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Biomedical subjects

P Paterson

Publications and source records attributed to P Paterson.

At least 37 records · Page 2Linked to original sources
PubMed1985

Sex differences in the effects of microsomal enzyme inducers on hepatic phase I drug metabolism in the rat.

This study investigates the sex-dependence of the effects of microsomal enzyme inducers (phenobarbitone, isosafrole and ethanol) on the hepatic phase I metabolism of lignocaine and imipramine. It is shown that all of the inducers exert sex-dependent effects on the enzymes activities known to be sex related in the rat, e.g. lignocaine N-deethylase activity is decreased by phenobarbitone pretreatment in the male but increased by the same treatment in the female. The inducers tend to decrease the sex differences seen in untreated animals. Ethanol may give this effect by its action of decreasing serum testosterone levels but the mechanism of action of the other compounds is uncertain. It is possible that the sex-dependent cytochrome P-450 species are selectively sensitive to the action of the compounds in terms of induction, repression or inhibition. It is clear, however, that the effects of the pretreatments are related to the sex differences in phase I metabolism in the rat.

Animals↗
PubMed1985

Influence of cytochrome P-450 type on the pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl or 4-methoxybiphenyl.

The rate of production of 4-hydroxybiphenyl from 4-methoxybiphenyl in hepatocytes isolated from untreated rats was essentially identical to that from biphenyl in hepatocytes isolated from rats pretreated with beta-naphthoflavone at 40 mg/kg. Similar results were obtained using liver microsomes isolated from untreated or treated rats. The selective inhibition of these reactions by metyrapone, alpha-naphthoflavone and ethanol demonstrated that different forms of cytochrome P-450 are responsible for O-demethylation of 4-methoxybiphenyl in livers of untreated rats and 4-hydroxylation of biphenyl in livers of pretreated rats. The pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl in hepatocytes isolated from pretreated rats was different from that for 4-hydroxybiphenyl generated from 4-methoxybiphenyl in hepatocytes isolated from untreated rats, there being a 60% decrease in sulphation measured after 60 min incubation with biphenyl. Glucuronidation of 4-hydroxybiphenyl was not affected. The sulphation of 4-hydroxybiphenyl added directly was significantly decreased in hepatocytes isolated from pretreated rats. The initial rate of glucuronidation of 4-hydroxybiphenyl added directly was not altered by the pretreatment, but there was a significant decrease in overall glucuronidation measured over a 60 min incubation. Similar results were obtained using liver slices. beta-Naphthoflavone added directly to liver slices significantly decreased the extent of sulphation of 4-hydroxybiphenyl but did not influence glucuronidation. There was evidence of a late decrease in biphenyl 4-hydroxylase activity in hepatocytes isolated from pretreated rats. It is concluded that the differences observed in the cellular metabolism of biphenyl and 4-methoxybiphenyl can be ascribed to competition between beta-naphthoflavone and/or its metabolites retained within the cells following pretreatment, and biphenyl and/or its metabolites for the pathways common to their metabolism. It is also concluded that the type of cytochrome P-450 involved in the generation of 4-hydroxybiphenyl does not, per se, influence the subsequent pattern of conjugation.

Animals↗
PubMed1984

Influence of cytochrome P-450 type on the pattern of conjugation of 7-hydroxycoumarin generated from 7-alkoxycoumarins.

Pretreatment of rats with phenobarbitone increased hepatic microsomal 7-methoxy-and 7-ethoxy-coumarin O-dealkylase activities. Pretreatment with beta-naphthoflavone increased only the 7-ethoxycoumarin O-dealkylase activity. The addition of metyrapone in vitro inhibited the O-dealkylations to different extents. Similar results were obtained with diphenyloxazole and ethanol. These results are taken to indicate that different forms of cytochrome P-450 are involved in the O-dealkylation of these two substrates. The pattern of metabolism (Phase I and Phase II) of each alkoxycoumarin in rat isolated hepatocytes was very similar. The sulphate conjugate was the major metabolite produced, the amount of which approached a plateau as the rate of O-dealkylation increased. It is concluded that the type of cytochrome P-450 involved in the initial Phase I metabolism does not influence the subsequent pattern of conjugation.

Animals↗
PubMed1983

The effect of ascorbic acid on the conjugation of 4-hydroxybiphenyl in rat isolated hepatocytes.

Ascorbic acid at high non-physiological levels inhibited the sulphation of 4-hydroxybiphenyl by rat isolated hepatocytes. Glucuronylation of 4-hydroxybiphenyl, formed from 4-methoxybiphenyl, was increased at ascorbic acid levels which inhibited sulphation. The glucuronylation of 4-hydroxybiphenyl added directly to the cells was enhanced at concentrations of ascorbic acid which did not inhibit sulphation. Ascorbic acid did not influence the cytochrome P-450-dependent O-demethylation of 4-methoxybiphenyl or the level of cellular lipid peroxidation.

Animals↗
PubMed1978

Tubal microsurgery--a review.

Microsurgery is being applied with considerable advantage to tubal reconstruction, particularly in relation to improved pregnancy rates. These results justify the additional costs in equipment and time which are required.

Animals↗
PubMed1978

Microvascular transplantation of the human fallopian tube.

An unsuccessful human fallopian tube transplant is reported. A microsurgical technique is described which initially secured a viable transplant. However, the allograft subsequently died, probably as a result of rejection. Immunosuppression of the patient caused no complications or difficulties, the donor sharing one HL-A haplotype with the patient. The operative procedure, the risks of immunosuppression, and the ethical aspects of the case are discussed in order to present the problems associated with fallopian tube transplantation.

Fallopian Tubes↗
PubMed1977

Microsurgical tubal anastomosis for sterilization reversal.

A series of patients requesting sterilization reversal has been reviewed. Microsurgical tubal anastomosis has been successfully employed and offers improved surgical results. Minimization of the length of tube damaged at sterilization procedures is probably a major factor in determining pregnancy rates should subsequent reversal be desired.

Fallopian Tubes↗