A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons., P. Kozler, O. Sobek, J. Pokorný., and Obsahuje bibliografii
Aerobic exercise showed beneficial influence on cardiovascular systems in aging, and mechanisms underlying vascular adaption remain unclear. Large-conductance Ca2+ -activated K+(BKCa) channels play critical role s in regulating cellular excitability and vascular tone. This study determin ed the effects of aerobic exercise on aging -associated functional changes in BK Ca channels in cerebrovascular myocytes, Male Wistar rats aged 20- 22 mo nths were randomly assigned to sedentary (O -SED), low training frequency (O-EXL), and high training frequency group (O -EXH). Young rats were used as control. Compared to young rats, w hole -cell BK Ca current was decreased, and amplitude of spontaneous transient outward currents were reduced. The open probability and Ca2+/voltage sensitivity of single BK Ca channel were declined in O -SED, accompanied with a reduction of tamoxifen-induced BK Ca activation; the mean open time of BK Ca channels was shortened whereas close time was prolonged. Aerobic exercise training markedly alleviated the aging-associated decline independent of training frequency. Exercise three times rather than five times weekly may be a time and cost-saving training volume required to offer bene ficial effects to offset the functional declines of BK Ca during aging., Na Li, Bailin Liu, Sharon Xiang, Lijun Shi., 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
Women with a positive history of gestational diabetes mellitus (GDM) face a higher risk of developing type 2 diabetes mellitus (T2DM) and metabolic syndrome later in life. The higher risk of these metabolic complications is closely associated with adipose tissue. In this review, the importance of adipose tissue is discussed in relation to GDM, focusing on both the quantity of fat deposits and the metabolic activity of adipose tissue in particular periods of life: neonatal age, childhood, adolescence, and pregnancy followed by nursing. Preventive measures based on body composition and lifestyle habits with special attention to the beneficial effects of breastfeeding are also discussed., D. Vejrazkova, M. Vankova, P. Lukasova, J. Vcelak, V. Cirmanova, M. Haluzik, B. Bendlova., and Obsahuje bibliografii
Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-hydroxy-DHEA, 7β-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16α-hydroxy-DHEA and plasma DHEAS, 7β-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia., L. Sosvorova, M. Mohapl, M. Hill, L. Starka, M. Bicikova, J. Vitku, R. Kanceva, J. Bestak, R. Hampl., and Obsahuje bibliografii
The local concentration of glucocorticoids is intensively regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). Human 11β-HSD 1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7β-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7α-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11β-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11β-HSD 1 in the liver., L. Máčová, L. Sosvorová, J. Vítků, M. Bičíková, M. Hill, H. Zamrazilová, B. Sedláčková, L. Stárka /., and Obsahuje bibliografii
Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial KATP opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated., M. Jašová, I. Kancirová, M. Muráriková, V. Farkašová, I. Waczulíková, T. Ravingerová, A. Ziegelhöffer, M. Ferko., and Obsahuje bibliografii
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of ou r study was to confirm the association between NYD-SP18 rs6971091 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the si multaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971091 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971091 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males., J. A. Hubacek, D. Dlouha, V. Lanska, V. Adamkova., and Obsahuje bibliografii
Self-organization in a polymer system appears when a balance is achieved between long-range repulsive and short-range attractive forces between the chemically different building blocks. Block copolymers forming supramolecular assemblies in aqueous media represent materials which are extremely useful for the construction of drug delivery systems especially for cancer applications. Such formulations suppress unwanted physicochemical properties of the encapsulated drugs, modify biodistribution of the drugs towards targeted delivery into tissue of interest and allow triggered release of the active cargo. In this review, we focus on general principles of polymer selforganization in solution, phase separation in polymer systems (driven by external stimuli, especially by changes in temperature, pH, solvent change and light) and on effects of copolymer architecture on the self-assembly process., M. Hrubý, S. K. Filippov, P. Štěpánek., and Obsahuje bibliografii
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impairment in social communication and presence of stereotyped/restricted behaviors. Children with ASD very often demonstrate co-morbid psychiatric problems, problems known to be affected by testosterone in neurotypical populations. However, there are few reports investigating relationships between testosterone and psychiatric conditions in children with ASD. The aim of this study was to determine the relationship between plasmatic levels of testosterone and behavioral/emotional problems in pre-pubertal boys with ASD. The study sample consisted of 31 pre-pubertal boys (ages 3-10) with ASD. Parents completed the Nisonger Child Behavior Rating Form (NCBRF) to assess specific behavioral/emotional problems as observed in the previous 2 months. Plasmatic testosterone levels were determined in boys according to standardized procedures. It was found that there were positive correlations between testosterone levels and the conduct problems subscale (p=0.034, rs=0.382) of NCBRF and also between testosterone levels and the hyperactive subscale (p=0.025, rs=0.402) of NCBRF. Findings in this study are in line with research conducted in the neurotypical population. This is the first large study investigating testosterone and emotional/behavioral problems in ASD and warrants further research in this field in order to clarify the etiopathogenesis of psychiatric co-morbidities and improve their treatment., A. Pivovarciova, J. Durdiakova, S. Hnilicova, D. Filcikova, D. Ostatnikova., and Obsahuje bibliografii