We studied the ability of the ECG to detect pathological changes in isoproterenol-induced remodeling of rat heart. Myocardial hypertrophy in rats was induced by repeated injections of isoproterenol (5 mg/kg s.c. 7 days, Iso5, n=7). Single overdose of isoproterenol (150 mg/kg s.c., Iso150, n=7) evoked myocardial infarction followed with ventricular remodeling. The electrocardiograms were recorded in anesthetized animals (thiopenthal 45 mg/kg i.p.) and myocardial contractile performance was analyzed in isolated hearts perfused according to Langendorff. The hypertrophic hearts were characterized by increased heart and left ventricular (LV) weight as well as by thicker LV free wall and interventricular septum. Mean values of LV contraction did not significantly differ from controls. Longer QT interval, QRS complex, negative Q and S waves, higher R amplitude were typical characteristics for Iso5 rats. Iso150 animals showed tendency to decreased systolic blood pressure and heart frequency. Decrease in the thickness of LV compared to Iso5 as well as impaired LV function were related to the dilated left ventricle. Iso150 ECG showed longer QRS and QT, deepened negativity of S wave and mild decrease of RII compared to Iso5. Voltage criteria showed that Sokolow-Lyon index is a good predictor of left ventricular hypertrophy in isoproterenol-induced cardiac remodeling without systemic hypertension., E. Kráľová, T. Mokráň, J. Murín, T. Stankovičová., and Obsahuje bibliografii a bibliografické odkazy
The aim of present study was to investigate functional and physical alterations in membranes of heart mitochondria that are associated with remodeling of these organelles in acute phase of streptozotocin-induced diabetes and to elucidate the role of these changes in adaptation of the heart to acute streptozotocin-induced diabetes (evaluated 8 days after single dose streptozotocin application to male Wistar rats). Action of free radicals on the respiratory chain of diabetic-heart mitochondria was manifested by 17 % increase (p<0.05) in oxidized form of the coenzyme Q10 and resulted in a decrease of states S3 and S4 respiration, the respiratory control index, rate of phosphorylation (all p<0.01) and the mitochondrial transmembrane potential (p<0.05), but the ADP/O ratio decreased only moderately (p>0.05). On the contrary, membrane fluidity and the total mitochondrial Mg2+-ATPase activity increased (both p<0.05). In diabetic heart mitochondria, linear regression analysis revealed a reciprocal relationship between the increase in membrane fluidity and decrease in trans-membrane potential (p<0.05, r = 0.67). Changes in membrane fluidity, transmembrane potential, Mg2+-ATPase activity and the almost preserved ADP/O ratio appear as the manifestation of endogenous protective mechanisms participating in the functional remodeling of mitochondria which contributes to adaptation of the heart to diabetes., M. Ferko, D. Habodászová, I. Waczulíková, J. Mujkošová, J. Kucharská, L. Šikurová, B. Ziegelhöffer, J. Styk, A. Ziegelhöffer., and Obsahuje bibliografii a bibliografické odkazy
Gastrointestinal form is the second stage of acute radiation syndrome (ARS) with a threshold dose of 8 Gy in man. It represents an absolutely lethal clinical-pathological unit, necro-hemorrhagic enteritis and proctocolitis, with unknown causal therapy. Elk-1 is a protein acting as a transcription factor activating specified genes. The purpose of our study was to examine the expression of phospho-Elk-1 in irradiated jejunum and transversal colon of rats with radiation-induced enterocolitis and to assess the importance of this transcriptional factor as a biodosimetric marker of radiation-induced enteropathy. The laboratory rats were randomly divided into 21 groups, 10 animals per group, and irradiated with whole body γ-irradiation of 1, 5, 10, 15, and 20 Gy. Samples of jejunum and transversal colon were taken 24, 48, 72, and 96 hours later, immunohisto-chemically stained, and the phospho-Elk-1 expression was examined using computer image analysis. A group of 10 sham-irradiated animals was used as control. Significantly increased expression of phospho-Elk-1 in rat jejunum has been found in all time intervals after irradiation by sublethal doses of 1 and 5 Gy, whereas after the irradiation by lethal doses, the expression of phospho-Elk-1 in rat jejunum varied considerably. Significantly increased expression of phospho-Elk-1 in transversal colon has also been found in the first days after irradiation by sublethal doses of 1 and 5 Gy. After irradiation by lethal doses, tere was no uniform pattern of the changes in the expression of phospho-Elk-1 in rat transversal colon. The detection of phospho-Elk-1 might be considered as a suitable and very sensitive biodosimetric marker of radiation-induced injury of small and large intestine. According to our knowledge, this is the first study on the phospho-Elk-1 expression in irradiated jejunum and transversal colon in the rat., D. Driák, J. Österreicher, Z. Řeháková, Z. Vilasová, J. Vávrová., and Obsahuje bibliografii a bibliografické odkazy
There is a growing interest for the beneficial effect of magnesium (Mg) in cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extracellular or intracellular concentrations of Mg. The efficiency of the preconditioning effect of Mg on cardiac function and infarct size in the globally ischemic-reperfused isolated rat heart was studied together with the role of ATP-sensitive potassium (KATP) channels in protection induced by Mg. Rat hearts were Langendorff perfused, subjected to 30 min of global ischemia and 90 min of reperfusion, including treatment groups which focused on different times of Mg (8 mmol/l) use. Infarct size was measured by triphenyltetrazolium chloride (TTC) method. The left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF). The administration of Mg before ischemia had an anti-infarct effect in rat hearts and improved cardiac function. The protective effects of magnesium was abolished by the blocking of KATP channels and suggests that K-ATP channel has an important role in the heart protection effect of Mg as a preconditioning agent., M. Bazargan, M. Faghihi, M. Chitsaz., and Obsahuje bibliografii a bibliografické odkazy
Flavin7 (F7) is a nutritional supplement often taken by cancer patients in Central Europe during chemo- and radiation therapy. In this study, investigation of the antiproliferative and antiangiogenic activities of this supplement were performed. Flavin7 showed antiprolif erative activity in Jurkat as well as in HeLa cells. It significantly reduced the growth of both cancer cell lines at the doses of 200 μg/ml to 20 μg/ml (p<0.001 and p<0.01, respectively). In F7-treated Jurkat cells we found a significant increase in the fraction of cells with sub-G0/G1 DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V staining and DNA fragmentation. Furthermore, F7 at the doses of 100 μg/ml to 4 μg/ml inhibited endothelial cell migration and capillary tube formation what indicates its potential antiangiogenic properties. Flavin7 also inhibited the activity of matrix metalloproteinases (MMPs), preferentially MM P-9, at the doses of 100 μg/ml to 4 μg/ml. Our data suggest that F7 possesses marked antiproliferative and antiangiogenic properties in vitro. Further research is needed to elucidate also its in vivo activities., J. Mojžiš, M. Šarišský, M. Pilátová, V. Voharová, L. Varinská, G. Mojžišová, A. Ostro, P. Urdzík, R. Dankovčik, L. Mirossay., and Obsahuje bibliografii a bibliografické odkazy
Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebro-ventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-L-cysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthine-oxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H2O2 injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection., A. Viggiano, E. Viggiano, M. Monda, A. Viggiano, S. Ascione, S. Amaro, B. de Luca., and Obsahuje bibliografii a bibliografické odkazy
The intracellular levels of antioxidant and free radical scavenging enzymes are gradually altered during the aging process. An age-dependent increase of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The current study examined the effects of L-malate on oxidative stress and antioxidative defenses in the liver and heart of aged rats. Sprague-Dawley male rats were randomly divided into four groups, each group consisting of 6 animals. Group Ia and Group IIa were young and aged control rats. Group Ib and Group IIb were young and aged rats treated with L-malate (210 mg/kg body weight per day). L-malate was orally administrated via intragastric canula for 30 days, then the rats were sacrificed and the liver and heart were removed to determine the oxidant production, lipid peroxidation and antioxidative defenses of young and aged rats. Dietary L-malate reduced the accumulation of reactive oxygen species (ROS) and significantly decreased the level of lipid peroxidation in the liver and heart of the aged rats. Accordingly, L-malate was found to enhance the antioxidative defense system with an increased activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased glutathione (GSH) levels in the liver of aged rats, a phenomenon not observed in the heart of aged rats. Our data indicate that oxidative stress was reversed and the antioxidative defense system was strengthened by dietary supplementation with L-malate., J.-L. Wu, Q.-P. Wu, X.-F. Yang, M.-K. Wei, J.-M. Zhang, Q. Huang, X.-Y. Zhou., and Obsahuje bibliografii a bibliografické odkazy
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (±LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium., P. Kaplán, M. Matejovičová, P. Herijgers, W. Flameng., and Obsahuje bibliografii a bibliografické odkazy
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28±35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C>T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms., L. Zlatohlávek, K, Zídková, M. Vrablík, T. Haas, M. Prusíková, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
The aim of this work is to present the efficacy of a previously introduced computational procedure, developed for evaluation of vascular responsiveness. On this reason, as an example a common study of noradrenaline (NA) effect on a rat renal artery under in vitro conditions was arbitrarily selected. The response of the arterial segment to NA doses (0.1-10 μg) was digitally recorded on a PC and employed to develop mathematical model of NA effect. Using the model, the following NA effect variables were determined: the vessel sensitivity parameter, mean effect time and rate constant, respectively, characterizing the effect intensity, duration, and regression and also classic response variables: the maximal effect and time of the maximal effect. The two-way analysis of variance followed by Bonferroni’s test revealed a significant influence of the increasing NA dose on the vessel sensitivity parameter and mean effect time. These findings indicated nonlinearity of processes underlying NA effect on the rat renal artery over the given range of NA doses. The procedure exemplified has the potential for use as an effective adjunct to routine studies of vascular responsiveness as it enables the extraction of meaningful information which cannot by obtained by common manual evaluation procedures., M. Ďurišová, L. Dedík, V. Kristová, R. Vojtko., and Obsahuje bibliografii a bibliografické odkazy