The aim of this study was to follow up whether the modification of pro-antioxidant status by oral thiol administration such as N- acetylcysteine and α-lipoic acid affects the hematological response. Twenty-eight healthy men participated in two independent experiments. Subjects were randomly assigned to one of four groups: controls (CNAC and CALA ), N-acetylcysteine (NAC) and α-lipoic acid (ALA). 1200 mg of N-acetylcysteine, 600 mg of α-lipoic acid or placebo were administered for 8 days in two doses. NAC or ALA administration significantly elevated plasma total antioxidant stat us (TAS) and reduced protein carbonylation (PC) and lipid peroxidation (TBARS) by more than 30 %. The reduced glutathione (GSH) and hematological parameters changed only in response to NAC administration. NAC significantly elevated the level of GSH (+33 %), EPO (+26 %), Hb (+9 %) and Hct (+9 %) compared with CNAC. The mean corpuscular volume (MCV) and the mean corpuscular hemoglobin (MCH) also increased by more than 12 % after NAC. The numerous negative or positive correlations between the measures of TAS, PC, TBARS and hematological parameters were found, which suggest the NAC-induced interaction between pro-antioxidant and hematological values. Our study has shown that both N-acetylcysteine and α-lipoic acid intake reveal an antioxidant action, but only N-acetylcysteine improves the haematological response., A. Zembron-Lacny ... [et al.]., and Obsahuje seznam literatury
The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascul ar disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and ty pe 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75 th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk., J. Piťha, J. A. Hubáček, P. Piťhová., and Obsahuje bibliografii
In order to assess whether intratesticular hormone content may be helpful for prediction of successful conception in men with fertility problems, five sex steroids, testosterone, dihydrotestosterone, androstenedione, estradiol and, for the first time epitestosterone, were measured in testicular tissue obtained by surgical retrieval from total 84 men. The group consisted of non-obstructive azoospermic men, aged 21-67 years who attended the centre for in vitro fertilization. Steroids after ether extraction and solvent partition were separated by high performance liquid chromatography and then measured by specific radioimmunoassays. The values varied considerably with means ± S.D. 2.43±2.47, 0.27±0.24, 0.080±0.13, 0.071± 0.089 and 0.31±0.27 for testosterone, dihydrotestosterone, androstenedione, estradiol and epitestosterone, respectively., L. Zamrazilová ... [et al.]., and Obsahuje seznam literatury
To test whether macrophages can play any role in hypoxic pulmonary vasoconstriction, we tested the in vitro response of rings from small pulmonary arteries to the activation of macrophages by FMLP, a substance stimulating predominantly membrane-bound NADPH oxidase. A small vessel myograph was used to measure the responses of rings from small pulmonary arteries (300-400 μ m) isolated from rat lungs. Rings from 5 rats were placed into both chambers of the myograph. The vessels were stabilized for 40 min and then normalized by automatic stretching to a wall tension equivalent to the intravascular pressure 30 mm Hg. At the start of each experiment, vessels were exposed to 80 mM K + to obtain maximal contractile response, which was used to normalize subsequent contractile responses. 2x10 6 viable macrophages, obtained by peritoneal lavage, were added into one chamber, then 5 μ M FMLP was administrated to both chambers and the tension measurement was started. The hydrogen peroxide concentration produced by stimulated macrophages was measured luminometrically. The concentrations of H 2 O 2 in specimens from chambers containing activated macrophages rose from 3.5±1.5 nM to 110±28 nM within 25 min of stimulation, while FMLP itself didn’t increase the H 2 O 2 concentration from the baseline value (4.5±3 nM) in samples from control chambers. After FMLP administration, the tension of the vessel rings in the presence of macrophages reached 0.23±0.07 of maximal contractile response, it did not change in controls. The additi on of ROS scavenger 4-hydroxy- TEMPO blocked the contractile response to the activation of macrophages. We conclude that the activation of macrophages stimulates the contraction of small pulmonary arteries and that this contraction is probably mediated by reactive oxygen species., M. Žaloudíková, J. Herget, M. Vízek., and Obsahuje bibliografii a bibliografické odkazy
The glycosaminoglycan (GAG) molecules are a group of high molecular weight, negatively charged polysaccharides present abundantly in the mammalian organism. By their virtue of ion and water binding capacity, they may affect the redistribution of body fluids and ultimately the blood pressure. Data from the literature suggests that the mitogens Vascular Endothelial Growth Factor (VEGF)-A and VEGF-C are able to regulate the amount and charge density of GAGs and their detachment from the cell surface. Based on these findings we investigated the relationship between the level of dietary sodium intake, the expression levels of VEGF-A and VEGF-C, and the amount of the skin GAGs hyaluronic acid and chondroitin sulfate in an in vivo rat model. Significant correlation between dietary sodium intake, skin sodium levels and GAG content was found. We confirmed the GAG synthesizing role of VEGF-C but failed to prove that GAGs are degraded by VEGF-A. No significant difference in blood pressure was registered between the different dietary groups. A quotient calculated form the ion and water content of the skin tissue samples suggests that - in contrast to previous findings - the osmotically inactive ions and bound water fractions are proportional., D. Sugár, R. Agócs, E. Tatár, G. Tóth, P. Horváth, E. Sulyok, A. J. Szabó., and Obsahuje bibliografii
The aim of the present study was to determine the optimal initial tension, i.e. initial stretch for rat coronary artery when using the multi-wire myograph system. We used the normalization procedure to mimic physiological conditions and to stretch the coronary arterial segments to normalized internal circumference (IC 1 ). It is determined the internal circumference when the vessel relaxed under a transmural pressure of 100 mm Hg (IC 100 ), and the IC 1 is calculated by multiplying the IC 100 by a factor k. The impact of different factor k on the initial stretch and agonist- induced tension of coronary arteries were investigated. The results showed that the maximal agonist-induced tension was achieved at the factor k value of 0.90 and the initial stretch tension was given 1.16±0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most appropriate initial tension was 1.16-1.52 mN/mm. Th e equilibration time of the coronary artery segments should be at least 1.0 h. In the same optimal initial tension, the agonist-induced tension increased as equilibration time lengthened., N.-N. Ping ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_Diabetes mellitus is not just a simple metabolic disorder, however, it is considered to be a cardiovascular disease of a metabolic origin. This is apparent especially when speaking about type 2 diabetes (DM II). The objective of our study was to determine whether a comprehensive spa treatment (procedures and drinking cure) may affect the level of the sympathetic tone of patients suffering from DM II. As an indicator of the sympathetic tone, selected electrocardiographic parameters derived from the heart rate variability and microwave alternans were chosen. There were 96 patients enrolled in our study: 38 patients with poorly controlled DM II and two control groups: 9 patients with compensated DM II and 49 patients, average age without diabetes or other disorders of the glucose metabolism. All received an identical spa treatment and continued their medical therapy. The electrophysiological examination of patients was performed before and after a three-week spa treatment using the KARDiVAR system. Parameters derived from the analysis of heart rate variability (HRV), microvolt T-wave alternans, and microvolt R-wave alternans were analyzed in order to evaluate the tones of the autonomic nervous system (ANS). The control group showed a slight increase of parameter the index of activity of regulatory systems (IRSA) (4.4±1.3 vs. 3.8±1.4; p=0.006) after the spa treatment, while increased heart rate (80.9±11.0 vs. 74.6±9.6; p=0.028), reduced index of centralization (IC) (1.3±0.6 vs. 2.9±1.4; p=0.027) and reduced index of myocardium (IM) (9.9±7.4 vs. 18.0±6.3; p=0.041) were found in patients with a compensated DM II. Patients with a poorly compensated DM II showed a decreased IM (10.9±8.6 vs. 16.9±5.2; p=0.001) and also a reduced IRSA (4.1±3.5 vs. 6.3±1.9; p=0.001)., a2_The results proved favorable changes in ANS cardiovascular control of patients with DM II after a spa treatment, especially in terms of reducing the sympathoadrenal system activity (decreased IRSA), improving electrical stability of the myocardium and increasing centrally controlled heart rate variability without overloading the cardiovascular system (drop of IM)., E. Fialová, O. Kittnar., and Obsahuje bibliografii
The mitochondrial DNA (mtDNA) amount in cells as the basis for mitochondrial energy generating system, which produces ATP, plays an important role in the fetal development and postnatal morbidity. Isolated human cord blood leukocytes (HCBL) contribute very little to the overall metabolic turnover, but they may serve as easily available marker cells for the study of the mtDNA amount changes in cord blood during fetal development. The aim of our study was to analyze the mtDNA amount in HCBL. HCBL were isolated from cord blood samples of 107 neonates born between the 25th and 41st week of gestation. The mtDNA amount was analyzed by the real-time PCR method. The significant negative correlations were found between the relative mtDNA amount in HCBL and gestational age (r = -0.54, p<0.01) and birth weight (r = -0.43, p<0.01), respectively. The results revealed that the mtDNA content per cell decreases in HCBL with progressing fetal development. This may be explained by gradual shift of the hematopoiesis from fetal liver to bone marrow during the second half of pregnancy presumably accompanied by decreasing cell volume of HCBL as it was shown similarly in red blood cells., M. Pejznochová, M. Tesařová, T. Honzík, H. Hansíková, M. Magner, J. Zeman., and Obsahuje bibliografii a bibliografické odkazy
Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients., V. Čertíková Chábová, L. Červenka., and Obsahuje bibliografii
Increased colonic Cl - secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl - secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist ca rbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba2+ to emphasize Cl - secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin al so significantly reduced TTX- sensitive current. On the 7 th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX- sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7 th day. Decreased and deformed current responses to serosal Ba 2+ were observed during colitis induct ion, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon., M. Hock ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy