Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflam matory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9±10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1β , IL-6, IL-8, tumor necrosis factor-α , and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48 % fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance., P. Maruna ... [et al.]., and Obsahuje seznam literatury
Tissue factor is a cell surface protein that is expressed constitutively by monocytes, macrophages and fibroblasts, but also by some other cells in response to a variety of stimuli. The main function of the tissue factor is to form a complex with factor VII/VIIa that converts factors IX and X to their active forms. Tissue factor is also involved in the pathophysiology of systemic inflammatory disorders, coagulopathies, atherosclerotic disease, tumor angiogenesis and metastasis. Increased tissue factor expression either locally in the coronary plaques or systematically on circulating blood elements of patients with acute coronary syndromes may be responsible for increased thrombin generation, thus leading to platelet activation and fibrin formation. Tissue factor therefore plays a pivotal role in the initiation of thrombotic complications in patients with coronary artery disease., J. Vojáček, J. Dušek, J. Bis, J. Šťásek, M. Blažek., and Obsahuje bibliografii a bibliografické odkazy
Although statins exert non-lipid cardioprotective effects, their influence on cell death is not fully elucidated. For this purpose, we investigated whether simvastatin treatment (S, 10 mg/kg, 5 days) is capable of mitigating ischemia/reperfusion-induced (IR) apoptosis in the isolated rat hearts, which was examined using immunoblotting analysis. In addition, the content of signal transducer and activator of transcription 3 (STAT3) and its active form, phosphorylated STAT3 (pSTAT3-Thr705), was analyzed. Simvastatin induced neither variations in the plasma lipid levels nor alterations in the baseline content of analysed proteins with the exception of upregulation of cytochrome C. Furthermore, simvastatin significantly increased the baseline levels of pSTAT3 in contrast to the control group. In the IR hearts, simvastatin reduced the expression of Bax and non-cleaved caspase-3. In these hearts, phosphorylation of STAT3 did not differ in comparison to the non-treated IR group, however total STAT3 content was slightly increased. The improved recovery of left ventricular developed pressure co-existed with the increased Bcl- 2/Bax ratio. In conclusion, pleiotropic action of statins may ameliorate viability of cardiomyocytes by favouring the expression of anti-apoptotic Bcl-2 and downregulating the proapoptotic markers; however STAT3 does not seem to be a dominant regulator of this anti-apoptotic action of simvastatin., T. Rajtík, ... [et al.]., and Obsahuje seznam literatury
Inherited disturbances of the mitochondrial energy generating system represent a heterogeneous group of disorders associated with a broad spectrum of metabolic abnormalities and clinical symptoms. We used the polarographic and spectrophotometric method for detection of mitochondrial disorders, because these two techniques provide a different insight into mitochondrial function. In six patients suspected of mitochondrial disease we found defects of complex I (two patients), complex III (one patient), complex IV (two patients) and a combination of defect of complex III and IV (one patient). Citrate synthase activity, used as the reference enzyme, was not changed. A comparison of the two methods showed several differences in evaluation of mitochondrial enzymes activity due to the fact that both methods used different conditions for enzyme activity measurements. In contrast to oxygen consumption measurements, where the function of the whole-integrated respiratory chain is characterized, spectrophotometric measurements characterize activities of isolated complexes in disintegrated membranes. However, it may be concluded from our experiments that both methods provide useful and complementary data about mitochondrial energetic functions. Whereas spectrophotometric data are suitable for evaluation of maximal enzyme activities of mitochondrial enzyme complexes, polarographic data provide better information about enzyme activities in cells with mitochondrial defects under in situ conditions., L. Wenchich, Z. Drahota, T. Honzík, H. Hansíková, M. Tesařová, J. Zeman, J. Houštěk., and Obsahuje bibliografii
Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modeling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0.1, 1, and 10 μM). Gene expression analyses were performed using RT-qPCR at days 4, 10, 21, 24, 28; p rotein l evels A kt a nd phosphorylated Akt (Phospho-Akt) by Western blot at days 4, and 21. PCB 153 treatment of h-ADMSCs only in lipid vehicle was associated with down regulation of key master genes of adipogenesis: PPARγ, SREBP-1, PPARGC1B, and PLIN2 during the whole process of differentiation; and with increased Akt and decreased Phospho-Akt protein level at day 21. We have shown that PCB 153, in concentration 0.1 μM, has a potential in lipid rich environment to modulate differentiation of adipocytes. Because European and U.S. adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity and insulin sensitivity., D. Mullerova, M. Pesta, J. Dvorakova, M. Cedikova, V. Kulda, P. Dvorak, V. Bouchalová, M. Kralickova, V. Babuska, J. Kuncova, J. Langmajerova, L. Muller., and Obsahuje bibliografii
Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the “gold standard” for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no except ion. The first GWAS focused on hypercholesterole mia and dyslipid emia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recogni ze the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analy zed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post -MONICA population sample (N= 2,559). We confirmed an association (all P<0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males (N= 1,194) and females (N =1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P<0.0005) and females (P<0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants., J. A. Hubacek, V. Adamkova, V. Lanska, D. Dlouha., and Obsahuje bibliografii
Inflammation is a vital defense mechanism of living organisms. However, persistent and chronic inflammation may lead to severe pathological processes and evolve into various chronic inflammatory diseases (CID), e.g. rheumatoid arthritis, multiple sclerosis, multiple sclerosis, systemic lupus erythematosus or inflammatory bowel diseases, or certain types of cancer. Their current treatment usually does not lead to complete remission. The application of nanotherapeutics may significantly improve CID treatment, since their accumulation in inflamed tissues has been described and is referred to as extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS). Among nanotherapeutics, water-soluble polymer-drug conjugates may be highly advantageous in CID treatment due to the possibility of their passive and active targeting to the inflammation site and controlled release of active agents once there. The polymer-drug conjugate consists of a hydrophilic biocompatible polymer backbone along which the drug molecules are covalently attached via a biodegradable linker that enables controlled drug release. Their active targeting or bio-imaging can be achieved by introducing the cell-specific targeting moiety or imaging agents into the polymer conjugate. Here, we review the relationship between polymer conjugates and inflammation, including the benefits of the application of polymer conjugates in inflammation treatment, the anti-inflammatory activity of polymer drug conjugates and potential polymer-promoted inflammation and immunogenicity., E. Koziolová, K. Venclíková, T. Etrych., and Obsahuje bibliografii