Risk factors (RF) of cardiovascular diseases associated with modern lifestyle, such as stress, chronically increased blood pressure, hyperglycemia and dyslipidemia have a negative impact on the heart exposed to ischemia: their may facilitate its lethal injury (myocardial infarction) and occurrence of sudden death due to ventricular arrhythmias. On the other hand, some stressful stimuli related to RF including reactive oxygen species, transient episodes of ischemia (hypoxia), high glucose and other may play a dual role in the pathogenesis of ischemia/reperfusion (I/R) injury (IRI). Besides their deleterious effects, these factors may trigger adaptive processes in the heart resulting in greater resistance against IRI, which is also a characteristic feature of the female myocardium. However, sensitivity to ischemia is increasing with age in both genders. Current research indicates that comorbidity related to lifestyle may impair the cardiac response to acute ischemia not only by interference with pathophysiological mechanisms of IRI per se, but via suppression of intrinsic protective mechanisms in the heart and its ability to tolerate the ischemic challenges, although the role of RF has not been unequivocally proven. Moreover, even pathologically altered myocardium need not completely lose its adaptive potential. In addition, increased ischemic tolerance can be induced by the pleiotropic (independent of the primary) effects of some hypolipidemic and antidiabetic drugs, even in the diseased myocardium. This review addresses the issue of the impact of RF on cellular cardioprotective mechanisms and the possibilities to restore adaptive potential in subjects challenged with several RF. Reactivation of adaptive processes in the myocardium taking into consideration gender and age can contribute to optimalization of antiischemic therapy., T. Ravingerová, ... [et al.]., and Obsahuje seznam literatury
Common alimentary obesity frequently occurs on a polygenic basis as a typical lifestyle disorder in the developed countries. It is associated with characteristic complex metabolic changes, which are the cornerstones for future metabolic syndrome development. The aims of our study were 1) to determine the incidence of metabolic syndrome (based on the diagnostic criteria defined by the International Diabetes Federation for children and adolescents) in Czech obese children, 2) to evaluate the incidence of insulin resistance according to HOMA-IR and QUICKI homeostatic indexes in obese children with and without metabolic syndrome, and 3) to consider the diagnostic value of these indexes for the early detection of metabolic syndrome in obese children. We therefore performed anthropometric and laboratory examinations to determine the incidence of metabolic syndrome and insulin resistance in the group of 274 children with obesity (128 boys and 146 girls) aged 9-17 years. Metabolic syndrome was found in 102 subjects (37 %). On the other hand, the presence of insulin resistance according to QUICKI <0.357 was identified in 86 % and according to HOMA-IR >3.16 in 53 % of obese subjects. This HOMA-IR limit was exceeded by 70 % children in the MS(+) group, but only by 43 % children in the MS(–) group (p<0.0001). However, a relatively high incidence of insulin resistance in obese children without metabolic syndrome raises a question whether the existing diagnostic criteria do not falsely exclude some cases of metabolic syndrome. On the basis of our results we suggest to pay a preventive attention also to obese children with insulin resistance even if they do not fulfill the actual diagnostic criteria for metabolic syndrome., D. Pastucha, ... [et al.]., and Obsahuje seznam literatury
The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3-oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptorchannel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus., E. Pryazhnikov ... [et al.]., and Obsahuje seznam literatury
The aim of the present study was to investigate the distribution and density of noradrenergic nerve fibres (NNFs), content of catecholamines (CATs) and steroids in the cystic ovaries of gilts receiving DXM from middle luteal phase. Cystic status of ovaries was induced by i.m. DXM injections on days 7-21 of the estrous cycle. During the same time, gilts in the control group received saline. The ovaries were collected on predicted day 11 of the second studied estrous cycle. The cystic ovaries were supplied by more numerous NNFs than the control gonads. Moreover after DXM injections, the content of CATs and progesterone and androstendione (A4) in the cystic wall were elevated, while the levels of A4, testosterone and estradiol-17β in the cystic fluid were lowered. Our results show that in the porcine cystic ovaries, induced by DXM injections from middle phase of estrous cycle, increased the density of NNFs and level of CATs, and that it was accompanied by changes in the content of steroids. Moreover, this study is a further confirmation that the morphological and functional changes of cystic ovaries are partly dependent on phase of the estrous cycle in which the induction of the ovarian cysts was initiated., A. Kozłowska, ... [et al.]., and Obsahuje seznam literatury
Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions., A. Veselá, J. Wilhelm., and Obsahuje bibliografii
Numerous abnormalities of thyroid hormones in end-stage renal disease (ESRD) have been described. Our aim was to analyze the impact of these abnormalities on survival. In 167 hemodialyzed ESRD patients, TSH and thyroid hormone levels (T4, fT4, T3, fT3, rT3) were determined. The patients were then prospectively followed up for up to 5 years and the possible impact of any observed abnormalities on their mortality was studied. Only 16.8 % patients had all six tests within the reference range. The pattern of nonthyroidal illness syndrome was found in 56.3 %. Low T3 was particularly common (44.3 %), and clearly associated with increased 6- and 12-month mortality and decreased overall survival (log rank test, P=0.007). Independent of T3 levels (Spearman correlation, NS), increased rT3 was more frequently observed (9.9 %) than expected from the literature, and was also related to increased mortality and decreased survival (log rank test, P=0.021). Increased rT3 may be more common in ESRD patients than previously described, and together with decreased T3 it may serve as an indicator of poor prognosis in subsequent months., J. Horáček ... [et al.]., and Obsahuje seznam literatury
Chronology of three consecutive mitotic events in human preimplantation embryos was examined by time-lapse imaging. In zygotes producing well-formed and pregnancy-yielding expanded blastocysts, uniform time-patterning of cleavage clusters (c) and interphases (i) was revealed: i2=11±1, i3=15±1, i4=23±1 h / c2=15±5, c3=40±10, c4=55±15 min. Oppositely, shortened or prolonged durations of one or more cell cycles were strongly predictive of poor implantation and development. Furthermore, trichotomic mitosis was discovered in 17 % of cases - zygotes cleaved into 3 blastomeres and 2-cell embryos into 5-6 cells (instead of normal 2 and 4). During conventional clinical assessment, such embryos are indistinguishable from normal, often considered just-in-course of the next cell cycle. Only detailed time-lapse monitoring paced at 10-minute intervals had proven all these embryos to be absolutely unviable, even in rare cases when they reduced their hypercellularity to normal cell counts via cell-cell fusion. Overall, we demonstrate that timelapse embryo cleavage rating (ECR) as a standalone diagnostic procedure allows for effective identification of viable early embryos with 90 % specificity, while elimination of good-looking but unviable embryos can be assumed with a specificity of 100 %. Thus, making this non-invasive and contactless approach worth of addition to routine embryo screening in clinical IVF programs., D. Hlinka ... [et al.]., and Obsahuje seznam literatury
Decades of liver regeneration studies still left the termination phase least elucidated. However regeneration ending mechanisms are clinicaly relevant. We aimed to analyse the timing and transcriptional control of the latest phase of liver regeneration, both controversial. Male Wistar rats were subjected to 2/3 partial hepatectomy with recovery lasting from 1 to 14 days. Time-series microarray data were assessed by innovative combination of hierarchical clustering and principal component analysis and validated by real-time RT-PCR. Hierarchical clustering and principal component analysis in agreement distinguished three temporal phases of liver regeneration. We found 359 genes specifically altered during late phase regeneration. Gene enrichment analysis and manual review of microarray data suggested five pathways worth further study: PPAR signalling pathway; lipid metabolism; complement, coagulation and fibrinolytic cascades; ECM remodelling and xenobiotic biotransformation. Microarray findings pertinent for termination phase were substantiated by real-time RT-PCR. In conclusion, transcriptional profiling mapped late phase of liver regeneration beyond 5th day of recovery and revealed 5 pathways specifically acting at this time. Inclusion of longer post-surgery intervals brought improved coverage of regeneration time dynamics and is advisable for further works. Investigation into the workings of suggested pathways might prove helpful in preventing and managing liver tumours., D. Rychtrmoc, ... [et al.]., and Obsahuje seznam literatury
Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may have considerable therapeutic value. We examined the effects of acute exposure to sustained and intermittent hypoxia on rat pharyngeal dilator muscle function. Additionally, we sought to test the efficacy of antioxidant treatment in ameliorating or preventing hypoxia-related muscle dysfunction. Isometric contractile and endurance properties of isolated rat sternohyoid muscle bundles were examined at 35 °C in vitro. Muscle bundles were exposed to one of four gas treatments: hyperoxia (control), sustained hypoxia (SH), intermittent hypoxia (IH) or hypoxia/reoxygenation (HR), in the absence or presence of the superoxide scavenger – Tempol (10 mM). Stress-frequency relationship was determined in response to electrical stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Muscle performance was also assessed during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2.5 min). Compared to control, IH and HR treatments significantly decreased sternohyoid muscle force. The negative inotropic effect of the two gas protocols was similar, but both were of lesser magnitude than the effects of SH. SH, but not IH and HR, increased muscle fatigue. Tempol significantly increased sensitivity to stimulation in all muscle preparations and caused a leftward shift in the stressfrequency relationship of IH and SH treated muscles. Tempol did not ameliorate sternohyoid muscle fatigue during SH. We conclude that Tempol increases upper airway muscle sensitivity to stimulation but only modestly ameliorates respiratory muscle weakness during intermittent and sustained hypoxic conditions in vitro. Respiratory muscle fatigue during sustained hypoxia appears unrelated to oxidative stress., J. R. Skelly, ... [et al.]., and Obsahuje seznam literatury
The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90±1.08 vs. 7.48±1.12 mmol/l, p=0.013). Consequently, adjusted ΔFPG was significantly higher in the AG+GG compared to the AA group (1.48±1.51 vs. 1.02±1.33 mmol/l, p=0.022). Similar trend was observed for HbA1c levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1., Z. Schroner ... [et al.]., and Obsahuje seznam literatury