The cytoskeleton plays a key role in cellular proliferation, cellshape maintenance and internal cellular organization. Cells are highly sensitive to changes in microgravity, which can induce alterations in the distribution of the cytoskeletal and cell proliferation. This study aimed to assess the effects of simulated microgravity (SMG) on the proliferation and expression of major cell cycle-related regulators and cytoskeletal proteins in human umbilical cord mesenchymal stem cells (hucMSCs). A WST-1 assay showed that the proliferation of SMG-exposed hucMSCs was lower than a control group. Furthermore, flow cytometry analysis demonstrated that the percentage of SMG-exposed hucMSCs in the G0/G1 phase was higher than the control group. A western blot analysis revealed there was a downregulation of cyclin A1 and A2 expression in SMG-exposed hucMSCs as well. The expression of cyclin-dependent kinase 4 (cdk4) and 6 (cdk6) were also observed to be reduced in the SMG-exposed hucMSCs. The total nuclear intensity of SMG-exposed hucMSCs was also lower than the control group. However, there were no differences in the nuclear area or nuclear-shape value of hucMSCs from the SMG and control groups. A western blot and quantitative RT-PCR analysis showed that SMG-exposed hucMSCs experienced a downregulation of β-actin and α-tubulin compared to the control group. SMG generated the reorganization of microtubules and microfilaments in hucMSCs. Our study supports the idea that the downregulation of major cell cycle-related proteins and cytoskeletal proteins results in the remodeling of the cytoskeleton and the proliferation of hucMSCs., Ho Nguyen Quynh Chi, Hoang Nghia Son, Doan Chinh Chung, Le Dinh Huan, Tran Hong Diem, Le Thanh Long., and Obsahuje bibliografii
Ghrelin is a gut peptide produced mainly by stomach, well known to induce appetite stimulatory actions. Obestatin, a recently identified peptide derived from preproghrelin, was initially described to antagonize stimulatory effect of ghrelin on food intake. The postprandial response of obestatin and its relationship with ghrelin in humans remains unknown. We therefore investigated the postprandial response of obestatin and total ghrelin, acyl and desacyl ghrelin and neuropeptide Y (NPY) to a high-carbohydrate breakfast (1 604 kJ) in eight healthy women (age: 24.2±0.82 years; BMI 21.6±0.61 kg/m2). Blood samples were collected before the meal, and 30, 60, 90, 120 and 150 min after the breakfast consumption. Postprandial plasma obestatin concentrations significantly decreased compared with preprandial levels as well as total ghrelin concentrations and reached the lowest values 90 and 120 min after the meal consumption, respectively (p 0.05). Plasma acyl and desacyl ghrelin concentrations decreased after the breakfast and reached lowest values in 30 and 60 min, respectively (p<0.05). Plasma NPY concentrations were lower than preprandial levels 90 and 150 min after consuming breakfast (p<0.05). In conclusion, we demonstrated in healthy young women that plasma obestatin concentrations decrease similarly to ghrelin after a high-carbohydrate breakfast., D. Sedláčková, I. Dostálová, V. Hainer, L. Beranová, H. Kvasničková, M. Hill, M. Haluzík, J. Nedvídková., and Obsahuje bibliografii a bibliografické odkazy
a1_Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol- lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection ag ainst myocardial ischemia- reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff- perfused hearts of healthy control (C) and diabetic- hypercholesterolemic (D-H; strept ozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium stai ning). Postischemic recovery of left ventricular developed pressu re (LVDP) in animals with D-H was improved by simvastatin therapy (62.7±18.2 % of preischemic values vs. 30.3±5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperf usion. Likewise, simvastatin shortened the duration of ventri cular tachycardia (10.2±8.1 s and 57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C., a2_The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals., A. Adameová, A. Harčárová, J. Matejíková, D. Pancza, M. Kuželová, S. Čarnická, P. Švec, M. Barteková, J. Styk, T. Ravingerová., and Obsahuje bibliografii
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) have been proven to reduce effectively cholesterol level and morbidity and mortality in patients with coronary heart disease and/or dyslipoproteinemia. Statins inhibit synthesis of mevalonate, a precursor of both cholesterol and coenzyme Q (CoQ). Inhibited biosynthesis of CoQ may be involved in some undesirable actions of statins. We investigated the effect of simvastatin on tissue CoQ concentrations in the rat model of NO-deficient hypertension induced by chronic L-NAME administration. Male Wistar rats were treated daily for 6 weeks with L-NAME (40 mg/kg) or with simvastatin (10 mg/kg), another group received simultaneously L-NAME and simvastatin in the same doses. Coenzyme Q9 and Q10 concentrations were analyzed by high performance liquid chromatography. L-NAME and simvastatin alone had no effect on CoQ concentrations. However, simultaneous application of L-NAME and simvastatin significantly decreased concentrations of both CoQ homologues in the left ventricle and slightly decreased CoQ9 concentration in the skeletal muscle. No effect was observed on CoQ level in the liver and brain. We conclude that the administration of simvastatin under the condition of NO-deficiency reduced the level of CoQ in the heart and skeletal muscle what may participate in adverse effect of statins under certain clinical conditions., J. Kucharská, A. Gvozdjáková, F. Šimko., and Obsahuje bibliografii
Sirtuin 1 (SIRT1) is involved in important biological processes such as energy metabolism and regulatory functions of the cell cycle, apoptosis, and inflammation. Our previous studies have shown hepatoprotective effect of polyphenolic compound resveratrol, which is also an activator of SIRT1. Therefore, the aim of our present study was to clarify the role of SIRT1 in process of hepatoprotection in animal model of drug-induced liver damage. Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by single dose of acetaminophen (APAP). Some rats and hepatocytes were treated by resveratrol or synthetic selective activator of sirtuin 1 (CAY10591). The degree of hepatotoxicity, the activity and expression of the SIRT1 were determined by biochemical, histological and molecular-biological assessments of gained samples (plasma, liver tissue, culture media and hepatocytes). Resveratrol and CAY attenuated APAP-induced hepatotoxicity in vivo and in vitro. Moreover, both drugs enhanced APAPreduced SIRT1 activity. Our results show that modulation of the SIRT1 activity plays a role in hepatoprotection. Synthetic activators of SIRT1 would help in understanding the role of SIRT1 and are therefore a major boost towards the search for specific treatment of liver disease., L. Wojnarová, N. Kutinová Canová, H. Farghali, T. Kučera., and Obsahuje bibliografii
Fourier spectral analysis of fore arm skin laser Doppler flowmetry (LDF) signal was performed in fifteen hypercholesterolemic patients (HP), without clinically manifest arterial diseases, and in fifteen age-matched healthy control subjects (CS), in order to investigate skin blood flowmotion (SBF). The LDF frequency intervals studied were: 0.01-1.6 Hz total spectrum, as well as 0.01-0.02 Hz (endothelial), 0.02-0. 06 Hz (sympathetic), 0.06-0.2 Hz (myogenic), 0.2-0.6 Hz (respiratory) and 0.6-1.6 Hz (cardiac). Skin microvascular reactivity (MVR ) to acetylcholine (ACh) and to sodium nitroprusside (SNP) iontophoresis was also investigated. HP showed a lower post-ACh increase in power spectral density (PSD) of the 0.01-0.02 Hz SBF subinterval compared to CS (1.80±1.73 PU 2 /Hz vs 3.59±1.78 PU 2 /Hz, respectively; p<0.005), while they did not differ in MVR from CS. In eleven HP the 0.01-0.02 Hz SBF subinterval showed a higher post-ACh PSD increase near to the statistical significance after 10 weeks of rosuvastatin therapy (10 mg/day) compared to pretreatment test (3.04±2.95 PU 2 /Hz vs 1.91±1.94 PU 2 /Hz; p=0.07). The blunted post-ACh increase in PSD of the 0.01-0.02 Hz SBF subinterval in HP suggests a skin endothelial dysfunction in these patients. This SBF abnormality showed a tendency to improve after rosuvastatin therapy in eleven treated patients., M. Rossi ... [et al.]., and Obsahuje seznam literatury
Sleep apnoea (SA) is common in patients with hypertension. Nowadays, limited data on the prevalence of SA in nocturnal hypertension (NH) exist. Therefore, we studied the occurrence of SA in Czech patients and its association with 24-h ambulatory blood pressure monitoring (ABPM), breathing disturbances in sleep, anthropometric data, Mallampati score and Epworth sleepiness scale (ESS) using the Apnea Link device. Undiagnosed SA was found in 72.9 % patients (29.3 % mild, 26.6 % moderate, 17.0 % severe) of 188 patients with NH measured by ABPM. The median of the apnoea-hypopnoea index (AHI) was 12.0 (25th-75th percentile 5.0-23.8). Moderate/severe SA (AHI≥15) was associated with BMI, waist circumference, mean night saturation (SpO2), t90, oxygen desaturation index (ODI), ESS (daytime BP only) (p≤0.032), but not ABPM parameters and Mallampati score (p>0.09). A likelihood of moderate/severe SA was enhanced by ODI>14.5 events/h (odds ratio=57.49, 95 % CI=22.79-145.01), t90>6.5 % (8.07, 4.09-15.92), mean night SpO2<93.5 % (3.55, 1.92-6.59), BMI>29.05 kg/m2 (6.22, 3.10-12.49), circum waist>105.5 cm (3.73, 1.57-8.83), but not by any ABPM parameter. In conclusion, a high incidence of SA (72.9 %) was observed in Czech patients with NH. SA severity was associated with body characteristics and oxygenation parameters, but not with ABMP parameters and Mallampati score., M. Hobzová, K. Šonka, M. Pretl, J. Václavík, E. Kriegová, M. Radvanský, J. Zapletalová, M. Placková, V. Kolek., and Seznam literatury
The high rate of occurrence of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD) prompted the idea that structural and neurotransmitter changes might give rise to specific sleep pattern abnormalities. The aim of this study was to evaluate the microstructure of sleep in children with ADHD who had no polysomnographically diagnosed sleep disorder, had never been treated for ADHD, and were free from any psychiatric comorbidity. Participants were 14 patients with ADHD (12 boys and 2 girls aged 7-12 years, mean age 9.6±1.6). ADHD was diagnosed according to DSM-IV criteria (Diagnostic and statistical manual of mental disorders). Psychiatric comorbidities were ruled out by detailed psychiatric examination. The patients underwent two consecutive overnight video-polysomnographic (PSG) recordings, with the sleep microstructure (cyclic alternating pattern – CAP) scoring during the second night. The data were compared with age- and sex-matched controls. Sleep microstructure analysis using CAP revealed no significant differences between the ADHD group and the controls in any of the parameters under study. In conclusions, no ADHD-specific alterations were found in the sleep microstructure., I. Příhodová ... [et al.]., and Obsahuje seznam literatury
Slow breathing training reduces resting blood pressure, probably by modifying central autonomic control, but evidence for this is lacking. The pressor response to static handgr ip exercise is a measure of autonomic control and the aim of this study was to determine whether slow breathing training modulates the pressor responses to exercise of untrained muscles. Twenty hypertensive patients trained for 8 weeks, 10 with unloaded slow breathing (Unloaded) and 10 breathing against an inspiratory load of 20 cm H 2 O (Loaded). Ten subjects were untrained controls. Subjects performed a 2 min handgrip pressor test (30 % MVC) pre - and post- training, and blood pressure and heart rate (HR) were measured before the contraction, at the end and following 2 min recovery. Resting systolic (sBP) and HR were reduced as a result of tra ining, as reported previously. After training there was both a smaller pressor response to hand grip exercise and a more rapid recovery of sBP and HR compared to pre -training. There were no changes in the Controls and no differences between the Unloaded and Loaded groups. Combining the two training groups, the sBP response to handgrip exercise after training was reduced by 10 mm Hg (95 % CI: - 7, - 13) and HR by 5 bpm (95 % CI: - 4, - 6), all p<0.05. These results are consistent with slow breathing training modifying central mechanisms regulating cardiovascular function., C. U. Jones, B. Sangthong, O. Pachirat, D. A. Jones., and Obsahuje bibliografii
We have investigated slow inactivation in a rat axonal K+ channel, the I channel. Using voltage steps to potentials between -70 mV and +80 mV, from a holding potential of -100 mV, we observed a marked slowing of inactivation at positive potentials: the time constant was 4.5±0.4 s at -40 mV (mean ± S.E.M.), increasing to 14.7±2.0 s at +40 mV. Slowed inactivation at positive potentials is not consistent with published descriptions of C-type inactivation, but can be explained by models in which inactivation is preferentially from closed states (which have been developed for Kv2.1 and some Ca2+ channels). We tested two predictions of preferential closed-state models: inactivation should be more rapid during a train of brief pulses than during a long pulse to the same potential, and the cumulative inactivation measured with paired pulses should be greater than the inactivation at the same time during a continuous pulse. The I channel does not behave according to these predictions, indicating that preferential closed-state inactivation does not explain the slowing of inactivation we observe at positive potentials. Inactivation of the I channel therefore differs both from C-type inactivation, as presently understood, and from the inactivation of Kv2.1., A. Babes, E. Lörinczi, V. Ristoiu, M.L. Flonta, G. Reid., and Obsahuje bibliografii