Biomedical subjects
Publications and source records attributed to L Macho.
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Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)--as well as CA-degrading enzymes-monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.
The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.
The activity of the catecholaminergic system was measured in the hypothalamus of rats which had experienced an 18.5-19.5-day-long stay in the state of weightlessness during space flights on board Soviet biosatellites of the type Cosmos. In the first two experiments, Cosmos 782 and 936, the concentration of norepinephrine and the activities of synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase and of the degrading enzyme monoamine oxidase were measured in the total hypothalamus. None of the given parameters was changed after space flight. In the light of the changes of these parameters recorded after exposure to acute stress on Earth, this finding indicates that long-term state of weightlessness does not represent an intensive stressogenic stimulus for the system studied. In the space experiment Cosmos 1129, the concentration of norepinephrine, epinephrine, and dopamine was studied in isolated nuclei of the hypothalamus of rats within 6-10 hr following return from space. Norepinephrine was found to be significantly reduced in the arcuate nucleus, median eminence and periventricular nucleus, epinephrine in the median eminence, periventricular and suprachiasmatic nuclei, whereas dopamine was not significantly changed after space flight. The decreased catecholamine levels found in some hypothalamic nuclei of rats which had undergone space flight indicate that no chronic intensive stressor could have acted during the flight, otherwise the catecholamine concentration would have been increased in the nuclei. The decreased levels must have been induced by the effect of a stressogenic factor acting for a short time only, and that either during the landing maneuver or immediately after landing. Thus long-term exposure of the organism to the state of weightlessness does not represent a stressogenic stimulus for the catecholaminergic system in the hypothalamus, which is one of the regulators of the activation of neuroendocrine reactions under stress.
The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.
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During a 25-day space mission of French cosmonaut on board Mir station, the joint Soviet-French Czecho-Slovak experiment "Minilab" has been conducted in order to evaluate a fluid-electrolyte metabolism status and its hormonal control at different flight stages and early postflight. In cosmonaut venous blood was drawn twice, and 24-hour urine samples were collected on mission Days 5 and 19. With the aid of Plasma-02 equipment the blood plasma and urinary samples were treated, frozen and maintained aboard the station. Postflight, frozen samples were delivered to the laboratory for further analyses. In-flight, urinary excretion of fluid and sodium decreased by 25-35%. On mission Day 9, the blood plasma levels of vasopressin increased by 450% and on Day 20 by 700% as opposed to the baseline levels, blood aldosterone content was also elevated with an increased renal excretion of both hormones. Blood plasma renin activity elevated two-fold, and atrio-natriuretic factor (ANF) content practically did not differ from a baseline value. In-flight circulating plasma volume (CPV) decreased by 20%. Postflight, there occurred the body hypohydration and activation of the hormonal systems providing a retention of body fluids and electrolytes to restore an adequate CPV and fluid-electrolyte homeostatic as a whole.
OBJECTIVE: Alterations in local concentrations of hormones, affecting directly synovial cells, could be involved in the modulation of the rheumatic inflammatory processes. The aim of present study was to investigate the levels of selected hormones (steroids, peptide and thyroid hormones) in synovial fluid of knee joint of patients with rheumatoid arthritis (RA) and control individuals with non-rheumatic exudate (with osteoarthrosis, OA). METHODS: Thirty-eight patients, 22 female and 16 males, with rheumatoid arthritis (RA) and 12 subjects with osteoarthrosis (OA, control group, 6 females and 6 males) participated in the study. Concentrations of cortisol (CS), 17-beta-estradiol (ES), dehydroepiandrosterone (DHEA), progesterone (PRG), aldosterone ALD), prolactin (PRL), insulin (INS), and C-peptide were determined by radioimmunoassay in synovial fluid. Insulin binding to isolated cell membrane of cells from synovial sediment was estimated by using radioiodine labeled insulin. In a group of patients (10 with RA and 4 with OS), the levels of free threeiodothyronine (FT3), TSH and growth hormone (GH) were also determined in synovial fluid. RESULTS: Increased levels of ES in synovial fluid of RA patients were observed, and higher differences were noted in men. TE concentrations were moderately elevated in synovial fluid of RA patients, however the ratio of ES/TE was significantly higher in male RA compared to OA patients. Higher levels of PRG, ALD and growth hormone were noted in synovial fluid of RA patients. Besides the steroid hormones the presence of insulin and C-peptide was noted in synovial fluid and the correlation between the levels of these two peptides was highly significant. The concentrations of INS and C-peptide in synovial fluid of patients from RA and OA group were not significantly different, however, highly significant increase of insulin binding to isolated membrane of synovial cells was found. Concentrations of cortisol, dehydroepiandosterone, prolactin, TSH and FT3 in synovial fluid were not significantly different in RA and OA groups. CONCLUSIONS: Besides the steroids also insulin, c-peptide, GH and FT3 were found in synovial fluid. The elevated ALD and GH levels in synovial fluid of RA patients and the presence of INS in synovial fluid with increase of INS binding to plasma membranes of cells from synovial fluid of RA patients suggest that besides the gonadal steroids also these hormones may affect the local inflammatory processes.
In searching for a genetic marker of type 2 diabetes we estimated the frequency of alleles of the Bgl II restriction fragment length polymorphism (RFLP) of the insulin receptor gene in a group of type II diabetic patients (n = 50), characterized by OGTT (glucose, insulin, C-peptide) and insulin receptor binding parameters. Leucocyte DNA was incubated with restriction endonuclease Bgl II and specific fragments were determined by Southern blot technique, using radioactive plasmid pINSR 13.1 as insulin receptor gene probe for hybridization. Insulin receptor numbers and receptor affinity were estimated by 125I-(Tyr-A-14)- insulin binding to red blood cells. Among control subjects the 20 kb fragment (allele Bgl II+) had a frequency of 0.21. In our group of diabetic patients this allele had a frequency of 0.10 (n.s., p greater than 0.05). In our study the insulin receptor genotype had no influence on body mass index, insulin and C-peptide during OGTT as well as insulin receptor binding data. So far, etiopathogenetic linkage between diabetes and insulin receptor variants (mutants) could unambiguously be proved in patients with extreme insulin resistance only. In our opinion, the estimation of the role of the gene as the reason underlying the disease inevitably requires the investigation of large families with multiple occurrence of type 2 diabetes.
Possible relationships between renal scars and P blood group have been recently emphasized. Urinary tract infections, an important factor in the production of renal scar, are mainly caused by specific types of E. coli, which has the ability to adhere through fimbriae, to receptors of the urinary tract epithelium that are structurally related to antigens detected in people with blood group P1. We looked for P1 sub-group in 30 children with vesicoureteral reflux and renal scar and 30 patients with equivalent degrees of reflux but without evidence of renal scar. Sex and age were unmatched. The frequency of P1 blood sub-group was similar in both kinds of patients (56.7% vs. 66.7, n.s.) so we could not demonstrate that P1 sub-group can be a useful indirect risk marker for renal scar formation.
The influence of some nutritional and hormonal factors in the growth failure detected in children of teenage mothers belonging to medium-low socioeconomic level (SEL) was studied. They were compared with children of mothers older than twenty years of the name SEL. Only growth retarded children of teenage mothers had significant delay in bone age, compared with chronological age (14.8 +/- 4.1 vs 18.2 +/- 2.2 months respectively). Children with growth failure had significantly lower plasma Zn (85.7 +/- 13.3 vs 94.6 +/- 17.9 micrograms/dl), Cu (106.2 +/- 32.5 vs 122.0 +/- 13.8 micrograms/dl) and hemoglobin (Hb) (11.7 +/- 2.1 vs 12.8 +/- 2.1 micrograms/dl) levels. No differences in plasmatic levels of thyrotropin, thyroid hormones and response of growth hormone to L-Dopa stimulation were detected in comparison with those of children with normal stature. We concluded that etiological factors of growth failure were similar in children of teenage and adult mothers according to the parameters analyzed. The increased prevalence of growth failure in children of teenage mothers may be due to a greater impact of the analyzed factors.
The concentration of ACTH, insulin, glucagon, glucose, epinephrine, norepinephrine, thyrotrophic hormone, thyroxine, and triiodothyronine was measured in plasma of the rats flown for 18.5 days on Cosmos-1129. As a result of the flight, the concentration of insulin, thyrotrophic hormone, and triiodothyronine increased and that of thyroxine decreased. It is suggested that the above changes have been induced by an acute stress associated with biosatellite reentry and touchdown.
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With the finding of HBV and HAV, it is possible at the present time to recognize according to its etiology three types of viral hepatitis: type A, Type B and type non-A-non-B. In this paper we have proved that a low socioeconomic status plays a very important role in the spreading of this disease. In a community with a low socioeconomic status, of forty children attending the fourth grade of a primary school, 97 percent were found to have anti-HA: while in a similar group of children with a higher socioeconomic background, we found only 40 per cent of positive cases. A positive sero convertion to anti-HA was found in 90 per cent of the 73 children with acute hepatitis; the remaining 10 per cent were non-A-non-B. A group of 61 children admitted to the L. Calvo Mackenna Children's Hospital with acute or chronic non hepatic disease were studied for anti-HA. We found 77% positive cases in the group of infants under 4 months old; in older infants, a low incidence of anti-HA was observed, but a notorious increase of positive cases was seen after the age of two years, reaching 100 percent of positive cases in children above four years of age. In ten patients studied with prolonged hepatitis, five of them could be possibly classified as having a non-A-non-B hepatitis.
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