D-Galactosamine/Lipopolysaccharide (D-GalN/LPS) is a well known model of hepatotoxicity that closely resembles acute liver failure (ALF) seen clinically. The role of sirtuin 1 in this model has not yet been documented. However, there have been a number of studies about the cytoprotective effects of resveratrol, a SIRT1 activator, in the liver. This study was aimed at elucidating the roles of SIRT1 protein expression or catalytic activity in DGalN/ LPS model of hepatotoxicity. ALF was induced in male Wistar rats by intraperitoneal injection of D-GalN and LPS. Some groups of animals were pretreated with resveratrol and/or EX-527 (SIRT1 inhibitor). The effects of these treatments were evaluated by biochemical and Western blot studies. D-GalN/LPS treatment was able to induce hepatotoxicity and significantly increase all markers of liver damage and lipid peroxidation. A dramatic decrease of SIRT1 levels in response to D-GalN/LPS treatment was also documented. Resveratrol pretreatment attenuated D-GalN/LPS-induced hepatotoxicity. EX-527 blocked the cytoprotective effects of resveratrol. However, both resveratrol and EX-527 pretreatments did not exhibit any significant effect on SIRT1 protein expression. Collectively, these results suggest that downregulation of SIRT1 expression is involved in the cytotoxic effects of D-GalN/LPS model and SIRT1 activity contributes to the cytoprotective effects of resveratrol in the liver., M. K. Kemelo, L. Wojnarová, N. Kutinová Canová, H. Farghali., and Obsahuje bibliografii
A daily rhythm in the oscillations of pineal dopamine, norepinephrine and epinephrine content was found in male Wistar:Han rats. The acrophases of the oscillations were localized in the first half of the dark period and generally higher values were found in the dark part of the day., I. Ahlers, B. Pástorová, P. Solár, E. Ahlersová., and Obsahuje bibliografii
We studied delayed effects of elevated plasma levels of corticosterone (Cort) on volumetry, neuronal quantity, and gross marks of neurodegeneration in the hippocampal formation of Long-Evans rats. Animals were exposed to increased CORT levels for three weeks via implanted subcutaneous pellets. Volumetry, neuronal quantification and gros s marks of degeneration were measured seven weeks after the termination of CORT treatment. We observed significant differences in volumes and especially in laterality of hippocampal subfields between control and CORT- treated animals. We found th at the left hippocampus was substantially larger than the right hippocampus in the corticosterone-treated group, but not in the control group. In the control group, on the other hand, right hippocampal volume was markedly higher than all other measured volumes (hippocampal left control, hippocampal left CORT-treated and hippocampal right CORT-treated). Left hippocampal volume did not differ between the groups., P. Zach, J. Mrzílková, L. Řezáčová, A. Stuchlík, K. Valeš., and Obsahuje bibliografii
This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases., J. Švíglerová, J. Kuncová, L. Nalos, J. Slavíková, M. Štengl., and Obsahuje bibliografii a bibliografické odkazy
Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical in terhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE., G. Tsenov, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Recent observations suggest the presence of 20S proteasomes (20S) in the lung epithelial lining fluid. However, the physiological relevance of 20S in the alveolar space and possible contribution to disease processes are unknown. Thus, we evaluated whether extracellular proteasomes could have a pathophysiological role in the injured lung using a rat model of lung contusion (LC). Bronchoalveolar lavage fluids (BALF) were obtained at various time points for up to 168 h after LC or sham procedure. Enzyme activities, ELISA and Western blots indicated enzymatically active 20S, the 19S subunit Rpt5 and ubiquitin in BALF. 20S and ubiquitin increased significantl y after LC, peaked at 24 h and normalized within 168 h. Mg 2+ /ATP-dependent peptidase activities were detectable 6-24 h after LC. BALF after LC also contained ubiquitin-protein-ligase activity. Addition of Mg 2+ /ATP to BALF after LC led to significant proteolysis and could be prevented with epoxomicin and EDTA. These data suggest for the first time that the Mg 2+ /ATP-dependent 26S proteasome complex exists outside the cell, is released into the lung epithelial lining fluid after LC and contribute s to the proteolysis of the bulk of protein in the alveolar space of the injured lung. We infer that proteasome complexes may have a pathophysiological role during lung edema clearance., M. Majetschak, L. T. Sorell, T. Patricelli, D. H. Seitz, M. W. Knöferl., and Obsahuje bibliografii
Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ETA and ETB) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca 2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes., J. Dřímal, M. Mislovičová, A. Ismail, F. Monček., and Obsahuje bibliografii
The effects of experimental warming on the growth and physiology of grass Elymus nutans and forb Potentilla anserina were studied by using open-top chambers (OTCs) in an alpine meadow of the eastern Tibetan Plateau. The warming treatment increased mean air and soil surface temperatures by 1.53°C and 0.50°C, respectively, but it reduced soil relative water content in the surface layer. Experimental warming enhanced the growth and gas exchange of E. nutans, while it reduced those of P. anserina. Experimental warming resulted in an increased efficiency of photosystem II (PSII) in E. nutans, while decreasing it in P. anserina; significantly stimulated non-photochemical quenching, antioxidative enzymes and non-enzymes in both species; and significantly reduced malondialdehyde content in E. nutans, while promoting it in P. anserina. The results of this study indicated that the two species showed different growth responses to experimental warming and their different physiological performances further indicated that experimental warming alleviated the negative effect of low temperature on the growth and development of E. nutans, but limited the competitive ability of P. anserina in the study region. and F. S. Shi ... [et al.].
The activity of 194 neurons was recorded in three subdivisions of the medial geniculate body (74 neurons in the ventral, 62 in the medial and 44 neurons in the dorsal subdivision, i.e. vMGB, mMGB and dMGB) of guinea pigs anesthetized with ketamine-xylazine. The discharge properties of neurons were evaluated by means of peristimulus time histograms (PSTHs), interval histograms (INTHs) and auto-correlograms (ACGs). In the whole MGB, the most frequent PSTH responses to pure tone stimuli were onset (43 %) or chopper (32 %). The onset responses were mostly present in the vMGB, whereas chopper responses dominated in the dMGB. In the whole MGB Poisson-like and bimodal INTHs were found in 46 % and 40 % of neurons, respectively. The mMGB revealed fewer bimodal and more symmetrical types of INTH. In the whole MGB, 60 % of units were found to have ACGs typical for short bursts (<100 ms), 23 % for long bursts (>100 ms) and 15 % of units fired without bursts. Neurons in the vMGB were characterized by short bursting, whereas those in the mMGB and dMGB expressed more activity in the long bursts. The results demonstrate that the type of information processing in the vMGB, which belongs to the ”primary” auditory system, is different from that in two other subdivisions of the MGB., E. Kvašňák, J. Popelář, J. Syka., and Obsahuje bibliografii
We aimed to determine the impact of Ca2+-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca2+ handling. Langedorffperfused rat or guinea pig hearts subjected to K+-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca2+ disturbances and Ca2+ overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca2+]i-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca2+-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias., N. Tribulova, V. Knezl, B. Szeiffova Bacova, T. Egan Benova, C. Viczenczova, E. Gonçalvesova, J. Slezak., and Obsahuje bibliografii