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Biomedical subjects

J Tremblay

Publications and source records attributed to J Tremblay.

At least 181 records · Page 10Linked to original sources

Delta 5-androstenediol: kinetics of metabolism and binding to plasma proteins in normal post-menopausal women.

Delta 5-androstenediol (delta 5-diol) while having minimal androgenic activity is of potential biological importance because it binds to oestrogen receptors and has oestrogenic activity in several systems. We have examined delta 5-diol metabolism in post-menopausal women utilizing the constant infusion technique. The metabolic clearance rate for 11 subjects was 763 +/- 50 1/24 h or 467 +/- 30 1/m2/24 h. Labelled dehydroepiandrosterone, testosterone, delta 4-androstenedione, androsterone and the sulphates of delta 5-diol, dehydroepiandrosterone and androsterone were found in the plasma. Of all the kinetic parameters only the conversion ratio for dehydroepiandrosterone sulphate was different from that for young women (4.958 +/- 0.410 for young women vs 3.084 +/- 0.220 for older women). The plasma concentration of delta 5-diol was 0.94 +/- 0.19 ng/ml and the calculated blood production rate was 686 +/- 80 micrograms/24 h. The per cent free plasma delta 5-diol was 4.6 +/- 0.25. These values are slightly lower but not significantly different from those previously reported for normal young women.

Aged↗

Purification and partial characterization of a plasma inhibitor of tonin.

A plasma inhibitor of tonin activity in the rat, was purified by ammonium sulfate precipitation, ion-exchange of chromatography, and gel filtration. Its purity was investigated by analytical electrophoresis on polyacrylamide gel and by ultracentrifugation sedimentation velocity. The molecular weight (360 000) of the purified inhibitor was determined by sodium dodecyl sulfate electrophoresis and its isoelectric point (4.5) by gel isoelectrofocusing. The Stokes radius (640 nm) was evaluated by gel filtration studies and a frictional ratio (f/fo) of 1.95 was calculated from the molecular weight and Stokes radius. Kinetic studies using angiotensin I as substrate showed that the inhibition of tonin by the purified inhibitor was noncompetitive and does not exceed 70%. Electrophoresis showed the same mobility for [125I]tonin bound to plasma proteins and for [125I]tonin bound to the purified inhibitor. The inhibitor may be a protein resembling half of the dimeric protease inhibitor rat alpha 1-macroglobulin or human alpha 2-macroglobulin.

Angiotensin-Converting Enzyme Inhibitors↗

Creating an appropriate climate for drug use review.

Methods of establishing an appropriate climate for drug use review (DUR) programs are discussed. Characteristics of DUR programs proposed as essential for their initial acceptance and eventual continuity include objectivity, neutrality, and confidentiality. A retrospective DUR program is used as an illustrative model. The need to establish positive interpersonal peer relations is stressed.

Drug Utilization↗

Bronchodilatation: noncholinergic, nonadrenergic mediation demonstrated in vivo in the cat.

The composite vagus nerve was stimulated during intravenous infusion of 5-hydroxytryptamine in cats subjected to pharmacologic autonomic blockade with atropine, propranolol, and phentolamine. Bronchial caliber, as assessed by changes in pulmonary resistance, demonstrated a marked dilatation, and dilatation could still be demonstrated after preliminary treatment with reserpine. By stimulating the component branches of the vagus nerve, it was determined that the parasympathetic branch is responsible for this phenomenon.

Airway Resistance↗

Interindividual and interspecies variation in the metabolism of the hallucinogen 4-methoxyamphetamine.

1. The qualitative and quantitative aspects of the urinary elimination of orally administered 4-methoxy[14C]amphetamine have been examined in the rat and guinea-pig and in three volunteer human subjects, to determine interspecies and interindividual variations in disposition of the drug. 2. Both rat and guinea-pig excreted 70--80% of the administered dose(6 mg/kg) in the urine within 24 h, mainly as metabolites. 3. In the guinea-pig, the drug was metabolized by O-demethylation to give 4-hydroxyamphetamine, which was excreted free (4% dose) and conjugated (73%). No other metabolite was detected. 4. The rat metabolizes the drug both by O-dealkylation and by side-chain oxidation, the products being 4-hydroxyamphetamine (5% of dose free and 60% conjugated) and 1-(4'-methoxyphenyl)propan-2-one oxime (5% dose, free and conjugated). 5. In man the drug (dose 5 mg) is metabolized by O-demethylation and by side-chain oxidation. Marked intersubject variations were observed both in the array and quantitative aspects of metabolite excretion. Two subjects excreted mainly 4-hydroxyamphetamine (free and conjugated) together with smaller amounts of 1-(4'-methoxyphenyl)propan-2-one oxime and 4-hydroxynorephedrine. The third subject, however, who was previously known to exhibit a genetically determined defect in drug oxidation, was defective in O-dealkylation of 4-methoxyamphetamine, and the main excretion products were the unchanged drug together with products of side-chain oxidation, namely, 1-(4'-methoxyphenyl)propan-2-one oxime, 1-(4'-methoxyphenyl)propan-2-one and 4-methoxybenzoic acid. 6. Inter-individual differences in oxidative O-demethylation of the drug are discussed in relation to current theories on the aetiology of schizophrenia and reported fatalities arising from abuse of the drug.

Adult↗

Kinetics of acetylcholine synthesis and hydrolysis in myasthenia gravis.

Kinetic studies for choline-O-acetyltransferase (CAT) (E.C. 2.3.1.6) and acetylcholinesterase (E.C. 3.1.1.7) were performed on serum, skin fibroblasts in culture, and biopsied sartorius muscle from normal and myasthenic subjects. There was a significant decrease of CAT activity per milligram of protein in myasthenic muscle compared to normal muscle, and there was no difference in acetylcholinesterase activity per milligram of protein in the same muscle homogenates. Substrate concentration curves for acetyl coenzyme A and CAT also showed a significant reduction in the maximum rate of product formation (V(max)) per milligram of protein between myasthenic and normal muscle. It is postulated that binding of substrate to CAT is being inhibited by an inhibitor present in muscle.

Acetylcholine↗