Immunorehabilitating effect of ultrahigh frequency electromagnetic fields in immunocompromised animals.

We observed immunorehabilitation effects of ultrahigh frequency electromagnetic fields (microwaves) in immunocompromised animals. It was shown that microwave irradiation of the thyroid gland area could abolish actinomycin D- and colchicine-induced immunosuppression and did not affect immunosuppression caused by 5-fluorouracil. These findings suggest that changes in the hormonal profile of the organism during microwave exposure can stimulate the processes of transcription and mitotic activity of lymphoid cells.

Identification of steroid biosynthetic defects in genotype-proven heterozygous individuals for 17alpha-hydroxylase/17,20-lyase deficiency.

OBJECTIVE: P450c17 deficiency (17alpha-hydroxylase/17,20-lyase deficiency, 17OHD) is a rare form of congenital adrenal hyperplasia caused by CYP17A1 gene mutations. The D487_F489 deletion in exon 8 and Y329fs in exon 6 are relatively frequent mutations of the CYP17A1 gene in China that completely abolish the enzyme activity of P450c17. However, little remains known about steroid biosynthetic functions in carriers with these mutations in a single allele of the CYP17A1 gene, who are assumed to have 50% P450c17 activity. We investigated adrenal steroidogenic function in genotype-proven heterozygotes carrying such mutations in the CYP17A1 gene in vivo. PATIENTS AND DESIGN: Eight patients and fourteen family members from five families with 17OHD were recruited. The mutations of the CYP17A1 gene in these individuals were screened by sequencing. The hormonal response to cosyntropin (ACTH) was evaluated in the 14 genotype-proven carriers and 45 age- and gender-matched normal controls. RESULTS: Fourteen carriers of the CYP17A1 mutation - seven with the D487_F489 deletion, six with Y329fs and one with H373L - were identified from the five families with 17OHD. Compared with normal controls, carriers showed lower basal and ACTH-stimulated cortisol levels but higher ACTH-stimulated corticosterone levels. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of the normal controls at the baseline and after cosyntropin stimulation. Similarly, the progesterone levels and the ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than those of the normal controls, both before and after ACTH stimulation. CONCLUSION: Genotype-proven carriers of the CYP17A1 mutation who lack apparent clinical symptoms exhibit decreased adrenal 17alpha-hydroxylase activity and altered adrenal gland reserve for steroid biosynthesis.

[Neurohumoral mechanisms of the rat heart adaptation to overload].

The present study confirms involvement of the sympathicoadrenal system in adaptation of heart to overload. Besides, at formation of chronic heart failure (CHF) there have been revealed a rise of the histamine and serotonin levels in blood plasma and myocardium as well as glucocorticoid hyperactivation.

Effects of metoclopramide and bromocriptine on the renin-angiotensin-aldosterone system in man. Dopaminergic control of aldosterone.

This study was designed to investigate the possible role of dopaminergic mechanisms in the control of the renin-angiotensin-aldosterone system in normal man. Six normal male subjects in metabolic balance at 150 meq sodium, 60 meq potassium constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. or placebo followed by angiotensin II infusion 1 h later on 2 consecutive days. Metoclopramide increased plasma aldosterone concentration from 8.2+/-2.2 to 21.0+/-3.3 ng/100 ml (P < 0.005) and plasma prolactin concentration from 18.0+/-4.0 to 91.7+/-4.0 ng/ml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrations remained elevated at 16.8+/-2.1 ng/100 ml (P < 0.01) and 86.8+/-15.9 ng/ml (P < 0.005), respectively. Angiotensin II at 2, 4, and 6 pmol/kg per min further increased plasma aldosterone concentration to 27.2+/-3.4, 31.9+/-5.7, and 36.0+/-6.7 ng/100 ml (P < 0.02), respectively. Placebo did not alter plasma aldosterone or prolactin concentrations, but angiotensin II increased plasma aldosterone concentration to 13.7+/-2.4, 19.0+/-1.9, and 23.3+/-3.2 ng/100 ml (P < 0.005). The increment of plasma aldosterone concentration in response to angiotensin II was similar after metoclopramide or placebo. The six subjects also received the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. followed by angiotensin II infusion on 2 consecutive d. Bromocriptine suppressed prolactin to <3 ng/ml. After placebo, plasma aldosterone concentration increased from 5.2+/-1.4 to 12.3+/-1.7, 17.2+/-2.2, and 21.8+/-3.5 ng/100 ml (P < 0.01) and after bromocriptine from 7.2+/-1.0 to 14.7+/-3.0, 19.8+/-3.2, and 23.4+/-1.6 ng/100 ml (P < 0.001) with each respective angiotensin II dose. No difference in the response to angiotensin II after bromocriptine or placebo was observed. Plasma renin activity, free 11-hydroxycorticoid concentration, and serum potassium concentration were unchanged by metoclopramide or bromocriptine. The results suggest that aldosterone production is under maximum tonic dopaminergic inhibition which can be overridden with stimulation by angiotensin II in normal man.

Adrenal function in 23 children with paracoccidioidomycosis.

Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies and in many clinical studies, but only in adults. Therefore, the aim of this study was to evaluate adrenal function in children with paracoccidioidomycosis. Twenty-three children with the systemic form of paracoccidioidomycosis were evaluated and divided in two Groups: Group A (n = 8) included children before treatment and Group B (n = 15) children after the end of treatment. Plasma cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium and potassium were measured. They were within normal range in all cases, except for renin activity and aldosterone, which were elevated in some cases. Group A patients showed basal and post-ACTH cortisol levels significantly greater than Group B patients. The results showed that adrenal function was not compromised in these children with paracoccidioidomycosis.

[Optimization of hepatoprotective therapy of viral hepatitis with consideration of neuromediatory link of pathogenesis].

AIM: To study therapeutic efficacy of hepatoprotective modalities on the experimental hepatitis model and in patients with parenteral hepatitis B and C regarding neurogenic amines and their coefficients. MATERIAL AND METHODS: 38 hepatoprotectors were screened for the highest activity in 1000 white rats with toxic hepatitis. Blood catecholamines (CA), histamine (H), serotonin (S), 11-oxycorticosteroids (11-OCS) were studied in 100 patients with acute hepatitis B and C. RESULTS: The recommended hepatoprotectors optimized treatment of hepatitis, led to rapid correction of abdominal and dyspeptic syndromes, normalization of bilirubin, alkaline phosphatase, cytolysis enzymes levels, improvement of neuromediatory balance. Six-month follow-up demonstrated improvement of biochemical indices in patients given hepatoprotectors with a confirmed action. CONCLUSION: Hepatoprotectors are necessary in pathogenetic treatment of acute hepatitis B and C.

[Effect of the perturbed geomagnetic field on the metabolism of the rat connective tissue during heat exposure].

The biochemical data of the researches of the perturbed geomagnetic field influence on the metabolism of the rat's connective tissue by the heating are presented. The possibility of adrenal glands reaction modification under using the perturbed geomagnetic field after high temperature is shown.

Insulin-induced hypoglycemia in conscious dogs. I. Dose-related pituitary and adrenal responses.

We have measured changes in plasma glucose, ACTH, corticosteroids, and vasopressin and hematocrit after five doses of insulin in six conscious dogs. We found insulin dose-related changes for each of these responses (P less than 0.01, by two-way analysis of variance). The increases in plasma ACTH and hematocrit correlated to the decrease in plasma glucose; the increase in plasma vasopressin was more strongly correlated with the increases in plasma Na+ than with the decreases in plasma glucose. Each dog appeared to have a characteristic ACTH response curve; therefore, the relationship between plasma glucose and plasma ACTH responses varied among dogs, but was significant in five of six dogs studied. Maximal plasma corticosteroid responses occurred with submaximal plasma ACTH responses (200-600 pg/ml). A single dose of insulin produced reproducible changes in plasma ACTH when given to five dogs in three separate experiments over a 2- to 6-month period. In these experiments, the measurement of ACTH allowed us to distinguish three levels of response to insulin, whereas measurement of the corticosteroid response allowed us to distinguish only two levels of response.

Prolonged corticotropic action of synthetic human ACTH in man.

The corticotropic activities of synthetic human ACTH (revised structure), synthetic porcine ACTH (unrevised structure) and synthetic 1-24ACTH were compared in 8 normal men by measuring the magnitude and duration of the elevation of plasma 11-hydroxy-corticosteroids following the injection of 1 mg of the peptides. The duration of response was significantly longer after human ACTH than following porcine or 1-24ACTH, although the initial responses were identical. This difference was noted after both intramuscular and intravenous administration. The data suggest that the carboxyterminal of the ACTH peptide is of some importance for biological activity and that biological species specificity may exist.

Virilizing adrenal adenoma stimulated by dexamethasone in a middle-aged woman.

In a middle-aged woman with virilizing adenoma, 2 mg dexamethasone increased urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids, whereas 8 mg dexamethasone increased urinary excretion only of 17-KS. With discontinuation of dexamethasone, 17-KS excretion returned to the predexamethasone level. Dexamethasone depressed the basal level of cAMP synthesis and basal testosterone production by the normal adrenal tissue in vitro. Dexamethasone also depressed the increase of cAMP produced by ACTH in the normal tissue. In contrast, dexamethasone increased basal cAMP synthesis and stimulated testosterone secretion in the tumor tissue. ACTH and dexamethasone were additive in their effects on cAMP and testosterone in the tumor tissue. It is suggested that dexamethasone acted directly on the adrenal tumor to stimulate steroid secretion in this patients.

Cortisol metabolism in chronic liver disease.

Impairment of cortisol metabolism, evidence of endogenous hypercortism and sensitivity to oral corticosteroids are known to occur in patients with chronic liver disease. Measurements were made of plasma 11-OHCS and urinary cortisol levels and other parameters of adrenal function in a group of such patients. The mean plasma total 11-OHCS was lower in patients than in control subjects, although this difference was not statistically significant and the normal circadian rhythm was maintained. However, in patients with chronic liver disease a greater proportion of the 11-OHCS was in the non-protein bound state resulting in an elevation of this fraction. This elevation of non-protein bound 11-OHCS must represent a resetting of the pituitary-adrenal feedback mechanism in these patients. Corticosteroid binding globulin was lower in patients than in control subjects, although the difference was not statistically significant. Urinary cortisol excretion was significantly reduced as was excretion of 17-ketosteroids. Cortisol secretion rate was found to be normal. It is suggested that elevation of plasma non-protein bound 11-OHCS, resulting from impaired metabolism and reduced protein binding of cortisol in patients with hepatic disease, may explain the features of endogenous hypercorticism seen in such patients. Moreover, in the presence of impaired steroid metabolism and reduced protein binding, these patients may exhibit an increased sensitivity to corticosteroid therapy, and therefore administration of a reduced dosage may be advisable.

Cushing's syndrome with fluctuation due to adrenal adenoma.

A case of fluctuating Cushing's syndrome due to an adrenal adenoma is described. Plasma corticosteroids were frequently low and urinary steroids fluctuated markedly over a 15-month period. Only the response to dexamethasone was consistently abnormal and indicative of Cushings's syndrome.

Altered hypothalamic-pituitary-adrenal responsiveness to dexamethasone-insulin tolerance test in active acromegaly.

Eight acromegalic patients showed a plasma cortisol (11-OHCS) rise after insulin hypoglycemia which was similar to that seen in control patients, with mean peak values (+/-SEM) of 23.2 +/- 3.5 mug/100 ml and 27.2 +/- 3.3 mug/100 ml, respectively. One mg of dexamethasone was given the evening prior to repeat insulin hypoglycemia (DEX-ITT). After dexamethasone, the control subjects showed a mean post hypoglycemic plasma 11-OHCS rise to 18.3 +/- 2.3 mug/100 ml. In contrast, acromegalic patients had a negligible rise is plasma 11-OHCS, despite a comparable degree of hypoglycemia. These data indicate that, in active acromegaly, abnormal hypothalamic-pituitary-adrenal suppressibility can be induced to insulin hypoglycemia after dexamethasone.

Diurnal rhythms of aminopyrine metabolism: failure to sleep deprivation to affect them.

After a single oral dose of aminopyrine (9 mg/kg), mean salivary aminopyrine half-lives (t 1/2s) and metabolic clearance rates in 12 normal male volunteers exhibited diurnal variations. Salivary aminopyrine t 1/2s were approximately 50% longer at 8 P.M. (2.1 +/- 0.7 hr) than at 8 A.M. (1.4 +/- 0.3 hr). Mean aminopyrine metabolic clearance rates decreased 20% from 8 A.M. (418.2 +/- 152.0 ml/min) to 8 P.M. (335.3 +/- 107.6 ml/min). There were large interindividual variations in the magnitude of these diurnal changes in aminopyrine t 1/2 and metabolic clearance rates. There were nonsignificant changes in mean aminopyrine apparent volumes of distribution (aVd) which increased only slightly from 53.1 +/- 20.6 L at 8 A.M. to 59.7 +/- 26.5 L at 8 P.M. There were diurnal variations in plasma 11-hydroxycorticosteroids (11-OHCS), mean values of which decreased 60% from 16.2 +/- 4.2 microgram/100 ml at 8 A.M. to 6.5 +/- 1.9 microgram/100 ml at 8 P.M. Sleeplessness for 24 or 48 hr under the conditions of this experiment failed to affect diurnal rhythms in aminopyrine metabolism or plasma 11-OHCS concentrations.

Temporal variations in acetaminophen and phenacetin half-life in man.

Acetaminophen (APAP) and phenacetin mean plasma half-lives were approximately 15% longer in normal male volunteers at 6 A.M. than at 2 P.M. as determined after oral administration of each drug at 6 A.M. and 2 P.M. Concentrations of plasma 11-hydroxycorticoids (11-OHCS) in these volunteers were approximately 42% higher at 6 A.M. than at 2 P.M. The mean apparent volume of distribution (aVd) of APAP decreased by approximately 13% from 6 A.M. to 2 P.M., whereas the mean metabolic clearance rate (MCR) of APAP did not change significantly. Neither the mean aVd nor the mean MCR of phenacetin changed significantly from 6 A.M. to 2 P.M. Measurement of urinary metabolites showed no alteration in APAP glucuronidation in the 8-hr period following APAP administration at 6 A.M. or 2 P.M., but indicated that after phenacetin administration 10% more of the dose was oxidatively metabolized to APAP during a 24-hr period beginning at 2 P.M. than at 6 A.M. Within each subject, plasma acetaminophen or phenacetin half-life at 2 P.M. or 6 A.M. was highly reproducible, but large interindividual variations occurred in the extent of temporal variation during this period.

The role of bacterial contamination in the isolation of apparent anti-inflammatory factors from rabbit anti-lymphocytic serum.

1 Rabbit anti-guinea-pig lymphocytic serum was fractionated by gel filtration to obtain partially purified materials possessing anti-inflammatory activity. The pharmacological properties of these materials were then studied. 2 Two fractions were found which reproducibly contained significant activity. One of these activities caused inflammation at the site of injection and was associated with high molecular weight protein (2008000). The other activity was found in low molecular weight fraction but was shown to be due to small amounts of endotoxin from Gram negative bacteria. These organisms contaminated the fractions in spite of the recommended precautions for gel filtration having been taken. 3 The endotoxin-containing fraction completely abolished leucocyte infiltration into the rat foot which had been injected with kaolin. It had no apparent effect on circulating haemolytic complement. It caused maximal elevation of serum 11-hydroxycorticosteroid concentrations and was found to cause the release of pharmacologically active amines. Many of the previously reported naturally occurring anti-inflammatory substances have similar pharmacological properties to those of the endotoxin-containing fraction. 4 It was concluded that doubt will exist about the presence of anti-inflammatory factors in mammalian body fluids unless stringent precautions are taken to exclude measurable bacterial contamination. 5 These experiments also cast doubt on the validity of accepted procedures for excluding microbial growth from columns used in the fractionation of serum.

Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog.

The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.

Studies on plasma corticosteroids in the rhesus monkey (Macaca mulatta).

The physiological regulation of the plasma corticosteroid concentration, measured by competitive protein-binding, was studied in female rhesus monkeys (M. mulatta) sedated with phencyclidine hydrochloride. Morning basal levels of plasma corticosteroids were found to be in the range 8-0-25-2 mug/100 ml, which is lower than that previously reported in this species. A circadian rhythm in plasma cortisol concentration was demonstrated. Prolonged sedation with phencyclidine was associated with a gradual increase in the plasma cortisol concentration. Synthetic alpha1-24 adrenocorticotrophic hormone given intravenously caused a rapid rise in plasma cortisol, the minimum effective dose was between 1 and 10 ng/kg body weight and the response was maximal after 1000 ng/kg. The administration of lysine-vasopressin and the induction of hypoglycaemia by insulin were both followed by an increase in the plasma corticosteroid concentration. Metyrapone caused a decline in plasma 11-hydroxycorticosteroids and a concomitant increase in total corticosteroids measured by competitive protein-binding. It is concluded that the hypothalamic-pituitary-adrenal system in the rhesus monkey functions in a manner which is qualitatively and quantitatively similar to that of man.

Effect of acute inhibition of adrenocorticotrophin secretion on plasma corticosteroids in the rhesus monkey (Macaca mulatta).

The half-life of plasma cortisol in the rhesus monkey (M. mulatta), determined by two methods, was about 130 min and longer than that in man; it was unaffected by administration of dexamethasone. Dexamethasone (5 mg, i.v.) immediately inhibited the secretion of ACTH from the monkey pituitary. The plasma half-life of NH2-terminal immunoreactive ACTH was found to be about 55 min which was much longer than the biological half-life. The adrenal synthesis of cortisol was inhibited by metyrapone which caused a prompt increase in the plasma concentration of ACTH and 11-deoxycortisol. The hypothalamic-pituitary-adrenal system of the rhesus monkey sedated with phencyclidine hydrochloride responded rapidly to alteration in the level of steroids in the circulation.

Periodic psychosis recurring in association with menstrual cycle.

We reported seven cases of patients with regularly recurring psychosis in close association with the menstrual cycle, who showed certain characteristics in common in regard to their age of onset, clinical picture, psychogenic factors, endocrine and EEG findings. In these patients, monoamine metabolisms in the central nervous system, fluctuating in connection with menstrual cycle, may be disturbed by emotional impact or other unknown causes thereby delicately deranging the central nervous system activity, mentally and physiologically.