Our own study as well as others have previously reported that hypoxia activates 15-lipoxygenase (15-LO) in the brain, causing a series of chain reactions, which exacerbates ischemic stroke. 15-hydroxyeicosatetraenoic acid (15-HETE) and 15-oxoeicosatetraenoic acid (15-oxo-ETE/15-KETE) are 15-LO-specific metabolites of arachidonic acid (AA). 15-HETE was found to be rapidly converted into 15-oxo-ETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in some circumstances. We have demonstrated that 15-HETE promotes cerebral vasoconstriction during hypoxia. However, the effect of 15-oxo-ETE upon the contraction of cerebral vasculature remains unclear. To investigate this effect and to clarify the underlying mechanism, we performed immunohistochemistry and Western blot to test the expression of 15-PGDH in rat cerebral tissue, examined internal carotid artery (ICA) tension in isolated rat ICA rings. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of voltage-gated potassium (Kv) channels (Kv2.1, Kv1.5, and Kv1.1) in cultured cerebral arterial smooth muscle cells (CASMCs). The results showed that the levels of 15-PGDH expression were drastically elevated in the cerebral of rats with hypoxia, and 15-oxo-ETE enhanced ICA contraction in a dose-dependent manner. This effect was more significant in the hypoxic rats than in the normoxic rats. We also found that 15-oxo-ETE significantly attenuated the expression of Kv2.1 and Kv1.5, but not Kv1.1. In conclusion, these results suggest that 15-oxo-ETE leads to the contraction of the ICA, especially under hypoxic conditions and that specific Kv channels may play an important role in 15-oxo- ETE-induced ICA constriction., Di Wang, Yu Liu, Ping Lu, Daling Zhu, Yulan Zhu., and Obsahuje bibliografii
Acrylamide (AA) is a highly reactive organic compound capable of polymerization to form polyacrylamide, which is commonly used throughout a variety of industries. Given its toxic effect on humans and animals, the last 20 years have seen an increased interest in research devoted to the AA. One of the main sources of AA is food. AA appears in heated food following the reaction between amino acids and reduced sugars. Large concentrations of AA can be found in popular staples such as coffee, bread or potato products. An average daily consumption of AA is between 0.3-2.0 μg/kg b.w. Inhalation of acrylamide is related with occupational exposure. AA delivered with food is metabolized in the liver by cytochrome P450. AA biotransformation and elimination result in formation of toxic glycidamide (GA). Both, AA and GA can be involved in the coupling reaction with the reduced glutathione (GSH) forming glutathione conjugates which are excreted with urine. Biotransformation of AA leads to the disturbance in the redox balance. Numerous research proved that AA and GA have significant influence on physiological functions including signal propagation in peripheral nerves, enzymatic and hormonal regulation, functions of muscles, reproduction etc. In addition AA and GA show neurotoxic, genotoxic and cancerogenic properties. In 1994, International Agency for Research on Cancer (IARC) classified acrylamide as a potentially carcinogenic substance to human., M. Semla, Z. Goc, M. Martiniaková, R. Omelka, G. Formicki., and Obsahuje bibliografii
Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pyloriinfected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori., J. Astl, I. Šterzl., and Obsahuje bibliografii
High -energy intake which exceeds energy expenditure leads to the accumulation of triglycerides in adipose tissue, predominantly in large -size adipocytes. This metabolic shift, which drives the liver to produce atherogenic dyslipidemia, is well documented. In addition, an increasing amount of monocytes/macrophages, predominantly the proinflammatory M1- type, cumulates in ectopic adipose tissue. The mechanism of this process, the turnover of macrophages in adipose tissue and their direct atherogenic effects all remain to be analyzed., R. Poledne, I. Králová Lesná, S. Čejková., and Obsahuje bibliografii
The function of adult neurogenesis in the dentate gyrus is not yet completely understood, though many competing theories have attempted to explain the function of these newly -generated neurons. Most theories give adult neurogenesis a role in aiding known hippocampal/dentate gyrus functions. Other theories offer a novel role for these new cells based on their unique physiological qualities, such as their low excitability threshold. Many behavioral tests have been used to test these theories, but results have been inconsistent and often contradictory. Substantial variability in tests and protocols may be at least partially responsible for the mixed results. On the other hand, conflicting results arising from the same tests can serve as aids in elucidating the function of adult neurogenesis. Here, we offer a hypothesis that considers the cognitive nature of tasks commonly used to assess the function of adult neurogenesis, and introduce a dichotomy between tasks focused on discrimination vs. generalization. We view these two aspects as opposite ends of the continuous spectrum onto which traditional tests can be mapped. We propose that high neurogenesis favors behavioral discrimination while low adult neurogenesis favors behavioral generalization of a knowledge or rule. Since many tasks require both, the effects of neurogenesis could be cancelled out in many cases. Although speculative, we hope that our view presents an interesting and testable hypothesis of the effect of adult neurogenesis in traditional behavioral tasks. We conclude that new, carefully designed behavioral tests may be necessary to reach a final consensus on the role of adult neurogenesis in behavior., A. Pistikova, H. Brozka, A. Stuchlik., and Obsahuje bibliografii
AMP -activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α 2-subunit deletion affects heart function and ische mic tolerance of adult and aged mice. AMPK α 2 -/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α 2-subunit protein level, but no difference in AMPK α 1-subunit was detected between the strains. Both α 1- and α 2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α 2-subunit deletion and high-fat feeding on heart function and myocardia l ischemic tolerance in aged female mice are not additive., K. Slámová, F. Papoušek, P. Janovská, J. Kopecký, F. Kolář., and Obsahuje bibliografii
Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca2+-activated K+ (BKCa) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR). Age-matched Wistar-Kyoto rats (WKYs) were used as normotensive controls. Exercise groups completed an 8-week exercise program. Elevation of the α and β1 proteins was unequal in MA myocytes from SHRs, with the β1 subunit increasing more than the α subunit. BKCa contribution to vascular tone regulation was higher in the myocytes and arteries of SHRs compared to WKYs. SHR BKCa channel subunit protein expression, β1/α ratio, whole cell current density and single-channel open probability was also increased compared with WKYs. Aerobic exercise lowered systemic blood pressure and normalized hypertension-associated BKCa alterations to normotensive control levels in the SHRs. These effects were more pronounced in the moderate-intensity group than in the low-intensity group. There is a dose-effect for aerobic exercise training in the range of low to moderate-intensity and accompanying volume for the correction of the pathological adaptation of BKCa channels in myocytes of MAs from SHR., Y. Zhang, Y. Chen, L. Zhang, N. Lu, L. Shi., and Obsahuje bibliografii
Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts., V. Nagibin, T. Egan Benova, C. Viczenczova, B. Szeiffova Bacova, I. Dovinova, M. Barancik, N. Tribulova., and Obsahuje bibliografii
Chronic airflow limitation, caused by chronic obstructive pulmonary disease (COPD) or by asthma, is believed to change the shape and the position of the diaphragm due to an increase in lung volume. We have made a comparison of magnetic resonance imaging (MRI) of diaphragm in supine position with pulmonary functions, respiratory muscle function and exercise tolerance. We have studied the differences between patients with COPD, patients with asthma, and healthy subjects. Most interestingly we found the lung hyperinflation leads to the changes in diaphragmatic excursions during the breathing cycle, seen in the differences between the maxim al expiratory diaphragm position (DPex) in patients with COPD and control group (p=0.0016) . The magnitude of the diaphragmatic dysfunction was significantly related to the airflow limitation expressed by the ratio of forced expiratory volume in 1 s to slow vital capacity (FEV 1 /SVC) , (%, p=0.0007); to the lung hyperinflation expressed as the ratio of the residual volume to total lung capacity (RV/TLC), (%, p=0.0018) and the extent of tidal volume constrain expressed as maximal tidal volume (V Tmax ), ([l], p=0 .0002); and the ratio of tidal volume to slow vital capacity (VT/SVC), (p=0.0038) during submaximal exercise. These results suggest that diaphragmatic movement fails to contribute sufficiently to the change in lung volume in emphysema. Tests of respiratory muscle function were related to the position of the diaphragm in deep expiration, e.g. neuromuscular coupling (P 0.1 /VT) (p=0.0232). The results have shown that the lung volumes determine the position of the diaphragm and function of the respiratory muscles. Chronic airflow limitation seems to change the position of the diaphragm, which thereafter influences inspiratory muscle function and exercise tolerance. There is an apparent relationship between the position of the diaphragm and the pulmonary functions and exercise tolerance., L. Hellebrandová, J. Chlumský, P. Vostatek, D. Novák, Z. Rýznarová, V. Bunc., 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