In most macrovascular endothelial cell (EC) preparations, resting membrane potential is determined by the inwardly rectifying K+ current (IK1), whereas in microvascular EC the presence of IK1 varies markedly. Cultured microvascular EC from small vessels of human omentum were examined by means of the voltage-clamp technique to elucidate the putative role of IK1 in maintaining resting membrane potential. Macrovascular EC from human iliac artery and bovine aorta served as reference. Human omentum EC showed an outwardly rectifying current-voltage relation. Inward current was hardly sensitive to variations of extracellular [K+] and Ba2+ block suggesting lack of IK1. However, substitution of extracellular [Na+] and/or [Cl-] affected the current-voltage relation indicating that Na+ and Cl- contribute to basal current. Furthermore, outward current was reduced by tetraethylammonium (10 mM), and cell-attached recordings suggested the presence of a Ca2+-activated K+ current. In contrast to human omentum EC, EC from human iliac artery and bovine aorta possessed inwardly rectifying currents which were sensitive to variations of extracellular [K+] and blocked by Ba2+. Thus, the lack of IK1 in human omentum EC suggests that resting membrane potential is determined by Na+ and Cl- currents in addition to K+ outward currents., H. M. Himmel, U. Rauen, U. Ravens., and Obsahuje bibliografii
Numerous countermeasures have been proposed to minimize microgravity-induced physical deconditioning, but their benefits are limited. The present study aimed to investigate whether personalized aerobic exercise based on artificial gravity (AG) mitigates multisystem physical deconditioning. Fourteen men were assigned to the control group (n=6) and the countermeasure group (CM, n=8). Subjects in the CM group were exposed to AG (2 Gz at foot level) for 30 min twice daily, during which time cycling exercise of 80-95 % anaerobic threshold (AT) intensity was undertaken. Orthostatic tolerance (OT), exercise tests, and blood assays were determined before and after 4 days head-down bed rest (HDBR). Cardiac systolic function was measured every day. After HDBR, OT decreased to 50.9 % and 77.5 % of pre-HDBR values in control and CM groups, respectively. Exercise endurance, maximal oxygen consumption, and AT decreased to 96.5 %, 91.5 % and 91.8 % of pre-HDBR values, respectively, in the control group. Nevertheless, there were slight changes in the CM group. HDBR increased heart rate, sympathetic activity, and the pre-ejection period, but decreased plasma volume, parasympathetic activity and left-ventricular ejection time in the control group, whereas these effects were eliminated in the CM group. Aldosterone had no change in the control group but increased significantly in the CM group. Our study shows that 80-95 % AT aerobic exercise based on 2 Gz of AG preserves OT and exercise endurance, and affects body fluid regulation during short-term HDBR. The underlying mechanisms might involve maintained cardiac systolic function, preserved plasma volume, and improved sympathetic responses to orthostatic stress., X.-T. Li, C.-B. Yang, Y.-S. Zhu, J. Sun, F. Shi, Y.-C. Wang, Y. Gao, J.-D. Zhao, X.-Q. Sun., and Obsahuje bibliografii
Transient receptor potential A1 (TRPA1) is an excitatory ion channel that functions as a cellular sensor, detecting a wide range of proalgesic agents such as environmental irritants an d endogenous products of inflammation and oxidative stress. Topical application of TRPA1 agonists produces an acute nociceptive response through peripheral release of neuropeptides, purines and other transmitters from activated sensory nerve endings. This, in turn, further regulates TRPA1 activity downstream of G-protein and phospholipase C -coupled signaling cascades. Despite the important physiological relevance of such regulation leading to nociceptor sensitization and consequent pain hypersensitivity, th e specific domains through which TRPA1 undergoes post -translational modifications that affect its activation properties are yet to be determined at a molecular level. This review aims at providing an account of our current knowledge on molecular basis of r egulation by neuronal inflammatory signaling pathways that converge on the TRPA1 channel protein and through modification of its specific residues influence the extent to which this channel may contribute to pain., A. Kádková, V. Synytsya, J. Krusek, L. Zímová, V. Vlachová., and Obsahuje bibliografii
This study was aimed to evaluate the role of commensal Gram-negative bacterium Bacteroides ovatus in murine model of chronic intestinal inflammation. The attempt to induce chronic colitis was done in Bacteroides ovatus-monoassociated, germ-free and conventional mice either in immunocompetent (BALB/c) mice or in mice with severe combined immunodeficiency (SCID), using 2.5 % dextran-sodium sulfate (DSS) in drinking water (7 days DSS, 7 days water, 7 days DSS). Conventional mice developed chronic colitis. Some of germ-free BALB/c and the majority of germ-free SCID mice did not survive the long-term treatment with DSS due to massive bleeding into the intestinal lumen. However, monocolonization of germ-free mice of both strains with Bacteroides ovatus prior to long-term treatment with DSS protected mice from bleeding, development of intestinal inflammation and precocious death. We observed that though DSS-treated Bacteroides ovatus-colonized SCID mice showed minor morphological changes in colon tissue, jejunal brush-border enzyme activities such as γ-glutamyltranspeptidase, lactase and alkaline phosphatase were significantly reduced in comparison with DSS-untreated Bacteroides ovatus-colonized mice. This modulation of the enterocyte γ-glutamyltranspeptidase localized to the brush border membrane has been described for the first time. This enzyme is known to reflect an imbalance between pro-oxidant and anti-oxidant mechanisms, which could be involved in protective effects of colonization of germ-free mice with Bacteroides ovatus against DSS injury., T. Hudcovic ... [et al.]., and Obsahuje seznam literatury
Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium., F. Novák ... [et al.]., and Obsahuje seznam literatury
An interaction between N-methyl-D-aspartate (NMDA) and MK-801 was examined in mice using a modified elevated plus-maze paradigm that allows assessment of the adaptive form of spatial memory. NMDA administered (s.c.) immediately after the acquisition session protected the animals against the amnesia induced by MK-801 given shortly before the retention session. Behavioral performance, expressed as the transfer latency, and therefore spatial memory potency of NMDA plus MK-801 treated animals was comparable with that of both NMDA-treated animals and the controls., Z. Hliňák, I. Krejčí., and Obsahuje bibliografii
Anthracyclines, e.g. doxorubicin, pirarubicin, are widely used as cytostatic agents in the polymer nanotherapeutics designed for the highly effective antitumor therapy with reduced side effects. However, their precise dosage scheme needs to be optimized, which requires an accurate method for their quantification of the cellular level in vitro during nanocarrier development and in body fluids and tissues during testing in vivo. Various methods detecting the anthracycline content in biological samples have already been designed. most of them are highly demanding and they differ in exactness and reproducibility. The cellular uptake and localization is predominantly observed and determined by microscopy techniques, the anthracycline content is usually quantified by chromatographic analysis using fluorescence detection. We reviewed and compared published methods concerning the detection of anthracycline nanocarriers., E. Koziolova, O. Janouskova, P. Chytil, M. Studenovsky, L. Kostka, T. Etrych., and Obsahuje bibliografii
The natriuretic peptides - atrial, brain and C-type - were discovered during the last tw enty years. Their effects on cardiovascular, renal, cerebral and other tissues through guanylyl cyclase were uncovered. Over the past decade natriuretic peptides (NPs) became a very useful tool in the management of heart failure patients. Results of many clinical trials have shown that BNP and NT-proBNP are helpful for diagnosis of heart failure. They are also independent markers of prognosis not only in heart failure patients but also in patients with other cardiovascular diseases. Recently published data document the utility of NPs in guiding treatment of heart failure patients. In this article, we focus on basic biochemical and physiological characteristics of NPs as well as on their significance in management of heart failure patients. Some limitations and pitfalls of NPs levels interpretation in diagnosing heart failure are also discussed., J. Krupička ... [et al.]., and Obsahuje seznam literatury
Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, rat hearts isolated on days 1, 4, 7 and 10 of po stnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC wa s induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol wa s then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life. and J. Doul, Z. Charvátová, I. Ošťádalová, M. Kohutiar, H. Maxová, B. Ošťádal.
The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH., H. Feng, Q. Wang, F. Guo, X. Han, M. Pang, X. Sun, Y. Gong, L. Xu., and Obsahuje bibliografii