Inese Z. Beitins

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 Regulation of Aldosterone Secretion in Anephric Man

The regulation of aldosterone secretion in anephric man was investigated in studies on nephrectomized patients who were being intermittently hemodialyzed while awaiting renal transplantation. The effects of supine and upright posture on the concentration of plasma aldosterone on the 1st day postdialysis and on a 3rd or 4th day postdialysis were compared to the effects of postural variation in normal subjects who were on a low sodium intake and on a high sodium intake. In contrast with the normal subjects who exhibited higher concentrations of plasma aldosterone after 2 hr of upright posture than in the supine position and low concentrations of plasma aldosterone on a high sodium intake, the anephric patients showed less consistent variations in plasma aldosterone due to changes in posture and exhibited higher concentrations of plasma aldosterone on the 3rd or 4th day postdialysis, despite an increase in body weight, than on the 1st day postdialysis. The increase in the concentration of plasma aldosterone in the anephric patients between the 1st day postdialysis and the 3rd or 4th day postdialysis indicates that aldosterone secretion is not responding primarily, in this situation, to volume-related stimuli. There was a high degree of correlation between the concentration of plasma aldosterone and the corresponding levels of serum potassium concentration, which also rose significantly between the 1st day postdialysis and the 3rd or 4th day postdialysis. Furthermore, when potassium accumulation between dialyses was prevented in three of these patients, the concentration of plasma aldosterone fell to minimally detectable levels. The results of these studies suggest that the primary regulator of aldosterone secretion in the absence of the kidneys is potassium.

Plasma Aldosterone Concentration at Delivery and during the Newborn Period

Aldosterone concentrations in plasma of women on normal sodium intake undergoing cesarean section were 3.7+/-1.4 ng/100 ml (mean+/-1 SD). These values were significantly lower (P < 0.001) than those observed in mothers on normal sodium diet, delivered by the vaginal route (14.9+/-7.0 ng/100 ml). A significant elevation (P < 0.001) of the concentrations was found if the mothers had been on sodium restriction and/or diuretics (44.9+/-24.2 ng/100 ml). In supine position, adult nonpregnant subjects have aldosterone concentrations in plasma of 1.7+/-1.4 ng/100 ml on normal sodium intake and of 16.7+/-8.1 ng/100 ml on low sodium diet.Simultaneous determinations of aldosterone levels in cord blood showed that cord values were significantly higher than those of the corresponding mother (P < 0.01 by paired t test). However, values in cord blood of infants born to mothers on a normal sodium intake were significantly lower (P < 0.005) than those of infants whose mothers had required low sodium diet and/or diuretics during their pregnancy. Aldosterone concentrations in plasma of infants 1-72 hr of age and born to mothers on normal sodium intake were 25.9+/-11.7 ng/100 ml (mean +/-1 SD). These values were significantly lower (P < 0.005) than those of infants born to mothers on restricted sodium intake with or without diuretics (80.3+/-54.4 ng/100 ml). The concentrations at birth were not significantly different from those observed during the first 3 days of life (P > 0.6).

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. 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.

A dynamic study of plasma renin activity and aldosterone concentration in normal and hypertensive subjects

Abstract Variations of plasma renin activity (PRA) and plasma aldosterone concentration have been studied after a water load with a 2-hour period of recumbency followed by furosemide infusion in five normal subjects and seven hypertensive patients. It has been found following furosemide infusion that there is a lag of 15 min between the increase in PRA and that of aldosterone. PRA and aldosterone levels are still elevated when diuresis and natriuresis have returned close to normal. Patients with essential hypertension behave like normal subjects during this dynamic test except for one patient with abnormally low PRA and low normal levels of plasma aldosterone. The two patients with primary aldosteronism were able to modify their aldosterone concentration as normal subjects did, but at all times their levels remained higher. Plasma aldosterone concentration as a diagnostic screening test should be performed in the upright position.