Depression of hepatic cytochrome P-450-dependent mixed function oxidases during infection with encephalomyocarditis virus

Infection of mice with encephalomyocarditis virus had a marked effect on drug biotransformation in the liver. the levels of cytochrome P-450 and cytochrome b₅ and aminopyrine N-demethylase activity were significantly decreased 3 days after the administration of lethal and sublethal doses of virus. Interferon was detected in serum at doses of virus that produced decreased drug biotransformation. Cytochrome P-450 content and aminopyrine N-demethylase activity remained at normal levels for the first 2 days following infection before reaching a maximum decrease on days 3 and 4. Concentration of interferon in the serum of infected mice appeared on day 2 of infection and reached peak levels on day 3. Increased heme oxygenase activity was associated with the decrease in cytochrome P-450 level during the infection. These studies indicate the existence of an interaction between virus infection and cytochrome P-450-dependent drug biotransformation. This may cause adverse toxic effects during the use of drugs that depend on the hepatic mixed function oxidases for elimination.     

Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil

Diltiazem and verapamil were found to be inhibitors of the cytochrome P-450-dependent biotransformation of drugs. Diltiazem and verapamil competitively inhibited the N-demethylation of aminopyrine in hepatic microsomes with Ki values of 100 and 140 microM respectively. Both diltiazem and verapamil were N-demethylated themselves by hepatic microsomes with Km values of 62 and 145 microM respectively. Both drugs also interacted directly with cytochrome P-450 as measured by difference spectra. Diltiazem caused a type I spectral change and verapamil caused a reverse type I spectral change. No metabolic intermediate complexes could be demonstrated for either drug. Inhibition also occurred in vivo as both drugs could prolong pentobarbital-induced sleeping times in mice at doses comparable to those used in man. These results suggest that diltiazem and verapamil may have the potential to cause drug interactions involving inhibition of drug biotransformation.     

Comparison of catgut and polyglycolic acid sutures in colonic anastomoses

In a randomized prospective trial performed on patients undergoing colonic surgery, comparison was made between catgut and polyglycolic acid sutures as a continuous all-coats layer in a two-layer anastomosis, where the seromuscular layer in all cases was interrupted silk. The incidence of anastomotic dehiscence was significantly less when polyglycolic acid sutures were used.

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Résumé Une étude prospective randomisée a été faite chez des opérés de chirurgie colique. Elle a comparé le catgut et l'acide polyglycolique comme matériaux de surjet total dans des sutures en deux plans où le plan séromusculaire a toujours été fait à la soie en points séparés. La fréquence des lâchages de suture est nettement moindre pour l'acide polyglycolique.