The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds - salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the 8th week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dtmax (r=-0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r=0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity., A. Potáčová, M. Adamcová, H. Čajnáková, L. Hrbatová, M. Štěrba, O. Popelová, T. Šimůnek, P. Poňka, V. Geršl., and Obsahuje bibliografii a bibliografické odkazy
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
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 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
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
The aim of this study was to determine whether excessive oxygen uptake (V.o2) occurs not only during exercise but also during recovery after heavy exercise. After previous exercise at zero watts for 4 min, the main exercise was performed for 10 min. Then recovery exercise at zero watts was performed for 10 min. The main exercises were moderate and heavy exercises at exercise intensities of 40 % and 70 % of peak V.o2, respectively. V.o2 kinetics above zero watts was obtained by subtracting V.o2 at zero watts of previous exercise (ΔV.o2). ΔV.o2 in moderate exercise was multiplied by the ratio of power output performed in moderate and heavy exercises so as to estimate the ΔV.o2 applicable to heavy exercise. The difference between ΔV.o2 in heavy exercise and ΔV.o2 estimated from the value of moderate exercise was obtained. The obtained V.o2 was defined as excessive V.o2. The time constant of excessive V.o2 during exercise (1.88±0.70 min) was significantly shorter than that during recovery (9.61±6.92 min). Thus, there was excessive V.o2 during recovery from heavy exercise, suggesting that O2/ATP ratio becomes high after a time delay in heavy exercise and the high ratio continues until recovery., T. Zano, T. Yunoki, R. Matsuura, T. Arimitsu, T. Kimura., and Obsahuje bibliografii a bibliografické odkazy
Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed., D. Marešová, I. Valkounová, K. Jandová, J. Bortelová, S. Trojan., and Obsahuje bibliografii
Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there are characteristic rapid transient changes of intracellular Ca2+ concentration ([Ca2+]i), while the resting cytosolic [Ca2+]i concentration is low. It is mainly caused by two components of the Ca2+ signaling pathways: Ca2+ entry via L-type voltagedependent Ca2+ channels and dynamic involvement of intracellular stores. Proliferative VSMC phenotype is characterized by long-lasting [Ca2+]i oscillations accompanied by sustained elevation of basal [Ca2+]i. During the switch from contractile to proliferative phenotype there is a general transition from voltagedependent Ca2+ entry to voltage-independent Ca2+ entry into the cell. These changes are due to the altered gene expression which is dependent on specific transcription factors activated by various stimuli. It is an open question whether abnormal VSMC phenotype reported in rats with genetic hypertension (such as spontaneously hypertensive rats) might be partially caused by a shift from contractile to proliferative VSMC phenotype., E. Misárková, M. Behuliak, M. Bencze, J. Zicha., and Obsahuje bibliografii