Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to noxious stimuli. Here we examined the electrophysiological and behavioral effects of these two agents for evidence of their interactions. Individual small-medium cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100 ng/ml, n=4), with increased numbers of action potentials and decreased slow K+ currents; pre-exposure to ET-1 potentiated NGF´s actions, but not vice versa. Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20 pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity, but their simultaneous injections sensitized the paw to both modalities. Daily i.pl. injections of low ET-1 doses in male rats caused tactile sensitization after 21 days, and enabled further tactile and thermal sensitization from low dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng NGF, without changing the paw’s tactile sensitivity by itself, acutely sensitized the ipsilateral paw to subsequent injections of low ET-1. The sensitization from repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were both significantly greater in female than in male rats. These findings reveal a synergistic interaction between cutaneously administered low doses of NGF and ET-1, which could contribute to cancer-related pain., A. Khodorova, Y. Zhang, G. Nicol, G. Strichartz., and Seznam literatury
Membrane fluidity is a widely recognized biophysical variable that provides information about structural organization of the subcellular membranes exhibiting physical characteristics of liquid crystals. The term “fluidity” reflects in this case the tightness in packing of acyl parts of the membrane phospholipid molecules, a feature that may influence considerably the molecular mobility and via that also the sensitivity and reactivity of membranebound transporters, receptors and enzyme systems. Data presented in this review are aimed to demonstrate the substantial role of changes in membrane fluidity occurring in the processes associated with endogenous protection observed in cardiac sarcolemma and mitochondria in diverse pathologies, particularly in diabetes and hypertension., A. Ziegelhöffer, ... [et al.]., and Obsahuje seznam literatury
The goal of the study was to determine whether postconditioning protects against different ischemia durations in the rabbit. Rabbits were assigned to a 20-, 25-, 45- or 60-min coronary occlusion followed by 24-h of reperfusion. Rabbits received no further intervention (control) or were postconditioned with four cycles of 30-s occlusion and 30-s reperfusion after myocardial infarction. Plasma levels of troponin I were quantified throughout reperfusion. In control conditions, infarct sizes (% area at risk using triphenyltetrazolium chloride) after 20, 25, 45 and 60 min of coronary occlusions were 23±3, 51±4, 70±3 and 81±3 %, respectively. With 20 and 25 min occlusion, postconditioning reduced infarct size by 43±10 and 73±21 %, respectively. On the other hand, with 45 or 60 min occlusion, postconditioning had no significant effects on infarct size (61±3 and 80±2 % of area at risk). Preconditioning protocol was performed with 25- and 60-min coronary occlusion. As expected, preconditioning significantly reduced infarct size. In conclusion, in the rabbit, the cardioprotection afforded by postconditioning is limited to less than 45 min coronary occlusion., R. Létienne, Y. Calmettes, B. Le Grand., and Obsahuje seznam literatury
Different mental operations were expected in the late phase of intracerebral ERPs obtained in the visual oddball task with mental counting. Therefore we searched for late divergences of target and nontarget ERPs followed by components exceeding the temporal window of the P300 wave. Electrical activity from 152 brain regions of 14 epileptic patients was recorded by means of depth electrodes. Average target and nontarget records from 1800 ms long EEG periods free of epileptic activity were compared. Late divergence preceded by almost identical course of the target and nontarget ERPs was found in 16 brain regions of 6 patients. The mean latency of the divergence point was 570±93 ms after the stimulus onset. The target post-divergence section of the ERP differed from the nontarget one by opposite polarity, different latency of the components, or even different number of the components. Generators of post-divergence ERP components were found in the parahippocampal gyrus, superior, middle and inferior temporal gyri, amygdala, and fronto-orbital cortex. Finding of late divergence indicates that functional differences exist even not sooner than during the final phase of the task., A. Damborská ... [et al.]., and Obsahuje seznam literatury
Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis., T. Štulc, M. Vrablík, Z. Kasalová, I. Marinov, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
Previous studies have reported a decreased incidence of delayed graft function after cadaveric transplantation with the use of lidocaine pretreatment of the donor. We evaluated the effects of lidocaine on prolonged cold ischemia and reperfusion injury in a canine model of isolated kidney perfusion (IPK). The purpose of this study was to evaluate the renal function of isolated perfused canine kidneys after 48 h of cold storage with Euro-Collins (EC) solution or EC solution plus lidocaine. Isolated perfused canine kidneys were randomized into four groups which contained six kidneys: I) cold flush with EC solution and immediately reperfused, II) cold flush with EC solution plus lidocaine and immediately reperfused, III) 48 h of cold storage with EC and reperfusion, IV) 48 h of cold storage with EC solution plus lidocaine and reperfusion. The measured renal functions were glomerular filtration rate, urine production, perfusate flow, urinary lactic dehydrogenase (ULDH), Na reabsorptive capacity, and tissue MDA levels. Histological examination was performed after reperfusion. The tubular functions of kidneys preserved with EC solution containing lidocaine were better when compared with the kidneys preserved with EC alone. Tubular injury marker levels (ULDH) in group IV were significantly lower than in group III and lidocaine also reduced lipid peroxidation during reperfusion. This is in agreement with the histological results. The results of the present study can be taken as evidence of the cytoprotective effect of lidocaine, which may therefore be accepted as a useful agent for kidney preservation., N. Erkasap, E. Ates, S. Erkasap, Z. Kaygisiz., and Obsahuje bibliografii
During the early postnatal age environmental signals underlie the development of sensory systems. The visual system is considered as an appropriate system to evaluate role of sensory experience in postnatal development of sensory systems. This study was made to assess the effect of visual deprivation on strategy of arm selection in navigation of radial arm maze. Six-week-old light- (LR, control) and dark-reared (DR) rats were trained for correct choices and adjacent arms tasks. Our results showed that both the LR and DR animals equally selected correct arms. In the adjacent arms task, however, the control group significantly outperformed the DR animals. While the LR males and females displayed some differences in performing the tasks, no sex dependency was found in the performance of the DR group. These findings indicate that the lack of visual experience is likely to influence the strategy selection as well as sex differences. Thus the difference in the performance of LR and DR animals seems to be due to the male rather than female behavior., M. Salami., and Obsahuje bibliografii a bibliografické odkazy
Over activation of the endothelin-1 (ET-1) system in disease states contributes to endothelial dysfunction. On the other hand, ET-1 promotes proliferation and survival of endothelial cells. Regulation of programmed cell death (PCD) pathways is critical for cell survival. Recently discovered necroptosis (regulated necrosis) is a pathological PCD mechanism mediated by the activation of toll like receptor 4 (TLR4), which also happens to stimulate ET-1 production in dendritic cells. To establish the effect of ET-1 on PCD and survival of human brain microvascular endothelial cells (BMVECs) under control and inflammatory conditions, BMVECs were treated with ET-1 (10 nM, 100 nM and 1 μM) or lipopolysaccharide (LPS, 100 ng/ml). ET receptors were blocked with bosentan (10 μM). Under normal growth conditions, exogenous ET-1 reduced BMVEC viability and migration at a relatively high concentration (1 μM). This was accompanied with activation of necroptosis and apoptosis marker genes. LPS decreased endogenous ET-1 secretion, increased ETB receptor expression and activated necroptosis. Even though ET-1 levels were low (less than 10 nM levels used under normal growth conditions), blocking of ET receptors with bosentan inhibited the necroptosis pathway and improved the cell migration ability of BMVECs, suggesting that under inflammatory conditions, ET-1 activates PCD pathways in BMVECs even at physiological levels., Y. Abdul, R. Ward, G. Dong, A. Ergul., and Seznam literatury