Acute liver failure (ALF) is a clinical syndrome resulting from widespread damage of hepatocytes, with extremely high mortality rate. Urgent orthotopic liver transplantation was shown to be the most effective therapy for ALF but this treatment option is limited by sca rcity of donor organs. Therefore, hepatocyte transplantation (Tx) has emerged as a new therapeutical measure for ALF, however, the first clinical applications proved unsatisfactory. Apparently, extensive preclinical studies are needed. Our aim was to exami ne if hepatocytes isolated from transgenic “firefly luciferase” Lewis rats into the recipient liver would attenuate the course of thioacetamide (TAA) -induced ALF in Lewis rats. Untreated Lewis rats after TAA administration showed a profound decrease in sur vival rate; no animal survived 54 h. The rats showed marked increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, in plasma level of bilirubin and ammonia (NH 3 ), and in a significant decrease in plasma albumin. Hepatocyte Tx attenuated the course of TAA -induced ALF Lewis rats which was reflected by improved survival rate and reduced degree of liver injury showing as lowering of elevated plasma ALT, AST, NH 3 and bilirubin levels and increasing plasma albumin. In addition, bioluminescence imaging analyses have shown that in the TAA- damaged livers the transplanted hepatocyte were fully viable throughout the experiment. In conclusion, the results show that hepatocyte Tx into the liver can attenuate the course of TAA- induced ALF in Lewis rats. This information should be considered in attempts to develop new therapeutic approaches to the treatment of ALF., E. Koblihová, O. Lukšan, I. Mrázová, M. Ryska, L. Červenka., and Obsahuje bibliografii
Hepatoprotective properties of rooibos tea (Aspalathus linearis) were investigated in a rat model of liver injury induced by carbon tetrachloride (CCl4). Rooibos tea, like N-acetyl-L-cysteine which was used for the comparison, showed histological regression of steatosis and cirrhosis in the liver tissue with a significant inhibition of the increase of liver tissue concentrations of malondialdehyde, triacylglycerols and cholesterol. Simultaneously, rooibos tea significantly suppressed mainly the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin concentrations, which are considered as markers of liver functional state. The antifibrotic effect in the experimental model of hepatic cirrhosis of rats suggests the use of rooibos tea as a plant hepatoprotector in the diet of patients with hepatopathies., O. Uličná, M. Greksák, O. Vančová, L. Zlatoš, Š. Galbavý, P. Božek, M. Nakano., and Obsahuje bibliografii
D-galactosamine is a hepatotoxic agent, which induces diffuse injury of liver tissue followed by the regeneration process. Our data showed a high increase of serum aminotransferases after D-galactosamine administration, which indicates a high extent of liver injury. When lipid emulsion was applied immediately after D-galactosamine, the increase of serum aminotransferases was greatly reduced. In addition, the decrease of the cytochrome c oxidase activity induced by D-galactosamine was not observed after lipid emulsion administration and the increase of total liver oxidative capacity in the regeneration period due to activated mitochondrial biogenesis was accelerated. All these findings indicate a protective effect of lipid emulsion administration against D-galactosamine toxicity., R. Ferenčíková, Z. Červinková, Z. Drahota., and Obsahuje bibliografii
Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheoch romocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine- producing tumors arising from sympathetic- or parasympathetic- derived chromaffin tissue. To date, eighte en PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIF α signaling has also been sh own to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors., I. Jochmanová, T. Zelinka, J. Widimský Jr., K. Pacak., and Obsahuje bibliografii
Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and/or oxidant mechanisms. Gum arabic (GA) is a complex po lysaccharide that acts as an anti-oxidant which can modulate inflammatory and/or immunological processes. Therefore, we tested here the effect of GA treatment (15 % in the drinking water for 4 weeks) in plasma and urine of rats, on a novel cytokine that has been shown to be pro-inflammatory, viz, DNA-binding high-mobility group box-1 protein (HMGB1). Adenine (0.75 % in the feed, 4 weeks) significantly increased indoxyl sulphate, urea and creatinine concentrations in plasma, an d significantly decreased the creatinine clearance. GA significantly abated these effects. The concentrations of HMGB1 in urine before the start of the experiment were similar in all four groups. However, 24 h after the last treatment, adenine treatment increased significantly the concentration of HMGB1 when compared with the control. GA treatment did not affect the HMGB1 concentration in urine. Moreover, the concentration of HMGB1 in plasma obtained 24 h after the last treatment in rats treated with adenine was drastically reduced compared with the control group. This may explain its significant rise in urine. In conclusion, HMGB1 can be considered a potentially useful biomarker in adenine induced CRF and its treatment., B. H. Ali, M. Al Za'abi, A. Al Shukaili, A. Nemmar., and Obsahuje bibliografii
In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute’s breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists., V. Lobellová, E. Brichtová, T. Petrásek, K. Valeš, A. Stuchlík., and Obsahuje bibliografii
A high VO2max in middle-age is related to high metabolic flexibility and lowered risk of metabolic diseases. However, the influence of a high VO2max induced by years of regular training in middle-age on protein expression related to muscle metabolism is not well studied. This study measures key proteins involved in mitochondrial oxidation, glucose and lipid metabolism in skeletal muscle of trained and untrained middle-aged men. 16 middle-aged men, matched for lean body mass, were recruited into an endurance trained (TR, n=8) or an untrained (CON, n=8) group based on their VO2max. A muscle biopsy was obtained from m. vastus lateralis and protein levels were analyzed by Western blotting. The TR had higher protein levels of mitochondrial complex III-V, endothelial lipase (EL) and perilipin 5 compared to the CON. Glycogen synthase (P=0.05), perilipin 3 (P=0.09) and ATGL (P=0.09) tended to be higher in TR than CON, but there was no difference in AKT I/II, HKII, GLUT4 and LPL protein expression. Lastly, there was a positive correlation between plasma HDL and EL (R2=0.53, P<0.01). In conclusion, a high VO2max in middle-aged men was as expected is reflected in higher muscle oxidative capacity, but also in higher endothelial lipase and perilipin 5 expression and a borderline higher glycogen synthase protein expression, which may contribute to a higher metabolic flexibility., A. Vigelsø, C. Prats, T. Ploug, F. Dela, J. W. Helge., and Obsahuje bibliografii
Hippocampus is a brain structure containing vasopressin (AVP) fibers and specific binding sites for this peptide. There is growing evidence that AVP and its metabolites participate in glutamate-mediated plasticity of the hippocampus. The aim of the present study was to evaluate the influence of NMDA on AVP release in the rabbit hippocampus. Caudate nucleus was chosen as the reference structure. The mentioned brain structures were simultaneously microdialyzed with 0.9 % NaCl solution. AVP was determined in the outflowing fluid by radioimmunoassay. The mean basal AVP content in the fluid outflowing from the hippocampus was significantly greater than that from the caudate nucleus. The addition of K+ into the fluid perfusing the probes implanted into the hippocampus and caudate nucleus significantly increased AVP release into the extracellular fluid of both brain structures. NMDA applied into the mentioned brain structures increased AVP release only from the hippocampus but not from the caudate nucleus. Our findings indicate a role which NMDA receptors play in AVP release into the extracellular fluid of the hippocampus., M. Orłowska-Majdak, W. Z. Traczyk, D. Szymański., and Obsahuje bibliografii
The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bureš and Olga Burešova. We use the occasion of Jan’s 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats., K. Ježek, M. Wesierska, A. A. Fenton., and Obsahuje bibliografii