Increased levels of plasma cysteine predispose to obesity and metabolic disturbances. Our recent genetic analyses in spontaneously hypertensive rats (SHR) revealed mutated Folr1 (folate receptor 1) on chromosome 1 as a quantitative trait gene associated with reduced folate levels, hypercysteinemia and metabolic disturbances. The Folr1 gene is closely linked to the Folh1 (folate hydrolase 1) gene which codes for an enzyme involved in the hydrolysis of dietary polyglutamyl folates in the intestine. In the current study, we obtained evidence that Folh1 mRNA of the BN (Brown Norway) origin is weakly but significantly expressed in the small intestine. Next we analyzed the effects of the Folh1 alleles on folate and sulfur amino acid levels and consecutively on glucose and lipid metabolism using SHR-1 congenic sublines harboring either Folr1 BN and Folh1 SHR alleles or Folr1 SHR and Folh1 BN alleles. Both congenic sublines when compared to SHR controls, exhibited significantly reduced folate clearance and lower plasma cysteine and homocysteine levels which was associated with significantly decreased serum glucose and insulin concentrations and reduced adiposity. These results strongly suggest that, in addition to Folr1 , the Folh1 gene also plays an important role in folate and sulfur amino acid levels and affects glucose and lipid metabolism in the rat., J. Šilhavý, J. Krijt, J. Sokolová, V. Zídek, P. Mlejnek, M. Šimáková, V. Škop, J. Trnovská, O. Oliyarnyk, I. Marková, M. Hüttl, H. Malínská, L. Kazdová, F. Liška, V. Kožich, M. Pravenec., and Obsahuje bibliografii
Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus- pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11 β -hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that re gulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions., P. Ergang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 μ mol/l) or pravastatin (P, 30 μ mol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30- min global isch emia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3±0.2 in C to 3.0±0 and 2.7±0.2 in S and P, respectively, (both P<0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27±2 % and 10±2 % in S and P groups, respectively, vs. 42±1 % in C; P<0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48±12 % of preischemic values vs. 25±4 % in C and 21± 7 % in P groups; P<0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprot ective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion., S. Čarnická ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
To study 3D nuclear distributions of epigenetic hist one modifications such as H3(K9) acetylation, H3(K4) dimethylation, H3(K9) dimethylation, and H3(K27) trimethylation, and of histone methyltransferase Suv39H1, we used advanced image analysis methods, comb ined with Nipkow disk confocal microscopy. Total fluorescence intensity and distributions of fluorescently labelled proteins were analyzed in formaldehyde-fixed interphase nuclei. Our data showed reduced fluorescent signals of H3(K9) acetylation and H3(K4) dimethylation (di-me) at the nuclear periphery, while di-meH3(K9) was also abundant in chromatin regions closely associated with the nuclear envelope. Little overlapping (intermingling) was observed for di-meH3(K4) and H3(K27) trimethylation (tri-me), and for di-meH3(K9) and Suv39H1. The histone modifications studied were absent in the nucleolar compartment with the exception of H3(K9) dimethylation that was closely associated with perinucleolar regions which are formed by centromeres of acrocentric chromosomes. Using immunocytochemistry, no di-meH3(K4) but only dense di-meH3(K9) was found for the human acrocentric chromosomes 14 and 22. The active X chromosome was observed to be partially acetylated, while the inactive X was more condensed, located in a very peripheral part of the interphase nuclei, and lacked H3(K9) acetylation. Our results confirmed specific interphase patterns of histone modifications within the interphase nuclei as well as within their chromosome territories., M. Skalníková, E. Bártová, V. Ulman, P. Matula, D. Svoboda, A. Harničarová, M. Kozubek, S. Kozubek., and Obsahuje bibliografii a bibliografické odkazy
Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 h oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load., D. Vejrazkova, O. Lischkova, M. Vankova, S. Stanicka, J. Vrbikova, P. Lukasova, J. Vcelak, G. Vacinova, B. Bendlova., and Obsahuje bibliografii
Pro populaci pacientů s diabetem 2. typu nejsou v současnosti v České republice dostupná data o distribuci hodnot glykovaného hemoglobinu. Plnému uplatnění výhod nových skupin antidiabetik pro časnou intervenci brání v současnosti indikační omezení, které omezuje úhradu této terapie pro nedostatečně kompenzované pacienty s hranicí definovanou hodnotou 60 mmol/mol (6 % IFCC). Analýza distribuce hodnot glykovaného hemoglobinu v náhodně vybrané populaci pacientů s diabetem 2. typu ve studii Valetudo ukazuje, že v rozmezí kritického intervalu od 43 mmol/mol do 80 mmol/mol je průměrná četnost pacientů z celé populace 1,88 %/1 mmol/mol glykovaného hemoglobinu. Interpretace dat z průřezových studií je velmi obtížná, jelikož zahrnuje pacienty před léčbou (případně před intenzifikací léčby) i pacienty úspěšně léčené., Currently, there are no available data on distribution of the values of glycated haemoglobin in patients with type 2 diabetes in the Czech Republic. More frequent, efficacy and early application of new antidiabetic agents is limited by indication criterion which restricts the payment of this therapy for patients with poorly compensated diabetes defined by threshold value of 60 mmol/mol (6% IFCC). The study Valetudo analyzed distribution of glycated haemoglobin values in the random population of patients with type 2 diabetes and showed that within the critical range from 43 mmol/mol to 80 mmol/mol is the average frequency of patients from the whole population of 1.88%/1 mmol/mol glycated haemoglobin. Interpretation of data from cross-sectional studies is very difficult as they involve patients before treatment (possibly before the intensification of therapy) and also patients successfully treated., and Milan Kvapil
Dryocosmus kuriphilus (Hymenoptera: Cynipidae), also known as the Asian chestnut gall wasp, is a non-native invasive species that has recently appeared in many regions of Europe, including the Iberian Peninsula. This species is an important pest of chestnut trees in several regions and is of concern for foresters in these areas. The results of this research revealed 14 different hotspots of infestation of D. kuriphilus and resulted in the development of models that predict the distribution of D. kuriphilus in Spain over the next 37 years (2019-2055). These results indicate a rapid spread in all Spanish chestnut forests and identify areas that are theoretically highly suitable and susceptible to colonization by this cynipid based on predictions of three different niche models. Although D. kuriphilus is able to induce galls on all chestnut trees, the models indicate that there are differences in the suitability of the different regions for this species. This differential suitability results in some areas having better environmental conditions than others for D. kuriphilus, which is a factor that should be taken into account in its management and biological control. This study of the current distribution, patterns of dispersal using GIS and potentially suitable areas for D. kuriphilus, using niche models will assist in the management and control of this pest in Spain., Diego Gil-Tapetado, José F. Gómez, Francisco J. Cabrero-Sañudo, José L. Nieves-Aldrey., and Obsahuje bibliografii
The ubiquitin-proteasome pathway fulfills major biological functions, but its physiologic tissue distribution and the interrelationship between pathway component activities and ubiquitin pools are unknown. Therefore, we analyzed free and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and chymotryptic- and tryptic-like proteasome peptidase activities in porcine skeletal muscle, heart, lung, liver, spleen and kidney (n=5 each). There were considerable differences between tissues (p<0.05 for all parameters). Lung and spleen showed high levels of free and conjugated ubiquitin and high UbPL. Proteasome activities were highest in kidney and heart. There were linear relationships between tryptic-like and chymotryptic-like proteasome peptidase activities (r2 = 0.624, p<0.001) and between free and conjugated ubiquitin tissue levels (r2 = 0.623, p<0.001). Tissue levels of free and conjugated ubiquitin correlated linear with UbPL (p<0.005), but they were not correlated with proteasome peptidase activities. The results suggest that tissue ubiquitin pools are tightly regulated and indicate a constant proportion of conjugated ubiquitin. They further support the hypothesis that ubiquitin-protein ligase systems, and probably deubiquitylating enzymes, are key regulators of ubiquitin homeostasis. The detected differences are suggestive of tissue-specific roles of ubiquitin-proteasome pathway components. Besides the known importance of the ubiquitin proteasome pathway in heart, kidney and the immune system, the results suggest the lung as another organ in which ubiquitin proteasome pathway components may also significantly contribute to disease processes., M. B. Patel, M. Majetschak., and Obsahuje bibliografii a bibliografické odkazy
Combustion of lignite with limestone, co-combustion of lignite with limestone and wood, and combustion of wood were performed in a circulating fluidised bed in 7 different combustion regimes. The in organic matter composition and properties of all input and output materials were characterized. For each com bustion regime the material streams and the boiler outputs were calculated. The total inorganic mass and the mass of selected trace elements in fuels (Cl, Zn, As, Se, Hg, and Pb) were based on the output of a 1 GW circulating fluidised-bed boiler; additionally, the concen trations of volatile elements (As, Se, Hg) in fly ash (FA) were evaluated in relation to the mass of FA. Element (Cl, Zn, As, Se, Hg, and Pb) enrichment in FA compared with BA was related to the ratio R between the co mbusted mass of organic wood wastes and total combusted fuel. Additionally, the unburned carbon in bottom ash (BA) and fly ash (FA) was determined, and sel ected elements were studied in unburned materials separated from BA. The results show that combustion of wood and/or co-combustion of lignite with wood waste brings about significant environmental benefits., Zdeněk Klika, Lucie Bartoňová and Jana Serenčíšová., and Obsahuje bibliografické odkazy
Nearly all epileptic seizures in patients are characterized by deranged consciousness. We started to study changes in motivated behavior (drinking in thirsty rats) as a possible analogue of compromised consciousness during and after epileptic seizures. Epileptic afterdischarges (ADs) were elicited by stimulation of the dorsal hippocampus and/or thalamus. Rats with implanted electrodes (deprived of water for 24 hours) were trained to lick water from a narrow tube. After pretraining ADs were elicited eight times in each animal and access to water was allowed during different phases of the AD. Stimulation did not affect licking if no AD was induced. If stimulation was successful, licking was stopped in nearly 70 % of stimulations and modified (biting the tube) in 30 %. Hippocampal ADs (characterized by serrated waves in the EEG and by an arrest of behavior with subsequent automatisms) completely blocked licking, signs of recovery appeared during the interval between the AD and recurrent AD and it progressed during recurrent ADs. Thalamic ADs abolished licking in 82% of cases and immediately after ADs normal licking reappeared in 49 % of these observations. Our results suggest that changes in motivated behavior might serve as an analogue of compromised human consciousness., P. Mareš, L. Chocholová., and Obsahuje bibliografii