Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Clin Sci Mol Med 1977 Mar
PMID:Concentrations of prostaglandin A-, E- and F-like substances in gastric mucosa of normal subjects and of patients with various gastric diseases. 84 56

Helicobacter pylori has been implicated in the genesis of human gastritis, dyspepsia, and peptic ulcers. However, its influence in the quality of experimental gastric ulcer healing has not been previously investigated. Standardized gastric fundic ulcers were produced in 50 male Sprague-Dawley rats (150-200 g) by a 4 mm in diameter focal, serosal application of 100% acetic acid. Thirty rats were administered 2 ml H. pylori suspension (urease producing, ATCC 43504) in normal saline (10(8) CFU/ml) 2x/day for 7 days. Twenty rats (controls) received 2 ml normal saline 2x/day for 7 days. Gastric ulcer surface area was measured under a dissecting microscope and mucosal specimens were obtained for qualitative and quantitative histology. No gross or microscopic duodenal abnormalities were identified at sacrifice. Ninety percent of control rats showed grossly and microscopically entirely healed ulcers. The remaining 10% showed partially reepithelialized ulcers (area, 0.78 to 1.77 mm2; mean, 1.27 +/- 0.7 mm2). The grossly "healed" mucosa demonstrated marked dilatation of gastric glands lined with mature surface epithelial cells. Parietal cells were scanty (5-10% of all cells). One hundred percent of the H. pylori-exposed rats showed persistence of chronic active ulcers (area, 1.76 to 19.63 mm2; mean, 8.95 +/- 6.15 mm2). The ulcer beds were infiltrated by acute and chronic inflammatory cells, abundant fibroblasts, and capillary networks. The raised ulcer borders were characterized by dilated glands lined by mature surface epithelial cells. Various special stains demonstrated the presence of H. pylori in the surface mucus and within the crypts.(ABSTRACT TRUNCATED AT 250 WORDS)
Exp Mol Pathol 1991 Dec
PMID:Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model. 174 15

Gastric mucosa obtained from the body and pyloric portions of the human stomach were observed by light and transmission electron microscopy. Ciliated cells were found in two of 18 subjects examined, one patient with gastric ulcer and the other one with gastric adenocarcinoma. The ciliated cells were found in epithelia at sites away from the main lesions. The tissues containing ciliated cells showed intestinal metaplasia combined with mild chronic gastritis in both cases. The epithelial layer facing the gastric lumen was composed of columnar cells with numerous uniform microvilli and goblet cells. This epithelium extended to the superficial parts of the tubules surrounded by the lamina propria. The deeper portions of the tubules were composed of mucous secretory, endocrine, and rarely ciliated cells. These ciliated cells were provided with numerous cilia the numbers of which varied considerably from cell to cell. This was in contrast to the primary cilium which is usually single. The central part of the apical cell membrane was sometimes concave in the area from where cilia tended to arise. It was also observed that numerous basal bodies as well as mucus-like granules were contained in the same cell. The axonemal pattern was different from that of ordinary cilia and showed 9 + 0 and 8 + 1 patterns. In longitudinal sections it was found that one peripheral doublet was displaced to the center of the axoneme as it left the basal body.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:The fine structure of atypical ciliated cells in the human gastric epithelium. 287 43

To clarify the role of glutathione (GSH), an antioxidative substance, and its association with the gastric mucosal defense mechanism, we examined the gastric mucosal GSH and GSH-dependent enzymes in gastric ulcer patients. The subjects of this study were 10 patients with active ulcer on the lesser curvature side in the lower part of the gastric body and 11 normal controls. At the time of gastric endoscopy, gastric mucosal specimens were obtained by routine forceps biopsy from a site several millimeters apart from the ulcer margin, and these specimens were used for measurement of GSH, glutathione peroxidase (GSH-Px), glutathione-S transferase (GST) and gamma-glutamyl transpeptidase (gamma-GTP). The GSH level and the GSH-Px and GST activities in the patients with gastric ulcer were lower than those in the control group. The GSH-Px activity at the healed stage after treatment was increased compared with the pre-treatment value, while the GSH level was not markedly increased and the GST and gamma-GTP activities were similar to the pre-treatment value. The GSH level and GSH-Px activity remained decreased in the non-responder group. These results suggest that gastric mucosal GSH and GSH-dependent enzymes are closely related to the etiology and course of gastric ulcer.
Res Commun Mol Pathol Pharmacol 1995 May
PMID:Changes in glutathione in gastric mucosa of gastric ulcer patients. 767 Aug 48

To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms.
Cell Mol Biol (Noisy-le-grand) 1995 Feb
PMID:Uptake site of lansoprazole, a proton pump inhibitor, in human fundic mucosa: possible relevance with fibroblast and Helicobacter pylori. 777 26

Glycine, a neutral amino acid has been studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without glycine treatment. Experimental gastric lesions were induced by hypothermic-restraint stress, indomethacin and necrotizing agents including 80% ethanol, 0.2 M sodium hydroxide and 0.6 M hydrochloric acid in rats. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that glycine dose dependently reduced the gastric secretions in rats. Pretreatment with glycine significantly protected animals against stress-, indomethacin- and necrotizing agents induced gastric lesions. The antiulcer activity of glycine was associated with significant inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. In conclusion, this study demonstrates that glycine possesses significant antiulcer and cytoprotective activity. However, further detailed studies are warranted to establish the mechanism(s) of action, and to determine its role in the prophylaxis and treatment of gastric ulcer disease.
Res Commun Mol Pathol Pharmacol 1997 Aug
PMID:Studies on the antisecretory, gastric anti-ulcer and cytoprotective properties of glycine. 934 31

The biosynthesis of sulfated mucin in gastric tissue was investigated in cold-stress and indomethacin (CSI)-induced gastric ulcer models. To examine the synthesis of gastric sulfated mucin, [35S]H2SO4 (sulfate) incorporation into gastric mucin was measured. The treatment of CSI inhibited the incorporation of [35S]sulfate after 2 hr. The gastric acid hypersecretion or the formation of severe ulcer was observed at 1 or 4 hr after the CSI-treatment, respectively. Pibutidine hydrochloride (IT-066), a novel H2-receptor antagonist, (0.3 mg/kg, s.c.) inhibited the formation of ulcer and reversed the inhibition of mucin sulfation by the CSI-treatment, whereas atropine sulfate, a muscarinic receptor antagonist, (1.0 mg/kg, s.c.) did not inhibit the development of ulcer nor decrease in the mucin sulfation at 6 hr after the CSI-treatment. IT-066 inhibited the total acid output (T.A.O.) due to the reduction of the acidity in the gastric juice, whereas atropine inhibited the T.A.O. due to that of the volume. These results indicated that a different mode of action between IT-066 and atropine on gastric acid secretion influences their actions in the incorporation of [35S]sulfate and the formation of ulcer in the CSI-treated rat. Therefore, it is considered that the reduction of biosynthesis of gastric sulfated mucin following acid hypersecretion may be responsible for the formation of gastric ulcer.
Res Commun Mol Pathol Pharmacol 1997 Nov
PMID:Effect of cold-stress and indomethacin on the biosynthesis of gastric sulfated mucin in rats. 946 26

This study investigates the effects of epidermal growth factor (EGF), urogastrone (UG) and transforming growth factor-alpha (TGFalpha) and its derivative on dimaprit- and pentagastrin-induced gastric acid secretion and on acidified ethanol (AE)-evoked ulcer formation in anaesthetized rats. EGF, TGFalpha and UG administered subcutaneously (s.c.) 30 min before dimaprit inhibited gastric acid secretion. Against pentagastrin-stimulated secretion, TGFalpha inhibited, while EGF and UG potentiated, acid secretion dose-dependently. Intraduodenal (i.d.) administration of TGFalpha and UG had no effect, while EGF potentiated, both secretagogue-induced acid secretion in the same dosage schedule. Administration of either EGF, UG or TGFalpha i.v. bolus, in response to continuous infusion of dimaprit resulted in a significant (p < 0.05-p < 0.001) inhibition of acid secretion which was transient and returned to normal within 30-45 min for UG while it slowly returned to normal for EGF and TGFalpha. The truncated form of TGFa (amino acids 34-43) did not show any antisecretory effect when administered parenterally. Acidified ethanol produced gastric haemorrhagic lesions in the rat 1 h after oral administration. The gastric mucosal protective effects of TGFalpha, EGF and UG administered either orally or s.c. 30 min before the administration of AE were dose-dependent against this model of ulcer induction. Indomethacin (Indo), administered 15 min before AE to inhibit prostanoids biosynthesis, significantly (p < 0.001) reduced the cytoprotective effects of TGFalpha, EGF and UG and aggravated the ulcer index when administered s.c. The results show that PGs may be involved in mediating the protective effects of the three growth factors. Administration of NG-nitro-L argininemethylester (L-NAME) 15 min prior to TGFa, EGF and UG s.c. or orally, significantly (p < 0.001) decreased the degree of ulcer indices and was able to reduce the protective effects of TGFalpha, EGF and UG, thus including the role of NO in mediating the protective effects of these growth factors. In conclusion, these results have demonstrated that EGF, UG and TGFalpha have a short and reversible inhibitory effect on dimaprit-stimulated gastric acid secretion and each is effective parenterally but not orally. UG and EGF potentiated, while, TGFa inhibited pentagastrin-stimulated acid secretion. In addition, TGFalpha seems to lose its activity when it is truncated from the C terminus. The present study also suggests that EGF, UG and TGFalpha are equally effective against AE-induced gastric ulcer and bring about their cytoprotective action through their reduction of acid secretion and through PG and NO pathways.
Mol Cell Biochem 2002 Jul
PMID:Comparison of the antisecretory and antiulcer activity of epidermal growth factor, urogastrone and transforming growth factor alpha and its derivative in rodents in vivo. 1219 Jan 25

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 decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.
Mol Cell Biochem 2003 Nov
PMID:Smoking and the pathogenesis of gastroduodenal ulcer--recent mechanistic update. 1461 84

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
Mol Pharmacol 2004 Dec
PMID:Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. 1545 96


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