The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome., F. Schinzari, M. Tesauro, C. Cardillo., and Seznam literatury
MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease., D.-F. Li ... [et al.]., and Obsahuje seznam literatury
The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats. Rat pups were exposed together with their mother in to an intermittent hypobaric hypoxia (simulated altitude of 7 000 m) since the day of birth till the 11th day (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was administered daily immediately before each hypoxia exposition. The duration of evoked afterdischarges (ADs) and the shape of evoked graphoelements were evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were prolonged in 35-day-old rats only after the first stimulation. Allopurinol shorted the duration of ADs only in 12-day-old pups. In older experimental group the effect of allopurinol treatment was less pronounced., K. Jandová, ... [et al.]., and Obsahuje seznam literatury
We studied the effects of administration of b-resorcylidene aminoguanidine (RAG) to Wistar strain rats with experimental diabetes mellitus (DM) induced by streptozotocin. The effects studied included antioxidant levels in plasma and the liver, oxidative damage of lipids represented by the formation of substances reacting with thiobarbituric acid (TBARP) and selected biochemical indicators. The administration of RAG did not significantly affect antioxidant status of diabetic rats or hemoglobin glycation and plasma concentration of fructosamine. In diabetic rats, application of RAG decreased formation of TBARP in plasma but not in the liver. Moderate steatosis of liver and increased plasma levels of triacylglycerols in diabetic rats were significantly improved by application of RAG., A. Liptáková, J. Čársky, O. Uličná, O. Vančová, P. Božek, Z. Ďuračková., and Obsahuje bibliografii
An ethanol vapor concentration of 1.6 mmol/l was used to test the diurnal variations of the olfactory response in two groups of snails, which were adapted to different light-dark cycles. The results revealed that the olfactory sensitivity to stimulation with ethanol was significantly increased during the day-time, which corresponds to the scotophase of the light-dark cycle, to which the animals had been adapted (c2-test, P < 0.01)., M. Voss, C. Büchert, C. Missfelder., and Obsahuje bibliografii
We reported previously that the nitric oxide synthesis inhibitor Nv-nitro-L-arginine methyl ester (L-NAME) decreases cardiac output. Several studies have shown that inhibition of nitric oxide synthesis decreases the heart rate. In the present study, we investigated the effect of a single bolus administration of L-NAME on blood pressure and heart rate monitored for one hour in anesthetized rats and the influence of vagotomy and b1-receptor blocker metoprolol on the L-NAME induced bradycardia. After L-NAME treatment, the blood pressure rose immediately after the injection of the drug (peak response in the third minute: +24 %, p<0.001) and fell to the control level in the 20th minute. The heart rate decreased immediately after L-NAME administration, the lowest value being reached in the 10th minute (-14 %, p<0.001). However, bradycardia was sustained even after the blood pressure had returned to the control level. Bilateral vagotomy failed to influence the negative chronotropic effect of L-NAME, but bradycardia was completely abolished by metoprolol pretreatment. We concluded that the bradycardia evoked by L-NAME is mainly due to the withdrawal of sympathetic tone upon the heart rate. However, the cause of sustained bradycardia after normalization of blood pressure cannot be elucidated., J. Vág, C. Hably, J. Bartha., and Obsahuje bibliografii
The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. The dopamine system participates in the reward effects of opiate use and the aversive effect of opiate abstinence. The amygdala is an essential neural substrate for associative learning of emotion. To establish a model of conditioned place aversion (CPA) in morphine-treated rats, we used different visual and tactual cues as conditioned stimuli (CS) within a conditioning apparatus. An injection of naloxone served as the unconditioned stimulus (US). The 6-hydroxydopamine (6-OHDA) lesion technique was used to investigate the effects of the dopaminergic system of the central nucleus of the amygdala (CeA) on naloxone-induced CPA. Rats were rendered physically dependent via administration of increasing doses of morphine delivered via intraperitoneal injection. Doses increased by 20 % each day for 14 days, starting from an initial dose of 6 mg/kg. All rats also received a low dose of naloxone (0.1 mg/kg) by injection 4 hours after morphine treatment on days 11 and 13 to induce CPA in a biased twocompartment conditioned place apparatus. Morphine-dependent rats with sham lesions were found to develop significant CPA after naloxone treatment. Bilateral 6-OHDA lesions of the CeA impaired the acquisition of CPA but had no effect on locomotor activity. These results suggest that the dopaminergic system of the CeA plays an important role in the negative affective state of opiate abstinence., W. Xu ... [et al.]., and Obsahuje seznam literatury
Uridine is postulated to participate in the development of insulin resistance. Since exercise is an effective tool in the treatment of insulin resistance it appeared justified to assess the impact of maximal exercise on plasma uridine and insulin sensitivity indices (e.g. insulin and HOMA-IR) in healthy subjects. The study included forty-four healthy males (18.5±2.92 years, VO2 max 50.2±6.26 ml kg-1 min-1). Subjects performed a single maximal exercise on a bicycle ergometer. Blood samples were taken three times: immediately before exercise, immediately after exercise and at the 30th min of rest. Uridine concentrations were determined in the whole blood using high-performance liquid chromatography. Serum insulin levels were measured by a specific ELISA method. Insulin sensitivity was assessed by homeostasis model assessment method (HOMA-IR). A maximal exercise-induced increase in the concentration of uridine correlated with post-exercise increases in insulin levels and HOMA-IR. Our results indicate a relationship between the concentration of uridine in the blood and indicators of insulin sensitivity in healthy subjects. We are the first to demonstrate that a maximal exercise-induced increase in the concentration of uridine is correlated with post-exercise increases in insulin levels and HOMA-IR in healthy subjects. It appears that uridine may be an indicator of insulin resistance., W. Dudzinska, ... [et al.]., and Obsahuje seznam literatury
Aim of the study was to evaluate serum levels of insulin-like growth factor binding protein-3 in patients with liver cirrhosis and to compare serum IGFBP-3 levels with other liver function tests. Fifty-one patients with liver cirrhosis were selected for our study. We measured IGFBP-3 (1.67±1.06 mg/l, mean ± SD), albumin (32±8 g/l), prealbumin (0.22±0.14 g/l), AST (2.29±2.38 mkat/l), ALT (2.11±4.83 mkat/l) and cholinesterase (mean 78.6±45.2 mkat/l) in the serum. There was a significant positive correlation of serum IGFBP-3 with serum albumin and serum cholinesterase. The correlation coefficient was much lower between serum IGFBP-3 and serum prealbumin. There was no significant correlation between serum AST, ALT and IGFBP-3. Serum IGFBP-3 proves to be a better marker for the hepatic synthetic capacity than serum albumin or cholinesterase., K. Šídlová, M. Pechová, K. Kotaška, R. Průša., and Obsahuje bibliografii
Catalase is an antioxidant enzyme the activity of which is crucial for the protection against damage caused by reactive oxygen species. The –262C>T polymorphism in the promoter region of catalase gene was found to be associated with altered catalase levels. In this study, peripheral blood mononuclear cells catalase activity was measured after H2 O2-induced oxidative stress. C/T and T/T genotypes were associated with the decrease of catalase levels in contrast to C/C donors who had elevated catalase activity in the presence of 0.4 and 0.7 mM H2 O2. Genotypedependent response of catalase activity to oxidative stress might be related to the predisposition of catalase mutant allele carriers to disorders mediated by oxidative stress., A. V. Komina, ... [et al.]., and Obsahuje seznam literatury