allopurinol and Helicobacter-Infections

This prospective randomized study investigated the possibility that duodenal ulcer relapse associated with Helicobacter Pylori infection is mediated by oxygen-derived free radicals. To this end, the radical scavengers allopurinol (50 mg 4 times daily) and dimethyl sulphoxide (DMSO, 500 mg 4 times daily) were administered orally. One hundred and forty-six consecutive patients with previous symptomatic endoscopy proven duodenal ulceration, which had been shown endoscopically to have healed in the presence of gastric mucosal infection with Helicobacter Pylori, were randomized to receive for the period of one year either placebo, or cimetidine 400 mg at bedtime, or allopurinol, or DMSO. In one hundred and twenty-six patients evaluable for efficacy, the cumulative relapse at one year was: placebo 47%, cimetidine 24%, allopurinol 6% and DMSO 6%. Cimetidine was significantly effective in preventing the relapse (p < 0.01), however allopurinol and DMSO were superior to cimetidine in this respect (p < 0.05). In the patients who relapsed, ulcer recurrence tended to occur early in those on placebo and cimetidine and to be evenly distributed over the year in those on free radical scavenging therapy. In all groups, ulcer recurrence throughout the maintenance year was more frequently symptomatic than silent. The incidence of infection with Helicobacter Pylori was not influenced by any of the regimens employed and the bacterium was detected with every relapse noted in this study and during the follow-up endoscopy which was carried out at 6 months and at 12 months during the maintenance year. The results suggest that oxygen-derived free radicals are involved in the relapse of duodenal ulceration in patients infected with Helicobacter Pylori.

Topics: Adult; Aged; Allopurinol; Cimetidine; Dimethyl Sulfoxide; Duodenal Ulcer; Female; Free Radical Scavengers; Free Radicals; Helicobacter Infections; Helicobacter pylori; Humans; Life Tables; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Reactive Oxygen Species; Recurrence; Treatment Outcome

Rebamipide, a gastroprotective drug, was developed in Japan and was proven to be superior to cetraxate, the former most prescribed drug of the same category, in 1989 in the treatment for gastric ulcers. The initially discovered basic mechanisms of action of rebamipide included its action as a prostaglandin inducer and oxygen free-radical scavenger. In the last 5 years, several basic and clinical studies have been performed for functional dyspepsia, chronic gastritis, NSAID-induced gastrointestinal injuries, gastric ulcer following eradication therapy for Helicobacter pylori, gastric ulcer after endoscopic surgery and ulcerative colitis. In addition, several molecules have been identified as therapeutic targets of rebamipide to explain its pleiotropic pharmacological actions. The aim of this article is to provide an update on the pharmacological and clinical profile of rebamipide and to explore further possibilities for additional indications.

Topics: Adult; Aged; Aged, 80 and over; Alanine; Alendronate; Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Drug Interactions; Gastritis; Helicobacter Infections; Humans; Male; Mice; Quinolones; Randomized Controlled Trials as Topic; Rats; Stomach Ulcer

The aim of this study was determination and comparison of the levels of myeloperoxidase (MPO), xanthine oxidase (XO), and superoxide dismutase (SOD) in gastric mucosa of children who were infected and noninfected with Helicobacter pylori (HP). The MPO, and XO enzyme activities were detected via kinetic measurement, and the MPO, XO and SOD enzyme protein levels were detected via Western blot, in antral mucosa specimens of 43 patients who underwent upper gastrointestinal endoscopy with various indications. The diagnosis of HP infection was made with a positive rapid urease test and histopathologic detection. MPO activity and enzyme protein levels were measured in 14 [8 HP (+) and 6 HP (-)], and in 9 [5 HP (+) and 4 HP (-)] while XO activity and enzyme protein levels were measured in 16 [10 HP (+) and 6 HP (-)] and in 9 [5 HP (+) and 4 HP (-)] patients, respectively. SOD protein level was detected in 13 [7 HP (+) and 6 HP (-)] patients. Of 43 patients 25 were HP (+) and 18 were HP (-). MPO activities were 75.6 +/- 40.5 and 98.8 +/- 44.1 U/g. protein (p = 0.302) while XO activities were 0.5 +/- 0.3 and 0.4 +/- 0.2 U/g. protein in HP (+) and HP (-) patients, respectively (p = 0.625). Measured enzyme protein levels of MPO, XO and SOD were found statistically indifferent in HP (+) and HP (-) patients (p = 0.327, p = 0.086, and p = 0.775, respectively). The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affected from HP presence. That's why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastric disease in children.

Topics: Adolescent; Child; Child, Preschool; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Peroxidase; Superoxide Dismutase; Xanthine Oxidase

Helicobacter pylori-associated inflammation leads to exposure of the gastric epithelium to reactive oxygen species (ROS) generated in the gastric mucosa. In some pathological conditions, such as those induced by nonsteroidal anti-inflammatory drugs, the gastric mucosa may become more susceptible to ROS.. To examine the effects of aspirin on antioxidant defenses as well as on oxidant injury in cultured rat gastric mucosal cells.. Primary monolayer cultures of rat gastric fundic mucosa were exposed to an ROS-generating system, hypoxanthine/xanthine oxidase (XOD). Cytotoxicity was quantified by measuring 51Cr release from prelabelled cells. The effects of aspirin on antioxidants and on cellular injury brought about by the ROS-generating system were determined.. XOD, in the presence of hypoxanthine, caused a dose-dependent increase in specific 51Cr release, which corresponded to the ability of XOD to produce ROS (as assessed by the production of uric acid from hypoxanthine). Incubation of cells with aspirin (1-100 microM) produced a dose-dependent increase in XOD-induced 51Cr release. Aspirin did not affect cellular glutathione content or activity of glutathione peroxidase, glutathione reductase or endogenous catalase. By contrast, aspirin caused a dose-dependent reduction in mucus synthesis. as assessed by incorporation of [3H]-glucosamine hydrochloride into the cells.. Aspirin at therapeutically relevant concentrations rendered cultured gastric cells more susceptible to subsequent exposure to ROS. Aspirin affected neither the glutathione redox cycle nor catalase activity. Thus, the enhancement of ROS-induced injury by aspirin may be accomplished through diminished gastric mucus synthesis, since mucus is a potent scavenger of ROS. These findings provide insight into how gastric inflammation and injury (such as that induced by H. pylori infection) in human gastric mucosa is modulated by the administration of nonsteroidal anti-inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspirin; Cells, Cultured; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Glutathione; Helicobacter Infections; Humans; Male; Mucus; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Xanthine Oxidase

The relationship between Helicobacter pylori (H. pylori), xanthine oxidase (XO)-induced oxygen derived free radicals (ODFR) and histamine in the induction of human gastroduodenal disorders was investigated.. Histamine concentration, XO and xanthine dehydrogenase (XD) activities were measured in endoscopically obtained biopsies from 66 symptomatic patients.. H. pylori infection was associated with lower oxyntic and duodenal histamine in 'normal' controls (group N) (p < 0.002 and p < 0.05, respectively). Patients with gastroduodenal disease tended to have reduced mucosal concentration of histamine, but comparing H. pylori positive and negative patients, infection did not lead to a further fall in histamine concentration. H. pylori positive duodenal ulcer (DU) patients tended to have higher XO activity than group N (p = 0.051) and had a significantly lowered activity of XD, the precursor of XO (p' < 0.05). Histamine concentration at the ulcer-edge was lower while XO activity was higher than in the distant normal mucosa (p < 0.05, respectively). Gastritis (group GL) with H. pylori also had lower XD than H. pylori positive group N (p' < 0.025) but no corresponding rise in XO activity. In group N, duodenal mucosal histamine and XD activity were inversely related (Rs = -0.51, p < 0.025).. These findings support the hypothesis that histamine, xanthine oxidase related ODFR, and H. pylori may be closely associated in the manifestations of chronic duodenal ulcer.

Topics: Adult; Aged; Endoscopy; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Intestinal Mucosa; Male; Middle Aged; Peptic Ulcer; Reactive Oxygen Species; Xanthine Dehydrogenase; Xanthine Oxidase