Advanced glycation end-products (AGEs) are key players in pathogenesis of long-term vasc ular diabetes complications. Several enzymes such as fructosamine 3-kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation processes. The aim of our study was to evaluate an association of FN3K (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of endothelial dysfun ction and soluble receptor for AGEs (sRAGE) in 595 diabetic and non-diabetic subjects. Genotypic and allelic frequencies of mentioned polymorphisms did not differ between subgroups. In diabetic patients significant differences were observed in sRAGE concentrations according to their rs1056534 and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutate d G allele were associated with significant decrease of sRAGE (GG: 1055±458 and CG: 983±363 vs. CC: 1796±987 ng/l, p<0.0001), in rs3848403 polymorphism TT genotype with mutated T allele was related with significant sRAGE increase (TT: 1365±852 vs. CT: 1016±401 and CC: 1087±508 ng/l, p=0.05). Significant differences in adhesion molecules were observed in genotype subgroups of GLO1 rs4746 polymorphism. In conclusion, this is the first study describing significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with concentration of sRAGE in patients with diabetes., J. Škrha Jr., A. Muravská, M. Flekač, E. Horová, J. Novák, A. Novotný, M. Prázný, J. Škrha, J. Kvasnička, L. Landová, M. Jáchymová, T. Zima, M. Kalousová., and Obsahuje bibliografii
There are conflicting results concerning the receptor subtype(s) involved in calcium-mediated endothelin signaling in the glial cells. In order to elucidate the role of endothelin A and B receptors in these processes, we have studied the effect of a complex spectrum of endothelin receptor ligands on intracellular calcium concentration changes in proliferating and differentiated C6 rat glioma cells. Cell differentiation was induced by dibutyryl-cAMP and assessed by the glial fibrillar acidic protein content. Intracellular calcium changes were measured in cell suspensions using fluorescent probe Fura-2. The specific endothelin B receptor agonists sarafotoxin S6c and IRL-1620 did not influence the intracellular calcium concentration. However, calcium changes induced by endothelin-1 and especially by endothelin-3 after the pretreatment of cells with one of these endothelin B receptor specific agonists were significantly enhanced even above the values attained by the highest effective endothelin concentrations alone. Such endothelin B-receptor ligand-induced sensitization of calcium signaling was not observed in differentiated C6 cells. Moreover, endothelin-induced calcium oscillations in differentiated C6 cells were less inhibited by BQ-123 and BQ-788 than in their proliferating counterparts. In conclusion, the specific activation of endothelin B receptor in C6 rat glioma cells does not affect intracellular calcium per se, but probably does so through interaction with the endothelin A receptor. The pattern and/or functional parameters of endothelin receptors in C6 rat glioma cells are modified by cell differentiation., R. Malík, K. Vlašicová, A. Šedo., and Obsahuje bibliografii
Neuroimaging methods have been used to study differences of brain function between males and females. Differences in working memory have been also investigated, but results of such studies are mixed with respect to behavioral data, reaction times and activated brain areas. We tried to analyze functional MRI data acquired during the working memory task and search for differences of brain activation between genders. 20 healthy righthanded volunteers (10 males and 10 females) participated in the study. All of them were university students or fresh graduates. Subjects underwent block designed verbal working memory task (Item Recognition Task) inside the MRI scanner. Standard singlesubject pre-processing and group fMRI analyses were performed using the FEAT software from FSL library. In the behavioral data, there was no statistically significant difference in the number of correct responses during the task. The task activated similar bilateral regions of frontal, parietal, temporal and occipital lobes, basal ganglia, the brainstem and in the cerebellum, which corresponds to the previous verbal working memory neuroimaging research. In direct comparison, there was no statistically significant difference in brain activation between small samples of male and female young healthy volunteers., Z. Tüdös, P. Hok, P. Hluštík, A. Grambal., and Obsahuje bibliografii
Inconsistent information from different modalities can be delusive for perception. This phenomenon can be observed with simultaneously presented inconsistent numbers of brief flashes and short tones. The conflict of bimodal information is reflected in double flash or fission, and flash fusion illusions, respectively. The temporal resolution of the vision system plays a fundamental role in the development of these illusions. As the parallel, dorsal and ventral pathways have different temporal resolution we presume that these pathways play different roles in the illusions. We used pathway-optimized stimuli to induce the illusions on separately driven visual streams. Our results show that both pathways support the double flash illusion, while the presence of the fusion illusion depends on the activated pathway. The dorsal pathway, which has better temporal resolution, does not support fusion, while the ventral pathway which has worse temporal resolution shows fusion strongly., P. Kaposvári, A. Bognár, P. Csibri, G. Utassy, Gy. Sáry., and Obsahuje bibliografii
Gastric or intestinal luminal tonometry is a method for monitoring critically ill patients. It offers an index of the adequacy of aerobic metabolism in a tissue that is particularly sensitive to alterations in its perfusion and oxygenation: the gut mucosa. It is based on the measuring the increase in tissue CO2 production that accompanies anaerobic metabolism. The method simply consists of a balloon in the stomach, which measures intramucosal pCO2. From this measurement and from the arterial bicarbonate concentration gastric intramucosal pH (pHi) can be calculated, assuming that bicarbonate concentration in the gastric mucosal tissue is in equilibrium with systemic arterial bicarbonate. Despite possible clinical benefit from the measurement and the therapy of low pHi values in critically ill patients, the theoretical, experimental and pathophysiological implications for the monitoring of intramucosal acidosis in the gut are not yet fully understood. There are still some open methodological questions crucial for further clinical interpretation., V. Černý, K. Cvachovec., and Obsahuje bibliografii
It has become increasingly apparent in recent years that there are important differences of many cardiovascular disorders including ventricular tachycardias in men and women. Nevertheless, so far just few studies have addressed possible gender differences in electrophysiological characteristics of idiopathic ventricular tachycardia from right ventricular outflow tract (RVOT-VT), other than epidemiological ones. This study explored possible gender differences in electrophysiological characteristics and catheter ablation outcome in RVOT-VT patients. Ninety-three patients (mean age 38.7±15.5 years, 30 males) with idiopathic RVOT-VT were enrolled and analyzed in our study. Male patients had longer QRS width (99.9±19.4 ms vs. 88.4±20.7 ms, p=0.02). Female patients had lower right ventricular mean voltage (3.0±0.7 mV vs. 3.7±0.9 mV, p=0.03), and more low voltage zone over the right ventricular outflow tract free wall (27.0 % vs. 6.7 %, p=0.02). Eighty-one patients passed catheter ablation (23 males). The acute success rate, repeated catheter ablation rate and VT recurrence rate were similar in both genders. The present study provides evidence of the gender differences in electrophysiological findings in patients with idiopathic RVOT-VT. Studies on gender-specific differences in arrhythmia could lead to a better understanding of its mechanism(s) and provide valuable information for the development of optimal treatment strategies., S.-G. Yang, M. Mlček, O. Kittnar., and Obsahuje bibliografii
Cold exposure of rats leads to ameliorated glucose and triglyceride utilization with fema les displaying better adaptation to a cold environment. In the current study, we used hairless rats as a model of increased thermo genesis and analyzed gender- related effects on parameters of lipid and glucose metabolism in the spontaneously hypertensive (SHR) rats. Specifically, we compared hairless coisogenic SHR- Dsg4 males and females harboring mutant Dsg4 (desmoglein 4) gene versus their SHR wild type controls. Two way ANOVA showed significant Dsg4 genotype (hairless or wild type) x gender interaction effects on palmitate oxidation in brown adipose tissue (BAT), glucose incorporation into BAT determined by microPET, and glucose oxidation in skeletal muscles. In addition, we observed significant interaction effects on sensitivity of muscle tissue to insulin action when Dsg4 genotype affected these metabolic traits in males, but had little or no effects in females. Both wild type and hairless females and hairless males showed increased glucose incorporation and palmitate oxid ation in BAT and higher tissue insulin sensitivity when compared to wild type males. These findings provide evidence for gender-related differences in metabolic adaptation required for increased thermogenesis. They are consistent with the hypothesis that increased glucose and palmitate utilization in BAT and muscle is associated with higher sensitivity of adipose and muscle tissues to insulin action, J. Trnovská, J. Šilhavý, V. Zídek, M. Šimáková, P. Mlejnek, V. Landa, S. Eigner, K. Eigner Henke, V. Škop, O. Oliyarnyk, L. Kazdová, T. Mráček, J. Houštěk, M. Pravenec., and Obsahuje bibliografii
A total genome scan and pharmacogenetic study were designed to search for genetic determinants of blood pressure (BP) as well as heart and kidney weights. Genome scanning was carried out in 266 F2 intercrosses from Prague hypertensive hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through the SNS, and these loci showed a positive contribution for relative kidney weight (KW/BW). On the other hand, baseline BP in females was controlled by two loci on Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO system. These loci did not show any effect for KW/BW. Negatively-linked loci for KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders. Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP through the SNS. This locus on Chr8 overlapped with a previously-reported modifier locus for polycystic kidney disease (PKD). In conclusion, this pharmacogenetic study determined two loci for BP and relative organ mass implicating sympathetic overactivity. Concordance of the identified locus for KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance of this region for renal complications in various diseases., T. Ueno, J. Tremblay, J. Kuneš, J. Zicha, Z. Dobešová, Z. Pausová, A. Y. Deng, Y. Sun, H. J. Jacob, P. Hamet., and Obsahuje bibliografii
Total genome scans of genetically segregating populations derived from spontaneously hypertensive rats (SHR) and other rat models of essential hypertension suggested a presence of quantitative trait loci (QTL) regulating blood pressure on multiple chromosomes, including chromosome 5. The objective of the current study was to test directly a hypothesis that chromosome 5 of the SHR carries a blood pressure regulatory QTL. A new congenic strain was derived by replacing a segment of chromosome 5 in the SHR/Ola between the D5Wox20 and D5Rat63 markers with the corresponding chromosome segment from the normotensive Brown Norway (BN/Crl) rat. Arterial pressures were directly monitored in conscious, unrestrained rats by radiotelemetry. The transfer of a segment of chromosome 5 from the BN strain onto the SHR genetic background was associated with a significant decrease of systolic blood pressure, that was accompanied by amelioration of renal hypertrophy. The heart rates were not significantly different in the SHR compared to SHR chromosome 5 congenic strain. The findings of the current study demonstrate that gene(s) with major effects on blood pressure and renal mass exist in the differential segment of chromosome 5 trapped within the new SHR.BN congenic strain., M. Pravenec, V. Křen, D. Křenová, V. Zídek, M. Šimáková, A. Musilová, J. Vorlíček, E. St. Lezin, T. W. Kurtz., and Obsahuje bibliografii
Graves' disease affects approximately 3 % of women and 0.5 % of men. The first-choice therapy is based on the administration of thyrostatic drugs. However, approximately half of patients relapse within two years of discontinuation. These patients must then decide whether to re-initiate thyrostatics, which may have serious side effects, or to undergo surgery or radioiodine treatment. Familial forms of Graves' disease indicate a significant genetic component, with twin studies demonstrating a contribution of genetic factors up to 70-80 %. The autoimmune nature of the disease involves the human leukocyte antigen (HLA) complex, which has a decisive impact on each individual's immune response. Within HLA, some variants of the DRB1 , DQA1 and DQB1 genes appear to be possible predictors of the development and recurrence of Graves' disease. Outside the HLA region, many variants of immunocompetent genes have also been identified as potential Graves' disease predictors. Apart from the immune system, some thyroid-specific genes have been described in relation to the disease. Here, we present current knowledge regarding the genetic components involved in the development and recurrence of Graves' disease. Further, we present original pilot results from a cohort of Czech Graves' disease patients regarding the HLA variants., D. Vejrazkova, J. Vcelak, E. Vaclavikova, M. Vankova, K. Zajickova, M. Duskova, J. Vrbikova, B. Bendlova., and Obsahuje bibliografii