We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin -like -growth- factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide -3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percenta ge of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA -IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF -binding protein-3 (IGFBP-3) expression that both positively correlated wit h serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA -IR while IGFBP -3 expression in SCAT was an independ ent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly., V. Touskova, J. Klouckova, V. Durovcova, Z. Lacinova, P. Kavalkova, P. Trachta, M. Kosak, M. Mraz, D. Haluzikova, V. Hana, J. Marek, M. Krsek, M. Haluzik., and Obsahuje bibliografii
7β-hydroxy-epiandrosterone (7β-OH-EpiA) is an endogenous androgen metabolite that has been shown to exert neuroprotective, anti-inflammatory and anti-estrogenic effects. However, to the best of our knowledge no information is available about this androgen steroid in relation to sperm quality. We analyzed 7β-OH-EpiA in plasma and seminal plasma using a newly developed isotope dilution ultra-high performance liquid chromatography - mass spectrometry method. Validation met the requirements of FDA guidelines. Levels of 7β-OH-EpiA were measured in 191 men with different degrees of infertility. One-way analysis of variance followed by multiple comparison and correlation analysis adjusted for age, BMI and abstinence time were performed to evaluate the relationships between this steroid and sperm quality. Concentrations of 7β-OH-EpiA in seminal plasma were significantly higher in severely infertile men in comparison with healthy men and slightly infertile men. The same trend was found when blood plasma was evaluated. Furthermore, plasma 7β-OH-EpiA negatively correlated with sperm concentration (-0.215; p<0.01) and total count (-0.15; p<0.05). Seminal 7β-OH-EpiA was negatively associated with motility (-0.26; p<0.01), progressively motile spermatozoa (-0.233; p<0.01) and nonprogressively motile spermatozoa (-0.188; p<0.05). 7β-OH-EpiA is associated with lower sperm quality and deserves more research in that respect., J. Vitku, L. Kolatorova, C. Ricco, C. Ferroud, O. Hennebert, T. Skodova, J. Heracek, L. Starka., and Obsahuje bibliografii
Autophagy is implicated in the maintenance of cardiac homeostasis. Autophagy is activated in heart failure, in which reactive oxygen species (ROS) are increased. Exogenous ROS have been shown to induce cardiomyocyte autophagy alterations. However, little is known about the influences of physiological levels of endogenous ROS on cardiomyocyte autophagy. In the present study, we tested the hypothesis that endogenous ROS in cardiomyocytes play an important role in inducing autophagy. Cultured H9C2 cardiomyocytes or Sprague-Dawley rats were treated with the antioxidant N-acetyl-cysteine (NAC) or the superoxide dismutase mimic tempol under the basal or nutrient deprivation conditions. The autophagic flux was assessed by the lysosomal inhibitor chloroquine. In H9C2 cardiomyocytes, under a basal condition, NAC or tempol increased the ratio of LC3 II/I proteins and reduced LC3 II autophagic flux. Under nutrient deprivation, NAC increased the LC3 II/I ratio and reduced LC3 II autophagic flux. In vivo studies in rats, NAC treatment increased the LC3 II/I ratio and p-Akt protein expression in myocardium. We concluded that the antioxidants reduced autophagic flux in cardiomyocytes under the basal or nutrient deprivation conditions, suggesting that endogenous ROS promote autophagy flux under physiological conditions, and this effect is mediated, at least in part, through Akt inhibition., J.-P. Wang, R.-F. Chi, J. Liu, Y.-Z. Deng, X.-B. Han, F.-Z. Qin, B. Li., and Seznam literatury
Recent studies focused on epicardial fat, formerly relatively neglected component of the heart, have elucidated some of its key roles. It possesses several properties that can distinguish it from other adipose tissue depots. Its unique anatomical location in the heart predisposes the epicardial fat to be an important player in the physiological and biochemical regulation o f cardiac homeostasis. Obesity is associated with an increase in epicardial fat mass. Excess of cardiac fat can contribute to greater left ventricular mass and work, diastolic dysfunction and attenuated septal wall thickening. Imbalance in adipokines levels secreted in autocrine or paracrine fashion by epicardial fat can contribute to the activation of the key atherogenic pathways in the setting of metabolic syndrome. Epicardial fat has also been identified as an important source of pro-inflammatory mediato rs worsening endothelial dysfunction, eventually leading to coronary artery disease. Increased production of pro-inflammatory factors by epicardial fat can also contribute to systemic insulin resistance in patients undergoing cardiac surgery. Here we revie w the most important roles of epicardial fat with respect to heart disease in the context of other underlying pathologies such as obesity and type 2 diabetes mellitus., Z. Matloch, T. Kotulák, M. Haluzík., and Obsahuje bibliografii
Protease-activated receptors (PARs) belong to the G-proteincoupled receptor family, that are expressed in many body tissues especially in different epithelial cells, mast cells and also in neurons and astrocytes. PARs play different physiological roles according to the location of their expression. Increased evidence supports the importance of PARs activation during nociceptive signaling and in the development of chronic pain states. This short review focuses on the role of PAR2 receptors in nociceptive transmission with the emphasis on the modulation at the spinal cord level. PAR2 are cleaved and subsequently activated by endogenous proteases such as tryptase and trypsin. In vivo, peripheral and intrathecal administration of PAR2 agonists induces thermal and mechanical hypersensitivity that is thought to be mediated by PAR2-induced release of pronociceptive neuropeptides and modulation of different receptors. PAR2 activation leads also to sensitization of transient receptor potential channels (TRP) that are crucial for nociceptive signaling and modulation. PAR2 receptors may play an important modulatory role in the development and maintenance of different pathological pain states and could represent a potential target for new analgesic treatments., P. Mrozkova, J. Palecek, D. Spicarova., and Obsahuje bibliografii
Deformability of red blood cells (RBC) is the ability of RBC to change their shape in order to pass through narrow capillaries in circulation. Deterioration in deformability of RBC contributes to alterations in microcirculatory blood flow and delivery of oxygen to tissues. Several factors are responsible for maintenance of RBC deformability. One of them is the Na,K-ATPase known as crucial enzyme in maintenance of intracellular ionic homeostasis affecting thus regulation of cellular volume and consequently RBC deformability. Decreased deformability of RBC has been found to be the marker of adverse outcomes in cardiovascular diseases (CVD) and the presence of cardiovascular risk factors influences rheological properties of the blood. This review summarizes knowledge concerning the RBC deformability in connection with selected risk factors of CVD, including hypertension, hyperlipidemia, and diabetes mellitus, based exclusively on papers from human studies. We attempted to provide an update on important issues regarding the role of Na,K-ATPase in RBC deformability. In patients suffering from hypertension as well as diabetes mellitus the Na,K-ATPase appears to be responsible for the changes leading to alterations in RBC deformability. The triggering factor for changes of RBC deformability during hypercholesterolemia seems to be the increased content of cholesterol in erythrocyte membranes., J. Radosinska, N. Vrbjar., and Obsahuje bibliografii
Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women., A. Pařízek, M. Dušková, L. Vítek, M. Šrámková, M. Hill, K. Adamcová, P. Šimják, A. Černý, Z. Kordová, H. Vráblíková, B. Boudová, M. Koucký, K. Malíčková, L. Stárka., and Obsahuje bibliografii
Dental management behavior problems are thought to be both multifactorial and multidimensional, consisting of physiological, behavioral and cognitive components. The stress response to pain or even the anticipation of distress initiates activation of the hypothalamic-pituitary-adrenal axis and causes an increase of cortisol and catecholamines. The literature on the role of hormones in dental management behavior problems comprises about one hundred papers, which have mainly been focused on this activation of the HPA axis in various situations in dental care. They have generally used salivary cortisol as a marker of the activity of the HPA axis, sometimes combined with salivary alpha amylase. Here we summarize the literature data on the role of stress hormones in dental management behavior problems., M. Dušková, J. Vašáková, J. Dušková, J. Kaiferová, Z. Broukal, L. Stárka., and Obsahuje bibliografii
In the following paper, authors describe glycans present on cell membranes as they affect the folding, the spatial arrangement, the behavior and the interaction with the substrate of some membrane proteins. Authors describe the synthesis and assembly of a glycan on a protein, the formation of N-glycans, the maturation of an N-glycan in different cellular compartments, the structure of the glycocalyx and how it interacts with any pathogens. The study of the E-cadherin and the potassium channel to demonstrate how glycans affect the spatial arrangement, the stability and activity of the glycoproteins on the membranes. Subsequently, authors analyze the correlation between disorder glycosylation and human health. Authors define glycosylation disorders as a genetic defect that alter the structure or biosynthesis of glycans (sugar chains) in one or more biosynthetic pathways. Human glycosylation disorders reflect the disruption of early steps in the pathways of glycan biosynthesis. More in details, authors analyze the role of glycoprotein in tumor cell adhesion, in particular, in cells MCF-7 and MDA-MB-231 on zeolite scaffold. In the same time, the role of metalloproteinase is described in the mobilization of cancer cells and in metastasis., P. Sprovieri, G. Martino., and Seznam literatury
The mood and behavior of individuals result from an orchestra of many factors. Among them steroids play an important role; however, only several common hormones have been investigated in this respect. It has been demonstrated that some steroid metabolites long considered merely the products of steroid hormone metabolism in fact possess considerable activity in the CNS. For this reason we studied the steroid metabolome including 50 analytes in 20 men with depression, 20 men with anxiety and 30 healthy controls. Significant differences were found not only between controls and men with either depression or anxiety, but also between men with depression and anxiety. Particularly striking were those steroids until now not generally associated with depression or anxiety, namely conjugated steroid forms, especially sulfates., M. Dušková, M. hill, M. Bičíková, M. Šrámková, D. Řípová, P. Mohr, L. Stárka., and Obsahuje bibliografii