Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes.

OBJECTIVES: Membrane toxicity induced by hydrophobic bile salts may be important in liver diseases. Administration of ursodeoxycholate reduces serum liver enzymes in chronic liver diseases, but the nature of this effect is still unclear. We aimed at establishing a convenient in-vitro system for investigating the hepatotoxic properties of hydrophobic bile salts and the putative hepatoprotective effect of ursodeoxycholate. METHODS: About 100 mg of freshly isolated rat hepatocytes were suspended on a resin column (Bio-Gel P4 fine) and perifused with different concentrations of bile salts. The effluent was collected at 5-min intervals and assayed for lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. Enzyme leakage induced by bile salts was compared with that induced by Triton X-100 (Union Carbide, Danbury, CT, USA) at different concentrations. After perifusion, hepatocytes were collected for electron microscopic observation. RESULTS: Cytotoxicity of individual bile salts, assessed by enzyme release, was time and concentration dependent and corresponded to their hydrophilic-hydrophobic balance. Perifusion with hydrophilic bile salts, cholate and ursodeoxycholate, did not result in a significant enzyme release in concentrations up to 5 mmol/l, whereas hydrophobic bile salts, chenodeoxycholate and deoxycholate, induced significant enzyme leakage even in low concentrations, 0.5 and 0.1 mmol/l, respectively. Addition of ursodeoxycholate significantly reduced the hepatotoxic effect of deoxycholate. This protective effect was evident within minutes. The ultrastructural appearance of hepatocytes exposed to hydrophobic bile salts was very similar to the non-specific cellular lysis observed after exposition to Triton X-100, suggesting that they act mainly in a detergent-like fashion. CONCLUSION: Perifused rat hepatocytes seem a convenient in-vitro system for investigating the hepatotoxic properties of bile salts and hepatoprotective effect of ursodeoxycholate, offering the opportunity to investigate the effects of bile salts under dynamic conditions, mimicking the in-vivo situation, and allowing continuous enzyme release monitoring. Hydrophobic bile salts seem to act mainly in a detergent-like fashion; ursodeoxycholate-related hepatoprotection could be due not only to a dilution effect of toxic bile salts, but also to a direct cytoprotective effect.

Brush cytology: a reliable method to detect Helicobacter pylori.

This study was conducted to verify the reliability of brush cytology in detecting Helicobacter pylori in an unselected group of patients with duodenal ulcer (DU) and nonulcer dyspepsia (NUD). Endoscopy was performed on 416 consecutive patients: group A, 94 with active DU; group B, 176 patients with DU after omeprazole (n = 78), ranitidine (n = 43), or triple anti-H. pylori therapy (n = 55); and group C, 146 patients with NUD. During endoscopy, the gastric mucosa was brushed and two biopsy samples from the antrum and body were obtained for histology. In 65 patients, culture of the brush-collected materials also was performed as was that from of biopsy samples. The overall frequency of H. pylori presence detected by brush cytology was significantly higher compared with that of histology (p < 0.001), particularly in group A (p < 0.05), group C (p < 0.05), and in patients with DU after omeprazole treatment (p < 0.01), but not in patients with DU after ranitidine or anti-H. pylori treatment. The overall frequency of H. pylori-positive cultures from the brush-collected material was higher compared with cultures from the biopsy samples (38.5% vs. 24.6%), particularly in the NUD group (32.6% vs. 16.3%). Brush cytology is more sensitive than histology, besides being faster and cheaper, for the assessment of H. pylori infection, particularly when the density of the bacteria is low.

High effectiveness and safety of one-week antibiotic regimen in Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori is strongly associated with peptic ulcer: H. pylori eradication markedly decreases the recurrence rate of duodenal and gastric ulcer, but the optimum length of antibiotic therapy in the eradication of H. pylori is still unclear. AIM: To verify the effectiveness and side-effect profile of an eradicating regimen consisting of omeprazole 20 mg daily for 4 weeks and, during the first week, combination antimicrobial treatment with tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. in patients with active duodenal and gastric ulcer. METHODS: One hundred and ninety-six duodenal ulcer patients and 27 gastric ulcer patients with H. pylori infection were admitted into an open prospective study. Compliance was assessed by an accurate interview. RESULTS: Overall, H. pylori was successfully eradicated in 201 of 223 patients (intention-to-treat 90.1%; 95% CI = 85-94%): 176 of 196 duodenal ulcer patients became H. pylori-negative (89.8%; CI = 85-94%) as well as 25 of 27 gastric ulcer patients (92.6%; CI = 76-99%). Compliance was excellent in 221 of 223 (99.1%) patients evaluated as having taken all the medication as prescribed. Sixteen patients (7.2%) developed mild side effects during treatment. CONCLUSION: This combination treatment had excellent results with almost absolute compliance and a very low rate of minor side effects.

[Long-term cyclic and periodic omeprazole in the prevention of recurrences of duodenal ulcer]. / Omeprazolo long-term a cicli e a domanda nella prevenzione delle recidive dell'ulcera duodenale.

The aim of this study was to establish if the discontinuous assumption of omeprazole was effective to reduce the recurrence of duodenal ulcer disease as the cyclic periodical assumptions of the same drug. Consequently two different posologies, after duodenal ulcer recovery, were compared, both based on omeprazole. In the first trial 20 mg/die were administrated for the first 15 days of every month, for 1 year. In the second, the same dose were administrated for 15 days only when symptoms occurred. It was not utilised a comparison with placebo or other drugs. Symptomatic score and recurrence rate were evaluated by means of EGDS after 6 months and 1 year. In some patients were also controlled the gastrinemia. Both trials were effective in the prevention of duodenal ulcer relapse, without increasing gastrinemia. Nevertheless patients assuming omeprazole only when symptomatic, showed a greater symptomatic score. Concluding, the assumption of omeprazole only when symptoms occur is effective in the prevention of relapse but require a close relation between patients and the medical team.

Misoprostol for the treatment of chronic erosive gastritis: a double-blind placebo-controlled trial.

OBJECTIVE: To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms. METHODS: We performed a double-blind controlled trial, administering 200-micrograms misoprostol tablets or placebo twice daily for 2 months to 48 patients with symptomatic chronic erosive gastritis. Symptomatology was assessed by means of a standard questionnaire at the beginning and at the end of the study, as well as endoscopic and histologic changes of the gastric mucosa. RESULTS: At the end of the treatment period, a significant reduction in symptom score was observed in misoprostol-treated (from 86.6 +/- 66.2 to 17.6 +/- 18.2, p < 0.001) but not in placebo-treated patients. Endoscopic score was significantly reduced at the end of the treatment period in the misoprostol group, compared with that of the placebo group (p < 0.05). A significant reduction in the activity of histologic gastritis was observed only in patients on misoprostol. The prevalence of gastric colonization by Helicobacter pylori was rather low (30%), and no effect of treatment was observed. CONCLUSIONS: Patients with symptomatic chronic erosive gastritis seem to profit from treatment with misoprostol: the treatment with misoprostol, but not with placebo, was effective in significantly reducing the extent of symptoms. Such an improvement was associated with a substantial improvement in the endoscopic and histologic appearance of the gastric mucosa.