Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies., P. Ivak, J. Pitha, P. Wohlfahrt, I. Kralova Lesna, P. Stavek, Z. dorazilova, J. Stepankova, J. Maly, M. Pokorny, I. Netuka., and Obsahuje bibliografii
a_1 We sought to examine the association between maternal erythrocyte omega-3, omega-6 and trans fatty acids and risk of preeclampsia. We conducted a case-control study of 170 women with proteinuric, pregnancy-induced hypertension and 185 normotensive pregnant women who delivered at Harare Maternity Hospital, Harare, Zimbabwe. We measured erythrocyte omega-3, omega-6 and trans fatty acid as the percentage of total fatty acids using gas chromatography. After multivariate adjustment for confounding factors, women in the highest quartile group for total omega-3 fatty acids compared with women in the lowest quartile experienced a 14 % reduction in risk of preeclampsia (odds ratio 0.86, 95 % confidence interval 0.45 to 1.63). For total omega-6 fatty acids the odds ratio was 0.46 (95 % confidence interval 0.23 to 0.92), although there was suggestion of a slight increase in risk of preeclampsia associated with high levels of arachidonic acid. Among women in the highest quartile for arachidonic acid the odds ratio was 1.29 (95 % confidence interval 0.66 to 2.54). A strong statistically significant positive association of diunsaturated fatty acids with a trans double bond with risk of preeclampsia was observed. Women in the upper quartile of 9-cis 12-trans octadecanoic acid (C18:2n6ct) compared with those in the lowest quartile experienced a 3-fold higher risk of preeclampsia (odds ratio = 3.02, 95 % confidence interval 1.41 to 6.45). Among women in the highest quartile for 9-trans 12-cis octadecanoic acid (C18:2n6tc) the odds ratio was 3.32 (95 % confidence interval 1.55 to 7.13)., a_2 Monounsaturated trans fatty acids were also positively associated with the risk of preeclampsia, although of much reduced magnitude. We observed a strong positive association of trans fatty acids, particularly diunsaturated trans fatty acids, with the risk of preeclampsia. We found little support for the hypothesized in verse association between omega-3 fatty acids and preeclampsia risk in this population. Polyunsaturated fatty acids, particularly omega-3 fatty acids, were comparatively lower in Zimbabwean than among US pregnant women. Given the limited inter-person variation in omega-3 fatty acids among Zimbabwean women, our sample size may be too small to adequately assess the relation in this population., K. Mahomed, M. A. Williams, I. B. King, S. Mudzamiri., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to investigate the effects of calcium channel blockers on tertbutyl hydroperoxide (TBH) induced liver injury using isolated perfused rat hepatocytes. Rat hepatocytes were immobilized in agarose threads and perfused with Williams E medium. Hepatocyte injury was induced by the addition of tertbutyl hydroperoxide (1 mM) to the perfusion medium 30 min after the addition of either verapamil or diltiazim. Hepatocyte injury was observed by monitoring the functional and metabolic competence of hepatocytes or by ultrastructural morphological examination of hepatocytes. Verapamil (0.5 mM) reduced lactate dehydrogenase leakage in TBH-injured hepatocytes as compared to the controls (154± 11 % vs. 247± 30 %). Lipid peroxides production was reduced after verapamil pretreatment as compared to the controls and oxygen consumption was increased by pretreatment of hepatocytes with verapamil. Verapamil pretreatment increased the protein synthesis activity at both levels of granular endoplasmic reticulum and free polysomes in cytoplasm and decreased ATPase activity. Diltiazem was qualitatively effective as verapamil. It is concluded that in hepatocyte oxidative injury, calcium channel blockers exhibited hepatoprotective properties. The hepatoprotective effect of calcium channel blockers was accompanied by a decrease in ATPase activity, which may implicate a normalization of Ca2+i after TBH intoxication., H. Farghali, E. Kmoníčková, H. Lotková, J. Martínek., and Obsahuje bibliografii
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
Both, severe hypo- or hyperthyroidism may alter hemodynamic parameters. The aim of our study was to ascertain, whether also distinct changes within normal range of free thyroxine (fT4) would be associated with an impairment of left ventricle function in patients with chronic heart failure. Hundred-forty-eight patients (m121, f27, mean age 63.8±1.14 years) with chronic heart failure, fT4 levels within the normal range (9-22 pmol/l) and without thyrostatics or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Patients with fT4 in the range 11.9-14.6 pmol/l [optimal, 2nd-3th quintile] had significantly lower NT-proBNP (718±70.4 pg/ml), than those with fT4<11.8 [low-normal, bottom quintile](1236±223.6 pg/ml; p<0.03) and those with fT4 over 14.6 pmol/l [high-normal, top two quintiles] (1192±114.9 pg/ml; p<0.0002). These differences remain significant, also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were also found in BNP, but only when optimal and high-normal fT4 ranges were compared. In conclusion, the severity of heart failure seems to be also influenced by only mild deviations of fT4 concentrations from optimal levels., O. Mayer Jr, J. Šimon, J. Čech, H. Rosolová, J. Hrbková, R. Pikner, L. Trefil., and Obsahuje bibliografii a bibliografické údaje
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
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
The effects of Lathyrus sativus neurotoxin were studied on the cell membrane potential and cellular cation composition in Retzius nerve cells of the leech Haemopis sanguisuga, with ion-selective microelectrodes using liquid ion-exchangers. Bath application of 10-4 mol/l Lathyrus sativus neurotoxin for 3 min depolarized the cell membrane potential and decreased the input resistance of directly polarized membrane in Retzius neurons. At the same time the cellular Na+ activity increased and cellular K+ activity decreased with slow but complete recovery, while the intracellular Ca2+ concentration was not changed. Na+-free Ringer solutions inhibited the depolarizing effect of the neurotoxin on the cell membrane potential. Zero-Ca2+ Ringer solution or Ni2+-Ringer solution had no influence on the depolarizing effect of the neurotoxin on the cell membrane potential. It is obvious that the increase in membrane conductance and depolarization of the cell membrane potential are due to an influx of Na+ into the cell accompanied by an efflux of K+ from the cell., D. Cemerikić, V. Nedeljkov, S. Lopičić, S. Dragović, B. Beleslin., and Obsahuje bibliografii