This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate., R. Janečková., and Obsahuje bibliografii
Lipid peroxidation of rat cerebral cortex membranes was induced by Fe2+/ADP and ascorbate. The rate of Na+/K+-ATPase inhibition was correlated with the increase of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD) and with membrane fluidity changes. Our data showed that membrane fluidity changes (evaluated by fluorescence steady-state anisotropy measurements) can participate in Na+/K+-ATPase inhibition during the initial period of lipid peroxidation process, whereas during the following period the enzyme inhibition correlates only with TBARS and CD production., H. Rauchová, Z. Drahota, J. Koudelová., and Obsahuje bibliografii
Endothelial dysfunction may be considered as the interstage between risk factors and cardiovascular pathology. An imbalance between the production of vasorelaxing and vasoconstricting factors plays a decisive role in the development of hypertension, atherosclerosis and target organ damage. Except vasorelaxing and antiproliferative properties per se, nitric oxide participates in antagonizing vasoconstrictive and growth promoting effects of angiotensin II, endothelins and reactive oxygen species. Angiotensin II is a potent activator of NAD(P)H oxidase contributing to the production of reactive oxygen species. Numerous signaling pathways activated in response to angiotensin II and endothelin-1 are mediated through the increased level of oxidative stress, which seems to be in casual relation to a number of cardiovascular disturbances including hypertension. With respect to the oxidative stress, the NO molecule seems to be of ambivalent nature. On the one hand, NO is able to reduce generation of reactive oxygen species by inhibiting association of NAD(P)H oxidase subunits. On the other hand, when excessively produced, NO reacts with superoxides resulting in the formation of peroxynitrite, which is a free radical deteriorating endothelial function. The balance between vasorelaxing and vasoconstricting substances appears to be the principal issue for the physiological functioning of the vascular bed., O. Pecháňová, F. Šimko., 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
Transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel activated by capsaicin, a pungent substance from chili peppers. It is considered to act as an integrator of various physical and chemical nociceptive stimuli, as it can be gated by noxious heat (>43ºC), low pH (protons) and also by recently described endogenous lipids. The structure and function of TRPV1 receptors was vigorously studied, especially since its cloning in 1997. However, most of the research was pointed towards the role of TRPV1 receptors in the peripheral tissues. Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission. The aim of this short review was to summarize the knowledge about TRPV1 receptors in the spinal cord dorsal horn, preferentially from morphological and electrophysiological studies on spinal cord slices and from in vivo experiments., D. Špicarová, J. Paleček., and Obsahuje bibliografii a bibliografické odkazy
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
The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of “cell-based coagulation model” which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs., M. A. Malý, P. Tomašov, P. Hájek, P. Blaško, I. Hrachovinová, P. Salaj, J. Veselka., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to explore changes in plasma vascular endothelial growth factor (VEGF) in aged patients who undergone transcatheter aortic valve implantation or balloon angioplasty for the treatment of aortic stenosis. Plasma VEGF was measured in subjects with diabetes mellitus type 2 (DM) (n=21, age 79.2±1.6 years) and in non-diabetic subjects (non-DM) (n=23, age 84.4±0.7 years), using an ELISA kit. Before the procedure plasma levels of VEGF were significantly lower in DM than in non-DM patients (P<0.05). Plasma VEGF significantly increased in both groups (DM and non-DM) 24 h (387±64 vs. 440±30 pg/ml, P<0.05) and 72 h (323±69 vs. 489±47 pg/ml, P<0.05) after the endovascular procedure. However, the VEGF in DM patients was significantly lower compared to non-DM subjects up to one month after the endovascular procedure (283±47 vs. 386±38 pg/ml, P<0.05). We conclude that increased plasma VEGF in aged patients associates with atherosclerotic aortic valve stenosis. In spite of that plasma VEGF in DM was constantly significantly lower than in non diabetic patients, both before and after the endovascular procedure, possibly reflecting a disturbance of angiogenic/antiangiogenic balance in diabetes., V. Bláha, J. Šťásek, J. Bis, J. Fortunato, C. Andrýs, V. Pavlík, P. Polanský, M. Brtko, L. Sobotka., and Obsahuje bibliografii