a1_Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI)., a2_We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD., Magdaléna Kovářová, Zuzana Žilinská, Ján Páleš, Zuzana Kužmová, Andrea Gažová, Juraj Smaha, Martin Kužma, Peter Jackuliak, Viera Štvrtinová, Ján Kyselovič, Juraj Payer., and Obsahuje bibliografii
There is increasing evidence that dietary saturated fatty acids (SAFA) have not only an indirect atherogenic effect due to increasing LDL-cholesterol concentration but also a direct effect by activating the inflammation process. This review summarizes several recent publications in this field. The effect of SAFA on the inflammation process mediated by Toll-like receptor 4/NF-κB pathway has been well documented in various in vitro culture studies of macrophages and adipocytes or in their co-culture. In contrast to these in vitro data, in vivo epidemiological studies or clinical experiments in men are less consistent. Well controlled cross-over studies in volunteers might enlighten the differences between saturated and unsaturated fatty acids dietary intake and proatherogenic inflammation effects., R. Poledne., and Obsahuje seznam literatury
Experimental data concerning the bioavailability of the different Mg-salts in human organism is inconsistent. Mg-absorption reported by clinical studies largely varies depending on the method used for evaluation. The aim of this study was to evaluate the bioavailability and accessibility of magnesium bound in different Mg-salt compounds, using an in vitro model of intestinal cell barrier. The study included a variety of inorganic (oxide, sulphate, chloride, carbonate) and organic salts (lactate, citrate, pidolate). Caco-2 cells were cultivated in a complete culture medium with different magnesium salts treatments in ascending concentrations. The viability and quantity of cells was analysed by FACS. Mg-absorption was analysed by a direct colorimetric assay, measured by spectrometry. T-test identified a significant decrease in cell count treatment with mg-lactate compared with citrate. Mg-pidolate showed a significantly higher cell viability compared with Mg-citrate, Mg-lactate and Mg-chloride. Even though the difference was not significant, we showed that an increase in Mg2+ salt concentration progressively decreased the cell count and the viability and the effect was universal for all the used Mg-salt treatments. Mg-citrate, chloride, and sulphate showed a significantly lower absorption compared to Mg-carbonate, pidolate and oxide. Our in vitro monolayer model of human intestinal transport showed that viability and quantity of cell decreased with increasing Mg-concentration. We admit that our experiment model may have some limitations in accurately describing an in vivo Mg2+ absorption. Moreover, it is also necessary to assess the relevance of our data in vivo and especially in clinical practice., Ján Kyselovič, Nikola Chomaničová, Adriana Adamičková, Simona Valášková, Barbara Šalingová, Andrea Gažová., and Obsahuje bibliografii
The purpose of the present study was to examine the role of the T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism on changes in renal hemodynamics and blood pressure due to Na+ loading. Twenty-eight older (63±1 years), moderately obese (39±2 % fat) hypertensives had th eir glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and plasma nitric oxide (NOx) levels determined after eight days of low (20 mEq) and high (200 mEq) Na+ diets. The two Na+ diets were separated by a 1-week washout period. Subjects were genotyped for the eNOS-786 site and were grouped on whether they were homozygous or heterozygous for the C allele (TC+CC, n=13) or only homozygous for the T allele (TT, n=15). The TC+CC genotype group had a significantly greater increase in diastolic (P=0.021) and mean arterial (P=0.018) BP and a significant decline in both RPF (P=0.007) and GFR (P=0.029) compared to the TT genotype group with Na+ loading. Furthermore, Na+ loading resulted in a significant (P=0.036) increase in plasma NOx in the TT, but not in the TC+CC genotype group as well as a trend (P=0.051) for an increase in urine NOx in TC+CC, but not in the TT genotype group. The increase in BP during Na+ loading in older hypertensives was associated with the eNOS genotype and may be related to changes in renal hemodynamics due to changes in NO metabolism., D. R. Dengel, M. D. Brown, R. E. Ferrell, T. H. Reynolds, M. A. Supiano., and Obsahuje bibliografii a bibliografické odkazy
Natural glucocorticoid hydrocortisone was suggested as a potent substitution for dexamethasone in the treatment of bronchopulmonary dysplasia in neonates. The aim of this study was to investigate whether hydrocortisone is able to affect the expression of apoptotic genes and the intensity of naturally occurring cell death in the developing rat hippocampus. Hormone treatment decreased procaspase-3 and active caspase-3 levels as well as DNA fragmentation intensity in the hippocampal formation of one-week-old rats in 6 h after injection. These changes were accompanied by an upregulation of antiapoptotic protein Bcl-XL, while expression of proapoptotic protein Bax remained unchanged. The action of hydrocortisone was glucocorticoid receptor-independent, as the selective glucocorticoid receptor agonist dexamethasone did not affect either apoptotic protein levels or DNA fragmentation intensity in the hippocampal region. The data are the first evidences for in vivo antiapoptotic effects of hydrocortisone in the developing hippocampus., P. N. Menshanov, ... [et al.]., and Obsahuje seznam literatury
Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions., M.A. Fahim ... [et al.]., and Obsahuje seznam literatury
We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs., L. Xu, Y. Liu., and Obsahuje seznam literatury
Advanced glycation end products (AGEs) may play an important adverse role in process of atherosclerosis, diabetes, aging and chronic renal failure. Levels of Ne-carboxymethyllysine and fluorescent AGE values were estimated in two nutritional population groups - alternative group (vegetarians - plant food, milk products, eggs) and traditional group (omnivorous subjects). Vegetarians have a significantly higher carboxymethyllysine content in plasma and fluorescent AGE values. Intake of proteins, lysine and monosaccharides as well as culinary treatment, consumption of food AGEs (mainly from technologically processed products) and the routes of Maillard reaction in organism are the substantial sources of plasma AGEs. Vegetarians consume less proteins and saccharides. Lysine intake is significantly reduced (low content in plant proteins). Subjects on alternative nutrition do not use high temperature for culinary treatment and consume low amount of technologically processed food. Fructation induced AGE fluorescence is greater as compared with that induced by glucose. It is due to higher participation of a more reactive acyclic form of fructose. Intake of vegetables and fruit with predominance of fructose is significantly higher in vegetarians. Comparison of nutrition and plasma AGEs in vegetarian and omnivorous groups shows that the higher intake of fructose in alternative nutrition of healthy subjects may cause an increase of AGE levels., M. Krajčovičová-Kudláčková, K. Šebeková, R. Schinzel., and Obsahuje bibliografii
Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11±1.15x103 AU/g vs controls 4.08±0.71x103 AU/g, p<0.001, vs DM1 4.14±0.86x103 AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50±75.15 mmol/l vs healthy subjects 79.80±23.72 mmol/l, p<0.001, vs DM1 97.50±30.91 mmol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products., M. Kalousová, J. Škrha, T. Zima., and Obsahuje bibliografii
Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that agerelated alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation., E. Babušíková ... [et al.]., and Obsahuje seznam literatury