1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) by intragastric administration of CCl4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dose of CCl4 was 20 microg and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals did not gain weight compared with controls (P < 0.05). A significant reduction of ICG clearance was observed in CCl4-treated rabbits compared with controls (P < 0.05). The AST, ALT, bilirubin and gamma-GGT levels were elevated in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.
Short-term treatment with omeprazole in H. pylori- positive volunteers reduces the amount of metronidazole transferred from plasma to gastric juice. This seems to occur in a pH-independent form.
1. The aim of the present study was to investigate neutrophil chemotaxis during the induction of liver cirrhosis in rabbits. 2. Liver cirrhosis was induced in male New Zealand white rabbits. The study consisted of three experimental groups: (i) group A (n=16) served as the control and received only normal chow and all rabbits in this group were killed at 16 weeks; (ii) group B rabbits (n=8) were killed immediately after the chemotaxis assay, which was performed 24 h after CCl4 administration, at weeks 2, 4, 6 and 8; and (iii) in group C rabbits (n=19), the chemotaxis assay was performed every second week on the day before CCl4 administration for 16 weeks and all animals in this group were killed at 16 weeks. 3. Four of six rabbits in group B had liver cirrhosis at week 8. In group C, liver cirrhosis occurred in seven of eight animals. All rabbits with liver cirrhosis had an inflammatory infiltrate of neutrophils. In group B, there was a significant increase in polymorphonuclear cells and neutrophil chemotaxis and a significant reduction in mononuclear leucocytes at week 8. The rabbits in group C showed a significant increase in total leucocyte and polymorphonuclear numbers at week 10. A significant increase in neutrophil chemotaxis was also observed from week 2 through to week 6. 4. The presence of neutrophils in the liver of all rabbits with cirrhosis, associated with an increase in polymorphonuclear cell chemotaxis during this process, supports the view that this cell type has an important role in the development of toxic liver damage.
Short-term treatment with omeprazole in H. pylori-positive volunteers increases the amount of clarithromycin transferred to the gastric juice, confirming a synergism between these drugs. Our results suggest the presence of an active transport mechanism for clarithromycin from plasma to the gastric lumen, which is influenced by omeprazole.
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