Biomedical subjects

J C Legrand

Publications and source records attributed to J C Legrand.

At least 109 records · Page 6Linked to original sources

PubMed1977

[Metabolism of o,p'-DDD (mitotane) in human and animals. Actual notions and practical deductions (author's transl)].

The metabolism of o,p'-DDD (mitotane), a well-known inhibitor of adrenal steroidogenesis in man and animal, is reviewed. Following oral administration, about 65% of the ingested drug were found to pass in the stool. The drug appeared in the urine in metabolized forms: o,p'-DDA and mono-and dihydroxylated derivatives of o.p'-DDA. These latters were found as well in the stools. An unsaturated metabolite, o,p'-DDE was described in plasma and tissues in man. Serum specimens of treated patients were analyzed for o,p'-DDD during various phases of therapy: the levels and the rate of rise during treatment were very variable (5 to 90 microng/ml). Tissue levels were obtained from animals (rats, dogs) or men (biopsy as well as autopsy): o,p'-DDD was primarily found stored in adipose tissue and fat-containing tissues, essentially adrenals. Practical conclusions can be drawn from these results: there is no correlation between the dose of o,p'-DDD administered and its blood level; there is no correlation between blood levels and the patient's responsiveness to the drug; there is a possibility that the molecule transformed in an active metabolite through its metabolism.

Animals↗

PubMed1976

Unusual low plasma renin hypertension in a child.

A four-year-old girl with hypertension (140/60) and chronic hypokalemic alkalosis was studied to determine the origin of this clinical feature. High exchangeable sodium (56.7 meq/kg vs. 45-55 meq/kg in controls) was associated with a low plasma renin activity (6 ng/1/min vs. 26 +/- 3.1 in controls) and reduced aldosterone secretion rate (5.56 mug/day; normal: 50-150 mug per day)). A low corticosterone secretion rate (0.228 mg/day vs. 0.50-0.65 in controls) and urinary tetrahydrodeoxycorticosterone (0.007 mg/day vs. 0.03-0.09 mg/day in controls) were found. The basal secretion rate of cortisol was also low (1.80 mg/m2/day vs. 5.4-16.7 mg/m2/day in controls) in spite of normal plasma ACTH: 78 pg/ml. The normal increase of the cortisol secretion rate (from 1.80 to 65 mg/m2/day) after synthetic ACTH stimulation ruled out a 17 alpha hydroxylase deficiency. The low sweat Na/K ratio (0.25) and the good suppressing efficacy of dexamethasone and of the spironolactones on hypertension and on the hypokalemic alkalosis agreed with the hypersecretion of a mineralocorticoid. The secretion rate of 18 hydroxydeoxycorticosterone was high (91 mug/day/1.73 m2 vs. 40-80 mug per day and per 1.73 m2). As the mineralocorticoid potency of this steroid is weak, we speculate that it might be the precursor of a more potent but unknown mineralocorticoid which could influence the ACTH secretion.

18-Hydroxydesoxycorticosterone↗

PubMed1976

Anti-adrenocortical activity of SKF 12185 and SKF 252 A.

The synthesis of aldosterone and 18-hydroxycorticosterone from triated corticosterone by sheep adrenal homogenate have been studied in presence of increasing concentrations of SKF 12185, a product already known as an inhibitor of cortisol synthesis. An approximately 98% inhibition of the synthesis of both steroids occurred with only 2 x 10(-4) M of the drug. In contrast, incubation of a structurally closely related compound (SKF 252 A) under the same experimental conditions resulted in an only 52% inhibition with higher concentrations (2 x 10(-3) M). These findings could explain the marked aldosterone fall that occurs in SKF 12185 treated subjects and supports the therapeutic use of this product in treatment of hyperaldosteronism.

18-Hydroxycorticosterone↗

PubMed1976

[Radioimmunoassay of tetrahydroaldosterone in urine].

A radioimmunoassay for urinary tetrahydroaldosterone is described. An antiserum, elicited by a 3-carboxy-methyloxime 18-21 aldosterone diacetate conjugated to bovine serumalbumine, with which tetrahydroaldosterone cross reacts, is used. The method is specific, sensitive (10 pg/tube), accurate, reproducible (7%), thus allowing sufficient reliability for clinical applications. In 19 normal adults subjects under unrestricted sodium intake, the urinary tetrahydroaldosterone averaged 59,8+/-29,4 mug/24 h.

Adult↗

PubMed1975

Aminoglutethimide and glutethimide: effects on 18-hydroxycorticosterone biosynthesis by human and sheep adrenals in vitro.

The conversion of [1,2-3H]corticosterone to 18-hydroxycorticosterone in vitro was studied on human and animal adrenal tissue homogenates. Human adrenals were surgically resected from a patient with Cushing's disease. Sheep adrenal homogenates were prepared from the pooled glands of 20 animals. Incubations supplemented with a NADPH generating system were performed in order to evaluate the effect of aminoglutethimide and its closely related compound glutethimide on corticosterone 18-hydroxylation in vitro. Increasing concentrations of the two drugs were assayed on both human and animal adrenal homogenates. Aminoglutethimide was clearly found to inhibit corticosterone 18-hydroxylation in sheep adrenal homogenates as a 72.6% inhibition occurred in the presence of only 0.2 mumole of the drug. Inhibition reached 91.1% in the presence of 0.5 mumole aminoglutethimide. When added to the human incubated adrenal, a 59.4% inhibition occurred in the presence of 0.5 mumole aminoglutethimide. Glutethimide, a sedative of wide clinical usage, was also found to inhibit corticosterone 18-hydroxylation but the inhibitory effect occurred only in the presence of much higher concentrations. In fact, 5.0 mumoles were necessary to obtain a 43.9% inhibition of 18-hydroxycorticosterone synthesis. This study clearly demonstrates the marked inhibitory effect of aminoglutethimide on corticosterone 18-hydroxylation. Glutethimide, to a lesser extent, also inhibits 18-hydroxycorticosterone synthesis.

18-Hydroxycorticosterone↗

PubMed1973