Several neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease, or vascular dementia and cognitive impairment, are associated with mild hyperhomocysteinemia. Hyperhomocysteinemia is defined as an increas e of the homocysteine (Hcy) level beyond 10 μM. Although the adverse effect of Hcy on neurons is well documented, knowledge about the impact of this amino acid on glial cells is missing. Therefore, with the aim to evaluate the neurotoxic properties of Hcy on glial cells, we used a glioblastoma cell line as a study model. The viability of cells was assayed biochemically and cytologically. At a concentration around 50 μM in the culture medium D,L -Hcy induced cell death. It is noteworthy that Hcy induces cell death of human glial cells at concentrations encountered during mild hyperhomocysteinemia. Therefore, we propose that Hcy -induced impairment of neuronal functions along with damage of glial cells may contribute to the etiopathogenesis of neurodegenerative diseases associated with hyperhomocysteinemia., H. Škovierová, S. Mahmood, E. Blahovcová, J. Hatok, J. Lehotský, R. Murín., and Obsahuje bibliografii
Experimental hypothermia caused extensive changes in the number of both classes of insulin receptors in different rat tissues. In the liver, the number of high affinity insulin receptors (HAIRs) decreased by 50 % (from 25.3 to 12.6 fmol/mg membrane protein), whereas number of low affinity insulin receptors (LAIRs) was almost unchanged in comparison to normothermic animals (5.63 and 4.39 pmol/mg, respectively). In the adipose tissue, number of both classes was reduced - HAIRs by 81 % (from 24.0 to 4.50 fmol/mg) and LAIRs by 92 % (from 16.0 to 1.29 pmol/mg). In the skeletal muscle, capacity of HAIRs was not changed (16.2 and 19.3 fmol/mg in normo- and hypothermic animals, respectively), whereas number of LAIRs increased by 150 % (from 6.65 to 16.6 pmol/mg). Hypothermic rats also showed lower amount (by 85 %) of LAIRs in the heart muscle (9.37 and 1.43 pmol/mg in control and experimental animals, respectively). Simultaneously, no significant changes were found in HAIRs (16.3 and 11.9 fmol/mg, respectively) and LAIRs (4.43 and 3.88 pmol/mg, respectively) in the brain. These differences in insulin receptors responses to hypothermia may reflect different physiological role of insulin in the regulation of target cell metabolism and/or the differences in tissue distribution of the insulin receptor isoforms., T. Torlinska, M. Perz, E. Madry, T. Hryniewiecki, K. W. Nowak, P. Mackowiak., and Obsahuje bibliografii
Potential changes in the activity of endocrine axes related to growth as a result of leptin administration during embryonic development of birds were evaluated in the Japanese quail as a model bird with fast growth and development. On day 5 of incubation, 0.1 µg or 1 µg of recombinant mice leptin in 50 µl of phosphate buffered saline were injected into the albumen of eggs. Animals from each group were killed by decapitation on day 0, 2, 5, 7, 14, 21, 28, 35, 42, 49 and 56 of life. Plasma concentrations of triiodothyronine (T3), thyroxin (T4), corticosterone, testosterone, total lipids, triacylglycerols, cholesterol, glucose and alkaline phosphatase activity were measured. Quail treated by leptin hatched earlier (5-24 hours) and had a higher body weight than the control group (P<0.05-0.001). Mean body weight across the whole observed period was higher in both treated groups as compared to the control group (P<0.05). Leptin in ovo administration was accompanied by changes of endocrine and metabolic parameters during postembryonic development. The most prominent changes appeared immediately after hatching (T3, T4, total lipids, triacylglycerols) and before sexual maturity. It is suggested that leptin acts as a general signal of low energy status to neuroendocrine systems in birds which improves utilization of nutrients., D. Lamošová, M. Máčajová, M. Zeman, Š. Mózeš, D. Ježová., and Obsahuje bibliografii
Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10-5mol.l-1) significantly increased the responses to single doses (0.1, 1, 10 m g) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone., V. Kristová, M. Kriška, R. Vojtko, A. Kurtanský., and Obsahuje bibliografii
Hypoxia has been identified as an important stimulus for gene expression during embryogenesis and in various pathological situations. Its influence under physiological conditions, however, has only been studied occasionally. We therefore investigated the effect of intermittent high altitude hypoxia on the mRNA expression of different cytokines and protooncogenes, but also of other genes described to be regulated by hypoxia, in the left ventricle (LV), the right ventricle (RV), atria and the lung of adult rats after simulation of hypoxia in a barochamber (5000 m, 4 hours to 10 days). Heme oxygenase-1 as well as transforming growth factor-β1 showed an increased expression in all regions of the heart and the lung at different periods of hypoxia. For lactate dehydrogenase-A, we found a significant up-regulation in the RV and the lung, for lactate dehydrogenase-B up-regulation in the RV, but down-regulation in the LV and the atria. Vascular endothelial growth factor was up-regulated in the RV, the LV and the lung, but down-regulated in the atria. Its receptor Flk-1 mRNA was significantly increased in the atria and RV only. Expression of c-fos was found in the LV and RV only after 4 hours of hypoxia. The level of c-jun was significantly increased in the LV but decreased in the atria. Our data clearly demonstrate that intermittent hypoxia is a modulator of gene expression under physiological conditions. It differently regulates the expression of distinct genes not only in individual organs but even within one organ, i.e. in the heart., E. Deindl, F. Kolář, E. Neubauer, S Vogel, W. Schaper, B. Ošťádal., and Obsahuje bibliografii
In the present study we used the primary cultures of chick embryonic muscle and liver cells as a model for potential mutual combination effects of leptin and insulin, respectively. The influence of both hormones on the proliferation and protein synthesis was dose-dependent and related to the age of embryos from which the cells were isolated. Leptin (10 and 100 ng/well) increased the proliferation (estimated by DNA content and incorporation of labeled thymidine into DNA) and protein synthesis (determined by incorporation of labeled leucine into proteins) of muscle cells. The effect of leptin and insulin in muscle cells was similar. In younger embryo (11-day-old) the lower dose of leptin was more effective than the higher one compared to the insulin effect. Mutual effects of leptin and insulin were neither additive nor synergistic and were equivalent to the effects of individual hormones. In hepatocytes the influence of leptin was dependent on the age at which the cells were isolated (11- and 19-day-old embryos). The presence of insulin neither potentiated nor inhibited the effect of leptin., D. Lamošová, M. Zeman., and Obsahuje bibliografii
The effects of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE/MLV, radioprotective immunomodulator; 10 mg/kg) and indomethacin (INDO, inhibitor of prostaglandin production; 2 mg/kg) on post-irradiation recovery of hematopoietic functions in mice were investigated. Two agents with distinct radioprotective mechanisms were administered alone or in combination 24 h and 3 h before exposure to 7 Gy 60Co radiation. In the post-irradiation period (3-14 days) combined pre-treatment of mice accelerated recovery of bone marrow cellularity, weight of spleen and myelopoietic and erythropoietic activity in both hematopoietic organs, compared to treatment with MTP-PE/MLV or indomethacin alone. In the peripheral blood, improved radioprotective effects of combined drug administration were found in the recovery of reticulocytes and platelet count. No further significant differences in the recovery of leukocyte count were observed in the examined groups until post-irradiation day 14. Within the first 3-6 post-irradiation days, the bone marrow and peripheral blood smears of mice pre-treated with indomethacin alone or its combination with MTP-PE/MLV more frequently featured blast cells and large cells with abundant cytoplasm which could be considered the hematopoietic stem cells., N. O. Macková, P. Fedoročko., and Obsahuje bibliografii
The aims of our study were to investigate into the effect of lithium on smooth muscle contraction and phosphorylation of myosin light chain (MLC20) by MLCK and to find out the clue of its mechanism. Isolated rabbit duodenum smooth muscle strips were used to study the effects of lithium on their contractile activity under the condition of Krebs’ solution by means of HW-400S constant temperature smooth muscle trough. Myosin and MLCK were purified from the chicken gizzard smooth muscle. Myosin phosphorylation was determined by Glycerol-PAGE, myosin Mg2+-ATPase activity was measured by Pi liberation method. Lithium (10-40 mM) inhibited the contraction in duodenum in a dose-related and time-dependent manner. Lithium could also inhibit the extent of myosin phosphorylation in a dose-related and time-dependent manner, whereas it inhibited Mg2+-ATPase activity in a dose-rel ated manner. Lithium inhibited smooth muscle contraction by inhibition of myosin phosphorylation and Mg2+-ATPase activity., Z. Y. Tang, Z. N. Liu, L. Fu, D. P. Chen, Q. D. Ai, Y. Lin., and Obsahuje bibliografii
The aim of this study was to investigate the effects of long-term stay of Japanese quail in simulated microgravity on some sexual features of males. As a model for simulating microgravity exposure of birds in laboratory conditions was used hypodynamia. The mean left testis weight in males reared under hypodynamia from day 3 up to 180 days of age was lower than that of control (P<0.05), but the right testis weight differences between both groups were not significant. Also the area, volume and foam production of cloacal gland was not significantly decreased in hypodynamia birds at the end of experiment. By contrast, the plasma testosterone concentration of males living in hypodynamia was reduced about 50 % at 90 and 180 days of age in comparison to control (P<0.05) suggesting some negative effects on sexual development. Our results demonstrated that male quail kept under simulated microgravity conditions were sexually competent although their sexual efficiency was reduced especially in terms of plasma testosterone., P. Škrobánek ... [et al.]., and Obsahuje seznam literatury
We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by NG -nitro-Larginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent., M. Chaswal ... [et al.]., and Obsahuje seznam literatury