ABSTRACT
c-Kit is a receptor tyrosine kinase, and it is encoded by the mouse W locus. Mutant W/Wv mice develop spontaneous gastric antral ulcers. The aim of the present study was to investigate the pathogenesis of these gastric ulcers and to examine the effects of two antiulcer drugs; a proton pump inhibitor (2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H -benzimidazole sodium salt, rabeprazole) and a mucosal protective drug (geranylgeranylacetone, GGA), on the gastric ulcers. The inhibition of the gastric acid secretion by rabeprazole (30 mg/kg body weight, subcutaneous injection once a day for six weeks) significantly increased the gastric ulcer formation compared to the controls. In contrast, the GGA treatment (100 mg/kg body weight, oral administration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen in these mutant mice, and they showed no cyclic intense contractions in the gastric antrum. These results suggest that bile reflux due to the disturbance of gastric antral movement is a cause of the spontaneous gastric ulcers in W/Wv mice.
Subject(s)
Bile Reflux/complications , Gastrointestinal Motility , Mice, Mutant Strains/physiology , Stomach Ulcer/etiology , 2-Pyridinylmethylsulfinylbenzimidazoles , Administration, Oral , Animals , Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Bile Acids and Salts/analysis , Bile Reflux/etiology , Diterpenes/administration & dosage , Drug Evaluation, Preclinical , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastrointestinal Motility/drug effects , Hydrogen-Ion Concentration , Injections, Subcutaneous , Male , Mice , Omeprazole/analogs & derivatives , Proton Pump Inhibitors , Rabeprazole , Stomach/pathology , Stomach Ulcer/drug therapy , Stomach Ulcer/pathologyABSTRACT
AIM: To examine the human leukocyte antigen (HLA)-DQA1 locus in patients harbouring Helicobacter pylori with chronic atrophic gastritis or duodenal ulcer as part of an investigation into immunogenetic differences in the host. SUBJECTS AND METHODS: We examined 116 patients harbouring H. pylori (55 patients with chronic atrophic gastritis, 61 with duodenal ulcers) and 28 H. pylori-negative healthy controls for HLA-DQA1 genotypes. H. pylori infection was determined by culturing biopsy samples from the gastric body and antrum and by enzyme-linked immunosorbent assay. HLA-DQA1 typing was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The allele frequency of DQA1*0102 was significantly higher in H. pylori-negative controls (0.250) than in H. pylori-positive duodenal ulcer patients (0.090). In contrast, the allele frequency of DQA1*0301 was significantly lower in H. pylori-negative controls (0.214) than in H. pylori-positive duodenal ulcer patients (0.418). CONCLUSION: These results suggest that there are genetic differences in the HLA-DQA1 locus between H. pylori-positive duodenal ulcer patients and H. pylori-negative healthy controls.
