Endothelium-protective properties of pharmacological agents may be assessed by using different experimental models of endothelial dysfunction or injury. The model of endothelial dysfunction induced by vessel perfusion with polymorphonuclear leukocytes (PMN) was used for evaluation of pentoxifylline (PTX) effects on vasoconstrictor responses to noradrenaline (NA) in the rabbit renal artery. Addition of PMN into the perfusion solution significantly increased the responses to NA at all doses. PTX administration (10-5 mol.l1) significantly diminished the constrictor responses to NA in vessels perfused with PMN+PTX when compared to the responses in PMN-perfused vessels (at dose 0.1 m g: 32.25 vs. 14.25, at dose 1 m g: 51 vs. 27.75 (p<0.01), at dose 10 m g 74.25 vs. 39.75 (p<0.05), all values expressed as median of perfusion pressure in mm Hg). The model of endothelial damage induced by repeated NA administration in 5 doses (10-50 m g of NA) was used for evaluation of the endothelium-protective effect of sulodexide (SLX). It was found that SLX (120 U/l) significantly decreased the number of desquamated endothelial cells (EC) compared to the control group (controls: 131.4± 20.1 EC, +SLX: 83.3± 13.8 EC, p<0.01). These results confirmed the favorable endothelium-protective effects of pentoxifylline and sulodexide in the two experimental models., V. Kristová, M. Kriška, P. Babál, M. N. Djibril, J. Slámová, A. Kurtanský., and Obsahuje bibliografii
Cortisone acetate test was performed in twelve young adult patients with diabetes mellitus type 1, after dexamethasone administration to suppress endogenous cortisol production. Previous screening revealed that all of the subjects had peak cortisol responses in the range from subnormal to normal, as determined by a low-dose Synacthen test. The aim was to find out whether these patients would exhibit different conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase. Using multifactorial ANOVA the following significant relationships were obtained between cortisol or cortisol/cortisone ratio measured during the test and other para meters examined a) before dexamethasone suppression and b) du ring the test: a) Cortisol at 120 th minute negatively correlated with daily insulin dose and positively with basal aldosterone. Cortisol/cortisone ratio at 60th, 120th, 180th, and 240th minute negatively correlated with basal aldosterone/plasma reni n activity ratio, urinary free cortisol/24 hours and positively with basal dehydroepindrosterone sulphate. b) Cortisol at 120th minute negatively correlated with suppressed basal serum glycemia; cortisol/cortisone ratio during the whole test negatively correlated with supressed basal ACTH. The examination of peripheral metabolism of cortisol using cortisone acetate test in patients with di abetes mellitus type 1 showed adaptive changes of 11β-hydroxysteroid dehydrogenace activity associated with altered cortisol tissue supply., K. Šimůnková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The ischemia and reperfusion of a jejunal graft during transplantation triggers the stress of endoplasmic reticulum thus inducing the synthesis of pro-inflammatory cytokines. Spreading of these signals stimulate immunological reactions in distal tissues, i.e. lung, liver and spleen. The aim of this study was to detect the molecular changes in liver and spleen induced by transplanted jejunal graft with one or six hours of reperfusion (group Tx1 and Tx6). Analysis of gene expression changes of inflammatory mediators (TNF-α, IL-10) and specific chaperones (Gadd153, Grp78) derived from endoplasmic reticulum (ER) was done and compared to control group. The qRT-PCR method was used for amplification of the specific genes. The levels of corresponding proteins were detected by Western blot with immunodetection. Protein TNF-α was in liver tissue significantly overexpressed in the experimental group Tx1 by 48 % (p<0.001). In the group Tx6 we found decreased levels of the same protein to the level of controls. However, the protein concentrations of TNF-α in spleen showed increased levels in group Tx1 by 31 % (p<0.001) but even higher levels in the group Tx6 by 115 % (p<0.001) in comparing to controls. Our data demonstrated that the spleen is more sensitive to posttransplantation inflammation than liver, with consequent stress of ER potentially inducing apoptosis and failure of basic functions of lymphoid tissue., P. Urban, M. Rabajdová, Š. Feterik, G. Bódy, T. Granda, M. Mareková, J. Veselá., and Obsahuje bibliografii
The present study describes the estimation of acetaminophen (AAP) toxicity in cultured rat hepatocytes. We used different concentrations of AAP - 1, 2. 5, 5, 10 and 20 mM, to test influence of AAP on cellular viability, functional capacity and oxidative status at given time intervals. WST-1 test showed decrease of dehydrogenase activity in 5, 10 and 20 mM AAP to 75 % of control values after 1 hour of incubation. At 12 h of treatment, all AAP concentrations decreased WST-1 signal; no enzyme activity was found since 18 h in cells treated with 20 mM AAP according to LDH leakage test performed at 24 h of incubation. Functional capacity was tested by albumin assay where the decrease was strictly related to AAP dose. Intracellular oxidative status was assessed by analysis of GSH/GSSG levels and time course of ROS production and glutathione reductase (GR) activity. Increased ROS prod uction was found already after 3 h of incubation in 2.5, 5, 10 and 20 mM AAP, respectively. The highest ROS production was measured after 12 h treatment. GR activity was decreased already after 3 h of incubation and remained also decreased in cells treated with 2.5, 5, 10 and 20 mM AAP during further incubation., Tomáš Roušar ... [et al.]., and Obsahuje seznam literatury
The benefit of percutaneous transluminal angioplasty (PTA) of transplant renal artery stenosis for ischemic nephropathy may be adversely affected by rejection or other complications. As a result, assessment of the effect of PTA on renal function or blood pressure is often difficult. In this paper, we evaluated the effect of PTA using the method of integrated glomerular filtration rate (GFR) based upon the area under the curve over a follow-up period (AUC0-t), to express the level of GFR in a simple manner despite its significant fluctuations. A similar procedure was used to evaluate mean arterial pressure (MAP). The method was employed to assess the outcome in 20 individuals before PTA, and 1, 3, 6, 9 and 12 months after PTA. In eight cases, rejection was detected while there was one case of glomerulonephritis in the graft during the follow-up period. Evaluation (AUCCcr)0-12 related to the integrated pre-PTA value of Ccr [(Ccr)0 x 12] revealed a rise in GFR by more than 20 % in 65 % of cases. No improvement was observed in seven individuals with post-PTA complications. When assessing the integrated value of MAP, success of PTA (a reduction by at least 10 %) was found in 85 % of cases. No significant correlation was found between the relative changes of integrated GFR and MAP. Our data suggest that evaluation of the integrated value of GFR or MAP on the basis of AUC0-t allows to characterize, in a simple manner, the level of graft function and MAP throughout the follow-up period in individual cases. Furthermore, it may provide additional information on the average values obtained at different time intervals after the therapeutic procedure., J. Stříbrná, O. Schück, J.H. Peregrin, D. Krajíčková, J. Skibová., and Obsahuje bibliografii
We investigated the utility of strain, strain rate, and tissue Doppler imaging (TDI) for the evaluation of the right ventricle (RV) impairment in patients with a hypertrophic obstructive cardiomyopathy (HOCM) who underwent a successful alcohol septal ablation (ASA) and were without RV hypertrophy. A group of 19 patients suffering from HOCM with 22 controls was compared. The parameters of TDI were evaluated in mitral and tricuspid annulus. Strain and strain rate derived from TDI were assessed in an apical free wall of RV, as well as in basal segments of the left ventricle. Between both groups, there were significant differences only in isovolumic pre-ejection time (79.2±17.3 ms vs. 58.5±8.1 ms, p<0.01), isovolumic relaxation time (104.7±26.2 ms vs. 77.3±24.5 ms, p<0.01), myocardial performance (Tei) index measured from TDI (0.61±0.14 vs. 0.49±0.09, p<0.01), and early peak diastolic velocity of TDI (10.6±1.67 cm/s vs. 12.6±2.21 cm/s; p<0.05). Our results suggest the impairment of both systolic and diastolic RV function in patients suffering from HOCM. TDI-related parameters appear to be more sensitive than strain and strain rate for evaluation., D. Zemánek ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Although many studies have investigated the relationships of several adipokines to metabolic syndrome (MetS), the interrelationships of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF 21) have not been described in detail. We examined 209 asymptomatic dyslipidemic patients divided into MetS+ (n=73) and MetS- (n=136) groups. The aim of study was to evaluate the relationships between observed adipokines, to compare the levels of total ADP, A-FABP and FGF 21 in individuals with and without MetS, and to elucidate the relationships of individual adipokines to lipid parameters, markers of insulin resistance and endothelial hemostatic markers in these groups. In MetS+ group, we found the independent positive association ADP with A-FABP (beta=0.4888, p=0.0382), A-FABP with FGF 21 (beta=0.3811, p=0.0002) and von Willebrand factor (beta=0.4502, p=0.0013), and FGF 21 with A-FABP (bet a=0.4422, p=0.0002). Our study has confirmed the well-established risk profile of subjects with MetS, although clinically asymptomatic. MetS+ patients had also lower levels of ADP and higher levels of A-FABP and FGF 21. Our study evaluated the interrelationships of ADP, A-FABP and FGF 21 in asymptomatic dyslipidemic subjects with diagnosis of MetS. Especially strong association between A-FABP and FGF 21 needs to be clarified in further studies., D. Novotny ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The effects of environmental salinity on physiological responses, growth, and survival of the Gulf corvina, C. othonopterus, were evaluated in a 6-week completely randomized design experiment. Corvina (17.2±2.3 g mean initial body weight) were subjected to salinities of 5, 15, 25, and 35 ‰ and fed a commercial feed with protein and lipid contents of 46 and 14 %, respectively. Plasma osmolality increased significantly with salinity, ranging from 335.1±5.3 mOsm/kg in fish maintained at 5 ‰, to 354.8±6.8 mOsm/kg in fish kept in seawater, while a significant inverse relationship was observed between salinity and moisture content of whole fish, ranging from 73.8±0.7 (measured at 5 ‰) to 76.9±1.0 % (measured at 35 ‰). In spite of this, growth indices (final weight, weight gain, specific growth rate, condition factor, survival) were not altered, suggesting that, like other members of the family Sciaenidae, the Gulf corvina is a strong osmoregulator. The isosmotic point for this species was estimated to correspond to a salinity of 9.8 ‰. The present study represents the first set of experimental data on salinity tolerance of C. othonopterus and confirms the euryhalinity of this species., M. Perez-Velazquez, P. Urquidez-Bejarano, M. L. González-Félix, C. Minjarez-Osorio., and Obsahuje bibliografii
The purpose of this study was to investigate the occurrence and time-course of apoptosis in soleus skeletal muscle during the first 48 hours of unloading. Fifty Charles River mice were randomly divided into five groups (n=10 each) according to the time of hindlimb suspension (HS). Mice we re suspended for 0 (Control), 6 (6HS), 12 (12HS), 24 (24HS), and 48 hours (48HS). Soleus muscle atrophy was confirmed by a significant decrease of 20 % in muscle-wet weight and of 5 % in the ratio protein concentration/muscle wet-weight observed after 48 hours of unloading. The apoptotic index, the AIF (apoptosis-inducing factor) and p53 expression presented th eir uppermost value (304 %, 241 % and 246 %, respectively) at 24HS, and were preceded by the highest activity of caspase-3 and -8 at 12HS (170 % and 218 %, respectively) and of Bax/Bcl-2 content at 6HS (160 %). There were no marked ultrastructural alterations until 24 hours of simulated weightlessness. Lysosomal autophagic activity and infiltration of phagocytic cells were observed at 24HS and 48HS and might have contributed to the degenerative changes noticed in both groups. Though not consistently supported by morphological evidences, the biochemical parameters sustain the concept that the occurrence of apoptosis parallels the soleus atrophic response in its early phase., R. Ferreira, M. J. Neuparth, R. Vittorino, H. J. Appell, F. Amado, J. A. Duarte., and Obsahuje bibliografii a bibliografické odkazy
Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA., J. Tumova, M. Andel, J. Trnka., and Obsahuje bibliografii