Left atrial (LA) volume (LAV) is used for the selection of patients with atrial fibrillation (AF) to rhythm control strategies. Calculation of LAV from the LA diameters and areas by two-dimensional (2D) echocardiography may result in significant error. Accuracy of atrial volume assessment has never been studied in patients with long-standing persistent AF (LSPAF) and significant atrial remodeling. This study investigated correlation and agreement between 2D echocardiographic (Simpson method) and electroanatomic (CARTO, Biosense Webster) left and right atrial (RA) volumes (LAVECHO vs. LAVCARTO and RAVECHO vs. RAVCARTO) in patients undergoing catheter ablation for LSPAF. The study enrolled 173 consecutive subjects (females: 21 %, age: 59±9 years). There was only modest correlation between LAVECHO (92±31 ml) and LAVCARTO (178±37 ml) (R=0.57), and RAVECHO (71±29 ml) and RAVCARTO (173±34 ml) (R=0.42), respectively. LAVECHO and RAVECHO underestimated LAVCARTO and RAVCARTO with the absolute bias (±1.96 standard deviation) of -85 (-148; -22) ml and -102 (-169; -35) ml, respectively, and with the relative bias of -48 (-75; -21) % and -59 (-88; -30) %, respectively (all P<0.000001 for their mutual difference). Significant confounders of this difference were not identified. In patients with LSPAF, 2D echocardiography significantly underestimated both LA and RA volumes as compared with electroanatomic reference. This disagreement was independent of clinical, echocardiographic and mapping characteristics., L. Škňouřil, Š. Havránek, V. Bulková, M. Dorda, T. Paleček, J. Šimek, Z. Fingrová, A. Linhart, J. Januška, D. Wichterle, M. Fiala., and Obsahuje bibliografii
V České republice se v roce 2011 diagnostikovalo 7076 nových případů karcinomu prsu (132 na 100 tisíc žen). U podstatné části z těchto pacientek se po onkologické léčbě daří dosáhnout dlouhodobé kompletní remise („vyléčení“), ovšem stále u nich hrozí jednak dlouhodobé komplikace způsobené onkologickou léčbou, jednak recidiva malignity. Dlouhodobá dispenzarizace pacientek s karcinomem prsu je oblastí zájmu nejen onkologů, ale i gynekologů, praktických lékařů a chirurgů. Klíčová slova: dispenzarizace – karcinom prsu – komplikace, In the Czech Republic 7076 new cases of breast cancer were diagnosed in 2011 (132 per 100,000 women). The majority of these patients will achieve long-term complete remission (“cure”) after cancer treatment. However, they still face the risk of long-term complications caused by cancer therapy as well the recurrence of malignancy. Long-term follow-up of patients with breast cancer is an area of interest not only for oncologists, but also for gynecologists, general practitioners, and surgeons. Key words: breast cancer – follow-up – complications, and Tomáš Büchler
a1_We hypothesize that hypokalemia-related electrolyte imbalance linked with abnormal elevation of intracellular free Ca2+ concentration can cause metabolic disturbances and subcellular alterations resulting in intercellular uncoupling, which favor the occurrence of malignant arrhythmias. Langendorff-perfused guinea pig heart (n = 44) was subjected to a standard Tyrode solution (2.8 mmol/l K+) followed by a K+-deficient solution (1.4 mmol/l K+). Bipolar ECG of the left atria and ventricle was continuously monitored and the incidence of ventricular fibrillation was evaluated. Myocardial tissue sampling was performed during stabilization, hypokalemia and at the onset of fibrillation. Enzyme activities of succinic dehydrogenase, glycogen phosphorylase and 5-nucleotidase were determined using in situ catalytic histochemistry. The main gap junction protein, connexin-43, was labeled using mouse monoclonal antibody and FITC conjugated goat antimouse antibody. Ultrastructure was examined by transmission electron microscopy. The free Ca2+ concentration was measured by the indo-1 method in ventricular cell cultures exposed to a K+-free medium. The results showed that sustained ventricular fibrillation appeared within 15-30 min of low K+ perfusion. This was preceded by ectopic activity, episodes of bigeminy and tachycardia. Hypokalemia induced moderate reversible and sporadically irreversible subcellular alterations of cardiomyocytes and impairment of intercellular junctions, which were heterogeneously distributed throughout myocardium. Patchy areas with decreased enzyme activities and diminished immunoreactivity of connexin-43 were found. Furthermore, lack of external K+ was accompanied by an increase of intracellular Ca2+. The prevention of Ca2+ overload by either 1 mmol/l Ni2+ (Na+/Ca2+ inhibitor), 2.5 mmol/l verapamil, 10 mmol/l d-sotalol or 10 mmol/l tedisamil was associated with the protection agains fibrillation., a2_The results indicate that hypokalemia induces Ca2+ overload injury and disturbances in intercellular coupling. Dispersion of these changes throughout the myocardium may serve as the basis for microreentry circuits and thus favor fibrillation occurrence., N. Tribulová, M. Manoach, D. Varon, L. Okruhlicová, T. Zinman , A. Shainberg., 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
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