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
This study aimed to investigate the vasoactivity of sulfur dioxide (SO2), a novel gas identified from vascular tissue, in rat thoracic aorta. The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers. After equilibrium, the rings were gradually stretched to a resting tension. Isometric tension was recorded under the treatments with vasoconstrictors, SO2 derivatives, and various drugs as pharmacological interventions. In endothelium-intact aortic rings constricted by 1 μM phenylephrine (PE), SO2 derivatives (0.5 – 8 mM) caused a dose-dependent relaxation. Endothelium removal and a NOS inhibitor L-NAME reduced the relaxation to low doses of SO2 derivatives, but not that to relatively high doses (≥ 2 mM). In endothelium-denuded rings, SO2 derivatives attenuat ed vasoconstriction induced by high K+ (60 mM) or CaCl2 (0.01-10 mM). The relaxation to SO2 derivatives in PE-constricted rings without endothelium was significantly inhibited by blockers of ATP-sensitive K+ (KATP) and Ca2+-activated K+ (KCa) channels, but not by those of voltage-dependent K+ channels, Na+-K+-ATPase or Na+-Ca2+ exchanger. SO2 relaxed vessel tone via endothelium-dependent mechanisms associated with NOS activation, and via endothelium-independent mechanisms dependent on the inhibition of voltage-gated Ca2+ channels, and the opening of KATP and KCa channels., Y.-K- Wang., and Obsahuje seznam literatury
The administration of creatine (5 g/day for one month) to 11 young active sportsmen affected their urinary excretion of creatine, creatinine, and thiodiglycolic acid (TDGA) as well as blood levels of homocysteine, vitamin B12 and folates. The probands were divided into four groups, according to the amount of creatine found in urine, and of folates and vitamin B12 determined in blood. The changes of folates and vitamin B12 were mutually reciprocal. Each group utilized CR as donor of one- and two-carbon (1C and 2C) units by means of homocysteine (HoCySH), folates, and vitamin B12, in different metabolic pathways. In 10 men the creatine administration was accompanied by an increase of HoCySH level in blood, while in the last man, with accidentally discovered hyperhomocysteinemia, the HoCySH level dropped by 50 %. Differences between initial and terminal TDGA levels indicate that creatine affects equilibria of redox processes. Creatinine excretion into urine changed in the dependence on the extent of metabolic disturbances., T. Navrátil ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the ai m of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45- min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial is chemia- and reperfusion-induced arrhythmias and lethal myocardial injury., H. Říha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas., Y. Nishiyama, ... [et al.]., and Obsahuje seznam literatury
Self-organization in a polymer system appears when a balance is achieved between long-range repulsive and short-range attractive forces between the chemically different building blocks. Block copolymers forming supramolecular assemblies in aqueous media represent materials which are extremely useful for the construction of drug delivery systems especially for cancer applications. Such formulations suppress unwanted physicochemical properties of the encapsulated drugs, modify biodistribution of the drugs towards targeted delivery into tissue of interest and allow triggered release of the active cargo. In this review, we focus on general principles of polymer selforganization in solution, phase separation in polymer systems (driven by external stimuli, especially by changes in temperature, pH, solvent change and light) and on effects of copolymer architecture on the self-assembly process., M. Hrubý, S. K. Filippov, P. Štěpánek., and Obsahuje bibliografii
The effect of suramin, an inhibitor of G protein regulated signalling, was studied on the membrane currents induced by noxious heat and by capsaicin in cultured dorsal root ganglia neurones isolated from neonatal rats. Whole-cell responses induced by a heat ramp (24-52 °C) were little affected by suramin. The noxious heat-activated currents were synergistically facilitated in the presence of 0.3 µM capsaicin 13.2-fold and 6.3-fold at 40 °C and 50 °C, respectively. In 65% of neurones, the capsaicin-induced facilitation was inhibited by 10 µM suramin to 35±6 % and 53±6 % of control at 40 °C and 50 °C (S.E.M., n=15). Suramin 30 µM caused a significant increase in the membrane current produced by a nearly maximal dose (1 µM) of capsaicin over the whole recorded temperature range (2.4-fold at 25 °C and 1.2-fold at 48 °C). The results demonstrate that suramin differentially affects the interaction between capsaicin and noxious heat in DRG neurones and thus suggest that distinct transduction pathways may participate in vanilloid receptor activation mechanisms., V. Vlachová, A. Lyfenko, L. Vyklický, † R.K. Orkand., and Obsahuje bibliografii
Materials on the basis of cycloolefin copolymers (COC) are suitable for subchondral defect repairs. The objective of this study was to evaluate the influence of surface modification of COC and COC/LLDPE blends on the viability and gene expression of chondrocytes. Human chondrocytes were incubated on the surface of the studied materials. Half of the materials were plasmatically modified with a subsequent type II collagen application. The gene expression of matrix metalloproteinases (MMP-1,-3,-13), pro-inflammatory cytokines (IL-1, TNF-alpha) and apoptotic molecules (BAX, Bcl-2) was evaluated using quantitative Taq-Man PCR after 48 h incubation. Chondrocyte viability was evaluated by the MTT test after 2, 4 and 8 days of incubation. The synthesis of MMPs was measured by ELISA assay in cell culture medium after 48 h of incubation. Chondrocytes incubated on plasmatically modified in contrast to unmodified materials demonstrated significantly increased gene expression of IL-1 (p<0.05), MMP-1 and MMP-3 (p<0.05 for both comparisons) as well as MMP-13 (p<0.001). Increased gene expression was confirmed by significantly increased production of active forms of particular MMPs into the cell culture medium. Unlike surface unmodified polymers, the modified materials showed timedependent reduction of chondrocyte viability. The gene expression of TNF-α and apoptotic molecules by chondrocytes was not significantly changed by different materials. Cycloolefin copolymers and their blends may represent suitable materials for tissue engineering, however, their surface modification followed by collagen type II application may, at least under in vitro conditions, reduce the viability of chondrocytes and induce their pro-destructive behavior. The potential benefit or disadvantage of surface modifications of materials for osteochondral defect repairs needs to be further elucidated., M. Polanská ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy