Ceskoslovenska fysiologie最新文献

Macrophages play an essential role not only in the defense against the infection, but are involved in many various pathological processes. They take an important part, e.g., in the development of hypoxic pulmonary hypertension (HPH). The production of reactive oxygen species (ROS) by macrophages causes the pulmonary tissue damage, which seems to play a key role in this process. This paper is focused on the NADPH-oxidase derived ROS production in alveolar macrophages and ways of its modification. NADPH-oxidase is activated via two different pathways by many stimulators. The role of the trigger can play, besides others, integrins, molecules mediating the adherence of cells. To test a role of adherence, we compared ROS production (measured as the amount of released hydrogen peroxide by the luminoldependent chemiluminescence (LDCL)) in alveolar and peritoneal macrophages. The adherence itself triggered significantly the H2O2 production only in the alveolar macrophages. Thus we suppose that the adherence is recognised as the pathological signal only in the alveolar macrophages and it can modify macrophages response to further stimuli.

The World Health Organization estimates that in 2020 will die of ischemic heart disease (CHD) 11.1 million people in the world, while in 2002 it was 7.22 million, of which in Europe nearly two million. High incidence particularly in developed countries emphasizes mainly on risk factors (RF) of lifestyle. Similar, not good, is the situation in Slovakia. Since the wrong habits, leading to the development of cardiovascular disease (CVD), are created in childhood and young age, we focused on the exploration of risk factors related to the lifestyle of young people in secondary schools in Slovakia (in capital city and regional city with a high proportion of students from rural areas). The survey results clearly confirm the high incidence of many RF in teenage age already, which in future may increase the risk of CVD and other civilization diseases.

Pulmonary hypertension (PH) is a syndrome characterized by elevated mean arterial pulmonary pressure. PH occurs in a variety of clinical situations (pulmonary arterial hypertension, cardiovascular and lung diseases, hypoxic states including high altitude sojourn, thromboembolic disease) and differs in etiology, prognosis and therapy. PAH (pulmonary arterial hypertension) is a serious and progressive dissease leading to right ventricular failure. Regarding treatment, causal therapy does not exist, conventional therapy prevails and several specific drugs are under clinical trial. The common feature of all groups of PH is the structural remodeling of peripheral pulmonary arteries. Recent studies confirm important role of activated mast cells in pathogenesis of pulmonary vessel wall remodeling. It was described in a variety of animal models, which allow testing of new pathways and drugs including mast cell targeted therapy.

VEGF, vascular endothelial growth factor, is a substance firstly described in 1983 as a tumor-secreted protein which causes the development of ascitic fluid in case of abdominal tumors. Its influence on angiogenesis was ascertained by many studies. The strongest stimulus for its production is hypoxia, which leads to higher secretion of VEGF and new angiogenesis of so affected tissue. The neurogenic effect was firstly mentioned in 1999. Its protective and proliferative influence both on CNS and peripheral nerves is now widely accepted. It was demonstrated that VEGF has more wide ranging effect than previously thought.

The airway hyperreactivity (AHR) is a symptom occurring in various diseases of the respiratory system. It is defined as an abnormal bronchoconstriction response to a different spectrum of biological, chemical and pharmacological stimuli. Pathogenesis of airway hyperreactivity is not well understood. The available literature data shows that in the AHR pathogenesis is important not only genetic predisposition or influence of combination environmental and genetic factors, but also the presence and activity of various inflammatory mediators and other endogenous factors (growth factors, nuclear transcription factors). In this process is also important role of neural regulation and release of pro-inflammatory neurotransmitters. Our aim was to provide a comprehensive overview of knowledge about the symptoms--from the risk factors and pathogenesis through the clinical importance to the need for better understanding new options in therapeutic interventions.

Subclinical inflammation that primarily arises in adipose tissue as a result of its excessive infiltration by immunocompetent cells represents one of the typical etiopathogenetic mechanisms underlying the development of insulin resistance and type 2 diabetes. Immunocompetent cells together with adipocytes are a major source of proinflammatory cytokines triggering proinflammatory cascades that in turn interfere with postreceptor insulin signalling cascade. Recent studies have suggested that inducible nitric oxide synthase plays a key role in this process. Obesity is associated with increased inducible nitric oxide synthase mRNA expression, with subsequent overproduction of nitric oxide and reactive nitrogen species leading to S-nitrosylation of proteins involved in insulin signalling cascade. These post-translational modifications decrease their activity and eventually lead to insulin resistance. Number of experimental studies demonstrated that inhibition of inducible nitric oxide synthase attenuates insulin resistance. The aim of this review is to summarize the current knowledge about the physiology and patophysiology of nitric oxide and inducible nitric oxide synthase with respect to its relationship to insulin resistance and to discuss the possibility of improvement of insulin resistance and type 2 diabetes mellitus by modulating inducible nitric oxide synthase activity.

Experimental studies published in past years have shown an important role of the vagus nerve in regulating immune functions. Afferent pathways of this cranial nerve transmit signals related to tissue damage and immune reactions to the brain stem. After central processing of these signals, activated efferent vagal pathways modulate inflammatory reactions through inhibiting the synthesis and secretion of pro-inflammatory cytokines by immune cells. Therefore, pathways localized in the vagus nerve constitute the afferent and efferent arms of the so-called "inflammatory reflex" that participates in negative feedback regulation of inflammation in peripheral tissues. Activation of efferent pathways of the vagus nerve significantly reduces tissue damage in several models of diseases in experimental animals. Clinical studies also indicate the importance of the vagus nerve in regulating inflammatory reactions in humans. It is suggested that alteration of the inflammatory reflex underlies the etiopathogenesis of diseases characterized by exaggerated production of pro-inflammatory mediators. Therefore, research into the inflammatory reflex may create the basis for developing new approaches in the treatment of diseases with inflammatory components.

Adrenergic system in the mammalian heart plays a pivotal role in regulation of contractility and/or heart rate. At present, nine subtypes of adrenergic receptors (AR) have been identified. Among these there are six AR localized in the plasma membrane of cardiomyocytes. They mediate their effects by increases in the intracellular level of various signaling molecules which initiate diverse cellular responses. The effects of stimulation of both beta-AR by catecholamines noradrenaline and adrenaline are consistent with coupling to the Gs protein-adenylyl cyclase-cAMP-protein kinase classical pathway, with consequent protein kinase A-catalysed phosphorylation of target enzymes responsible for increased contractility and hastening of relaxation. In contrast to beta1-AR, beta2-AR can also couple to G(i) protein which causes cAMP-independent control of calcium signaling and contraction. Activation of beta-AR obviously couples to a G(i)/ nitric oxide pathway and mediates a decrease in contractile force, whereas stimulation of alpha-AR increases contractility via G protein/phospholipase C/diacylglycerol/inositoltrisphosphate/protein kinase C pathway. These findings reveal the diversity and specifity of AR subtypes and G protein interactions. They also provide new insights in understanding the differential regulation and functionality of AR subtypes in healthy and diseased hearts.

The local signs of inflammation are redness, oedema, increased temperature and pain. Local inflammatory changes are often followed by systemic non- specific alterations. Fever, which is usually the first sign of systemic inflammation, is accompanied by other systemic inflammatory changes like pain and anorexia. The systemic non-specific inflammatory symptoms also include changes in general activity, cognition, and affection. Sickness behaviour syndrome increases survival of the organism affected by inflammation. Many of sickness symptoms are regulated centrally by the brain. IL-1beta holds a privilege in regulation of sickness symptoms.

Cardiovascular diseases, including hypertension, represent serious medical and social problem because they affect many people in industrialized countries in the world and, unfortunately, their incidence has not decreasing tendency. Human essential hypertension is a chronic, slowly developing disease, which is a consequence of abnormalities in the development of cardiovascular system and its regulation, which are subsequently reflected in pathological rise of blood pressure. In general, blood pressure increases slowly and gradually and this may last several years. Myocardial hypertrophy and structural alterations of the vessel system frequently occur. As hypertension is already established, then complete normalization of blood pressure is difficult to obtain. Therefore, it is necessary to focus on its prevention, this means, to intervene before blood pressure elevation in individuals with significant genetic predisposition to this disease. Moreover, it is well known that cardiovascular system of the young organism is very sensitive to various environmental influences, and one can expect that it may also be more susceptible to vasoactive substances in prevention and treatment of cardiovascular diseases. Hypertension and its pharmacological treatment should therefore be studied with regard to the maturity of an individual. In accordance with the hypothesis of developmental plasticity of organisms, it may be possible (by pharmacological intervention in early ontogenetic stages of predisposed individual) to achieve such a setting of structural and functional parameters which could reduce the subsequent clinical manifestation of genetically induced hypertensive state.