We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO-dependent vasorelaxant effects and stimulate cardiac function. In the present study, we aim to investigate the effect of CPC on both nitric oxide (NO) and superoxide anions (O2-) production in cultured human endothelial cells. In addition, its effect on the bradykinin (BK)-induced NO production was also tested. The role and sources of O2- in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O2- signals were measured using electron paramagnetic resonance technique using specific spin trappings. Both, CPC and BK induced an in crease in NO production in human endothelial cells. The combination of both further enhanced NO release. The capacity of CPC plus BK to increase NO signal was blunted by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, and was enhanced in the presence either of superoxide dismutase or catalase. Moreover, CPC plus BK response was greater after inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol but it was not affected by rotenone. CPC did not affect O2- level either alone or after its increase upon lipopolysaccharide treatment. Finally, the capacity of BK alone to increase NO was enhanced either by apocynin or allopurinol. Altogether, these data demonstrate that CPC is able to directly increase NO production without affecting O2- and enhances the BK-induced NO production in human endothelial cells. The data highlight the ability of BK to stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive mechanisms that reduce its efficiency in increasing NO either alone or in the presence of CPC. These results bring pharmacological evidence for vascular protection by CPC via its potentiating effect of BK response in terms of endothelial NO release., A. Sall Diallo, M. Sarr, H. A. Mostefai, N. Carusio, M. Pricci, R. Andriantsitohaina., and Obsahuje bibliografii a bibliografické odkazy
The aim of the present study was to investigate the impact of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult male rats tested in Morris water maze (MWM). Adult male rats prenatally exposed to MA (5 mg/kg), saline or no injection were examined. Half of the animals were injected daily with MA (1 mg/kg) after finishing the testing. Three types of tests were used: (1) “Place navigation test” (Learning), (2) “Probe test” and (3) “Retention memory test” (Memory). Our results showed that prenatal MA exposure did not affect the test of learning and the Probe test. In the test of memory prenatally MA-exposed rats showed smaller search errors and used spatial strategies more than both control groups. Further, MA application in adulthood prolonged trajectories, increased the incidence of random search and decreased the incidence of direct swim in the Place navigation test. In addition, MA administration in adulthood increased the speed of swimming regardless of prenatal exposure. The present study thus demonstrates that 1) Prenatal MA exposure does not affect learning in the MWM, 2) Prenatal MA exposure improves performance in the Retention memory test in the MWM, and 3) MA application in adulthood impairs learning in the Morris water maze., B. Schutová ... [et al.]., and Obsahuje seznam literatury
Spatiotemporal dynamics of event-related potentials (ERP) evoked by non-target stimuli in a visual oddball experiment and the presence of coherent oscillations in beta 2 frequency band of decomposed EEG records from peristimulus period were investigated by means of intracranial electrodes in humans. Twenty-one patients with medically intractable epilepsy participated in the study. The EEG signal was recorded using platinum electrodes implanted in several cortical and subcortical sites. Averaged 2 s EEG records were analyzed. Task-specific EEG changes were found in each patient, ERPs were derived from 92 electrodes used (96 % of possible cases). In the majority of analysed cases, ERPs were composed of several distinct components, and their duration was mostly longer than 1 s. The mean onset of the first ERP component was 158±132 ms after the stimulus (median 112 ms, minimum value 42 ms, maximum value 755 ms), and large variability of these onset times was found in all the investigated structures. Possible coherence between neural activities of remote brain sites was investigated by calculating running correlations between pairs of decomposed EEG records (alpha, beta 1, beta 2 frequency bands were used, total number of correlated pairs was 662 in each frequency band). The record pairs exhibiting highly correlated time segments represented 23 % of all the investigated pairs in alpha band, 7 % in beta 1 band, and 59 % in beta 2 band. In investigated 2 s record windows, such segments were distributed evenly, i.e. they were also found before the stimulus onset. In conclusion, the results have implicated the idea that a lot of recorded ERPs was more or less by-products of chance in spreading a signal within the neuronal network, and that their functional relevance was somewhat linked with the phenomenon of activity synchronization., M. Kukleta ... [et al.]., and Obsahuje seznam literatury
The main pathological condition in patients with impaired wound healing is diabetes mellitus. These patients have significantly low circulating nitric oxide (NO) levels because the stimulatory action of insulin on NO synthesis is absent. Additionally, asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, is increased owing to the generation of oxidative stress. NO was thought to contribute to wound healing. Hyperbaric oxygen (HBO) treatment is generally used in order to accelerate the healing of wounds. The aim of this study was to determine the changes in plasma procollagen type I and III N-terminal peptides (PINP and PIIINP), total nitrite/nitrate (NOx) and ADMA levels; and to evaluate their relation to healing during the HBO treatment of foot ulcers. Data obtained from 18 diabetic patients before and after the HBO therapy were compared statistically by the Wilcoxon test. NOx was increased in 11 and ADMA was decreased in 12 patients following HBO treatment. Both PINP (32.6±29.4 μg/l vs 44.3±33.4 μg/l) and PIIINP (6.97±3.01 μg/l vs 7.92±2.49 μg/l) were significantly increased (p<0.05). Progressive reductions were observed in wound areas, as assessed by the digital wound imaging. In 12 patients, wounds healed by 50 % or higher; whereas only two subjects had minimal improvements (15 % or less healing). The duration of diabetes correlated negatively with wound healing (r = -498, p<0.05). This study suggests that increased collagen synthesis is associated with wound healing during hyperbaric oxygen therapy. Nitric oxide generation may also contribute to the healing process., F. Gurdol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Rat liver myofibroblasts (MFB) were isolated by repeated passaging of nonparenchymal liver cell fraction. They were cultured on polystyrene Petri dishes, on fibrin or on type I collagen gels for 5 days. Quantitative RT-PCR, Western blotting, zymography and immunocytochemistry were used to study differences in cell morphology and protein expression. MFB were large and spread on plastic substrate, with prominent α-smooth muscle (α-SMA) fibres. They turned much smaller and elongated on collagen which was accompanied by the rearrangement of the cytoskeleton and a decrease in α-SMA and β-actin content. Collagen gel induced the expression of a group of metalloproteinases (MMP-2, -3, -9, -13), on mRNA and protein level which resulted in the degradation of the gel. This response was accompanied by changes in the mRNA expression of cytokines of TGF-β family, CTGF and interleukin-6, as well as of osteopontin and thrombospondin-2 that are involved in metalloproteinases (MMPs) regulation. The expression of MMPs substrates, collagen types I, IV and XII did not change or decreased. The effects of fibrin gels on MFB were milder than those of collagen. MFB assumed to deposit collagen and other ECM components in fibrotic liver, besides hepatic stellate cells, also possess a great collagenolytic potential., A. Jiroutová, ... [et al.]., and Obsahuje seznam literatury
Combined administration of drugs elevating extracellular adenosine, namely dipyridamole and adenosine monophosphate, together with granulocyte colony-stimulating factor was shown to enhance granulopoietic recovery in the bone marrow of mice treated with 5-fluorouracil. Enhanced regeneration was found both at the level of hematopoietic progenitor cells for granulocytes and macrophages and in the compartment of morphologically recognizable granulocyte precursors. The results might have positive clinical impact. The adjunct use of drugs elevating extracellular adenosine might reduce the cost expenditure of therapy with granulocyte colony-stimulating factor., M. Hofer, M. Pospíšil, L. Weiterová, V. Znojil, J. Vácha, J. Holá, A. Vacek, I. Pipalová., and Obsahuje bibliografii
The aim of the present study was to test the hypothesis that chronic hypoxia would aggrav ate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased ac tivity of endogenous renin- angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks' hypoxi a. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks' exposure to chroni c hypoxia did not alter SBP and MAP. Surprisingly, in TGR it de creased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposu re to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR., L. Červenka, J. Bíbová, Z. Husková, Z. Vańourková, H. J. Kramer, J. Herget, Š. Jíchová, J. Sadowski, V. Hampl., and Obsahuje bibliografii
Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349±148 vs. 506±206 s-1, p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= –0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects., J. Malík ... [et al.]., and Obsahuje seznam literatury
Gum acacia (GA) is used in pharmaceutical, cosmetic and food industries as an emulsifier and stabilizer, and in some countries in the traditional treatment of patients with chronic kidney disease (CKD). We have previously found that GA ameliorates adenine -induced chronic renal failure (CRF) in rats. Different brands of GA are commercially available, but their comparative efficacy against adenine-induced CKD is unknown. Here, we explored the effects of three different brands of GA (Sudanese GA, SupergumTM and GA from BDH) on some physiological, biochemical, and histological effects of adenine-induced CRF in rats. Adenine (0.75 %, w/w in feed, four weeks) reduced body weight, and increased urine output. It also induced significant increases in blood pressure, and in creatinine, urea, several inflammatory cytokines in plasma, and indices of oxidative stress, and caused histological damage in kidneys. Treatment of rats concomitantly with any of the three GA brands, significantly, and to a broadly similar extent, mitigated all the signs of CRF. The results suggested equivalent efficacy of these brands in antagonizing the CRF in this animal model. However, to enable standardization of different brands between laboratories, the use of the chemically well-characterized GA preparation (such as SupergumTM) is recommended., B. H. Ali, ... [et al.]., and Obsahuje seznam literatury