In order to ascertain the kinetics of absorption and metabolism of transdermally administered dehydroepiandrosterone (DHEA), 10 men 29-72 years old (mean 52.4±14.5) received 50 mg DHEA/day in a gel applied onto the skin of the abdomen for 5 consecutive days. The objective was to establish the extent to which DHEA influences the levels of gonadotropins, sex hormone-binding globulin and lipids. It was found that DHEA is well absorbed and rapidly metabolized to its sulfate (DHEAS), androstenedione, and consequently to testosterone and estradiol. The DHEA levels that markedly increased after the first doses gradually declined already during the application, and this decline proceeded even after it was discontinued, reaching levels significantly lower than the original ones. On the other hand, the levels of DHEA metabolites (with the exception of DHEAS) rose during the application and reached values significantly higher than the basal ones within 5 weeks. This effect was accompanied by significantly decreased levels of LH. The serum levels of lipids, namely of cholesterol (both HDL and LDL cholesterol), triglycerides, apolipoproteins A-I and B and lipoprotein(a) after DHEA application were not changed significantly, and the atherogenic index (AI) remained unaltered. However, some correlations between hormones and lipids were found. Negative correlations concerned the following indices: DHEA/Lp(a); DHEAS/cholesterol; DHEA, DHEAS, testosterone/TG; testosterone/AI. On the other hand, LH, FSH/cholesterol, FSH, SHBG/LDL cholesterol, FSH/Apo B, Lp(a) correlated positively. It can be concluded that transdermal short-time application of DHEA results in a decrease of endogenous DHEA after finishing the treatment, with a parallel marked increase in the levels of sex hormones. Using this application protocol, exogenous DHEA neither altered the lipid spectrum, nor did it influence the atherogenic index., J. Šulcová, M. Hill, R. Hampl, Z. Mašek, A. Nováček, R. Češka, L. Stárka., and Obsahuje bibliografii
Exposure to chronic stress stimulates the hypothalamic-pituitaryadrenal (HPA) axis and then simultaneously inhibits hypothalamic-pituitary-gonadal axis (HPG) axis activity. The inhibition formed by the HPA axis is the main mechanism of action of stress on reproductive function. HPG axis activity is known to be changed by various factors, including exercise. Exercise has been found to have a number of positive effects on sexual behavior, reproductive hormones, and sperm parameters in studies with animal models for many years. The main aim of this study is to investigate the effects of chronic treadmill exercise on chronically stressed-male rats’ sexual behavior, reproductive hormones, and sperm parameters. A total of 40 sexually adult male rats were randomly and equally divided into four groups as control, stress, exercise, and stress+exercise. Animals in the exercise group were subjected to the chronic treadmill exercise (moderate intensity) for 33 days with a periodic increase in speed and duration. Animals in the stress group were exposed to restraint stress for 1 h, 2 h, and 3 h during the first, second and third 15 days respectively. Sexual behavior parameters, hormone measurements, and sperm parameters were evaluated. The main effects of chronic exercise on sexual behavior were centered on a significant increase in the ejaculation frequency (EF) in the stress+exercise group. Also, sperm concentration and motility in the stress group significantly decreased, and then sperm motility was improved by exercise in the stress+exercise group. In sum, our results show that chronic treadmill exercise may improve the adverse effects of chronic stress on sexual behavior and sperm parameters in male rats in terms of some parameters., Haluk Kelestimur, Ozgur Bulmus, Ihsan Serhatlioglu, Zubeyde Ercan, Seyma Ozer Kaya, Ahmet Yardimci, Nazife Ulker, Emine Kacar., and Obsahuje bibliografii
The in vivo effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) administration on endogenous IL-1 levels in the circulation and conditioned media (CM) from different immunohematopoietic organ/tissues were studied in CBA mice under steady state and postirradiation conditions. In normal mice, constitutive IL-1 levels were demonstrated in the plasma, CM of peritoneal exudate cells and full-thickness skin explants with low or undetectable levels in CM of splenic and bone marrow cell suspensions. In irradiated mice (2 Gy, X rays) on day 3 post exposure a significant increase of IL-1 levels was seen in the circulation and CM of peritoneal exudate cells, with no significantly different levels in postirradiation bone marrow, spleen and skin. After rhIL-1Ra treatment of the animals (2 x 50 mg/mouse, i.p.), significantly elevated IL-1 levels were observed in the skin and CM of peritoneal exudate cells in normal mice, whereas slightly increased levels were detected in CM of splenic cells. The rhIL-1Ra administration in irradiated mice led to decreased IL-1 concentrations in the circulation, and CM of peritoneal exudate cells and skin. The results pointed out the importance of IL-1 secretion and receptor expression in the maintenance of homeostasis in steady state, as well as during recovery after irradiation. Modulatory effects of IL-1Ra on IL-1 production were dependent on basic endogenous IL-1 concentration., D. Bugarski, G. Jovčić, M. Kataranovski, Z. Ivanović, M. Petakov, N. Stojanović, P. Milenković., and Obsahuje bibliografii
Both prostaglandins (PGs) and vitamin E are known to deeply affect immune responses. It is shown here that they both influence T cell-mediated immunity through reciprocal interference on the expression of cyclic-AMP responsive element binding (CREB) family proteins. CREB1 protein of human T lymphocytes was significantly modulated by a brief treatment of 5 to 10 min with PGE2. On the contrary, vitamin E appeared to be ineffective on the CREB1 behavior, while it abolished the PGE2-induced modulation of this protein. The CREB2 protein expression was also affected by PGE2 treatment, but a longer period of incubation (>20 min) was needed to observe these changes. Vitamin E showed a strong enhancing effect on CREB2 that was partially reversed by the subsequent treatment with PGE2. Our results support the idea that there is reciprocal interference between PGE2 and vitamin E on PGE2-induced signals in T lymphocytes. These data are in agreement with the reports concerning different cell systems and experimental conditions., A. Valenti, I. Venza, M. Venza, V. Fimiani, D. Teti., and Obsahuje bibliografii
To evaluate the preclinical efficacy and safety of human mesenchymal stem cells (hMSC) rapidly expanded in growth medium for clinical use with human se rum and recombinant growth factors, we conducted a controlled, randomized trial of plasma clots with hMSC vs. plasma clots only in critical segmental femoral defects in rnu/rnu immunodeficient rats. X-ray, microCT and histomorphometrical evaluation were pe rformed at 8 and 16 weeks. MSC were obtained from healthy volunteers and patients with lymphoid malignancy. Human MSC survived in the defect for the entire duration of the trial. MSC from healthy volunteers, in contrast to hMSC from cancer patients, significantly improved bone healing at 8, but not 16 weeks. However, at 16 weeks, hMSC significantly improved vasculogenesis in residual defect. We conclude that hMSC from healthy donors significantly contributed to the healing of bone defects at 8 weeks and to the vascularisation of residual connective tissue for up to 16 weeks. We found the administration of hMSC to be safe, as no adverse reaction to human cells at the site of implantation and no evidence of migration of hMSC to distant organs was detected., R. Pytlík, C. Rentsch, T. Soukup, L. Novotný, B. Rentsch, V. Kanderová, H. Rychtrmocová, M. Kalmárová, D. Stehlík, M. Trněný, O. Slanař., and Obsahuje bibliografii
Two exogenous NO donors were used to act as substitutes for impaired endogenous nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks' lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) induced stabilized hypertension. Simultaneously administered isosorbide-5-mononitrate did not prevent the development of hypertension. Molsidomine, administered concomitantly with L-NAME, significantly attenuated the BP increase. However, BP was still found to be moderately increased compared to the initial values. Remarkable alterations in the geometry of the aorta, carotid and coronary artery found in NO-deficient hypertension were prevented in rats administered L-NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the maximum hypotensive value did not differ from the values recorded in the controls or in animals treated with L-NAME plus molsidomine. Notably enough, the hypotension was similar to that found in rats administered L-NAME alone for six weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute and molsidomine substitute only partially the impaired endogenous NO production., M. Gerová, F. Kristek., and Obsahuje bibliografii
An increased risk of myocardial ischemic changes was demonstrated in patients suffering from panic disorder (PD). Using classical ECG methods, this risk cannot be evaluated in most patients. We measured the vectocardiogram (VCG) using Frank orthogonal leads and body surface maps (BSM) including 12-lead ECG. In our study of 11 PD patients (2 men, 9 women), without any seizures and pharmacological treatment and without cardiovascular symptoms, we found marked sinus tachycardia (heart rate 90.1±12.2 min-1) and a shorter R-R interval (678±93.6 ms) than in 27 controls (heart rate 73.6±7.7min-1, R-R 822.7±86.4 ms) (5 men, 22 women) (p<0.001). The VCG measured spatial QRS-STT angle was more opened (70.3±24.5°) than in the control group (49.5±19.5°) (p<0.05). The maximum (extremum) in depolarization (DIAM max 30, 40) and repolarization (RIAM max 35) of body surface isoarea and isointegral (RIIM max) maps was less positive (p<0.001) and the minimum (DIAM min 40) was less negative than in the controls (p<0.05) even in the period free of a panic attack. Our results showed the changes in the heart electric field parameters occurred in PD patients when compared to the control group., K. Pišvejcová, I. Paclt, J. Slavíček, O. Kittnar, A. Dohnalová, E. Kitzlerová., and Obsahuje bibliografii
Diabetes mellitus (DM) has been known for many years to be associated with poor cardiovascular prognosis. Due to the sensitive neuropathy, the coronary artery disease in diabetic patients is frequently asymptomatic. Also twelve leads resting ECG can be within normal limits even in an advanced stage of coronary artery disease. Therefore in addition to the standard ECG other electrocardiographic procedures started to be studied in order to find some typical signs of myocardial damages caused by DM. Repeatedly reported results showed in DM patients without cardiovascular complications the tachycardia, shortening of the QRS and QT intervals, increase of the dispersion of QT interval, decreased amplitudes of depolarization waves, shortened activation time of ventricular myocardium and a flattening of T waves confirmed by the lower value of maximum and minimum in repolarization body surface isopotential maps. Most of these changes are even more pronounced in patients with cardiac autonomic neuropathy. Comparison with similar ECG changes in other diseases suggests that the electrocardiographic changes in DM patients are not specific and that they are particularly caused by an increased tone of the sympathetic nervous system what was indirectly confirmed by the heart rate variability findings in these patients., O. Kittnar., and Obsahuje bibliografii
Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavíček et al. 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMD£10; age 40±5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66±0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations., I. Paclt, J. Slavíček, A. Dohnalová, E. Kitzlerová, K. Pišvejcová., and Obsahuje bibliografii
We studied the ability of the ECG to detect pathological changes in isoproterenol-induced remodeling of rat heart. Myocardial hypertrophy in rats was induced by repeated injections of isoproterenol (5 mg/kg s.c. 7 days, Iso5, n=7). Single overdose of isoproterenol (150 mg/kg s.c., Iso150, n=7) evoked myocardial infarction followed with ventricular remodeling. The electrocardiograms were recorded in anesthetized animals (thiopenthal 45 mg/kg i.p.) and myocardial contractile performance was analyzed in isolated hearts perfused according to Langendorff. The hypertrophic hearts were characterized by increased heart and left ventricular (LV) weight as well as by thicker LV free wall and interventricular septum. Mean values of LV contraction did not significantly differ from controls. Longer QT interval, QRS complex, negative Q and S waves, higher R amplitude were typical characteristics for Iso5 rats. Iso150 animals showed tendency to decreased systolic blood pressure and heart frequency. Decrease in the thickness of LV compared to Iso5 as well as impaired LV function were related to the dilated left ventricle. Iso150 ECG showed longer QRS and QT, deepened negativity of S wave and mild decrease of RII compared to Iso5. Voltage criteria showed that Sokolow-Lyon index is a good predictor of left ventricular hypertrophy in isoproterenol-induced cardiac remodeling without systemic hypertension., E. Kráľová, T. Mokráň, J. Murín, T. Stankovičová., and Obsahuje bibliografii a bibliografické odkazy