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Biomedical subjects

P Mavier

Publications and source records attributed to P Mavier.

At least 55 records · Page 3Linked to original sources
PubMed1983

[The mechanism of action of cyproterone acetate in the treatment of hirsutism].

Cyproterone acetate (CPA) in association with percutaneously offinistered estradiol has been used for the treatment of 150 hirsute patients for periods ranging from 6 months to 3 years. A spectacular clinical improvement ensued. Plasma testosterone (T) and androstenedione (A) fell from 69 +/- 24 to 33 +/- 8 and 210 +/- 103 to 119 +/- 25 ng/dl (mean +/- SD) respectively after 3 months of treatment and remained low thereafter. In contrast, T glucuronide (Tg) and 3 alpha-androstanediol (Adiol) remained high during the whole course of treatment: 37 +/- 9 and 115 +/- 43 micrograms/24 h respectively. In vitro T 5 alpha-reductase activity (5 alpha-R) in pubic skin decreased from 147 +/- 34 to 79 +/- 17 fmol/mg skin after 1 year of treatment. To elucidate the discrepancy between plasma and urinary androgens levels, T production rate (PR) and metabolic clearance rate (MCR) were measured with the constant infusion technique in 6 patients before and after 6 months of treatment. PR decreased from 988 +/- 205 to 380 +/- 140 micrograms/24 h (mean +/- SD). In contrast MCRT increased from 1275 +/- 200 to 1632 +/- 360 1/24 h; this increase in MCRT explains the striking plasma T concentration fall and the high TG and Adiol excretion relative to the decrease in PR. Antipyrine clearance rate (n = 8) increased from 36.3 +/- 5.2 to 51.5 +/- 7.4 ml/min whereas urinary/6 beta hydroxycortisol remained unchanged. In conclusion, CPA acts through several mechanisms:(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

[Comparison of the effects of cimetidine and ranitidine in vivo and in vitro on the hepatic microsomal enzyme system in rats].

Cimetidine, administered intraperitoneally to male rats (20 mg/kg and 40 mg/kg) induced a 125 p. 100 and 325 p. 100 increase in the hexobarbital sleeping time, respectively. Ranitidine, at the same dosage, had no effect. Cimetidine (40 mg/kg) decreased the aminopyrine metabolic clearance by 73 p. 100, whereas ranitidine caused no change. In vitro, cimetidine (1 mM) decreased 3 oxiding enzymatic activities, ethylmorphine demethylase, aniline hydroxylase and aminopyrine demethylase, measured in a 9,000 g supernatant fraction of rat liver, by 29 p. 100, 45 p. 100 and 73 p. 100, respectively. Ranitidine (1 mM) did not modify ethylmorphine and aminopyrine demethylase activities and induced a slight decrease of aniline hydroxylase activity (10 p. 100). Bilirubin and p-nitrophenol UDP-glucuronosyltransferase activities, measured on the microsomal fraction, were slightly inhibited (5 p. 100 and 4 p. 100, respectively) by cimetidine (1 mM). Ranitidine (1 mM) did not change these enzymatic activities. The effects of cimetidine and ranitidine on both the oxidizing and conjugating enzymatic activities were not notably affected by pretreatment with phenobarbital (100 mg/kg, intraperitoneally for 3 days). These results point out that: 1) in vivo and in vitro, ranitidine, in contrast with cimetidine, does not inhibit the microsomal drug-oxidizing system; 2) neither ranitidine nor cimetidine decrease the activity of the microsomal drug-conjugating system. They clearly explain why cimetidine interferes with the disposition of drugs oxidized but not of drugs conjugated by the liver.

Animals↗
PubMed1981

Characterization of microsomal bilirubin and p-nitrophenol uridine diphosphate glucuronosyltransferase activities in human liver: a comparison with rat liver.

The bilirubin and p-nitrophenol uridine diphosphate glucuronosyltransferase (UDP-GT) activities have been characterized from human liver microsomes and compared to those from rat liver. This study was performed on large samples of human liver obtained from 20 organ donors. The kinetic constants as well as sensitivities to digitonin, temperature, pH and diethylnitrosamine were determined. Our results suggest that UDP-GT activities have characteristics different in human and rat liver microsomal membranes. Moreover, differences in digitonin-induced activation, in thermodenaturation and in the response to diethyl-nitrosamine were found between bilirubin and p-nitrophenol UDP-GT activities. This supports the hypothesis of the probable heterogeneity of UDP-GT.

Animals↗
PubMed1979

[Deviation in cortisol metabolism induced by rifampicin. Therapeutic consequences in adrenal failure (author's transl)].

Deviation of cortisol metabolism in favour of its 6 beta-hydroxylated derivative was demonstrated in two patients with adrenal failure receiving substitution corticosteroid therapy and rifampicin. The existence of a frank increase in the metabolic clearance antipyrin was in favour of an hepatic enzyme induction. After rifampicin treatment was stopped, the 24 hour urinary excretion of 6 beta-OH-F returned to normal, demonstrating the responsability of the drug. This enzyme induction results in a need to increase the dose of hydrocortisone substitution therapy in patients with Addison's disease treated with rifampicin.

Addison Disease↗
PubMed1977

RMI 12330 A, an inhibitor of adenylate cyclase in rat liver.

RMI 12330 A, (N,-(cis-2-phenylcyclopentyl) azacyclotridecan-2-imine hydrochloride), has been reported to inhibit choleratoxin-induced intestinal hypersecretion, presumably via an inhibition of mucosal adenylate cyclase (ATP:pyrophosphate-lyase (cyclizing), EC 4.6.1.1). We report here that the adenylate cyclase activity of a rat liver plasma membrane preparation was inhibited by concentrations of RMI 12330 A ranging from 10 muM to 5mM. Similar effects were observed when the adenylate cyclase preparation was assayed in the presence of 10 mM NaF, 0.1 muM glucagon or 1 muM (--)-epinephrine plus 10 muM GTP. The effect of RMI 12330 A was not due to the inhibition of the regenerating system present in the incubation medium, since the effect was preserved in its absence. The inhibition brought about by RMI 12330 A was due to a decrease in the maximal velocity of the reaction; the affinity of the enzyme for the substrate remained unmodified. The inhibition was immediate and irreversible, even after several washes of the membranes previously preincubated with the drug. Complete inhibition of cyclase was obtained at a concentration of 370 nmol of RMI 12330 A per mg of membrane protein. The drug acted with a similar dose-response curve upon intact as well as detergent-dispersed cyclase preparations.

Adenylyl Cyclase Inhibitors↗
PubMed1977

Induction of hepatic microsomal enzymes after brief administration of rifampicin in man.

The inducing effect of rifampicin (600 mg per day) on the hepatic microsomal drug-metabolizing system has been studied in 7 patients with normal liver after 6 days of oral administration. Using the plasma disappearance rate of antipyrine (15 mg per kg of body weight) as an index of liver microsomal metabolism, a significant decrease in the half-life of antipyrine has been observed: 11.7 +/- (1 sd) 4.7 hr before treatment as compared to 6.9 +/- 2.3 hr on the 7th day. Concomitantly, the half-life of rifampicin was 5.3 +/- 2.1 and 2.7 +/- 0.8 hr on the 1st and 7th day, respectively. These results demonstrate that rifampicin administration for only 6 days leads to the induction of the microsomal mixed function oxidase system in liver. These data are in agreement with the recent hypothesis that rifampicin may play a role in the hepatotoxicity of isoniazid by enhancing its microsomal transformation to a toxic metabolite.

Adult↗
PubMed1975

Adenylate cyclase from rat-liver plasma membrane: inhibition by mersalyl and other mercurial derivatives.

The adenylate cyclase activity from a rat liver plasma membrane preparation was inhibited by low concentrations (1-10 muM) of the mercurial diuretic mersalyl. Complete inhibition was obtained with 0.1 mM mersalyl. Similar effects were observed whether the adenylate cyclase preparation was assayed in the presence of 10 muM GTP, 0.1 muM glucagon, 10 mM NaF or without any addition. The effect of mersalyl was not due to inhibition of the regenerating system present in the incubation medium, since the effect of mersalyl was preserved and even enhanced in its absence. The inhibition brought about by mersalyl was due to both a decrease of the maximal velocity of the reaction and of the affinity of the enzyme for the substrate. It was immediate, and irreversible spontaneously, but it was reversed by the simultaneous additions of 2-mercaptoethanol, in a dose-dependent fashion. Other -SH reagents were found to have an effect equal to, or lower than, that of mersalyl. Mersalyl had no effect upon Mg2+-ATPase, although it inhibited the (Na+-K+) activated ATPase. Since mersalyl is known to be a 'non-penetrant' reagent, it is postulated that a catalytically important, mercurial-sensitive, part of adenylate cyclase is at the surface of the plasma membrane. This view is supported by the following facts: (a) mersalyl acted with a similar dose-response curve upon an intact as well as a detergent-dispersed cyclase preparation while no effect was observed upon a solubilized Mg2+-ATPase preparation; (b) a covalent p-chloromercuribenzoate-Sephadex preparation (but not its supernatant) inhibited the cyclase from intact membranes. It is proposed that mercurial derivatives, by their relative specificity of action (no effect on Mg2+-ATPase), can serve as useful probes in the elucidation of the multicomponent structure of the cyclase system.

Adenosine Triphosphatases↗
PubMedDate not supplied

Peripheral T-cell lymphoma presenting as predominant liver disease: a report of three cases.

Three cases of a peculiar form of peripheral T-cell lymphoma presenting as predominant hepatic disease with splenomegaly are reported. The three patients had marked liver enlargement without lymphadenopathy; white blood cell count was normal, and modifications of hepatic tests were mild. In the three cases, the diagnosis of the lymphoma was mainly based on the results of hepatic morphological changes. Liver involvement was histologically characterized by a predominantly sinusoidal infiltration by tumor cells in the three cases, associated with perisinusoidal fibrosis in two of them; portal infiltration was noted in two patients. Immunopathological study showed that tumor cells were T-lymphoid cells that were different from normal T-lymphocytes by the lack of expression of one T-cell membrane antigen, i.e., Leu-1. These findings suggest that a distinct clinical, pathological and immunopathological entity might be individualized within the large group of T-cell lymphomas.

Adult↗
PubMedDate not supplied

In vitro toxicity of polymorphonuclear neutrophils to rat hepatocytes: evidence for a proteinase-mediated mechanism.

Human polymorphonuclear neutrophils, when exposed to soluble or particulate stimuli, can destroy various types of cells. The aim of this study was to investigate their toxicity against hepatocytes. Human polymorphonuclear neutrophils were incubated in basal conditions and after stimulation with 5 mg per ml opsonized zymosan in the presence of rat hepatocytes isolated by collagenase digestion. Cytotoxicity was quantified by the percentage of ALT activity released by hepatocytes in culture medium. Whereas unstimulated neutrophils exhibited only minor effects, opsonized zymosan-stimulated neutrophils induced, after 16 hr incubation, a 24.0 +/- 4.1% (mean +/- 1 S.E.) ALT activity release at a neutrophil/hepatocyte ratio of 5, and a 51.7 +/- 6.8% ALT activity release at a ratio of 20. At this ratio of 20, the ALT activity release was 9.0% at 1 hr and 24.0% at 4 hr. Three proteinase inhibitors (i.e., soybean trypsin inhibitor, alpha 1-proteinase inhibitor and fetal calf serum) decrease cytotoxicity by 78, 76 and 78%, respectively. The protective effect of proteinase inhibitors was not due to a nonspecific effect of proteins, since bovine serum albumin did not decrease the toxicity of stimulated polymorphonuclear cells. The supernatant of stimulated neutrophils was also found to be toxic against hepatocytes, and again, this effect was inhibited by soybean trypsin inhibitor, alpha 1-proteinase inhibitor and fetal calf serum. Finally, the role of proteinases was supported by the demonstration of a cytotoxic effect of two purified proteinases: porcine pancreatic elastase and human neutrophil cathepsin G. The toxicity of these proteinases was also markedly reduced by the specific inhibitors used in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗