epidermal-growth-factor and Peptic-Ulcer

Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine

Topics: Animals; Epidermal Growth Factor; Gastric Mucosa; Histamine; Humans; Mast Cells; Neutrophils; Nicotine; Nitric Oxide; Peptic Ulcer; Rats; Reactive Oxygen Species; Smoking; Vasopressins

Topics: Animals; Anti-Ulcer Agents; Drugs, Chinese Herbal; Epidermal Growth Factor; Gastric Mucosa; Heat-Shock Proteins; Humans; Peptic Ulcer; Phytotherapy; Prostaglandins; Recurrence

A huge variety of peptides and cytokines are involved in the maintenance of mucosal integrity and in the inflammatory response at sites of ulceration. Most studies have focused on the effects of an individual factor in this complex process. However, it is becoming increasingly apparent that, to fully understand their importance in vivo, we should consider their function as part of a highly integrated system. It is also becoming clear that a relatively small number of common pathways are brought into play by the host in response to a wide variety of intestinal insults.

Topics: Cytokines; Epidermal Growth Factor; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Transforming Growth Factors; Trypsin Inhibitor, Kazal Pancreatic

In recent years, increasing interest has been focused on peptide growth factors, and impressive progress has been made in the understanding of their role in tumor development and progression. However, evidence is mounting that peptides such as epidermal growth factor and transforming growth factor-alpha may be of much more physiological than pathological importance. This brief article is intended to give a rapid overview of the available data supporting a role for epidermal growth factor and its human homologue urogastrone in peptic ulcer healing.

Topics: Animals; Epidermal Growth Factor; Humans; Peptic Ulcer; Wound Healing

Topics: Epidermal Growth Factor; Fibroblast Growth Factors; Free Radicals; Hepatocyte Growth Factor; Humans; Peptic Ulcer; Prostaglandins

The pathogenesis of gastroduodenal ulceration has been investigated mostly from the point of view of aggressive factors; the therapeutic interventions affected the healing process only indirectly. With the discovery of the potent healing capacity of growth factors, direct treatment of ulcers is now possible regardless of HCl and pepsin secretion. We review our recent data on how growth factors (e.g., bFGF, PDGF in comparison with EGF) can promote ulcer healing.. Treatment of rats with bFGF, PDGF accelerated the healing of experimental chronic duodenal and gastric ulcers without suppressing gastric acid secretion and resulted in superior quality of ulcers healed. We also detected additive or synergistic action between bFGF and cimetidine or bFGF and sucralfate in the healing of chemically induced chronic duodenal ulcers and chronic erosive gastritis.. We conclude that growth factors such as bFGF, PDGF can promote ulcer healing without the need to neutralize gastric secretion and may lead to a direct and efficient therapeutic regime.

Topics: Animals; Anti-Ulcer Agents; Cimetidine; Drug Interactions; Epidermal Growth Factor; Fibroblast Growth Factors; Peptic Ulcer; Platelet-Derived Growth Factor; Rats; Sucralfate

Topics: Animals; Epidermal Growth Factor; Gastric Mucosa; Granulocytes; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Prostaglandins

Gastrointestinal mucosa is one of the most rapidly proliferating tissues in the body and the alteration in the balance between cell regeneration and cell loss may lead to mucosal lesions and ulcerations. Mucosal growth is under the influence of various growth factors, among which epidermal growth factor (EGF) and polyamines seem to play a crucial role. EGF is produced in large quantities in salivary and pancreatic glands and secreted mainly into the gut lumen and partly released into the bloodstream from where it is cleared by the kidneys and excreted into the urine as urogastrone. The physiological role of EGF is still under active investigations but it appears that EGF may be required for the maintenance of mucosal integrity and healing of mucosal defects due to its accumulation in the lesion area and local stimulation of healing processes. The mechanism of protective and ulcer healing effects of EGF involves the activation of ornithine decarboxylase (ODC), the key enzyme in the biosynthesis of polyamines, which play a crucial role in the growth-promoting action of EGF. Substances that affect the generation and/or catabolism of polyamines affect the gastroprotective and ulcer healing effect of EGF but not that of exogenous polyamines. Mucosal generation of protective prostaglandins appears to be essential mainly for the gastro-protective effects of EGF but seem to be of little importance in the healing effects of EGF on acute and chronic gastroduodenal ulcerations.

Topics: Animals; Eflornithine; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Humans; Ornithine Decarboxylase Inhibitors; Peptic Ulcer; Rats; Spermine; Wound Healing

Proliferation and growth of gastroduodenal mucosal cells represent important elements of mucosal defense and any alterations in the balance between cell proliferation and cell loss may lead to trophic changes in mucosa. Acute mucosal lesions induced by local irritants such as bile salts, ethanol, aspirin, or stress are accompanied by widespread damage of surface epithelium followed by almost immediate repair due to mucosal cell restitution, which is unrelated to cell proliferation but does depend on the intrinsic property of mucosal cells to cover superficial defects. Cytoprotection involves the protection of the regeneration zone and the maintenance of blood flow to the mucosa. Various factors that exhibit mucosal growth-promoting action include EGF, gastrin, growth hormone, and GH-releasing factor. These factors protect the mucosa against acute injury but the mechanism of this effect is not clear. These trophic agents, especially EGF, accelerate the healing of chronic gastroduodenal ulceration and may contribute to the healing effects of sucralfate or De-Nol. These effects of trophic substances are related to their stimulation of cell proliferation and DNA, RNA, and protein synthesis and can be reversed by the suppression of mucosal growth. Prostaglandins, especially their stable methylated analogs, display trophic effects on the gastric mucosa but neither gastroprotective nor ulcer healing actions of PG can be attributed to their trophic effect. With increasing attention being paid to mucosal growth and repair as components of mucosal defense, the emphasis of drug therapy of acute or chronic gastroduodenal lesions is likely to move toward strengthening mucosal defense rather than the inhibition of aggressive factors.

Topics: Animals; Duodenum; Epidermal Growth Factor; Gastrins; Growth Substances; Humans; Peptic Ulcer; Prostaglandins; Secretin; Somatostatin; Stomach

Topics: Animals; Digestive System; Epidermal Growth Factor; ErbB Receptors; Gastric Acid; Humans; Peptic Ulcer

Drugs which abolish acid secretion and promise improved ulcer healing rates have produced dysplasia and tumours in experimental animals given large doses for long periods. Solutions to this problem will be based on better understanding of the mechanisms involved. Healing rates might be improved by combining inhibitors of acid secretion with ulcer protectors which, unlike currently available agents, are designed to work well in the presence of diminished acid secretion. Drugs which increase mucosal defence might best be used to prevent ulceration, so the need is to develop agents which are safe for long term use.

Topics: Animals; Anti-Ulcer Agents; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Humans; Pepsin A; Peptic Ulcer; Proglumide; Prostaglandins E, Synthetic; Somatostatin; Stomach; Wound Healing

Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2-receptor antagonists show most promise at present. The prostaglandins and gastro-intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future.

Topics: Animals; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrointestinal Hormones; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Peptic Ulcer; Prostaglandin Antagonists; Prostaglandins A; Prostaglandins E; Secretin; Somatostatin; Zollinger-Ellison Syndrome

To investigate the effect of Anwei Qingyou formula on the clinical treatment of patients with peptic ulcer (PU) and its effect on the levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2).. Medical records of 83 patients with PU, treated in our hospital from January 2020 to January 2021, were retrospectively analyzed. Among them, 40 patients received conventional triple therapy (scheme I), that is, oral omeprazole, clarithromycin and amoxicillin, twice a day, and 43 patients received conventional triple therapy + Anwei Qingyou formula, taken orally twice a day (scheme II). The improvement of clinical symptoms, the quality of ulcer healing, clinical effectiveness and recurrence rate were analyzed after 4 weeks of treatment. Patients were followed up for six months.. After treatment with corresponding regimen, the total clinical effective rate of scheme II was 97.57% (42/43), which was significantly higher than 82.50% (33/40) of scheme I. Six-month follow-up results showed that the recurrence rate in scheme II patients was 4.65% (2/43), which was significantly lower than 20.00% (8/40) in the scheme I group (χ 2 = 5.479, 4.607, all P < .05). After one course of treatment, the levels of serum EGF and PGE2 in scheme II group were higher than those in scheme I group (P < .05).. In combination with the conventional western medicine treatment, Anwei Qingyou formula administration in PU patients effectively improves the overall control of the disease and therapeutic effectiveness.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Dinoprostone; Drug Therapy, Combination; Epidermal Growth Factor; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Peptic Ulcer; Retrospective Studies

Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg

Topics: Acetic Acid; Animals; Anthocyanins; Antioxidants; Biomarkers; Cyclooxygenase 1; Disease Models, Animal; Duodenum; Epidermal Growth Factor; Ethanol; Gastric Mucosa; Gene Expression Regulation; Indomethacin; Inflammation; Male; Matrix Metalloproteinase 9; Mice; Oxidative Stress; Peptic Ulcer; Polypharmacy; Protective Agents; Reperfusion Injury; Stomach Ulcer; Tight Junctions; Wound Healing

The gastrointestinal (GI) endoscopy has become a standard diagnostic tool for GI ulcers and cancer. In this study we studied endoscopic application of epidermal growth factor-containing chitosan hydrogel (EGF-CS gel) for treatment of GI ulcer. We hypothesized that directional ulcer-coating using EGF-CS gel via endoscope would precipitate ulcer-healing. EGF-CS gel was directly introduced to the ulcer-region after ulceration in acetic acid-induced gastric ulcer (AAU) and mucosal resection-induced gastric ulcer (MRU) rabbit and pig models. The ulcer dimensions and mucosal thicknesses were estimated and compared with those in the control group. Healing efficacy was more closely evaluated by microscopic observation of the ulcer after histological assays. In the AAU model, the normalized ulcer size of the gel-treated group was 2.3 times smaller than that in the non-treated control group on day 3 after ulceration (P < 0.01). In the MRU model, the normalized ulcer size of the gel-treated group was 5.4 times smaller compared to that in the non-treated control group on day 1 after ulceration (P < 0.05). Histological analysis supported the ability of EGF-CS gel to heal ulcers. The present study suggests that EGF-CS gel is a promising candidate for treating gastric bleeding and ulcers.

Topics: Animals; Chitosan; Disease Models, Animal; Endoscopy, Gastrointestinal; Epidermal Growth Factor; Female; Gastric Mucosa; Hydrogels; Peptic Ulcer; Rabbits; Swine; Wound Healing

Wound healing of the gastrointestinal mucosa is essential for the maintenance of gut homeostasis and integrity. Enteric glial cells play a major role in regulating intestinal barrier function, but their role in mucosal barrier repair remains unknown. The impact of conditional ablation of enteric glia on dextran sodium sulfate (DSS)-induced mucosal damage and on healing of diclofenac-induced mucosal ulcerations was evaluated in vivo in GFAP-HSVtk transgenic mice. A mechanically induced model of intestinal wound healing was developed to study glial-induced epithelial restitution. Glial-epithelial signaling mechanisms were analyzed by using pharmacological inhibitors, neutralizing antibodies, and genetically engineered intestinal epithelial cells. Enteric glial cells were shown to be abundant in the gut mucosa, where they associate closely with intestinal epithelial cells as a distinct cell population from myofibroblasts. Conditional ablation of enteric glia worsened mucosal damage after DSS treatment and significantly delayed mucosal wound healing following diclofenac-induced small intestinal enteropathy in transgenic mice. Enteric glial cells enhanced epithelial restitution and cell spreading in vitro. These enhanced repair processes were reproduced by use of glial-conditioned media, and soluble proEGF was identified as a secreted glial mediator leading to consecutive activation of epidermal growth factor receptor and focal adhesion kinase signaling pathways in intestinal epithelial cells. Our study shows that enteric glia represent a functionally important cellular component of the intestinal epithelial barrier microenvironment and that the disruption of this cellular network attenuates the mucosal healing process.

Topics: Analysis of Variance; Animals; Caco-2 Cells; Cell Shape; Coculture Techniques; Culture Media, Conditioned; Dextran Sulfate; Diclofenac; Disease Models, Animal; Enteritis; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Focal Adhesion Kinase 1; Glial Fibrillary Acidic Protein; Humans; Intestinal Mucosa; Intestine, Small; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neuroglia; Paracrine Communication; Peptic Ulcer; Phosphorylation; Protein Precursors; Rats; RNA Interference; Signal Transduction; Simplexvirus; Thymidine Kinase; Time Factors; Transfection; Wound Healing

The aim of the present study is to investigate the antiulcerogenic effects of the essential oil (EO) of Croton cajucara Benth in rats fed with a normal protein (NP) and low-protein diet (MN). NP and MN rats were treated with the essential oil for 15 days after chronic ulceration was induced. The EO accelerated healing of acetic acid-induced gastric lesions in NP and MN rats (p<0.05). In a similar experiment on chronic ulceration, Epidermal Growth Factor (EGF) mRNA expression increased in NP rats but not in MN rats. In assays of acute antiulcerogenic activity, C. cajucara increased somatostatin plasma levels and decreased gastrin plasma levels in both animal groups. The EO significantly prevented ethanol-induced gastric ulcers in NP and MN rats (p<0.001). Histological examination showed initial regeneration, formation of inflammatory infiltrate and angiogenesis in the epithelium surface of acetic acid-induced ulcers in NP and MN rats. C. cajucara prevented gastric lesions in both animal groups when ethanol methodology was used. We concluded that the EO showed an antiulcerogenic activity mediated by increased somatostatin secretion and EGF mRNA expression.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Base Sequence; Croton; Dietary Proteins; DNA Primers; Epidermal Growth Factor; Female; Gastrins; Malnutrition; Peptic Ulcer; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin

The epidermal growth factor (EGF) has been shown to promote the proliferation of various types of cells, to maintain the physiological function of the mucosa of the digestive tract, and to promote the healing of the gastric and duodenal ulcers. It has been expressed in many types of bacteria and yeasts. In this article, a bio-reactor was constructed, namely, the human EGF (hEGF) transgenic mini-tomato. On the basis of hEGF gene sequence, a tomato codon preference hEGF gene was chemically synthesized, and it was constructed into the plant expression vector pCAMBIA2300. The transgenic tomato plants containing gene hEGF were obtained through Agrobacterium-mediated transformation. The expression product was determined by radioimmunoassay (RIA) and showed a yield of 3.48 +/- 1.01 ng/g fresh fruits. The intragastric gavage (ig) administration of the rhEGF-containing juice of the transgenic tomato (equivalent to 24 ng rhEGF per mouse a day) for 15 days could significantly protect mice against the alcohol-induced ulceration. The ulcer index, expressed as a degree of the stomach lesion, decreased from 42.20 +/- 18.13 to 16.25 +/- 9.57.

Topics: Animals; Base Sequence; Beverages; Epidermal Growth Factor; Ethanol; Female; Fruit; Gene Expression; Genetic Vectors; Humans; Male; Mice; Molecular Sequence Data; Peptic Ulcer; Plants, Genetically Modified; Polymerase Chain Reaction; Radioimmunoassay; Sequence Analysis, DNA; Solanum lycopersicum; Stomach; Stomach Ulcer

Saliva plays a role in mucosal protection and ulcer healing.. : To study whether decreased salivary production leads to peptic ulcer disease in connective tissue disease patients associated with xerostomia.. Two hundred and two connective tissue disease patients (90 with xerostomia and 112 without xerostomia) were enrolled. Their demographic data and use of medications were recorded. Peptic ulcer disease was confirmed by endoscopy. The stimulated salivary output and secretory epidermal growth factor level were measured.. Compared with non-xerostomic counterparts, xerostomic patients manifested a higher occurrence of peptic ulcer disease (31% vs. 12%, P = 0.001), lower stimulated salivary output (9.3 +/- 4.1 vs. 22.9 +/- 5.9 mL/15 min, P < 0.001) and lower stimulated salivary epidermal growth factor output (1.40 +/- 0.77 vs. 3.00 +/- 0.96 ng/min, P < 0.001). Multivariate analysis disclosed that an older age (> or = 60 years) (odds ratio, 4.71; P < 0.001), xerostomia with stimulated salivary output of < or =1 mL/min (odds ratio, 7.54; P = 0.014) and the use of non-steroidal anti-inflammatory drugs (odds ratio, 5.76; P = 0.031) were the risk factors leading to peptic ulcer disease. In addition, xerostomic connective tissue disease patients receiving non-steroidal anti-inflammatory drugs manifested an extremely high risk of development of peptic ulcer disease (odds ratio, 19.78; P < 0.001).. Ageing, the use of non-steroidal anti-inflammatory drugs and poor salivary function are potential risk factors for the development of peptic ulcer disease in patients with connective tissue disease. If these xerostomic subjects consume non-steroidal anti-inflammatory drugs, they will encounter an extremely high peptic ulcer disease risk.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Connective Tissue Diseases; Dyspepsia; Epidermal Growth Factor; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Regression Analysis; Risk Factors; Xerostomia

Hemodialysis (HD) patients are prone to developing peptic ulcers. However, of all the risk factors associated with peptic ulcers, none have been shown to be more prevalent in HD patients than in the general population. However, salivary epidermal growth factor (EGF) may play a role in peptic ulcer diseases.. Salivary EGF levels and bioactivities were assayed in 47 maintenance HD patients and 30 normal controls, and the molecular weights of EGF were assessed using high-performance liquid chromatography (HPLC).. Salivary EGF levels were not different between both groups of subjects (4.2 +/- 0.34 vs. 5 +/- 0.54 ng/mg protein, NS), and HPLC revealed that salivary EGF in both groups had similar molecular weights. However, salivary EGF bioactivity was significantly depressed in the HD patients as compared to the normal controls (0.59 +/- 0.08 vs. 1.55 +/- 0.15 ng/mg protein, p < 0.01). Stepwise multiple regression showed that the low salivary EGF levels were associated with female gender (p < 0.05), while low salivary EGF bioactivity was associated with HD per se (p < 0.05). In the 22 HD patients who underwent gastric endoscopy, salivary EGF bioactivity was significantly lower in those with peptic ulcers than in those without (0.38 +/- 0.08 vs. 0.69 +/- 0.08 ng/mg protein, p < 0.05).. Decreased salivary EGF bioactivity may contribute to peptic ulcer disease among maintenance HD patients.

Topics: Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Peptic Ulcer; Renal Dialysis; Risk Factors; Saliva

A large number of growth factors have been described and their action and interaction is proving to be complex. The presence study estimated the epidermal growth factor (EGF) in portal hypertension patients with chronic liver disease due to bilharziasis or viral infection as well as in patients with peptic ulcers. The results showed different statistical values regarding liver cirrhosis, oesophageal varices, and bleeding. No doubt, the EGF was indirectly stimulated by the schistosomal and/or viral infection.

Topics: Epidermal Growth Factor; Hepatitis, Viral, Human; Humans; Hypertension, Portal; Liver Cirrhosis; Peptic Ulcer; Radioimmunoassay; Schistosomiasis

Acute exposure to Helicobacter pylori causes cell damage and impairs the processes of cell migration and proliferation in cultured gastric mucosal cells in vitro. EGF-related growth factors play a major role in protecting gastric mucosa against injury, and are involved in the process of gastric mucosal healing. We therefore studied the acute effect of H. pylori on expression of EGF-related growth factors and the proliferative response to these factors in gastric mucosal cells (MKN 28) derived from gastric adenocarcinoma. Exposure of MKN 28 cells to H. pylori suspensions or broth culture filtrates upregulated mRNA expression of amphiregulin (AR) and heparin-binding EGF-like growth factor (HB-EGF), but not TGFalpha. This effect was specifically related to H. pylori since it was not observed with E. coli, and was independent of VacA, CagA, PicA, PicB, or ammonia. Moreover, H. pylori broth culture filtrates stimulated extracellular release of AR and HB-EGF protein by MKN 28 cells. AR and HB-EGF dose-dependently and significantly stimulated proliferation of MKN 28 cells in the absence of H. pylori filtrate, but had no effect in the presence of H. pylori broth culture filtrates. Inhibition of AR- or HB-EGF- induced stimulation of cell growth was not mediated by downregulation of the EGF receptor since EGF receptor protein levels, EGF binding affinity, number of specific binding sites for EGF, or HB-EGF- or AR-dependent tyrosine phosphorylation of the EGF receptor were not significantly altered by incubation with H. pylori broth culture filtrates. Increased expression of AR and HB-EGF were mediated by an H. pylori factor > 12 kD in size, whereas antiproliferative effects were mediated by both VacA and a factor < 12 kD in size. We conclude that H. pylori increases mucosal generation of EGF-related peptides, but in this acute experimental model, this event is not able to counteract the inhibitory effect of H. pylori on cell growth. The inhibitory effect of H. pylori on the reparative events mediated by EGF-related growth factors might play a role in the pathogenesis of H. pylori-induced gastroduodenal injury.

Topics: Adenocarcinoma; Amphiregulin; Cell Division; Cell Line; EGF Family of Proteins; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastritis; Glycoproteins; Growth Substances; Helicobacter Infections; Helicobacter pylori; Heparin; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Peptic Ulcer; Recombinant Proteins; RNA, Messenger; Stomach Neoplasms; Transforming Growth Factor alpha; Up-Regulation; Virulence

Topics: Costs and Cost Analysis; Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Peptic Ulcer; Recombinant Proteins

Helicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastric acid secretion, and is a powerful mitogen.. We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effects of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease.. GL-EGF was reduced in smokers compared to controls (p = .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p = .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p = .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p = .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU associated and non-ulcer-associated gastritis.. Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals and Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Epidermal Growth Factor; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastritis; Gastrointestinal Contents; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Peptic Ulcer; Smoking

Hyperplastic polyps are common benign lesions of uncertain histogenesis, which occur in the colon in populations at risk for colorectal carcinoma. They contain neutral/MUC1 gene-related mucin which in turn is closely associated with the trefoil-peptide pS2, a major component of the ulcer-associated cell lineage, previously termed pseudopyloric metaplasia. We have examined 17 hyperplastic polyps for expression of the trefoil-peptides pS2 and human spasmolytic polypeptide by in situ hybridization and immunohistochemistry, as well as by using antisera to epidermal growth factor/urogastrone and its receptor and to epitopes of the product of the MUC1 gene to characterize any further similarity between these lesions and the ulcer-associated cell lineage and thus help elucidate the nature of the lesions. Our investigations show both human spasmolytic polypeptide and pS2 messenger RNA within the polyps, whereas only pS2 peptide could be demonstrated immunohistochemically. Epidermal growth factor/urogastrone, its receptor, and antisera to the MUC1 gene also showed widespread staining of these polyps. We suggest that hyperplastic polyps are formed of a lineage that both synthesizes and secretes trefoil-peptides and the MUC1 mucin and that hyperplastic polyps may be related to the phenotypically similar ulceration-associated cell lineage.

Topics: Cell Line; Colonic Polyps; Epidermal Growth Factor; ErbB Receptors; Humans; Hyperplasia; Immunohistochemistry; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Membrane Glycoproteins; Mucin-1; Mucins; Muscle Proteins; Neoplasm Proteins; Neuropeptides; Peptic Ulcer; Peptides; Phenotype; Proteins; RNA, Messenger; Staining and Labeling; Tissue Distribution; Trefoil Factor-1; Trefoil Factor-2; Trefoil Factor-3; Tumor Suppressor Proteins

Duodenal biopsies obtained from seven normal subjects and six ulcerous patients were cultured in vitro for 30 min at 37 degrees C under various experimental conditions. Epidermal growth factor (EGF) and somatostatin released in the culture medium were determined by radioimmunoassay. Under basal conditions, EGF and somatostatin levels were significantly higher in normal subjects (11.49 +/- 3.07 ng/mg protein and 3.06 +/- 0.8 ng/mg protein, respectively) than in ulcerous patients (6.9 +/- 1.98 ng/mg protein and 1.75 +/- 1.23 ng/mg protein, respectively). However, when antibodies to somatostatin and vasoactive intestinal polypeptide (VIP) were added together to the culture media, in ulcerous patients, EGF levels also were lower as absolute values, but were higher as a percentage of variation than controls (p less than 0.05). The fall of EGF secretion from tissue cultures of ulcerous patients could be the consequence of endocrine cellular loss or damage, rather than the cause of ulceration. Moreover, the EGF-producing cells around the lesion in ulcerous patients seems to be hyperactive, and this hyperfunction of EGF-producing cells might contribute to the in vivo repair of tissue damage.

Topics: Adult; Antibodies; Biopsy; Culture Techniques; Epidermal Growth Factor; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Somatostatin; Vasoactive Intestinal Peptide

Recent animal studies suggest salivary epidermal growth factor (EGF) has a cytoprotective effect in the upper GI tract and is one of the important factors to promote the healing of experimental ulcer. The present study was undertaken to clarify the role of salivary EGF in peptic ulcer patients. Saliva samples were collected from 129 endoscopically normal subjects and 232 peptic ulcer patients. Salivary EGF concentration was measured by RIA. Salivary EGF output in normal subjects was 5.26 +/- 0.26 (ng/5 min) (mean +/- SE). Those in patients with gastric ulcer (GU), duodenal ulcer (DU) and gastroduodenal ulcer (GDU) were 10.74 +/- 0.15, 8.13 +/- 0.83 and 9.79 +/- 0.91. EGF output in GU and GDU patients were higher than that in normal subjects respectively. Tractable GU patients (healed within 3 months with regular regimen) had higher EGF output than intractable GU patients. Among tractable GU patients, those who had healing within 8 weeks had higher output. EGF output in patients with recurrent GU was lower than that in non-recurrent GU patients. In 10 GU patients, EGF output became higher in healing stage than in active stage. Salivary EGF may promote the healing and prevent the recurrence of human gastric ulcer.

Topics: Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Saliva

Sucralfate prevents the formation of acute gastric lesions induced by various ulcerogens and enhances the healing of chronic gastroduodenal ulcerations, but the mechanism of these effects has not been fully explained. This study was designed to determine the importance of intragastric pH in the sucralfate-induced gastroprotection against 100% ethanol, acidified aspirin, taurocholate, or stress, and in the healing of chronic gastroduodenal ulcerations induced by acetic acid. Sucralfate acidified to pH 2.0 showed significantly stronger protective activity against all four irritants, its protective potency against 100% ethanol being about eight times greater and the duration of the protection about four times longer than those obtained with sucralfate at its pH of 5.0. Pretreatment with indomethacin to suppress mucosal generation of prostaglandin or the removal of salivary glands to eliminate the endogenous source of epidermal growth factor failed to affect sucralfate-induced gastroprotection. In contrast, the rate of healing of chronic gastric ulcerations was significantly delayed by indomethacin or sialoadenectomy; but sucralfate enhanced the healing, and a marked inhibition of gastric acid secretion by ranitidine did not eliminate this enhancement. We conclude that the protective activity of sucralfate depends on the presence of acid milieu in the stomach, but that the ulcer-healing effects of this drug occur even after a marked inhibition of gastric acid secretion.

Topics: Animals; Chronic Disease; Combined Modality Therapy; Disease Models, Animal; Drug Therapy, Combination; Epidermal Growth Factor; Female; Gastric Acid; Gastric Mucosa; Hydrogen-Ion Concentration; Indomethacin; Male; Peptic Ulcer; Prostaglandins E; Ranitidine; Rats; Rats, Inbred Strains; Salivary Glands; Sucralfate; Wound Healing

Ulceration anywhere in the gastrointestinal tract induces a novel cell lineage, which grows from the bases of existing crypts, ramifies to form a new gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, and secretes abundant immunoreactive epidermal growth factor/urogastrone (EGF/URO). All gastrointestinal stem cells can produce this cell lineage following mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal ulceration, and we propose that a major in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut via induction of this cell lineage in the adjacent mucosa. EGF/URO should therefore be assessed in the conservative management of inflammatory bowel disease.

Topics: Crohn Disease; Epidermal Growth Factor; Gastric Mucosa; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Peptic Ulcer; Stem Cells; Wound Healing

The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.

Topics: Cell Line; Crohn Disease; Epidermal Growth Factor; Estrogens; Gastric Mucosa; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Intestine, Small; Mucins; Muscle Proteins; Neoplasm Proteins; Neuropeptides; Pancreatic Ducts; Pancreatitis; Peptic Ulcer; Peptide Biosynthesis; Peptides; Proteins; RNA, Messenger; Trefoil Factor-1; Trefoil Factor-2; Trefoil Factor-3; Tumor Suppressor Proteins

Epidermal growth factor, and its human homologue urogastrone (EGF/URO), are secreted by the gut-associated salivary and Brunner's glands. Recombinant EGF/URO is a powerful stimulator of cell proliferation and differentiation in the rodent and neonatal human intestine. But EGF/URO is not absorbed from the adult gut and has no action when given through the gut lumen; thus the role of secreted EGF/URO is unknown. We now report that ulceration of the epithelium anywhere in the human gastrointestinal tract induces the development of a novel cell lineage from gastrointestinal stem cells. This lineage initially appears as a bud from the base of intestinal crypts, adjacent to the ulcer, and grows locally as a tubule, ramifying to form a new small gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, is nonproliferative, and contains and secretes abundant immunoreactive EGF/URO. We propose that all gastrointestinal stem cells can produce this cell lineage after mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal mucosal ulceration, and we conclude that a principal in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut through induction of this cell lineage in the adjacent mucosa.

Topics: Crohn Disease; Epidermal Growth Factor; Histocytochemistry; Humans; Intestinal Mucosa; Metaplasia; Mucins; Peptic Ulcer

Epidermal growth factor inhibits gastric acid secretion and has a cytoprotective effect on the upper gastrointestinal tract. This study was undertaken to determine whether patients with endoscopically proven active peptic ulcer disease have a salivary deficiency of human epidermal growth factor (hEGF), compared to patients with a normal esophagogastroduodenoscopy (EGD). Saliva was collected from fasting subjects prior to EGD. The levels of EGF were measured by radioimmunoassay. Statistical evaluation was performed by analysis of variant followed by Student's t test. The concentrations of the peptide were lower in patients with active peptic ulcer disease (3.1 +/- 0.54 ng/ml, mean +/- SE, n = 25) compared with normal subjects (4.9 +/- 0.56 ng/ml, n = 58, p less than 0.03). No significant differences in salivary hEGF were noted between patients with a normal EGD and patients with gastritis (3.85 +/- .86 ng/ml, n = 13), esophagitis (4.5 +/- 1.3 ng/ml, n = 7), or Barrett's esophagus (5.3 +/- 1.5 ng/ml, n = 6). There were no differences in the salivary levels of hEGF between males and females, or between smokers and nonsmokers. There was no correlation of hEGF levels with age. The pathophysiologic significance of this finding is uncertain. Lower salivary hEGF may reduce one of the defensive mechanisms responsible for protecting the gastroduodenal mucosa from injury by physicochemical agents, thus contributing to ulcer development.

Topics: Analysis of Variance; Duodenoscopy; Epidermal Growth Factor; Esophageal Diseases; Esophagoscopy; Female; Gastritis; Gastroscopy; Humans; Male; Peptic Ulcer; Radioimmunoassay; Saliva

Antacids show gastroprotective action against various irritants in experimental animals and enhance the healing of chronic gastroduodenal ulcers in humans but the mechanisms of these effects are unknown. The present study was designed to determine whether prostaglandin (PG) and epidermal growth factor (EGF), which also have protective and antiulcer properties, contribute to the action of antacids on rat's stomach. It was found that Maalox 70 and its active component, Al(OH)3, enhance significantly the healing of chronic gastric and duodenal ulcers observed during 7 and 14 days after their induction. Pretreatment with indomethacin caused a significant prolongation of ulcer healing, and this was accompanied by a significant reduction in PG and EGF formation, suggesting that both factors may be involved in ulcer healing. Maalox and Al(OH)3 failed to prevent the suppression of PG by indomethacin but were equally effective in ulcer healing in rats without and with indomethacin administration, suggesting that endogenous PG may not play any important role in the healing process by these drugs. Removal of salivary glands, the major source of EGF, also prolonged ulcer healing but, again, Maalox was as effective in ulcer healing as in rats with intact salivary glands. Our findings that Maalox at pH above 3.0 binds significant amounts of EGF, enhances the binding of EGF to the ulcer area, and stimulates mucosal growth, suggest that EGF may be involved in ulcer healing; however, because antacids are also effective after sialoadenectomy, EGF does not seem to be the major factor in ulcer healing by these drugs.

Topics: Aluminum Hydroxide; Animals; Antacids; Drug Combinations; Epidermal Growth Factor; Hydrogen-Ion Concentration; Indomethacin; Magnesium; Magnesium Hydroxide; Peptic Ulcer; Prostaglandins; Rats; Time Factors; Wound Healing

Sucralfate exhibits gastroprotective properties in laboratory animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether or not epidermal growth factor (EGF), which also has gastroprotective and ulcer-healing properties, contributes to the action of sucralfate in rat stomach. It was confirmed that sucralfate, like 16,16-dimethyl prostaglandin E2, protects the gastric mucosa against ethanol damage and increases mucosal generation of prostaglandins. Removal of the endogenous source of EGF (sialoadenectomy) did not abolish the protective and prostaglandin-stimulating effects of sucralfate. Exogenous EGF and 16,16-dimethyl prostaglandin E2 were also protective in rats with intact and removed salivary glands. Sucralfate, like EGF, enhanced the healing of chronic gastric and duodenal ulcerations induced by serosal application of acetic acid. Sucralfate was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer areas. Thus, the peptide is available locally in high concentrations to accelerate tissue repair and the healing process in ulcerated mucosa. The ulcer-healing effects of sucralfate were reduced with sialoadenectomy and partially restored with oral administration of EGF. It was concluded that EGF is not essential for the gastroprotection induced by sucralfate, but seems to play an important role in the ulcer-healing action of this drug.

Topics: 16,16-Dimethylprostaglandin E2; Acetates; Acetic Acid; Acute Disease; Animals; Chronic Disease; Dinoprostone; Epidermal Growth Factor; Ethanol; Gastric Mucosa; Male; Peptic Ulcer; Rats; Rats, Inbred Strains; Submandibular Gland; Sucralfate; Wound Healing

Although modern medicine therapy reliably heals peptic ulcers, relapse is the rule and remains a major challenge to investigators and practitioners alike. Several factors associated with ulcer recurrence have been identified but pathogenetic mechanisms are obscure. Some recent studies suggest that the type of treatment used to heal the initial ulcer influences the propensity to recurrence. Although there is circumstantial evidence that relapse may be accelerated after initial treatment with H2-receptor antagonists, overall it appears that differences in recurrence rates are more likely due to the influence of colloidal bismuth subcitrate in reducing recurrence rates. Several mucosal abnormalities have been identified in patients with peptic ulcer disease in remission. These include defective gastric mucus, reduced duodenal bicarbonate secretion and altered synthesis of certain prostaglandins, particularly of the E series. Decreased salivary secretion of epidermal growth factor and gastric Campylobacter pylori infections have also received much attention recently. It is postulated that the cause of recurrent ulceration, like that of initial ulceration, is multifactorial, and that local factors caused by the initial ulcer may contribute to the propensity of recurrence.

Topics: Bicarbonates; Epidermal Growth Factor; Gastric Mucosa; Humans; Mucus; Peptic Ulcer; Prostaglandins; Recurrence; Smoking

Growth hormone-releasing factor (GRF) was reported to possess the growth-promoting action on the gastroduodenal mucosa that can be augmented by removal of endogenous somatostatin. Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats. GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA. GRF also significantly increased serum gastrin levels and the tissue contents of epidermal growth factor (EGF) in salivary glands, duodenum and pancreas, suggesting that both gastrin and EGF could contribute to mucosal trophic and ulcer healing effects of GRF. Somatostatin (100 micrograms/kg/day for 7 days) abolished almost completely the ulcer healing and mucosal growth-promoting effects of GRF and this was accompanied by the reduction in serum gastrin level and the tissue contents of EGF suggesting that the suppression of gastrin and EGF release could contribute to the observed effects of somatostatin. We conclude that GRF has both the ulcer healing and the mucosal trophic actions which can be antagonized by somatostatin and that gastrin and EGF may be implicated in these actions.

Topics: Acetates; Acetic Acid; Animals; Epidermal Growth Factor; Gastric Mucosa; Gastrins; Growth Hormone-Releasing Hormone; Intestinal Mucosa; Male; Peptic Ulcer; Rats; Somatostatin; Wound Healing

Solcoseryl, a deproteinized extract of calf blood, and EGF, produced by salivary glands, have been shown to enhance the healing of peptic ulcerations, but the mechanism of this effect is unknown. Since both solcoseryl and EGF have been reported to stimulate cell proliferation, we designed the study to compare the ulcer healing and growth promoting actions of these two agents in the same animals. Gastric and duodenal ulcerations were produced by serosal application of 100% acetic acid on an area of 13.8 mm2 of gastric and duodenal wall, respectively. In the control animals, 7 days after ulcer induction, the mean ulcer area was reduced to 7.1 +/- 1.2 mm2 in the stomach, and to 6.1 +/- 0.8 mm2 in the duodenum. After 14 days all ulcers were healed, both in the stomach and duodenum. Oral administration of solcoseryl (10 ml/kg-day) or EGF (30 micrograms/kg-day) for 7 days after ulcer induction resulted in a significant reduction in the ulcer area in the stomach, and to a greater extent in the duodenum. This enhancement of ulcer healing by solcoseryl was accompanied by a significant increase in the weight of the duodenal mucosa and the total contents of DNA and RNA after 7 days of treatment, and in the weight and nucleic acid contents in both the gastric and duodenal mucosa after 14 days of treatment. EGF also increased the weights and the nucleic acid contents in gastric and duodenal mucosa, but this was significant only after 14 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actihaemyl; Animals; Epidermal Growth Factor; Female; Gastric Mucosa; Intestinal Mucosa; Male; Peptic Ulcer; Rats; Rats, Inbred Strains; Tissue Extracts; Wound Healing

Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Anti-Ulcer Agents; Bismuth; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Male; Organometallic Compounds; Peptic Ulcer; Rats; Rats, Inbred Strains; Submandibular Gland

EGF is reported to have a potent protective effect on peptic ulcer formation in rats. In this study, we measured the IR-hEGF concentrations in the saliva of normal human subjects and patients with peptic ulcer disease or non-peptic ulcer gastroduodenal disease. In normal subjects, the level of salivary IR-hEGF was highest in the early morning, and the values in individuals on different days showed small variations. There were no sex differences or age-related changes in the salivary IR-hEGF levels. The concentrations of the peptide were lower in patients in the active (0.96 +/- 26 ng/ml, mean +/- SE, n = 4) and healing stages (1.06 +/- 0.24 ng/ml, n = 8) of peptic ulcer disease as compared with those in normal subjects (3.19 +/- 0.46 ng/ml, n = 47). No significant differences in salivary IR-hEGF levels were observed between normal subjects and patients in the scaring stage of peptic ulcer disease (2.40 +/- 0.42 ng/ml, n = 21), or those with gastric cancer (2.44 +/- 0.27 ng/ml, n = 21) and atrophic or superficial gastritis (2.31 +/- 0.34 ng/ml, n = 28). Although the pathophysiological significance of these lower salivary IR-hEGF levels in patients with peptic ulcer disease is unclear, it is possible that the low level of hEGF in saliva may decrease the resistance of the mucosa to physicochemical stress, and thus participate in the development of the diseases.

Topics: Circadian Rhythm; Epidermal Growth Factor; Female; Gastritis; Humans; Male; Peptic Ulcer; Radioimmunoassay; Saliva; Stomach Neoplasms

This study was designed to test the effects of pentagastrin and epidermal growth factor (EGF) on stress-induced ulceration and on the antral content of gastrin and somatostatin (SLI) in rats. Four groups of 14 to 15 rats had been prepared for 7 days by one of the following methods: saline injection (control); injection of pentagastrin (250 micrograms/kg, 3 times/day); injection of EGF (10 micrograms/kg, 3 times/day); or injection of EGF plus pentagastrin. At the end of the treatment period, half of each group of rats were sacrificed (nonstress group). There were no ulcers in the nonstress control groups of rats. Stress was applied by water immersion in the remaining half of the rats. The injections of pentagastrin and/or EGF resulted in substantial increase in antral content of SLI. After 20 hours of stress, the ulcer index was 40.5 +/- 3.3 in the controls, compared to 6.4 +/- 1.2 and 16.2 +/- 2.3 in rats that received pentagastrin or EGF, respectively. Injections of both pentagastrin and EGF resulted in an ulcer index of 26.2 +/- 2.0, which was significantly lower than that in controls, but higher than that in rats treated with either peptide alone. The stress resulted in significant decrease in antral SLI in all groups of rats, whereas SLI content in rats treated with pentagastrin and/or EGF remained significantly higher than that of controls. Antral content of gastrin did not differ significantly in the four groups tested. The ulcer index was inversely correlated with antral SLI content. We confirm and extend previous observations that pentagastrin and EGF prevent stress ulcer formation, and suggest that endogenous SLI may account, at least in part, for their antiulcer activity.

Topics: Animals; Epidermal Growth Factor; Gastrins; Immersion; Male; Pentagastrin; Peptic Ulcer; Radioimmunoassay; Rats; Rats, Inbred Strains; Somatostatin; Stomach; Stress, Physiological

Topics: Epidermal Growth Factor; Gastric Juice; Gastrointestinal Hormones; Humans; Peptic Ulcer

Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +/- 3.0 and 52.0 +/- 3.5 (mean +/- SE) micrograms/total vol, or 29.7 +/- 1.1 and 39.8 +/- 1.7 micrograms/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +/- 2.7 micrograms/g creatinine; P less than 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and beta-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +/- 2.6 micrograms/g creatinine) than normal men, but this was not significant (P greater than 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

Topics: Adult; Aged; Circadian Rhythm; Contraceptives, Oral; Cross Reactions; Eating; Epidermal Growth Factor; Female; Gastrointestinal Diseases; Humans; Immune Sera; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Reference Values; Skin Diseases

Topics: Alkalies; EGF Family of Proteins; Epidermal Growth Factor; Gastrointestinal Hormones; Nutrition Therapy; Peptic Ulcer; Ulcer; Vitamin U; Vitamins

Topics: EGF Family of Proteins; Epidermal Growth Factor; Humans; Peptic Ulcer

Topics: EGF Family of Proteins; Epidermal Growth Factor; Humans; Peptic Ulcer; Ulcer

Topics: Carboxylic Acids; Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Peptic Ulcer; Peptides; Quinolines; Stomach Ulcer

Topics: EGF Family of Proteins; Epidermal Growth Factor; Humans; Peptic Ulcer

Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Peptic Ulcer; Peptides

Topics: EGF Family of Proteins; Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Peptic Ulcer; Peptides

Topics: Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Mucous Membrane; Peptic Ulcer; Peptides

Topics: Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Intestines; Peptic Ulcer; Peptides; Research; Stomach