Nearly 60 years has elapsed since the first isolation and identification of 7α-hydroxy-dehydroepiandrosterone, and in that time much information has been gained on its occurrence, metabolism, ontogeny, immunomodulatory activity, cell proliferation, cortisol control in local tissues and neuroactivity. Additional knowledge about this steroid may elucidate its role in obesity, neurodegenerative disturbances such as Alzheimer’s disease, or psychiatric disorders such as schizophrenia or depression. This review aims to provide a comprehensive summary of the available literature on 7α-hydroxydehydroepiandrosterone., L. Stárka., and Obsahuje bibliografii
Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropanoyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl- phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and β-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine., R. Pola, O. Janoušková, T. Etrych., and Obsahuje bibliografii
The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel contains 12 transmembrane (TM) regions that are presumed to form the channel pore. However, t here is no direct evidence clearly illustrating the involvement of these transmembr ane regions in the actual CFTR pore structure. To obtain insight into the architecture of the CFTR channel pore, we used patch clamp recording techniques and a strategy of comutagenesis of two potential pore-forming transmembrane regions (TM1 and TM6) to investigate the collaboration of these two TM regions. We performed a range of specific functional assays comparing the single channel conductance, anion binding, and anion selectivity properties of the co -mutated CFTR variants, and the results indicated that TM1 and TM6 play vital roles in forming the channel pore and, thus, determine the functional properties of the channel. Furthermore, we provide d functional evidence that the amino acid threonine (T338) in TM6 has synergic effects with lysine (K95) in TM1. Therefore, we propose that these two residues have functional collaboration in the CFTR channel pore and may collectively form a selective filter ., F. Qian, L. Liu, Z. Liu, C. Lu., and Obsahuje bibliografii
The purpose of this study was to compare markers of glycolytic metabolism in response to the Wingate test and the incremental test in road and mountain bike cyclists, who not different performance level and aerobic capacity. All cyclists executed the Wingate test and incremental test on a cycle ergometer. Maximal power and average power were determined during the Wingate test. During the incremental test the load was increased by 50 W every 3 min, until volitional exhaustion and maximal aerobic power (APmax), maximal oxygen uptake (VO2max), and time of VO2max plateau (Tplateau) were determined. Post-exercise measures of oxygen uptake (VO2post), carbon dioxide excretion, (VCO2post), and the ratio between VCO2/VO2 (RERpost) were collected for 3 min immediately after incremental test completion. Arterialized capillary blood was drawn to measure lactate (La-) and hydrogen (H+) ion concentrations in 3 min after each test. The data demonstrated significant differences between mountain bike and road cyclists for Tplateau, VO2post, VCO2post, La- which was higher-, and RERpost which was lower-, in mountain bike cyclists compare with road cyclists. No differences were observed between mountain bike and road cyclists for APmax, VO2max, H+ and parameters measured in the Wingate test. Increased time of VO2max plateau concomitant to larger post-exercise La- and VO2 values suggests greater anaerobic contribution during incremental testing efforts by mountain bike cyclists compared with road cyclists., P. Hebisz, R. Hebisz, J. Borkowski, M. Zatoń., and Obsahuje bibliografii
Electrogastrography (EGG) is a non-invasive method for the assessment of gastric myoelectrical activity. Porcine EGG is comparable with human one. The purpose of this study was to evaluate the effect of atropine and neostigmine on the EGG in experimental pigs. Adult female pigs were administrated atropine (1.5 mg i.m., n=6) and neostigmine (0.5 mg i.m., n=6) after the baseline EGG, followed by a 90-min trial recording (MMS, Enschede, the Netherlands). Running spectral analysis was used for the evaluation. The results were expressed as dominant frequency of slow waves and EGG power (areas of amplitudes). Neostigmine increased continuously the dominant frequency and decreased significantly the EGG power. Atropine did not change the dominant frequency significantly. However, atropine increased significantly the EGG power (areas of amplitudes) from basal values to the maximum at the 10-20-min interval. After that period, the areas of amplitudes decreased significantly to the lowest values at the 60-90-min interval. In conclusion, cholinergic and anticholinergic agents affect differently EGG in experimental pigs., J. Květina, I. Tachecí, M. Pavlík, M. Kopáčová, S. Rejchrt, T. Douda, M. Kuneš, J. Bureš., and Obsahuje bibliografii
This study investigated the value of oxygen (O2) pulse curves obtained during cardiopulmonary exercise testing (CPET) for the diagnosis of coronary artery disease (CAD). Forty patients with known coronary anatomy (35.0 % normal, 27.0 % single-vessel and 38.0 % multivessel CAD) underwent CPET with radiotracer injection at peak exercise, followed by myocardial scintigraphy. O2 pulse curves were classified as: A-normal, B-probably normal (normal slope with low peak value); C-probably abnormal (flat, with low peak value); or D- definitely abnormal (descending slope). Sensitivity, specificity, positive and negative predictive values of the O2 pulse curve pattern (A or B vs. C or D) for the diagnosis of CAD were, respectively, 38.5 %, 81.3 %, 76.9 %, and 44.8 %. The concordance rate between the abnormal O2 pulse curve pattern and ischemia in myocardial scintigraphy was 38.1 %. Age and the extent of scintigraphic perfusion defect, but not the abnormal O2 pulse curve patterns (B or C or both combined) were independently associated with CAD. In conclusion, the O2 pulse curve pattern has low diagnostic performance for the diagnosis of obstructive CAD, and the abnormal curve pattern was not associated with myocardial ischemia defined by scintigraphy., A. De Lorenzo, C. L. Da Silva, F. C. Castro Souza, R. De Souza Leão Lima., and Obsahuje bibliografii
Visfatin is a multi-functional molecule that can act intracellularly and extracellularly as an adipokine, cytokine and enzyme. One of the main questions concerning visfatin is the mechanism of its secretion; whether, how and from which cells visfatin is released. The objective of this in vitro study was to observe the active secretion of visfatin from 3T3-L1 preadipocytes and adipocytes, HepG2 hepatocytes, U-937, THP-1 and HL-60 monocytes and macrophages. The amount of visfatin in media and cell lysate was always related to the intracellular enzyme, glyceraldehyde-3- phosphate dehydrogenase (GAPDH), to exclude the passive release of visfatin. Visfatin was not found in media of 3T3-L1 preadipocytes. In media of 3T3-L1 adipocytes and HepG2 hepatocytes, the ratio of visfatin to the amount of GAPDH was identical to cell lysates. Hence, it is likely that these cells do not actively secrete visfatin in a significant manner. However, we found that significant producers of visfatin are differentiated macrophages and that the amount of secreted visfatin depends on used cell line and it is affected by the mode of differentiation. Results show that 3T3-L1 adipocytes and HepG2 hepatocytes released visfatin only passively during the cell death. U-937 macrophages secrete visfatin in the greatest level from all of the tested cell lines., P. Svoboda, E. Křížová, K. Čeňková, K. Vápenková, J. Zídková, V. Zídek, V. Škop., and Obsahuje bibliografii
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