Immunomodulatory steroids, dehydroepiandrosterone and its 7-hydroxylated metabolites and sex hormone-binding globulin (SHBG) were determined in sera of 88 women aged 18-75 years. The group consisted of 34 healthy women, 37 women with subclinical and 17 women with manifest hypothyroidism. In all subjects the laboratory parameters of thyroid function (thyrotropin, free thyroxine and triiodothyronine) and thyroid autoantibodies to thyroid peroxidase and thyroglobulin were determined. The aim was to find out 1) whether the above steroids and SHBG levels differ in individual groups according to thyroid status, 2) whether correlations exist among investigated steroids and thyroid laboratory parameters, and 3) whether the respective steroid and SHBG levels differ according to the presence of principal thyroid autoantibodies. With the exception of 7β-hydroxy-dehydroepindrosterone levels, which were decreased in patients with manifest hypothyroidism (p<0.05), no significant differences in steroid and SHBG levels among groups according to diagnosis were found. On the other hand, significantly decreased levels of all the immunomodulatory steroids studied were found in subjects with positive titres of thyroid autoantibodies. This finding was supported by a tight negative correlation among the above steroids and thyroid autoantibodies. In addition, these steroids correlated negatively with thyrotropin and positively with free thyroid hormones. The results point to a negative relationship between the above mentioned immunoprotective steroids and the extent of the autoimmune process in hypothyroidism., K. Drbalová, P. Matucha, M. Matějková-Běhanová, R. Bílek, L. Kříž, H. Kazihnitková, R. Hampl., and Obsahuje bibliografii a bibliografické odkazy
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
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 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
The electrical properties of the supported lipid bilayer membrane (s-BLM) of egg phosphatidylcholine (PC) selfassembled on agar surface were examined. To characterize the insulating properties of s-BLMs, electrochemical impedance spectroscopy (EIS) was used. The analysis of impedance spectra in terms of an equivalent circuit of agar/electrolyte and agar/s-BLM/electrolyte in the frequency range of 0.1 Hz-10 kHz was performed. The high-density lipoproteins (HDL)/s-BLM interaction in the concentration range from 20 μg/ml to 80 μg/ml of HDL was investigated. It is evident that treatment of s-BLM with HDL resulted in an increase of the lipid film resistance and a decrease of membrane capacitance., M. Legiň, G. Laputková, J. Sabo, L. Vojčíková., and Obsahuje bibliografii
There are five subtypes of muscarinic receptors that serve various important physiological functions in the central nervous system and the periphery. Mental functions like attention, learning, and memory are attributed to the muscarinic M1 subtype. These functions decline during natural aging and an early deficit is typical for Alzheimer´s disease. In addition, stimulation of the M1 receptor increases non-amyloidogenic processing of the amyloid precursor protein and thus prevents accumulation of noxious β-amyloid fragments. The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site among receptor subtypes. Herein we summarize some recent studies with the functionally-selective M1 agonist xanomeline that indicate complex pharmacological profile of this drug that includes interactions with and activation of receptor from both orthosteric and ectopic binding sites, and the time-dependent changes of ligand binding and receptor activation. These findings point to potential profitability of exploitation of ectopic ligands in the search for truly selectiev muscarinic receptor agonists., J. Jakubík, P. Michal, E. Machová, V. Doležal., and Obsahuje bibliografii a bibliografické odkazy
Autophagy is the basic catabolic mechanism that involves degradation of dysfunctional cellular components through the action of lysosome as well as supplying energy and compounds for the synthesis of essential biomacromolecules. This process enables cells to survive stress from the external environment like nutrient deprivation. Autophagy is important in the breakdown of proteins, carbohydrates and lipids as well. Furthermore, recent studies have shown that autophagy is critical in wide range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including lysosomal storage disease, myopathies, neurodegeneration and various metabolic disorders. This review summarizes the most up-to-date findings on what role autophagy plays in metabolism., Z. Papáčková, M. Cahová., and Obsahuje bibliografii
The electrical parameters of the cell membrane are mostly estimated employing ac methods. The measurement is based on the analysis of the current(s) flowing through an access resistance and the membrane. A current/potential transducer is used at the input of the device. The parameters of this transducer, especially its feedback capacity, degrades the accuracy of the measurement and hence diminishes the suppression of mutual influences of the individual parameters. The paper suggests a possible software correction and is supplemented by remarks for practical application., V. Rohlíček, F. Rech., and Obsahuje bibliografii