A L Blum

Effect of Whey-Based Culture Supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori Infection in Humans

Background: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. acidophilus can survive transiently in the human stomach, it may downregulate Helicobacter pylori infection. Methods: The ability of L. acidophilus (johnsonii) La1 supernatant to interfere with H. pylori bacterial growth, urease activity, and adhesion to epithelial cells was tested in vitro. Its effect on H. pylori infection in volunteers was monitored in a randomized, double-blind, controlled clinical trial, using a drinkable, whey-based, La1 culture supernatant. H. pylori infected volunteers were treated 14 days with 50 ml of La1 supernatant four times a day combined with either omeprazole 20 mg four times a day or with placebo. Infection was assessed by breath test, endoscopy, and biopsy sampling, performed at inclusion, immediately at the end of the treatment (breath test only), and 4 weeks after the end of the treatment. Results: La1 supernatant inhibited H. pylori growth in vitro, regardless of previous binding of H. pylori to epithelial cells. In 20 subjects (8 females, 12 males, mean age 33.1 years) a marked decrease in breath test values was observed immediately after treatment with La1 supernatant, both in the omeprazole and in the placebo group (median 12.3 vs. 28.8 and 9.4 vs. 20.4, respectively; p < 0.03). In both treatment groups, breath test values remained low 6 weeks after treatment (omeprazole treated 19.2, placebo treated 8.3; p < 0.03 vs. pretreatment), but the persistence of H. pylori infection was confirmed in gastric biopsies. Conclusion: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.

Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole.

To test the hypothesis that Helicobacter pylori infection is associated with a decreased intragastric acidity during omeprazole therapy, ambulatory 24 hour dual point gastric pH recordings were performed in 18 H pylori positive and 14 H pylori negative subjects. There was a four to six week washout period between the two pH recordings made in each subject after one week courses of placebo or omeprazole, 20 mg daily. During placebo, median 24 hour pH values were not different in the corpus (H pylori positive = 1.5, negative = 1.4; p = 0.9) or antrum (H pylori positive = 1.3, negative = 1.2; p = 0.1). However, during omeprazole treatment, median 24 hour pH values were higher in H pylori positive subjects, both in the corpus (H pylori positive = 5.5, negative = 4.0; p = 0.001) and antrum (H pylori positive = 5.5, negative = 3.5; p = 0.0004). During placebo treatment, the only difference between the two groups was a higher later nocturnal pH in the antrum in the H pylori positive group. During omeprazole treatment, gastric pH was higher both in the corpus and in the antrum in the H pylori positive group for all periods, except for mealtime in the corpus. These data indicate that omeprazole produces a greater decrease in gastric acidity in subjects with H pylori infection than in those who are H pylori negative. It is not, however, known whether there is a causal relationship between H pylori infection and increased omeprazole efficacy.

Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole

It has been shown that omeprazole treatment produces higher intragastric pH values in Helicobacter pylori positive subjects than in H pylori negative subjects. This study aimed to investigate the effect of curing H pylori on the intragastric pH in both the presence and absence of omeprazole therapy. Twenty four hour intragastric pH recordings were performed before and after a one week course of omeprazole (20 mg once daily) in 18 H pylori positive subjects and were repeated after the infection had been cured. In the absence of omeprazole, the total 24 hour pH values before cure did not differ from those afterwards. During omeprazole treatment the 24 hour pH values were much higher before (median (95% CI) 5.4: 4.3, 6.0), than after cure of infection (3.6: 2.1, 4.4; p < 0.001). The omeprazole induced fall in H+ activity before cure of H pylori did not, however, differ from that afterwards. It is concluded that the apparently greater antisecretory effect of omeprazole during H pylori infection may be a result of the production of acid neutralising compounds by the H pylori. Although a direct interaction between H pylori and omeprazole cannot be excluded, it seems unlikely.

Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.

Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds.

Previous studies have suggested that profound inhibition of gastric acid secretion may increase exposure to potentially carcinogenic N-nitroso compounds. The aim of this study was to find out if the proton pump inhibitor omeprazole (20 mg daily) is associated with increased concentrations of potentially carcinogenic N-nitroso compounds in gastric juice. The volume of gastric contents, number of bacteria, and concentrations of nitrates, nitrites, and N-nitroso compounds was determined in gastric aspirates obtained after an overnight fast in 14 healthy volunteers (7M:7F) after one week of treatment with placebo, and one and two weeks treatment with omeprazole. Median bacterial concentrations were 1.0 x 10(4) (range 5.0 x 10(3)-5.0 x 10(6)) colony forming units (CFU)/ml after one weeks treatment with placebo and increased significantly to 4.0 x 10(5) (0-3.3 x 10(7)) CFU/ml after two weeks treatment with omeprazole (p < 0.05). A similar increase was seen in the concentration of nitrate reducing bacteria. There was no difference in the volume of gastric aspirates after treatment with omeprazole when compared with placebo (65 (29-155) ml v 42 (19-194) ml). The concentration of N-nitroso compounds was 0.13 (0-1.0) mumol/l after two weeks of omeprazole, which was not significantly different from that seen with placebo (0.15 (0-0.61) mumol/l). There was also no increase in the concentrations of nitrates or nitrites. It is concluded that omeprazole (20 mg once daily) for two weeks in healthy volunteers is associated with gastric bacterial proliferation but does not increase concentrations of N-nitroso compounds.

Intragastric pH during Treatment with Omeprazole: Role of Helicobacter pylori and H. pylori-Associated Gastritis

BACKGROUNDnOmeprazole treatment produces lower intragastric pH values 4 weeks after cure of Helicobacter pylori infection than before. We therefore investigated the effect of healing H. pylori-associated gastritis on intragastric pH in the presence and in the absence of omeprazole therapy.nnnMETHODSnBefore and on day 8 of omeprazole, 20 mg once daily, 24-h intragastric pH-recordings were performed in 14 subjects with H. pylori infection and repeated 4 and 52 weeks after cure of infection. Gastritis severity in corpus and antrum was graded by using a modified Sydney system.nnnRESULTSnIn the absence of omeprazole administration, median 24-h pH values before cure did not differ from those 4 and 52 weeks after cure. On day 8 of omeprazole administration, 24-h pH values were much higher before cure (median, 5.15; 95% confidence interval (CI), 4.3-6.0) than 4 weeks (3.6; 2.1-4.4; P < 0.001) and 52 weeks after cure (3.0; 2.1-4.4; P < 0.001). The activity of corpus and antral gastritis was not associated with the magnitude of H+ change induced by omeprazole.nnnCONCLUSIONnThe increased pH produced by omeprazole during H. pylori infection is likely to be due to neutralizing substances produced by H. pylori and not to H. pylori-induced gastritis.

Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice

Homeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)‐induced colitis. Sonicates of Gram‐positive, Gram‐negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1u2003mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1–14); median (range)) compared with PBS‐fed control animals (15 (7–19); Pu2003<u200a0·05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6–11); Pu2003<u200a0·05 versus control), but not in mice fed a pool of Gram‐positive and ‐negative sonicates (16 (12–16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS‐fed control animals. DSS‐induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.

Effect of curing Helicobacter pylori infection on intragastric acidity during treatment with ranitidine in patients with duodenal ulcer.

BACKGROUND: In patients with duodenal ulcer cure of Helicobacter pylori infection resulted in a pronounced decrease in intragastric pH during treatment with omeprazole. AIM: To test the hypothesis that treatment of H pylori adversely affects the pH response to ranitidine. PATIENTS: Eighteen patients with duodenal ulcer who were infected with H pylori were studied. METHODS: Twenty four hour pH recordings were performed during treatment with ranitidine (300 mg) at night before and four to six weeks after cure of H pylori infection. Presence of H pylori was assessed by a rapid urease test, culture, histology, and a 13C urea breath test. Also, the fasting gastrin concentrations were measured before and after treatment for H pylori infection. RESULTS: Cure of H pylori infection resulted in a considerable improvement in both antral and corpus gastritis and a decrease in fasting gastrin concentrations. As a result of the cure the night time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v 5.4; p = 0.007), whereas the acidity during the daytime was not affected. CONCLUSIONS: In patients with duodenal ulcer the intragastric pH during treatment with ranitidine depends on H pylori. However, the loss of effectiveness in altering pH seems to be less pronounced than previously found with omeprazole.

Effects of Omeprazole and Lansoprazole on 24-Hour Intragastric pH in Helicobacter pylori-Positive Volunteers

BACKGROUNDnThe comparative effects of omeprazole and lansoprazole on gastric acidity in Helicobacter pylori-positive subjects and the clearance of H. pylori are unknown.nnnMETHODSnEighteen asymptomatic H. pylori-positive subjects were studied. Each volunteer received 7 days of omeprazole, lansoprazole, or placebo in a randomized, double-blind, crossover study, with a washout period of 4-6 weeks between treatments. At the end of each treatment period 24-h dual-point intragastric pH-metry was performed, and H. pylori clearance was assessed.nnnRESULTSnBoth omeprazole (corpus/antrum pH: 5.5/5.5) and lansoprazole (5.4/5.4) increased intragastric pH compared with placebo (1.5/1.3). Over the 24-h recording there was no difference between the two treatments with regard to control of intragastric pH or clearance of H. pylori.nnnCONCLUSIONnOmeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, are comparably effective antisecretory agents in H. pylori-positive subjects. Both agents provide only transient clearance of H. pylori in a few subjects.

Prevalence of Helicobacter pylori infection and chronic dyspeptic symptoms among immigrants from developing countries and people born in industrialized countries

The relationship between Helicobacter pylori infection and chronic dyspepsia is controversial. To determine the effect of H. pylori infection on dyspeptic symptoms, we compared the prevalence of H. pylori infection in immigrants from developing countries and people born in industrialized countries. Upper abdominal symptoms were assessed by a questionnaire and H. pylori infection was determined with a 13C-urea breath test and serology. H. pylori infection was found in 63% of subjects from developing countries and 11% of subjects from industrialized countries. There was no difference in the prevalence of dyspeptic symptoms between the 2 groups. The lack of difference in chronic dyspeptic symptoms between the groups, despite a major difference in the H. pylori prevalence, suggests that H. pylori infection is not a major contributor to chronic dyspepsia.