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
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
Diabetic heart is suggested to exhibit either increased or decreased resistance to ischemic injury. Ischemic preconditioning suppresses arrhythmias in the normal heart, whereas relatively little is known about its effects in the diseased myocardium. Our objective was to investigate whether development of diabetes mellitus modifies the susceptibility to ischemia-induced arrhythmias and affects preconditioning in the rat heart. Following 1 and 9 weeks of streptozotocin-induced (45 mg/kg, i.v.) diabetes, the hearts were Langendorff-perfused at constant pressure of 70 mm Hg and subjected to test ischemia induced by 30 min occlusion of the left anterior descending (LAD) coronary artery. Preconditioning consisted of one cycle of 5 min ischemia and 10 min reperfusion, prior to test ischemia. Susceptibility to ischemia-induced arrhythmias was lower in 1-week diabetics: only 42 % of diabetic hearts exhibited ventricular tachycardia (VT) and 16 % had short episodes of ventricular fibrillation (VF) as compared to VT 100 % and VF 70 % (including sustained VF 36 %) in the non-diabetics (P<0.05). Development of the disease was associated with an increased incidence of VT (VT 92 %, not significantly different from non-diabetics) and longer total duration of VT and VF at 9-weeks, as compared to 1-week diabetics. Preconditioning effectively suppressed arrhythmias in the normal hearts (VT 33 %, VF 0 %). However, it did not provide any additional antiarrhythmic protection in the acute diabetes. On the other hand, in the preconditioned 9-weeks diabetic hearts, the incidence of arrhythmias tended to decrease (VT 50 %, transient VF 10 %) and their severity was reduced. Diabetic rat hearts are thus less susceptible to ischemia-induced arrhythmias in the acute phase of the disease. Development of diabetes attenuates increased ischemic tolerance, however, diabetic hearts in the chronic phase can benefit more from ischem preconditioning, due to its persisting influence., T. Ravingerová, R. Štetka, D. Pancza, O. Uličná, A. Ziegelhöffer, J. Styk., and Obsahuje bibliografii
Novel star polymers based on the water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer and cyclodextrin were synthesized and the physico-chemical behavior of these precursors was studied. Semitelechelic HPMA copolymers were grafted onto the cyclodextrin core, thus forming star-like structure. Both prepared systems were designed as possible polymer carriers for the controlled release of cytostatic drugs, which after the drug release and degradation will be eliminated from the organism. Two synthesis approaches were used to obtain similar polymer carriers with different degradation rates. All the polymers were prepared by reversible additionfragmentation chain-transfer polymerization, which guarantees low dispersity of the prepared systems., L. Kotrchová, T. Etrych., and Obsahuje bibliografii
Tissue engineering (TE) and regenerative medicine are progressively developed areas due to many novel tissue replacements and implementation strategies. Increasing knowledge involving the fabrication of biomaterials with advanced physicochemical and biological characteristics, successful isolation and preparation of stem cells, incorporation of growth and differentiation factors, and biomimetic environments gives us a unique opportunity to develop various types of scaffolds for TE. The current strategies for soft tissue reconstitution or regeneration highlight the importance of novel regenerative therapies in cases of significant soft tissue loss and in cases of congenital defects, disease, trauma and ageing. Various types of biomaterials and scaffolds have been tested for soft tissue regeneration. The synthetic types of materials have gained great attention due to high versatility, tunability and easy functionalization for better biocompatibility. This article reviews the current materials that are usually the most used for the fabrication of scaffolds for soft TE; in addition, the types of scaffolds together with examples of their applications for the regenerative purposes of soft tissue, as well as their major physicochemical characteristics regarding the increased applicability of these materials in medicine, are reviewed., O. Janoušková., and Obsahuje bibliografii
Chronic volume overload (VO) on the left ventricle (LV) augments redox stress and activates matrix metalloproteinase (MMP) which causes the endocardial endothelial-myocyte (EM) disconnection leading to myocardial contractile dysfunction. VO-induced MMP-9 activation impairs cardiac functions, in part by endothelial endocardial apoptosis, but the role of MMP-9 on EM functions remains obscure. We conjecture that chronic VO activates MMP-9 and causes EM uncoupling. Arteriovenous fistula (AVF) was created in genetically identical wild type (WT) mice (FVB/NJ) and MMP-9 knockout mice (MMP-9KO, FVB.Cg-MMP9tm1Tvu/J). Sham-operated mice were used as controls. Before experimentation the phenotype analysis of MMP-9KO mice was carried out. In-gel-gelatin zymography for MMP-9 activation was performed on LV homogenates. The EM functions were determined on LV rings using tissue myobath. We report a decrease in MMP-9 activity in left ventricular myocardial extracts in MMP-9 deficient mice after AVF. The responses to drugs affecting cardiac functions (acetylcholine (Ach), nitroprusside and bradykinin) were attenuated in AVF mice suggesting the impairment of EM coupling. Interestingly, the EM functions were restored in the MMP-9 deficient mice after AVF. We suggest a direct cause-and-effect relationship between MMP-9 activation and EM uncoupling in LV myocardium after chronic VO and the possible involvement of MMP-9 in myocardial contractile performance., K. S. Moshal, W. E. Rodriguez, U. Sen, S. C. Tyagi., and Obsahuje bibliografii a bibliografické odkazy
The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning., I. Moron, M.A. Ballesteros, A. Candido, M. Gallo., and Obsahuje bibliografii