b1_We previously demonstrated in rats that noninvasive delayed limb ischemic preconditioning (LIPC) induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb per day for three days confers the sa me cardioprotective effect as local ischemic preconditioning of the heart, but the mechanism has not been studied in depth. The aim of this project was to test the hypothesis that delayed LIPC enhances myocardial antioxidative ability during ischemia-reperfusion by a mitochondrial KATP channel (mito KATP)-dependent mechanism. Rats were randomized to five gr oups: ischemia-reperfusion (IR)- control group, myocardial ischemic preconditioning (MIPC) group, LIPC group, IR-5HD group and LIPC-5HD group. The MIPC group underwent local ischemic precondi tioning induced by three cycles of 5-min occlusion and 5-min reperfusion of the left anterior descending coronary arteries. The LIPC and LIPC-5HD groups underwent LIPC induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb using a modified blood pressure aerocyst per day for three days. All rats were subjected to myocardial ischemia-reperfu sion injury. The IR-5HD and LIPC-5HD groups received the mito KATP channel blocker 5-hydroxydecanoate Na (5-HD) before and during the myocardial ischemia-reperfusion injury. Compar ed with the IR-control group, both the LIPC and MIPC groups showed an amelioration of ventricular arrhythmia, reduced my ocardial infarct size, increased activities of total superoxide dismutase, manganese-superoxide dismutase (Mn-SOD) and glutathione peroxidase, increased expression of Mn-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration. These beneficial effects of LIPC were prevented by 5-HD. In conclusion , delayed LIPC offers similar cardioprotecti on as local IPC., b2_These results support the hypothesis that the activation of mito K ATP channels enhances myocardial antioxidat ive ability during ischemia- reperfusion, thereby contributing, at least in part, to the anti- arrhythmic and anti-infarct effects of delayed LIPC., Y.-N. Wu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Portal-systemic shunting is an important circulatory abnormality in patients with liver cirrhosis. Glyceryl trinitrate (GTN) that is normally subject to first pass elimination, may exhibit higher bioavailability in these patients. This study compares the pharmacodynamic effects of GTN after peroral and sublingual administration for noninvasive assessment of shunting. Six control subjects and 15 patients with cirrhosis were studied after oral and sublingual application of 0.5 mg of GTN. Liver cirrhosis was complicated by portal hypertension in 7 of the patients and 4 patients had surgically implanted portocaval anastomosis. Digital plethysmography, which is highly sensitive and is essentially noninvasive in nature, was used to assess and compare the pharmacodynamic effects of GTN. The following values of the ratio of areas under the pharmacodynamic effects/time curve were obtained: 0.08±0.06 in healthy subjects, 0.52±0.21 in patients with uncomplicated cirrhosis, 0.99±0.34 in patients with portal hypertension and 1.24±0.43 in patients with portal-systemic shunts. We conclude that increased bioavailability of GTN reflects portal-systemic shunting and might be used providing that the pharmacodynamic data reflect both pharmacokinetic variability and the pharmacokinetic-pharmacodynamic interrelations., O. Slanař, J. Aubrecht, F. Perlík., and Obsahuje bibliografii
High frequency oscillatory ventilation (HFOV), contrary to conventional ventilation, enables a safe increase in tidal volume (VT) without endangering alveoli by volutrauma or barotrauma. The aim of the study is to introduce the concept of normocapnic high frequency oscillatory hyperventilation and to assess its effect upon oxygen gain under experiment al conditions. Laboratory pigs (n=9) were investigated under total intravenous anesthesia in three phases. Phase 1: Initial volume controlled HFOV period. Phase 2 : Hyperventilation - VT was increased by (46 ± 12) % when compared to normocapnic VT during phase 1. All other ventilatory parameters were unchanged. A significant increase in PaO 2 (by 3.75 ± 0.52 kPa, p<0.001) and decrease in PaCO 2 (by -2.05 ± 0.31 kPa, p<0.001) were obtained. Phase 3: Normocapnia during hyperventilation was achiev ed by an iterative increase in the CO 2 fraction in the inspiratory gas by a CO2 admixture. All ventilatory parameters were unchanged. A significant increase in PaO2 (by 3.79 ± 0.73 kPa, p<0.001), similar to that which was observed in phase 2, was preserved in phase 3 whereas normocapnia was fully re-established. The concept of high frequency normocapnic hyperventilation offers a lung protective strategy that significantly improves oxygenation whilst preserving normocapnia., K. Roubík, J. Pachl, V. Zábrodský., and Obsahuje bibliografii a bibliografické odkazy
Cardiac fibroblast-myofibroblast transformation (CMT) is a critical event in the initiation of myocardial fibrosis. Notch signaling has been shown to regulate myofibroblast transformation from other kinds of cells. However, whether Notch signaling is also involved in CMT remains unclear. In the present study, expressions of Notch receptors in cardiac fibroblasts (CFs) were examined, effects of Notch signaling inhibi tor N-[N-(3,5-difluorophenacetyl)- l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and transforming growth factor-β1 (TGF-β1) on CMT were determined by increasing alpha-smooth muscle actin (α-SMA) expression and collagen synthesis, and Notch signaling was examined by analyzing expressions of Notch receptors. The results showed that: (1) Notch receptor 1, 2, 3 and 4 were all expressed in CFs; (2) DAPT promoted CMT in a time -dependent manner; (3) During the period of CMT induced by TGF-β1, expressions of Notch receptor 1, 3 and 4 in CFs were down-regulated, whereas there was no change for Notch receptor 2. Moreover, the downtrends of Notch 1, 3 and 4 were corresponding to the trend growth of α-SMA expression and collagen synthesis. These results suggested that inhibiting of Notch signaling might promote CMT. The down-regulations of Notch receptor 1, 3 and 4 induced by TGF-β1 may facilitate CMT. In conclusion, inhibition of Notch signaling might be a novel mech anism of CMT in myocardial fibrosis., Y.-H. Fan ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF- 21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA., H. Hulejová ... [et al.]., and Obsahuje seznam literatury
Excessive production of reactive oxygen species (ROS) are implicated in the pathogenesis of numerous disease states. However, direct measurement of in vivo ROS in humans has remained elusive due to limited access to appropriate tissue beds and the inherently short half-lives and high reactivity of ROS. Herein, we describe a novel technique by which to measure in vivo ROS in human skeletal muscle. Microdialysis probes were inserted into the vastus lateralis of eight healthy volunteers. Amplex Ultrared, a highly specific fluorogenic substrate for hydrogen peroxide (H2O2), and horseradish peroxidase (HRP), were perfused through microdialysis probes, and outflowing dialysate was collected and fluorescence was measured. Extracellular H2O2 that crossed the microdialysis membrane was measured via fluorescence of the dialysate. Superoxide dismutase (SOD) was then added to the inflowing perfusion media to convert any superoxide crossing the microdialysis membrane to H2O2 within the microdialysis probe. Fluorescence significantly increased (P=0.005) upon SOD addition. These data demonstrate the feasibility of measuring both in vivo H2O2 and superoxide in the extracellular environment of human skeletal muscle, providing a technique with a potential application to a wide range of circulatory and metabolic studies of oxidative stress., J. D. La Favor, E. J. Anderson, R. C. Hickner., and Obsahuje bibliografii
We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106±12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334±12 vs. 125±32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2±7.2 vs. 7.3±2.2 vs. 8.3±5.5 min, p=0.003), cessation of LVMA (11.3±5.6 vs. 4.4±0.4 vs. 7.4±2.9 min, p=0.027) and cessation of microcirculation (25.3±12.6 vs. 13.4±2.4 vs. 23.2±8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA., R. Skulec, D. Astapenko, R. Cerna Parizkova, B. Furst, M. Bilska, T. Parizek, T. Hovanec, N. Pinterova, J. Knor, J. Dudakova, A. Truhlar, V. Radochova, Z. Zadak, V. Cerny., and Obsahuje bibliografii
The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury., M. Barančík, L. Grešová, M. Barteková, I. Dovinová., and Obsahuje bibliografii
Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting as early- onset mitochondrial encephalo- cardiomyopathies. Up to now, mutations in four nuclear genes were associated with isolated deficiency of ATP synthase. Two of them, ATP5A1 and ATP5E encode enzyme’s st ructural subunits α and ε , respectively, while the other two ATPAF2 and TMEM70 encode specific ancillary factors that facilitate the biogenesis of ATP synthase. All these defects share a similar biochemical phenotype with pronounced decrease in the content of fully assembled and functional ATP synthase complex. However, substantial differences can be found in their frequency, molecular mechanism of pathogenesis, clinical manifestation as well as the course of the disease progression. While for TMEM70 the number of reported patients as well as spectrum of the mutations is steadily increasing, mutations in ATP5A1, ATP5E and ATPAF2 genes are very rare. Apparently, TMEM70 gene is highly prone to mutagenesis and this type of a rare mitochondrial disease has a rather frequent incidence. Here we present overview of individual reported cases of nuclear mutations in ATP synthase and discuss, how their analysis can improve our understanding of the enzyme biogenesis., K. Hejzlarová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. In addition to the genetic, epigenetic and immunological components, various other factors, e.g. unhealthy dietary habits, play a role in the MS pathogenesis. Dietary intervention is a highly appealing approach, as it presents a simple and relatively low risk method to potentially improve outcomes in patients with brain disorders in order to achieve remission and improvement of clinical status, well-being and life expectancy of patients with MS. The importance of saturated fat intake restriction for the clinical status improvement of MS patients was pointed for the first time in 1950s. Recently, decreased risk of first clinical diagnosis of CNS demyelination associated with higher intake of omega-3 polyunsaturated fatty acids particularly originating from fish was reported. Only few clinical trials have been performed to address the question of the role of dietary intervention, such is e.g. low saturated fat diet in MS treatment. This review summarizes current knowledge about the effect of different dietary approaches (diets low in saturated fat and dietary supplements such as fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, seeds oils, high fiber diet, vitamin D, etc.) on neurological signs, patient’s well-being, physical and inflammatory status. So far the results are not conclusive, therefore much more research is needed to confirm and to understand the effectiveness of these dietary interventions in the long term and well defined studies., A. Penesová, Z. Dean, B. Kollár, A. Havranová, R. Imrich, M. Vlček, Ž. Rádiková., and Obsahuje bibliografii