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Biomedical subjects

Y Touitou

Publications and source records attributed to Y Touitou.

At least 163 records · Page 9Linked to original sources

Serum magnesium circadian rhythm in human adults with respect to age, sex and mental status.

25 subjects volunteered to document circadian changes in serum magnesium. 4 groups were formed: 7 healthy young males (24.0 years +/- 3.9), 6 elderly males (82.5 years +/- 7.5), 6 elderly females 81.2 years +/- 10.7) and 6 elderly insame subjects of both sexes (80.5 years +/- 8.6). They were socially synchronized with a diurnal activity (07.00 to 21.00 for the old subjects; 07.00 to 23.00 for the young ones) and nocturnal rest. The subjects followed a spontaneous diet. Venous blood was sampled at 4-h intervals and fixed clock hours (07.45, 11.45, 15.45, 19.45, 23.45, 03.45) during 24 h. The single cosinor method was used for the statistical analysis of the time series. A statistically significant circadian rhythm is detected in three of the groups: young males, elderly males and elderly females (no rhythm detection in elderly insane subjects). The 24-h mean is higher in elderly subjects than in the young one. The rhythm amplitude is larger in elderly males than in young ones. The acrophase (peak time) location in the 24-h scale is 10.12 h for elderly females, 11.35 h for elderly males and 16.36 h for young males.

Adult↗

Circadian and circannual rhythms in plasma hormones and other variables of five healthy young human males.

Every other month (plasma) and every month (urine) circadian rhythms were documented during the course of 14 months. Annual changes were validated in the 24 h mean of: plasma FSH (annual crest time: February), LH (March), thyroxine (September), cortisol (February), renin activity (April), testosterone (October), urinary 17-hydroxycorticosteroids (March), aldosterone (March), potassium (May) as well as sexual activity (September) [self-recorded daily]. Plasma prolactin did not show an annual variation. In addition, annual changes in the circadian acrophase (crest time location in the 24 h scale) occurred for some of the documented variables: plasma thyroxine, cortisol, renin activity, testosterone, urinary aldosterone and potassium.

17-Hydroxycorticosteroids↗

[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↗

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↗

[Circadian variations of 17-hydroxycorticosteroids and of tetrahydro-11-deoxycortisol in the healthy man: effect of the continuous administration of metyrapone (SU 4885)].

In eight apparently healthy young men a circadian rhythm (P less than 0,05) in urinary 17-hydroxycorticosteroids (17 OHCS) and tetrahydro-11-deoxycortisol (THS) has been demonstrated before (A), during (B) and after (C) a 36 h sustained oral administration of metyrapone (7.50 g in ten doses of 0.75 g every 4 h). Subjects synchronization: light-on 0715; light-off 2300. 17 OHCS have the acrophase phi located at 1430 (2:30 p.m.) in the three circumstances. Only traces of THS are excreted during A. During B and C when THS is excreted, a circadian rhythm is validated (p less than 0.05) with a phi at 1430.

17-Hydroxycorticosteroids↗

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↗

Circadian rhythms of adenosine deaminase activity in human erythrocytes: a transverse study on young, elderly and senile demented subjects.

Adenosine deaminase activity (ADA) was determined around the clock in human plasma from different groups of subjects: presumably clinically healthy women in Minneapolis, USA; healthy medical students, healthy elderly men and women, and mentally ill patients in Paris, France. In addition to analyses of variance, circadian characteristics were estimated individually and summarized by population-mean cosinor for each group. Technical and sampling considerations are documented: the individualized assessment of a circadian rhythm in adenosine deaminase is feasible in 8 out of 11 series from clinically healthy women covering 24h at 20-min intervals. A circadian population rhythm could be determined for the elderly men and women (p less than 0.05) and tentatively (p = 0.053) for the senile demented patients. A difference in circadian group rhythm characteristics found between the healthy elderly subjects and patients with senile dementia deserves further exploration.

Adenosine Deaminase↗