Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation.

BACKGROUND: E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients. AIM: To examine if eradication of H pylori could reverse E-cadherin methylation. METHODS: Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing. RESULTS: Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5). CONCLUSION: H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.

Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.

BACKGROUND: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole. AIM: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori. METHODS: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively. RESULTS: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001). CONCLUSION: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.

Optimal serological tests for the detection of Helicobacter pylori infection in the Chinese population.

BACKGROUND: Numerous serological tests for the detection of Helicobacter pylori infection have been developed. However, many perform poorly when evaluated in the Chinese population. AIM: To search for optimal serological tests for the detection of H. pylori infection in Chinese patients. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, gastric biopsies were taken for the CLOtest and histological examination. Patients were then given a 13C-urea breath test. Sera were used to test for H. pylori infection, employing three commercial enzyme-linked immunosorbent assay kits (pylori DTect, HP IgG and GAP IgG). Results were compared with the gold standard defined by the CLOtest, histology and 13C-urea breath test. RESULTS: Among the 142 patients (47 male, 95 female; mean age, 49 years) recruited, 81 (57%) were H. pylori-positive, 57 (40%) were H. pylori-negative and four (3%) were defined to be indeterminate. Using a self-defined cut-off value after calculation, the best accuracies for the pylori DTect, HP IgG and GAP IgG tests were 97%, 91% and 80%, respectively. CONCLUSIONS: The pylori DTect test is an optimal serological test for the detection of H. pylori infection in Hong Kong Chinese patients. The HP IgG test may be used as an alternative.