A human in vitro model to study the interaction between Helicobacter pylori and gastric epithelial cells was developed using primary cultures of gastric mucosal cells (isolated from gastric biopsies or operative specimen and maintained in culture for 2 weeks) as well as the well-differentiated human gastric carcinoma cell line HM02, the undifferentiated gastric tumour cell line HM51, and the laryngeal epithelial cell line HEp-2. Primary cultures and all cell lines were exposed to seven isolates of H. pylori isolated from gastritis and duodenal ulcer patients. Microbial adherence was assessed by microscopical evaluation of Giemsa-stained preparations and by culturing the viable bacteria attached to the epithelial cells. All H. pylori isolates adhered to the gastric cells in primary culture, to HM02 cells, and to HEp-2 cells with the greatest binding affinity found in primary gastric cells. No adherence was detected in HM51 cells. H. pylori adherence was dependent on bacterial load, incubation time, and temperature. There was no difference in microbial binding between H. pylori isolates derived from gastritis and duodenal ulcer patients. The effect of antiulcer drugs on H pylori adherence was investigated by pre-incubating isolates of H. pylori with omeprazole, cimetidine, and bismuth subcitrate. Omeprazole and cimetidine failed to significantly influence microbial adherence. In contrast, bismuth subcitrate already in concentrations below the MIC range decreased H. pylori adherence in gastric epithelial cells and in HEp-2 cells substantially. Our study shows that primary cultured human gastric mucosal cells and the human gastric carcinoma cell line HM02 provide suitable in vitro models for the study of the interactions between H. pylori and the gastric epithelium. This gastric cell model is characterized by a high affinity for H. pylori binding.
With the approval of boceprevir and telaprevir the standard treatment of chronic hepatitis C virus (HCV) genotype 1 infection will be the triple therapy of a HCV protease inhibitor together with pegylated interferon alfa and ribavirin. In clinical studies a significant increase of sustained virological response rates from 38 - 44 % to 63 - 75 % for treatment-naïve and from 17 - 21 % to 59 - 66 % in treatment-experienced patients in comparison to the dual combination therapy with pegylated interferon alfa and ribavirin alone has been demonstrated. In addition, a large number of treatment-naïve patients and relapsers benefit from shorten treatment durations to 24 - 28 weeks. However, important differences exist between the administration of boceprevir and telaprevir in terms of a pegylated interferon alfa/ribavirin lead-in phase, the duration of dosing of the protease inhibitor, the overall treatment duration, HCV RNA measurements for response guided treatment durations and stopping rules. Furthermore, triple therapies with boceprevir and telaprevir may be associated with selection of resistant viral variants, new adverse events and clinically relevant drug-drug interactions. The present review gives an overview on the results of underlying clinical studies together with a guideline for the practical management of boceprevir- and telaprevir-based triple therapies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.