We tested whether the known cytochrome c oxidase (COX) inhibition by nitric oxide (NO) could be quantified by VO 2 kinetics during constant load supra-Anaero bic Threshold (AT) exercises in healthy trained or untrained subjects following aerobic training or nitrate administration. In cycle er gometer constant load exercises supra-AT, identified in previous incremental tests, VO 2 kinetics describe a double exponential curve, one rapid and one appreciably slower, allowing the area between them to be calculate in O 2 l. After training, with increased NO availability, this area decreases in inverse ratio to treatment efficacy. In fact, in 11 healthy subjects after aerobic tr aining for 6-7 weeks, area was decreased on average by 51 %. In 11 untrained subjects, following the assumption of an NO donor, 20 mg isosorbide 5 mononitrate, area was decrea sed on average by 53 %. In conclusion, supra-AT VO 2 kinetics in constant load exercises permit the quantification of the inhibitory effect NO-dependent on COX after either physical training or nitrate assumption., D. Maione ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
It is well known that antagonists of N-type voltage-gated calcium channels inhibit the evoked quan tal release of acetylcholine in amphibian neuromuscular synapses. This, however, does not exclude the functional expression of other types of voltage-gated calcium channels in these nerve terminals. Using immunocytochemistry, we detected the expression of the α1A subunit of P/Q-type calcium channels (that is otherwise typical of mammalian motor nerve endings) in the frog neuromuscular junction. In addition, we demonstrated that the P/Q-type channel blocker ω-agatoxin IVA (20 nM) reduced the action potential- induced calcium transient and significantly decreased both spontaneous and evoked mediator release. Our data indicates the functional expression of P/Q-type calcium channels in the frog motor nerve ending which participate in acetylcholine release., L. F. Nurullin ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor – marked prolongation of ADs in all three age groups – suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures., P. Mareš, H. Kubová., and Obsahuje bibliografii a bibliografické odkazy
The quality of stored blood can be deteriorated by hemolysis caused by free radicals. The purpose of this study was to elucidate whether neutrophile leukocytes are the source of free radicals in stored blood as in hemodialyzed patients. Resuspensions with low (LL) or high (HL) leukocyte concentrations were prepared from samples of twenty healthy volunteers. The samples were incubated for 10 days at 4 °C and then for one day at 37 °C. Markers of hemolysis and free radical metabolism were examined before and after incubation in LL and HL samples. In spite of the difference of leukocytes counts in LL and HL resuspensions (p<0.0001), the pre-incubation values of all laboratory parameters were practically identical. In post-storage samples, superoxide dismutase and glutathione peroxidase activities did not differ in either group. Reduced glutathione in erythrocytes and extracellular antioxidant capacity were insignificantly lower in HL resuspensions, but the increase of malondialdehyde was much more pronounced in the HL samples (p<0.0001). The degree of hemolysis, expressed as the extracellular increase of potassium (p<0.001), hemoglobin (p<0.05) and lactate dehydrogenase (p<0.05), was higher in the HL samples. Our results support the hypothesis that leukocytes participate in free radical production in stored blood., J. Racek, R. Herynková, V. Holeček, J. Faltysová, I. Krejčová., and Obsahuje bibliografii
The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance., P. Soucek, V. Hlavac, K. Elsnerova, R. Vaclavikova, R. Kozevnikovova, K. Raus., and Obsahuje bibliografii
Purkinje fibers were the first discovered component of the cardiac conduction system. Origin ally described in sheep in 1839 as pale subendocardial cells, they were found to be present, although with different morphology, in all mammalian and avian hearts. Here we review differences in their appearance and extent in different species, summarize the current state of knowledge of their function, and provide an update on markers for these cells. Special emphasis is given to popular model species and human anatomy., D. Sedmera, R. G. Gourdie., and Obsahuje bibliografii a bibliografické odkazy
Wnt/β-catenin signaling is involved in virtually every aspect of embryonic development and also controls homeostatic selfrenewal in a number of adult tissues. Recently, emerging evidence from researches of organ fibrosis suggest that sustained Wnt/β-catenin pathway reactivation is linked to the pathogenesis of fibrotic disorders. Here we focus on Wnt/β-catenin-related pathogenic effects in different organs, such as lung fibrosis, liver fibrosis, skin fibrosis and renal fibrosis. Additionally, Wnt/β- catenin signaling works in a combinatorial manner with TGF-β signaling in the process of fibrosis, and TGF-β signaling can induce expression of Wnt/β-catenin superfamily members and vice versa. Moreover, network analysis, based on pathway databases, revealed that key factors in the Wnt pathway were targeted by some differentially expressed microRNAs detected in fibrosis diseases. These findings demonstrated the crosstalks between Wnt/β-catenin pathway and TGF-β signalings, and microRNAs, highlighting the role of Wnts in organ fibrogenesis. Most importantly, nowadays there is a variety of Wnt pathway inhibitors which give us the potential therapeutic feasibility, modulation of the Wnt pathway may, therefore, present as a suitable and promising therapeutic strategy in the future., Y. Guo ... [et al.]., and Obsahuje seznam literatury
Metabolic syndrome is a prevalent, complex condition. The search for genetic determinants of the syndrome is currently undergoing a paradigm enhancement by adding systems genetics approaches to association studies. We summarize the current evidence on relations between an emergent new candidate, zinc finger and BTB domain containing 16 (ZBTB16) transcription factor and the major components constituting the metabolic syndrome. Information stemming from studies on experimental models with altered Zbtb16 expression clearly shows its effect on adipogenesis, cardiac hypertrophy and fibrosis, lipid levels and insulin sensitivity. Based on current evidence, we provide a network view of relations between ZBTB16 and hallmarks of metabolic syndrome in order to elucidate the potential functional links involving the ZBTB16 node. Many of the identified genes interconnecting ZBTB16 with all or most metabolic syndrome components are linked to immune function, inflammation or oxidative stress. In summary, ZBTB16 represents a promising pleiotropic candidate node for metabolic syndrome., O. Šeda, L. Šedová, J. Včelák, M. Vaňková, F. Liška, B. Bendlová., and Obsahuje bibliografii
The data derived from rat models and the preliminary results of human studies provide strong indices of involvement of common ZBTB16 variants in a range of cardiovascular and metabolic traits. This cross-sectional study in the Caucasian cohort of 1517 Czech adults aimed to verify the hypothesis that ZBTB16 gene variation directly affects obesity and serum lipid levels. Genotyping of nine polymorphisms of the ZBTB16 gene (rs11214863, rs593731, rs763857, rs2846027, rs681200, rs686989, rs661223, rs675044, rs567057) was performed. A multivariate bidirectional regression with the reduction of dimensionality (O2PLS model) revealed relationships between basal lipid levels and anthropometric parameters and some minor ZBTB16 alleles. In men, the predictors - age and presence of minor ZBTB16 alleles of rs686989, rs661223, rs675044, rs567057 - were associated with significantly higher body mass index, waist to hip ratio, body adiposity index, waist and abdominal circumferences, higher total cholesterol and LDL cholesterol and explained 20 % of variability of these variables. In women, the predictors - age and presence of the rs686989 minor T allele - were also associated with increased anthropometric parameters and total cholesterol and LDL cholesterol but the obtained O2PLS model explained only 7.8 % of the variability of the explained variables. Our study confirmed that the selected gene variants of the transcription factor ZBTB16 influence the obesity-related parameters and lipid levels. This effect was more pronounced in men., B. Bendlová, M. Vaňková, M. Hill, G. Vacínová, P. Lukášová, D. Vejražková, L. Šedová, O. Šeda, J. Včelák., and Obsahuje bibliografii