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)

Ornithine decarboxylase (ODC) activity has been associated with mucosal growth and injury, yet, little information is available on ODC activity during gastric ulcer healing. We measured ODC activity in the ulcer base submucosa and the surrounding mucosa at 1 cm and 2 cm and assessed ulcer surface healing and a histologic score in experimentally induced ulcers (Quinton ulcer-maker) at 0 and 5 hr and at one, two, three, four, and seven days. A total of 26 dogs were studied, eight of which received 2% difluoromethylornithine (DFMO, a specific inhibitor of ODC) in drinking water. Ulcer healing was assessed by digitizing initial (plug size), and final ulcer surface area and was expressed as percent ulcer surface reduction. A histologic score was assessed by two independent pathologists unaware of the treatment. ODC induction was observed in the submucosa of the ulcer base but not in the surrounding mucosa. The baseline submucosal ODC activity was measured at 0.2 +/- 0.1 pmol (14CO2)/mg protein/hr, and at one day the ODC activity increased to 4.0 +/- 0.7, at three days to 15.2 +/- 5.5, and at seven days to 2.6 +/- 1.0 (P less than 0.001). DFMO treatment delayed GU healing significantly up to three days, but no difference was noted at seven days. The assessed histologic parameters did not correlate with ODC activity, and DFMO treatment did not alter the histologic score. These data suggest that polyamine biosynthesis occurs in the ulcer base submucosa during the first seven days of experimentally placed gastric ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ornithine decarboxylase activity during gastric ulcer healing in dogs. 161 50

It has been reported that an extract from Angelica sinensis mainly consisting of polysaccharides (95%) prevented ethanol- or indomethacin-induced gastric mucosal damage (Cho CH et al. Planta Med 2000;66:348-51). However, it is not known whether Angelica sinensis has a direct stimulatory effect on the healing of gastric mucosal lesions. To study the hypothesis that Angelica sinensis has a direct mucosal healing effect in rats and in isolated gastric epithelial cells, we assessed the wound repair in both animals and normal cell culture (RGM-1), as well as [3H]thymidine incorporation, ornithine decarboxylase (ODC) activity, and ODC protein and c-Myc protein expression after different treatments in RGM-1 cells. We found that Angelica sinensis crude extract (ASCE) dose-dependently enhanced gastric ulcer healing in rats and promoted wound repair in RGM-1 cells. It also significantly stimulated [3H]thymidine incorporation and ODC activity in RGM-1 cells in a concentration-dependent manner. ODC and c-Myc protein expression was also increased as a result of this process. DL-alpha-difluoromethyl-ornithine repressed the [3H]thymidine incorporation and ODC activity induced by ASCE. Pretreatment with c-Myc antisense oligodeoxynucleotides blocked the stimulatory action of ASCE on [3H]thymidine incorporation and ODC protein expression. These data suggest that ASCE has a direct mucosal healing effect on gastric epithelial cells, while ODC and c-Myc are closely associated with this effect.
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PMID:A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line. 1133 Oct 80

The association between cigarette smoking and peptic ulcer diseases has been well established. Ornithine decarboxylase (ODC) is crucial for the gastroprotective and mucosal growth promoting effects in gastric ulcer healing. The aim of this study is to elucidate the possible mechanism of how inhibition of ODC activity is involved in the delay of ulcer healing, if any, by cigarette smoke extracts (CSE). CSE were fractionated into chloroform extract (CE) and ethanol extract (EE). In in vivo study, rats with acetic acid-induced ulcers were given CE or EE intragastrically (2.5 or 5 mg/kg) once daily for 3 days. Ulcer sizes were significantly larger after CE or EE administration, followed by an increase in myeloperoxidase activity and a reduction in cell proliferation. However, both CSE stimulated the number of microvessels following the increase of basic fibroblast growth factor. In in vitro studies, the effect of CE or EE (10, 40, or 100 microg/ml) on cell migration and cell proliferation were measured using an in vitro wound model and [(3)H]-thymidine incorporation assay, respectively. Both CSE delayed cell migration and decreased cell proliferation, which were accompanied with a reduction in ODC activity. Exogenous spermidine (5 or 10 microM) could reverse the inhibitory action on cell proliferation and ODC activity induced by CSE. In conclusion, both CSE significantly delayed ulcer healing as a result of reduction in cell proliferation and cell migration. All these effects are, in part, related to the reduction of polyamine synthesis.
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PMID:Cigarette smoke extracts delay wound healing in the stomach: involvement of polyamine synthesis. 1181 75

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.
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PMID:Smoking and the pathogenesis of gastroduodenal ulcer--recent mechanistic update. 1461 84

Probiotics are widely used as functional foods which have been advocated for the maintenance of gastrointestinal microflora equilibrium and treatment of gastrointestinal disorders. However, studying the role of probiotics in peptic ulcer disease is limited. The aim of the present study is to investigate the effect of a probiotic strain Lactobacillus rhamnosus GG on gastric ulcer and to elucidate the mechanisms involved. Gastric kissing ulcers were induced in rats by acetic acid (60% v/v). L. rhamnosus GG was given intragastrically at 10(8) cfu/day or 10(9) cfu/day for three consecutive days after ulcer induction. L. rhamnosus GG successfully colonized in the gastric mucosa especially at the ulcer margin. It also significantly and dose-dependently reduced gastric ulcer area. Cell apoptosis to cell proliferation ratio was strongly decreased and accompanied by significant up-regulation of ornithine decarboxylase (ODC) and B-cell lymphoma 2 (Bcl-2) protein expression at the ulcer margin. Angiogenesis was also significantly stimulated together with the induction of vascular endothelial growth factor (VEGF) expression. Furthermore, L. rhamnosus GG up-regulated the phosphorylation level of epidermal growth factor receptor (EGF receptor) without altering the total EGF receptor expression. These findings suggested that L. rhamnosus GG enhanced gastric ulcer healing via the attenuation of cell apoptosis to cell proliferation ratio and increase in angiogenesis. Regulators of these processes such as ODC, Bcl-2, VEGF and EGF receptor are likely to be involved in the healing action of L. rhamnosus GG for gastric ulcer.
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PMID:Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats. 1739 75