Prolonged exposure to alveolar hypoxia induces physiological changes in the pulmonary vasculature that result in the development of pulmonary hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is influenced by vasoconstrictor and vasodilator factors secreted from the endothelium, lung parenchyma and in the circulation. During chronic hypoxia, production of vasoconstrictors such as endothelin-1and angiotensin II is enhanced locally in the lung, while synthesis of vasodilators may be reduced. Altered reactivity to these vasoactive agonists is another physiological consequence of chronic exposure to hypoxia. Enhanced contraction in response to endothelin-1 and angiotensin II, as well as depressed vasodilation in response to endothelium-derived vasodilators, has been documented in models of hypoxic pulmonary hypertension. Chronic hypoxia may also have direct effects on pulmonary vascular smooth muscle cells, modulating receptor population, ion channel activity or signal transduction pathways. Following prolonged hypoxic exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current, membrane depolarization, elevation in resting cytosolic calcium and changes in signal transduction pathways. These changes in the electrophysiological parameters of pulmonary vascular smooth muscle cells are likely associated with an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary arterial myocyte function, changes in synthesis of vasoactive factors and altered vasoresponsiveness to these agents may shift the environment in the lung to one of contraction instead of relaxation, resulting in increased pulmonary vascular resistance and elevated pulmonary arterial pressure., L. A. Shimoda, J. S. K. Sham, J. T. Sylvester., and Obsahuje bibliografii
CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients. Plasma sCD163 levels were increased in obese and T2DM subjects relative to control subjects (467.2±40.2 and 513.8±37.0 vs. 334.4±24.8 ng/ml, p=0.001) and decreased after both interventions. Obesity decreased percentage of CD163+CD14+ monocytes in peripheral blood compared to controls (78.9±1.48 vs. 86.2±1.31 %, p=0.003) and bariatric surgery decreased CD163+CD14+HLA-DR+ macrophages in SAT (19.4±2.32 vs. 11.3±0.90 %, p=0.004). Our data suggest that increased basal sCD163 levels are related to obesity and its metabolic complications. On the contrary, sCD163 or CD163 positive cell changes do not precisely reflect metabolic improvements after weight loss., A. Cinkajzlová, Z. Lacinová, J. Kloučková, P. Kaválková, P. Trachta, M. Kosák, J. Krátký, M. Kasalický, K. Doležalová, M. Mráz, M. Haluzík., and Obsahuje bibliografii
5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (ISC), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline ISC and 5-HT-induced ISC responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT4 receptor antagonist, SB204070, inhibited the 5-HT-induced colonic ISC response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT3 receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced ISC responses under either set of conditions. Total protein expression of both the mucosal 5-HT3 receptors and the 5-HT4 receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced ISC responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT4 receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved., Y. Li, L. S. Li, X. L. Zhang, Y. Zhang, J. D. Xu, J. X. Zhu., and Obsahuje bibliografii
Senile dementia of Alzheimer´s type (AD) is commonly characterized as a neurodegenerative disorder, which exhibits gradual changes of consciousness, loss of memory, perception and orientation as well as loss of personality and intellect. AD prevalence increases dramatically with age and is the fourth cause of death in Europe and in the USA. Currently, there are no available biological markers, which gives clinicians no other alternative than to rely upon clinical diagnosis by exclusion. There is no assay of objective ante mortem biochemical phenomena that relate to the pathophysiology of this disease. The pathophysiology of AD is connected with alterations in neurotransmission, plaque formation, cytoskeletal abnormalities and disturbances of calcium homeostasis. The search for a test, which is non-invasive, simple, cheap and user-friendly, should be directed at accessible body fluids. Only abnormalities replicated in large series across different laboratories fulfilling the criteria for a biological marker are likely to be of relevance in diagnosing AD. To date, only the combination of cerebrospinal fluid t and Ab42 most closely approximate an ideal biomarker of Alzheimer´s disease. A short review on the role of biological markers in AD on the basis of the literature, contemporary knowledge and our own recent findings are presented., D. Řípová, A. Strunecká., and Obsahuje bibliografii
The hormone leptin, which is thought to be primarily produced by adipose tissue, is a polypeptide that was initially characterized by its ability to regulate food intake and energy metabolism. Leptin appears to signal the status of body energy stores to the brain, resulting in the regulation of food intake and whole-body energy expenditure. Subsequently, it was recognized as a cytokine with a wide range of peripheral actions and is involved in the regulation of a number of physiological systems including reproduction. In the fed state, leptin circulates in the plasma in proportion to body adiposity in all species studied to date. However other factors such as sex, age, body mass index (BMI), sex steroids and pregnancy may also affect leptin levels in plasma. In pregnant mice and humans, the placenta is also a major site of leptin expression. Leptin circulates in biological fluids both as free protein and in a form that is bound to the soluble isoform of its receptor or other binding proteins such as one of the immunoglobulin superfamily members Siglec-6 (OBBP1). Although the actions of leptin in the control of reproductive function are thought to be exerted mainly via the hypothalamicpituitary-gonadal axis, there have also been reports of local direct effects of leptin at the peripheral level, however, these data appear contradictory. Therefore, there is a need to summarize the current status of research outcomes and analyze the possible reasons for differing results and thus provide researchers with new insight in designing experiments to investigate leptin effect on reproduction. Most importantly, our recent experimental data suggesting that reproductive performance is improved by decreasing concentrations of peripheral leptin was unexpected and cannot be explained by hypotheses drawn from the experiments of excessive exogenous leptin administration to normal animals or ob/ob mice., M. Herrid, S. K. A. Palanisamy, U. A. Ciller, R. Fan, P. Moens, N. A. Smart, J. R. McFarlane., and Obsahuje bibliografii
a1_Using magnetic resonance imaging (MRI) in conjunction with synchronized spirometry we an alyzed and compared diaphragm movement during tidal breathing and voluntary movement of the diaphragm while breath holding. Breathing cycles of 16 healthy subjects were examined using a dynamic sequence (77 slices in sagittal plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24, FA90, TSE1, FOV 328). The amplitude of movement of the apex and dorsal costophren ic angle of the diaphragm were measured for two test conditions: tidal breathing and voluntary breath holding. The maximal inferior and superior positions of the diaphragm were subtracted from the corresponding positions during voluntary movements while breath holding. The average amplitude of inferio-superior mo vement of the diaphragm apex during tidal breathing was 27.3±10.2 mm (mean ± SD), and during voluntary movement while breath holding was 32.5±16.2 mm. Movement of the costophrenic angle was 39±17.6 mm during tidal breathing and 45.5±21.2 mm during voluntary movement while breath holding. The inferior position of the diaphragm was lower in 11 of 16 subjects (68.75 %) and identical in 2 of 16 (12.5 %) subj ects during voluntary movement compared to the breath holding. Pearson’s correlation coefficient was used to demonstrate that movement of the costophrenic angle and apex of the diaphragm ha d a linear relationship in both examined situations (r=0.876). A correlation was found between the amplitude of diaphragm movement during tidal breathing and lung volume (r=0.876). The amplitude of movement of the diaphragm with or without breathing showed no correlation to each other (r=0.074). The moveme nt during tidal breathing shows a correlation with the changes in lung volumes. Dynamic MRI demonstrated that individuals are capable of moving their diaphragm voluntarily, but the amplitude of movement differs from person to person., a2_In this study, the movements of the diaphragm apex and the costophr enic angle were synchronous during voluntary movement of the diaphragm while breath holding. Although the sample is small, this study confirms that the function of the diaphragm is not only respiratory but also postural and can be voluntarily controlled., P. Kolář, J. Neuwirth, J. Šanda, V. Suchánek, Z. Svatá, J. Volejník, M. Pivec., and Obsahuje bibliografii
Anemia frequently complicates chronic kidney disease (CKD). We investigated here the effect of adenine-induced CKD in rats on erythrocyte count (EC), hematocrit (PCV) and hemoglobin (Hb) concentration, as well as on the activity of L-γ-glutamyl transferase (GGT) and the concentrations of iron (Fe), transferrin (Tf), ferritin (F), total iron binding capacity (TIBC) / unsaturated iron binding capacity (UIBC) and hepcidin (Hp) in serum and erythropoietin (Epo) in renal tissue. Renal damage was assessed histopathologically, and also by measuring the serum concentrations of the uremic toxin indoxyl sulfate (IS), creatinine, and urea, and by creatinine clearance. We also assessed the influence of concomitant treatment with gum acacia (GA) on the above analytes. Adenine feeding induced CKD, accompanied by significant decreases (P<0.05) in EC, PCV, and Hb, and in the serum concentrations of Fe, Tf, TIBC, UIBC and Epo. It also increased Hp and F levels. GA significantly ameliorated these changes in rats with CKD. A general improvement in the renal status of rats with CKD after GA is shown due to its antiinflammatory and anti-oxidant actions, and reduction of the uremic toxin IS, which is known to suppress Epo production, and this may be a reason for its ameliorative actions on the indices of anemia studied., B. H. Ali, M. Al Za'Abi, A. Ramkumar, J. Yasin, A. Nemmar., and Obsahuje bibliografii
Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). It is clinically important to investigate the markers of a poor prognosis. The levels of angiotensinogen (AGT) and interleukin-18 (IL-18) in serum and urine were evaluated. Study was conducted in 29 children with a history of HUS. Serum and urine AGT concentration was significantly higher in children after HUS as compared to the control group. No differences depending on the type of HUS and gender were noted. The serum concentration of IL-18 in children after HUS was significantly lower, whereas in urine did not differ significantly between the sick and healthy children. A negative correlation between the concentration of AGT in serum and albuminuria in patients after HUS was detected. The results indicate that the concentration of AGT in serum and urine in children after HUS increases, which may indicate the activation of the intrarenal renin-angiotensin-aldosterone system. The statement, that AGT may be a good biomarker of CKD after acute kidney injury due to HUS requires prospective studies with follow-up from the acute phase of the disease on a larger group of patients. Reduced IL-18 serum concentration in children after HUS with no difference in its urine concentration may indicate a loss of the protective effects of this cytokine on renal function due to previously occurred HUS., K. Lipiec, P. Adamczyk, E. Świętochowska, K. Ziora, M. Szczepańska., and Obsahuje bibliografii
Autoimmune thyropathies are frequently linked to many infections, such as Helicobacter pylori, which are also supposed to play a role in their pathogenesis. The aim of this study was to evaluate the relationships between thyroid and gastric autoimmunity and H. pylori infection on a large sample of Czech population (n=1621) by monitoring the autoantibodies against thyroglobulin (anti-Tg) and thyroid peroxidase (anti-TPO) and gastric parietal cell (anti-GPC, representing thyrogastric syndrome) in correlation with antibodies against Helicobacter pylori (anti-H. pylori) of classes IgG and IgA. The interrelation between autoantibodies and H. pylori antibodies was assessed by H. pylori seropositivity. In H. pylori seropositive persons as compared to seronegative irrespective of age and sex, a higher occurrence of anti-TPO (10.4 % vs. 5.8 %, p=0.001) and anti-GPC (6.1 % vs. 1.7 %, p<0.001) was found. Differences in anti-TPO occurrence were significant in both men (7.0 % vs. 3.3 %, p=0.03) and women (12.7 % vs. 8.0 %, p=0.02), differences in anti-GPC occurrence were significant only in women (7.2 % vs. 1.7 %, p<0.001). Results of this study support the idea of a connection between infection of H. pylori and the occurrence of anti-TPO autoantibodies representing thyroid autoimmunity and gastric parietal cells autoantibodies representing the thyrogastric syndrome., I. Šterzl, P. Hrdá, P. Matucha, J. Čeřovská, V. Zamrazil., and Obsahuje bibliografii a bibliografické odkazy