Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.     

Renin angiotensin aldosterone axis, including aldosterone binding globulin and blood pressure in three species of nonhuman primates

Variables of renin-angiotensin-aldosterone axis with inclusion of protein binding to specific plasma globulin (ABG), plasma cortisol, and the blood pressure (BP) were measured in 24 chimpanzees, 4 gorillas, and 16 cynomolgus monkeys. ABG activity was readily detected in plasma from the primates. In chimpanzees and gorillas, all the variables under baseline conditions were similar to those in humans. In cynomolgus (Macaca fascicularis), both the ABG binding capacity for aldosterone and the diastolic or systolic BP were significantly higher (p less than 0.001 and p less than 0.01 respectively) than in chimpanzees and gorillas.     

Simple reproducible competitive radioligand assay for plasma protein binding of aldosterone

A simple reliable and specific binding assay for the estimation of plasma (or serum) aldosterone-binding globulins (ABGs) is described. The method is based on the determination of the aldosterone-binding capacity of diluted plasma (with water 1:5), and relating it to the total aldosterone concentration in the same sample. The method distinguishes between the heat-labile and heat-stable ABG, the binding to the latter being determined following heating of plasma at 60 degrees C for 25 min. The binding to the heat-labile protein is determined by subtraction of the value for the binding to the heat-stable protein from the binding of the nonheated diluted plasma. Free aldosterone is separated from the bound fraction by adsorption of the former to dextran-coated charcoal. Two different concentrations of [3H]-aldosterone are used throughout the assay. Data obtained by incorporating chromatographic separation into the cross-reactivity procedure using several steroids are presented as evidence for the specificity of the method. This chromatography separates plasma ABG from corticosteroid-binding globulin. In 316 male or female controls, ABG capacity was 9.7 +/- 0.38% (SE)-range 2-17. Samples in females were taken during the first 8 days from the onset of menstruation. Higher ABG-binding capacity (p less than 0.001) was found during pregnancy.     

Plasma cortisol and corticosteroid-binding globulin in essential hypertension

Plasma concentration of cortisol, total CBG-binding capacity, and blood pressure were measured in control subjects (n = 171), patients with essential hypertension (EH; n = 210) and their first-degree normotensive (NR; n = 84) or hypertensive (HR; n = 66) relatives. Mean (+/- SD) plasma cortisol was significantly (p less than 0.001) decreased in EH (10.1 +/- 4.3 g/dl) patients and HR (11.7 +/- 4.1). Plasma cortisol in NR did not differ from control values (14.3 +/- 4.5) but the distribution of individual values covered the entire control-EH (14.6 +/- 5.5) range. Mean (+/- SD) CBG-binding capacity was significantly (p less than 0.001) lower in EH (14.4 +/- 3.0), NR (17.5 +/- 2), HR (17.6 +/- 2.2) as compared to controls (20.9 +/- 2.1), indicating that the decline in EH and in most relatives was mainly in plasma CBG-bound cortisol. The plasma CBG-binding capacity for cortisol was significantly negatively correlated with mean arterial pressure (MAP) in both controls (p less than 0.001) and NR (p less than 0.01) but not in either HR (r = 0.02) or never-treated EH patients. Total afternoon plasma aldosterone was higher (p less than 0.01 vs. controls) in 93 untreated EH patients (11.2 +/- 4.8 ng/dl) than in either 161 first-degree relatives (8.1 +/- 3.4 ng/dl) or 117 controls (7.6 +/- 3.5 ng/dl). The respective aldosterone-binding globulin (ABG) binding capacities for aldosterone were 21.2 +/- 6.7, 20.1 +/- 9.3 and 9.8 +/- 4.0%. In all these subjects taken together, there was a positive correlation between MAP and ABG-binding capacity (r = 51; p less than 0.001). The association of reduced plasma cortisol and decreased CBG binding capacity in EH may be closely related to altered steroid metabolism, which may be partly explained by an abnormality resembling a relative deficiency in adrenal 17 alpha- and 11 beta-hydroxylation. In some EH patients, hypertension may be the result of the ineffectiveness of plasma cortisol in preventing slightly elevated endogenous ACTH levels leading to an increase in ACTH-sensitive steroids.     

Absence of plasma protein binding of aldosterone in normal and estrogen-treated rabbit

In experiments on direct effects of prolonged administration of estrogen on In experiments on direct effects of prolonged administration of estrogen on mean arterial pressure (MAP) and plasma corticosteroid-binding variables in the rabbit the following observations were made. Estrogen had no effect on MAP but resulted in a nonsignificant stimulation of total plasma corticosteroids and a marked increase in corticosteroid-binding globulin (CBG) binding capacity which increased from a control value of 18.8 +/- (SD) 1.2 micrograms/100 ml to 28.1 +/- 2.3 micrograms/100 ml (p less than 0.001) following the administration of estrogen for the first 21 days (approx. 10 micrograms/day) and then further to 31.4 +/- 2.8 (p less than 0.001 vs. control values) after a higher estrogen dose of approximately 30 micrograms/day for the next 30 days, respectively. Plasma aldosterone concentration was not affected by estrogen treatment. In contrast to CBG, binding of aldosterone to plasma aldosterone-binding globulin was totally absent before and following the estrogen treatment. The striking difference between the rabbit showing an absence of plasma protein binding of aldosterone and several other animal species is perhaps of great importance for the blood pressure regulation and for understanding of the particular resistance of blood pressure to salt or mineralocorticoids reported in this species.     

Regulation of cardiac and renal mineralocorticoid receptor expression by captopril following myocardial infarction in rats

Myocardial infarction (MI) activates the renin-angiotensin system in the heart and increases local production of aldosterone. This hormone may increase reactive fibrosis in the myocardium favoring heart failure development. To elucidate the potential contribution of aldosterone to cardiac remodeling following MI, we evaluated the expression of mineralocorticoid receptors (MCR) in the left ventricle (LV) and kidney of rats after MI and captopril treatment. MI was induced by ligation of the coronary artery in Wistar rats, which were separated into (1) sham-operated group, (2) MI group, (3) MI-captopril treated group (cap, 50 mg kg(-1) day(-1)). One month later angiotensin converting enzyme (ACE) activity was assayed in the plasma, LV and kidney. Cardiac and renal angiotensin II (Ang II) levels were determined by ELISA and MCR mRNA expression and protein were measured by Taqman RT-PCR and Western blot, respectively. Cardiac MCR mRNA and protein levels increased nearly by 80% after MI and Cap treatment normalized cardiac MCR protein and mRNA expression. Kidney MCR expression was not affected. ACE activity increased 34% in the plasma and 83% in the LV after MI. This increase was prevented by Cap. Ang II concentration increased 225% in the LV and 193% in kidney, which was partially attenuated by Cap. Our data demonstrate upregulation of MCR in the heart following MI what may facilitate the effects of aldosterone in the ventricular remodeling process. ACE inhibitors may reduce reactive fibrosis not only by decreasing Ang II production but also by attenuating the aldosterone-signaling pathway by decreasing the expression of MCR receptors.     

Reduced urinary aldosterone excretion rates with normal plasma concentrations of aldosterone in the very elderly

Although aldosterone production declines with age, so does the aldosterone metabolic clearance rate (MCR), and the net effect of age on the circulating level of aldosterone may be less than can be predicted from production rates alone. The effect of age on aldosterone production and plasma levels was studied in a group of elderly individuals at a very advanced age when susceptibility to the impacts of age might be particularly pronounced. Seventeen nursing home patients, ages 75-99 (mean age 86 years), had aldosterone production assessed from the urinary excretion rate of the acid hydrolyzable 18-glucuronide conjugate of aldosterone. Aldosterone excretion was low in the elderly when compared to a group of healthy, young to middle-aged subjects: 123 +/- 19 (SEM) vs. 234 +/- 18 ng/h (P less than 0.001). However, plasma aldosterone concentrations in the elderly were well within a range observed in much younger and fully ambulatory subjects: 14.1 +/- 1.3 in the elderly vs. 15.9 +/- 1.8 ng/dL in the young. The plasma aldosterone concentration was apparently maintained at a normal level by a coincident decrease in both the metabolic clearance rate and the aldosterone production rate. In conclusion, an aldosterone deficiency state resulting from an age-correlated reduction in aldosterone production is probably uncommon in the elderly.     

Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters

The binding of sex steroids to plasma proteins was examined in post-natal Djungarian and golden hamsters. With dihydrotestosterone or testosterone as ligands, steady-state polyacrylamide gel electrophoresis revealed 2 androgen binding components in the plasma of young Djungarian hamsters of both sexes. The fast-moving component exhibited a low affinity and high capacity for androgens and corresponded to albumin in stained gels. In contrast, the slow moving component was a beta-globulin with high affinity (Ka = 10(9) M-1) and low capacity for androgens, and was identified as a specific sex steroid-binding protein (SBP; also SHBG). This SBP did not bind oestrogens or corticosteroids and was electrophoretically distinct from corticosteroid-binding globulin (CBG). In addition, this protein did not appear to be of testicular origin because it was present in immature females and in immature males that had been castrated for 8 days. Plasma concentrations of SBP in males as measured by a diethyl-aminoethyl-cellulose binding assay were low at birth, became significantly elevated shortly thereafter when plasma androgen values were also elevated, and subsequently fell to low levels during puberty. These changes follow the same general pattern that has been described for other mammals, including humans, during this period of reproductive development. Although the significance of elevated SBP concentrations during prepuberty has yet to be determined, it appears that the increased concentrations of high-affinity androgen binding in the plasma of Djungarian hamsters plays a role in the asynchronous pubertal development of the testes and accessory organs which occurs in this species. The post-natal SBP pattern in females was similar to that observed in males. Plasma SBP levels were low or undetectable in adults of both sexes. As previously described for adult golden hamsters, the plasma of post-natal male and female golden hamsters lacked a specific SBP: androgen binding in this species is apparently limited to albumin and CBG.     

Experimental studies on the annual cycles of thyroid and adrenocortical functions in relation to the reproductive cycle of drakes.

The annual variations in the basal plasma contents of testosterone, thyroxine and corticosterone have been measured in Peking drakes living outdoors, in Southern France. 10 The plasma testosterone titer underwent a more than 20-fold increase during the vernal reproductive period (March-April). In early June the circulating testosterone fell to near autumnal values, and the testosterone MCR was augmented. These were the first manifestations of the cessation of the vernal reproductive period. 20 The plasma thyroxine levels were minimal in autumn, moderately augmented (40%) in winter (January-March), but exhibited a 3-fold increase in early June. The resulting steep (13-fold) increase of the plasma thyroxine/testosterone ratio preceded the onset of the post-nuptial moult. 30 Modifications of testosterone secretion and clearance rate similar to those occurring in June were initiated in spring by i.m. injections of thyroxine at a dosage (1 mg/d) that induced June-July thyroxine plasma levels. On the other hand, an experimentally induced steep decrease of testosterone (castration) induced enhanced plasma thyroxine concentrations similar to the June values, while an induced (10 mg/d testosterone i.m.) hypertestosteronemia corresponding to the reproductive period depressed the plasma thyroxine levels. Strong reciprocal negative interactions between testis and thyroid might therefore afford a partial explanation of the peculiar thyroxine/testosterone imbalance that occurred in June immediately prior to the moult. 40 Cold-exposed "short-day" (December) ducks exhibited a marked increase in plasma thyroxine levels, while exposure of December ducks to "long days" (18L-6D) at 25 degrees C depressed the thyroxine titers. The inhibitory effect of "long days" on the blood level of thyroxine was further evident in castrated ducks. Exposure of "short day" ducks (December) to a combined treatment by "long days" (18L-6D) and cold (4 degrees C) produced an endocrine picture similar to the January-March pattern, i.e. highly increased testosterone plasma levels, but unaffected testosterone MCR, together with a moderate increase in plasma thyroxine concentration. 50 Corticosterone plasma concentrations increased during the reproductive season, as a result of a seasonally augmented binding-capacity of the CBG. Exogenous testosterone (10 mg/d) which induced spring-like circulating levels of male hormones, caused a similar increase in CBG-bound and total corticosterone levels. 60 In June the MCR of both corticosterone and aldosterone were elevated (as was the testosterone MCR). Similarly enhanced MCR of both corticosteroids were brought on in spring by an exogenous thyroxine treatment, leading to a June-like state of hyperthyroxinemia.     

Aldosterone and renin in essential hypertension.

A review of some recent laboratory findings indicates definite disturbances in aldosterone metabolism and regulation in patients with mild essential hypertension: (a) a significant mean increase in plasma aldosterone concentration in patients with mild and stable essential hypertension, in contrast to the absence of any difference in patients with labile borderline essential hypertension when in a normotensive phase, compared with control subjects; and (b) a significant mean decrease in metabolic clearance rate of aldosterone, associated with a 12% decrease in hepatic blood flow and an increased binding of aldosterone to a transcortin-like plasma globulin. The secretion rate of 18-hydroxy-11-deoxycorticosterone is above the upper range of normal in 60% of patients with mild, uncomplicated essential hypertension. The incidence of low-renin hypertension, when age and race are taken into account, is much lower than previously assumed. Unless measurements are repeated over a long period, one or two low values of plasma renin cannot be considered a permanent marker indicating a special category of patients with essential hypertension. Tonin, a new enzyme discovered by Boucher, which forms angiotensin II directly from a plasma protein, from the tetradecapeptide substrate and from angiotensin I, is present in most tissues, but in highest concentration in the submaxillary gland. This enzyme is under the control of beta-adrenergic receptors.     

Differential regulation of adrenal corticosteroids after restriction-induced drinking in rats

Water-restricted rats exhibit a rapid decrease in plasma corticosterone after drinking. The present study examined the effect of restriction-induced drinking on plasma aldosterone and plasma clearance of corticosterone. Rats were water restricted for 6-7 days and then killed before or 15 min after water administration; plasma and adrenal hormones were assayed. Plasma and adrenal corticosterone decreased after drinking without a change in plasma corticosteroid-binding globulin; plasma ACTH decreased or did not change. In contrast, plasma aldosterone did not change or increased after drinking; plasma renin activity was elevated by water restriction and increased further after drinking. In another experiment, rats were adrenalectomized, and corticosterone and aldosterone were replaced with pellets and osmotic minipumps, respectively. Rats were water restricted and killed. There was a small decrease in plasma corticosterone but no change in aldosterone after drinking in adrenalectomized animals. These data suggest that changes in plasma steroids after restriction-induced drinking result from zone-specific responses of the adrenal to known secretagogues, with minimal contribution from increased plasma clearance.     

Comparison of Surgery and Prolonged Spironolactone Therapy in Patients with Hypertension,Aldosterone Excess,and Low Plasma Renin

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery.Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment.In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied.Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped.In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.     

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.     

Effects of neurotrophic stress on maternal metabolism and binding of plasma cortisol in late pregnant guinea-pigs and their fetuses

The maternal metabolic clearance rate (MCR) and the binding of cortisol in the plasma of fetus and mother were estimated 8 days before term in conscious pregnant guinea-pigs, control or subjected to a neurotrophic stress (they were immobilized for 3 h in a dark room in front of an intermittent luminous flash). The maternal MCR of cortisol dropped during pregnancy related to an increase in corticosteroid binding globulin (CBG) and the stress mimicked these changes with a decrease in MCR and a rise in CBG. The increase in cortisol concentrations occurring in the fetal plasma after maternal stress could be related to the increase in free cortisol in the stressed mother. Nevertheless, although the fetal CBG did not rise after maternal stress, the increase in free cortisol in the fetal plasma remained moderate, due to the numerous free sites of CBG and albumin for cortisol.     

Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men.

Effects of an orally active angiotensin I-converting enzyme inhibitor, SQ 14225, on the actions of angiotensin I (AI) infused intravenously for 120 to 390 min were studied in 5 normal men. When 20 ng/kg/min of AI infusion was started immediately after a single oral administration of 100 mg of SQ 14225, a significant rise in blood pressure (BP) was observed for the first 15 min, but BP began to fall from 17 min and returned to the pretreatment level at 45 min. This BP level continued at least to 120 min and in one subject to 180 min. In this subject BP began to rise again from 185 min and reached the level of 15 min at 390 min. Plasma AI level increased gradually from 45 min. At 15 min plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased, but then PRA began to increase and PA began to decrease. At 120 min the values of PRA and PA were similar to the pretreatment values. In one subject plasma AI and PRA began to decrease and PA began to increase after 120 or 180 min. On the other hand, in the 5 men sole AI infusion caused a continued BP rise, PRA decrease and PA increase, and sole SQ 14225 administration caused increases in plasma AI and PRA and a decrease in PA but no BP change. From these results it was concluded that complete blockade and partial inhibition of AI conversion by 100 mg of oral SQ 14225 lasted for about 2.5 and 6.5 hr, respectively and that BP rise, PRA suppression and aldosterone stimulation after AI infusion were entirely due to the actions of angiotensin II converted from AI.     

Aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of the Australian common brushtail possum,Trichosurus vulpecula

Plasma aldosterone concentrations and the magnitude of amiloride-sensitive Na(+) transport in the proximal and distal colon of newly caught wild possums, and of possums maintained on either low or high Na(+) diets, were determined to evaluate their role in the regulation of salt content of faeces in common brushtail possums. Wild animals had a plasma aldosterone concentration of 439+/-115 pmol l(-1) and high levels of amiloride-sensitive Na(+) transport in both the proximal and distal colon. Animals maintained on a low Na(+) diet for 14 days excreted very little Na(+) in the urine and had an elevated aldosterone concentration (840+/-246 pmol l(-1)), but levels of amiloride-sensitive Na(+) transport in the proximal and distal colon were similar to those in wild animals. Conversely, while provision of a high Na(+) diet (7 days or 14 days) resulted in increased urinary Na(+) excretion and a fall in aldosterone (approximately 250 pmol l(-1)), there was no reduction in the amount of amiloride-sensitive Na(+) transport in either the proximal or distal colon. These data strongly indicate that aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of possums and that the colon is not involved in the regulation of salt content of the faeces in this species.     

Cultured epithelial cells from patients with cystic fibrosis have an increased expression of the 14 kDa Ca2(+)-binding protein CFA

The Cystic Fibrosis antigen (CFA) is a 14 kDa. Ca2(+)-binding protein known to be expressed in cells of myeloid origin during normal cell differentiation. CFA serum levels are elevated in Cystic Fibrosis (CF) patients and heterozygotes. We examined the expression of CFA in different cultured epithelial cells from controls and patients with CF. The steady state level of CFA was in general higher in epithelial cells from CF patients compared to control cells and was found to increase during cell aging. The latter difference could be attributed to an increased rate of CFA synthesis rather than to an impairment of CFA degradation or secretion, as shown by pulse chase experiments.     

Problems posed by the preparation of specific anti-cytomegalovirus immunoglobulins

The authors describe the preparation of a first batch of intravenous cytomegalovirus (CMV) immune globulin at the Nancy Regional blood transfusion centre. Immune plasmas were selected from 3 640 healthy volunteer blood donors on the basis of CF antibody titers to CMV (Kolmer's method modified) of, at least, 1:8; plasmas from approximately 10% of the donors were therefore selected. The 68 liters of pooled immune plasma had à CF antibody titer of 1:16 (CMV antibody titers of 1: 10 000 and 1: 640 when tested in the ELISA assay and passive hemagglutination assay respectively). Intravenous immune globulin was produced from pooled plasma by Cohn fractionation and treatment with pepsin at pH 4; 4.8 liters of immune globulin were prepared and divided in 96 doses of 50 ml each. The final product was found to have a CMV antibody titer of 1: 32 (CF) 1: 50 000 (ELISA) or 1: 2 560 (passive hemagglutination). Recent reports on the preparation of CMV immune globulin are briefly reviewed.     

Influence of exposure to moderate altitude on the plasma concentraton of cortisol, aldosterone, renin, testosterone, and gonadotropins

The influence of 11 days at moderate altitude (2,000 m) combined with exercise on plasma concentration of testosterone, FSH (follicle-stimulating hormone), LH (luteinizing hormone), cortisol, aldosterone, and renin activity was studied in ten healthy subjects. Within 48 h of arrival at moderate altitude a significant increase in testosterone was found whereas FSH had decreased significantly and LH showed a tendency to decrease. Cortisol increased significantly at the beginning and reached a maximum at the end of altitude exposure. The plasma aldosterone level rose continuously and on the last day of altitude was significantly elevated. Plasma renin activity showed a tendency to decrease. On return to low land all measured parameters returned to base line values within 2 days. The findings of increases in plasma levels of aldosterone and testosterone (and serum T3 and T4, as reported by others) are in contrast to the previously found decrease of urinary excretion of all these hormones. This appears to be a distinct dissociation of serum levels of adrenal (and thyroid) hormones from their urinary excretion. The observed increase in plasma aldosterone is probably mediated through ACTH and the rise in plasma potassium, since plasma renin activity showed an opposite trend. The rise in plasma testosterone is probably of adrenal origin since plasma gonadotropins declined simultaneously. The increase of plasma levels of glucocorticoids, mineralocorticoids, and androgens after an ascent from 600 m to 2,000 m above sea level is compatible with an ACTH-mediated stimulation of the entire adrenal cortex and/or a diminished elimination of adrenal steroids: The concomitant fall of FSH, LH, and plasma renin would then be a consequence of a direct negative feedback inhibition of these hormones.     

High-performance liquid chromatographic separation of corticosteroids in plasma of rats. Its application to the determination of the circadian rhythm of 18-hydroxycorticosterone related to aldosterone and corticosterone

An efficient separation of corticosteroids in plasma of rats was obtained by reversed-phase high-performance liquid chromatography (HPLC). Plasma corticosteroid assays with HPLC separation were used to determine the circadian rhythm of 18-hydroxycorticosterone (18-OHB) and its possible relationship to aldosterone or corticosterone in conscious rats under standard conditions (regular diet; 12-hour light and 12-hour dark cycle). Significant circadian rhythms of plasma corticosterone, 18-OHB and aldosterone were observed with peak values at 20.00 h and nadir values at 08.00 h. The mean ratio of plasma 18-OHB to aldosterone during 24 h was 2.4. The circadian rhythm of 18-OHB was also correlated with that of plasma aldosterone or corticosterone.