Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients’ peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-γ) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis., L. Stranavová, P. Hrubá, E. Girmanová, I. Tycová, A. Slavčev, J. Fronek, J. Slatinská, P. Reinke, H.-D. Volk, O. Viklický., and Seznam literatury
This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid peroxidation, nitric oxide production and antioxidant systems in rats exposed to chronic restraint stress. Twenty four male Wistar rats, aged three months, were divided into four groups: control (C), the group treated with LA (L), the group exposed to restraint stress (S) and the group exposed to stress and treated with LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Restraint stress significantly decreased brain copper/zinc superoxide dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the control group. Thiobarbituric acid reactive substances (TBARS), nitrite and nitrate levels were significantly increased in the tissues of the S group compared with the C group. LA produced a significant decrease in brain and retina TBARS, nitrite and nitrate levels of the L and LS groups compared to their corresponding control groups. LA increased all enzyme activities in the tissues of the LS group compared to the S group. Our study indicated that LA is an ideal antioxidant candidate for the prevention of stress-induced lipid peroxidation., D. Akpinar, P. Yargiçoğlu, N. Derin, Y. Alicigüzel, A. Ağar., and Obsahuje bibliografii a bibliografické odkazy
In cardiac surgical patients we investigated the effects of cardiopulmonary bypass (CPB) with a hollow fiber membrane oxygenator on blood clotting measured by thromboelastography (TEG). We found only a minimal change in the strength of blood clot described either by the TEG parameter MA (maximum amplitude) or by the shear modulus G calculated from MA. After CPB there was also a significant tendency towards hypercoagulation as defined by shortened parameters R, K and increased ?-angle. After comparison with published data obtained in cardiac surgical patients using a bubble oxygenator we conclude that currently used extracorporeal technology exerts a less negative influence on blood clotting than had been conceived previously., M. Horáček, K. Cvachovec., and Obsahuje bibliografii
The functional aversive stimulus properties of several IP doses of (±)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg 1) were measured with the conditioned taste aversion (CTA) paradigm. A two bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (±)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (±)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (±)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (±)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives., A.J. Greenshaw, S. Turkish, B.A. Davis., and Obsahuje bibliografii
Doctor David J. Webb MD, DSc, FRCP, FRSE, FMedSci, a clinical pharmacologist specialising in the management of cardiovascular disease, is the recipient of The Fourth Tomoh Masaki Award , a bi-annual prize presented on the occasion of the International Conferences on Endothelin to scientists for outstanding contributions and achievements in the field of endothelin research. The Fourth Tomoh Masaki Award was presented to Doctor Webb at the Fifteenth International Conference on Endothelin which was held at Duo Hotel, Prague, Czech Republic, in October 2017. The award was granted to Dr. Webb during the Award Ceremony in Troja Chateau “In Recognition of his Outstanding Contributions to Science and Endothelin Research in Particular”. This article summarises the career and the scientific achievements of David J. Webb viewed by his former student Dr. Neeraj Dhaun, known to everybody as ‘Bean’., N. Dhaun., and Seznam literatury
The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH., J. Honda, T. Kimura, S. Sakai, H. Maruyama, K. Tajiri, N. Murakoshi, S. Homma, T. Miyauchi, K. Aonuma., and Seznam literatury
It is well known that the training level of a muscle belongs to the parameters that affect the H-reflex response amplitude. The aim of this study was to investigate the effects of training type on H- and T-reflex response parameters. For this purpose, 20 long-distance athletes (group I, test group), 18 short-distance athletes (group II, test group) and 20 non-trained subjects (group III, control group) were involved in this study in which the H- and T-reflex amplitude and latency values were measured. The H-reflex amplitude and latency values found in groups I, II and III were 3.64±0.28 mV and 26.88±1.45 ms, 3.17±0.26 mV and 26.19±1.89 ms, and 6.07±0.34 mV and 26.77±1.32 ms, respectively. The T-reflex amplitude and latency values of the groups I, II and III were 3.30±0.18 mV and 32.01±1.02 ms, 3.11±0.20 mV and 31.47±1.16 ms, 4.24±0.21 mV and 31.47±1.16 ms, respectively. There was no statistically significant difference between the groups with respect to latencies of H- and T-reflexes (p>0.05). In both test groups, the amplitudes of the H-reflex and T-reflex were significantly smaller than the control group (p<0.05). The results of this study suggest that training of muscles affect the H- and T-reflex response parameters., R. Ozmerdivenli, S. Bulut, T. Urat, A. Ayar., and Obsahuje bibliografii
We investigated the actions of dantrolene Ca2+-induced on Ca2+-release (CICR) evoked by action potentials in cultured rat sensory neurons. The effect of dantrolene on action potential after-depolarization and voltage-activated calcium currents was studied in cultured neonatal rat dorsal root ganglion cells (DRG) using the whole-cell patch-clamp technique. Depolarizing current injection evoked action potentials and depolarizing after-potentials, which are activated as a result of CICR following a single action potential in some cells. The type of after-potentials was determined by inducing action potentials from the resting membrane potential. Extracellular application of dantrolene (10 mM) abolished after-depolarizations without affecting action potential properties. Furthermore, dantrolene significantly reduced repetitive action potentials after depolarizing current injection into these neurons, but had no significant effect on the steady-state current voltage relationship of calcium currents in these neurons. We conclude that dantrolene inhibits the induction of action potential after depolarizations by inhibiting CICR in cultured rat sensory neurons., A. Ayar, H. Kelestimur., and Obsahuje bibliografii
a1_In a series of studies in the late 1950s and early 1960s, Jan Bures introduced cortical spreading depression to the field of behavioral neuroscience (eg. Bures 1960). This technique offered a unique way to study the role of cortex in learning and memory, and attracted the attention of many who began their graduate studies at that time, including one of us (LN, cf. Nadel 1966). An NIH postdoctoral fellowship to study with the master himself brought LN to Prague in September 1967. Thus began a relationship that included science, politics, and personal life, and has lasted over 30 years1,2. The first scientific exchange began with Jan pulling a piece of paper from his desk with a long list of possible experiments written on it -- “pick one”, he said. This led to a series of studies on interhemispheric transfer of learning under conditions of monocular input, demonstrating, amongst other things, that such transfer is not a uniform process. Depending on the kind of trials given with both hemispheres intact, and the eye which remained open to input, transfer can either be non-specific, likely involving some kind of procedural knowledge, or highly specific, likely involving knowledge about the trained discrimination itself (Nadel and Buresova, 1970). These studies anticipated LN’s future work on multiple memory systems, a research enterprise pursued in the following decades by many labs (including LN’s: e.g. Nadel and O’Keefe 1974, O’Keefe et al. 1975). In this paper we focus on several scientific issues that Jan has been thinking about for the past 25 years. In particular, we consider spatial learning, the hippocampus, and memory. To this mix we add stress, something well known to anyone living in Prague in 1968., a2_LN left Prague after the 1968 invasion and stayed in London for seven months, during which time arrangements were made for an eventual return to the Medical Research Council Cerebral Functions Research Group in 1970. Thus it was that LN happened to be down the hall when John O’Keefe and Jonathan Dostrovsky discovered place cells (O’Keefe and Dostrovsky 1971) and began the program of research leading to the cognitive map theory of hippocampal function (O’Keefe and Nadel 1978)., L. Nadel, J.D. Payne., and Obsahuje bibliografii