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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by beta-methasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.
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PMID:[Irritative activity of antiinflammatory agents, betamethasone 17-valerate, beclomethasone 17, 21-dipropionate, betamethasone 17, 21-dipropionate, or indomethacin on the gastrointestinal tract in rats and dogs (author's transl)]. 71 Oct 34

The effects of aspirin, salicylate formulations and substitutes, smoking (nicotine), indomethacin, corticosteroids, phenylbutazone, ethanol, caffeine and reserpine on the gastric mucosa are discussed. The damaging effects of the drugs are considered in terms of the gastric mucosal barrier, gastric erosions, microbleeding and haematemesis and melaena and finally whether they cause peptic ulcer. There is suggestive evidence that unbuffered aspirin is a cause of haematemesis and melaena and of gastric ulcer but the incidence rates for hospital admission are low, being 10 to 15 per 100,000 heavy users per year. Aspirin in solution as acetylsalicylate buffered to maintain a neutral pH protects against gastric damage. Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated. Smoking is definitely associated with peptic ucler but the mechanism is unknown. Corticosteroids are probably not ulcerogenic despite clinical bias that they are. Indomethacin and phenylbutazone may be ulcerogenic but there is insufficient evidence to make firm judgements. Ethanol, caffeine and reserpine, on available evidence, are probably not ulcerogenic.
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PMID:Drugs and gastric damage. 126 29

We studied the upper gastrointestinal (GI) tract lesions by endoscopy, and evaluated the relationship between the lesions and clinical characteristics in 154 patients with rheumatoid arthritis (RA). Eighty-six (55.8%) had drug-induced ulcers and/or erosions, which were present mostly at the antrum as multiple lesions. A history of gastric ulcer, positive tests for fecal occult blood and progression of anemia were noticed more frequently in the patients with gastric ulcers and/or erosions, compared to those with normal mucosa. Indomethacin and prednisolone (15mg/day) were also used more frequently in the patients with gastric ulcers. Twelve patients showed amyloid depositions in the gastric mucosa, of which 8 patients had gastric ulcers and/or erosions. These results indicate that the incidence of GI tract lesions is significantly high in RA patients and that the endoscopic examination should be performed during the course of RA treatment.
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PMID:[Upper gastrointestinal tract lesions in rheumatoid arthritis]. 194 53

The effects of dopamine (DA) agonists and antagonists were investigated on indomethacin--and restraint stress (6 hr at RT)--induced gastric ulcer formation in rats. The DA-agonists, apomorphine and bromocryptine (both at 5 mg/kg) significantly attenuated the frequency and severity of gastric mucosal lesions in both experimental models. The DA-antagonist, haloperidol (0.05 and 1.0 mg/kg) aggravated the gastric ulcerogenesis of both indomethacin and stress, the effects with the lower dose being statistically significant. Haloperidol (0.05 mg/kg) also prevented the cytoprotective effects of apomorphine on indomethacin-ulcers. The atypical DA-antagonist, sulpiride (10 and 50 mg/kg), however, showed differential dose- and model-specific effects. Whereas, the lower dose attenuated indomethacin-ulcers, the higher dose (50 mg/kg) tended to aggravate this phenomenon. The trend of results were reversed in the restraint stress model. Indomethacin (1 mg/kg) aggravated stress-ulcers, an effect which was also appreciably neutralised by apomorphine (5 mg/kg) pretreatment. These results are discussed in light of possible prostaglandin-DA interactions during such experimental gastric pathology.
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PMID:Possible prostaglandin-dopamine interactions during experimental gastric ulcer formation. 197 10

The possible role of sulfhydryls in indomethacin-induced gastric mucosal injury was studied. No significant decrease of the contents of both non-protein and protein-binding sulfhydryls was observed in the gastric mucosa during injury. Indomethacin-induced gastric ulcer was inhibited by cysteamine of 132 and 264 mumol, i.g. or of 132 mumol, s.c. by 82%, 92% and 75% respectively. Such protective effect was not observed with cysteine in equal molar dose. Subcutaneously injected cysteamine (132 mumol) inhibited gastric acid secretion by 46% in indomethacin-treated rats, while no effect was observed on acid secretion when cysteamine was given intragastrically. Cysteamine, given through both routes, did not affect gastric barrier mucus secretion. It is suggested that sulfhydryls in gastric mucosa are not involved in the mechanism of indomethacin-induced injury and that the potent cytoprotective effect of cysteamine against indomethacin-induced ulcer maybe not caused by its sulfhydryl group.
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PMID:[The role of sulfhydryls in indomethacin-induced gastric mucosal injury in rats]. 260 58

The effect of nonsteroidal antiinflammatory drugs (NSAIDs) on duodenal mucosa was assessed both retrospectively and prospectively. In 444 patients with duodenal ulcer, the incidence of upper gastrointestinal bleeding was five times higher in 56 patients who were treated with NSAIDs than in those who did not receive NSAIDs. Indomethacin and naproxen had the most potent damaging effects. In a control group of patients with gastric ulcer, nine out of 134 had taken NSAIDs. The incidence of bleeding in these patients was three times higher than in those who were not on NSAIDs. The effect of indomethacin, 150 mg/day, on the upper gastrointestinal tract was examined in a prospective study of 75 patients with acute musculoskeletal disorders. Endoscopy after 1 week of therapy showed that 45% had mucosal damage in the duodenum, and this was as frequent and as severe as the gastric mucosal damage. In most instances, the duodenal damage was erosive duodenitis.
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PMID:Duodenal mucosal injury with nonsteroidal antiinflammatory drugs. 349 47

Indomethacin produces gastric corpus erosions in the fasted rat and small intestinal ulcers in the conventionally fed rat. We found that in rats fed chow pellets for 1 h after a 24-h fast, indomethacin given within 2 h after refeeding produced lesions in the gastric antrum, primarily along the lesser curvature, and also in the small intestine. The antral lesions reached a maximum size in 6-10 h, penetrated the muscularis mucosae within 3 days, and did not diminish for at least 7 days. The formation of the antral ulcer was prevented by prostaglandins or adrenalectomy, but was not affected by cimetidine, atropine, and/or vagotomy. In contrast, the gastric corpus erosions produced by indomethacin in the fasted rat were prevented by antisecretory drugs or vagotomy, and were aggravated by adrenalectomy. It is concluded that: (a) the chronic antral ulcers produced by indomethacin in a refed rat mimic human gastric ulcer with regard to location and histology; and (b) the mechanism of antral ulcer formation is different from corpus erosion formation, in that it was resistant to antisecretory drugs and vagotomy and was prevented by adrenalectomy. This experimental ulcer model could prove useful for studies of the etiology and therapy of gastric ulcer disease.
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PMID:Indomethacin produces gastric antral ulcers in the refed rat. 726 16

Nonsteriodal antiinflammatory drugs initiate gastric ulceration and delay gastric ulcer healing. This study aimed to investigate the role of epithelial cell proliferation in delayed ulcer healing and to identify the most reproducible technique for measuring cell proliferation. Rats with acetic acid-induced gastric ulcers were treated for two weeks with indomethacin (1 mg/kg), aspirin (200 mg/kg), or vehicle control. Ulcers were assessed by macroscopic measurement of ulcer area, quantitative histological measurement of mucosal regeneration, and 5-bromo-2'-deoxyuridine immunohistochemistry to assess epithelial cell proliferation. Indomethacin and aspirin significantly delayed ulcer healing and inhibited mucosal regeneration. Three techniques for assessing cell proliferation were compared, and a scoring system, designed to take into account the entire tissue, was shown to be the most reproducible technique. Indomethacin significantly enhanced cell proliferation in the fundic area of ulcer and aspirin had no effect on cell proliferation. We conclude that aspirin and indomethacin delay ulcer healing by an inhibition of mucosal regeneration, but they do not inhibit epithelial cell proliferation.
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PMID:NSAID-induced delay in gastric ulcer healing is not associated with decreased epithelial cell proliferation in rats. 853 32

Indomethacin induces gastric ulcerations and decreases cell proliferation in the gastric ulcer margin. Since epithelial cell proliferation is under control of epidermal growth factor (EGF), we studied whether indomethacin may affect specific binding of [125I]-EGF to its receptors in cultured human gastric KATO III cells. To assess effects of EGF, indomethacin and their combination on cell proliferation, KATO III cells were incubated for 24 h with either (a) vehicle (b) indomethacin (doses from 10(-5) to 10(-3) M), EGF (doses 0.01, 0.05 or 0.1 microgram/ml) or (d) a combination of b and c, and the bromodeoxyuridine labeling index was determined. Indomethacin in a dose which did not affect cell viability significantly (by 21.5%) decreased [125I]-EGF binding to the KATO III cells and decreased the bromodeoxyuridine labeling index. Epidermal growth factor significantly increased cell proliferation and increased the labeling index from 28.9 +/- 0.6% in the vehicle group to 36.2 +/- 0.5%. Co-treatment with indomethacin significantly reduced the proliferative response of KATO III cells to EGF. In conclusion, indomethacin, in a dose which does not affect cell viability, decreased binding of EGF to cultured gastric KATO III cells and decreased their proliferative response to EGF.
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PMID:Indomethacin interferes with epidermal growth factor binding and proliferative response of gastric KATO III cells. 854 78

The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50 micrograms/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.
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PMID:Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-infiltration and increases future ulcer recurrence. Possible mediation of prostaglandins. 888 21


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