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
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
The aim of this work was to investigate the effect of 10 weeks of lisinopril treatment to spontaneously hypertensive rats (SHRs) on day/night variations of blood pressure, heart rate and autonomic cardio-regulation parameters. Male SHR with surgically implanted radio-telemetry implant that provided direct measurements of arterial pressure and electrocardiogram wave were used. Animals were allocated to two groups (n=5 each). The first group was treated with lisinopril (20 mg/kg by gavage) daily for 10 weeks (treated group); whereas the second was gavaged daily with tap water (untreated group). Arterial blood pressure, ECG and other telemetry parameters were recorded at the start and at the end of 10-week treatment. Collected data were analyzed using specialized software and were statistically tested. In addition to the expected lowering of blood pressure, spectral analysis of R-R intervals revealed that lisinopril treatment for 10 weeks significantly caused 2-3 fold increase in heart rate variability (HRV) during both active and inactive periods. However, R-R interval durations demonstrated variable distribution patterns during those periods. The cause of observed distribution pattern of R-R intervals during active and inactive periods may be of significance to better understand HRV changes and warrants further investigations., S. Albarwani, S. Al-Siyabi, M. O. Tanira., and Obsahuje seznam literatury
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
Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg⋅kg-1) or high dose (80 mg⋅kg-1) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy., O. Uličná ...[et al.]., and Obsahuje seznam literatury
The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve - AUC or Sommers´ D - Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy-AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models., P. Honzík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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