Biomedical subjects
Publications and source records attributed to A Riondel.
In the crystal structure of the title compound, C(9)H(14)N(2)O(3), the molecules are linked by N-H.O=C bonds into chains parallel to [001]. Large crystals are readily obtained, presumably because of the hydrogen bonds and an energetically stable conformation of the molecule.
Angiotensin II (Ang II) and potassium (K+) increase aldosterone (Aldo) production in vitro via Ca2+-dependent mechanisms. To determine the effects of Ca2+ antagonism in vivo, we examined the influence of nifedipine on the Aldo response to Na+ depletion and K+ loading in 11 healthy subjects. On the fifth day of a low-Na+/high-K+ diet (10 mmol Na+/100 mmol K+) the subjects were randomly given either nifedipine 30 mg po or placebo, and on the sixth day they received the alternative drug. KCl in 5% glucose was infused on days 5 and 6 from 10:00 to 12:00 AM (0.6 mmol/kg over 2 hours). Dexamethasone was given to suppress adrenal corticotrophic hormone. Plasma renin activity (PRA) and plasma Aldo were determined every 20 minutes. Nifedipine induced a rise in heart rate at 60 minutes but did not change blood pressure. During KCl/glucose infusions, plasma glucose increased significantly, but plasma K+ remained stable. PRA, but not baseline plasma Aldo, was stimulated by nifedipine. KCl provoked a significant and similar Aldo rise (P less than .01) under placebo and nifedipine. Baseline Aldo/PRA ratio was reduced under nifedipine when compared to placebo (P less than .01), whereas during KCl infusions this ratio was similarly elevated under placebo and nifedipine. We conclude that acute inhibition of slow Ca2+ channels does not interfere with K+-induced Aldo secretion in man, suggesting that adaptive mechanisms operate in vivo.
Plasma cortisol levels and the response of the adrenal gland to 0.25 mg ACTH administration were measured in 12 patients receiving 15 mg or more of a short-acting steroid (fluocortolone or prednisone) on three out of four days, in 10 patients on daily steroid treatment (15 mg prednisone or more per day), and in 9 normal subjects. The basal plasma cortisol level of the first group was between that of patients on daily prednisone treatment and that of normal subjects. The adrenal function in patients on the three out of four day treatment schedule appeared to be slightly diminished, yet still within the accepted limits for adrenals capable of responding adequately to stress. The adrenal function proved insufficient in all patients on daily steroids. The three out of four day steroid regimen thus offers a solution with many advantages over continuous steroid treatment for patients refractory to the alternate-day schedule.
RU 486 is a synthetic steroid hormone antagonist which acts at the receptor level. It has both intrinsic anti-progesterone and antiglucocorticosteroid properties in animals. We investigated the antiglucocorticosteroid activity in humans by evaluating the pituitary-adrenal response to RU 486 in men and in pregnant and nonpregnant women. In non-pregnant women, RU 486 (approximately equal to 1 mg/kg of body weight per day) produced an interruption of the luteal phase without affecting the pituitary-adrenal axis, thereby indicating a more potent anti-progesterone than antiglucorticosteroid effect. In the course of pregnancy interruption by RU 486 (approximately equal to 4 mg/kg per day), there was a significant increase in plasma corticotropin, beta-lipotropin, and cortisol concentrations. In normal men, RU 486 administration led to a dose-dependent stimulation of plasma corticotropin, beta-endorphin, and cortisol. This disinhibition of the pituitary-adrenal axis was only observed during the morning hours of the circadian rhythm. When administered concomitantly with 1 mg of dexamethasone at midnight, 6 mg of RU 486 per kg completely suppressed the dexamethasone inhibitory effect on the pituitary-adrenal axis. These results indicate that RU 486 is an antiglucocorticosteroid that disrupts the negative pituitary feedback of both the morning cortisol rise and administered dexamethasone. Furthermore, they demonstrate the possibility of optimizing the anti-progestational effect of the compound and its potential use for human fertility control by modifying the dose and the time of administration of the drug and thereby minimizing the antiglucocorticosteroid effect.
1. The influence of four diuretics on renal prostaglandins was investigated in a study designed in two parts (A and B): A, 24 normal subjects on a constant sodium intake received frusemide (80 mg daily), or hydrochlorothiazide (100 mg), or triamterene (200 mg) or spironolactone (300 mg); B, the same subjects were pretreated for 3 days with indomethacin (150 mg daily), which was continued during the 3 day administration of the respective diuretics and during a 2 day post-diuretic period. 2. In study A, only triamterene provoked a rise in urinary prostaglandins E2 and F2 alpha (+ 474 +/- SEM 92%, P less than 0.01, and + 192 +/- 7%, P less than 0.01). In study B, prostaglandins were significantly inhibited in all subjects. After indomethacin, the natriuretic effect of frusemide and spironolactone was reduced by 80 +/- 12% (P less than 0.01) and 54 +/- 11% (P less than 0.001), whereas the natriuresis induced by hydrochlorothiazide and triamterene was unchanged. No correlation was found between urinary PGE2 and F2 alpha and natriuresis. 3. When triamterene was associated with indomethacin, two subjects developed reversible acute renal failure. 4. Plasma renin activity and urinary aldosterone were stimulated by the four diuretics in study A, but their response was blunted in study B. Urinary antidiuretic hormone was not modified by diuretics but was suppressed by indomethacin. 5. Diflunisal, a structurally unrelated nonsteroidal anti-inflammatory drug, given to 12 of the subjects provoked similar interactions with frusemide, hydrochlorothiazide and spironolactone. 6. The results suggest that prostaglandins contribute to the natriuretic effects of frusemide and spironolactone, but not to those of hydrochlorothiazide and triamterene.
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RU-486 is a steroid which possesses a great affinity for the progesterone receptor, does not have a progesterone activity, but is indeed a strong antagonist of progesterone effects in animals. Oral administration induces the interruption of the luteal phase of the menstrual cycle and that of early pregnancy in women. Its mode of administration and its properties enable us to envisage a new methodology for menstrual cycle regulation and human birth control.
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The influence of the dopaminergic agent 2-bromoergocryptine on plasma aldosterone response to acute stimulations was assessed in 14 normal male volunteers. Without modifying basal plasma aldosterone levels or urinary aldosterone excretion, bromocriptine retarded and diminished significantly the plasma aldosterone response to angiotensin II or ACTH, but did not alter the response to upright posture. These results point to a bromocriptine-induced modulation of the plasma aldosterone response to direct stimulations at the adrenal level. The present work brings further evidence for an effect of the dopaminergic system on the physiological control of aldosterone.
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Treatment of urine or of a urine extract with periodate followed by treatment of the acidic oxidation products with sodium bismuthate gave a mixture of neutral end products consisting only or predominantly of 17-oxoandrostanes derived from the corresponding urinary pregnane-17,21-diol-20-ones. The mixture of end products was resolved by gas-liquid or paper chromatography. The latter technique was used to determine cortisol secretion rates and the results were found to be in reasonable agreement with those obtained by a double-isotope method. Gas-liquid-chromatographic characterization of steroidal 4-en-3-ones is described.
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To assess the relationship between pressor and depressor factors in essential hypertension, the urinary excretion rates of prostaglandins E2 and F2 alpha, kallikrein, vasopressin and aldosterone were compared between 53 untreated hypertensive patients and 53 age- and sex-matched normotensive controls. Mean basal levels of plasma renin activity and of urinary prostaglandins, vasopressin and aldosterone were similar in both groups, but urinary kallikrein was significantly lower in the hypertensive patients. A weak relationship was found in the hypertensives between diastolic blood pressure, and vasopressin or aldosterone, and between vasopressin and prostaglandin E2, and in the normotensives between vasopressin and prostaglandin F2 alpha. In conclusion, these results do not provide evidence for an important imbalance between pressor and depressor factors in essential hypertension, as reflected by the urinary excretion of the major humoral factors and hormones involved in the regulation of blood pressure.