We measured plasma concentrations, adipose tissue and placental mRNA expression of hepatokines fetuin A, fetuin B and fibroblast growth factor 21 (FGF21) in 12 healthy pregnant women (P group), 12 pregnant women with gestational diabetes (GDM) and 10 healthy non-pregnant women (N group) to explore their potential role in the etiopathogenesis of GDM. GDM and P group had comparable BMI, C-reactive protein (CRP) and glycated hemoglobin levels while IL-10 and TNF-α levels were higher in GDM group. Fetuin A and fetuin B levels were higher in pregnancy as compared to N group and decreased after delivery with no apparent influence of GDM. In contrast, the pattern of changes of circulating FGF21 levels differed between GDM and P group. Fetuin A concentrations positively correlated with CRP, TNF-α mRNA expression in adipose tissue and IL-6 mRNA expression in placenta. Fetuin B positively correlated with CRP. FGF21 levels correlated positively with IFN-γ mRNA in adipose tissue and inversely with IL-8 mRNA in the placenta. Taken together, fetuin A and fetuin B levels were increased during pregnancy regardless of the presence of GDM. In contrast, FGF21 patterns differed between healthy pregnant women and GDM patients suggesting a possible role of this hepatokine in the etiopathogenesis of GDM., P. Šimják, A. Cinkajzlová, K. Anderlová, J. Kloučková, H. Kratochvílová, Z. Lacinová, P. Kaválková, H. Krejčí, M. Mráz, A. Pařízek, M. Kršek, M. Haluzík., and Obsahuje bibliografii
Tissue differentiation and proliferation throughout fetal development interconnect with changes in the oxidative phosphorylation system (OXPHOS) on the cellular level. Reevaluation of the expression data revealed a significant increase in COX4 and MTATP6 liver transcription levels after the 22nd gestational week (GW) which inspired us to characterize its functional impact. Specific activities of cytochrome c oxidase (COX), citrate synthase (CS), succinate-coenzyme Q reductase (SQR) and mtDNA determined by spectrophotometry and RT-PCR were studied in a set of 25 liver and 18 skeletal muscle samples at 13th to 29th GW. Additionally, liver hematopoiesis (LH) was surveyed by light microscopy. The mtDNA content positively correlated with the gestational age only in the liver. The activities of COX, CS and SQR in both liver and muscle isolated mitochondria significantly decreased after the 22nd GW in comparison with earlier GW. A continuous decline of LH, not correlating with the documented OXPHOS-specific activities, was observed from the 14th to the 24th GW indicating their exclusive reflection of liver tissue processes. Two apparently contradictory processes of increasing mtDNA transcription and decreasing OXPHOS-specific activities seem to be indispensable for rapid postnatal adaptation to high energy demands. The inadequate capacity of mitochondrial energy production may be an important factor in the mortality of children born before the critical developmental point of the 22nd GW., H. Kolarová, J. Křížová, M. Hůlková, H. Hansiková, H. Hůlková, V. Smid, J. Zeman, T. Honzík, M. Tesarová., and Seznam literatury
The aim of this study was to measure expression levels of microRNAs (miRNAs) (miRNA-1, -15b and -21) in the rat myocardium after a single dose of ionizing radiation (6-7 Gy/min, total 25 Gy). The rats were treated with selected drugs (Atorvastatin, acetylsalicylic acid (ASA), Tadalafil, Enbrel) for six weeks after irradiation. MiRNAs levels were measured by RT-qPCR. Irradiation down-regulated miRNA-1 in irradiated hearts. In Tadalafil- and Atorvastatin-treated groups, miRNA-1 expression levels were further decreased compared with irradiated controls. However, Enbrel increased miRNA-1 level in irradiated hearts similarly to that in non-irradiated untreated group. Increase of miRNA-15b is pro-apoptotic in relationship with ischemia. Irradiation caused down-regulation of miRNA-15b. Administration of ASA in the irradiated group resulted in the increase of miRNA-15b expression compared to non-treated controls without irradiation. After Enbrel administration, miRNA-15b levels were overexpressed compared to non-treated normal group. MiRNA-21 belongs to the most markedly up-regulated miRNAs in response to cardiogenic stress. MiRNA-21 was increased nearly 2-fold compared to non-treated hearts whereas Tadalafil reduced miRNA-21 levels (about 40 %). Our study suggests that Enbrel and Tadalafil changed miRNAs expression values of the irradiated rats to the values of nonirradiated controls, thus they might be helpful in mitigation of radiation-induced toxicity., B. Kura, C. Yin, K. Frimmel, J. Krizak, L. Okruhlicova, R. C. Kukreja, J. Slezak., and Obsahuje bibliografii
Smoking during pregnancy presents health risks for both the mother and her child. In this study we followed changes in the production of steroid hormones in pregnant smokers. We focused on changes in steroidogenesis in the blood of mothers in their 37th week of pregnancy and in mixed cord blood from their newborns. The study included 88 healthy women with physiological pregnancies (17 active smokers and 71 nonsmokers). We separately analyzed hormonal changes associated with smoking according to the sex of newborns. In women with male fetuses, we found higher levels of serum cortisone, dehydroepiandrosterone (DHEA), 7α-OH-DHEA, 17-OH pregnenolone, testosterone, and androstenedione in smokers at the 37th week compared to non-smokers. In women with female fetuses, we found lower serum levels of 7β-OH-DHEA and higher androstenedione in smokers at the 37th week. We found significantly higher levels of testosterone in newborn males of smokers and higher levels of 7α-OH-DHEA in female newborns of smokers. Smoking during pregnancy induces changes in the production of steroids in both the mother and her child. These changes are different for different fetal sexes, with more pronounced changes in mothers carrying male newborns as well as in the newborn males themselves., K. Adamcová, L. Kolátorová, T. Chlupáčová, M. Šimková, H. Jandíková, A. Pařízek, L. Stárka, M. Dušková., and Obsahuje bibliografii
The lipid molecule, lysophosphatidylinositol (LPI), is hypothesis ed to form part of a novel lipid signalling system that involves the G protein- coupled receptor GPR55 and distinct in tracellular signalling cascades in endothelial cells. This work aimed to study the possible mechanisms involved in LPI -evoked cytosolic Ca 2+ mobilization in human brain microvascular endothelial cells. Changes in intracellular Ca 2+ concentrations were meas ured using cell population Ca 2+ assay. LPI evoked biphasic elevation of intracellular calcium concentration, a rapid phase and a sustained phase. The rapid phase was attenuated by the inhibitor of PLC (U 73122), inhibitor of IP 3 receptors, 2 -APB and the de pletor of endoplasmic reticulum Ca 2+ store, thapsigargin. The sustained phase, on the other hand, was enhanced by U 73122 and abolished by the RhoA kinase inhibitor, Y -27632. In conclusion, the Ca 2+ signal evoked by LPI is characterised by a rapid phase of Ca 2+ release from the endoplasmic reticulum, and requires activation of the PLC -IP 3 signalling pathway. The sustained phase mainly depends on RhoA kinase activation. LPI acts as novel lipid signalling molecule in endothelial cells, and elevation of cytosolic Ca 2+ triggered by it may present an important intracellular message required in gene expression and controlling of vascular tone., Y. M. Al Suleimani, C. R. Hiley., and Obsahuje bibliografii
Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178±14 μm and 171±9 μm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5±1.9 % vs. 12.9±0.9 %), which resulted in a reduced lumen size (144±9 μm vs. 167±12 μm), thicker vascular wall (22.6±1.8 μm vs. 17.4±1.6 μm) and decreased tangential wall stress (16.8±1.1 kPa vs. 20.5±1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8±2.5 % vs. 5.7±1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall., A. Monori-Kiss, F. Kiss, J. M. Restifo, E. Monos, G. L. Nadasy., and Obsahuje bibliografii
Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission., I. Cundrle Jr., P. Suk, V. Sramek, Z. Lacinova, M. Haluzik., and Obsahuje bibliografii
Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1±10.3 to 32.3±10.9 to 38.1±10.3 μg.ml-1, p=0.015; from 0.52±0.09 to 0.58±0.06 to 0.62±0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r 2=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p<0.001, r 2=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients., I. Trojová, M. Kozarová, D. Petrasová, Z. Malachovská, I. Paranicová, P. Joppa, R. Tkacová., and Seznam literatury
The effect of β3-adrenoceptor (β3-AR) agonists on adipocytes treated or not tr eated with signaling modulators has not been sufficiently elucidated. Using rat epididymal adipocytes (adipocytes) labeled with [ 32 P]orthophosphate, we found that treatment with the selective β3-AR agonist CL316243 (CL; 1 μ M) induces phosphatidylinositol (PI) 3,4,5-triphosphate (PI[3,4,5]P3) production and that this response is inhibited by adenosine deaminase (ADA, an adenosine -degrading enzyme; 2 U/ml), pertussis toxin (PTX, an inactivator of inhibitory guanine-nucleotide-binding protein; 1 μ g/ml), or wortmannin (WT, a PI -kinase inhibitor; 3 μ M). The results showed that CL induced PI(3,4,5)P 3 production in intact adipocytes and that this production was affected by signaling modulators. Taken together, our findings indicate that CL produces PI(3,4,5)P3 in an ADA-sensitive, PTX-sensitive, or WT-sensitive manner and will advance understanding of the effect of β3-AR agonists on adipocytes., Y. Ohsaka, Y. Nomura., and Obsahuje bibliografii
There exists no examination of what is the minimum anti - hypertensive threshold intensity for isometric exercise training. Twenty two normotensive participants were randomly assigned to training intensities at either 5 % or 10 % of their maximal contraction. Twenty participants completed the study. Clinical meaningful, but not statistically significant, reductions in systolic blood pressure were observed in both 5 % and 10 % groups -4.04 mm Hg (95 % CI -8.67 to +0.59, p=0.08) and -5.62 mm Hg (95 % CI -11.5 to +0.29, p=0.06) respectively after 6 weeks training. No diastolic blood pressure reductions were observed in either 5 % -0.97 mm Hg (95 % CI -2.56 to +0.62, p=0.20) or 10 % MVC +1.8 mm Hg (95 % CI -1.29 to +4.89, p=0.22) groups respectively after training. In those unable to complete isometr ic exercise at the traditional 30 % intensity, our results suggest there is no difference between 5 and 10 % groups and based on the principle of regression to the mean, this could mean both interventions induce a similar placebo-effect., N. C. L. Hess, D. J. Carlson, J. D. Inder, E. Jesulola, J. R. McFarlane, N. A. Smart., and Obsahuje bibliografii