We performed measurement of mechanical atri oventricular conduction time intervals in human fetuses assessed by Doppler echocardiography and provided re ference values. We found that atrioventricular cond uction time interval was prolonged with gestational age and decreased with increasing fetal heart rate. No correlation between gestat ional age and heart rate was found. Using normal limits established by this study, mechanical atrioventricular interval >135 ms in the 20th week and/or >145 ms in the 26th week of gestation could be suspected of having the first-degree AV block. We compared reference values with fetuses of mothers with anti-SSA Ro/SSB La autoantibodies, being in risk of isolated congenital heart block development. One of 21 fetuses of mothers with positive autoantibodies was affected by prolonged atrioventricular interval according to the established limits, with sinus rhythm after the birth., V. Tomek ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male SpragueDawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action., P. Gál ... [et al.]., and Obsahuje seznam literatury
Cardiovascular prosthetic bypass grafts do not endothelialize spontaneously in humans, and so they pose a thrombotic risk. Seeding with cells improves thei r performance, particularly in small-caliber applications. Knitted tubular polyethylene- terephthalate (PET) vascular pros theses (6 mm) with commercial type I collagen (PET/Co) were modified in the lumen by the adsorption of laminin (LM), by coating with a fibrin network (Fb) or a combination of Fb and fibronectin (Fb/FN). Primary human saphenous vein endothelial cells were seeded (1.50 × 10 5 /cm 2 ), cultured for 72 h and exposed to laminar shear stress 15 dyn/cm 2 for 40 and 120 min. The control static grafts were excluded from shearing. The cell adherence after 4 h on PET/Co, PET/Co +LM, PET/Co +Fb and PET/Co +Fb/ FN was 22 %, 30 %, 19 % and 27 % of seeding, respectively. Comp ared to the static grafts, the cell density on PET/Co and PET/Co +LM dropped to 61 % and 50 %, respectively, after 120 min of flow. The cells on PET/Co +Fb and PET/Co +Fb/FN did not show any detachment during 2 h of shear stress. Pre-coating the clinically-used PET/Co vascular prosthesis with LM or Fb/FN adhesive protein assemblies promotes the adherence of endothelium. Cell retention under flow is improved particularly on fibrin-containing (Fb and Fb/FN) surfaces., J. Chlupáč ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
We performed a systematic study to check whether neurons in the area TE (the anterior part of inferotemporal cortex) in rhesus monkey, regarded as the last stage of the ventral visual pathway, could be modulated by auditory stimuli. Two fixating rhesus monkeys were presented with visual, auditory or combined audiovisual stimuli while neuronal responses were recorded. We have found that the visually sensitive neurons are also modulated by audiovisual stimuli. This modulation is manifested as the change of response rate. Our results have shown also that the visual neurons were responsive to the sole auditory stimuli. Therefore, the concept of inferotemporal cortex unimodality in information processing should be re-evaluated., P. Kaposvári ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
Visfatin was originally described as an adipokine with insulin mimetic effects. Recently, it was found that visfatin is identical with the Nampt (nicotinamide phosphoribosyltransferase) gene that codes for an intra- and extracellular NAD biosynthetic enzyme and is predominantly expressed outside the adipose tissue. In the current study, we found strong protein and mRNA expression of visfatin in rat heart, liver, kidney, and muscle, while the expression of visfatin in visceral fat was significantly lower and undetectable in subcutaneous fat. The insulin-mimetic effects of visfatin (extracellular form of Nampt or eNampt) are controversial and even less is known about autocrine effects of visfatin (intracellular form of Nampt or iNampt). Since liver plays a major role in glucose metabolism, we studied visfatin effects on insulin-stimulated cellular glucose uptake in Fao rat hepatocytes using RNA interference (RNAi). RNAi-mediated downregulation of visfatin expression in Fao cells was associated with significantly reduced NAD biosynthesis (0.3±0.01 vs. 0.5±0.01 mmol/h/g, P<0.05) and with significantly decreased incremental glucose uptake after stimulation with insulin when compared to controls with normal expression of visfatin (0.6±0.2 vs. 2.2±0.5 nnmol/g/2 h, P=0.02). These results provide evidence that visfatin exhibits important autocrine effects on sensitivity of liver cells to insulin action possibly through its effects on NAD biosynthesis., V. Škop ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We present data supporting the hypothesis that the lysosomalautophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in “starving” (amino-acid poor medium) or “fed” (serum-supplemented medium) conditions, VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern., V. Škop ... [et al.]., and Obsahuje seznam literatury
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