Parameters of branched-chain amino acids (BCAA; leucine, isoleucine and valine) and protein metabolism were evaluated using L-[1-14C]leucine and a-keto[1-14C]isocaproate (KIC) in the whole body and in isolated perfused liver (IPL) of rats fed ad libitum or starved for 3 days. Starvation caused a significant increase in plasma BCAA levels and a decrease in leucine appearance from proteolysis, leucine incorporation into body proteins, leucine oxidation, leucine-oxidized fraction, and leucine clearance. Protein synthesis decreased significantly in skeletal muscle and the liver. There were no significant differences in leucine and KIC oxidation by IPL. In starved animals, a significant increase in net release of BCAA and tyrosine by IPL was observed, while the effect on other amino acids was non-significant. We conclude that the protein-sparing phase of uncomplicated starvation is associated with decreased whole-body proteolysis, protein synthesis, branched-chain amino acid (BCAA) oxidation, and BCAA clearance. The increase in plasma BCAA levels in starved animals results in part from decreased BCAA catabolism, particularly in heart and skeletal muscles, and from a net release of BCAA by the hepatic tissue., M. Holeček, L. Šprongl, I. Tilšer., and Obsahuje bibliografii
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [3 H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [3 H]-DHEAS to [ 3 H]-androstenedione, [3 H]-testosterone, [3 H]-estrone and [ 3 H]-17β-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E1 S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [3 H]-estrone to [3 H]-17β- estradiol. This is the first demonstration that human platelets are able to import DHEAS and E1 S using the OATP family and to convert DHEAS to active DHEA, and to transform E1 S to 17β- estradiol., A. Garrido ... [et al.]., and Obsahuje seznam literatury
Reactive dicarbonyls stimulate production of advanced glycation endproducts, increase oxidative stress and inflammation and contribute to the development of vascular complications. We measured concentrations of dicarbonyls - methylglyoxal (MG), glyoxal (GL) and 3-deoxyglucosone (3-DG) - in the heart and kidney of a model of metabolic syndrome - hereditary hypertriglyceridemic rats (HHTg) and explored its modulation by metformin. Adult HHTg rats were fed a standard diet with or without metformin (300 mg/kg b.w.) and dicarbonyl levels and metabolic parameters were measured. HHTg rats had markedly elevated serum levels of triacylglycerols (p<0.001), FFA (p<0.01) and hepatic triacylglycerols (p<0.001) along with increased concentrations of reactive dicarbonyls in myocardium (MG: p<0.001; GL: p<0.01; 3-DG: p<0.01) and kidney cortex (MG: p<0.01). Metformin treatment significantly reduced reactive dicarbonyls in the myocardium (MG: p<0.05, GL: p<0.05, 3-DG: p<0.01) along with increase of myocardial concentrations of reduced glutathione (p˂0.01) and glyoxalase 1 mRNA expression (p˂0.05). Metformin did not have any significant effect on dicarbonyls, glutathione or on glyoxalase 1 expression in kidney cortex. Chronically elevated hypertriglyceridemia was associated with increased levels of dicarbonyls in heart and kidney. Beneficial effects of metformin on reactive dicarbonyls and glyoxalase in the heart could contribute to its cardioprotective effects., H. Malínská, V. Škop, J. Trnovská, I. Marková, P. Svoboda, L. Kazdová, M. Haluzik., and Seznam literatury
Epilepsie je složité neurologické onemocnění s mnoha projevy, jímž v České republice trpí na 80 tisíc lidí; v celosvětovém měřítku se toto číslo pohybuje kolem neuvěřitelných 50 milionů. V řadě případů je příčina neznámá. Pacienty však netrápí jen sama choroba a její příznaky - což nemusí být pouze záchvaty, ale také další projevy včetně úzkostí, deprese, poruch paměti, pozornosti, chování atd. Život jim ztěžuje též určitá stigmatizace, jelikož společnost stále ještě vnímá toto onemocnění značně nepříznivě. and Jana Olivová.
The objective of this study was to assess a possible link between microalbuminuria (MA), a major ri sk factor of the cardiorenal syndrome and the brain natriuretic peptide (BNP), a marker of cardiac hypertrophy. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (weighing 220-250 g). Rats were randomized into four groups for 8 weeks: Sham, not treated; Bos, treated with bosentan; Cap, treated with captopril; Bos/Cap, treated with both drugs. Blood pressure, plasma BNP and transforming growth factor β1 (TGF-β1) concentrations, microalbuminuria and creatininemia as well as cardiac mass, BNP, α- and β-myosin heavy chain (MHC) gene expression and kidney histology were determined. Following stenosis, Sham rats developed hypertension (p<0.001), an increase in BNP (p<0.05) and TGF-β1 (p<0.005) concentrations, creatinine levels (p<0.001), and urinary albumin (p<0.001). Under drug treatment, decreases in blood pressure (p<0.001), creatinine levels (p<0.05), plasma TGF-β1 (p<0.005) and BNP (p<0.05) concentrations, were co ncomitant with the absence of MA which was significantly correlated with reductions in cardiac mass (p<0.05) and hypertrophy markers (BNP and β-MHC gene expression) (p<0.005) as well as in renal fibrosis. These findings suggest a potential link between microalbuminuria evolution and BNP as well as a possible effect of microalbuminuria-lowering therapy on halting the progression, or even inducing the regression of cardiac hypertrophy., Y. Saliba, E. Chouery, A. Mégarbané, H. Jabbour, N. Farès., and Obsahuje bibliografii
The left and right ventricle originate from distinct parts of the cardiac tube, and several genes are known to be differentially expressed in these compartments. The aims of this study were to determine developmental differences in gene expression between the left and right ventricle, and to assess the effect of altered hemodynamic loading. RNA was extracted from isolated left and right normal chick embryonic ventricles at embryonic day 6, 8, and 10, and from day 8 left atrial ligated hearts with hypoplastic left and dilated right ventricles. cRNA was hybridized to Affymetrix Chicken Genome array according to manufacturer protocols. Microarray analysis identified 302 transcripts that were differentially expressed between the left and right ventricle. Comparative analysis detected 91 genes that were different in left ventricles of ligated hearts compared to age-matched ventricles, while 66 were different in the right ones. A large number of the changes could be interpreted as a delay of normal maturation. The approach described in this study could be used as one of the measures to gauge success of surgical procedures for congenital heart disease and help in determining the optimal time frame for intervention to prevent onset of irreversible changes., E. Krejčí, ... [et al.]., and Obsahuje seznam literatury
The microcirculation, like all physiological systems undergoes modifications during the course of pregnancy. These changes aid the adaption to the new anatomical and physiological environment of pregnancy and ensure adequate oxygen supply to the fetus. Even though the microcirculation is believed to be involved in major pregnancy related pathologies, it remains poorly understood. The availability of safe and non-interventional technologies enabling scientists to study the intact microcirculation of the pregnant patient will hopefully expand our understanding. In this article we review the physiological changes occurring in the microcirculation during pregnancy and the role of the microcirculation in gestational related pathologies. We will also describe the available techniques for the measurement and evaluation of the microcirculation. Lastly we will highlight the possible fields in which these techniques could be utilized to help provide a clearer view of the microcirculation in the pregnant woman., I. Abdo, R. B. George, M. Farrag, V. Cerny, C. Lehmann., and Obsahuje bibliografii
Salusin-β is newly identified bioactive peptide of 20 amino acids, which is widely distributed in hematopoietic system, endocrine system, and the central nervous system (CNS). Although salusin- β extensively expressed in the CNS, the central cardiovascular functions of salusin-β are unclear. Our main objective was to determine the cardiovascular effect of microinjection of salusin-β into the nucleus tractus solitarii (NTS) in anesthetized rats. Bilateral or unilateral microinjection of salusin-β (0.94-94 μg/rat) into the NTS dose-dependently decreased blood pressure and heart rate. Bilateral NTS microinjection of salusin-β (9.4 μg/rat) did not alter baroreflex sensitivity. Prior application of the glutamate receptor antagonist kynurenic acid (0.19 μg/rat, n=9) into the NTS did not alter the salusin-β (9.4 μg/rat) induced hypotension and bradycardia. However, pretreatment with the GABA receptor agonist muscimol (0.5 ng/rat) within the rostral ventrolateral medulla (RVLM) completely abolished the hypotension (-14±5 vs. -3±5 mm Hg, P <0.05) and bradycardia (-22±6 vs. -6±5 bpm, P <0.05) evoked by intra-NTS salusin-β (9.4 μg/rat). In addition, we found that vagotomy didn’t influence the actions of salusin-β (9.4 μg/rat) in the NTS. In conclusion, our present study shows that microinjection of salusin-β into the NTS significantly produces hypotension and bradycardia, presumably by suppressing the activities of presympathetic neurons in the RVLM., Y. Lu, Y. S. Wu, D. S. Chen, M. M. Wang, W. Z. Wang, W. J. Yuan., and Obsahuje bibliografii
In most macrovascular endothelial cell (EC) preparations, resting membrane potential is determined by the inwardly rectifying K+ current (IK1), whereas in microvascular EC the presence of IK1 varies markedly. Cultured microvascular EC from small vessels of human omentum were examined by means of the voltage-clamp technique to elucidate the putative role of IK1 in maintaining resting membrane potential. Macrovascular EC from human iliac artery and bovine aorta served as reference. Human omentum EC showed an outwardly rectifying current-voltage relation. Inward current was hardly sensitive to variations of extracellular [K+] and Ba2+ block suggesting lack of IK1. However, substitution of extracellular [Na+] and/or [Cl-] affected the current-voltage relation indicating that Na+ and Cl- contribute to basal current. Furthermore, outward current was reduced by tetraethylammonium (10 mM), and cell-attached recordings suggested the presence of a Ca2+-activated K+ current. In contrast to human omentum EC, EC from human iliac artery and bovine aorta possessed inwardly rectifying currents which were sensitive to variations of extracellular [K+] and blocked by Ba2+. Thus, the lack of IK1 in human omentum EC suggests that resting membrane potential is determined by Na+ and Cl- currents in addition to K+ outward currents., H. M. Himmel, U. Rauen, U. Ravens., and Obsahuje bibliografii