Streptozotocin (STZ) is used to induce experimental diabetes in animals and is also applied for the treatment of patients with insulinoma. The aim of the present work was to investigate the direct effect of STZ on lipolysis in isolated rat adipocytes. After the isolation, the cells were incubated in a Krebs-Ringer buffer of pH 7.4, at the temperature 37 °C for 90 min with different concentrations of STZ: 0.5, 1 or 2 mmol/l. STZ caused a significant rise in basal values (99 %, 199 %, and 377 %, respectively) and epinephrine-stimulated (1 µmol/l) lipolysis (15 %, 24 % and 46 %, respectively). Augmentation of basal lipolysis by STZ was neither restricted by insulin (1 nmol/l) nor by H-89 (an inhibitor of protein kinase A, 50 µmol/l). These results indicate the stimulatory influence of STZ on the action of hormone-sensitive lipase in isolated cells of white adipose tissue. The obtained outcomes suggest that in studies employing STZ, it is necessary to consider its direct effect upon lipolysis in adipocytes., T. Szkudelski, K. Szkudelska., and Obsahuje bibliografii
In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a ne w analytical approach to EDA asymmetry description., M. Světlák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The role of the striatal adenylyl cyclase (AC) and cholinergic systems in the learning and expression of new forepaw movements (reaching with prolonged pushing on a fixed piston) was studied in male Wistar rats. Motor learning processes, prenatal hypoxia, and cholinergic drugs changed the properties of the AC system in the striatum. After learning, the striatal basal AC activity was decreased compared to untrained control rats. In addition, the AC activity was more decreased in animals with a good ability to learn compared to poor learners (up to 31 % and 51 %, correspondingly; p<0.01). Rats subjected to prenatal hypoxia (13-14th days of embryogenesis) had a lower ability to learn the new movements requiring tactile control and the striatal AC activity in these rats was 1.8 times higher (p<0.001) than controls. In vitro application of the cholinergic agonist carbachol (CARB) 10-5 M (corresponding to ~ 0.3 µg), as well as the antagonist scopolomine (SCOP) 10-5 M (~ 0.3 µg) decreased AC activity in the synaptosomal fraction of the striatum. In vivo injections of CARB (0.3-3 µg/1µl) or SCOP (0.3-3 µg/1µl) into the ventral striatum (nucleus accumbens) modified the newly learned sensorimotor skill. After CARB injections the rats performed slower movements with more prolonged pushing. After SCOP the rats could not retain the learned pushing movement. These in vivo and in vitro data suggest that the cholinergic mediator system of the striatum is involved in learning sensory-controlled forepaw movements as well as the regulation of new motor skills by modulating the AC signal transduction process in the striatum. The data confirmed that modification of the striatal AC system resulted in the modulation of reaching behavior and better expression of the learned reflex., I. A. Zhuravin, N. M. Dubrovskaya, S. A. Plesneva., and Obsahuje bibliografii
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of ou r study was to confirm the association between NYD-SP18 rs6971091 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the si multaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971091 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971091 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males., J. A. Hubacek, D. Dlouha, V. Lanska, V. Adamkova., and Obsahuje bibliografii
NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are also characterized by use-independent unblock, compatible with minimal disruption of normal synaptic transmission. Thus, neurosteroids are a promising class of NMDA receptor modulators that may lead to the development of neuroprotective drugs with optimal therapeutic profiles., V. Vyklicky ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Agonist-induced subcellular redistribution of G-protein coupled receptors (GPCR) and of trimeric guanine-nucleotide binding regulatory proteins (G-proteins) represent mechanisms of desensitization of hormone response, which have been studied in our laboratory since 1989. This review brings a short summary of these results and also presents information about related literature data covering at least small part of research carried out in this area. We have also mentioned sodium plus potassium dependent adenosine triphosp hatase (Na, K-ATPase) and 3H-ouabain binding as useful reference standard of plasma membrane purity in the brain., Z. Drastichová, L. Bouřová, V. Lisý, L. Hejnová, V. Rudajev, J. Stöhr, D. Durchánková, P. Ostašov, J. Teisinger, T. Soukup, J. Novotný, P. Svoboda., and Obsahuje bibliografii a bibliografické odkazy
Kainic acid (KA) is a potent neurotoxic substance valuable in research of temporal lobe epilepsy. We tested how subconvulsive dose of KA influences spontaneous behavior of adult Wistar rats. Animals were treated with 5 mg/kg of KA and tested in Laboras open field test for one hour in order to evaluate various behavioral parameters. Week after the KA treatment animals were tested again in Laboras open field test. Finally, rat’s brains were sliced and stained with Fluoro-Jade B to detect possible neuronal degeneration. Treatment with KA increased the time spent by locomotion (p<0.01), exploratory rearing (p<0.05) and animals traveled longer distance (p<0.01). These parameters tended to increase thirty minutes after KA administration. Week after the treatment we did not found differences in any measured behavioral parameter. Histology in terms of Fluoro-Jade B staining did not reveal any obvious neuronal damage in hippocampus. These results demonstrate that subconvulsive KA dose changes the behavioral parameters only transiently. Clarification of timing of the KA induced changes may contribute to understand mutual relationship between non-convulsive seizures and behavioral/cognitive consequences., V. Riljak, D. Marešová, J. Pokorný, K. Jandová., and Obsahuje bibliografii
Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 ºC). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy., C. Neacsu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Cardiovascular (CV) mortality was reduced more than 50 % in the Czech population at the turn of the century, due to an improvement of major CV risk factors in the general population, interventional procedures implemented into the treatment of acute coronar y events, and new drugs (ACE inhibitors, statins etc.) for CV prevention (Czech MONICA and post-MONICA studies, 1985-2008). An insufficient level of preventive efforts is described in the Czech patients after acute coronary syndrome (Czech part of the EURO ASPIRE studies, 1995-2013). Drug underdosing and wrong patients’ compliance to life style and drug therapy recommendations represent two main reasons of this unsatisfactory situation. The residual vascular risk of patients with stable coronary heart diseas e (CHD) is still high due to a poor control of conventional risk factors on the one hand, and due to increasing weight and glucose metabolism abnormalities on the other hand. Patients with insulin resistance and glucose dis orders have more frequently non-LDL-C dyslipidemia (atherogenic dyslipidemia), hypertriglyceridemic waist and high atherogenic index of plasma (AIP>0.24), i.e. markers of residual CV risk. Among others increased dose of statins and combined lipid modifying therapy should be implemented in patients with CHD, diabetes or metabolic syndrome., H. Rosolová, B. Nussbaumerová, O. Mayer Jr., R. Cífková, J. Bruthans., and Obsahuje bibliografii
The most common cause of sudden cardiac death is ventricular fibrillation (VF). In addition to the status, size and location of the ventricular focus, a major pathogenic mechanism triggering VF is autonomic dysbalance (d isturbance). This term refers to a wide range of reflex changes in the ratio of sympathetic to vagal ventricular activation over time, occurring immediately after coronary artery occlusion at the onset of acute myocardial infarction (AMI). Another trigger of VF is autonomic disturbance due to emotional stress. Experimental and clinical research into autonomic disturbances associated with coronary artery occlusion and emotional stress was given considerable attention as early as some 30 years ago when researchers were already searching for ways of inhibiting autonomic disturbances using predominant sympathetic and vagal activation by beta-blockers (BB) and atropine, respectively. The aim of our paper is to compare results obtained 30 years ago with current status of experimental and clinical research into SCD preven tion. Another aim is to identify questions that have remained unanswered to date; answers to these outstanding questions could help further reduce the risk of SCD., J. Pokorný, V. Staněk, M. Vrána., and Obsahuje bibliografii a bibliografické odkazy