Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu2+ induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern., R. Večeřa, N. Škottová, P. Váňa, L. Kazdová, Z. Chmela, Z. Švagera, D. Walterová, J. Ulrichová, V. Šimánek., and Obsahuje bibliografii
Various reactive oxygen species (ROS) may be produced from normal biochemical, essential metabolic processes or from external sources as exposure to a variety of agents presented in the environment. Lipids, proteins, carbohydrates and DNA are all capable of reacting with ROS and can be implicated in etiology of various human disorders (rheumatoid arthritis, reperfusion injury, atherosclerosis, lung diseases etc.). In the organism damage by ROS is counteracted with natural antioxidants (glutathione peroxidases, superoxide dismutases, catalase, glutathione, ubiquinol, uric acid, and essential minerals) and nutritional antioxidants from diet (i.e. vitamins E, C, carotenoids). Possible mechanisms of nutritional depletion and side effects of high intake are in the article described., Z. Zadák ... [et al.]., and Obsahuje seznam literatury
Impaired cerebrovascular reactivity (CVR), an important risk factor for future stroke, is affected by a presence carotid stenosis. However, in some cases CVR can be impaired in the absence of carotid stenosis due to several poorly characterized mechanisms. We hypothesized that arterial stiffening as observed in coronary heart disease (CHD) could be associated with alteration in CVR in CHD patients without carotid stenosis. The study population consisted of patients referred for coronary angiography without significant carotid stenosis (<50 %). CVR was evaluated by breath holding index (BHI) measured with transcranial color code duplex ultrasound. Arterial stiffness was assessed by pulse wave velocity (PWV) measured by the oscillometric method. The extent of coronary atherosclerosis was quantified by Gensini score (GS). Out of 186 subjects, sixty-two patients fulfilled the inclusion and exclusion criteria. BHI decreased with increasing PWV (r = -0.47, p<0.001). Decrease in BHI was significantly inversely associated with GS (r = -0.61, p<0.001). GS was associated with PWV (p<0.001). In conclusion, impaired CVR was associated with increased arterial stiffening in CHD patients in the absence of significant carotid stenosis. Thus, we speculate that increased arterial stiffness may at least partially contribute to the pathophysiology of CVR alteration in coronary artery disease., D. Rucka, J. Marek, Z. Rucklova, J.-C. Lubanda, S. Havranek, J. Skvaril, P. Varejka, M. Chochola, D. Karetova, J. Korinek, A. Linhart., and Obsahuje bibliografii
We assessed association between novel biomarkers of cardiovascular disease and conven tional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER HDL (cholesterol esterifi cation rate in HDL plasma), AIP - Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Un ivariate analyses confirmed correlation between AIP, FERHDL and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FERHDL in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER HDL was best explained by AIP (R2 =0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG leve ls explained 43 % of the FER HDL variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FERHDL and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FERHDL supports its role in lipid metabolism., K. Rašlová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aldosterone synthase gene (CYP11B2) is an important candidate gene region in essential hypertension. We therefore studied the association of -344T/C polymorphism of the CYP11B2 gene with the presence and severity of hypertension in a case-control study. We studied 369 individuals, of whom 213 were hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive) and 156 were healthy normotensive subjects. The -344T/C polymorphism of the CYP11B2 gene was determined using polymerase chain reaction - restriction fragment length polymorphism analysis. The distribution of genotypes in normotensive controls and hypertensive subjects were: TT 25.6 vs. 31.9 %, TC 51.9 vs. 57.3 % and CC 22.4 vs. 10.8 %. The -344T/C variant was associated with hypertension. Subjects carrying the -344T allele had a greater risk of hypertension compared to those having C allele (χ2=5.89, p<0.05). The frequency of CC genotype was significantly lower in hypertensive patients than in normotensive controls ( χ2=9.44, p<0.01). A stepwise logistic regression analysis confirmed these findings. We did not find an association of -344T/C variant with the resistance of hypertensive patients to combination therapy, but we observed an association of -344T/C polymorphism of aldosterone synthase gene with increased risk of hypertension. These results support a potential role of -344T/C CYP11B2 gene polymorphism in genetic predisposition to develop hypertension., Z. Hlubocká ... [et al.]., and Obsahuje seznam literatury
Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50±0.45 vs 2.11±0.35 μmol/l, P<0.01) and was lower comparing to Grou II (P<0.01), SC and EPC also decreased (2816±600 vs 2071±480 cells/ml resp. 194±87 to 125±67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05)., V. Teplan, I. Králová Lesná, J. Piťha, A. Mahrová, J. Racek, I. Valkovský, A. Sekerková, M. Štollová., and Obsahuje bibliografii
Each cell types or tissues contain certain “physiological” levels of R-2-hydroxyglutarate (2HG), as well as enzymes for its synthesis and degradation. 2HG accumulates in certain tumors, possessing heterozygous point mutations of isocitrate dehydrogenases IDH1 (cytosolic) or IDH2 (mitochondrial) and contributes to strengthening their malignancy by inhibiting 2-oxoglutaratedependent dioxygenases. By blocking histone de-methylation and 5-methyl-cytosine hydroxylation, 2HG maintains cancer cells de-differentiated and promotes their proliferation. However, physiological 2HG formation and formation by non-mutant IDH1/2 in cancer cells were neglected. Consequently, low levels of 2HG might play certain physiological roles. We aimed to elucidate this issue and found that compared to highest 2HG levels in hepatocellular carcinoma HepG2 cells and moderate levels in neuroblastoma SH-SY5Y cells, rat primary fibroblast contained low basal 2HG levels at early passages. These levels increased at late passage and likewise 2HG/2OG ratios dropped without growth factors and enormously increased at hypoxia, reaching levels compared to cancer HepG2 cells. Responses in SH-SY5Y cells were opposite. Moreover, external 2HG supplementation enhanced fibroblast growth. Hence, we conclude that low 2HG levels facilitate cell proliferation in primary fibroblasts, acting via hypoxia-induced factor regulations and epigenetic changes., A. Dvořák, J. Zelenka, K. Smolková, L. Vítek, P. Ježek., and Obsahuje bibliografii
1a_It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase., 2a_The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms/mmHg should be given care and intensively motivated to change their lifestyle including a change in diet and increase in physical activity., and N. Honzíková, B. Fišer.
In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeabili ty transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to prev iously published data, we found that phenformin, after a 5 min pr e-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potent ial. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca 2+ ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity., Z. Drahota ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes., J. Beneš, P. Šunka, J. Králová, J. Kašpar, P. Poučková., and Obsahuje bibliografii