Biomedical subjects

D Brügmann

Publications and source records attributed to D Brügmann.

2 recordsLinked to original sources

PubMed1995

[Helicobacter pylori and azithromycin].

Helicobacter pylori is a Gram-negative bacterium with man as the unique reservoir and where the niche is the stomach. Transmission between individuals could be by fecal and oral route. In the stomach, the bacterium is mainly located at the mucus level and adhere to antral cells which are the privileged target. Within the colonized mucosa, H. pylori generates or secretes different deleterious compounds against the epithelial cells: urease, hydrolyzing urea into ammonia, a cytotoxic agent: monochloramine also cytotoxic, various enzymes and a vacuolyzing cytotoxin; all of these also contribute to the pathogenic potential. In addition the associated inflammatory reaction probably plays a part in the lesion process. One important consequence is peptic ulcer disease and particularly duodenal ulcer which can further degenerate into a precancer lesion and to a lesser extent some dyspeptic syndromes. Bacterial eradication can be obtained by the combination of an antisecretory drug with an antibiotic. Macrolides have a good activity against this bacterium. The azithromycin MIC50 is 0.12 mg/l. A bactericidal activity is observed at concentrations equal or higher than 0.10 mg/l. After a single dose of 500 mg, azithromycin concentrations are 0.48 micrograms/g in the mucus and 4 micrograms/g in the gastric tissue. Concentrations persist for a long time, due to long half life (3 days). In pilot clinical trials, with a tritherapy combining azithromycin with metronidazole and omeprazole, 80% of bacterial eradication was obtained. These promising need to be validated by larger clinical trials.

Anti-Bacterial Agents↗

PubMed1992

Further evidence of the toxic effect of ammonia produced by Helicobacter pylori urease on human epithelial cells.

Former studies have shown that Helicobacter pylori can induce vacuolation of vacuolation of epithelial cells in vitro and possibly in vivo, either by direct action of a cytotoxin or by the action of its strong urease, which breaks down the urea physiologically present in the stomach into cytotoxic ammonia. We have developed a test using HEp2 cells with adherent H. pylori bacteria in order to compare the effects of an H. pylori urease-negative variant with those of its urease-positive parent strain in the presence of 10 mM urea. The level of ammonia production as well as cell vacuolation and viability were monitored for 72 h. The ammonia produced (20 mM) was found to be the essential determinant of the degree of cell vacuolation and viability of HEp2 cells. However, the addition of acetohydroxamic acid (200 mg/liter), a potent urease inhibitor which inhibits ammonia production, did not completely restore cell growth, suggesting the difficulty of neutralizing the ammonia in the vicinity of the cells. Antibodies directed against H. pylori did not neutralize the urease activity. When H. mustelae was tested in the same manner, the detrimental effects were not observed because a lower quantity of ammonia (5 mM) was generated. This was due to a lower urease activity, although the adherence properties of H. mustelae were different from those of H. pylori both quantitatively (greater adherence) and qualitatively (localized instead of diffuse adherence). We conclude that H. pylori-induced ammonia is an essential determinant of its cell toxicity as well as its adherence properties, which allow a high concentration of ammonia at the cellular level.

Ammonia↗