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
The atherogenic impact and functional capacity of LCAT was studied and discussed over a half century. This review aims to clarify the key points that may affect the final decision on whether LCAT is an anti-atherogenic or atherogenic factor. There are three main processes involving the efflux of free cholesterol from peripheral cells, LCAT action in intravascular pool where cholesterol esterification rate is under the control of HDL, LDL and VLDL subpopulations, and finally the destination of newly produced cholesteryl esters either to the catabolism in liver or to a futile cycle with apoB lipoproteins. The functionality of LCAT substantially depends on its mass together with the composition of the phospholipid bilayer as well as the saturation and the length of fatty acyls and other effectors about which we know yet nothing. Over the years, LCAT puzzle has been significantly supplemented but yet not so satisfactory as to enable how to manipulate LCAT in order to prevent cardiometabolic events. It reminds the butterfly effect when only a moderate change in the process of transformation free cholesterol to cholesteryl esters may cause a crucial turn in the intended target. On the other hand, two biomarkers - FERHDL (fractional esterification rate in HDL) and AIP [log(TG/HDL-C)] can offer a benefit to identify the risk of cardiovascular disease (CVD). They both reflect the rate of cholesterol esterification by LCAT and the composition of lipoprotein subpopulations that controls this rate. In clinical practice, AIP can be calculated from the routine lipid profile with help of AIP calculator www.biomed.cas.cz/fgu/aip/calculator.php., M. Dobiášová., and Obsahuje bibliografii
a1_In this study we compared several parameters characterizing differences in the lipoprotein profile between members of families with a positive or negative family history of coronary artery disease (CAD). In addition to regular parameters such as the body mass index (BMI), total plasma cholesterol (TC), low density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we estimated the fractional esterification rate of cholesterol in apoB lipoprotein-depleted plasma (FERHDL) which reflects HDL and LDL particle size distribution. A prevalence of smaller particles for the atherogenic profile of plasma lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index of plasma (AIP) was calculated and correlated with other parameters. The cohort in the study consisted of 29 young (< 54 years old) male survivors of myocardial infarction (MI), their spouses and at least one offspring (MI group; n=116). The control group consisted of 29 apparently healthy men with no family history of premature CAD in three generations, their spouses and at least one offspring (control group; n=124). MI families had significantly higher BMI than the controls, with the exception of spouses. Plasma TC did not significantly differ between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C had MI survivors only, while lower HDL-C had both MI survivors and their spouses compared to the controls. FERHDL was significantly higher in all the MI subgroups (probands 25.85±1.22, spouses 21.55±2.05, their daughters 16.93±1.18 and sons 19.05±1.33 %/h) compared to their respective controls (men 20.80±1.52, spouses 14.70±0.98, daughters 13.23±0.74, sons 15.7±0.76 %/h, p<0.01 to p<0.05). Log (TG/HDL-C) ranged from negative values in control subjects to positive values in MI probands., a2_High correlation between FERHDL and Log (TG/HDL-C) (r = 0.80, p<0.0001) confirmed close interactions among TG, HDL-C and cholesterol esterification rate. The finding of significantly higher values of FERHDL and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein phenotype in members of MI families. The possibility that, in addition to genetic factors, a shared environment likely contributes to the familial aggregation of CAD risk factors is supported by a significant correlation of the FERHDL values within spousal pairs (control pairs: r = 0.51 p<0.01, MI pairs: r = 0.41 p<0.05)., M. Dobiášová, K. Rašlová,H. Rauchová, B. Vohnout, K. Ptáčková, J. Frohlich., and Obsahuje bibliografii
Attention deficit/hyperactivity disorder (ADHD) is associated with complex neurocardiac integrity. We aimed to study heart rate time asymmetry as a nonlinear qualitative feature of heart rate variability indicating complexity of cardiac autonomic control at rest and in response to physiological stress (orthostasis) in children suffering from ADHD. Twenty boys with ADHD and 20 healthy age-matched boys at the age of 8 to 12 years were examined. The continuous ECG was recorded in a supine position and during postural change from lying to standing (orthostasis). Time irreversibility indices - Porta’s (P%), Guzik’s (G%) and Ehlers’ (E) - were evaluated. Our analysis showed significantly reduced heart rate asymmetry indices at rest (P%: 49.8 % vs. 52.2 %; G%: 50.2 % vs. 53.2 %; p<0.02), and in response to orthostatic load (P%: 52.4 % vs. 54.5 %, G%: 52.3 % vs. 54.5 %; p<0.05) associated with tachycardia in ADHD children compared to controls. Concluding, our study firstly revealed the altered heart rate asymmetry pattern in children suffering from ADHD at rest as well as in response to posture change from lying to standing (orthostasis). These findings might reflect an abnormal complex cardiac regulatory system as a potential mechanism leading to later cardiac adverse outcomes in ADHD., I. Tonhajzerová, I. Ondrejka, I. Farský, Z. Višňovcová, M. Mešťaník, M. Javorka, A. Jurko Jr., A. Čalkovská., and Obsahuje bibliografii
The reports of analgesic effects of benzodiazepines are inconsistent. There is evidence of a hyperalgesic effect induced by activation of supraspinal GABAA receptors and an antinociceptive effect induced by activation of receptors located in the spinal cord (dorsal horns). The aim of the study was to discover whether the systemic administration of a benzodiazepine agent alprazolam increases the systemic analgesic efficacy of non-opioid analgesic ibuprofen. Experimental studies combining these agents have not yet been published. We used three experimental methods - writhing test (with acetic acid), tail-flick test and plantar test to assess analgesic action. The drugs were administered orally. Augmentation of the analgesic effect of ibuprofen by alprazolam was proved for the writhing test at a dose of 30 mg/kg of ibuprofen and alprazolam 1 mg/kg. The reaction time of the combination was significantly prolonged in comparison with ibuprofen alone. The results of the tail-flick test and plantar test were negative. The effect of ibuprofen was not enhanced by alprazolam in tests of acute thermal pain. Our results have demonstrated that the analgesic action of ibuprofen is only weakly enhanced by alprazolam., T. Doležal, M. Kršiak., 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
Baroreflex control of heart rate was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats that were subjected to chronic dietary sodium chloride loading (for 4 weeks) either in youth or only in adulthood, i.e. from the age of 4 or 12 weeks. Using phenylephrine administration to pentobarbital-anesthetized male rats we have demonstrated the decreased baroreflex sensitivity (lower slope for reflex bradycardia) in young prehypertensive SS/Jr rats fed a low-salt diet as compared to age-matched SR/Jr animals. High salt intake further suppressed baroreflex sensitivity in young SS/Jr but not in SR/Jr rats. Baroreflex sensitivity decreased with age in SR/Jr rats, whereas it increased in SS/Jr rats fed a low-salt diet. Thus at the age of 16 weeks baroreflex sensitivity was much higher in SS/Jr than in SR/Jr animals. High salt intake lowered baroreflex sensitivity even in adult SS/Jr rats without affecting it in adult SR/Jr rats. Nevertheless, baroreflex sensitivity was significantly lower in young SS/Jr rats with a severe salt hypertension than in adult ones with a moderate blood pressure elevation. It is concluded that the alterations of baroreflex sensitivity in young inbred SS/Jr rats (including the response to high salt intake) are similar to those described earlier for outbred salt-sensitive Dahl rats. We have, however, disclosed contrasting age-dependent changes of baroreflex sensitivity in both inbred substrains of Dahl rats., J. Nedvídek, J. Zicha., and Obsahuje bibliografii
Sympathetic overactivity and low parasympathetic activity is an autonomic dysfunction (AD) which enhances cardiac mortality. In the present study, the impact of AD on the mortality in patients after myocardial infarction was evaluated. We examined 162 patients 7-21 days after myocardial infarction, 20 patients of whom died in the course of two years. Baroreflex sensitivity (BRS) was estimated by spectral analysis of spontaneous fluctuations of systolic blood pressure and cardiac intervals (Finapres, 5 min recording, controlled breathing 20/min). The heart rate variability was determined as SDNN index (mean of standard deviations of RR intervals for all 5-min segments of 24-hour ECG recordings). BRS < 3 ms/mm Hg and/or SDNN index < 30 ms were taken as markers of AD. The risk stratification was performed according to the number of the following standard risk factors of increased risk of cardiac mortality (SRF): ejection fraction < 40 %, positive late potentials and the presence of ventricular extrasystoles > 10/h. No difference in mortality between patients with AD (4 %) and without AD (4.5 %) was found in 92 patients without SRF, the mortality in 6 patients with three SRF was 66.6 %. Five of these patients had AD. Out of 64 patients with one or two SRF, 32 had AD. The mortality of patients without AD was 6.25 % and 31.2 % of those with AD (p<0.025). It is concluded that AD enhanced two-years mortality five fold in our patients with moderate risks., N. Honzíková, B. Semrád, B. Fišer, R. Lábrová., and Obsahuje bibliografii
At present, there are insufficient information about baroreflex sensitivity (BRS) and factors that determine BRS in premature newborns. The objective of this study was to determine the relationship between BRS and the characteristics that reflecting the intrauterine development (gestational age and birth weight), as well as postnatal development (postconception age and the actual weight of the child at the time of measurement). We examined 57 premature infants, who were divided into groups according to gestational age and postconception age as well as birth weight, and weight at the time of measurement. Continuous and noninvasive registration of peripheral blood pressure (BP) was perf ormed in every child within 2-5 m in under standard conditions using a Portapres (FMS) device. The results showed a close correlation of baroreflex sensitivity, heart rate and respiratory rate with gestational age, postconception age, birth weight and actual weight at the time of measureme nt premature newborns. An increase in the characteristics (ages and weights) resulted in increased BRS and diastolic arterial pressure (DAP), and in decreased heart and respiratory rates. Baroreflex sensitivity in the first week was in the group of very premature newborns the lowest (4.11 ms/mmHg) and in the light premature newborns was almost double (8.12 ms/mmHg). BRS increases gradually in relation to postnatal (chronological) and to postconception age as well as to birth and actual weight. The multifact or analysis of BRS identified birth weight and postconception age as the best BRS predictors. The two independent variables together explained 40 % of interindividual BRS variability., K. Haskova, M. Javorka, B. Czippelova, M. Zibolen, K. Javorka., and Obsahuje bibliografii