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Biomedical subjects

A Bogdan

Publications and source records attributed to A Bogdan.

At least 73 records · Page 4Linked to original sources
PubMed1984

11 beta-Hydroxy-11-ketosteroids equilibrium, a source of misinterpretation in steroid synthesis: evidence through the effects of trilostane on 11 beta-hydroxysteroid dehydrogenase in sheep and human adrenals in vitro.

Trilostane is known as an inhibitor of 3 beta-hydroxysteroid dehydrogenase. Conflicting data published on this drug led us to look for the effects of 0.02 to 0.5 mM of trilostane on the in vitro steroid synthesis in sheep adrenals and human adrenals (Cushing's or Conn's syndrome) in the presence of an NADPH-generating system. The synthesis of 4-androstenedione, 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione were studied either from dehydroepiandrosterone or 4-androstenedione or 11 beta-hydroxyandrostenedione. The synthesis of 11-deoxycortisol, cortisol, cortisone, 4-androstenedione, 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione were studied either from 17-hydroxyprogesterone or 11-deoxycortisol or cortisol. This study showed that trilostane inhibited 3 beta-hydroxysteroid dehydrogenase whereas it had no effect on 21-, 11- and 17-hydroxylase. Trilostane was responsible for an increased 11 beta-hydroxysteroid dehydrogenase activity in vitro, resulting in low yields of cortisol and 11 beta-hydroxyandrostenedione, and high yields of cortisone and 11-ketoandrostenedione. This unexpected effect of trilostane allowed us to show that erroneous conclusions (in this case: pseudo inhibition of 11 beta-hydroxylase) can be drawn if all the metabolic pathways from a determined precursor are not exhaustively documented when studying the effects of drugs on steroid synthesis in vitro. The decrease of cortisol synthesis by trilostane may thus be related to the effects of the drug on both 3 beta-hydroxysteroid-dehydrogenase (inhibitory effect) and 11 beta-hydroxysteroid-dehydrogenase (stimulatory effect). This latter effect was found to be species-dependent.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1984

Patterns of plasma melatonin with ageing and mental condition: stability of nyctohemeral rhythms and differences in seasonal variations.

Effects of ageing and mental condition on the nyctohemeral and seasonal rhythms of plasma melatonin in human subjects were investigated. Four groups of subjects were formed for a transverse study: 7 healthy young men (24 years), 6 elderly women, 6 elderly men and 6 elderly patients (2 men and 4 women) suffering from senile dementia (70-80 years). The subjects were synchronized. Blood samples were taken every 4 h during 24 h in January, March, June and October. In comparison to young men, the plasma levels of melatonin were markedly decreased (by about one half) in elderly subjects without any difference according to sex or mental condition. Nyctohemeral rhythms of the hormone were validated in all groups and at all sampling sessions. The nyctohemeral acrophases were remarkably stable (around 03.00 h) whatever the season, age or sex. A seasonal variation was found in all groups (except elderly women) with differences between young and elderly subjects: plasma melatonin levels were significantly lower in January than in June in young men, whereas in elderly subjects they were significantly lower in October than in January/March. No significant difference was observed in mesor, amplitude or acrophase of nyctohemeral and seasonal rhythms of plasma melatonin in patients with senile dementia when compared with healthy elderly subjects. The stability of the nyctohemeral peak time whatever the age group or season as opposed to the differences in the seasonal pattern of plasma melatonin according to the age groups raises the problems of both outdoor photoperiod and ageing in ruling the secretion of melatonin in man.

Adult↗
PubMed1983

Experimental evidence for biosynthesis of steroids in metastatic tissue originating from a primitive adrenocortical carcinoma.

1. Cortisol, cortisone, 11-deoxycortisol and deoxycorticosterone were synthesized in large amounts in vitro by a metastatic tissue from an adrenocortical carcinoma. 2. Both 11 beta- and 21-hydroxylase were very active. 3. A secreting metastasis can be thus responsible for a biological relapse. 4. A metastasis originating from another secreting adrenocortical carcinoma was found to be non-secreting.

Adrenal Cortex Neoplasms↗
PubMed1983

Seasonal rhythms of plasma gonadotrophins: their persistence in elderly men and women.

Circannual changes of immunoreactive LH and FSH were documented on a circadian basis in January, March, June and October in four groups of subjects: seven young men, six elderly men, six elderly women and six men and women suffering from senile dementia. The sampling was serially dependent only for the young men and the core subgroups of elderly men and elderly women. A circadian rhythm for FSH was not detected in any group of subjects during any of the sampling sessions, whereas a circadian rhythm for LH was detected twice (June and October) in young men, once (October) in elderly demented patients, and not at all in the groups of elderly men and women. Both 24-h and yearly mean levels of gonadotrophins were higher in elderly subjects (two-to 25-fold according to the hormone, sex and season) than in young men. Circannual rhythms of plasma LH with large amplitudes were validated by the cosinor method, with an acrophase located in April or May. A circannual rhythm of plasma FSH was validated only in young men, with an acrophase in October. The persistence of a circannual rhythm of plasma LH with large amplitude in elderly subjects, associated with high mean levels of the hormone, especially in elderly women, suggests that this bioperiodicity of the pituitary gland is independent of gonadal function.

Adult↗
PubMed1983

Adrenocortical hormones, ageing and mental condition: seasonal and circadian rhythms of plasma 18-hydroxy-11-deoxycorticosterone, total and free cortisol and urinary corticosteroids.

The circannual rhythms of plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and free cortisol have been documented on a circadian basis in January, March, June and October in seven young men (24 years old), six elderly men, six elderly women and six elderly demented subjects, both men and women, in their eighties. Blood samples were drawn every 4 h over a 24-h period at each sampling session and urine samples were collected at 4-h intervals only from the young men. A circadian rhythm of 17-hydroxy-corticosteroids (17-OH-CS), 17-ketosteroids (17-KS), urinary free cortisol and 18-OH-DOC was defined for each of the four seasons with stable acrophases throughout the year and the same excretory profiles. A circannual rhythm was validated in young men for 17-OH-CS, urinary free cortisol and 18-OH-DOC but not for 17-KS. A circadian rhythm of plasma free cortisol, the active form of the hormone, plasma total cortisol and plasma 18-OH-DOC was validated in all groups and at all the seasons at which samples were taken. The secretory profiles of 18-OH-DOC, free and total cortisol were very similar, with no differences attributable to age, sex or mental condition except for the levels of plasma free cortisol and 18-OH-DOC which were higher and lower respectively in the elderly subjects. Whereas a circannual rhythm of plasma 18-OH-DOC was validated for all groups, a circannual rhythm of both free and total cortisol in the plasma was validated in young men but not in any group of elderly subjects. This loss of the circannual rhythmicity of cortisol in the elderly may reflect the decrease with age of the capacity to adapt to seasonal external factors.

17-Hydroxycorticosteroids↗
PubMed1983

Differences in the seasonal rhythmicity of plasma prolactin in elderly human subjects: detection in women but not in men.

Effects of age, sex and mental condition on the circadian and circannual rhythmicity of plasma prolactin in human subjects were investigated. Circannual changes were recorded on a circadian basis in January, March, June and October in four groups of subjects: seven young men, six elderly men, six elderly women and six senile demented patients (two men and four women). Blood samples were drawn every 4 h over a 24-h period at the four sampling sessions. Circadian rhythms of the hormone were validated in all groups and at all sampling sessions except twice in elderly demented subjects. The 24-h mean levels of prolactin in plasma were approximately the same in young and elderly subjects. The circadian acrophases were most often located in the vicinity of 02.00-04.00 h. The circannual rhythmicity of the hormone showed a sex difference; the rhythm was not validated in either young or elderly men but was detected in the groups of elderly women and elderly demented patients (mainly women). The acrophases were located in May. This paper strongly suggests a sex difference in the circannual rhythmicity of plasma prolactin levels in elderly subjects.

Adult↗
PubMed1983

Alterations in circadian rhythmicity in calcium oxalate renal stone formers.

The circadian (circannual for oxalic acid) variations of 13 urinary variables (volume, creatinine, calcium, oxalic acid, glycolic acid, 17-ketosteroids, 17-hydroxycorticosteroids, phosphates, urea, uric acid, chloride, sodium, and potassium) have been documented in 7 calcium oxalate renal stone formers and 7 healthy men (control group). Urine was collected every 4 h over a period of 24 h. All subjects had the same synchronization: diurnal activity from 07(00) to 23(00) +/- 1 h and nocturnal rest; meals were given at fixed clock hours (08(00), 12(30) and 20(00) +/- 1 h). A statistically-significant rhythm (p less than 0.05) was validated for all variables except urea and calcium in healthy men. In renal stone formers, 6 variables (calcium, oxalic acid, and glycolic acid in particular) had no detectable circadian rhythm. However, a periodicity of c. 8 h (ultradian rhythm) was demonstrated for calcium and oxalic acid with peaks being located around 02(00), 10(00), and 18(00). No circannual variations in oxalic acid output could be observed. The present study shows an alteration of the periodicity of calcium and oxalic metabolisms, i.e. the loss of a circadian (24-h) rhythm and the occurrence of an ultradian rhythm of 8 h. The risk of calcium-oxalate crystallisation appears thus greater at 02(00), 10(00), and 18(00). Furthermore, any study dealing with oxalic acid excretion should state the season of urine collection when comparing renal stone formers and healthy subjects, as significant differences in oxaluria may appear during the summer months and not during the rest of the year.

Adult↗
PubMed1982

Adrenal circadian system in young and elderly human subjects: a comparative study.

Circadian changes in plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and unbound cortisol were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients of both sexes. The daily activities of the subjects were synchronous; blood samples were taken every 4 h and 4 hourly urine samples were collected only from the young men. A circadian rhythm was defined for plasma 18-OH-DOC, total and unbound cortisol in all groups; the secretory patterns of these steroids were parallel, as were the profiles of urinary 18-OH-DOC and unconjugated cortisol. When compared with respect to sex, the 24-h mean level of total cortisol was higher in women; that of unbound cortisol was higher in the three groups of elderly patients than in the young men. No major changes in plasma steroids were observed between elderly demented patients (mainly women) and healthy elderly women. The phasing of total and unbound cortisol showed no major modifications with age, sex or senile dementia. Acrophases of 18-OH-DOC were earlier in elderly patients than in young men. Amplitudes were not modified with sex in elderly patients but were always lower in the demented patients. A circadian rhythm was defined for 18-OH-DOC, unconjugated cortisol, 17-hydroxycorticosteroids (17-OH-CS) and 17-ketosteroids in the urine of the young men. The acrophases of 18-OH-DOC and unbound cortisol were close, as were those of 17-OH-CS and 17-ketosteroids. The lag was short between the acrophases of 18-OH-DOC in plasma and urine and between those of plasma unbound cortisol and urinary unconjugated cortisol; it was much larger between the acrophases of plasma total cortisol and 17-OH-CS. Thus, the process of ageing, and the possible alterations in the central nervous system which are often seen in normal ageing, induced no major modifications in the temporal organization of adrenocortical function, even in subjects who were very advanced in age.

17-Hydroxycorticosteroids↗
PubMed1981

Age- and mental health-related circadian rhythms of plasma levels of melatonin, prolactin, luteinizing hormone and follicle-stimulating hormone in man.

Circadian changes in plasma levels of melatonin, prolactin, LH and FSH were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients (two men and four women). The daily activities of the subjects were synchronous and blood samples were taken every 4 h. The 24-h mean concentrations of prolactin in plasma were the same in all groups, whereas those of LH and FSh were twice as high in the elderly as in the young men and eight and 23 times higher respectively in the elderly women. The 24-h mean plasma levels of melatonin in the elderly were half those in the young, but were not influenced by the sex or mental condition of the subjects. A statistically significant circadian rhythm for melatonin was defined in the four groups, for prolactin in all groups except the elderly men and for LH only in the demented patients and in the young men. No circadian rhythm could be detected for FSH in any of the four groups. The acrophases of melatonin and prolactin ranged between 02.30 and 04.00 h, those of LH (when a rhythm was validated) clustered around 01.00 h. The circadian rhythms of plasma levels of melatonin, prolactin and LH are not modified in old age nor in dementia. A positive correlation has been demonstrated in young men between melatonin and LH and between melatonin and prolactin, but no such correlation could be found in the elderly.

Adult↗
PubMed1979

In vitro biosynthesis of 18-hydroxy-11-deoxycorticosterone from deoxycorticosterone by human adrenal glands removed from patients with hypercorticism.

The biosynthesis of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) was studied by in vitro incubations of human adrenals resected from patients with Cushing's syndrome, using deoxycorticosterone as precursor. 18-OH-DOC synthesis was similar in adrenals from normal subjects and in those derived from patients with different types of Cushing's syndrome (hyperplasia, adenoma, carcinoma). The in vitro addition of o,p'-DDD (5 x 10(-3) M) to an adrenocortical carcinoma incubation did not alter 18-OH-DOC biosynthesis. By contrast, treatment of the patient with o,p'-DDD prior to adrenalectomy resulted in a low production of 18-OH-DOC in vitro but only when cortisol synthesis was drastically decreased.

18-Hydroxydesoxycorticosterone↗
PubMed1979

Glucocorticoid and mineralocorticoid pathways in two adrenocortical carcinomas: comparison of the effects of o,p'-dichlorodiphenyldichloroethane, aminoglutethimide and 2-p-aminophenyl-2-phenylethylamine in vitro.

The synthesis of glucocorticoids and mineralocorticoids in vitro was studied in an adrenocortical carcinoma after alblation from an 11.5-year-old boy. This patient had been unsuccessfully treated with high doses of o,p'-dichlorodiphenyldichloroethane (o,p'-DDD) and aminoglutethimide. These in-vitro results were compared with those obtained with another adrenocortical carcinoma removed from a 26-year-old woman who had received no preoperative treatment. The sensitivity of these adrenocortical carcinomas to o,p'-DDD, aminoglutethimide and 2-(p-aminophenyl)-2-phenylethylamine (SKF 12185) was investigated. Synthesis of cortisol (47%) and corticosterone (45%) in control incubations showed that 11 beta-hydroxylase activity was not affected by the treatment. This explains the raised level of plasma cortisol in the treated child. All three compounds inhibited both 11 beta-hydroxylase and 18-hydroxylase activities up to 95%, depending on the inhibitor. This study shows (a) an inhibitory effect of o,p'-DDD on the steroidogenesis of an adrenocortical carcinoma in vitro, an effect not previously reported in man or laboratory animals, and (b) the in-vitro efficacy of o,p-DDD and aminoglutethimide on corticosteroidogenesis by a carcinoma unresponsive to treatment in vivo. This discrepancy between data obtained in vivo and in vitro could possibly be explained by either an insufficient ratio of ingested dose: tumour mass, or a malabsorption of the drugs in this patient.

Adrenal Cortex Neoplasms↗
PubMed1978

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↗
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↗