Comparison of omeprazole, metronidazole and clarithromycin with omeprazole/amoxicillin dual-therapy for the cure of Helicobacter pylori infection

In this randomized, multicenter trial, we evaluated the effectiveness and side effect profile of a modified omeprazole-based triple therapy to cure Helicobacter pylori infection. The control group consisted of patients treated with standard dual therapy comprising omeprazole and amoxicillin. One hundred and fifty-seven H. pylori infected patients with duodenal ulcers were randomly assigned to receive either a combination of omeprazole 10 mg, clarithromycin 250 mg and metronidazole 400 mg (OCM) given three times daily for 10 days (n = 81),or a combination of omeprazole 20 mg and amoxicillin 1 g (OA) given twice daily for 14 days (n = 76). Prior to treatment and after 2 and 6 weeks, gastric biopsies from the antrum and corpus were obtained for histology and H. pylori culture. H. pylori infection was cured in 97.4% after OCM and in 65.8% after OA in the per-protocol analysis (p < 0.001) (intention-to-treat analysis: 93.4% and 63.2%, respectively). H. pylori was successfully cultured in 122 patients (77%). The overall rate of metronidazole resistance was 19.7% (24/122), no primary resistance to clarithromycin or amoxicillin was found. In the OCM group, all patients infected with metronidazole-sensitive H. pylori strains (n = 51) and those infected with strains of unknown susceptibility to metronidazole (n = 14)were cured (100%), while 77% (10/13) of those harboring metronidazole-resistant. strains were cured of the infection (p = 0.36). Side effects leading to premature termination of treatment occurred in 2.5% of the patients in the OCM group and in 1.4 % of the OA group. We conclude that combined treatment with omeprazole, clarithromycin and a higher dose of metronidazole is highly effective in curing H, pylori infection, Helicobacter pylori omeprazole and that this regimen remains very effective in the presence of metronidazole resistant strains

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the <it>Cox-2 </it>gene is up-regulated in the gastric mucosa during <it>H. pylori </it>infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an <it>in vivo </it>model, thereby identifying potential targets for the study of the role of Cox- 2 in <it>H. pylori </it>pathogenesis and the initiation of pre- cancerous changes.</p> <p>Results</p> <p>Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after <it>H. pylori </it>infection. <it>H. pylori </it>infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of <it>H. pylori </it>infection. The Cox-2 dependent subset included those influencing gastric physiology (<it>Gastrin, Galr1</it>), epithelial barrier function (<it>Tjp1, connexin45, Aqp5</it>), inflammation (<it>Icam1</it>), apoptosis (<it>Clu</it>) and proliferation (<it>Gdf3, Igf2</it>). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression.</p> <p>Conclusion</p> <p>This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by <it>H. pylori </it>infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.</p

DNA copy number profiles of gastric cancer precursor lesions

<p>Abstract</p> <p>Background</p> <p>Chromosomal instability (CIN) is the most prevalent type of genomic instability in gastric tumours, but its role in malignant transformation of the gastric mucosa is still obscure. In the present study, we set out to study whether two morphologically distinct categories of gastric cancer precursor lesions, i.e. intestinal-type and pyloric gland adenomas, would carry different patterns of DNA copy number changes, possibly reflecting distinct genetic pathways of gastric carcinogenesis in these two adenoma types.</p> <p>Results</p> <p>Using a 5K BAC array CGH platform, we showed that the most common aberrations shared by the 11 intestinal-type and 10 pyloric gland adenomas were gains of chromosomes 9 (29%), 11q (29%) and 20 (33%), and losses of chromosomes 13q (48%), 6(48%), 5(43%) and 10 (33%). The most frequent aberrations in intestinal-type gastric adenoma were gains on 11q, 9q and 8, and losses on chromosomes 5q, 6, 10 and 13, whereas in pyloric gland gastric adenomas these were gains on chromosome 20 and losses on 5q and 6. However, no significant differences were observed between the two adenoma types.</p> <p>Conclusion</p> <p>The results suggest that gains on chromosomes 8, 9q, 11q and 20, and losses on chromosomes 5q, 6, 10 and 13, likely represent early events in gastric carcinogenesis. The phenotypical entities, intestinal-type and pyloric gland adenomas, however, do not differ significantly (P = 0.8) at the level of DNA copy number changes.</p

Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2–64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128ΔcagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4–8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies