The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH., J. Honda, T. Kimura, S. Sakai, H. Maruyama, K. Tajiri, N. Murakoshi, S. Homma, T. Miyauchi, K. Aonuma., and Seznam literatury
It is well known that the training level of a muscle belongs to the parameters that affect the H-reflex response amplitude. The aim of this study was to investigate the effects of training type on H- and T-reflex response parameters. For this purpose, 20 long-distance athletes (group I, test group), 18 short-distance athletes (group II, test group) and 20 non-trained subjects (group III, control group) were involved in this study in which the H- and T-reflex amplitude and latency values were measured. The H-reflex amplitude and latency values found in groups I, II and III were 3.64±0.28 mV and 26.88±1.45 ms, 3.17±0.26 mV and 26.19±1.89 ms, and 6.07±0.34 mV and 26.77±1.32 ms, respectively. The T-reflex amplitude and latency values of the groups I, II and III were 3.30±0.18 mV and 32.01±1.02 ms, 3.11±0.20 mV and 31.47±1.16 ms, 4.24±0.21 mV and 31.47±1.16 ms, respectively. There was no statistically significant difference between the groups with respect to latencies of H- and T-reflexes (p>0.05). In both test groups, the amplitudes of the H-reflex and T-reflex were significantly smaller than the control group (p<0.05). The results of this study suggest that training of muscles affect the H- and T-reflex response parameters., R. Ozmerdivenli, S. Bulut, T. Urat, A. Ayar., and Obsahuje bibliografii
We investigated the actions of dantrolene Ca2+-induced on Ca2+-release (CICR) evoked by action potentials in cultured rat sensory neurons. The effect of dantrolene on action potential after-depolarization and voltage-activated calcium currents was studied in cultured neonatal rat dorsal root ganglion cells (DRG) using the whole-cell patch-clamp technique. Depolarizing current injection evoked action potentials and depolarizing after-potentials, which are activated as a result of CICR following a single action potential in some cells. The type of after-potentials was determined by inducing action potentials from the resting membrane potential. Extracellular application of dantrolene (10 mM) abolished after-depolarizations without affecting action potential properties. Furthermore, dantrolene significantly reduced repetitive action potentials after depolarizing current injection into these neurons, but had no significant effect on the steady-state current voltage relationship of calcium currents in these neurons. We conclude that dantrolene inhibits the induction of action potential after depolarizations by inhibiting CICR in cultured rat sensory neurons., A. Ayar, H. Kelestimur., and Obsahuje bibliografii
a1_In a series of studies in the late 1950s and early 1960s, Jan Bures introduced cortical spreading depression to the field of behavioral neuroscience (eg. Bures 1960). This technique offered a unique way to study the role of cortex in learning and memory, and attracted the attention of many who began their graduate studies at that time, including one of us (LN, cf. Nadel 1966). An NIH postdoctoral fellowship to study with the master himself brought LN to Prague in September 1967. Thus began a relationship that included science, politics, and personal life, and has lasted over 30 years1,2. The first scientific exchange began with Jan pulling a piece of paper from his desk with a long list of possible experiments written on it -- “pick one”, he said. This led to a series of studies on interhemispheric transfer of learning under conditions of monocular input, demonstrating, amongst other things, that such transfer is not a uniform process. Depending on the kind of trials given with both hemispheres intact, and the eye which remained open to input, transfer can either be non-specific, likely involving some kind of procedural knowledge, or highly specific, likely involving knowledge about the trained discrimination itself (Nadel and Buresova, 1970). These studies anticipated LN’s future work on multiple memory systems, a research enterprise pursued in the following decades by many labs (including LN’s: e.g. Nadel and O’Keefe 1974, O’Keefe et al. 1975). In this paper we focus on several scientific issues that Jan has been thinking about for the past 25 years. In particular, we consider spatial learning, the hippocampus, and memory. To this mix we add stress, something well known to anyone living in Prague in 1968., a2_LN left Prague after the 1968 invasion and stayed in London for seven months, during which time arrangements were made for an eventual return to the Medical Research Council Cerebral Functions Research Group in 1970. Thus it was that LN happened to be down the hall when John O’Keefe and Jonathan Dostrovsky discovered place cells (O’Keefe and Dostrovsky 1971) and began the program of research leading to the cognitive map theory of hippocampal function (O’Keefe and Nadel 1978)., L. Nadel, J.D. Payne., and Obsahuje bibliografii
The system of IGF-I and its binding proteins may be involved in the pathogenesis of vascular damage in Type 1 diabetes. The aim of this study was to analyze the relationship between this system and the microvascular reactivity in Type 1 diabetes as measured by laser-Doppler flowmetry. Twenty-two Type 1 diabetic patients (13 women and 9 men) with microangiopathy and fifteen healthy subjects (8 women and 7 men) were examined clinically, underwent laser-Doppler flowmetry and intima-media thickness measurements. Fasting serum levels of IGF-I, free IGF-I, IGFBPs and lipids were examined. The microvascular reactivity was impaired in Type 1 diabetic patients. Maximal perfusion during post-occlusive reactive hyperemia (PORHmax) and during thermal hyperemia (THmax) was significantly decreased in Type 1 diabetes (p<0.01). Percentage perfusion increase in both tests (PORH and TH) was lower in Type 1 diabetes mellitus (p<0.01) and the reaction after heating was slower in diabetic patients (THmax/t) (p<0.01). We did not find any significant dependence of microvascular reactivity on the parameters of IGF-I or its binding proteins. We conclude that the microvascular reactivity is impaired in Type 1 diabetes mellitus, but this impairment is not clearly dependent on the activity of the IGF-I system. It is probably only a complementary pathogenic factor., M. Kršek, M. Prázný, J. Škrha, V. Justová, Z. Lacinová, T. Haas., and Obsahuje bibliografii
Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions., A. Veselá, J. Wilhelm., and Obsahuje bibliografii
Autophagy is implicated in the maintenance of cardiac homeostasis. Autophagy is activated in heart failure, in which reactive oxygen species (ROS) are increased. Exogenous ROS have been shown to induce cardiomyocyte autophagy alterations. However, little is known about the influences of physiological levels of endogenous ROS on cardiomyocyte autophagy. In the present study, we tested the hypothesis that endogenous ROS in cardiomyocytes play an important role in inducing autophagy. Cultured H9C2 cardiomyocytes or Sprague-Dawley rats were treated with the antioxidant N-acetyl-cysteine (NAC) or the superoxide dismutase mimic tempol under the basal or nutrient deprivation conditions. The autophagic flux was assessed by the lysosomal inhibitor chloroquine. In H9C2 cardiomyocytes, under a basal condition, NAC or tempol increased the ratio of LC3 II/I proteins and reduced LC3 II autophagic flux. Under nutrient deprivation, NAC increased the LC3 II/I ratio and reduced LC3 II autophagic flux. In vivo studies in rats, NAC treatment increased the LC3 II/I ratio and p-Akt protein expression in myocardium. We concluded that the antioxidants reduced autophagic flux in cardiomyocytes under the basal or nutrient deprivation conditions, suggesting that endogenous ROS promote autophagy flux under physiological conditions, and this effect is mediated, at least in part, through Akt inhibition., J.-P. Wang, R.-F. Chi, J. Liu, Y.-Z. Deng, X.-B. Han, F.-Z. Qin, B. Li., and Seznam literatury
In the following paper, authors describe glycans present on cell membranes as they affect the folding, the spatial arrangement, the behavior and the interaction with the substrate of some membrane proteins. Authors describe the synthesis and assembly of a glycan on a protein, the formation of N-glycans, the maturation of an N-glycan in different cellular compartments, the structure of the glycocalyx and how it interacts with any pathogens. The study of the E-cadherin and the potassium channel to demonstrate how glycans affect the spatial arrangement, the stability and activity of the glycoproteins on the membranes. Subsequently, authors analyze the correlation between disorder glycosylation and human health. Authors define glycosylation disorders as a genetic defect that alter the structure or biosynthesis of glycans (sugar chains) in one or more biosynthetic pathways. Human glycosylation disorders reflect the disruption of early steps in the pathways of glycan biosynthesis. More in details, authors analyze the role of glycoprotein in tumor cell adhesion, in particular, in cells MCF-7 and MDA-MB-231 on zeolite scaffold. In the same time, the role of metalloproteinase is described in the mobilization of cancer cells and in metastasis., P. Sprovieri, G. Martino., and Seznam literatury
In order to obtain basic information on the transport properties of differentiating embryonic nephrons, we examined the 7-day-old chick mesonephros by measuring the transtubular epithelial potential difference (TPD) and by histochemical detection of Na,K-ATPase activity. TPD as an indicator of the electrogenic transport was measured in individual segments of superficial nephrons in vivo. Their electric polarity was always lumen-negative. TPD was reduced by addition of 10 mM KCN applied to the mesonephric nephrons from the outside. In the proximal tubules, TPD was significantly lower (mean±SD: -1.0±0.5 mV) than in the distal and collecting tubules (-2.2±1.0 mV, pŁ0.05). Activity of the sodium pump was evaluated histochemically by detection of ouabain-sensitive potassium-dependent p-nitrophenyl phosphatase in cryostat sections of the mesonephros. The enzyme activity was demonstrated only in distal tubules and in the collecting ducts, but not in the proximal tubules. These findings have revealed significant differences between embryonic nephron segments: the distal tubule, in contrast to the proximal one, is supplied by the sodium pump and is able to generate higher TPD. Therefore, we consider that it is only the distal nephron, which possesses the ability of active transport., Z. Zemanová, E. Ujec., and Obsahuje bibliografii
Mild hyperhomocysteinemia has been established as a new independent risk factor for atherosclerosis and thrombosis. The metabolic syndrome of insulin resistance is associated with a high risk of coronary heart disease. Our objective was to determine if any relationship exists between the metabolic syndrome of insulin resistance in non-diabetic subjects and total serum homocysteine levels. Sixty-six healthy volunteers (33 males and 33 females) were selected from the population of Pilsen. Insulin resistance was measured by the Insulin Suppression Test using Octreotide. Steady-state plasma glucose concentrations at the end of the test period provided a quantitative measure of insulin resistance. Serum homocysteine level was estimated by high-pressure liquid chromatography. Serum folate and vitamin B12 were estimated using commercial kits on an Abbott IMx analyzer. All other laboratory tests were performed by standard methods in a routine biochemical laboratory. Subjects with the highest tertile of steady-state plasma glucose showed a significantly higher body mass index, blood pressure, fasting plasma triglyceride levels, plasminogen activator inhibitor-1 and lower HDL-cholesterol, i.e. an insulin resistance pattern. These subjects had significantly lower serum homocysteine levels compared with non-insulin resistant subjects. The negative association of insulin resistance and serum homocysteine was unexpected. The contribution of plasma folate levels to serum homocysteine levels and serum creatinine was significantly negative and positive, respectively., H. Rosolová, J. Šimon, O. Mayer Jr., J. Racek, T. Dierzé, D. W. Jacobsen., and Obsahuje bibliografii