Hormone and mediator content in the blood of the adrenals and in the peripheral blood in hypertension]

The concentration of the fractions of corticosteroids, aldosterone, catecholamines, and cyclic nucleotides (cAMP and cGMP) in blood of the adrenal veins and the activity of renin in blood of the renal veins were studied in 22 patients with stages IIA and IIB hypertensive disease. At the same time the content of these substances in the peripheral blood was determined and compared with the level of steroid and catecholamine excretion in the daily urine. An increase in the content of free 11 OCS and F fractions in the peripheral blood and blood of the adrenal veins was revealed in all patients examined.     

Iodine deficiency in the world and in the Czech Republic--current status and perspectives

Iodopenia is importance world-wide problem--the cause of spectrum of iodine deficiency disorders (IDD). The "simple" way for its compensation is iodine supplementation--preferably by iodinization of salt: in the Czech Republic prevalence of IDD was very high in the past. The complex program for compensation of iodine deficiency realized in the CR includes improvement of salt iodization, supplementation of pregnant and lactating women, fortification of products for babies' nutrition and increasing use of iodinized salt in general population incl. food industry. Thus CR is country with compensated iodine deficiency according to criteria WHO, UNICEF, ICCIDD. In future, however, systematic interest should be focused on optimalization of iodine saturation, esp. in pregnant women and evaluation of possible risk of supranormal iodine intake (impairment of thyroid function, activation of thyroid autoimmunity). Taking in account, the changes of nutrition and life style systematic monitoring of quality of iodine supplementation seems to be essential.     

Involvement of the adrenal gland in the suckling-induced decrease in LH and FSH secretion and the concomitant increase in prolactin secretion in the rat

The role of the adrenal gland in the regulation of gonadotrophin and prolactin secretion in the lactating rat was investigated. Changes in secretion of LH, FSH, prolactin, ACTH, beta-lipotrophin (beta-LPH), inhibin, corticosterone and progesterone after adrenalectomy were examined during the second half of lactation. Follicular maturation was determined by the ability of the follicles to ovulate in response to 10IU human chorionic gonadotrophin (hCG). Adrenalectomy on day 10 of lactation prevented an increase in plasma concentrations of LH and FSH in response to ovariectomy performed at the same time as adrenalectomy, and markedly stimulated secretion of ACTH, beta-LPH and prolactin. Adrenalectomy reduced the number of follicles capable of ovulating in response to hCG. Concentrations of inhibin and progesterone in the plasma significantly decreased after adrenalectomy, indicating that development of ovulatory follicles and luteal function had been suppressed. Abolishing the increase in plasma concentrations of LH and inducing a decrease in FSH in the plasma by adrenalectomy therefore prevented maturation of a new set of follicles usually seen during the second half of lactation in rats. The decrease in plasma concentrations of LH also inhibited the ability of the corpus luteum to secrete progesterone, although high concentrations of plasma prolactin were maintained in adrenalectomized lactating rats. These results indicate that the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotrophin and prolactin as well as the maintenance of ovarian function during lactation in the rat.     

Intrapulmonary chemotaxins in the normal and in the cyclophosphamide-treated host

The kinetics of intrapulmonary chemotactic activity and the generation of a pulmonary polymorphonuclear leukocytic (PMN) response during experimental Pseudomonas aeruginosa pneumonia were studied in normal and in cyclophosphamide-treated guinea pigs. In normal animals, chemotactic activity for PMN appeared in airways promptly (2 h) after infection and preceded the influx of PMN to infected airways. Week-long regimens of intraperitoneally administered cyclophosphamide, in dosages of 7.5 mg/kg/day (low-dose) or 15 mg/kg/day (high-dose), resulted in systemic myelosuppression accompanied by a dose-related decrease in recruitment of PMN to infected airways. The chemotactic activity assayed in bronchoalveolar fluids obtained from low-dose-treated animals was not affected by cyclophosphamide. However, chemotactic activity in bronchoalveolar fluids was significantly reduced (p less than 0.01) in animals receiving the high-dose cyclophosphamide regimen. Gel chromatography of bronchoalveolar fluids from infected animals revealed that a high molecular weight (20,000 daltons or greater) and a low molecular weight (5,000 daltons) chemotactic factor were present in normal specimens, and that both were absent from specimens obtained from animals receiving the high-dose treatment. Hemolytically active C5 was detected in infected bronchial fluids, but cyclophosphamide treatment did not reduce amounts of C5 in infected airways. These data suggest that in addition to myelosuppression, cyclophosphamide treatment impairs the capacity for pulmonary inflammation by reducing the normal intrapulmonary chemotactic gradient during infection.     

Fluoro-fatty acids and the impairment of cardiac function in the rat in vivo and in vitro

Summary Dichapetalum toxicarium seeds contain long chain fluoro-fatty acids, particularly fluorooleic acid, which in doses as low as 10 mg/kg can cause death. We have used the rat heart both in vivo and in vitro to assess the cardiovascular effects of various doses of the fluoro-oleic acid extract of the seeds ofDichapetalum toxicarium. Intraperitoneal administration of 0.25 ml of seed extract solution/kg body weight (estimated to be equivalent to 10 mg fluoro-oleic acid/kg body weight) or 0.5 ml/kg body weight (equivalent to 20 mg fluoro-oleic acid/kg body weight) resulted in death in all animals (n–6 in each group). The mean time from administration to death was 36.4±4 h and 21.0±2 h, respectively. Death was attributable to severe bradycardia which developed progressively throughout the experiment. Thus, during the first 6 h, heart rate fell by 32.2% from 450±7 beats/min to 305±36 beats/min (p<0.01) in the 0.25 ml/kg group and by 66±10% to 150±20 beats/min (p<0.001) in the 0.5 ml/kg group. Administration of the extract solution alone or oleic acid alone (equivalent to 0.5 ml/kg seed extract) to control rats had no effect. Investigating the effects of the seed extract in vitro, hearts (n=6 in each group) were perfused with buffer containing 0.5 ml/l seed extract (equivalent to 20 mg fluoro-oleic acid/l) or with buffer containing extract solution alone. In control hearts, there were no changes in heart rate or LVEDP over 150 min of aerobic perfusion; there were small declines in coronary flow, LVDP and LVdP/dt_max. Perfusion with seed extract resulted in a progressive decline in heart rate which, over the first 60 min of perfusion, fell by 53±7% from its control value of 323±11 beats/min to 153±20 beats/min (p<0.001). Similarly, significant declines in coronaryflow (fell by 53±12% over 60 min), LVDP (fell by 61±12% over 60 min) and LVdP/dt_max (fell by 63±7% over 60 min) were observed. LVEDP began to increase after 30 min and by 60 min had increased to 2.8±0.4 kPa (control value=0 kPa). Perfusion with oleic acid (20 mg/l) alone had no adverse effect on cardiac contractile function. Metabolic studies showed that the administration of the seed extract resulted in a loss of myocardial high energy phosphates. Thus, ATP and creatine phosphate fell from their control values of 20.6±0.4 and 27.8±0.6 mol/g dry weight to 3.9±0.4 and 2.4±0.4 mol/g dry weight (p<0.001 in each instance), respectively. Lactic acid content increased from 1.4±0.2 to 21.7±1.4 mol/g dry weight (p<0.001). In conclusion, our results indicate that the fluoro-oleic acid-containing extract ofDichapetalum toxicarium exerts its toxic effects by severely reducing cardiac function. In vivo this can lead to death of the animal.     

Calcitonin-like immunoreactivity and calcitonin gene expression in the placenta and in the mammary gland of the rat

Recently, the presence of monomeric CT in plasma and milk was reported by others in a lactating woman surgically thyroidectomized. Similarly, the placenta was thought to be a possible source of CT. Since such findings were based exclusively on immunological arguments, we have investigated the CT gene expression in these rat tissues. CT mRNAs were detected by dot-blot hybridization of total RNAs extracted from rat tissues with a 32P-labelled human CT cDNA probe. Subcellular fractions of each tissue were screened for CT-like immunoreactivity using two different antibodies. With one antibody, extracts of the mammary gland and placenta both produced full displacement of labelled human CT from the antiserum and serial dilutions of the extracts gave displacement curves parallel to that of synthetic human CT, which suggests immunological similarity. However, dilution curves were not parallel for the second antibody, and for both antisera, CT-like immunoreactivity was found in all subsellular fractions from nuclei to cytosols. Immunoprecipitation of translation products from poly (A)+RNAs of placenta showed two major bands around 30 kD. Under stringent conditions, the weak hybridization of placental RNAs seen by dot-blot under less stringent conditions disappeared. Northern analyses of total RNAs from the placenta failed to detect mRNA of 1 k base size like in thyroid glands, but hybridization under weak stringent conditions occurred with larger mRNAs (around 4.4 and 2.4 k bases). Immunoprecipitation of translation products from mRNAs of rat mammary glands showed three major bands around 46, 30 and 20 kD. Dot-blot hybridization of total RNAs extracted from mammary glands was also negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peptidergic vasodilator nerves in the peripheral circulation and in the vascular beds of the heart and brain

This overview focusses on the ubiquitous presence of immunohistochemically visible peptidergic nerves with vasodilatory function. The nerve fibres are primarily related to the parasympathetic system (vasoactive intestinal polypeptide or VIP), the sympathetic system including the adrenal medulla (enkephalins) and to the sensory system (substance P as well as calcitonin gene-related peptide, CGRP). Substance P and probably also CGRP seem to be the mediators of antidromic vasodilatation. Enkephalins appear to be released both from nerve endings and from the adrenomedullary cells. The vasodilatory nerve fibres in the heart distribute both to the coronary vessels and to functionally important parts of the myocardium, where interesting relations exist between the peptidergic flow regulation and contractile force. In the brain the sensory and parasympathetic pathways for VIP and substance P/CGRP have recently been mapped in detail, and a new peptidergic intracranial ganglion has been discovered. The selective electrical stimulation of the sensory and postganglionic parasympathetic fibres, respectively, in the brain circulation has been found to evoke a pronounced flow increase which does not appear to involve cholinergic mediation. There is also experimental evidence that the mentioned systems of fibres may interact with each other and with the sympathetic nervous system by way of neuronal cross-talk.