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
The FTO gene variants are the most important genetic determinants of body weight and obesity known so far, but the mechanism of their effect remain s unclear. We have analyzed FTO rs17817449 variant (G>T in first intron) in 6024 adults aged 45-69 years to assess the potential mediating role of diet and physical activity. Diet was assessed by a 140-item food frequency questionnaire. Physical activity was measured by hours spent during a typical week by sport, walking and other activities outside of work requiring heavy and medium physical activity. Basal metabolic rate was calculated according Schofield formula. The FTO variant was significantly associated with body mass index (means in GG, GT and TT ca rriers were 28.7, 28.2 and 27.8 kg/m 2 , p<0.001) and basal metabolic rate (BMR) (means in GG, GT and TT were 1603, 1588 and 1576 kcal per day, respectively, p<0.008) but it was not associated with physical activity, total energy intake or with energy intakes from fat, carbohydrates, proteins or alcohol. Results were essentially similar in men and women and the adjustment for physical activity or dietary energy intake did not reduce the effect of the FTO polymorphism. Means of BMR per kg of body weight was lowest in GG carriers (20.09, 20.21 for GT and 20.30 for TT, p< 0.006) and this effect was more pronounced in females. These results suggest that the effect of the FTO rs17817449 variant on BMI in Caucasian adults is not mediated by energy intake or physical activity, but some effect on BMR per kg of body weight is possible., J. A. Hubáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Spontaneous and electrically-elicited motor activity was recorded by triple organ bath in rat segment-model preparation as display of excitation of local nerve networks and ascending or descending reflex pathways underlying contractile potency and functional coordination of colonic longitudinal and circular muscles. Spontaneous high-amplitude contractions, but not relaxations, appeared synchronously in both muscles. Electrical field stimulation applied to proximal or distal part of segments elicited both tetrodotoxin (0.1 μM)-sensitive local motor responses of the stimulated part and ascending or descending motor responses of the contralateral, nonstimulated part of the preparations. Contract ions characterized the local response of longitudinal muscle. The circular muscle responded with relaxation followed by contraction. Synchronous ascending contractions and descending contraction of the longitudinal muscle and relaxation followed by contraction of the circular muscle were observed when the middle part of segments was stimulated, thus indicating that locally-induced nerve excitation propagated via intrinsic ascending or descending nerve pathways that could be synchronously coactivated by one and the same stimulus. The ascending motor responses were more pronounced and the motor responses of longitudinal muscle were expressed more than those of circular muscle suggesting an essential role of ascending reflex pathways and longitudinal muscle in the coordinated motor activity of colon., N. Nedialkova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms., S. Ankarali, H. C. Ankarali, C. Marangoz., and Obsahuje seznam literatury
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
Gain-of-function (GOF) mutations in ion channels are rare events, which lead to increased agonist sensitivity or altered gating properties, and may render the channel constitutively active. Uncovering and following characterization of such mutants contribute substantially to the understanding of the molecular basis of ion channel functioning. Here we give an overview of some GOF mutants in polymodal ion channels specifically involved in transduction of painful stimuli - TRPV1 and TRPA1, which are scrutinized by scientists due to their important role in development of some pathological pain states. Remarkably, a substitution of single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently associat ed with familial episodic pain syndrome. This mutation increases chemical sensitivity of TRPA1, but leaves the voltage sensitivit y unchanged. On the other hand, mutations in the analogous regi on of TRPV1 (R557K and G563S) severely affect all aspects of channel activation and lead to spontaneous activity. Comparison of the effects induced by mutations in homologous positions in different TRP receptors (or more generally in other distan tly related ion channels) may elucidate the gating mechanisms conserved during evolution., S. Boukalova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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