The aim of this study was to determine the effect and mechanism of low concentration of lidocaine on subthreshold membrane potential oscillations (SMPO) and burst discharges in chronically compressed dorsal root ganglion (DRG) neurons. DRG neurons were isolated by enzymatic dissociation method. SMPO, burst discharges and single spike were elicited by whole cell patch-clamp technique in current clamp mode. Persistent Na+ current (INaP) and transient Na+ current (INaT) were elicited in voltage clamp mode. The results showed that SMPO was suppressed and burst discharges were eliminated by tetrodotoxin (TTX, 0.2 μ mol/l) in current clamp mode, INaP was blocked by 0.2 μ mol/l TTX in voltage clamp mode. SMPO, burst discharges and INaP were also suppressed by low concentration of lidocaine (10 μ mol/l) respectively. However, single spike and INaT could only be blocked by high concentration of lidocaine (5 mmol/l). From these results, it is suggested that INaP mediates the generation of SMPO in injured DRG neurons. Low concentration of lidocaine (10 μ mol/l) suppresses SMPO by selectively inhibiting INaP, but not INaT, in chronically compressed DRG neurons., H. Dong, Y.-H. Fan, Y.-Y. Wang, W.-T. Wang, S.J. Hu., 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
Obesity is linked to a wide range of serious illnesses. In addition to the important impact on the health of the individual, obesity also has a substantial impact on the economy. Disruption of physiological day-night cycles could contribute to the increased incidence of obesity. According to the American National Sleep Federation, the percentage of the people who reported a sleep duration of six hours or less increased from 12 to 37 % over ten years. Insufficient sleep leads not only to an increase of the total calorie intake but changes the meal preference in favor of palatable foods and meals with high carbohydrate content. A decrease of leptin and increase of ghrelin levels caused by sleep deficiency can also play a role. In addition to the higher caloric intake, the timing of food consumption should be taken into account. The same meal eaten during the night versus the day is associated with increased postprandial glucose and triglyceride levels. The gut microbiome has also been recently understood as an endocrine system, with links between the gut microbiome and circadian rhythm changes possibly influencing increased obesity., B. Rácz, M. Dušková, L. Stárka, V. Hainer, M. Kunešová., and Obsahuje bibliografii
Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK)., M. Cahová, D. Habart, T. Olejár, Z. Berková, Z. Papáčková, H. Daňková, A. Lodererova, M. Heczková, F. Saudek., and Obsahuje bibliografii
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
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