No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats., P. D. Broulík, V. Tesař, T. Zima, M. Jirsa., and Obsahuje bibliografii
The normal retinal development is interrupted by preterm birth and a retinopathy of prematurity (ROP) may develop as its consequence. ROP is characterised by aberrant vessel formation in the retina as a response to multiple risk factors influencing the process of retinal angiogenesis. Insulin-like growth factor I (IGF -1) and vascular endothelial growth factor (VEGF) play an important role in the process of normal retinal vascularisation. Insufficient nutrition during the first 4 postnatal weeks results in low serum levels of IGF-1, which is essential for correct retinal vessels formation, ensuring survival of the newly formed endothelial cells. Low IGF-1 level results in stop of angiogenesis in the retina, leaving it avascular and prompting the onset of ROP. Keeping the newborns in a positive energetic balance by providing enough nutrients and energy has a beneficial impact on their growth, neurodevelopment and decreased incidence of ROP. The best way to achieve this is the early parenteral nutrition with the high content of nutrients combined with early enteral feeding by the own mother's breast milk. Multiple studies confirmed the safety and efficacy of early aggressive nutrition but information about its long-term effects on the metabolism, growth and development is stil needed., N. Lenhartova, K. Matasova, Z. Lasabova, K. Javorka, A. Calkovska., and Obsahuje bibliografii
The impact of high -intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain -derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it r emained stable in EAE. BDNF -responses were not affected by EAE or exercise. In conclusion, EAE affected CSA -properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE -animals. However, exercise was not able to prevent muscle fiber atrophy., I. Wens, U. Dalgas, K. Verboven, L. Kosten, A. Stevens, N. Hens, B. O. Eijnde., and Obsahuje bibliografii
Statins are the most commonly used drugs in patients with dyslipidemia. Among the patients, a significant inter-individual variability with supposed strong genetic background in statin treatment efficacy has been observed. Genome wide screenings detected variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes that are among the candidates potentially modifying response to statins. Ten variants (SNPs) within these genes (rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs6235, rs11206510) were analyzed in 895 (46 % men, average age 60.3±13.1 years) patients with dyslipidemia treated with equipotent doses of statins (~90 % on simvastatin or atorvastatin, doses 10 or 20 mg) and selected 672 normolipidemic controls (40 % men, average age 46.5 years). Lipid parameters were available prior to the treatment and after 12 weeks of therapy. Statin treatment resulted in a significant decrease of both total cholesterol (7.00±1.53→5.15±1.17 mmol/l, P<0.0001) and triglycerides (2.03±1.01→1.65±1.23 mmol/l, P<0.0005). Rs599838 variant was not detected in first analyzed 284 patients. After adjustment for multiple testing, there was no significant association between individual SNPs and statin treatment efficacy. Only the rs4420638 (APOE/C1/C4 gene cluster) G allele carriers seem to show more profitable change of HDL cholesterol (P=0.007 without and P=0.06 after adjustment). Results demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes do not modify therapeutic response to statins., M. Vrablík, ... [et al.]., and Obsahuje seznam literaury
Perinatal ischemic stroke is a leading cerebrovascular disorder occurring in infants around the time of birth associated with long term comorbidities including motor, cognitive and behavioral deficits. We sought to determine the impact of perinatal induced stroke on locomotion, behavior and motor function in rats. A photothrombotic model of ischemic stroke was used in rat at postnatal day 7. Presently, we induced two lesions of different extents, to assess the consequences of stroke on motor function, locomotion and possible correlations to morphological changes. Behavioral tests sensitive to sensorimotor changes were used; locomotion expressed as distance moved in the open field was monitored and histological changes were also assessed. Outcomes depicted two kinds of lesions of different shapes and sizes, relative to laser illumination. Motor performance of rats submitted to stroke was poor when compared to controls; a difference in motor performance was also noted between rats with small and large lesions. Correlations were observed between: motor performance and exposition time; volume ratio and exposition time; and in the rotarod between motor performance and volume ratio. Outcomes demonstrate that photothrombotic cerebral ischemic stroke induced in early postnatal period and tested in adulthood, indeed influenced functional performance governed by the affected brain regions., T. Brima, A. Mikulecká, J. Otáhal., and Obsahuje seznam literatury
Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K+ and Cl- channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide)., M. Pintérová ... [et al.]., and Obsahuje seznam literatury
The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, m mol/kg/min) (18.7± 6 vs. 29.3± 4), decreased tissue insulin sensitivity index (M/I, m mol/kg/min per mU/l x100) (23.7± 9.8 vs. 37.5± 11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8± 1.5 vs. 7.0± 1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension., J. Widimský Jr., G. Šindelka, T. Haas, M. Prázný, J. Hilgertová, J. Škrha., and Obsahuje bibliografii
The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing’s syndrome. Twenty-nine patients with active Cushing’s syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-β-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8±74.2 vs. 210.9±56.3 ng.ml-1, p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3±13.0 vs. 63.3±32.4 PU, p<0.01, and 90.4±36.6 vs. 159.2±95.3 PU, p<0.05, respectively ) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2±1.5 vs. 5.2±3.4 PU.s-1, p<0.05, and 0.95±0.6 vs. 1.8±1.1 PU.s-1, p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus., M. Prázný, J. Ježková, E. Horová, V. Lazárová, V. Hána, J. Kvasnička, L. Pecen, J. Marek, J. Škrha, M. Kršek., and Obsahuje bibliografii a bibliografické odkazy
The aim of the study was to evaluate the impact of simulated acute hyperglycemia (HG) on PI3K/Akt signaling in preconditioned and non -preconditioned isolated rat hearts perfused with Krebs -Henseleit solution containing normal (11 mmol/l) or elevated (22 mmol/l) glucose subjected to ischemia -reperfusion. Ischemic preconditioning (IP) was induced by two 5 -min cycle s of coronary occlusion followed by 5 -min reperfusion. Protein levels of Akt, phosphorylated (activated) Akt (P-Akt), as well as contents of BAX protein were assayed (Western blotting) in cytosolic fraction of myocardial tissue samples taken prior to and a fter 30 -min global ischemia and 40- min reperfusion. In “normoglycemic ” conditions (NG), IP significantly increased P -Akt at the end of long -term ischemia, while reperfusion led to its decrease together with the decline of BAX levels as compared to non- pre conditioned hearts. On the contrary, under HG conditions, P -Akt tended to decline in IP - hearts after long -term ischemia, and it was significantly higher after reperfusion than in non -preconditioned controls . No significant influence of IP on BAX levels at the end of I/R was observed under HG conditions . It seems that high glucose may influence IP -induced activation of Akt and its downstream targets, as well as maintain persistent Akt activity that may be detrimental for the heart under above conditions., M. Zálešák, P. Blažíček, I. Gablovský, V. Ledvényiová, M. Barteková, A. Ziegelhöffer, T. Ravingerová., and Obsahuje bibliografii
We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of γ-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. These findings were related to the previous observations concerning the detrimental influence of the COX-2 genetic disruption on hematopoiesis in sublethally irradiated mice. Deteriorated postirradiation survival of COX-2 KO mice confirmed the previously anticipated conclusion regarding negative influence of the antiinflammatory action of COX-2 deficiency under the conditions of exposure of the animals to ionizing radiation., M. Hofer, Z. Hoferová, A. Gruzdev, L. Dušek, M. Falk., and Obsahuje bibliografii