Avinoam Kowarski

The transplacental passage of prednisone and prednisolone in pregnancy near term

The transplacental passage of prednisone and prednisolone was studied in late pregnancy during a constant infusion of the radioactive steroids to mothers at the time of elective cesarean section. The metabolic clearance rates, conversion ratios, and transfer constants of prednisone and prednisolone of the mothers were compared with those of normal women and women receiving contraceptives. It was found that irrespective of whether 3 H-prednisone or 3 H-prednisolone was infused, the concentration of 3 H-prednisolone in the maternal plasma was significantly higher than that of 3 H-prednisone. The maternal 3 H-prednisone concentration was similar to the fetal 3 H-prednisone concentration. The fetal 3 H-prednisone concentration was not significantly different from the fetal 3 H-prednisolone concentration which was, however, about 8-to 10-fold less than the maternal 3 H-prednisolone concentration. Pregnancy and contraceptive-medication had no effect on the metabolic clearance rates of prednisone or the conversion ratio of prednisone to prednisolone. The metabolic clearance rate of prednisolone was significantly lower than that of prednisone in both pregnant and nonpregnant women.

The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia

The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH.

Estimation of the Secretion Rate of Insulin from the Urinary Excretion Rate of C-Peptide: Study in Obese and Diabetic Subjects

Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its urinary clearance (UCI-C) is constant and unaffected by plasma C-peptide concentration, body mass, or diabetes. We measured clearance ratios of C-peptide/creatinine (CR) in the fasting state and integrated 0–1, 1–3, and 3–5 h after 100 g of glucose p.o. as well as over a full 24-h in eight obese, eight lean, and six maturity-onset diabetic subjects. CR did not differ significantly when values in the fasting state were compared with those in the postprandial periods and was therefore unaffected by plasma C-peptide concentration. Furthermore, CR was similar in the lean, obese, and diabetic subjects. SR-C, determined as the product of the metabolic clearance rate of C-peptide and its fasting or integrated plasma concentrations, correlated significantly with U-C in all the subjects (r = 0.87, P < 0.0001). The correlation of U-C with SR-C in the diabetic subjects alone was also significant (r = 0.88, P < 0.0001). In conclusion, our data support the use of U-C as an indirect measure of SR-C and therefore of SR-I.

Fetal and Maternal Secretion Rate of Cortisol in Sheep: Diffusion Resistance of the Placenta

Extract: Three pregnant ewes and their fetuses, in utero, were infused constantly with 14C-cortisol and 3H-cortisol. The maternal concerntrations of cortisol in plasma were 5.24±1.15 μg/100 ml and the fetal concentrations in plasma were 2.39±0.25 μg/100 ml. Metabolic clearance rates were estimated to have a mean of 1,397 liters/24 h in the ewes and 92 liters/24 h in the fetuses. The mean rates of blood production for the ewe and the fetus were 73.6 and 2.14 mg/24 h, respectively. Application of the theoretical model presented, allowed us to calculate the contribution the mother was making to the cortisol concentration in the plasma of the fetus and vice versa. We also calculated the ratio of relative resistance for transplacental passage of cortisol.Speculation: From the model proposed, it was calculated that the fetus contributed very little to the maternal cortisol levels. In two experiments, more than 60% of the fetal origin, while in another experiment, almost all the cortisol was produced by the fetus. We speculate, therefore, that a ‘plcental barrier’ exists in sheep during pregnancy. The physiological role of this barrier remains to be determined.

Comparison of competitive protein binding radioassay of cortisol to double isotope dilution and Porter Silber methods.

Abstract The competitive protein binding radioassay of corticoids was performed on 4 pools of plasma, and the results compared to those obtained on the same pools by paper chromatography and protein binding, double isotope dilution, and colorimetric (Porter-Silber reaction) techniques. In the low and normal ranges, the colorimetric method was the only one significantly different, i.e., higher. In the high ranges the colorimetric method was significantly higher; while the paper chromatography and protein binding techniques were significantly lower than the protein binding radioassay for corticoids.

The effect of acth administration on plasma testosterone, dihydrotestosterone and serum lh concentrations in normal men

Abstract Plasma cortisol (F), testosterone (T), dihydrotestosterone (DHT) and serum luteinizing hormone (LH) concentrations were measured in 8 normal young men at 8 AM on two control days. Exogenous adrenocorticotrophin (ACTH) 20 U.S.P. units per m 2 of body surface area every 12 or 6 hours was administered intramuscularly for 4 days. Twenty-four hours after starting ACTH administration, the plasma T and DHT concentrations were significantly lower than those of the control days on a paired t test. No significant change in serum LH concentration could be demonstrated. Similar results were observed after 48, 72 and 96 hours of ACTH stimulation.

Measurement of plasma dihydrotestosterone by competitive protein-binding analysis

Abstract A competitive protein binding method for the measurement of dihydrotestosterone (DHT) concentration in plasma is described. The mean recovery throughout the procedure was 75 ± 11%. Water blanks (10 ml) ranged from 0 to 0.2 ng per sample. The precision and accuracy were good. The specificity was checked by preparation of two further derivatives of DHT. Mean plasma values of DHT for normal adult women and men were respectively 21.7 ± 4.3 (S.D.) and 50.1 ± 14.4 (S.D.) ng/100 ml. Simultaneously by taking a smaller aliquot following the paper chromatography, plasma testosterone (T) concentrations could be measured by competitive protein binding.

Adrenal function in normal infants and in marasmus and kwashiorkor: Plasma aldosterone concentration and aldosterone secretion rate

In normal infants 2.1 to 3.2 months of age and in those 4.8 to 10.6 months of age, plasma aldosterone concentrations were, respectively, 88±42 and 61±43 ng. per 100 ml. (S.D.) and the aldosterone secretion rates were 75±21 and 70±36 μg per 24 hours. Older infants, 12.5 to 18.5 months of age, had plasma aldosterone levels of 17±7 ng. per 100 ml. and aldosterone secretion of 73±43 μg per 24 hours. The plasma aldosterone concentrations of the two younger groups were significantly higher than that of the 12.5-to 18.5-month-old children (p

A 24-hr monitoring of the integrated plasma concentration of aldosterone and cortisol in manic patients

Abstract (1) A 24-hr continuous monitoring of the fluctuations of plasma levels of cortisol and aldosterone was carried out in three manic-depressive patients during the manic phase. This study was done using a newly developed, portable, non-thrombogenic, constant blood-withdrawal system, that made possible the collection of blood samples for a 24-hr period, without interfering with the activity of the patient. The integrated concentration of aldosterone and cortisol in the plasma of the patient was determined every 20 min using radioimmunoassay, and competitive protein binding method respectively. The results of these studies were compared with those obtained in six normal subjects during a day of normal activity. (2) The 24-hr integrated concentration of aldosterone in patients was found to be 11.2, 13.6 and 14.2 ng/100 ml. These results were above the range found in healthy subjects (3.8–10.7 ng/100 ml). These findings are in agreement with the higher than normal levels of plasma aldosterone obtained from single blood samples in seven manic patients. (3) The 24-hr integrated concentration of cortisol of the three manic patients were 8.6, 8.2 and 11.4 μg/100 ml (normal range: 3.7–8.4 μg/100 ml). The previously described peaks of cortisol levels in normal subjects, which have been shown to be often related to emotional stress (De Lacerda, Kowarski & Migeon, 1973) were also present in manic patients. However, the underlying diurnal variation detected in all control individuals was not present in the manic patients. This could be related to the lack of regular sleeping pattern in patients during their manic phase.

Adrenal function in normal infants and in marasmus and kwashiorkor. Cortisol secretion, diurnal variation of plasma cortisol, and urinary excretion of 17-hydroxycorticoids, free corticoids, and cortisol.

Normal infants exhibited circadian rhythmicity of plasma F concentration. Infants from 2.1 to 3.2 months of age had CSR significantly higher than those of older infants. THF/THE urinary excretion ratios increased with age. The 17OHCS excretion was higher in the younger infants. Urinary excretions of free corticoids and cortisol were similar in all age groups. In marasmus, plasma F concentrations in the morning and evening were significantly elevated. Normal diurnal variation returned following therapy. CSR and 17OHCS excretions were not different from age controls, but were significantly lower than size controls, THF/THE ratios, urinary excretion of free corticoids and cortisol were normal. In marasmic kwashiorkor, plasma F concentrations were significantly elevated in the morning and evening. There was a suggestive decrease with therapy. CSR was low before and after treatment. THF/THE ratios, urinary 17OHCS excretion, and urinary free corticoids and cortisol were not significantly different from infants matched for size or patients with marasmus.