The aim of our study was to evaluate the potential differences in blood pressure (BP) profile in subjects with different forms of primary aldosteronism (PA). Simultaneously, we studied the effects of PA treatment on BP curve. We therefore monitored 24-hour ambulatory blood pressure values in 22 subjects with aldosterone-producing adenoma (APA), 22 subjects with idiopathic hyperaldosteronism (IHA) and 33 subjects with essential hypertension (EH) as controls. We found a significantly attenuated nighttime systolic BP decline in the APA group (P=0.02). Patients with IHA had lower nighttime systolic BP values (P=0.01) and also a diastolic BP decline (P=0.02) during the night in comparison with EH. We did not detect any significant differences in BP profile characteristics between APA and IHA. Specific treatment of primary aldosteronism (adrenalectomy, treatment with spironolactone) led to the normalization of the BP curve with a marked BP decline. Our study thus demonstrates a blunted diurnal BP variability in patients with primary aldosteronism the specific treatment of which normalized previously attenuated nocturnal BP fall., T. Zelinka, J. Widimský., and Obsahuje bibliografii
The aim of our study was to develop a model producing obese mice in early adulthood (4-6 weeks) based on their over-nutrition during fetal and early postnatal development. The fertilized dams of the parental generation were fed the standard diet supplemented with high-energy nutritional product Ensure Plus during gestation and lactation. De livered weanlings were then fed with standard or supplemented diet and assessed for body fat deposits using EchoMRI at the ti me of early and late adulthood. Maternal over-feeding during th e period before weaning had the most significant effect on obesity development in the filial generation. In weanlings, signific antly higher body fat deposits and average body weight were recorded. Later, further significant increase in percentage of body fat in both male and female mice was observed. Withdrawal of the Ensure Plus supplement caused a decrease in the percentage of body fat in part of the filial generation. In offspring fed the standard diet, higher fat deposits persisted till the time of late adulthood. We conclude that this diet-induced obesity model might be used in exploration of the effects of elevated body fat on physiological functions of various organ systems during juvenile and early adulthood periods of life of a human being., J. Kubandová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Ulinastatin [or called as urinary trypsin inhibitor (UTI)] plays a role in regulating neurological deficits evoked by transient cerebral ischemia. However, the underlying mechanisms still need to be determined. The present study was to examine the effects of UTI on autophagy, Nrf2-ARE and apoptosis signal pathway in the hippocampus in the process of neurological functions after cerebral ischemia using a rat model of cardiac arrest (CA). CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Western blot analysis was employed to determine the expression of representative autophagy (namely, Atg5, LC3, Beclin 1), p62 protein (a maker of autophagic flux), and Nrf2-ARE pathways. Neuronal apoptosis was assessed by determining expression levels of Caspase-3 and Caspase-9, and by examining terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL). The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats. Our results show that CA amplified autophagy and apoptotic Caspase-3/Caspase-9, and downregulated Nrf2-ARE pathway in the hippocampus CA1 region. Systemic administration of UTI attenuated autophagy and apoptosis, and largely restored Nrf2-ARE signal pathway following cerebral ischemia and thereby alleviated neurological deficits with increasing survival of CA rats. Our data suggest that UTI improves the worsened protein expression of autophagy and apoptosis, and restores Nrf2-ARE signals in the hippocampus and this is linked to inhibition of neurological deficiencies in transient cerebral ischemia. UTI plays a beneficial role in modulating neurological deficits induced by transient cerebral ischemia via central autophagy, apoptosis and Nrf2-ARE mechanisms., Xiao-Ming Jiang, Jing-Hai Hu, Lu-Lu Wang, Chi Ma, Xu Wang, Xiao-Liang Liu., and Obsahuje bibliografii
Genetic predisposition and social stress may represent important risk factors in etiology of hypertension associated with endothelial dysfunction. Perturbations of endothelial structural integrity are also critical for the pathogenesis of vascular diseases. We examined effect of chronic social stress on structure of aortic endothelium in bord erline hypertensive (BHR) and normotensive Wistar rats. Male BHR – offspring of Wistar mothers and SHR fathers and age-matched W were exposed to 6-week crowding stress (5 rats/cage, 200 cm2/rat). Aortic tissue was processed for electron microscopy and NO synthase activity measurement. Crowding stress significantly increased blood pressure in BHR compared to basal values (140±3 mm Hg vs. 130±3 mm Hg, p<0.05) and reduced enzyme activity by 37 % (p<0.01) in the aorta of BHR. Local slight structural alterations of endothelium were found in non-stressed BHR (p<0.001) when compared with Wistar rats. Chronic stress caused marked (p<0.005) subcellular injury of endothelial cells in aorta of BHR characterized by mitochondrial damage, presence of vacuoles, increased number of lysosomes, Weibel-Palade bodies, changes of intercellular connections and local disruption of endothelium, while only slight changes were seen in Wistar rats. Results suggest increased sensitivity of aortic endothelium of BHR to chronic crowding that may contribute to acceleration of arterial dysfunction., Ľ. Okruhlicová, K. Dlugošová, M. Mitašíková, I. Bernátová., and Obsahuje bibliografii a bibliografické odkazy
Impaired calcium homeostasis and altered expression of Ca2+-binding proteins are associated with cardiomyopathies, myocardial hypertrophy, infarction or ischemia. S100A1 protein with its modulatory effect on different target proteins has been proposed as one of potential candidates which could participate in these pathological processes. The exact localization of S100A1 in human heart cells on the ultrastructural level accompanied with biochemical determination of its target proteins may help clarify the role of S100A1 in heart muscle. In the present study the distribution of the S100A1 protein using postembedding (Lowicryl K4M) immunocytochemical method in human heart muscle has been determined quantitatively, relating number of antigen sites to the unit area of a respective structural component. S100A1 antigen sites have been detected in elements of sarcoplasmic reticulum (SR), in myofibrils at all levels of sarcomere and in mitochondria, the density of immunolabeling at Z-lines being about 3 times and at SR more than 5 times higher than immunolabeling of remaining structural components. The presence of the S100A1 in SR and myofibrils may be related to the known target proteins for S100A1 at these sites., B. Maco, A. Mandinová, M.B. Dürrenberger, B.W. Schäfer, B. Uhrík, C.W. Heizmann., and Obsahuje bibliografii
Mild hyperhomocysteinemia has been established as a new independent risk factor for atherosclerosis and thrombosis. The metabolic syndrome of insulin resistance is associated with a high risk of coronary heart disease. Our objective was to determine if any relationship exists between the metabolic syndrome of insulin resistance in non-diabetic subjects and total serum homocysteine levels. Sixty-six healthy volunteers (33 males and 33 females) were selected from the population of Pilsen. Insulin resistance was measured by the Insulin Suppression Test using Octreotide. Steady-state plasma glucose concentrations at the end of the test period provided a quantitative measure of insulin resistance. Serum homocysteine level was estimated by high-pressure liquid chromatography. Serum folate and vitamin B12 were estimated using commercial kits on an Abbott IMx analyzer. All other laboratory tests were performed by standard methods in a routine biochemical laboratory. Subjects with the highest tertile of steady-state plasma glucose showed a significantly higher body mass index, blood pressure, fasting plasma triglyceride levels, plasminogen activator inhibitor-1 and lower HDL-cholesterol, i.e. an insulin resistance pattern. These subjects had significantly lower serum homocysteine levels compared with non-insulin resistant subjects. The negative association of insulin resistance and serum homocysteine was unexpected. The contribution of plasma folate levels to serum homocysteine levels and serum creatinine was significantly negative and positive, respectively., H. Rosolová, J. Šimon, O. Mayer Jr., J. Racek, T. Dierzé, D. W. Jacobsen., and Obsahuje bibliografii
M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16- ) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection., Lenka Čurnová, Kristýna Mezerová, Veronika Švachová, Martina Fialová, Marek Novotný, Eva Čečrdlová, Ondřej Viklický, Ilja Stříž., and Obsahuje bibliografii
The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area ( Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy., D. Spicarova, V. Nerandzic, J. Palecek., and Obsahuje bibliografii a bibliografické odkazy
The main aim of the present investigation was to verify the effects of three overtraining (OT) protocols performed in downhill (OTR/down), uphill (OTR/up) and without inclination (OTR) on the protein levels of Akt (Ser473), AMPKα (Thr172), PGC-1α, plasma membrane GLUT-1 and GLUT-4 as well as on the glycogen contents in mice gastrocnemius. A trained (TR) protocol was used as positive control. Rodents were divided into naïve (N, sedentary mice), control (CT, sedentary mice submitted to the performance evaluations), TR, OTR/down, OTR/up and OTR groups. At the end of the experimental protocols, gastrocnemius samples were removed and used for immunoblotting analysis as well as for glycogen measurements. There was no significant difference between the experimental groups for the protein levels of pAkt (Ser473), pAMPKα (Thr172), PGC-1α, plasma membrane GLUT-1 and GLUT-4. However, the OTR/up protocol exhibited higher contents of glycogen compared to the CT and TR groups. In summary, the OTR/up group increased the gastrocnemius glycogen content without significant changes of pAkt (Ser473), pAMPKα (Thr172), PGC-1α, plasma membrane GLUT-1 and GLUT-4., G. P. Morais, A. Da Rocha, A. P. Pinto, L. Da C. Oliveira, L. G. De Vicente, G. N. Ferreira, E. C. De Freitas, A. S. R. Da Silva., and Seznam literatury