Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SAC NS ) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryo nic ventricular myocytes were used for single - channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS , on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKc a channels but possibly also blocks SACNS , and thus decreases the stretch -induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential)., H. Jin, G. Iribe, K. Naruse., and Obsahuje bibliografii
Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there are characteristic rapid transient changes of intracellular Ca2+ concentration ([Ca2+]i), while the resting cytosolic [Ca2+]i concentration is low. It is mainly caused by two components of the Ca2+ signaling pathways: Ca2+ entry via L-type voltagedependent Ca2+ channels and dynamic involvement of intracellular stores. Proliferative VSMC phenotype is characterized by long-lasting [Ca2+]i oscillations accompanied by sustained elevation of basal [Ca2+]i. During the switch from contractile to proliferative phenotype there is a general transition from voltagedependent Ca2+ entry to voltage-independent Ca2+ entry into the cell. These changes are due to the altered gene expression which is dependent on specific transcription factors activated by various stimuli. It is an open question whether abnormal VSMC phenotype reported in rats with genetic hypertension (such as spontaneously hypertensive rats) might be partially caused by a shift from contractile to proliferative VSMC phenotype., E. Misárková, M. Behuliak, M. Bencze, J. Zicha., and Obsahuje bibliografii
In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-α and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-α (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71- 1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35±1.42 vs. 5.97±1.29 109 l); APA vs. IHA: TNF-α (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63- 1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37±1.41 vs. 5.71±1.21 109 l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] μg/l, p≤0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA., Z. Šomlóová, O. Petrák, J. Rosa, B. Štrauch, T. Indra, T. Zelinka, M. Haluzík, V. Zikán, R. Holaj, J. Widimský Jr., and Obsahuje bibliografii
The two i nferior colliculi (IC) are paired structures in the midbrain that are connected to each other by a bundle of commissural fibers. The fibers play an important role in coordinating sound signal processing between the two inferior colliculi. This study examined inter-collicular suppression on sound signal processing in amp litude domain of mice by measuring the rate-amplitude functions (RAFs) of neurons in one IC during the electrical stimulation of the opposite IC. Three types (monotonic, saturated and non-monotonic) RAFs of collicular neurons were measured before and durin g inter-collicular suppression. Inter-collicular suppression significantly increased the slope, decreased the dynamic range and narrowed down the responsive amplitude of all RAFs to high amplitude level but did not change the type of most (36/43, 84 % ) RAFs. As a result, all types of RAFs were compressed at a greater degree at low than at high sound amplitude during inter-collicular suppression. These data indicate that inter-collicular suppression improve sound processing in the high amplitude domain., Liang Cheng, Hui-Xian Mei, Yun Huang., 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
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
The maintenance of plasma sodium concentration within a narrow limit is crucial to life. When it differs from normal physiological patterns, several mechanisms are activated in order to restore body fluid homeostasis. Such mechanisms may be vegetative and/or behavioral, and several regions of the central nervous system (CNS) are involved in their triggering. Some of these are responsible for sensory pathways that per ceive a disturbance of the body fluid homeostasis and transmit information to other regions. These regions, in turn, initiate adequate adjustments in order to restore homeostasis. The main cardiovascular and autonomic responses to a change in plasma sodium concentration are: i) changes in arterial blood pressure and heart rate; ii) changes in sympathetic activity to the renal system in order to ensure adequate renal sodium excretion/absorption, and iii) the secretion of compounds involved in sodium ion home ostasis (ANP, Ang-II, and ADH, for example). Due to their cardiovascular effects, hypertonic saline solutions have been used to promote resuscitation in hemorrhagic patients, thereby increasing survival rates following trauma. In the present review, we exp ose and discuss the role of several CNS regions involved in body fluid homeostasis and the effects of acute and chronic hyperosmotic challenges., M. C. Dos Santos Moreira, L. M. Naves, S. M. Marques, E. F. Silva, A. C. S. Rebelo, E. Colombari, G. R. Pedrino., and Obsahuje bibliografii
Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described., M. Wackermannová, L. Pinc, L. Jebavý., and Obsahuje bibliografii