pyloric Antrum; Stomach Ulcer

Gastrin- and somatostatin-immunoreactive cells in biopsies taken from the prepyloric portion of the antrum from 15 patients with duodenal ulcer, 16 patients with gastric ulcer, and a control group of 19 patients without histopathological alterations of the antral mucosa were studied using peroxidase anti-peroxidase and immunogold-silver staining methods in combination with morphometry. Numerical densities and sizes (immunoreactive areas) of the cells demonstrated were measured and compared between all three groups. Gastrin- and somatostatin-immunoreactive cells were located most frequently in the lower midzone of the gastric crypts. None of the parameters measured showed a correlation with age or sex. The group with duodenal ulcer tended to exhibit gastrin- and somatostatin-cell-hyperplasia whereas the size of both cell types remained unchanged. In comparison with the control group, the numerical density of gastrin-immunoreactive cells was significantly increased in gastric ulcer patients, whereas the numerical density of somatostatin-immunoreactive cells was decreased in this group. Immunoreactive areas of both cell types were significantly increased in patients with gastric ulcer.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Mucous Membrane; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Amino Acid Sequence; Chromatography; Gastric Mucosa; Gastrins; Glicentin; Glucagon; Glucagon-Like Peptides; Histamine; Humans; Molecular Sequence Data; Omeprazole; Peptide Fragments; Protein Conformation; Protein Precursors; Stomach Ulcer

The metabolism of histamine in the human gastric mucosa was studied in the basal state and during pentagastrin stimulation. Studies were made in healthy volunteers and in patients with peptic ulcer disease. Mucosal biopsies were taken from antral and oxyntic gland areas whereupon histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Histamine content of the oxyntic gland mucosa was decreased as a consequence of pentagastrin administration in all groups studied, and this decrease was numerically largest in patients with duodenal ulcer disease. Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer. The highest rates of histamine formation were present in the oxyntic mucosa of patients with Zollinger-Ellison syndrome. The activity of histamine methyltransferase was the same in all groups studied and was not changed by pentagastrin. In conclusion, pentagastrin administration in humans is followed by a significant mobilization of histamine only from the oxyntic gland mucosa, an effect that is more pronounced in patients with duodenal ulcer disease.

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Stimulation, Chemical; Stomach Ulcer; Zollinger-Ellison Syndrome

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.

Topics: Calcium; Duodenal Ulcer; Gastrins; Humans; Hyperparathyroidism; Parathyroid Glands; Parathyroid Neoplasms; Stomach Ulcer

Anatomically, functionally, and clinically, peptic ulcer patients are a heterogeneous group of subjects. These patients can be classified according to the anatomic localization of the niche. The functional state of the gastric mucosa was studied in 30 gastric ulcer patients, 25 duodenal ulcer patients, and 10 normal controls. The classification of the first group was based on Johnson's criteria, with the following results: 10 individuals were type I, 10 were type II, and 10 were type III. Pepsinogen I levels and gastric acid secretion were measured in all 65 subjects under basal conditions and after subcutaneous pentagastrin stimulation. Both basal and stimulated serum pepsinogen I values were significantly higher (p less than 0.05) in gastric ulcer type III patients than in the other four groups. These values in gastric ulcer type I were similar to those of the controls. Gastric ulcer type II patients showed an intermediate functional state similar to that of duodenal ulcer patients. In both gastric ulcer type II and duodenal ulcer patients, the basal and stimulated pepsinogen I levels were significantly higher (p less than 0.05) than those found in controls, whereas the basal serum gastrin levels were similar in the five groups. In conclusion, different HCl and pepsinogen I secretory patterns, with functional heterogenicity of the gastric mucosa, are shown here for the anatomically defined gastric ulcer subsets.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Stomach Ulcer

In our previous reports, low dose acid secretagogues caused increase in corpus mucus glycoprotein content in rats. This increase was not due to the direct action of protons. The present study was conducted to determine whether this increase has a mucosal function or not Rats were given histamine (0.8 mg/kg) intraperitoneally or tetragastrin (12 micrograms/kg) subcutaneously. One hour following the acid secretagogues administration, the animals were given 1 ml of 30, 40 or 50% ethanol orally and then sacrificed after one hour. Gastric mucus glycoproteins were isolated from the corpus region of stomach. The following results were obtained: 1) Histamine prevented the gastric mucosal damage and the decrease of corpus mucus glycoprotein content induced by 40% ethanol ingestion. 2) Tetragastrin prevented the gastric mucosal damage induced by 30 approximately 50% ethanol ingestion and the decrease of corpus mucus glycoprotein content induced by 40 approximately 50% ethanol ingestion. Based on these results, the increase of corpus mucus glycoprotein content induced by acid secretagogues has a mucosal function. Moreover, tetragastrin strengthened the mucosal defence together with acid secretion.

Topics: Animals; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Glycoproteins; Histamine; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Tetragastrin

Complex examination of 73 patients with ulcer disease (bulbus duodeni location) revealed regularities of evacuation of a test breakfast from the stomach depending on the phase of the disease. Significant disorders of the motor-emptying gastric and duodenal function were found that are to be considered in the treatment of this category of patients.

Topics: Adult; Biopsy; Duodenal Ulcer; Duodenoscopy; Duodenum; Female; Gastric Acidity Determination; Gastric Emptying; Gastrins; Gastrointestinal Motility; Gastroscopy; Humans; Male; Stomach; Stomach Ulcer

A total of 36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with omeprazole 20-60 mg/day, for periods up to 3 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a mean of 81.5 to 206 pg/ml; a slight decrease was observed thereafter. There was no significant increase in the volume density of argyrophilic cells in the oxyntic mucosa. No clusters of endocrine cells were found in the oxyntic mucosa and no change of G-cell volume density occurred in the antral mucosa under therapy. Omeprazole therapy did not result in any changes in gastrin levels or oxyntic argyrophilic cells in the antrectomized patients. It is concluded that the moderate hypergastrinaemia observed during long-term omeprazole treatment in man does not induce hyperplasia of argyrophilic cells in the oxyntic mucosa.

Topics: Biopsy; Cell Count; Esophagitis, Peptic; Gastric Acid; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Long-Term Care; Omeprazole; Stomach Ulcer

Topics: Actihaemyl; Adult; Cyclic AMP; Cyclic GMP; Drug Evaluation; Duodenal Ulcer; Female; Gastrins; Humans; Insulin; Male; Middle Aged; Stomach Ulcer; Tissue Extracts

Gastric acid secretions and serum gastrin levels have been examined in 128 patients with early gastric cancer and in 98 gastric ulcer patients. Gastric cancer patients were found to have lower acid secretions than did gastric ulcer patients, and those with elevated types of a differentiated adenocarcinoma had lower acid secretions than did those with depressed types of an undifferentiated adenocarcinoma. Gastric acid secretions in patients with both a gastric ulcer and cancer were found to decrease with aging. However, the serum gastrin levels were found to be decreased in patients with a gastric ulcer and to be increased in patients with a gastric cancer. Incidences of a differentiated adenocarcinoma increased with aging. From these observations, it has been speculated that the carcinogenesis of a differentiated adenocarcinoma may be related to increasing endogenous gastrin levels and decreasing gastric acid secretions. These results suggest that a continuous check of the serum gastrin levels might be a good marker for cancer detection and that gastrin antibodies might be useful for treatment.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Adult; Aged; Aging; Biomarkers, Tumor; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer

Gastrin and somatostatin-like immunoreactivity (SLI) levels were studied by means of radioimmunoassay in peripheral venous blood of healthy volunteers and patients suffering from gastric adenocarcinoma or duodenal and gastric ulcers. Gastrin and SLI levels were also evaluated in patients in blood drawn from gastric veins during surgery. The elevations of gastrin and SLI levels were found in patients with gastric cancer as compared with healthy people and patients suffering from ulcers. The impairment of the negative feedback between gastrin and somatostatin secretions in patients with gastric cancer was suggested.

Topics: Adenocarcinoma; Adult; Aged; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Somatostatin; Stomach Neoplasms; Stomach Ulcer

A different pathophysiological mechanism is widely accepted for gastric and duodenal ulcer. In particular, the exact role of gastrin in the determinism of nonhormone-dependent peptic ulcer disease has been completely clarified. The aim of the present study was to analyse fasting and postprandial serum gastrin levels in 99 duodenal ulcer patients, 17 gastric ulcer patients and 11 subjects presenting an association of gastric and duodenal ulcer. The possible correlation between postprandial gastrin concentrations and basal and maximal acid output in the 3 groups of patients has also been investigated. Fasting serum gastrin levels do not appear different among the 3 classes of patients, while postprandial gastrin concentrations are statistically higher at 15 minutes in duodenal ulcer patients and in subjects with the association of gastric and duodenal ulcer as compared to gastric ulcer patients. Mean fasting and stimulated gastrin levels are higher in gastric ulcer females than in males during the entire test and with a statistically significant difference at 30 minutes. The concentrations of the hormone are not different in males of the 3 groups of patients at basal time, while they are statistically lower at 15 and 30 minutes in gastric ulcer males compared to those with duodenal ulcer and the association of the localization. Finally, positive correlation has been observed between B.A.O. and M.A.O. and postprandial gastrin concentration in the 3 groups of patients, while there is an inverse correlation between the previous parameters as regards sex, both in gastric and duodenal ulcer.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Feeding Behavior; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Sex Characteristics; Stomach Ulcer; Time Factors

Cholecystokinin (CCK) is a polypeptid released postprandially by the upper intestinal mucosa. There are several biological active forms of CCK. Radioimmunological measurements of CCK may not detect all biological active forms or may have the disadvantage of crossreacting with gastrin. In the following we describe a modification of a bioassay for CCK which was first developed by Liddle et al. (J Clin Invest 1985). By means of this bioassay pre- and postprandial plasma CCK-levels of healthy male volunteers are compared with CCK-levels of patients with partial gastric resections and excluded duodenum. Both groups showed similar basal CCK-values (about 1 pM) and a food induced increase of this hormone by reaching maximal values after 15 to 30 min (control: 4.30 +/- 0.65 vs. operated: 13.37 +/- 2.83 pM). Patients with gastric resections, however, had about three times more CCK released over the 60 min time period studied as compared to controls. Thus exclusion of the duodenum, the supposed main place of CCK production, does not cause a lower but rather higher increase of postprandial CCK release.

Topics: Adult; Aged; Anastomosis, Roux-en-Y; Cholecystokinin; Duodenal Ulcer; Gastrectomy; Gastric Emptying; Gastrins; Humans; Intestinal Absorption; Middle Aged; Peptic Ulcer Hemorrhage; Postoperative Complications; Radioimmunoassay; Stomach Ulcer

1. The comparative gastric toxicology and pharmacokinetics of two phenoxyisobutyrate derivatives have been evaluated in the Fischer rat. 2. After oral administration of single daily doses for 7 days, the plasma elimination half-life for bezafibrate was rapid (t1/2 of 4-5 h) in comparison to ciprofibrate (t1/2 of 76 h). 3. The area under the plasma drug concentration versus time curve (AUC) 0-24 (micrograms.h/ml +/- SD) for bezafibrate (dose 125 mg/kg per day) was 1553 +/- 334, which was less than half the value of 3748 +/- 358 achieved by ciprofibrate (10 mg/kg per day) after 7 days. 4. Oral administration of ciprofibrate at 10 mg/kg every 48 h produced similar sustained plasma concentrations to those achieved by bezafibrate 125 mg/kg dosed every 12 h. The AUC 0-48 values (micrograms.h/ml +/- SD) achieved were 5124 +/- 450 for bezafibrate compared to 4207 +/- 240 for ciprofibrate. 5. In chronic oral multidose studies with ciprofibrate and bezafibrate, similar gastric toxicity (neuroendocrine cell hyperplasia) occurred in the rat when dose regimens were adjusted to compensate for the pharmacokinetic differences between these two drugs.

Topics: Administration, Oral; Animals; Bezafibrate; Clofibric Acid; Dose-Response Relationship, Drug; Fibric Acids; Gastric Mucosa; Gastrins; Hypolipidemic Agents; Male; Neurosecretory Systems; Rats; Rats, Inbred F344; Stomach Ulcer

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action.

Topics: Administration, Oral; Animals; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastrins; Infusions, Parenteral; Intestinal Mucosa; Male; Nucleic Acids; Rats; Rats, Inbred Strains; Somatostatin; Stomach Ulcer; Wound Healing

The number of gastrin cells (G cells) and somatostatin cells (D cells) per surface unit, and the G/D cell ratio were estimated in biopsy specimens of the antrum from normal subjects without hypergastrinemia, and from patients with hypergastrinemia not induced by gastrinoma or supra selective vagotomy. Compared with normal subjects, antral G cell density and G/D cell ratio were significantly increased in patients with hypergastrinemia. A significant correlation was found between G cell density or G/D cell ratio and the integrated gastrin output values. A quantitative estimation appears therefore possible in biopsy specimens.

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Biopsy; Female; Gastrins; Gastroscopy; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Animals; Cats; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastrins; Hexosamines; Male; Pepsin A; Pirenzepine; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Nucleotides, Cyclic; Stomach Ulcer

Campylobacter pylori may cause gastritis and has been proposed as an etiologic factor in the development of peptic ulcer. However, it may be an acid-sensitive microbe and before it can be implicated in the pathogenesis of peptic ulcer, it should be consistently found in ulcer patients with normal acid secretion. Thirty-six patients with C. pylori by Warthin-Starry stain underwent gastric analysis; 25 were normochlorhydric and 11 hypochlorhydric. Ulcers were present in 19 normochlorhydric patients (10, gastric; 9, duodenal) and 2 hypochlorhydric patients (gastric). Median basal acid output was higher for those with duodenal ulcer (38 mmol/h) than gastric ulcer (28 mmol/h) or miscellaneous endoscopic features (33 mmol/h). The hypergastrinemia seen in 12 patients with negative secretin provocation tests was believed to be due to various nongastrinoma conditions. Campylobacter pylori was found in 6 normogastrinemic patients with elevated acid output and in 1 gastrinoma patient with marked acid hypersecretion. Histologic chronic gastritis was present in all subjects and 29 had active chronic gastritis. Twenty-three patients were taking H2-receptor antagonists at the time of diagnosis which did not seem to interfere with culture results. Using standard acid secretory tests, we conclude that C. pylori can survive in a wide range of acid conditions.

Topics: Adult; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Humans; Male; Stomach Ulcer

The consequences of deviation of pancreatic juice and bile after gastric resection were studied in an experimental animal model in 66 rats. After hemigastrectomy and Billroth I resp. Billroth II anastomoses papilla vateri was transplanted into a deep jejunal limb in a B I and a B II group each. Absence of alkaline secretions of Papilla vateri was followed by a marked increase in acidity in the gastric remnant and connected intestine. Especially in the Billroth II operated stomach we found an increased ulcer risk under these circumstances. With additional histamine-stimulation frequency of ulcer was 75% in Billroth II but only 33% in Billroth I animals. When alkaline reflux was preserved the ulcer rate ranged from 15 to 40% in all groups. These results confirmed the protective property of postresectional reflux for the integrity of anastomoses after gastric resection. The increased resistance of Billroth I anastomoses in spite of deficient luminal acid buffers could be explained by the mucus-bicarbonate-barrier of the duodenal mucosa.

Topics: Anastomosis, Surgical; Animals; Bile; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrins; Male; Pancreatic Juice; Rats; Rats, Inbred Strains; Risk Factors; Stomach Ulcer; Wound Healing

Topics: Adult; Age Factors; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Sex Factors; Stomach Ulcer

We investigated whether the trophic actions of prostaglandins, omeprazole, and indomethacin on gastric mucosa lead to accelerated healing of gastric ulcers in the rat. Cryoulcers were produced in the corpus area and treated with 16,16-dimethyl prostaglandin E2 (5 or 100 micrograms/kg b.i.d., intragastrically), omeprazole (40 mumol/kg once daily, subcutaneously), indomethacin (2 mg/kg b.i.d., subcutaneously), or placebo. At the end of the treatment, plasma gastrin, cell labeling index (autoradiography with [3H]thymidine), and the size and depth of mucosal defects were measured. Compared with placebo, omeprazole accelerated ulcer healing as indicated by a smaller ulcer area [1.1 +/- 0.2 vs. 4.8 +/- 1.2 mm2 (mean +/- SEM)] and smaller ulcer depth (383 +/- 31 vs. 488 +/- 41 microns) after 10 days of treatment. Prostaglandins did not affect ulcer healing despite thickening of gastric corpus mucosa. Indomethacin delayed ulcer healing and reduced the labeling index. Omeprazole induced a marked hypergastrinemia (208 +/- 12 vs. 66 +/- 12 pmol/L on day 5, and 469 +/- 23 vs. 58 +/- 16 pmol/L on day 10). The results indicate that abolishment of acid secretion by omeprazole accelerates healing. Trophic actions and "cytoprotective" effects by prostaglandins are not relevant for ulcer healing in this model.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Autoradiography; Body Weight; Gastric Mucosa; Gastrins; Indomethacin; Male; Omeprazole; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer

36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with 40-60 mg of omeprazole daily for periods between 1 and 2 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a medium level of 81.5 to 206 pg/ml, a slight decrease was seen thereafter. In 10 patients investigated before the start of the treatment and after 1 and 2 years, the volume density of argyrophilic cells in the oxyntic mucosa increased from 0.43 +/- 0.08 to 0.91 +/- 0.14% during the first year; this change was statistically significant. No further increase was observed thereafter. No such difference could be demonstrated between a larger group of 18 patients investigated before and after 1 year of treatment with omeprazole (0.806 +/- 0.1 vs. 0.93 +/- 0.08%) and between a larger group of 22 untreated patients and 17 patients treated for 17-24 months with omeprazole (0.73 +/- 0.1 vs. 0.86 +/- 0.09%). The volume density of argyrophilic cells found in 8 patients with gastrinoma amounted to 1.37 +/- 0.22%. No clusters of endocrine cells were found in omeprazole-treated patients. The D cell volume density in the antral mucosa decreased significantly during the first months of treatment, but steadily increased thereafter to reach pretreatment values after 17 months. There was no change in G cell volume density under therapy. No changes in gastrin levels or oxyntic argyrophilic cells were observed in the antrectomized patients. It is concluded that the hyperplasia of argyrophilic cells observed in some patients during long-term omeprazole treatment is mediated by hypergastrinaemia.

Topics: Female; Gastric Mucosa; Gastrins; Humans; Male; Omeprazole; Parietal Cells, Gastric; Peptic Ulcer; Ranitidine; Stomach Ulcer; Time Factors

94 patients with peptic ulcerations of duodenum, stomach, and esophagus, who did not respond to 3 or more months high-dose (450 or 600 mg) treatment with ranitidine, were treated orally with 40 mg omeprazole daily. After healing all patients were offered long-term maintenance therapy with the same dose for 5 years. In 75 patients the peptic ulcerations healed within 4 weeks, in 13 patients within 8 weeks, and in 3 patients only after an increase to 60 mg omeprazole daily. In 3 patients the ulcers did not heal. So far 83 patients have entered long-term maintenance therapy. 59 of these patients are on the drug between 1 and 4 years. During maintenance therapy with 40 mg omeprazole no relapses have occurred up to now as demonstrated by endoscopy and no drug-related adverse effects were observed. Routine laboratory tests remained without significant changes in all patients including 18 patients with concomitant liver cirrhosis. Serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (106 +/- 15.4 pg/ml). 4 weeks after the start of omeprazole treatment serum gastrin levels rose to 4 times normal levels (195 +/- 28 pg/ml). Thereafter, no further increase in serum gastrin was observed even up to 4 years of continuous observation. It is therefore concluded that omeprazole is highly effective in healing ranitidine-resistant peptic ulcerations and that omeprazole maintenance therapy with 40 mg omeprazole is safe during the time observed and highly effective in the prevention of ulcer recurrence.

Topics: Adult; Aged; Duodenal Ulcer; Esophagitis, Peptic; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Ranitidine; Stomach Ulcer; Time Factors

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.

Topics: Adult; Aged; Anemia, Pernicious; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer

This study compares the prophylactic effects of two different diets and routes of feeding on restraint stress-induced gastric erosions in the rat. Thirty male Sprague-Dawley rats were food-deprived and immobilized for 24 hours using a steel wire mesh. A small silicone tube was placed into either the proximal jejunum or the stomach via a laparotomy. There were three groups of ten rats (five jejunum-fed, five stomach-fed), receiving infusions (50 ml/24 h) of: (A) normal saline; (B) free amino acids (Vivonex HN, Norwich Eaton Pharmaceuticals) (60 cal and 0.318 G nitrogen); or (C) a peptide diet, with the nitrogen source as lactalbumin hydrolysate, otherwise identical to B. Gastric acidity was measured every 4 hours. At 24 hours, blood was collected and serum gastrin levels determined. The animals were then sacrificed and the stomachs examined. The results were analyzed using one-way analysis of variance. Fewer gastric erosions and lower serum gastrin levels and gastric acidity were found in animals fed diets B and C, versus animals fed normal saline (p less than 0.05). There was no difference between groups B and C. Our results also show that enteral diets using the jejunal route are better than those using the gastric route in reducing the incidence of stress-induced gastric erosions in rats.

Topics: Amino Acids; Animals; Enteral Nutrition; Food, Formulated; Gastric Acidity Determination; Gastrins; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Psychological

I investigated the significance of bile reflux, when vagotomy was done to stress ulcer, by means of measuring gastric ulcer index, gastric pH and serum gastrin levels of rats. And in order to examine influence of alkali factor of bile, I measured gastric acid output and serum gastrin levels after alkali or acid solution was infused into the untreated rat's stomach. Results were summarized as follows: 1. When I infused alkali solution into the untreated stomach, there was no significant change in serum gastrin level but gastric acid output was significantly accelerated, as compared with infusing acid solution. On the other hand, when I infused alkali solution into the vagotomized stomach, serum gastrin level increased significantly and gastric acid output was significantly accelerated, as compared with infusing acid solution, so, acceleration of acid output observed when I infused alkali solution into the untreated stomach was not suppressed in spite of vagotomy operation. 2. In the vagotomized group, gastric acid output was significantly suppressed and serum gastrin level increased significantly as compared with the untreated group. But, when bile was led into the stomach in the vagotomized group, acid output was accelerated and serum gastrin level also showed a tendency to increase as compared with the group of vagotomy alone. 3. When mild stress was inflicted, stress ulcer formation was significantly prevented in the bile reflux group (vagotomy + pyloroplasty) as well as in the non-bile reflux group (vagotomy + pyloric ligation + gastroileostomy) if vagotomy was done. But, when severe stress was inflicted, stress ulcer formation was significantly prevented in the non-bile reflux group, but not prevented in the bile reflux group. As mentioned above, it was proved that stress ulcer formation was not prevented under a severe stress, if bile reflux existed, even though vagotomy was done. So, if we do vagotomy operation, we need to choose the operation method not to induce bile reflux as much as possible.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Gastric Acid; Gastrins; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Vagotomy

We have established an experimental model of chronic gastric ulcer, in rats which transection of the lower horizontal portion of the duodenum and anastomosis of the forestomach to the upper part of the jejunum caused regurgitation of all duodenal juice into the stomach. After 3, 6, 12, and 30 wk, all treated rats developed an ulcer in the prepyloric region on the lesser curvature of the stomach. More than half of the antrum was finally involved in the ulcer. Histologic studies revealed chronic ulcers quite similar to human ones. As a control series, transection at the pylorus failed to produce an ulcer. Although many papers have appeared regarding the experimental production of chronic gastric ulcer, most of the studies reported have applied chemicals, drugs, or mechanical injury to the gastric mucosa. Our model produced chronic regurgitation of duodenal juice as a natural phenomenon, and uniformly resulted in ulcer formation. Intragastric total bile acid concentrations were significantly elevated in the reflux group. Serum gastrin levels, the thickness of the fundic mucosa, and the height of fundic gland were also significantly increased. Thus, the detergent action of bile acids and the increased acid secretion were assumed to play an important role in ulcer formation. Further studies using this model are warranted on the pathogenesis of chronic peptic ulceration.

Topics: Animals; Bile Acids and Salts; Chronic Disease; Disease Models, Animal; Duodenogastric Reflux; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Circadian Rhythm; Duodenal Ulcer; Gastrins; Humans; Pepsinogens; Peptic Ulcer; Stomach Ulcer

The present study explored the 24-hr variations in serum gastrin and pepsinogen in clinically healthy subjects and in patients with gastric ulcer, duodenal ulcer, and erosive gastroduodenopathy. Time-qualified data were analyzed by means of cosinor procedures. Significant changes in rhythmometric properties were documented in patients with peptic disease when compared to clinically healthy subjects. In essence, it was discovered that gastric ulcer patients exhibit a higher mesor and amplitude for both gastrin and pepsinogen, whereas duodenal ulcer patients and those with erosive gastroduodenopathy show only a significant increase in the pepsinogen mesor. These characteristics are so specific in the groups investigated that one can hypothesize that the disorders in the circadian rhythmicity of gastrin and pepsinogen have a role in determining the clinical manifestations of peptic disease.

Topics: Circadian Rhythm; Duodenal Ulcer; Female; Gastrins; Humans; Male; Pepsinogens; Stomach Ulcer

Three patients with juxtapyloric ulcers and hypergastrinemia are presented. Fasting and food-stimulated serum gastrin concentration (SGC) were measured in 1970, 1972 and 1973 before the primary ulcer operation (selective gastric vagotomy and Jaboulay gastroduodenostomy; SGV + GD). Fasting SGC were 105, 149 and 158 pg/ml and the postprandial concentrations were 400, greater than 800 and greater than 800 pg/ml, respectively. The pentagastrin-stimulated acid secretion was within the normal range. After SGV + GD, only a slight decrease in acid secretion was observed. The hypergastrinemia persisted unchanged or decreased slightly in 1 patient. A recurrent ulcer developed and a precise antrectomy was carried out. Postoperatively, the fasting SGC was markedly reduced and the postprandial gastrin response abolished. The resected specimens were subjected to immunocytochemical gastrin cell quantitation. The number of gastrin cells was elevated in all 3 patients and the gastrin cell topography was distorted, with cells being present both in the lower and upper thirds of the antropyloric glands.

Topics: Adult; Female; Gastric Acid; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Radioimmunoassay; Recurrence; Stomach Ulcer

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with the biochemical indices of growth in gastric and duodenal mucosa in the following three groups of rats: (a) chow-fed, (b) fed an isocaloric liquid diet, (c) fed the liquid diet plus pentagastrin injections (250 micrograms/kg, 3 times/day). Animals received the diet regimen for 10 days from 1 day after induction of ulcer (day 0). Following the feeding regimens, serum gastrin levels, oxyntic gland mucosal DNA synthesis, and gastric secretory function were significantly lowered in the rats fed liquid diets. DNA synthesis in the duodenal mucosa was not different from the pre-ulcer levels. Pentagastrin significantly restored the DNA synthetic and gastric secretory activity of the liquid diet-fed rats toward the levels in the chow-fed group. In the latter group, a significant increase in DNA synthesis and levels of serum gastrin was found at day 6 (after 5 days feeding), which corresponded with a rapid, spontaneous healing of ulcers. Feeding rats liquid diet significantly delayed the healing of gastric, but not duodenal ulcers. Repeated administration of pentagastrin accelerated gastric ulcer healing in the liquid diet group toward the rate observed in the chow-fed group, but had no effect on the healing of duodenal ulcers. These results indicate that cell proliferation is an important factor in the healing of gastric ulcers.

Topics: Animals; Cell Division; DNA; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Pentagastrin; Rats; Rats, Inbred Strains; RNA; Stomach Ulcer; Wound Healing

Grimelius reaction and immunohistochemical PAP method were used to study endocrine cells producing gastrin (G-cells), somatostatin (D-cells) and gamma-endorphin (GER-cells) in gastric and duodenal mucosa of 95 males with atrophic gastritis with intestinal and pyloric metaplasia. The number of cells was counted per 1 mm2 of the mucosa. In the cases of marked intestinal metaplasia the number of G-, GER- and especially D-cells in the pyloric region non-metaplastic epithelium decreases and is approaching to its number in the duodenum of the control group. In the foci of marked pyloric metaplasia of gastric corpus the number of G- and GER-cells is almost the same as in the zones of gastric metaplasia of duodenum, and is approximating their number in the pyloric region of controls, thus allowing the designation of pyloric metaplasia as a complete one.

Topics: Adolescent; Adult; Aged; APUD Cells; Biopsy; Duodenal Ulcer; Duodenum; Endorphins; gamma-Endorphin; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Histocytochemistry; Humans; Immunoenzyme Techniques; Metaplasia; Middle Aged; Pylorus; Somatostatin; Stomach Ulcer

In the rat, both partial resection of the pancreas and occlusion of the side branches of the biliodigestive duct were investigated with respect to their influence on gastric secretion (acid, pepsin, sodium), gastric mucosal blood flow (MBF), development of gastric ulcers, and gastrin and somatostatin in the blood. On the 14th postoperative day the exocrine pancreatic function is reduced and ulcer index and severity are significantly enhanced. There are no simultaneous changes in gastric secretion or MBF. Aortal gastrin was decreased and somatostatin was unchanged. We conclude that: in the rat, reduction of exocrine pancreatic function should be considered an ulcerogenic factor; factors others than gastric hypersecretion or reduced MBF are responsible for ulcer formation, and an etiological role of either circulating gastrin or somatostatin is doubtful.

Topics: Animals; Aorta; Duodenogastric Reflux; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Male; Pancreatectomy; Pancreatic Ducts; Pepsin A; Portal Vein; Postoperative Complications; Rats; Rats, Inbred Strains; Regional Blood Flow; Sodium; Somatostatin; Stomach Ulcer

Serotonin-containing EC cells in human fetal, infantile and adult stomachs both normal and affected by gastritis, were studied by immunohistochemical, electron microscopic and autoradiographic methods. EC cells were sparse in fetal and infantile stomachs, while they occurred in the lower half of the gastric mucosa in adult stomachs showing no atrophic changes and their distribution density was higher than that of D cells. With the progress of chronic gastritis, the number of EC cells gradually decreased, but intestinal type of EC cells appeared in intestinalized gastric mucosa, often showing hyperplasia. Most of EC cells showed argyrophil reaction, but only about 10-20% of them were positive with argentaffin. Epithelial cells with 3H-TdR labeled nuclei were frequently detected in the gastric mucosa where EC cells were sparse or almost absent. Electron microscopically, EC cells had typical electron dense granules in both the normal gastric mucosa and in the intestinal metaplastic glands, but the number of secretory granules was greater in the latter than in the former. These findings suggested that EC cells are preferentially present in the gastric mucosa with a small number of labeled nuclei and have morphological heterogeneity.

Topics: Adult; Aged; Autoradiography; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Histocytochemistry; Humans; Infant; Microscopy, Electron; Pregnancy; Serotonin; Somatostatin; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Male; Pyloric Antrum; Somatostatin; Stomach Ulcer

The number of G cells and D cells per area unit and the G cell/D cell ratio was studied in control subjects and patients with duodenal or gastric ulcer. A great inter-individual variation in the population density of both types of cells was observed in the three groups studied. G cell density was significantly decreased in both duodenal and gastric ulcer patients, when compared with controls; whereas no difference in G cell density was seen between duodenal ulcer patients and gastric ulcer patients. However, D cell density was significantly decreased in duodenal ulcer patients when compared with control subjects and gastric ulcer patients. In this latter group, D cell density was also lower than in control subjects. A significant positive linear correlation between G cell number and D cell number was found in the three groups studied. The G cell/D cell ratio was significantly increased in duodenal and gastric ulcer patients when compared with controls. This was mainly due to a decrease in D cell numbers. It is concluded that a local deficit in antral D cells in patients with peptic ulcer may favor the pathogenesis of ulcer disease.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Animals; Gastric Mucosa; Gastrins; Male; Pentagastrin; Rats; Stomach Ulcer; Stress, Physiological

A reproducible model of acute gastric stress ulceration has been described in the tetraplegic rat. The characteristics of the development of acute gastric ulceration and the concentrations of plasma gastrin have been examined. There was a significant increase in gastric stress ulceration within 4 h of producing the tetraplegia. The ulceration was confined to the glandular portion of the stomach and occurred equally on crests and rugal troughs. Plasma gastrin concentrations were not changed by spinal cord section. This characterized model can serve as a basis for further investigation of the aetiology and prophylaxis of acute gastric ulceration in quadriplegia.

Topics: Animals; Body Temperature; Disease Models, Animal; Erythrocyte Volume; Female; Gastric Mucosa; Gastrins; Male; Quadriplegia; Rats; Rats, Inbred WKY; Spinal Cord Injuries; Stomach Ulcer; Stress, Physiological

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Male; Middle Aged; Stomach Ulcer

Topics: Adult; Aged; Female; Gastrins; Humans; Male; Middle Aged; Ranitidine; Stomach Ulcer; Time Factors

The purpose of this experiment was to determine whether chronic gastric ulcers in the rat are predisposed to tumor formation when exposed to a usually noncarcinogenic dose of the carcinogen, N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG). Two groups of rats were prepared; one subjected to a standard ulcer-producing operation, the other as control. Both groups were given oral MNNG (100 mg/liter as drinking water) for 12 weeks, the carcinogen was then stopped and replaced with tap water, and the experiment terminated at 52 weeks. Results showed that a low dose of carcinogen (200 mg) did not induce tumor formation in any of the normal rats. In the presence of a chronic gastric ulcer, only intestinal metaplasia and hyperplastic glandular nodules were observed, but there were no gastric tumors. It is concluded that the presence of a chronic gastric ulcer did not increase the likelihood of gastric tumor formation in rats treated with a noncarcinogenic dose of the carcinogen MNNG.

Topics: Animals; Carcinogens; Female; Gastric Acid; Gastrins; Liver; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms; Stomach Ulcer

Duodenal gastrin concentration was measured in endoscopic forceps biopsy specimens of the juxta-pyloric duodenal mucosa in patients with various gastrointestinal disorders. Duodenal gastrin concentration was 5.9 +/- 1.2 ng/mg (mean +/- 1 SEM) in control patients. Duodenal gastrin concentration was similar to control values in patients with duodenal ulcer, pyloric channel ulcer, vagotomy and pyloroplasty, and gastric atrophy and hypergastrinemia. In gastric ulcer patients, duodenal gastrin concentration, 2.8 +/- 0.6 ng/mg, was significantly less than the control value (P less than 0.05). Duodenal gastrin concentration was approximately one third of antral gastrin concentration in control, duodenal ulcer, and gastric ulcer patients and was approximately one fifth of antral gastrin concentration in vagotomy and pyloroplasty patients and gastric atrophy patients. Duodenal and antral gastrin concentrations were significantly correlated in normal controls and in gastric ulcer patients. The finding of normal duodenal gastrin concentration in patients with vagotomy and pyloroplasty and patients with gastric atrophy suggests that, unlike antral gastrin concentration, duodenal gastrin concentration is unaffected by a decrease in acid secretion rate. The low duodenal gastrin concentration in gastric ulcer patients indicates that the duodenum may be involved in the pathophysiology of gastric ulcer disease.

Topics: Biopsy; Duodenal Ulcer; Duodenum; Gastrins; Gastritis, Atrophic; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Pyloric Antrum; Stomach Ulcer

Antral somatostatin-immunoreactive cells (D cells) were counted pre- and postoperatively in 20 patients with duodenal ulcer and in 8 patients with gastric ulcer. Counts were obtained either over a 2-yr postoperative period (duodenal ulcer patients) at intervals of 0.5, 1, and 2 yr or over a greater than or equal to 4-yr postoperative period (gastric ulcer patients) at intervals of 1-2 yr. In patients with a normal population of gastrin-immunoreactive cells (G cells), the D cells were within the normal range (mean value 0.53% in duodenal ulcer patients and 0.67% in gastric ulcer patients). High G-cell values were accompanied by high D-cell values (e.g., in gastrin-cell hyperplasia) and low G-cell values were accompanied by low D-cell values. The G-cell to D-cell ratio was 8:1 and 6.6:1 in duodenal and gastric ulcer patients, respectively. After selective proximal vagotomy and pyloroplasty, the following observations were made: the relation of number of G cells to number of D cells remained unchanged; the postoperative rise in G-cell population was accompanied by a rise in D-cell population; hypertrophy of the D cells was apparent as was postoperative hyperplasia, with a postoperative increase in D-cell size. Morphologic coupling of the gastrin-somatostatin system in the antrum is assumed. This is constant in ulcer disease both before and after vagotomy.

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Hyperplasia; Hypertrophy; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer; Vagotomy

Gastric acid secretion, incidence of gastric mucosal lesion, and gut hormone responses were studied in 24 patients with liver cirrhosis. Gastric acid output in these subjects showed normal acidity and was nearly similar to that in patients with gastric ulcer. The incidence of gastric mucosal lesion was high, especially in patients whose plasma disappearance rate of indocyanine green was low. Plasma levels of both gastrin and gastric inhibitory polypeptide were higher in cirrhotic patients than in control subjects both in the fasting state and after the ingestion of a test meal. Gel chromatography of the postprandial plasma of cirrhotics showed a higher immunoreactivity at the second peak than in controls. This is because cirrhotics have a higher percentage of authentic gastric inhibitory polypeptide, although the elution patterns were similar in both groups. It is suggested that impairment of extraction of some molecular components of both gastrin and gastric inhibitory polypeptide may occur in the cirrhotic liver.

Topics: Adult; Aged; Blood Glucose; Chromatography, Gel; Female; Gastric Acid; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Mucous Membrane; Stomach; Stomach Diseases; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

Topics: Adult; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Pepsin A; Recurrence; Stomach Ulcer; Tetragastrin

Misoprostol, a synthetic derivative of prostaglandin E1, was tested and shown to be an effective gastric antisecretory agent against histamine-, pentagastrin-, and meal-stimulated acid secretion in dogs. Misoprostol reduced the volume of acid secretion as well as the hydrogen ion concentration. Misoprostol did not reduce gastric mucosal blood flow, nor did it alter meal-stimulated serum gastrin levels. Misoprostol inhibited acid secretion in histamine-stimulated isolated gastric glands indicating a direct antisecretory effect on parietal cells. The potency of misoprostol was greatest when administered in direct contact with the gastric mucosa indicating local absorption and action. Misoprostol strengthened the gastric mucosal barrier as shown by the attenuation of aspirin-induced lowering of transmucosal electrical potential differences. Misoprostol protected the gastric mucosa of rats subjected to ethanol-, taurocholate-, pyloric ligation-, stress- and indomethacin-induced damage. Misoprostol also protected against indomethacin-induced intestinal lesions in rats and reduced duodenal ulcer formation in guinea-pigs and cats. The doses of misoprostol required to protect against gastric damage were about one-tenth of those required to inhibit acid secretion. The results of these and other studies indicate that misoprostol is a safe agent with unique properties that should provide a new approach for treatment of ulcer diseases of the gastrointestinal tract.

Topics: Airway Resistance; Alprostadil; Animals; Anti-Ulcer Agents; Diarrhea; Drug Contamination; Drug Evaluation, Preclinical; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Hemodynamics; Isomerism; Membrane Potentials; Misoprostol; Regional Blood Flow; Stomach Ulcer

The effects of tripotassium dicitrato bismuthate (TDB) on gastric acid, pepsin and mucoprotein secretion in rats and on hydrochloric-peptic secretion and plasma gastrin levels in dogs were investigated. In Shay rats, TDB did not affect acid secretion but significantly lowered pepsin concentration and increased the amount of bound mucoproteins. In addition, gastric mucosal lesions were significantly prevented by the drug. In dogs, chronically fitted with both gastric fistulae and Heidenhain pouches, acid secretion and plasma gastrin levels stimulated by a meat meal were unaffected by TDB, while pepsin concentration and pepsin output were significantly decreased. On the basis of these results, the antiulcer activity of TDB appears to be ascribed to the protection of the gastric mucosa through an increase in mucoprotein synthesis and a decrease of pepsin activity.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Dogs; Female; Gastric Acid; Gastric Mucosa; Gastrins; Mucoproteins; Organometallic Compounds; Pepsin A; Rats; Rats, Inbred Strains; Species Specificity; Stomach Ulcer; Time Factors

Topics: Antigens; Biopsy; Carcinoembryonic Antigen; Cytodiagnosis; Endoscopy; Gastric Acidity Determination; Gastrins; Glycoproteins; Humans; Pepsinogens; Prostaglandins E; Stomach Neoplasms; Stomach Ulcer; Tomography, X-Ray Computed

A marked increase in the number and size of the antral gastrin cells and parietal cells could be shown in long term examinations of the antrum mucosa after SPV and pyloroplasty. Twenty-five patients with UD, 12 with UV and five with Dragstedt combination (UV and UD) were examined over a period of five to seven years. A significant correlation of parietal cell increase and a positive reaction to insulin was found. The findings were compared with the changes in the fundic mucosa, where a marked decrease of parietal cells occur after SPV.

Topics: Cell Count; Cell Division; Duodenal Ulcer; Follow-Up Studies; Gastric Fundus; Gastrins; Humans; Parietal Cells, Gastric; Pyloric Antrum; Stomach Ulcer; Vagotomy; Vagotomy, Proximal Gastric

The sulfation of gastrin in serum, antrum and duodenum was studied in 22 normo- and 20 hypergastrinemic patients. The ratio between gastrin-17 and gastrin-34 was measured in antrum and duodenum. The degree of sulfation was reduced in the antrum of hypergastrinemic patients (35.3 +/- 1.3%, mean +/- SEM) compared with 48.0 +/- 2.1% in normo-gastrinemic patients (p less than 0.001). The degree of sulfation in serum and duodenum was similar to that of the antral gastrins in all patients. The percentage of gastrin-34 in antrum was increased (7.3 +/- 0.7%) in hypergastrinemic compared with 4.9 +/- 0.3% in normogastrinemic patients (p less than 0.01). In the duodenum the percentage of gastrin-34 was similar in normo- and hypergastrinemia. When classified according to clinical diagnosis, sulfation of antral gastrin was normal in duodenal ulcer (47.6 +/- 4.5%) but decreased in gastric ulcer (36.7 +/- 1.6%, p less than 0.01) and pernicious anemia (31.3 +/- 1.9%, p less than 0.001) compared with 48.2 +/- 2.2% in control patients. In pernicious anemia a larger proportion of antral gastrins occurred as gastrin-34 (8.2 +/- 0.9%) compared with 4.8 +/- 0.4% in control patients (p less than 0.01). Our study suggests that both sulfation and proteolytic processing of the gastrin precursor is diminished in hypergastrinemia of antral origin.

Topics: Anemia, Pernicious; Duodenal Ulcer; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer; Sulfuric Acids

Since many of the proposed etiologic factors leading to gastric stress ulceration involve stimulation of calcium influx, the effect of verapamil, a potent calcium channel blocker, on the gastric mucosa in cold-restrained inbred rats was assessed. Twenty-nine rats received intraperitoneal normal saline (2 ml) while the experimental group (N = 29) received 1 mg/kg verapamil in an equal volume of normal saline intraperitoneally. All animals were then stressed at 4 degrees C for 4 hr and sacrificed. Gastrin and fatty acid levels were measured and blinded ulcer scoring of the gastric mucosa was carried out. Verapamil-treated animals had decreased frequency and severity of gastric stress ulceration as assessed by ulcer index, ulcer grade, and number of ulcers/animal. In addition, the plasma gastrin levels tended to be lower in the verapamil group. Fatty acid levels were similarly depressed following cold restraint in both groups. Pretreatment with verapamil significantly decreased gastric ulcerative response to cold-restraint stress in the rat. This effect of verapamil pretreatment may be secondary to cytoprotection of the gastric mucosa, preservation of gastric mucosal blood flow, or blockade of calcium-mediated ulcerogenic stimuli.

Topics: Animals; Cold Temperature; Fatty Acids; Gastrins; Male; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Physiological; Verapamil

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer; Time Factors

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.

Topics: Acute Disease; Animals; Burns; Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastric Emptying; Gastrins; Humans; Intestinal Mucosa; Peptic Ulcer; Recurrence; Spinal Cord Injuries; Stomach Ulcer; Stress, Physiological

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.

Topics: Cimetidine; Duodenal Ulcer; Eating; Gastrins; Humans; Protein Precursors; Stomach Ulcer; Time Factors

Hanisch E, Schwille PO. Effects of various vagotomies and sympathectomies on gastric secretory function in the non-stressed and by immobilization stressed rat. Scand J Gastroenterol 1984, 19, Suppl 89, 99-104 The aim of the present study was to study several gastrointestinal parameters (acid, pepsin secretion, ulcer index, gastrin, somatostatin, glucagon) following various forms of sympathectomies in comparison with vagotomies under two different states of sympatho-adrenal activation in male gastric fistula rats. It is concluded that acid and pepsin appear regulated by the autonomous nervous system, even in the basal state. Gastric ulcer formation/prevention depends on gastric sympathetic innervation and on the state of activation of the adrenal medulla. Basal gastrin, somatostatin, glucagon may be modified by both limbs of the autonomous nervous system.

Topics: Animals; Gastric Acid; Gastric Juice; Gastrins; Glucagon; Male; Pepsin A; Rats; Restraint, Physical; Somatostatin; Stomach Ulcer; Stress, Physiological; Sympathectomy; Sympathectomy, Chemical; Vagotomy

Topics: Aluminum; Antacids; Anti-Ulcer Agents; Cimetidine; Duodenal Ulcer; Gastrectomy; Gastric Acid; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Histamine H2 Antagonists; Humans; Intestinal Absorption; Metoclopramide; Mucus; Parasympatholytics; Ranitidine; Smoking; Stomach Ulcer; Sucralfate; Vagotomy

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Gastric Acid; Gastric Mucosa; Gastrins; Glomerulonephritis; Humans; Insulin; Kidney Failure, Chronic; Pentagastrin; Risk; Stomach Ulcer

The concentrations of gastrins containing the active C-terminal tetrapeptide amide (mainly gastrin-34 and gastrin-17) and the N-terminal tridecapeptide fragment of gastrin-17 were measured in antral and duodenal biopsy specimens. The antral concentration of the N-terminal gastrin fragment was much higher in patients with active duodenal ulcer (33.4 +/- 6.8 nmol g-1, mean +/- SEM, n = 15) than in controls (5.6 +/- 2.9 nmol g-1, n = 10), patients with gastric ulcer (5.6 +/- 1.8 nmol g-1, n = 10) or patients with pernicious anaemia (7.7 +/- 2.5 nmol g-1, n = 6). No differences were found between the groups regarding gastrin-34 and gastrin-17 concentrations. In duodenal extracts, the N- and C-terminal gastrin concentrations were similar in all groups of patients. These data suggest that the posttranslational processing of antral gastrin is abnormal in patients with active duodenal ulcer disease.

Topics: Adult; Aged; Anemia, Pernicious; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Hormones; Humans; Male; Middle Aged; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Humans; Stomach Ulcer

The serum values of PG I and gastrin have been established in a normal population and in several clinical diseases. The PG I is raised in duodenal, gastric, and pyloric ulcer even though the gastrin is normal. Both PG I and gastrin values are raised in renal insufficiency and the Zollinger-Ellison syndrome. The PG I is lowered in atrophic gastritis and alcoholic cirrhosis, and is at the limit of detection in Biermer anemia and total gastrectomy. Insulin and sham-feeding are stimulants for PG I release by patients with duodenal ulcer, but no correlation is observed between PG I output and PAO in the studied group. The results show that PG I is able to distinguish between associated hypergastrinemia and hypoacidity (Biermer anemia type) or a hyperacidity (Zollinger-Ellison syndrome type), and that PG I is a good indicator for gastric hypoacidity. Overlapping between normal and ulcer subjects is comparable to those obtained in acid output determinations.

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Gastritis, Atrophic; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Pepsinogens; Reference Values; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Methods; Middle Aged; Stomach Ulcer

Topics: Animals; Anti-Ulcer Agents; Dermatitis; Gastric Acid; Gastric Mucosa; Gastrins; Male; Oligopeptides; Rabbits; Rats; Rats, Inbred Strains; Stomach Ulcer; Vaccinia

The ulcer risk of the Roux-Y anastomosis following gastric resection was analyzed experimentally in 82 rats. After 1/3 gastric resection a Roux-Y gastrojejunostomy with jejunal loops of 3, 6, 9 and 15 cm was performed. 10 months postoperatively a follow-up was performed consisting of endoscopy, measurement of pH-values, analysis of gastric secretion and serum gastrin, gastric emptying tests and histamine stimulation. Endoscopically there was a high rate of stomal ulceration related to the length of the jejunal loop. In long Roux-Y loops (9 and 15 cm), that means under reflux-free conditions, ulcer incidence ranged from 72% to 92%. In short loops with reflux-exposed stomachs the frequency of ulceration was only 9%. With additional histamine stimulation there were stomal ulcers in 100% of the reflux-free animals, but only in 60% of the rats with short Roux-Y loops. In spite of resection acidity was high (pH 1.8) in reflux-free stomachs. Only the volume of gastric secretion and the amount of acid-output was reduced. Gastric acid secretion unbuffered by duodenal content is discussed as the major factor in the etiology of stomal ulcer in reflux-free stomachs. So the Roux-Y anastomosis following gastric resection is a modification of the Mann-Williamson experiment. Therefore reflux-free operations are heavily ulcer prone.

Topics: Animals; Gastrectomy; Gastric Acidity Determination; Gastric Emptying; Gastric Mucosa; Gastrins; Intestinal Mucosa; Jejunum; Male; Postgastrectomy Syndromes; Rats; Rats, Inbred Strains; Risk; Stomach Ulcer; Vagotomy, Proximal Gastric

Topics: Duodenal Ulcer; Gastrins; Humans; Pancreatic Function Tests; Pancreatitis; Peptic Ulcer Hemorrhage; Secretin; Stomach Ulcer

There are few detailed studies of patients with pathological hypergastrinaemia of antral origin. We have identified four patients with severe acid hypersecretion associated with peptic ulcer disease and in whom no evidence for gastrinoma or isolated retained antrum could be found. Three of these patients also had hypergastrinaemia. In two patients, one with gastric ulcers and one with duodenal ulcer disease, the hypergastrinaemia appeared to be due to antral gastrin cell hyperfunction and there was also evidence for mild antral gastrin cell hyperplasia. In the other hypergastrinaemic patient, a primary intestinal gastrin cell hyperfunction syndrome was suspected, but a hidden gastrinoma could not be excluded. The remaining patient had nearly fatal hypersecretory ulcer disease and cimetidine failed to control the hypersecretory state. In this patient the hypersecretion responded to a more potent H2 antagonist with resolution of a metabolic encephalopathy. No general pathophysiological mechanism could be identified in these patients or in larger groups of patients with gastric or duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Humans; Male; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Cimetidine, 75 mg/kg body weight, was given twice daily by gastric tube to rats with experimental gastric ulcers. After 130 days' treatment the rats were killed, and sections from the wounds and normal mucosa were prepared for light and electron microscopy. Light microscopic studies showed that the regenerating mucosa in the wounds was thicker in the cimetidine-treated animals than in the controls. Stereological analyses demonstrated no differences in mean size of the parietal cells or in parietal cell volume density between the cimetidine-treated and the untreated groups, but an increase in the secretory surface density was detected in the parietal cells from rats that had been given cimetidine.

Topics: Animals; Cimetidine; Gastric Mucosa; Gastrins; Male; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Regeneration; Stomach Ulcer; Wound Healing

Topics: Acetylcholine; Animals; Benzodiazepinones; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Humans; Pirenzepine; Rats; Stomach Ulcer

The secretory and motor function of the stomach and gastrin incretion were investigated in 68 patients with peptic ulcer of variable localization. In addition, a retrospective analysis of the course of prepyloric gastric ulcer and Billroth I resection was performed in 62 patients. Results show that gastric acid secretion and velocity of gastric emptying diminish significantly with increasing height of the localization of the ulcer. Prepyloric gastric ulcer cannot be likened to the duodenal ulcer. Moreover, experimental and clinical results suggest that prepyloric ulcer represents a disease entity per se requiring separate therapeutic approaches (gastric resection following Billroth I).

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

Seven of nine patients with ulcers recurring after a variety of gastric operations enjoyed loss of dyspeptic symptoms within 2 days of taking cimetidine, 1,200 mg/day for 6 weeks, and endoscopic confirmation of healing of the recurrent ulcer was established within 6 weeks of therapy. Once ulcer healing had been achieved in these seven patients, symptomatic remission persisted for over 19 months without maintenance therapy with cimetidine, and no complications suggestive of recurrent ulcerations occurred during this period in these seven patients. The eighth patient with a recurrent ulcer after vagotomy and pyloroplasty had symptoms suggestive of a gastric outlet obstruction in association with a bezoar and an elevated fasting serum gastrin concentration; cimetidine failed to heal the ulcer and a partial gastrectomy with Billroth I anastomosis was undertaken. The ninth patient lost his dyspeptic symptoms while on cimetidine, but 1 month after stopping therapy he succumbed to a massive hemorrhage; autopsy revealed a large pyloric channel ulcer. We suggest that cimetidine is helpful for the control of symptoms and the healing of recurrent ulcers after gastric surgery, but that endoscopy be repeated after an appropriate interval while such patients remain on cimetidine to assure that the disappearance of symptoms is truly associated with a lack of peptic ulceration. If the ulceration persists, we believe that cimetidine should be continued for a longer period.

Topics: Adult; Aged; Cimetidine; Dyspepsia; Female; Follow-Up Studies; Gastrectomy; Gastrins; Gastroscopy; Guanidines; Humans; Male; Middle Aged; Postoperative Complications; Recurrence; Reoperation; Stomach Ulcer; Vagotomy

Topics: Acromegaly; Adenocarcinoma; Adolescent; Adult; Chromaffin System; Enterochromaffin Cells; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms; Stomach Ulcer

The chronic antral ulcer developed spontaneously in (WB X C57BL/6)F1-W/WV mice. Natural history of the ulcer was investigated to make clear the mechanisms involved in the development of ulcer in this mutant mouse. Although no histopathologic abnormalities of the stomach were detected at the fifth day after birth, erosions developed at the tenth day and the severity of the ulcerative lesions advanced with age. Antral pH of the W/WV mice was higher than that of the congenic +/+ mice, and the content of gastrin in the glandular stomach of the former was lower than that of the latter. Therefore, hyperacidity cannot be the cause of the ulcer in the W/WV mice. Bilirubin was demonstrable in the stomach contents of the suckling W/WV mice. After subcutaneous injection of [35S]sulfobromophthalein, the 35S radio-activity in the stomach contents of the 10-day-old W/WV mice was about 40 times as great as that observed in the +/+ littermates. As the peak of the bile reflux occurred shortly before the development of obvious ulcer that penetrated beyond the muscularis mucosae, the bile reflux could be a cause rather than a result of the ulcer.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Bilirubin; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Male; Mice; Mice, Mutant Strains; Pyloric Antrum; Rats; Stomach Ulcer

In a small percentage of patients with ulcer disease, a gastrinoma may be ultimately discovered. In most institutions, a fasting serum gastrin determination and gastric analysis are as first-line tests to identify this subgroup of patients with ulcer disease. The blood test is relatively inexpensive and well accepted by patients. Gastric analysis is uncomfortable and required a well-equipped facility staffed by skilled personnel. A prospective study designed to assess the diagnostic usefulness of these tests and, particularly, whether combining both tests adds to the individual value of each, revealed that gastric analysis does not improve the diagnostic ability of the fasting serum gastrin test. Therefore, gastric analysis probably is not indicated for determining whether a patient with active ulcer disease has a gastrinoma. The fasting serum gastrin test will suffice, and abnormal values on this test should be verified by the use of other tests such as responses to gastrin provocative tests.

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Stomach Ulcer; Zollinger-Ellison Syndrome

The course of gastric acid secretion and serum gastrin level before and after operation was studied in 41 patients suffering from a gastroscopically determined ulcer disease. In 15 patients suffering from duodenal ulcer, a highly selective vagotomy without pyloroplasty was performed and in 26 patients suffering from peptic ulcer (duodenal or gastric ulcer) a partial gastrectomy (Billroth I). After a highly selective vagotomy without pyloroplasty a reduction in the secretory response to pentagastrin and a significant rise of the basic and postprandial gastrin concentration could be observed. Both methods are suitable to determine the completeness of vagotomy. The estimation of the course of serum gastrin level after vagotomy only reveals a temporary disorder of the antrum-pylorus mechanism. In our opinion a pyloroplasty is not necessary.

Topics: Adult; Duodenal Ulcer; Gastrectomy; Gastric Acid; Gastrins; Humans; Middle Aged; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Vagotomy; Vagotomy, Proximal Gastric

In order to explore secretory mechanisms in peptic ulcer, the plasma secretin response to an intraduodenal load of gastric acid stimulated with tetragastrin was studied in 10 patients with duodenal ulcer, nine with gastric ulcer, and five young healthy volunteers. After the injection of tetragastrin plasma secretin level was significantly increased in all subjects. The integrated incremental secretin output significantly correlated with the incremental acid output in the duodenal ulcer group as well as the gastric ulcer group. THere was no significant difference in the integrated incremental secretin output among the three groups. However, the integrated incremental secretin output per unit amount of gastric acid loaded in the duodenum was significantly lower in the duodenal ulcer group than in the other two groups. These results suggest that in patients with duodenal ulcer the secretin release in response to an intraduodenal load of endogenous acid is impaired.

Topics: Adult; Duodenal Ulcer; Duodenum; Female; Gastric Acid; Gastrins; Humans; Hydrochloric Acid; Male; Middle Aged; Peptic Ulcer; Secretin; Stomach Ulcer; Tetragastrin; Time Factors

Gastric acid secretion and plasma gastrin response to test meals were examined in 110 patients with gastric cancer and a comparative study was made in accordance with depth of invasion, macroscopic shape, histological type, location and size of the lesion. Cases were classified into two large groups by the depth of invasion: early cancer (invasion was limited to the mucosa and submucosa) and advanced cancer (invasion reached the muscularis propria or deeper). Patients showed hypoacidity on the whole. Cases of early cancer showed significantly higher acid secretion than cases of advanced cancer, although no significant differences were observed in gastrin release. Among the cases of early cancer, cases of the elevated shape showed significantly lower acid secretion and higher gastrin release than cases of the depressed shape, and cases of the histologically differentiated type showed significantly higher acid secretion than cases of the undifferentiated type although no significant differences were observed in gastrin release. Among the cases of advanced cancer, cases with large carcinomas in the corpus tended to show low acid secretion and cases with large carcinomas in the antrum tended to show low gastrin release. High gastrin release was observed in cases of the Borrmann IV type with giant folds.

Topics: Aged; Eating; Endoscopy; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Stomach Ulcer

In order to evaluate whether prepyloric ulcer (PPU) could be classified as an intermediate ulcer type between duodenal ulcer (DU) and gastric ulcer (GU), fasting serum gastrin as well as basal and pentagastrin-stimulated acid secretion were studied. The fasting serum gastrin values in the three groups were not significantly different. Patients with PPU and DU showed a higher basal acid output compared to GU patients. The basal acid output in DU patients increased in the last two periods before stimulation, and in the last basal period it was significantly higher compared to PPU patients. Patients with GU showed the lowest basal and stimulated acid output. However, the higher stimulated acid output in DU patients was insignificantly different from that of PPU patients. The results indicate that basal and stimulated gastric acid secretion values in PPU patients are closer to those of DU patients than of GU patients. Furthermore, it is concluded that PPU is a homogeneous ulcer type without secretory overlap with the GU group.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Stomach Ulcer

The effects of various antiulcer drugs and hormones on the cell kinetics of the mouse gastric mucosa were studied using an autoradiographic technique with 3H-thymidine. The drugs or hormones were administered orally or parenterally once or twice a day for 7 consecutive days, and 3H-thymidine was injected after the last administration of the drug. The autoradiograph was prepared and then the labeling index was counted. Cimetidine (100 mg/kg X 2/day, p.o.), geranylgeranylacetone (GGA, 100 mg/kg X 2/day, p.o.) and Cu-chlorophyllin-Na (300 mg/kg X 2/day, p.o.) did not show any effect on the labeling indices in both the tissues of the fundic and pyloric glands, while carbenoxolone (100 mg/kg X 2/day), p.o.) reduced the labeling index in the pyloric glands. Tetragastrin (1 mg/kg X 1/day, i.m.) increased the labeling index in the fundic glands, whereas secretin did not affect it. Hydrocortisone (100 mg/kg X 1/day, S.C.) reduced the labeling index in the fundic glands, and this reducing effect was prevented by combining hydrocortisone with GGA. From these results, it was indicated that the labeling index in the normal mouse gastric generative zone was no influenced by the tested antiulcer drugs, except carbenoxolone; but the index was influenced by tetragastrin and hydrocortisone, especially in the fundic glands. It was also suggested that the changes in the cell kinetics of the gastric mucosa could be related to the etiology of gastric ulcer since there was a possibility that geranylgeranylacetone could control the action of hydrocortisone, an ulcerogenic agent, on the gastric mucosal cell-cycle.

Topics: Animals; Carbenoxolone; Cell Cycle; Chlorophyllides; Cimetidine; Diterpenes; Gastric Mucosa; Gastrins; Hydrocortisone; Kinetics; Male; Mice; Secretin; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Secretin; Stomach Ulcer

A dose of exogenous serotonin (0.1 mg/kg/min) previously described to cause maximal acid inhibition, was infused into six chronically awake dogs and significantly inhibited acid output. Integrated basal gastrin output was inhibited from a mean of 232.6 pg-min/ml to 31.6 pg-min/ml (p < 0.05) by serotonin infusion. Antral explantation significantly increased gastrin levels from a mean control level of 163 +/- 71.1 pg/ml to a mean of 991.0 +/- 663.4 pg/ml (p < 0.05). These elevated gastrin levels were then not significantly inhibited by serotonin. The effect of serotonin on gastrin output has not previously been documented. Whereas acid inhibition was uniformly achieved, serotonin inhibited basal gastrin output (integrated gastrin output) but not a stimulated level of gastrin output. Serotonin may be an important 'enterogastrone', and its release may play a role both in acid inhibition and in preventing ulcer disease.

Topics: Animals; Disease Models, Animal; Dogs; Gastric Acid; Gastrins; Infusions, Intravenous; Pyloric Antrum; Radioimmunoassay; Serotonin; Serotonin Agents; Stomach Ulcer

A histological and immunohistological investigation was performed on biopsy specimens from ten patients 3 to 35 years after antrectomy, to study the type of epithelium and the possible occurrence of gastrin-producing cells (G cells) in the distal stump of the stomach remnant. The study showed that parietal cells were present in all patients, whereas G cells could not be demonstrated, although areas of pyloric-type epithelium (pseudopyloric metaplasia, were seen in eight. We conclude that the pyloric-type metaplasia, which occurs in the fundic mucosa after antrectomy, does not involve the G cells. It is suggested that the normal levels of fasting serum gastrin in these patients originate from outside the gastric mucosa, presumably from the duodenal bulb.

Topics: Adenocarcinoma; Biopsy; Epithelium; Fibrosis; Follow-Up Studies; Gastrectomy; Gastric Acid; Gastrin-Secreting Cells; Gastrins; Gastritis, Atrophic; Gastroscopy; Humans; Postoperative Period; Pyloric Antrum; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer; Time Factors

Topics: Animals; Antacids; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gastric Juice; Gastric Mucosa; Gastrins; Glucagon; Hormones; Humans; Male; Pilot Projects; Rats; Regional Blood Flow; Somatostatin; Stomach Ulcer; Stress, Psychological

Topics: Bile Acids and Salts; Cholestyramine Resin; Duodenum; Gastric Juice; Gastrins; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Intestinal Secretions; Metoclopramide; Stomach Ulcer

Glucagon provocation test was performed in the patients with hypergastrinemia and hyperchlorhydria to investigate its diagnostic value. A paradoxical response of plasma gastrin level in the patients with the Zollinger-Ellison syndrome and a marked decrease of plasma gastrin level in the patients with gastric ulcer, duodenal ulcer, excluded gastric antrum, multiple endocrine adenomatosis, pernicious anemia and chronic renal failure were demonstrated by glucagon infusion. Glucagon provocation test, therefore, was considered to be of great value in the diagnosis of the Zollinger-Ellison syndrome, particularly, in the case of an excluded gastric antrum in which secretin provocation test caused the false positive result because of a marked increase of pancreatic secretion. Glucagon provocation test in combination with secretin provocation test, therefore, is at present the most preferable diagnostic procedure for detecting the Zollinger-Ellison syndrome.U

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Glucagon; Humans; Kidney Failure, Chronic; Middle Aged; Multiple Endocrine Neoplasia; Pyloric Antrum; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

As an attempt to approach the pathogenesis of peptic ulcer disease, antral gastrin and somatostatin concentrations were studied in normal subjects, patients with duodenal ulcer and gastric ulcer. In the patients with peptic ulcer, antral somatostatin concentrations were significantly lower than those in normal subjects. In non-ulcer subjects, including normal subjects and patients with atrophic gastritis, antral somatostatin concentrations were correlated inversely with the degree of antral gastritis, while in the patients with peptic ulcer, especially in duodenal ulcer, they were low, irrespective of histological picture of antral mucosa. In the patients with duodenal ulcer, low antral somatostatin concentrations with high antral gastrin/somatostatin ratio may cause increased serum gastrin levels and increased gastric acid secretion. From the above findings, it has been concluded that low antral somatostatin levels may be related to the pathogenesis of duodenal ulcer disease.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Adolescent; Adult; Aged; C-Peptide; Cyclic AMP; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Glucagon; Humans; Insulin; Male; Middle Aged; Pancreatic Hormones; Stomach Ulcer

Topics: Drug Tolerance; Duodenal Ulcer; Gastrins; Glutamine; Humans; Patient Compliance; Proglumide; Receptors, Cell Surface; Stomach Ulcer

The effects of pirenzepine on the serum gastrin levels in the basal state and in response to a liquid test meal were investigated in nine patients with gastric ulcer. Single-dose administration of the drug caused a significant decrease in the basal gastrin level and significant inhibition of the serum gastrin response. When measured 12 h after the end of drug treatment for 7 days, the serum gastrin levels in the basal state and in response to a test meal tended to be high, but the differences were not statistically significant.

Topics: Adult; Aged; Anti-Ulcer Agents; Benzodiazepinones; Depression, Chemical; Female; Gastrins; Humans; Male; Middle Aged; Piperazines; Pirenzepine; Radioimmunoassay; Stomach Ulcer; Time Factors

Of 114 patients with chronic pancreatitis, 19 (16.7%) has gastric or duodenal ulcers. Patients with moderate pancreatic exocrine dysfunction tended to show high acid output and low serum gastrin levels, while those with severe dysfunction had slightly lower acid output and higher serum gastrin levels. The higher the degree of pancreatic fibrosis, the higher tended to be the acid output and serum gastrin levels. Not all patients with ulcers developed hypergastrinemia. The mechanism of acid hypersecretion and ulcer formation in patients with chronic pancreatitis cannot be explained solely by pancreatic deterioration, fibrosis or gastrin release; a decrease in the production and release of gastric inhibitory hormone should be taken into consideration.

Topics: Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Stomach Ulcer

Topics: Adult; China; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Singapore; Stomach Ulcer

Plasma gastrin and pepsinogen were measured at weekly intervals in 38 pigs from weaning at about four weeks of age until slaughter at 24 weeks. Plasma gastrin was 104 +/- 6.2, 85 +/- 11.2, 126 +/- 11.67 mol per litre in the pigs aged four, five and six weeks and 43 +/- 2.57, 31 +/- 2.29, 17 +/- 0.87 mol per litre when they were 21, 22 and 23 weeks old. Sixteen of the pigs had apparently normal stomachs, the remainder had some degree of epithelial hyperplasia and, or, ulceration of the pars oesophagea of the stomach. No differences were detected between plasma gastrin and plasma pepsinogen in pigs with normal stomachs and those showing evidence of epithelial hyperplasia or ulceration of the pars oesophagea. If ulcers of this region arise from hypersecretion of gastric acid some factor(s) other than gastrin appear to be involved. The possibility is discussed that the progressive decline in plasma gastrin is part of the maturation process.

Topics: Animals; Cardia; Female; Gastrins; Pepsinogens; Stomach Ulcer; Swine; Swine Diseases; Weaning

In 67 patients with two-thirds gastrectomy and endoscopically proven stomal ulcer, serum gastrin levels were measured under basal conditions and after intravenous infusion of bombesin (15 ng/kg/min), calcium (4 mg/kg/hour) and secretion (2 units/kg). All patients underwent medical or surgical therapy. The long-term results were evaluated according to the Visick grading system (average follow-up, 3.1 years).

Topics: Antacids; Bombesin; Calcium; Cimetidine; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parasympatholytics; Recurrence; Secretin; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Female; Gastric Juice; Gastrins; Humans; Liver Cirrhosis; Male; Middle Aged; Pepsin A; Secretin; Stomach Ulcer

The G-cell population in the pyloric antrum and proximal duodenum was studied quantitatively by immunofluorescence in specimens from 10 gastric and 12 duodenal ulcer patients. In both groups, G-cell density was highest in the pyloric antrum and much lower in the intermediate zone and proximal duodenum, and G-cell counts were statistically higher at the greater than the lesser curvature. The estimated total number of G cells in the whole pyloric antrum including the intermediate zone in the duodenal ulcer group was (1.806 +/- 0.347) x 10(7), this value was significantly greater (P less than 0.05) than that of (0.872 +/- 0.207) x 10(7) in the gastric ulcer group. This difference was due to a higher incidence of intestinal metaplasia and a decrease in the thickness of the antral mucosa in the latter group. The estimated total number of G cells showed a significant negative correlation not only with the patient age (P less than 0.01) but also with the degree of intestinal metaplasia of the antral mucosa (P less than 0.01) in both duodenal and gastric ulcer patients.

Topics: Adult; Cell Count; Chromaffin System; Duodenal Ulcer; Duodenum; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Metaplasia; Middle Aged; Pyloric Antrum; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Insulin; Male; Middle Aged; Pyloric Stenosis; Stimulation, Chemical; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Humans; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

The serum gastrin responses after ingestion of hard boiled eggs and Nutrient Broth solution were examined in peptic ulcer patients and normal subjects. The values observed of the serum gastrin response to these test meals were compared and contrasted. A significant enhancement of gastrin release in response to protein was obtained. There were no significant differences between the releases of gastrin after the two test meals.

Topics: Adult; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

Twenty-two duodenal and 16 gastric ulcer patients were treated with 400 mg cimetidine twice daily for one year after their ulcers had healed. No change in gastric acid secretion was observed before and after treatment in 20 duodenal and 13 gastric ulcer patients. Similarly, the inhibitory effect of 200 mg cimetidine on gastric acid secretion was unaltered in 11 duodenal and 6 gastric ulcer patients studied and cimetidine blood concentration were unchanged in 9 duodenal and 4 gastric ulcer patients after one year. In 7 duodenal and 6 gastric ulcer patients the serum gastrin response to a standard test meal before and after treatment was identical.

Topics: Cimetidine; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Guanidines; Humans; Middle Aged; Recurrence; Stomach Ulcer

In large groups of control subjects and gastric, prepyloric, and duodenal ulcer patients basal gastrin concentration as basal and maximal acid output was measured. All groups had equal basal gastrin concentrations, except gastric ulcer patients, who had higher values (p less than 0.001). A significant negative correlation was found between acid output and basal gastrin in controls and prepyloric ulcer patients. In duodenal ulcer a similar correlation was seen only after exclusion of gastrin and basal acid hypersecretors, and in gastric ulcer no correlation could be found. The characteristic pattern for gastrin and acid secretion was in prepyloric ulcer patients almost like that in controls, whereas gastric ulcer patients seemed more heterogeneous. In duodenal ulcer differences may be explained by a defective feedback inhibition of acid.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

Topics: Adenocarcinoma; Animals; Gastrectomy; Gastric Juice; Gastrins; Intestinal Polyps; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Stomach Neoplasms; Stomach Ulcer

The relation between the incidence of gastric ulceration, basal acid output and serum gastrin concentration was studied in the pyloric-ligated normal rat and the rat with established adjuvant disease (polyarthritis). Although there was no significant difference in either gastric secretions or basal acid output, serum gastrin was significantly higher in the adjuvant rat than in the normal rat, independent of the nutritional state of the animal. The incidence of the gastric lesions was eight times greater in adjuvant rats compared to controls in a 6-hour pyloric-ligation period. When the period of pyloric ligation was increased from 6 to 17 hr, there was 91% increase in gastric lesions in polyarthritic rats. Histopathology of the lesions in the polyarthritic rat showed diffuse and focal submucosal edema with polymorphonuclear inflammatory cell infiltration in the submucosa of the fundic and antral areas of the stomach. The increased susceptibility of the polyarthritic rat to gastric ulceration could be related to a combination of experimental stress and hypergastrinemia. Since similar elevations in serum gastrin have been reported in the rheumatoid arthritis in man, it is herein proposed that the polyarthritic rat could be used as a screening model for the evaluation of the ulcerogenicity potential of nonsteroidal anti-inflammatory drugs.

Topics: Animals; Arthritis; Arthritis, Experimental; Gastric Juice; Gastrins; Male; Models, Biological; Rats; Stomach; Stomach Ulcer; Stress, Physiological; Time Factors

The total number of gastrin (G) cells in the stomach was determined by using a histologic counting method and planimetry in ulcerous and nonulcerous patients. The preoperative basal and postprandial serum gastrin values and the gastrin cell mass in the gastrectomy specimen could be compared in 16 surgical patients. There was a significant correlation between the integrated gastrin response to feeding and the total gastrin cell number in the stomach. No correlation was found between the basal serum gastrin level and the total gastrin cell count. A total gastrin cell number higher than 50 million was found in the stomach of three duodenal ulcer patients with preoperative postprandial hypergastrinemia as well as in one patient with normal serum gastrin values. Gastrin cell counts between 6 and 42 million were found in control stomachs and in patients with gastric ulcer. Preoperative feeding tests could be useful to select patients with an elevated antral G cell number.

Topics: Cell Count; Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Pyloric Antrum; Recurrence; Stomach Ulcer; Vagotomy

The relationship between histopathological alterations and G-cell population in the stomach was studied in l4 resected stomachs from patients with chronic peptic ulcer disease (6 with duodenal ulcer and 8 with gastric ulcer). G-cells were identified by indirect immunoperoxidase method. When atrophy was graded three steps (0, 1, 2), the average grade of DU and GU was 0.23 and 0.89, respectively. There was a significant correlation (r=0.871, p less than 0.005) between atropic grade and G-cell population in each stomach. The mean occupation rate with intestinal metaplasia was 0.9% in DU and 35.8% in GU. There was no correlation between total pyloric area and G-cell population, however residual pyloric area excluding intestinal metaplasia correlated significantly with G-cell population (r=0.557, p less than 0.05). There was a significant difference in the mean G-cell population which were 26.5 millions in DU and 8.9 millions in GU. The mean integrated gastrin response to Cimetidine-OXO test meal were 559+/-236 pg/ml in DU and 216+/-124 pg/ml in GU, and there was significant correlation (r=0.889, p less than 0.005) between G-cell population and integrated gastrin response. The average age of both groups, however, was 27.7 in DU and 52.8 in GU, so that these differences of G-cell population and functional G-cell mass in both groups might originate in the histopathological alterations accompanying with the aging.

Topics: Adolescent; Adult; Aged; Chromaffin System; Cimetidine; Duodenal Ulcer; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Guanidines; Humans; Middle Aged; Peptic Ulcer; Pylorus; Stomach; Stomach Ulcer

Antral gastrin concentratin (AGC) was measured in forceps biopsy specimens of prepyloric mucosa obtained at endoscopy in 65 patients with various kinds of gastric ulcer and in 31 nonulcer control patients. AGC in 32 patients with a lesser curvature gastric ulcer, 10.0 +/- 2.0 (mean +/- 1 SE) ng gastrin/mg tissue was significantly less (P < 0.01) than AGC in 31 nonulcer control patients, 14.4 +/- 1.4. AGC was similar to the control values in 23 patients with a pyloric channel ulcer, 15.2 +/- 1.7; 5 patients with a greater curvature ulcer, 15.0 +/- 4.8; and 3 patients with both duodenal and gastric ulcers, 15.8 +/- 0.7. AGC was significantly greater (P < 0.01) than the control values in 3 patients with a vagotomy and pyloroplasty and a gastric ulcer, 29.8 +/- 5.0. In contrast with most lesser curvature gastric ulcer patients who had low AGC, 3 gastric ulcer patients had antral gastrin values which were about three times the mean AGC of the controls. Two of these patients had fasting serum gastrin values which were more than twice the mean control fasting serum gastrin. Meal-stimulated integraed gastrin responses in these 3 patients ranged from three to nine times the mean control response. These findings suggest that a high AGC may account for a few instances of increased serum gastrin concentrations in gastric ulcer patients.

Topics: Adult; Aged; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach; Stomach Ulcer

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Stomach Ulcer

Basal and histalog-stimulated gastric acid secretion and serum gastrin levels before and after a standard protein meal were compared in eight children with active duodenal ulcer (DU), four with active gastric ulcer (GU), and in seven children with recurrent abdominal pain (RAP) of undetermined etiology. There was no discernible difference in the pattern of abdominal pain in DU, GU, and RAP. Basal acid output, peak and maximal acid output, whether expressed as milliequivalents per hour or as milliequivalents per kilogram per hour, were comparable in children with DU, GU, and RAP. In contrast, serum gastrin levels, 1 and 2 hours after standard protein meal, were significantly higher in the DU children than in the GU or RAP group. These studies have suggested that hypersecretion of gastric acid may not be associated with duodenal ulcer or gastric ulcer disease in children, and that increased gastrin secretion and possible reduced acid responsiveness coexist in children with duodenal ulcers.

Topics: Abdomen; Acute Disease; Adolescent; Child; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Pain; Recurrence; Stomach Ulcer

Measurements of serum epinephrine and gastrin, simultaneously, gastric mucosal blood flow and gastric secretion were carried out in cinchophen treated dogs. No significant changes in either serum concentrations of epinephrine and gastrin or fundic mucosal microcirculation after a single 100 mg/kg cinchophen administration were found while gastric secretion increased markedly after the medication. On the other hand, a significant increase in serum epinephrine and gastrin levels was observed while gastric secretion decreased significantly after large doses of cinchophen (300 mg/kg) were injected intravenously. Here gastric mucosal microcirculation is decreased. Repeated administration of 100 mg/kg cinchophen for 3 to 7 days brought about an increase in epinephrine and gastrin levels and caused an occurrence of fundic mucosal hemorrhage. Sympathetic discharge and gastrin release were not seen after a 3-week period of cinchophen administration. Cinchophen ulcers were produced, even when contact between the bile and the stomach mucosa was avoided. Vagotomy had no connection with ulceration and gastric secretion.

Topics: Animals; Dogs; Epinephrine; Gastric Juice; Gastric Mucosa; Gastrins; Male; Microcirculation; Quinolines; Stomach Ulcer

The effect of a single dose of 400 mg of the H2-receptor antagonist cimetidine on protein meal stimulated immunoreactive gastrin was assessed in ten patients with gastric ulcer and ten patients with duodenal ulcer. In gastric ulcer patients, serum gastrin (mean +/- SE) rose from 34 +/- 2.2 pmol.l-1 to a peak of 80 +/- 5.0 pmol.l-1 at 45 minutes without and from 36 +/- 2.2 to 107 +/- 8.0 pmol.l-1 at 60 minutes with cimetidine; in duodenal ulcer it rose from 26 +/- 3.0 to 47 +/- 5.1 pmol.l-1 at 45 minutes without and 26 +/- 3.2 to 52 +/- 5.1 pmol.l-1 at 60 minutes with cimetidine. Integrated gastrin responses in gastric ulcer were 4900 +/- 800 pmol.l-1 120 minutes without and 7000 +/- 900 pmol.l-1 120 minutes with cimetidine and 1560 +/- 300 pmol.l-1 120 minutes without and 2620 +/- 400 pmol.l-1 120 minutes with cimetidine in duodenal ulcer patients. These gastrin increases after cimetidine are comparable to those achieved with continuous intragastric neutralisation with alkali.

Topics: Adult; Aged; Antigens; Cimetidine; Dietary Proteins; Duodenal Ulcer; Female; Food; Gastrins; Guanidines; Humans; Male; Middle Aged; Stomach Ulcer

Topics: Animals; Diet; DNA; Fasting; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Immersion; Male; Pentagastrin; Pepsin A; Rats; RNA; Secretory Rate; Sodium Chloride; Stomach Ulcer; Stress, Psychological

Measurements of serum cortisol and gastrin along with gastric acid-pepsin secretion in the resting state were carried out in gastric and duodenal ulcer patients. Increased basal corticosteroid concentrations were observed in patients with duodenal ulcer and gastric ulcer. Higher concentrations of the hormone were observed in the former group (P less than 0.05 for the latter). Fasting gastrin levels were significantly higher in gastric ulcer patients where gastric secretion is low than those in duodenal ulcer patients (P less than 0.001). These results suggest that the effect of adrenal cortical hormone on lowering the threshold of oxyntic gland cell reactivity against gastrin is an important factor in duodenal ulcer etiology. Extra-antral control mechanism(s) of gastric acid-pepsin secretion should not be overlooked.

Topics: Adrenal Cortex Hormones; Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrocortisone; Middle Aged; Pepsin A; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

Plasma concentrations of prostaglandins E and F have been measured by radioimmunoassay in patients undergoing diagnostic upper intestinal endoscopy. The results fail to support a previously reported deficiency of plasma PGE in duodenal ulcer patients. Plasma prostaglandin concentrations failed to correlate with the parameters of gastric secretion studied; and were unaffected by histamine H2-receptor blockade or the activity of duodenal ulceration. During combined pentagastrin and insulin secretory studies there was a significant correlation between the outputs of PGE and acid into gastric juice.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Stomach Ulcer

The influence of restraint stress on serum calcium (Ca) and phosphate was studied in normal and thyroidectomized rats. In addition the response of gastric stress ulcer index, blood gastrin and glucagon to exogenous Ca was investigated. In intact as well as in thyroidectomized animals serum total, ionised and previously injected radioactive Ca decrease during an 8h stress period, whereas inorganic phosphate increases. Together with a constant specific activity these findings are consistent with hypoparathyroidism and calcitonin independent hypocalcemia during stress. Intragastric infusion of 45 mg/kg Ca-gluconate per 8h proves to be a potent anti-stress ulcer regimen in intact and neck-sham operated, but not in thyroidectomized rats without and with additional adrenal demedullation. Gastrin and glucagon were not correlated with calcemia during either stress alone or stress combined with intragastric Ca infusion. It is suggested that the development of gastric stress ulcerations can be prevented by a Ca-mediated release of endogenous calcitonin.

Topics: Adrenal Medulla; Animals; Calcitonin; Calcium; Calcium Carbonate; Calcium Gluconate; Gastrins; Hypocalcemia; Lactates; Male; Rats; Restraint, Physical; Stomach Ulcer; Stress, Physiological; Thyroidectomy

Topics: Adolescent; Adult; Aged; Child; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Reference Values; Stomach Ulcer

131 patients operated on for gastric ulcer according to Gillroth II were investigated with gastroscopy and biopsy. The histology of the gastric mucosa was correlated with the time elapsed since resection. In most cases gastritis shows no difference between anastomosis and stump. In up to 12% gastritis in the stump was more pronounced that at the anastomosis. In the stump any form of gastritis can be seen even more than 20 years afer resection. Atrophic changes are more often to be found in the resected stomach and develop more rapidly than in the normal stomach. They probably result from the coincidence of the lost protective function of the mucous membrane after resection of the gastrin-producing antrum with the potentially damaging action of the contents of small intestine.

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Postgastrectomy Syndromes; Stomach Ulcer; Time

Topics: Animals; Anura; Bombesin; Dogs; Duodenal Ulcer; Gastrins; Gastritis; Gastrointestinal Diseases; Humans; Peptic Ulcer; Peptides; Stomach Ulcer; Zollinger-Ellison Syndrome

Different pathogenetic mechanisms lead to the formation of ulcers in stomach and duodenum. They must be taken into consideration, when selecting operative procedures. In the patient with duodenal ulcer we have with the selective proximal vagotomy a procedure at hand that in effective reduction of the secretion of the stomach and in preservation of the form and function of the stomach fulfills all criteria of a functional gastric surgery. At present in patients with gastric ulcers dominate still methods of resection with the aim of the removal of the ulcer and thus healing. The practicability and effectiveness of non-resecting methods is shown also in this case. But it should be controlled in larger clinical studies.

Topics: Adolescent; Adult; Aged; Child; Cimetidine; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastrins; Humans; Middle Aged; Pyloric Antrum; Recurrence; Stomach Ulcer; Vagotomy

The blood serum levels of gastrin and insulin and arterial blood levels of glucose were determined immediately before intravenous injection of 1 mg of glucagon, and 10, 20, 40 and 60 minutes later in 12 gastric ulcer patients, 14 duodenal ulcer patients and 12 controls using the radioimmunological and orthotoluidine methods respectively. Following glucagon administration the gastrin levels dropped in the controls and the gastrin patients, and increased in the duodenal patients by an average of 30%. Insulin levels increased in all three groups, but the increase was statistically significant in the two patients groups. Glucose levels in the blood also increased with no significant differences between the groups. It is suggested that the different effect of glucagon on gastrin levels may be due to gastrin-insulin interaction; the levels of the two hormones in the blood of duodenal patients were higher than in the other two groups studied.

Topics: Adolescent; Adult; Blood Glucose; Duodenal Ulcer; Gastrins; Glucagon; Humans; Insulin; Stomach Ulcer

In normal, duodenal ulcer, and gastric ulcer subjects the two main forms of gastrin, G17 and G34, were estimated by radioimmunoassay in fasting serum and after feeding. Two antisera were used: one showing high specificity for G17, the other specific for the common COOH-terminus of G17 and G34 and so allowing estimation of G34 by difference. Basal G17 was similar in gastric ulcer, duodenal ulcer, and normal subjects and the increases of G17 after feeding were also similar in these groups. In contrast, basal G34 was similar in normal and duodenal ulcer subjects but raised in gastric ulcer subjects. After a meal the G34 concentration in both gastric and duodenal ulcer patients was significantly higher than normal. It is concluded that the higher post-prandial gastrin responses in peptic ulcer that have been previously described are due largely to increased G34.

Topics: Adult; Antibody Specificity; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged; Monoamine Oxidase; Pylorus; Stomach Ulcer

An ulcer was induced in the anterior wall of the antrum of cats by local injection of acetic acid solution. Carbonized microspheres, 15 +/- 5 microns in diameter, labelled with 141Ce, were used to measure blood flow in different regions and layers of the stomach wall. The radioactivity of a blod reference sample and of tissue samples was determined, and the blood flow was calculated for each tissue sample. The gastric tissue samples were examined microscopically, and the level of gastrin in serum was determined. Two groups of anaesthetized animals were used: in one group of animals blood flow was determined 24 h after ulcer induction and in a group of control animals 24 h after laparotomy. In the ulcer animals the gastric blood flow as increased both in the mucosa and in the muscularis in a zone around the ulcer. Microscopic examination revealed tissue necrosis corresponding to the floor of the ulcer and acute inflammatory changes in the gastric wall around the necrotic area. The serum gastrin concentration tended to increase after ulcer induction.

Topics: Acute Disease; Animals; Cardiac Output; Cats; Female; Gastric Mucosa; Gastrins; Laparotomy; Male; Necrosis; Pyloric Antrum; Regional Blood Flow; Stomach; Stomach Ulcer

Twenty-one consecutive patients with endoscopically proven recurrent ulcer were treated continuously with cimetidine, 1 g daily for 8 weeks. After 4 weeks' treatment 18 (86%) of the patients were free of symptoms, and the ulcers had healed in 17 (81%). At the 8th-week examination symptoms had disappeared, and ulcers were healed in 19 patients (91%). Within 6 weeks after withdrawal of cimetidine six patients (28%) presented recurrence of ulcers and symptoms. This study demonstrates that recurrent ulcer patients respond to cimetidine with regard to healing of ulcers and disappearance of symptoms, as do unoperated duodenal ulcer patients. Because operation for recurrent ulcer carries an increased mortality, we suggest that cimetidine should be attempted in the treatment.

Topics: Adult; Aged; Cimetidine; Drug Evaluation; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Middle Aged; Recurrence; Stomach Ulcer

The authors explored the gastric function of 20 volunteers by classical methods and by the assessment of gastric 99Tc pertechnetate clearance. From a comparison of results obtained with the various methods they come to the conclusion that the pertechnetate clearance method is dependable, easy to perform, and noninvasive; accordingly, they recommend its use as the method of choice for monitoring the treatment of duodenal ulcers and evaluating its results.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach; Stomach Ulcer; Technetium

Gastric acid secretion stimulated by a normally eaten beefsteak meal was measured for 4 h in 16 patients with duodenal ulcer disease (DU), in 9 patients with gastric ulcer disease (GU), and in 14 controls by intragastric titration with bicarbonate to a constant pH 5.5. Reproducibility of the method investigated in 6 DU and in 5 controls gave similar acid secretory values (var. coeff. = 7.5%). DU produced acid on a higher level and with longer duration after food than controls and GU (p less than 0.001). Apart from the second half of the first hour after food, when the acid secretion was higher in controls than in GU (p less than 0.025), there was no significant difference in acid output after food between GU and controls. Maximum gastrin values and 'total gastrin output' after food were significantly higher in GU than in controls, but these differences were not significant between GU and DU and between DU and controls. Fasting gastrin and gastrin levels after food were not correlated to basal acid output or acid output after pentagastrin or food in any of the groups. The maximal acid output after food was higher than the peak acid output after pentagastrin in controls, DU and GU. The relation between food- and pentagastrin-stimulated acid output was not statistically significantly different between the three groups. Instead, acid secretion after food was well correlated to acid secretion after pentagastrin in controls, DU and GU (r = 0.85).

Topics: Adult; Aged; Bicarbonates; Duodenal Ulcer; Female; Food; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Methods; Middle Aged; Secretory Rate; Stomach Ulcer

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Staining and Labeling; Stomach; Stomach Neoplasms; Stomach Ulcer; Uremia

The distribution and numbers of G cells and of parietal cells were related to the distribution and severity of histopathological alterations (inflammatory cell infiltration, atrophy and intestinal metaplasia) in corresponding mucosal tissue blocks from resected stomachs (12 patients with gastric ulcer, 11 with duodenal ulcer, and 14 with duodenal ulcer and uremia). In all patients the histopathological features were more severe in the pyloric antrum than in the body, and the change in severity corresponded well with the disapperance of G cells at the body-antrum border. The transitional body-antrum zone was histopathologically similar to the remaining antrum. A marked individual heterogeneity of the histopathological alterations was observed. An increasing grade of atrophy was associated with increased severity of inflammation, and the presence of intestinal metaplasia was especially associated with atrophy. No significant correlation was found between the antral G-cell number and the grade of antral inflammatory cell infiltration, whereas there was a reduction in cell number with increasing grade of atrophy in all patient categories. The parietal-cell density in the body mucosa was decreased with increasing grade of inflammation as well as with increasing grade of atrophy. The presence of patchy intestinal metaplasia resulted in a complete absence of G cells and of parietal cells from the corresponding part of the mucosa in the antrum and body respectively.

Topics: Adult; Aged; Atrophy; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastrins; Gastritis; Humans; Intestinal Mucosa; Intestines; Male; Metaplasia; Middle Aged; Pyloric Antrum; Pylorus; Staining and Labeling; Stomach Ulcer; Uremia

Previous studies have shown that bile duct ligation in pigs results in gastric ulceration. It has been suggested in human peptic ulceration that there may be no associated rise in the serum gastrin level. This study was conducted to determine the portal and peripheral gastrin levels in sham-operated and bile-duct-ligated pigs, together with the basal acid concentration and the response to a protein meal. There was an increase in basal acid concentration in bile-duct-ligated animals, but the serum gastrin levels remained in the normal range. Two of the six sham-operated control pigs had peptic ulcers at the time of sacrifice, and these two were the only sham-operated control pigs which did not demonstrate a significant postoperative rise in the serum gastrin level. At no stage was a significant difference between portal and peripheral vein serum gastrin levels demonstrated. These studies suggest that the increased gastric acid secretion in this form of peptic ulceration in the pig may not be entirely gastrin-mediated.

Topics: Animals; Bile Ducts; Dietary Proteins; Female; Gastric Juice; Gastrins; Ligation; Male; Stomach Ulcer; Swine; Swine Diseases

The effect of Mucaine and Aludrox on basal and food stimulated immunoreactive gastrin has been assessed in normal control subjects and patients with duodenal or gastric ulcer. No differences in gastrin responses were observed either in the basal period or after the protein meal with the two antacids. As previously described, release of gastrin was greatest in gastric ulcer patients but in contrast to previous results,normal subjects seemed to show a greater response than duodenal ulcer patients but this was not statistically significant. Thus the combination of a local anaesthetic oxethazaine with aluminium hydroxide gel does not lead to diminished gastrin release and is not the prime mechanism of action of this agent.

Topics: Adult; Aged; Aluminum Hydroxide; Antacids; Duodenal Ulcer; Ethanolamines; Gastrins; Humans; Middle Aged; Peptic Ulcer; Stomach Ulcer

The mucosal distribution of G cells was quantitatively mapped in resected stomachs from 42 patients (12 with gastric ulcer, 11 with duodenal ulcer, 14 with duodenal ulcer and uremia, and 5 with gastric cancer). Along the histological border of the proximal part of the pyloric antrum there was in all patient categories a transitional zone of varying extent, with a low G-cell density before the cells disappeared in the body of the stomach. The proximal end of the duodenum contained considerably fewer G cells than in the antrum, and the number was virtually equal in all groups. Within the antrum there was in the material as a whole a gradual increase in G-cell density from the proximal to the distal part, but this difference was not apparent for the gastric ulcer patients. When corresponding antral segments were compared between the various patient groups, the G-cell density was found to be significantly decreased in the distal antrum of the gastric ulcer patients. In all patient categories, except the duodenal ulcer group with uremia, the circumferential distribution of G cells showed reduced density along the curvatura minor. For the material as a whole there were great individual variations in the overall antral G-cell density, in the antral area corresponding to the distribution of G cells and in the total G-cell mass; these three variables were not significantly related to diagnosis, age or sex.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms; Stomach Ulcer; Uremia

The stimulating effect of AOC-tetragastrin, caerulein, Histalog and secretin on human gastric acid and pepsin secretion was studied in gastric ulcer patients. The pattern of gastric acid and pepsin secretion after the administration of caerulein was closely resembled to that of gastrin. Slight increase of pepsin secretion after gastrin or caerulein could be based on "wash-out" action caused by the increase of acid secretion after the stimulants. Stimulating effect on gastric pepsin secretion of histalog and secretin would be independent of gastric acid secretion.

Topics: Ceruletide; Gastric Juice; Gastrins; Humans; Pepsin A; Secretin; Stomach Ulcer

Gastric acid secretion basally and in response to intragastric meat extract instillation or to tetragastrin, and circulating gastrin concentration basally and after meat extract stimulation were studied in 67 patients with gastroduodenal ulcer, 30 patients after highly selective vagotomy or selective vagotomy for duodenal ulcer, 12 patients after antrectomy for or gastric ulcer and 10 control subjects. Circulating gastrin concentration increased significantly after meat extract stimulation in control subjects, patients with ulceration and patients after highly selective vagotomy, and acid secretion in each group was increased significantly above basal level. In patients after selective vagotomy, significant increase of circulating gastrin concentration was observed, but it was not associated with significant increase of acid secretion. After antrectomy, neither gastrin nor acid secretion increased significantly after meat extract stimulation. In conclusion, present study suggested that (1) gastric acid secretion in response to intragastric meat extract is chiefly affected by the responsiveness of oxyntic cells and release of antral gastrin and that (2) the presence of the antrum is almost essential for acid secretion after a test meal, and release of duodenal gastrin after antrectomy would not be so potent biologically as to result in an acid secretion.

Topics: Adult; Duodenal Ulcer; Eating; Gastric Juice; Gastrins; Humans; Meat; Middle Aged; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Vagotomy

1. Maximal acid output after pentagastrin stimulation, and fasting and postprandial serum gastrin concentrations were determined in 25 normal subjects, 30 patients with corpus gastric ulcers, 10 patients with prepyloric ulcers and 30 patients with both duodenal and gastric ulcers. 2. Corpus ulcers and prepyloric ulcers formed one distinct group. Maximal acid output was abnormally low in the corpus ulcer patients and no different from normal in prepyloric ulcer patients, whereas fasting serum gastrin and postprandial integrated gastrin response was abnormally high in the former and no different from the normal in the latter. Furthermore, as in the normal subjects, a significant negative correlation between maximal acid output expressed in mmol h(-1) kg(-1) body weight and postprandial integrated gastrin response was observed in the corpus and prepyloric ulcer patients taken as a group. 3. In complete contrast patients with both duodenal and gastric ulcers, in whom postprandial integrated gastrin response was statistically highest amongst the three types of gastric ulcers, had a significantly positive correlation between maximal acid output and the integrated gastrin response. 4. These findings suggest the operation of different pathophysiological mechanisms in gastric ulcers with and without associated duodenal ulcers.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Stomach Ulcer

Topics: Gastrins; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Liver Neoplasms; Male; Middle Aged; Somatostatin; Stomach Ulcer

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Duodenum; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Humans; Peptic Ulcer; Stomach Ulcer

The fasting serum concentration and the first-hour serum gastric response to a protein-rich meal were related to the antral G-cell population in 14 patients with peptic ulcer. They were divided into a uremic (n=5) and non-uremic group (n=9). Fasting serum gastrin correlated significantly with the total antral G-cell mass only in the non-uremic patients who showed a relatively narrow transitional body-antrum zone. Conversely, the integrated serum gastric response was inversely related to the size of this zone in both groups of patients. A presumptive endocrine G-cell mass was estimated by subtracting the G cells in the transitional zone from the total antral G-cell population. Total gastrin output correlated positively with this estimated mass in the non-uremic group and in the material as a whole. Also, the integrated gastrin response was positively correlated with the presumptive endocrine G-cell mass in the whole material. It was concluded that G cells in the transitional body-antrum zone, where also parietal cells are present, do not release gastrin into the circulation during meal stimulation like G cells in the remaining part of the pyloric antrum. On the basis of these results and our previous morphological observations (19), we propose that the G cells in the transitional zone are involved in a paracrine interrelationship with the surrounding parietal cells rather than contributing to the circulating pool of gastrin.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Fasting; Female; Food; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Stomach Ulcer; Uremia

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and after the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal of similar weight to that of the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional normal subject and one duodenal ulcer patient the constant intravenous infusion of Aminosol for 2 h produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers, and, furthermore, that this effect is mediated by proteins in the gastrointestinal tract.

Topics: Adolescent; Adult; Duodenal Ulcer; Esophagogastric Junction; Food; Gastrins; Humans; Manometry; Middle Aged; Pressure; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Liver Cirrhosis; Male; Middle Aged; Stomach Ulcer

Pigs develop gastric ulceration spontaneously and after bile duct ligation. Despite increased basal acid secretion, serum gastrin levels are not elevated, and a possible 'protective' role of gastrin was proposed. Continuous intravenous infusion of synthetic human gastrin did not protect from gastric ulceration, but was associated with simultaneous duodenal ulceration. Another ulcerogenic mechanism must be invoked.

Topics: Animals; Bile Ducts; Duodenal Ulcer; Gastrins; Infusions, Parenteral; Stomach Ulcer; Swine

The distribution of parietal cells in the body mucosa, and of G cells in the antral mucosa, was quantitatively mapped in resected stomachs from 42 patients (12 with gastric ulcer, 11 with duodenal ucler, 14 with duodenal ulcer and uremia, and 5 with gastric cancer) who preoperatively had had their gastric acid secretion measured. In the material as a whole there was a significant positive correlation between the parietal-cell density and maximal acid output (MAO), and a significant negative correlation between the parietal-cell density and patient age. A significant positive correlation was found between the antral G-cell mass and basal acid output (BAO). When the individual patient categories were analyzed, the correlation between parietal-cell density and MAO were significant in the group with duodenal ulcer and uremia, and in the group with gastric cancer. Correlation between parietal-cell density and age was found only in the group with duodenal ulcer and uremia. There was no correlation between the parietal-cell density and various parameters of the antral G-cell population in the material as a whole or in any of the individual groups.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach; Stomach Neoplasms; Stomach Ulcer; Uremia

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal similar in weight to the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional nromal and one duodenal ulcer, the constant intravenous infusion of Aminosol during 2 hours produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers; furthermore, that this effect is mediated by proteins in the gastrointestinal tract.

Topics: Adult; Duodenal Ulcer; Eating; Esophagogastric Junction; Gastrins; Humans; Middle Aged; Pressure; Stomach Ulcer

By arranging a series of psychological contingencies (unpredictability, uncontrollability, conflict), coupled with delivery of a physical stimulus (electric shock), we produced gastroduodenal mucosal lesions in 7 of 8 rhesus monkeys. The most severe conflict paradigm most consistently produced lesions across subjects. Of the 30 lesions observed by endoscopy, 80% occurred near the anatomic junction of gastric body and antrum, in the antrum, or in the duodenum. Lesions varied in severity from discolorations of the mucosa to disruptions of mucosal integrity. Lesions in the stomach generally disappeared in several days despite the continuation of stress; some duodenal lesions were equally evanescent, but in 2 monkeys, lesions lasted over a week. Hydrogen ion kinetics were measured in 2 monkeys that developed gastric lesions and 2 that developed duodenal lesions. The rate at which hydrogen ion entered the duodenum was uniformly suppressed for all 4 monkeys during their first session of shock avoidance; during their last session, the gastric subgroup continued to show suppression while the duodenal subgroup returned towards control levels. Serum gastrin levels were unchanged by the multiple-stress procedures. Our finding of consistently producible, stress-induced gastroduodenal pathology in anatomic areas similar to those involved in man suggests that the subhuman primate is suitable for further efforts to produce an animal model of psychosomatic ulcer disease.

Topics: 17-Hydroxycorticosteroids; Animals; Behavior, Animal; Duodenal Ulcer; Electroshock; Gastric Juice; Gastric Mucosa; Gastrins; Haplorhini; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Kinetics; Macaca mulatta; Male; Peptic Ulcer; Stomach Ulcer; Stress, Psychological

Gastroduodenal ulceration occurred in 45 patients during the post-transplantation period in a series of 500 transplantations of 434 patients. The mortality rate of this complication was high, 42%. Bleeding and perforation were the main problems. These complications occurred frequently during treatment for acute rejection. Present day prophylaxis, which is based on the use of antacids, seems to be inadequate for controlling these complications. Other possibilities for reducing the incidence of gastroduodenal ulceration in transplant patients are discussed. Since increased serum gastrin concentrations are often observed in these patients, prophylactic treatment should be based on preoperative evaluation of gastric secretion and serum gastrin determinations. The new histamine (H2) blocking agents should be evaluated in these patients.

Topics: Cimetidine; Duodenal Ulcer; Gastrins; Histamine H2 Antagonists; Humans; Kidney Transplantation; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Stomach Ulcer; Transplantation, Homologous

Topics: Carbohydrates; Gastric Juice; Gastrins; Gastritis; Glycoproteins; Humans; Pepsin A; Stomach Diseases; Stomach Ulcer

After administration of antacids, gastric stress lesions due to hemorrhagic shock appear in the pig stomach quicker and more markedly than in animals which have been similarly treated with an indifferent substance or not at all. However, once treated, the administration of antacids seems to favor the healing of mucosal lesions after the end of the stress. At the same time it was observed that after administration of antacids in hemorrhagic shock, the serum gastrin level rises and does not remain constant, as in the control group. An attempt is made to explain the favorable effect of antacids on the genesis of hemorrhagic stress lesions in the pig's stomach through this observation.

Topics: Animals; Antacids; Disease Models, Animal; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hemorrhage; Male; Shock, Hemorrhagic; Stomach Diseases; Stomach Ulcer; Stress, Physiological; Swine; Time Factors

Topics: Adult; Duodenal Ulcer; Eating; Gastrectomy; Gastrins; Humans; Middle Aged; Stomach Neoplasms; Stomach Ulcer; Vagotomy

Topics: Adult; Aged; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer

Topics: Adult; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer

Topics: Adult; Gastric Juice; Gastrins; Humans; Middle Aged; Stomach Ulcer; Vagus Nerve

In rats the influence of arresting free motions (= controls; mild stress) and of restraint (= severe stress) without and with additional somatostatin (SRIF) on gastric secretion, mucosal microcirculation and stress ulcer formation was studied. Severe stress alone reduces volume, acid and pepsin secretion, acid concentration, aminopyrine clearance and ratio. The ulcer index is elevated. Under both conditions SRIF inhibits in a dose-dependent manner volume and acid secretion, and ulcer incidence is lower. The interaction between severe stress and the antiulcer component of SRIF is characterized as non-competitive. Under these conditions and a continuous infusion of SRIF (10.0 microgram/kg.h over 8 h) acid concentration, acid and pepsin secretion fall subtotally, ulcer index to 50 percent of vehicle (saline) treated rats, if gastric fistula drains juice outside stomach. Microcirculation and serum gastrin are unchanged. In animals with closed fistula ulcer index is reduced by 85 percent, average gastrin again is unchanged. It is concluded that stress ulcers develop at a low secretory and microcirculatory state of gastric mucosa. The prophylactic effect of SRIF results from direct inhibition of parietal and chief cells and additional yet unknown factors.

Topics: Animals; Anti-Ulcer Agents; Crowding; Dose-Response Relationship, Drug; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Microcirculation; Rats; Secretory Rate; Somatostatin; Stomach Ulcer; Stress, Psychological

Topics: Calcium; Gastrectomy; Gastrins; Humans; Methods; Postgastrectomy Syndromes; Postoperative Complications; Preoperative Care; Recurrence; Secretin; Stomach Ulcer; Vagotomy

Topics: Basal Metabolism; Duodenal Ulcer; Fasting; Gastrins; Humans; Stomach Ulcer

Antral gastrin concentration (AGC) was measured in prepyloric mucosa specimens obtained by forceps biopsy during endoscopic examination of 174 clinic and hospital patients. AGC in 32 patients who had normal endoscopic findings, the control group, varied widely from 2 to 38.6 ng gastrin/mg tissue. The mean AGC of the control patients was 14.2 +/- 1.4 (mean +/- 1 SE) ng gastrin/mg tissue. AGC was similar to control values in 18 patients with duodenal ulcer, 14.7 +/- 2.1; 12 patients with a pyloric channel or antral ulcer, 16.4 +/- 3.5; and 48 patients with miscellaneous diagnoses, 14.3 +/- 1.5. AGC was significantly less than control values in 13 patients with a ulcer in the body or fundus of the stomach, 5.9 +/- 1.5, and 4 patients with the Zollinger-Ellison syndrome, 4.9 +/- 2.4. AGC was significantly greater than in control values in 16 patients with gastritis, 25.8 +/- 4.3;22 patients with esophagitis, 23.2 +/- 3.0; and 9 patients with gastric atrophy and fasting serum hypergastrinemia 44.6 +/- 12.3. In group of 77 of these patients with heterogeneous diagnoses, meal-stimulated 3-hr integrated gastrin output was directly related to AGC (r = 0.47, P less than 0.001). In a group of 106 patients AGC was inversely related to histalogstimulated maximum acid output. The correlation was very weak (r = -0.20) but significant (P less than 0.05).

Topics: Atrophy; Biopsy; Duodenal Ulcer; Esophagitis; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Humans; Pyloric Antrum; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

1. Prostaglandin A-, prostaglandin E- and prostaglandin F-like substances were determined radioimmunologically in antral biopsy material obtained by endoscopy. 2. In patients with gastritis, the concentrations of prostaglandin (E+A)-like substances were six times as high and of prostaglandin F-like substances twice as high as in normal subjects. In chronic atrophic gastritis, the concentrations of prostaglandin (E+A)-like material was four times as high as in normal subjects whereas prostaglandin-F like material remained unchanged. In acute gastric ulcer, prostaglandin (E+A)-like material reached concentrations four times times higher than in normal subjects, accompanied by a fivefold increase of prostglandin F-like substances. After healing of the gastric ulcer, prostaglandins returned to normal values. 3. There was no correlation between gastrin and prostaglandins in all biopsy specimens.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Stomach Diseases; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Fasting; Female; Gastrectomy; Gastrins; Humans; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hypothalamus, Posterior; Intestinal Secretions; Pentagastrin; Secretin; Stomach; Stomach Ulcer; Stress, Physiological; Vagus Nerve

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Peptic Ulcer; Pylorus; Recurrence; Stomach Ulcer; Vagotomy

There is well documented evidence indicating in-appropriately high basal gastrins in patients with duodenal ulcer disease. After stimulation by protein meals, calcium infusion, and insulin-induced hypoglycemia there appears to be an exaggerated release of gastrin in patients with duodenal ulcers compared to control subjects. Vagotomy in general tends to increase serum gastrin by decreasing acid secretion and allowing less inhibition for antral gastrin release. This increase appears less with selective vagotomy and parietal cell vagotomy compared to truncal vagotomy, suggesting vagal inhibition of gastrin release outside the antrum. Antrectomy may decrease serum gastrins by removing a major source of the hormone. However, extra antral gastrin sources, if stimulated properly, may result in little postoperative change.

Topics: Calcium; Dietary Proteins; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Hypoglycemia; Proteins; Pyloric Antrum; Pylorus; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Thirteen patients with pancreaticoduodenectomy were studied. In three patients presenting with stomal ulcer or bleeding stomitis, endoscopic biopsies showed the presence of retained antral mucosa (RAM). No disease and no RAM was present in the remaining ten patients. Bombesin (BBS) infusion augmented both gastric acid and gastrin secretion in the group with RAM, whereas no change was apparent in the remaining ten patients. The BBS infusion test is useful in detecting stomal ulcer high risk pancreaticoduodenectomy patients.

Topics: Adult; Aged; Duodenum; Female; Follow-Up Studies; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pancreatectomy; Pyloric Antrum; Stomach Ulcer

In patients with gastric cancer who were to undergo gastrectomy, the fasting serum gastrin concentration in the peripheral vein was estimated by radioimmunoassay. The blood samples were also collected from the gastric veins and artery during the time of operations. These gastrin values were compared with morphological findings in the resected stomach. No significant differences in serum gastrin concentration was found between the patients of gastric cancer and normal subjects. In the patients with mucosal atrophy in the oxyntic gland area but with no atrophy in the pyloric gland area, however, significant increase in serum gastrin concentration was observed. In cases where fundal atrophy was accompanied by atrophy in the pyloric gland area, the increase was not observed. The amount of gastrin content in cancer tissue was negligible. These results indicate that the increase in serum gastrin concentration in some patients with gastric cancer might be due to the accompanied atrophy of oxyntic glands in the stomach.

Topics: Adult; Aged; Atrophy; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer

In 15 patients with uncomplicated gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0 +/- 1.3 (SEM) mEq H+/hr], the mean peak acid output (29.5 +/- 5.1 mEq H+/hr), and the mean fasting serum gastrin level (80.3 +/- 16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.

Topics: Gastric Juice; Gastrins; Humans; Male; Stomach Ulcer

Topics: Duodenal Ulcer; Duodenum; Feedback; Gastrins; Hydrogen-Ion Concentration; Molecular Weight; Peptic Ulcer; Stomach; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

1. Both gastrin and the vagus nerve play a part in the pathogenesis of the duodenal ulcer. Which of these two factors is of greater significance--this problem is still subject to discussion as is the question whether other factors such as duodenal neutralization are more important than hitherto assumed. 2. At this time no reliable and harmless drugs that speed up the healing of duodenal ulcers and prevent relapses are yet available. Candidates for this are H2 receptor blockers, prostaglandines and possibly substances resembling secretin. 3. Only some of the participants considered it necessary to do endoscopic and radiological follow-ups in duodenal ulcers. 4. Proximal gastric vagotomy for the treatment of duodenal ulcers is still undergoing clinical trials. At present this method should only be used by surgeons with a special interest in gastric surgery who also dispose of the technology and the staff for careful postoperative checks on these patients. The advantages of proximal gastric vagotomy consist in sparing truncation, low mortality and good functional results. 5. In gastric ulcers--contrary to duodenal ones--malignancy should always be suspected. If medical treatment does not lead to complete remission within a few months, surgery must be performed. 6. Many surgeons still prefer resection to vagotomy and excision in the management of gastric ulcers.

Topics: Duodenal Ulcer; Gastrins; Gastrointestinal Hormones; Histamine H1 Antagonists; Humans; Prostaglandins; Stomach Ulcer; Vagotomy; Vagus Nerve

Topics: Antacids; Duodenal Ulcer; Gastric Juice; Gastrins; Gastritis; Histamine Release; Humans; Hydrogen-Ion Concentration; Parasympatholytics; Pentagastrin; Pepsin A; Peptic Ulcer; Stomach Ulcer

Direct immunofluorescence technique with rhodamine-labelled rabbit anti-gastrin IgG conjugate was used for systematic mapping of the G-cell distribution in 16 resected stomachs (8 gastric ulcer patients and 8 duodenal ulcer patients with uraemia). Along the anatomical border of the proximal part of the antrum there was in both groups of patients a tranzitional zone with a low G-cell number per unit mucosa until the cells abruptly disappeared in the body of the stomach. The proximal end of the duodenum contained considerably fewer G cells than the antrum, and the number was equal in both groups. Within the antrum there was in the duodenal ulcer group a gradual increase in G-cell number from the proximal to the distal end, whereas in the gastric ulcer group no significant difference was found in different parts of the antrum. When corresponding antral parts were compared between the two groups, the only significant difference was that the distal part contained more G cells in the duodenal ulcer patients. In both groups the antral G-cell number showed no difference in circumferential distribution.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Female; Fluorescent Antibody Technique; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Stomach Ulcer

Selective proximal vagotomy with pyloroplasty is a method which permits ulcers to be operated on with less morphological and pathophysiological disturbances than is possible with any other method. After ingestion, a reactive yet reduced acid secretion is still possible through the gastrin stimulus. The retained vagal antral release of gastrin seems to be without importance to the denervated delomorphous cells. Side effects of this type of vagotomy are small. The disturbances of motility and evacuation which also occur here can easily be corrected by an additional pyloroplasty suitable in shape and function.

Topics: Animals; Bile; Dogs; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Motility; Glucose Tolerance Test; Humans; Insulin; Pancreatic Juice; Postgastrectomy Syndromes; Prognosis; Prospective Studies; Pylorus; Recurrence; Stomach Ulcer; Vagotomy

The mean concentration of gastrin in serum was determined in healthy fasting persons (n = 27), it amounted to 56.8 pg/ml (SD = 19.8 PG/ML). The values of gastrin in serum of patients, who were grouped by endoscopicbioptic criteria of antral mucosa and who exceptionally showed diffuse inflammation of gastric mucosa, amounted to 73.2 pg/ml in patients with mild superficial gastritis (n = 24), to 73.4 pg/ml in those with severe superficial gastritis (n = 55), to 82.3 pg/ml in patients with chronic atrophic gastritis (n = 11) and to 70.7 pg/ml in those with chronic atrophic gastritis and intestinal metaplasia (n = 17). The concentration of serum gastrin in patients with additional pathological processes of gastric or duodenal mucosa was also determined. Patients with gastric resection according to Billroth II (n = 15) revealed gastrin values of 47.8 pg/ml, those with duodenal ulcer (n = 5) of 58.5 pg/ml, with gastric ulcer (n = 50) of 61.3 pg/ml, with polyps in stomach (n = 10) of 109.6 pg/ml and with neoplasms of the stomach (n = 27) of 77.7 pg/ml. Gastrin values were not correlated to age or sex. The difference between the mean gastrin concentrations of the mentioned groups of patients however is not marked enough and the range of values is too wide to characterize those groups by specific gastrin levels. The determination of gastrin in serum of fasting patients is not helpful for diagnosis of gastritis without antibodies to intrinsic factor or for diagnosis of certain localized pathological conditions in stomach or duodenum obviously.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Metaplasia; Middle Aged; Polyps; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Humans; Peptic Ulcer; Stomach Ulcer

The clinical symptomatology of the Zollinger-Ellison-syndrome, the diagnostic treatment and the surgical procedure are reviewed. The syndrome with excessive non-regulated gastrin release from the ZE-tumor is the only form of ulcer disease with importance for the surgeon. The development of a sensitive radioimmunoassay for circulating gastrin facilitated its diagnosis. The possibility of Zollinger-Ellison-syndrome should always be considered if ulcer recur after surgical procedure by simple ulcer disease. If ulcers are located at atypical sites, if multiple ulcer are found, the diagnosis of a Zollinger-Ellison-syndrome should be established by measuring serum gastrin levels.

Topics: Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Stomach Ulcer; Zollinger-Ellison Syndrome

The effect of short-term infusion of a large dose of pentagastrin and a small dose of synthetic human gastrin I (SHG) on the rate of cell proliferation in gastric mucosa was studied in normal human subjects. Moreover, the kinetic parameters were compared with the serum gastrin concentrations in fasting patients. Endoscopic biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. In healthy volunteers infusion of a large dose of pentagastrin (10 mug/kg per hour) was followed by a marked increase in the labelling index in fundic mucosa. The antral mucosa was not responsive to this effect. In the same subjects, infusion of a low dose of SHG (8 ng/kg per min) did not affect the rate of cell proliferation, either in fundic or in antral mucosa. In 46 patients with different gastric diseases no correlation between the serum gastrin concentrations and the labelling indices was found. The results suggest that human fundic mucosa is responsive to a trophic action of pentagastrin. If it exists, however, a physiological action of gastrin as a trophic hormone for human gastric mucosa must be considerably more complex than previously believed.

Topics: Adult; Aged; Autoradiography; Cell Division; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Stomach Ulcer

Restraint stress ulcers in rats were developed and procedures evaluated designed at preservation of intact gastric microcirculation (pO2). Neither prior truncal vagotomy, splanchnicotomy nor combined dissection of abdominal autonomic nerves were effective in preventing the stress mediated fall of mucosal pO2 and the rise in plasma glucagon. The ulcer index remained elevated and gastrin essentially was unchanged. Prophylactic injection of increasing doses (1, 2, 4, 8, 16 U/kg secretin maintained microcirculation at pO2-levels subnormal for unstressed animals (Vmax 15.53 mm Hg; Km. 0.99 U/kg), but simultaneously brought about a continuous rise in serum gastrin. Up to 8 U/kg plasma glucagon was higher than in saline control groups reaching a peak value with 2 U/kg when ucler index showed its nadir. Secretin therapy (4, 8 U/kg) markedly improves both mucosal pO2 and ulcer index. It is suggested that breakdown of gastric microcirculation may not be solely responsible for stress ulcer development.

Topics: Animals; Gastric Mucosa; Gastrins; Glucagon; Male; Microcirculation; Oxygen; Partial Pressure; Rats; Secretin; Splanchnic Nerves; Stomach Ulcer; Stress, Physiological; Vagotomy

In rats, antrectomy results in a decrease of ulcer rate by immobilization without statistic significance. Stress ulcer rate is also lowered by antral vagotomy, with statistically significant decrease of acid production. By antrectomy as well as by antral vagotomy just the acid production but not the circulatory disturbance in the mucosa of corpus is influenced, which is primarily responsible for the development of stress ulcers. This fact gives an explantation for the relatively high ulcer rate, compared with the conduction in rats after truncal vagotomy. Unclear remains whether antrectomy with consecutive total gastrin elimination is merely working by inhibiting the secretion, or if gastrin has a circulatory effect too.

Topics: Animals; Gastric Mucosa; Gastrins; Immobilization; Pyloric Antrum; Rats; Regional Blood Flow; Stomach Ulcer; Vagotomy

Topics: Animals; Blood Proteins; Gastrins; Humans; Rabbits; Stomach Ulcer

Gastric secretion was evaluated in 9 male patients with chronic renal failure on maintenance hemodialysis. Five secreted low or normal quantities of acid and 4 exhibited hypersecretion, 2 of whom had associated peptic ulcer disease. Serum gastrin responses to a protein meal were comparable to control subjects. Calcium infusion in two basal hypersecretors depressed acid secretion. The only statistically significant correlation observed was between basal acid output ans serum levels of parathormone. These studies suggest that while acid secretory abnormalities vary in patients with chronic renal failure on hemodialysis, there is no apparent sensitivity of the gastrin-secreting cells to protein or calcium ion which might account for acid hypersecretion. Secondary hyperparathyroidism may influence the occurrence of acid secretory abnormalities.

Topics: Adult; Aged; Calcium; Gastric Juice; Gastrins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Stomach Ulcer

Topics: Adult; Chronic Disease; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Hepatitis; Humans; Liver; Liver Cirrhosis; Middle Aged; Peptic Ulcer; Stomach Ulcer

Topics: Adult; Diagnosis, Differential; Gastrectomy; Gastrins; Humans; Male; Pyloric Antrum; Recurrence; Stomach Ulcer

A total of 1 035 routine serum gastrin investigations was undertaken with a commercially available kit. Levels in 49 normal subjects were similar to those found in 200 patients with duodenal ulcertaion, in 42 patients with gastric ulcers, in 9 patients with carcinoma of the stomach, in 55 patients with chronic alcohol-induced pancreatitis, and in 27 with iron deficiency anaemia. Significantly raised levels of serum gastrin were found in 32 patients with megaloblastic anaemias, where the rise in serum gastrin concentration correlated with a fall in maximal acid output, and in 14 patients with complete vagotomies. It is suggested that a level of less than 2 mEq/h of acid after insulin and a raised serum gastrin level are useful criteria of completeness of vagotomy.

Topics: Adult; Anemia, Hypochromic; Anemia, Megaloblastic; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gastrointestinal Diseases; Humans; Male; Pancreatitis; Stomach Neoplasms; Stomach Ulcer; Vagotomy

Ten dogs were used to study antral gastrin secretion in hemorrhagic shock. Dogs that had a vagotomy were compared with normal dogs. Acute hemorrhage, imposed upon operative stress, produced increased gastrin secretion in normal dogs but not in dogs after vagotomy. During the acute hemorrhage, the level of circulating gastrin in normal dogs increased to about 50 to more than 100 per cent of the control values. The concentration of gastrin in the dogs having a vagotomy was essentially unchanged in the face of acute hemorrhage. Results of this study suggest that the increased concentration of circulating gastrin in normal dogs subjected to severe stress may play a role in the development of a stress ulcer.

Topics: Animals; Blood Glucose; Disease Models, Animal; Dogs; Gastrins; Insulin; Pyloric Antrum; Secretory Rate; Shock, Hemorrhagic; Stomach Ulcer; Vagotomy

Gastric bypass as a 90 per cent gastric exclusion operation was used in 393 patients with massive obesity to limit food intake. Stomal ulcer has occurred in 1.8 per cent of such patients or one ulcer per 140 man years of observation. The studies of indwelling fundic pH and of gastric acid secretion from the excluded stomach indicate that acid secretion is reduced after gastric bypass but that the acid, unbuffered by food in the excluded stomach, results in a lowered gastrin secretion after a meal. Thus, gastric bypass in inhibitory to acid secretion in most morbidly obese patients who do not have known acid peptic disease.

Topics: Achlorhydria; Analysis of Variance; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastroenterostomy; Humans; Obesity; Peptic Ulcer; Stomach Ulcer

Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms.

Topics: Adult; Cell Count; Colon; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Histamine; Humans; Malabsorption Syndromes; Male; Mast Cells; Middle Aged; Stomach Ulcer; Urticaria; Urticaria Pigmentosa

Serum group I pepsinogen (PG I) levels have been determined before and at intervals after the administration of betazole hydrochloride (Histalog) in 50 symptomatic postoperative patients, 20 with and 30 without recurrent ulcer, after either a vagotomy and gastric resection or a drainage procedure. In patients with recurrent ulcer, mean serum PG I levels increased after betazole and reached a maximum of 116.5 +/- 2.2% (SE) of basal at 2 hr; range 98.9 to 135.7%. In contrast, mean serum PG I levels decreased in patients without recurrent ulcer and reached a nadir of 75.0 +/- 4.3% of basal at 2 hr; range 46.9 to 142.4%. All 20 patients with recurrent ulcer and 5 patients without recurrence had a 2-hr serum PG I level of more than 98% of basal, while each of the remaining 25 patients without recurrent ulcer had a 2-hr level of less than 92% of basal. A 2-hr serum PG I level of more than 98% of basal was also correlated with a vagotomy and drainage, a peak acid output of more than 11 mEq per hr, and a positive insulin test, while a level of less than 92% of basal was correlated with a vagotomy and gastric resection, a peak acid output of less than 11 mEq per hr, and a negative insulin test. In addition, basal serum PG I and serum gastrin levels were significantly higher (P less than 0.001) in patients with the former type of PG I response than in those with the latter type of response. The cause of each type of response is not certain, but the data suggest that one of the determinants may be the completeness of vagotomy.

Topics: Adult; Aged; Betazole; Drainage; Female; Gastric Juice; Gastrins; Humans; Insulin; Male; Middle Aged; Pepsinogens; Pyrazoles; Recurrence; Stomach; Stomach Ulcer; Vagotomy

Topics: Esophagogastric Junction; Fasting; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Peptic Ulcer; Pressure; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Bile Acids and Salts; Duodenal Ulcer; Duodenum; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Intestinal Secretions; Specimen Handling; Stomach Ulcer

A retrospective study was made of 34 cases of recurrent ulcer following gastric resection. Males, especially above the age of 40, were shown to be particularly susceptible. The intact vagus apparently plays the most important role in the pathogenesis. Radiological examination and endoscopy are of the greatest diagnostic importance. Truncal vagotomy must be regarded as the treatment of choice in uncomplicated recurrent ulcer. Resection procedures are indicated in perforating ulcer, gastrojejunocolic fistula, antral remains and Zollinger-Ellison syndrome.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Germany, West; Humans; Male; Middle Aged; Peptic Ulcer; Postgastrectomy Syndromes; Recurrence; Retrospective Studies; Sex Factors; Stomach; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Fasting serum gastrin was determined in 30 Chinese patients with duodenal ulcer, 43 Chinese patients with gastric ulcer, 23 Chinese control subjects, 14 European control subjects and ten Indian control subjects. Basal and pentagastrin-stimulated peak acid outputs were also determined in the Chinses patients with duodenal or gastric ulceration. The mean (+/- SD) basal serum gastric level for Chinese controls and Chinese patients with duodenal and gastric ulcer were 24-6 pg/ml (+/- 13.7 pg/ml), 18-5 pg/ml (+/- 8-9 pg/ml), and 33-9 pg/ml (+/- 27-7 pg/ml), respectively. Statistical analysis showed no significant difference between the Chinese control subjects and the Chinese patients with duodenal or gastric ulcer, but the mean fasting serum gastrin level of Chinese gastric ulcer patients was significantly higher than that of Chinese duodenal ulcer patients. Comparison of the mean fasting serum gastrin level of the Chinese, European, and Indian control subjects showed no significant difference. Statistical analysis also showed no significant correlation between fasting serum gastrin level and both basal and peak acid outputs, in Chinese patients with duodenal or gastric ulcer.

Topics: Adolescent; Adult; Age Factors; Aged; China; Duodenal Ulcer; Ethnicity; Europe; Female; Gastrins; Humans; India; Male; Middle Aged; Sex Factors; Singapore; Stomach Ulcer

Topics: Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Pepsin A; Stomach; Stomach Ulcer

50 cases of interposition of jejunal loop (32 for gastric cancer and 18 for ulcerous pathology) carried out over the last 3 years are reported. From a technical point of view and as an alternative to degastroenteroanastomosis, interposition of the loop is preferred in partial oral end-to-end on the stomach. In neoplastic lesions, Mouchet-Camey type reconstruction was adopted as a routine measure. After describing the complications of the operation and analyzing the causes, the long-term results are evaluated using absorption curves with 131-I labelled oleic acid. The excellent weight increase in the inflammatory forms, and the lack of reflow and dumping in patients subjected to total gastrectomy for cancer, confirm the value of the technique.

Topics: Adult; Aged; Dumping Syndrome; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Iodine Radioisotopes; Jejunum; Middle Aged; Neoplasm Metastasis; Oleic Acids; Peptic Ulcer; Postoperative Complications; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Bicarbonates; Duodenal Ulcer; Endocrine System Diseases; Esophagitis, Peptic; Esophagus; Gastric Juice; Gastrins; Humans; Hyperplasia; Intestines; Kidney Failure, Chronic; Pancreas; Pheochromocytoma; Pyloric Antrum; Stomach; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

A method for measurement of gastrin in gastric mucosa has been developed, and distribution of gastrin in the stomach of pig, dog, cat, rabbit, and man was examined. Measurable amounts of gastrin were found in corpus of all species, but the content in the antrum was considerably higher. The highest concentration of gastrin was seen in man. The borderline between corpus and antrum was abrupt, and in both parts of the stomach gastrin was evenly distributed. In 44 patients with duodenal ulcer the antral gastrin concentration was 21.3 mug eqv. per g mucosa, in 15 patients with prepyloric ulcer 23.0, in 10 patients with gastric ulcer 5.9, and in 16 patients with gastric carcinoma 7.9. The control group consisted of 10 healthy volunteers and 12 patients with minor abdominal complaints. Mean antral gastrin concentrations were 28.1 and 20.7 respectively. No significant relationship was observed between PAO and gastrin content of antral mucosa in any group.

Topics: Adult; Animals; Cats; Dogs; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Rabbits; Radioimmunoassay; Species Specificity; Stomach Neoplasms; Stomach Ulcer; Swine

Whereas 67 patients with duodenal ulcer had fasting and 30-minute postprandial mean serum gastrin levels not substantially different from 32 normal subjects, they had substantially higher fasting and histamine-stimulated gastric acid secretion. The increased acid secretion found in patients with duodenal ulcer is not caused by increased serum gastrin levels. Ten patients with recurrent ulcer, after incomplete vagotomy and gastric resection, had high gastric acid secretion and normal serum gastrin levels. Three patients with recurrent ulcer following complete vagotomy and gastric resection, but with retained antrum, had both high gastric acid secretion and high fasting and postprandial secrum gastrin levels. Three patients with Zollinger-Ellison tumors had even higher basal acid outputs and serum gastrin levels. The combination of basic gastric acid secretory studies and serum gastrin determinations may identify three causes of recurrent ulcer: incomplete vagotomy, retained antrum, and Zollinger-Ellison tumor.

Topics: Duodenal Ulcer; Fasting; Food; Gastric Juice; Gastrins; Histamine; Humans; Peptic Ulcer; Prospective Studies; Pyloric Antrum; Recurrence; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

To investigate both the cause and reversibility of pyloric sphincter dysfunction in patients with gastric ulcer, pyloric sphincter pressures were measured in 10 normal subjects and 13 patients with gastric ulcer before and during gastric acidification. Fasting serum gastrin concentration was significantly higher in patients with gastric ulcer than in normal subjects. Compared to normals, patients with gastric ulcer had significantly lower pyloric pressures in response to intraduodenal amino acids and sodium oleate. However, during gastric acidification, these same patients demonstrated normal pyloric responses to these stimuli. Serum gastrin concentrations did not change during gastric acidification. These studies show that: (1) in patients with gastric ulcer the pyloric sphincter does not respond normally to intraduodenal stimulation; (2) fasting serum gastrin concentration is elevated in patients with gastric ulcer; and (3) in these patients, pyloric sphincter dysfunction can be reversed by gastric acidification. The mechanism of pyloric dysfunction in patients with gastric ulcer remains unknown.

Topics: Adult; Amino Acids; Female; Gastric Juice; Gastrins; Humans; Hydrochloric Acid; Male; Middle Aged; Oleic Acids; Pylorus; Secretory Rate; Sodium; Stimulation, Chemical; Stomach Ulcer

The importance of beta-adrenergic receptor activity for ulcer formation was studied. In rats fasted for 48 hours, ulcers in the rumen were produced constantly after 17 hours of pyloric ligation. d,1,Propranolol in doses of 1 to 30 mg/kg given 4 times during 12 hours caused a dose-dependent inhibition of ulcer formation. The ulcero-protective potency of d,1,propranolol was about 20 times that of d,propranolol. No explanation of the ulcero-protective effect was observed when the gastric acid secretion was studied after 17 hours. Serum gastrin concentration after 17 hours of ligation was in all animals less than 5 pmol per liter, i.e. below one-third of the normal fasting value. For all pharmacological effects apart from beta-adrenergic blockage, d,1, and d,propranolol do not differ, while the results presented here suggest that intact beta-adrenergic receptor activity is important for the development of gastric ulcers in the pylorus-ligated rat. The mechanism behind the ulcero-protective effect of beta-adrenergic blockage remains to be solved.

Topics: Animals; Depression, Chemical; Gastric Juice; Gastrins; Ligation; Male; Propranolol; Pylorus; Rats; Receptors, Adrenergic; Secretory Rate; Stimulation, Chemical; Stomach Ulcer

The gastric secretion of acid was examined 30 minutes basally (BAO) and in response to stepwise increasing doses of pentagastrin in subjects with (n = 51) and without (n = 40) peptic ulcer disease. None of them showed basal anacidity. Before insertion of the gastric tube, blood was taken for radioimmunological determination of the serum gastrin concentration (SG). A significant positive correlation was found between SG and BAO in the subjects without ulcer. This was mainly due to a close correlation in 20 healthy young volunteers. When BAO and SG was expressed as proportions of calculated maximal acid response (Vmax) and half maximal dose of pentagastrin (Km), respectively, the positive correlation between SG and BAO was improved and reached significance also in the individuals with peptic ulcer disease. The findings suggest that the serum concentration of gastrin plays a role in the basal gastric secretion.

Topics: Duodenal Ulcer; Fasting; Gastric Juice; Gastrins; Humans; Pentagastrin; Secretory Rate; Stimulation, Chemical; Stomach Ulcer

The course reviews the present status in the field of Vagotomy with reference to pathophysiology, gastrin release, anatomy, neural changes in the antrum, acid secretion, GI hormones, gastric motility, pepsin concentration, mucus production, O2 tension in the gastric mucosa, changes in the numbers of parietal cells, glucose tolerance, indications, diagnosis, necessity for drainage, acute complications, exclusion of malignancy in gastric ulcer; technique, intraoperative tests, results with TV, SV with antrectomy, recurrences, SPV and pyroplasty (controlled study), training. Nonresecting surgery of GDU is possible if vagotomy (SPV) and drainage (pyloroplasty) are correctly combined.

Topics: Adult; Drainage; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Recurrence; Stomach Ulcer; Vagotomy

Topics: Gastric Acidity Determination; Gastrins; Humans; Hyperplasia; Precancerous Conditions; Pyloric Antrum; Stomach; Stomach Neoplasms; Stomach Ulcer

Topics: Gastrins; Humans; Hyperplasia; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Recurrence; Stomach Ulcer; Terminology as Topic; Zollinger-Ellison Syndrome

Topics: Alcoholic Beverages; Diet; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hormones; Histamine Release; Humans; Indomethacin; Peptic Ulcer; Salicylates; Secretin; Smoking; Stomach Ulcer; Stress, Psychological; Vagus Nerve

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Secretory Rate; Specimen Handling; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Gastritis; Histamine H1 Antagonists; Humans; Metoclopramide; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Vagotomy

Topics: Adenylyl Cyclase Inhibitors; Calcium; Cyclic AMP; Digestive System; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Glucagon; Humans; Stomach Ulcer

Topics: Adult; Aged; Chronic Disease; Dumping Syndrome; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Gastroscopy; Humans; Hypotension; Male; Middle Aged; Pain, Postoperative; Pentagastrin; Postgastrectomy Syndromes; Pyloric Antrum; Pylorus; Radiography; Stomach; Stomach Ulcer; Tachycardia; Vomiting

Topics: Anemia, Pernicious; Animals; Biological Assay; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Rats; Secretory Rate; Stomach Ulcer; Swine; Zollinger-Ellison Syndrome

Topics: Administration, Oral; Adolescent; Adult; Aged; Biopsy; Endoscopy; Fatty Acids, Unsaturated; Female; Gastric Juice; Gastric Mucosa; Gastrins; Hexosamines; Histocytochemistry; Humans; Male; Middle Aged; Radioimmunoassay; Stomach; Stomach Ulcer; Terpenes

Topics: Adult; Aged; Digestion; Female; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Humans; Male; Middle Aged; Stomach Ulcer

Topics: Animals; Gastric Mucosa; Gastrins; Hemodynamics; Histamine; Norepinephrine; Rabbits; Stomach Ulcer

Topics: Blood Glucose; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Insulin; Pepsin A; Radioimmunoassay; Secretory Rate; Serum Albumin, Radio-Iodinated; Stimulation, Chemical; Stomach Ulcer; Time Factors

Topics: Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Esophageal Achalasia; Gastrins; Gastritis; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Peptic Ulcer; Secretin; Stomach Neoplasms; Stomach Ulcer

Topics: Anemia, Pernicious; Animals; Antibody Specificity; Cross Reactions; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Immune Sera; Insulin; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Stomach Ulcer; Swine; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Gastric Mucosa; Gastrins; Glucagon; Hypocalcemia; Male; Oxygen; Rats; Regional Blood Flow; Stomach Ulcer; Stress, Physiological

Topics: Animals; Gastric Acidity Determination; Gastric Juice; Gastrins; Ligation; Male; Portacaval Shunt, Surgical; Pylorus; Rats; Stomach; Stomach Ulcer; Stress, Physiological; Vagotomy; Vagus Nerve

Topics: Adolescent; Adult; Animals; Brain Injuries; Cattle; Craniocerebral Trauma; Gastrins; Humans; Male; Military Medicine; Rabbits; Radioimmunoassay; Spinal Cord Injuries; Stomach Ulcer; Stress, Psychological; Vietnam; Wounds and Injuries

Topics: Bile; Gastric Juice; Gastrins; Gastroesophageal Reflux; Histamine Release; Humans; Pylorus; Stomach Ulcer

Topics: Animals; Electric Stimulation; Gastric Mucosa; Gastrins; Gastrointestinal Hemorrhage; Hypothalamus; Injections, Intravenous; Rats; Stimulation, Chemical; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Pepsin A; Peptic Ulcer; Pyloric Stenosis; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Chronic Disease; Duodenal Ulcer; Epithelial Cells; Fluorescence; Gastric Mucosa; Gastrins; Gastritis; Humans; Immune Sera; Metaplasia; Methods; Stomach Neoplasms; Stomach Ulcer

Topics: Bile Acids and Salts; Duodenum; Gastric Juice; Gastrins; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Pressure; Pylorus; Stomach Ulcer

Topics: Adult; Age Factors; Anemia, Pernicious; Charcoal; Duodenal Ulcer; Evaluation Studies as Topic; Female; Gastrins; Glycols; Heparin; Humans; Ion Exchange Resins; Male; Polymers; Radioimmunoassay; Serum Albumin; Sex Factors; Sodium Chloride; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Anemia, Pernicious; Duodenal Ulcer; Ethylamines; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Insulin; Male; Middle Aged; Postoperative Complications; Pyrazoles; Recurrence; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Duodenal Ulcer; Eating; Electric Stimulation; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Parasympatholytics; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Secretin; Secretory Rate; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Bicarbonates; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Glucagon; Humans; Immunochemistry; Intestinal Mucosa; Intestine, Small; Pancreas; Secretin; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Stomach Ulcer

Topics: Adrenal Cortex Hormones; Calcium; Gastric Mucosa; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism; Multiple Endocrine Neoplasia; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Charcoal; Duodenal Ulcer; Gastrins; Humans; Iodine Isotopes; Methods; Middle Aged; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

1. A radio-immunoassay for gastrin has been developed using partially purified porcine gastrin to raise antibodies and highly purified natural porcine gastrin I for radio-iodination with (125)I. The separation of antibody-bound from free hormone was performed by a double-antibody method.2. In this assay highly purified natural porcine gastrin I, synthetic human gastrin I, radio-iodinated porcine gastrin I, gastrin in the plasma of a healthy volunteer, a patient with pernicious anaemia and another patient with the Zollinger-Ellison syndrome were immunologically identical.3. The fasting plasma gastrin concentration of fourteen gastric ulcer patients was significantly higher than that of the 113 hospital controls with no history of gastro-intestinal disease, while twenty-seven duodenal ulcer patients had gastrin levels within the normal range.4. Plasma gastrin concentration was significantly elevated in pernicious anaemia (fifty-one patients), achlorhydria (thirty-three patients), hypochlorhydria (eleven patients) and in nine patients with histologically proven Zollinger-Ellison syndrome.5. In human volunteers a protein meal stimulated endogenous gastrin release while a carbohydrate meal did not. Atropine sulphate I.M., and hydrochloric acid orally, produced a significant fall in the level of circulating gastrin.

Topics: Achlorhydria; Anemia, Pernicious; Animals; Atropine; Dietary Proteins; Duodenal Ulcer; Gastrins; Guinea Pigs; Humans; Hydrochloric Acid; Iodine Isotopes; Methods; Rabbits; Radioimmunoassay; Stimulation, Chemical; Stomach Ulcer; Sucrose; Swine; Zollinger-Ellison Syndrome

Topics: Antacids; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Osmosis; Stomach Ulcer

Topics: Adult; Aged; Circadian Rhythm; Cross Reactions; Duodenal Ulcer; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Immune Sera; Intestinal Obstruction; Iodine Isotopes; Male; Middle Aged; Peptic Ulcer; Peptides; Radioimmunoassay; Stomach; Stomach Ulcer; Time Factors

Basal serum gastrin in 40 patients with benign gastric ulcer was 103 +/- 10.7 pg/ml, a level significantly higher than corresponding estimations in normal subjects and patients with duodenal ulcer. Following stimulation by a protein meal, a mean rise of 124 pg/ml was achieved at 75 minutes and prior atropinization induced a rise of 208 pg/ml at 90 minutes. Insulin hypoglycaemia produced a rise of 63 pg/ml which was not significantly changed with concomitant neutralization of gastric contents. These results suggest that patients with gastric ulcer have higher basal gastrin levels than normal and this is probably related to the lowered antral acidity. In addition, the protein meal and insulin hypoglycaemia responses suggest an increased antral G cell mass and the possibility of additional gastrin release from sites outside the antrum. It is doubtful whether the relative hypergastrinaemia has an aetiological role in gastric ulcer but it may have a role in the maintenance of gastric ulcer.

Topics: Adult; Aged; Atropine; Bicarbonates; Blood Glucose; Dietary Proteins; Female; Gastrins; Humans; Immunoassay; Insulin; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer; Time Factors

Topics: Duodenal Ulcer; Female; Gastrins; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Male; Radioimmunoassay; Stomach Ulcer; Time Factors; Vagotomy; Vagus Nerve

A perfused rat stomach technique which can detect synthetic human gastrin I in amounts greater than 10 ng and measure by block assay amounts greater than 50 ng was used to study circulating gastrin-like activity in normal subjects, patients with peptic ulcer, and patients with the Zollinger-Ellison syndrome. No detectable activity was found in normal subjects or patients with gastric ulcer before or after meals. No activity was found in the fasting plasma of patients with duodenal ulcer but after meals activity could be detected in duplicate samples in seven of 20 patients. In nine proven cases of the Zollinger-Ellison syndrome, gastrin-like activity in the plasma ranged from 15 to 356 ng/ml. The gastrin-like content of two tumours was 6.4 and 29.1 mug/g of tissue. The significance of these findings in relation to immunoassay is described.

Topics: Adult; Aged; Animals; Biological Assay; Duodenal Ulcer; Female; Gastrins; Humans; Male; Methods; Middle Aged; Peptic Ulcer; Rats; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Chondroitin; Duodenal Ulcer; Electrophoresis; Gastric Juice; Gastrins; Glycoproteins; Glycosaminoglycans; Humans; Insulin; Peptides; Stimulation, Chemical; Stomach Ulcer; Sulfates

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Cross Reactions; Duodenal Ulcer; Fasting; Gastrins; Humans; Peptides; Pheochromocytoma; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Secretions; Pepsin A; Peptic Ulcer; Secretin; Stomach Ulcer

Topics: Adult; Aged; Caffeine; Female; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer

Fasting serum gastrin has been measured by radioimmunoassay in 72 patients with duodenal ulcer and compared with that in normals, patients with gastric ulcer, and with the Zollinger-Ellison syndrome. The mean (+/- SEM) gastrin levels were 15.7 +/- 1.5 pg/ml in the duodenal ulcer group, 32.1 +/- 4.3 pg/ml in normals, 118 +/- 18.1 pg/ml in gastric ulcer, and between 450 and 2,000 pg/ml in the Zollinger-Ellison syndrome. There were no difficulties in distinguishing simple ulcer from the Zollinger-Ellison syndrome as the presence of hyperchlorhydria in combination with hypergastrinaemia led to a confident diagnosis of the latter disease.The effect of protein, glucose, and cream feeding with and without atropine was also assessed in a group of these patients with duodenal ulcer. As in normals, there was no stimulation of gastrin release by either atropine alone, distilled water, glucose, or cream. However, protein alone produced a greater rise in serum gastrin levels compared with that in normals and prior atropinization augmented this response greatly in duodenal ulcer. This indicates an increased amount of releasable gastrin in the latter disease, the release of which, under basal conditions, is suppressed by the high acidity in the antrum.

Topics: Adult; Aged; Atropine; Diagnosis, Differential; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Duodenal Ulcer; Fasting; Female; Food; Gastrins; Glucose; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Diseases; Humans; Male; Middle Aged; Pyrazoles; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Stomach Ulcer

Topics: Duodenal Ulcer; Fasting; Gastric Juice; Gastrins; Gastrointestinal Diseases; Histamine; Humans; Radioimmunoassay; Secretory Rate; Serum Albumin, Radio-Iodinated; Stimulation, Chemical; Stomach Ulcer

Topics: Achlorhydria; Chronic Disease; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Hydrogen-Ion Concentration; Hypertrophy; Insulin; Intubation, Gastrointestinal; Protein-Losing Enteropathies; Stimulation, Chemical; Stomach; Stomach Diseases; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Histamine; Humans; Injections, Intravenous; Pepsin A; Secretory Rate; Stimulation, Chemical; Stomach Ulcer

Topics: Adult; Aged; Animals; Dogs; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged; Pepsin A; Stimulation, Chemical; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Pepsin A; Peptic Ulcer; Stomach Ulcer; Vagus Nerve

Topics: Achlorhydria; Adult; Age Factors; Aged; Duodenal Ulcer; Fasting; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

The fasting serum level of gastrin was determined by radioimmunoassay in 41 normal subjects, 27 patients with duodenal ulceration, 12 patients with gastric ulceration, and 8 patients following "complete" vagotomy. The patients with duodenal ulceration had significantly higher serum levels of gastrin (1.3 +/- S.D. 0.7 ng./ml.) than normal subjects (0.4 +/- S.D. 0.3 ng./ml.), patients with gastric ulceration (0.4 +/- S.D. 0.4 ng./ml.), or post-vagotomy patients (0.15 +/- S.D. 0.2 ng./ml.).The gastrin secretion in both normal subjects and patients with duodenal ulceration was responsive to protein ingestion, but a larger incremental secretion of gastrin occurred in the latter group. Hyperglycaemia significantly suppressed the serum level of gastrin in both groups. The patients with gastric ulceration had fasting and postprandial serum gastrin levels not significantly different from normal subjects.

Topics: Dietary Proteins; Duodenal Ulcer; Fasting; Food; Gastrins; Humans; Hyperglycemia; Injections, Intravenous; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagotomy

Topics: Adult; Carcinoma; Computers; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged; Peptides; Pyrazoles; Statistics as Topic; Stimulation, Chemical; Stomach Neoplasms; Stomach Ulcer

Topics: Bicarbonates; Cholecystokinin; Enteritis; Gallbladder Diseases; Gastric Acidity Determination; Gastrins; Gastritis; Pancreas; Pancreatitis; Pyrazoles; Secretin; Stimulation, Chemical; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Hyperparathyroidism; Peptic Ulcer; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Afferent Loop Syndrome; Cholecystokinin; Chronic Disease; Gastrectomy; Gastrins; Humans; Methods; Recurrence; Secretin; Stomach Ulcer

Topics: Anemia, Pernicious; Animals; Antibodies; Blood Glucose; Duodenal Ulcer; Female; Gastrins; Humans; Male; Methods; Middle Aged; Rabbits; Radioimmunoassay; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Dextrans; Gastric Juice; Gastrins; Infusions, Parenteral; Male; Pepsin A; Pyrazoles; Rats; Rumen; Sodium Chloride; Stomach Ulcer

Topics: Antacids; Diet Therapy; Duodenal Ulcer; Estrogens; Gastrins; Glycyrrhiza; Humans; Hypothermia, Induced; Male; Parasympatholytics; Pepsin A; Peptic Ulcer; Plants, Medicinal; Stomach; Stomach Ulcer; Terpenes

Topics: Adult; Biopsy; Diabetes Mellitus; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Histological Techniques; Humans; Injections, Intravenous; Peptides; Stimulation, Chemical; Stomach; Stomach Ulcer

Topics: Adrenalectomy; Alkaloids; Animals; Atropine; Blood Pressure; Cats; Dogs; Fasting; Gastric Juice; Gastrins; Guinea Pigs; Hexosamines; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Mucins; Plants, Medicinal; Rats; Reserpine; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Hydrogen-Ion Concentration; Stomach Ulcer

Topics: Animals; Duodenal Ulcer; Gastrins; Guinea Pigs; Stomach Ulcer; Vagotomy

Topics: Gastrectomy; Gastrins; Gastroenterostomy; Humans; Methods; Postoperative Complications; Prognosis; Pylorus; Retrospective Studies; Stomach Ulcer; Vagotomy

Topics: Aged; Esophageal Achalasia; Gastrins; Humans; Male; Stomach Ulcer; Vagus Nerve

Topics: Adult; Age Factors; Aged; Body Weight; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Methods; Middle Aged; Peptic Ulcer; Secretory Rate; Sex Factors; Stomach Ulcer; Time Factors; Vagus Nerve

Topics: Antiemetics; Duodenal Ulcer; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Motility; Humans; Male; Procainamide; Secretory Rate; Stomach; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastroenterostomy; Hernia, Diaphragmatic; Humans; Methods; Pylorus; Stomach Ulcer; Vagotomy

Topics: Gastrins; Humans; Hydrochloric Acid; Stomach; Stomach Ulcer

Topics: Diet; Digestion; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Motility; Humans; Stomach; Stomach Ulcer; Time Factors

Topics: Adult; Age Factors; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Injections, Subcutaneous; Intrinsic Factor; Male; Methods; Middle Aged; Radioimmunoassay; Stomach Ulcer; Time Factors; Vitamin B 12

Topics: Age Factors; Chronic Disease; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Glycyrrhiza; Humans; Male; Plants, Medicinal; Regeneration; Stomach Ulcer; Terpenes

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Nitrogen; Stomach Ulcer

Topics: Adult; Blood Transfusion; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Histamine; Humans; Middle Aged; Peptic Ulcer; Secretory Rate; Stomach Ulcer

Topics: Diagnosis, Differential; Gastric Juice; Gastrins; Histamine; Humans; Nitrogen; Pyrazoles; Stimulation, Chemical; Stomach Neoplasms; Stomach Ulcer

Topics: Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroenterostomy; Humans; Middle Aged; Pylorus; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastrectomy; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Pyloric Stenosis; Pylorus; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastrins; Hemorrhage; Humans; Peptic Ulcer; Pyloric Stenosis; Stomach Ulcer; Vagotomy

Topics: Endocrine System Diseases; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Pharmacology; Stomach Ulcer; Surgical Procedures, Operative; Vagotomy; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Pyloric Stenosis; Stomach Ulcer; Vagotomy

Topics: Adenocarcinoma, Scirrhous; Carcinoma; Cats; Duodenal Ulcer; Duodenum; Gastric Mucosa; Gastrins; Histamine; Physiology; Stomach Neoplasms; Stomach Ulcer

Topics: Gastric Juice; Gastrins; Gastroenterostomy; Gastrointestinal Hormones; Pathology; Pylorus; Rabbits; Research; Stomach Ulcer; Surgical Procedures, Operative; Vagotomy

Topics: Dogs; Gastric Acidity Determination; Gastric Juice; Gastrins; Isotonic Solutions; Liver; Physiology; Pylorus; Research; Stomach Ulcer; Therapeutic Irrigation

These three papers present studies on gastrin. The first paper describes a method of biological assay using the rat. The second paper demonstrates that the highest concentration of gastrin-like activity occurs in the antral mucosa, with a clear gradient of concentration of activity down the gut. However, it is to be noted that the total amount of extractable activity is greatest in the duodenum, although the concentration there is less than in the antrum. No activity was detected in the pancreas. The third paper studies the contents of gastrin-like activity in patients with duodenal ulcer and demonstrates higher figures when stenosis is present. Patients with benign gastric ulcer and carcinomata showed results equal to or greater than in those with the average uncomplicated duodenal ulcer. It was noted that two patients with dilated antra both had very low total gastrin-like activity. There was no correlation between total activity and maximal histamine-stimulated output of acid. There was, however, a positive correlation between the insulin-stimulated acid secretion and the total gastrin-like activity in the cases of uncomplicated duodenal ulcers. The clinical studies are still tentative in view of the several variables present, but it seems likely that they will in due course clarify the role of gastrin in the ulcer problem.

Topics: Biological Assay; Biomedical Research; Colon; Duodenal Ulcer; Duodenum; Freeze Drying; Gastrectomy; Gastric Mucosa; Gastrins; Histology; Humans; Ileum; Insulin; Jejunum; Pancreas; Rats; Research; Statistics as Topic; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Amino Acids; Autonomic Nervous System Diseases; Cholecystitis; Duodenal Ulcer; Fatty Liver; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Pancreatitis; Proctitis; Stomach Ulcer