In the mammalian autonomic nervous system, tonic and phasic neurons can be differentiated on firing patterns in response to long depolarizing current pulse. However, the similar firing patterns in the somatic primary sensory neurons and their functional significance are not well investigated. Here, we identified two types of neurons innervating somatic sensory in rat dorsal root ganglia (DRG). Tonic neurons fire action potentials (APs) in an intensity-dependent manner, whereas phasic neurons typically generate only one AP firing at the onset of stimulation regardless of intensity. Combining retrograde labeling of somatic DRG neurons with fluorescent tracer DiI, we further find that these neurons demonstrate distinct changes under inflammatory pain states induced by complete Freund’s adjuvant (CFA) or bee venom toxin melittin. In tonic neurons, CFA and melittin treatments significantly decrease rheobase and AP durations (depolarization and repolarization), enhance amplitudes of overshoot and afterhyperpolarization (AHP), and increase the number of evoked action potentials. In phasic neurons, however, the same inflammation treatments cause fewer changes in these electrophysiological parameters except for the increased overshoot and decreased AP durations. In the present study, we find that tonic neurons are more hyperexcitable than phasic neurons after peripheral noxious inflammatory stimulation. The results indicate the distinct contributions of two types of DRG neurons in inflammatory pain., Y.-Q. Yu, X.-F. Chen, Y. Yang, F. Yang, J. Chen., and Obsahuje bibliografii
This study has observed possible effect of ellagitannins - compounds from pomegranate on process of steroidogenesis in ovaries. The aim of the study was to investigate the possible effect of punicalagin on secretion of steroid hormones - progesterone, androstenedione, testosterone and 17β-estradiol by ovarian fragments of rabbits in vitro. Ovarian fragments from sexually mature female New Zealand white rabbits (n=20) were incubated without (control group) or with punicalagin at various doses 1, 10 and 100 μg.ml−1 for 24 h. Hormones were evaluated by ELISA (The Enzyme-Linked Immunosorbent Assay). Data showed that progesterone and 17β-estradiol (but not androstenedione and testosterone) release by rabbit ovarian fragments was significantly affected by punicalagin addition at various doses. Punicalagin (at 100 μg.ml-1) significantly (P<0.05) increased progesterone secretion. On the other hand, the release of 17β-estradiol was significantly (P<0.005) decreased by punicalagin addition (at 10 μg.ml-1). Our results suggest that punicalagin could have dose-dependent impact on secretion of steroid hormones progesterone and 17β-estradiol by rabbit ovarian fragments and it may be effector in process of ovarian steroidogenesis., D. Packova, A. A. Carbonell-Barrachina, A. Kolesarova., and Obsahuje bibliografii
After menopause, when estrogen levels decrease, there is room for the activity of anthropogenic substances with estrogenic properties - endocrine disruptors (EDs) - that can interfere with bone remodeling and changes in calcium-phosphate metabolism. Selected unconjugated EDs of the bisphenol group - BPA, BPS, BPF, BPAF, and the paraben family - methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens - were measured by high performance liquid chromatography-tandem mass spectrometry in the plasma of 24 postmenopausal women. Parameters of calcium-phosphate metabolism and bone mineral density were assessed. Osteoporosis was classified in 14 women, and 10 women were put into the control group. The impact of EDs on calcium-phosphate metabolism was evaluated by multiple linear regressions. In women with osteoporosis, concentrations of BPA ranged from the lower limit of quantification (LLOQ) - 104 pg/ml and methyl paraben (MP) from LLOQ - 1120 pg/ml. The alternative bisphenols BPS, BPF and BPAF were all under the LLOQ. Except for MP, no further parabens were detected in the majority of samples. The multiple linear regression model found a positive association of BPA (β=0.07, p<0.05) on calcium (Ca) concentrations. Furthermore, MP (β=-0.232, p<0.05) was negatively associated with C-terminal telopeptide. These preliminary results suggest that these EDs may have effects on calcium-phosphate metabolism., J. Vitku, L. Kolatorova, L. Franekova, J. Blahos, M. Simkova, M. Duskova, T. Skodova, L. Starka., 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
The aim of present study was to investigate functional and physical alterations in membranes of heart mitochondria that are associated with remodeling of these organelles in acute phase of streptozotocin-induced diabetes and to elucidate the role of these changes in adaptation of the heart to acute streptozotocin-induced diabetes (evaluated 8 days after single dose streptozotocin application to male Wistar rats). Action of free radicals on the respiratory chain of diabetic-heart mitochondria was manifested by 17 % increase (p<0.05) in oxidized form of the coenzyme Q10 and resulted in a decrease of states S3 and S4 respiration, the respiratory control index, rate of phosphorylation (all p<0.01) and the mitochondrial transmembrane potential (p<0.05), but the ADP/O ratio decreased only moderately (p>0.05). On the contrary, membrane fluidity and the total mitochondrial Mg2+-ATPase activity increased (both p<0.05). In diabetic heart mitochondria, linear regression analysis revealed a reciprocal relationship between the increase in membrane fluidity and decrease in trans-membrane potential (p<0.05, r = 0.67). Changes in membrane fluidity, transmembrane potential, Mg2+-ATPase activity and the almost preserved ADP/O ratio appear as the manifestation of endogenous protective mechanisms participating in the functional remodeling of mitochondria which contributes to adaptation of the heart to diabetes., M. Ferko, D. Habodászová, I. Waczulíková, J. Mujkošová, J. Kucharská, L. Šikurová, B. Ziegelhöffer, J. Styk, A. Ziegelhöffer., and Obsahuje bibliografii a bibliografické odkazy
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
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
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