As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7β-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fattyliver index, triglycerides, cytokines (IL-2, IL-13, IFN-γ). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms., Markéta Šimková, Jana Vítků, Lucie Kolátorová, Jana Vrbíková, Michala Vosátková, Josef Včelák, Michaela Dušková., and Obsahuje bibliografii
Endotoxin lipopolysaccharide (LPS) affects the ruminant health and animal performance. The main purposes of this study were to investigate the potential effects of GH/IGF system and lipoprotein lipase (LPL) concentration on resistance the circulating LPS concentration increased in liver with high concentrate diet treatment. Non- lactating goats were randomly allocated to two groups : a high -concentrate diet (HCD ) or a low - concentrate diet (LCD ) in cross over design and the blood collection at different time points after feeding at the end of the experiment. The average rumen pH was significantly reduced (P<0.05) , but the duration with pH was not more than 120 min in the HCD group. T he plasma LPL concentration w as significantly raised (P<0.05) . However, fr om 2 h onwards, LPS concentration was significantly reduced (P<0.0 1) in the H CD group compared with LCD group. In addition , the plasma IGF1 concentration and the hepatic i nsulin -like growth factor -1 receptor ( IGF1R) mRNA expression were markedly reduced (P<0.0 5). However, g rowth hormone (GH) secretion at 15, 30, and 45 min after feeding and growth hormone receptor (GHR) mRNA expression in the liver was significantly increased (P<0.05) in HCD group. The correlation analysis showed that the plasma LPL concentration was positive ly correlated with hepatic GHR mRNA expression (P<0.05) . Conversely, the plasma LPS concentration was negatively correlate d with LPL concentration (P<0.05). These findings reveal that alterations in GH/IGF system function in response to a hi gh -concentrate diet are accompanied by corresponding changes in systemic LPL in non -lactating goats ’ liver in presence of endogenous LPS stress., Z. L. Xie, P. S. Ye, S. K. Zhang, Y. S. Zhang, X. Z. Shen., and Obsahuje bibliografii
This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K+ and Ca2+ in excitatory influx, the very low Na+, Ca2+ and Mg2+ concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a ‘normal’ composition is discussed. It is concluded that the unique endolymph cation content is more than an energy saving mechanism that avoids disturbing circulatory vibrations to achieve a much better mechanosensory resolution. It is the only possible way to fulfil the requirements for a precise ciliary mechanoelectrical transduction in conditions where pressure events with quite diverse amplitudes and duration are transformed into adequate hair cell membrane depolarizations, which are regulated by a sensitive Ca2+-dependent feedback tuning., H. Gagov, M. Chichova, M. Mladenov., and Seznam literatury
Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies., P. Ivak, J. Pitha, P. Wohlfahrt, I. Kralova Lesna, P. Stavek, Z. dorazilova, J. Stepankova, J. Maly, M. Pokorny, I. Netuka., and Obsahuje bibliografii
This study examined nitric oxide (NO) production, oxidative load and endothelium-dependent rela xation (NO-depe ndent and NO-independent) in adult male borderline hypertensive (BHR) and spontaneously hypertensive (S HR) rats as compared to normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined by tail-cuff. NO production was determined by conversion of [3 H]-L-arginine. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured for assessment of oxidative load. Vascular function was investigated in ri ngs of the femoral artery (FA) using a wire myograph. BP of WKY, BHR and SHR was 106 ± 2, 143 ± 3 and 191 ± 3 mm Hg, respectively (p<0.01 for each). Significant left ventricle (LV) hy pertrophy and elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared to WKY. NO production was elevated significantly in the aorta of BHR and SHR vs. WKY as well as in the LV of SHR vs. WKY. Acetylcholine (ACh)-induced relaxation of the FA was reduced significantly in both BHR and SHR vs. WKY. The NO-dependent component of ACh-induced relaxation had increasing tendency in hypertensive groups and it correlated positively with BP. The NO-independent component of vasorelaxation was reduced significantly in BHR and SHR vs. WKY and it correlated negatively with BP. In conclusion, the results showed that endothelial dysfunction in the experimental model of borderline hypertensive and hypertensive rats is NO-independent. The results suggest that borderline hypertension represents a risk of other cardiovascular disorders wh ich is qualitatively similar to that of fully developed hypertension., A. Púzserová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
In the present study we aimed to evaluate whether oxidative stress and inflammation induced by strenuous exercise affect glycocalyx integrity and endothelial function. Twenty one young, untrained healthy men performed a maximal incremental cycling exercise - until exhaustion. Markers of glycocalyx shedding (syndecan-1, heparan sulfate and hyaluronic acid), endothelial status (nitric oxide and prostacyclin metabolites - nitrate, nitrite, 6-keto-prostaglandin F1α), oxidative stress (8-oxo-2’- deoxyguanosine) and antioxidant capacity (uric acid, nonenzymatic antioxidant capacity) as well as markers of inflammation (sVCAM-1 and sICAM-1) were analyzed in venous blood samples taken at rest and at the end of exercise. The applied strenuous exercise caused a 5-fold increase in plasma lactate and hypoxanthine concentrations (p<0.001), a fall in plasma uric acid concentration and non-enzymatic antioxidant capacity (p<10−4), accompanied by an increase (p=0.003) in sVCAM-1 concentration. Plasma 6-keto-prostaglandin F1α concentration increased (p=0.006) at exhaustion, while nitrate and nitrite concentrations were not affected. Surprisingly, no significant changes in serum syndecan-1 and heparan sulfate concentrations were observed. We have concluded, that a single bout of severe-intensity exercise is well accommodated by endothelium in young, healthy men as it neither results in evident glycocalyx disruption nor in the impairment of nitric oxide and prostacyclin production., J. Majerczak, K. Duda, S. Chlopicki, G. Bartosz, A. Zakrzewska, A. Balcerczyk, R. T. Smoleński, J. A. Zoladz., and Obsahuje bibliografii
Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. Given that endothelial cells are the main source of ET-1 and ET-1 from other cells may encounter difficulty penetrating vascular compartments, we hypothesize that endothelial-derived ET-1 promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They were given intratracheal bleomycin and euthanized at day 28. We quantified pulmonary fibrosis, measured lung ET-1 and its receptors’ expression, and assessed pulmonary vascular remodeling by calculating medial wall index, muscularization index, adventitial collagen and adventitial fibroblast and macrophage accumulation. Right ventricle remodeling was also assessed. Both VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p<0.01). Expression of both ET-1 receptors mRNAs were increased in fibrosis models. Bleomycin-induced fibrosis VEETKO mice had significantly less muscularized arterioles, lower muscularization index and attenuated adventitial collagen, fibroblast and macrophage accumulation as compared to that of Wild type mice. Right ventricular pressure, hypertrophy and fibrosis did not increase both in VEETKO and Wild type mice despite the more enhanced vascular remodeling in Wild type. In conclusion, endothelialderived endothelin-1 promotes pulmonary vascular remodeling secondary to bleomycin-induced pulmonary fibrosis., A. B. Hartopo, N. Arfian, K. Nakayama, Y. Suzuki, K. Yagi, N. Emoto., and Seznam literatury
Heart remodeling occurs as a compensation mechanism for the massive loss of tissue during initial heart failure and the consequent inflammation process. During heart remodeling fibroblasts differentiate to myofibroblasts activate their secretion functions and produce elevated amounts, of extracellular matrix (ECM) proteins, mostly collagen, that form scar tissue and alter the normal degradation of ECM. Scar formation does replace the damaged tissue structurally; however, it impedes the normal contractive function of cardiomyocytes (CMs) and results in longlasting effects after heart failure. Besides CMs and cardiac fibroblasts, endothelial cells (ECs) and circulating endothelial progenitor cells (cEPCs) contribute to heart repair. This review summarizes the current knowledge of EC-CM crosstalk in cardiac fibrosis (CF), the role of cEPCs in heart regeneration and the contribution of Endothelial-mesenchymal transition (EndoMT)., Barbara Šalingová, Zdenko Červenák, Andriana Adamičková, Nikola Chromanicová, Simona Valášková, Andrea Gažová, Ján Kyselovič., and Obsahuje bibliografii
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects. The vasodilator response to the ET-1 antagonist BQ123 (1 μM) was significantly higher in arteries from obese hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries from obese hypertensive patients. The present study show that hypertension yet prevail after gastric bypass surgery and the ETA receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients., K. Gradin, B. Persson., and Seznam literatury
The global epidemic of diabetes is of significant concern. Diabetes associated vascular disease signifies the principal cause of morbidity and mortality in diabetic patients. It is also the most rapidly increasing risk factor for cognitive impairment, a silent disease that causes loss of creativity, productivity, and quality of life. Small vessel disease in the cerebral vasculature plays a major role in the pathogenesis of cognitive impairment in diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors (ETA and ETB), is a likely candidate that may be involved in many aspects of the diabetes cerebrovascular disease. In this review, we took a brain-centric approach and discussed the role of the ET system in cerebrovascular and cognitive dysfunction in diabetes., W. Li, Y. Abdul, R. Ward, A. Ergul., and Seznam literatury