The aim of the study was to char acterize a) the lipofuscin-like pigment (LFP) accumulation (an indicator of ROS production) in the rat heart during early postnatal period and b) possible antioxidative role of selenium. Experimental animals received Na 2 SeO 3 in drinking water during gravidity and up to day 15 post partum . Two fluorophores of LFP in the hearts of 1-, 4-, 7- and 15-day-old rats were evaluated by fluorescent analysis. The highest level of heart/body weight ratio in control rats was observed on day 4, in the Se-supplemented rats on day 7. Cardiac LFP content in controls increased from postnatal day 4, in the hearts of Se-supplemented rats the LFP content increased already from day 1. As compared with the Se-supplemented group the LFP content of control hearts was significantly higher on day 1 but significantly lower on day 4. LFP concentration in control hearts decreased from postnatal day 1 to 4; this decrease was followed by significant increa se until day 7 and decrease to day 15. LFP concentration in the Se-supplemented hearts was the highest on postnatal day 7; it differed from controls on day 1 and 4. Significant changes of LF P suggest an important role of ROS during critical ontogenetic period., I. Ošťádalová, Z. Charvátová, J. Wilhelm., and Obsahuje bibliografii
Alzheimer’s disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats’ response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD., R. Zakaria, W. M. H. Wan Yaacob, Z. Othman, I. Long, A. H. Ahmad, B. Al-Rahbi., and Obsahuje bibliografii
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
In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hyperchole sterol emic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6 ±13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterol emia (FH): 5 homozygous, 9 hetero zygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using h emorheopheresis. Immunoapheretic interventions decreased LDL-cholesterol (82 ±1 %), ApoB (73 ±13 %) and even Lp(a) by 82 ±19 %, respectively. Selected non-invasive methods are important for long -term and repeated follow -up. Carotid intima-media thickness showed improvement or stagnation in 75 % of the patients. Biomarkers of endothelial dysfunction such as endoglin (in the control group: 3.85 ±1.25 μ g/l, in lipoprotein apheresis-treated hypercholesterol emic individuals 5.74 ±1.47 μ g/l), CD40 ligand (before lipoprotein apheresis: 6498 ±2529 ng/l, after lipoprotein apheresis: 4057 ±2560 ng/l) and neopterin (before lipoprotein apheresis: 5.7 ±1.1 nmol/l, afte r lipoprotein apheresis: 5.5 ±1.3 nmol/l) related to the course of atherosclerosis, but did not reflect the actual activity of the disease nor facilitate the prediction or planning of therapy. Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other microcirculation disorders via significantly decreased activity of thrombomodulin (p<0.0001), tissue factor (p<0.0001), aggregation of thrombocytes (p<0.0001) and plasma and whole blood viscosity (p<0.0001). In conclusion, lipoprotein apheresis and hemorheopheresis substantially lowered LDL-cholesterol in severe hypercholesterolemia. Our experience with long-term therapy also shows good tolerance and a small number of complications (6,26% non-serious clinical compl.), V. Bláha, M. Bláha, M. Lánská, D. Solichová, L. Kujovská Krčmová, E. Havel, P. Vyroubal, Z. Zadák, P. Žák, L. Sobotka., and Obsahuje bibliografii
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
To investigate lisinopril effect on the contribution of nitric oxide (NO) and KCa channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensi ve WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K Ca channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SKCa and IKCa channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SKCa and BKCa proteins. Lisinopril treatment increased expression of eNOS, SKCa , BKCa channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SKCa and IKCa channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SKCa and IKCa channels is reduced, S. Albarwani, S. Al-Siyabi, I. Al-Husseini, A. Al-Ismail, I. Al-Lawati, I. Al-Bahrani, M. O. Tanira., and Obsahuje bibliografii
Distribution of LiCl/pilocarpine status epilepticus-induced neuronal damage was studied in the piriform cortex and in adjoining structures in 12-day-old, 25-day-old and adult rats. No distinct structural and neuronal alterations were detected in the basal telencephalon in 12-day-old rats surviving status epilepticus (SE) for one week or two months. In 25-day-old rats a decrease in Nissl staining was evident. There was also cell loss and gliosis in the caudal 2/3 of the piriform cortex, in the superficial amygdaloid nuclei, in the dorsal and ventral endopiriform nucleus and in the rostrolateral part of the entorhinal cortical area. In adult animals, the topography of neuropathological changes in the basal telencephalon was comparable to those in 25-day-old rats. The damage in the caudal 2/3 or caudal half of the piriform cortex in adult rats with survival times one week or two months was characterized by a marked loss of neurons and striking glial infiltration. The thickness of the piriform cortex and superficial amygdaloid nuclei was significantly reduced. In 25-day-old and in adult animals the sublayer IIb and layer III of the piriform cortex was more affected, while sublayer IIa was less damaged. Parvalbumin (PV) immunocytochemistry revealed a significant decrease in the number of PV-immunoreactive neurons in the rostral piriform cortex and in the dorsal claustrum in animals surviving for two months., R. Druga, H. Kubová, L. Suchomelová, R. Haugvicová., and Obsahuje bibliografii
Uni-quantal endplate currents (EPCs) were recorded extracellularly at the frog neuromuscular synapse and their latency dispersions expressed as P90 were estimated in the presence of acetylcholine. Stimulation-evoked EPCs with long release latencies increased in number when acetylcholine was applied. P90, which is designated as the interval between the minimal synaptic delay and the time at which 90 % of all measured uni-quantal EPCs had occurred, was significantly and reversibly increased by 66% from 0.51 ms to 0.85 ms in the presence of 5x10-4 M acetylcholine. This indicates that the evoked release pattern is less synchronous and the increased asynchrony leads to a substantial drop (by 28%) in the amplitude of reconstructed multi-quantal currents., D. Samigullin, E. A. Bukharaeva, E. Nikolsky, S. Adámek, F. Vyskočil., and Obsahuje bibliografii
NG-nitro-D-arginine-methyl ester (D-NAME) is considered to be an inactive enantiomer of L-NAME and is generally used as the negative control for NO synthase inhibition with L-NAME. With the aim to compare the effects of 4-week L-NAME and D-NAME treatments on hemodynamic and cardiovascular structural parameters, four groups of male Wistar rats were investigated: the controls and groups administered 40 and 20 mg/kg/day of L-NAME and 40 mg/kg/day of D-NAME. At the end of the experiment, myocardial NO synthase activity decreased by 42, 24 and 25 %; aortic NO synthase activity decreased by 35, 15 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The DNA concentrations in the myocardium and the aorta increased significantly after L-NAME and D-NAME treatments. The inhibition of NO synthase was accompanied by a significant elevation in systolic blood pressure in all three groups. The LVW/BW ratio increased by 27, 14 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The aortic wall mass, measured as the crossectional area, increased by 45, 17 and 25 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. Myocardial fibrosis represented 0.94 % in the controls, but 7.96, 4.70 and 5.25 % in L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. It is concluded that D-NAME, although less affective than L-NAME, inhibits NO synthase activity resulting in hemodynamic and structural changes in the cardiovascular system similar to the changes induced by half the dose of L-NAME. Thus, the consideration of D-NAME as an inactive enantiomer and its use as the negative control needs to be reevaluated., P. Babál, O. Pecháňová, I. Bernátová., and Obsahuje bibliografii