Some aspects of olfactory sensitivity in the pulmonate Helix pomatia L. were studied by means of neurophysiological and behavioral methods. Single fiber recordings were carried out in the olfactory nerve of the posterior tentacles. Olfactory stimulations with different odors were performed by means of a continuous air stream. The order of neuronal sensitivity to different odors was as follows: ethanol³ ethyl acetate > pentanol > hexanol > octanol > diethyl malonate > vanillin. Furthermore, the results revealed a relative specificity for some substances. A comparison between neurophysiological and behavioral data shows that those substances, which cause the highest increases in impulse frequency, also evoke a behavioral avoidance reaction., M. Voss., and Obsahuje bibliografii
Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnenolone sulphate (3α5βS). While PS effect is most pronounced when its application precedes that of glutamate, 3α5βS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3α5βS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3α5βS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action., M. Sedláček, M. Kořínek, M. Petrovič, O. Cais, E. Adamusová, H. Chodounská, L. Vyklický Jr., and Obsahuje bibliografii a bibliografické odkazy
The main neuromodulatory methods using neurostimulation principles are described. It concerns peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), deep brain stimulation (DBS), motor cortex stimulation (MSC), and repetitive transcranial magnetic stimulation (rTMS). For each method the history, pathophysiology, the principles for use and the associated diagnoses are mentioned. Special attention is focused on the most common neuromodulatory invasive methods like SCS and MCS and non-invasive methods such as rTMS. In addition to the positive effects, side effects and complications are described and discussed in detail. In conclusion, neuromodulatory (neurostimulatory) techniques are highly recommended for the treatment of different types of pharmacoresistant pain., R. Rokyta, J. Fricová., and Obsahuje seznam literatury
The availability of the human genome sequence and the recently completed draft sequences of two major mammalian model species, the mouse (Mus musculus) and the rat (Rattus norvegicus), allow researchers to apply novel approaches for gene identification and characterization, using methods of comparative and functional genomics. Recently, a new gene coding for apolipoprotein A-V was identified in the vicinity of APOA-I/C-III/A-IV cluster on human chromosome 11q23 by comparative sequencing method. In a relatively short time, compelling evidence accumulated for the substantial role of APOA-V in lipid metabolism. Studies in knock-out and transgenic mice revealed that its expression pattern correlates negatively with triglyceride levels. This observation was verified in human population studies in variety of ethnic and age groups. Several single nucleotide polymorphisms were described and particular SNP alleles and haplotypes in the APO A-V gene region were shown to be associated with dyslipidemia. The discovery and characterization of the APO A-V demonstrates current possibilities of the integrative approaches in biology, boosted by the available bioinformatic tools., O. Šeda, L. Šedová., and Obsahuje bibliografii
The kidney is a common “victim organ” of various insults in critically ill patients. Sepsis and septic shock are the dominant causes of acute kidney injury, accounting for nearly 50 % of episodes of acute renal failure. Despite our substantial progress in the understanding of mechanisms involved in septic acute kidney injury there is still a huge pool of questions preclusive of the development of effective ther apeutic strategies. This review briefly summarizes our current knowledge of pathophysiological mechanisms of septic acute kidney injury focusing on hemodynamic alterations, peritubular dysfunction, role of inflammatory mediators and nitric oxide, mitochondrial dysfunction and structural chan ges. Role of proteomics, new promising laboratory method, is mentioned., J. Chvojka, R. Sýkora, T. Karvunidis, J. Raděj, A. Kroužecký, I. Novák, M. Matějovič., and Obsahuje bibliografii
Monophasic action potential (MAP) recording plays an important role in a more direct view of human myocardial electrophysiology under both physiological and pathological conditions. The procedure of MAP measuring can be simply performed using the Seldinger technique, when MAP catheter is inserted through femoral vein into the right ventricle or through femoral artery to the left ventricle. The MAP method represents a very useful tool for electrophysiological research in cardiology. Its crucial importance is based upon the fact that it enables the study of the action potential (AP) of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. This can be particularly helpful in the case of arrhythmias. There are no doubts that physiological MAP recording accuracy is almost the same as transmembrane AP as was recently confirmed by anisotropic bidomain model of the cardiac tissue. MAP recording devices provide precise information not only on the local activation time but also on the entire local repolarization time course. Although the MAP does not reflect the absolute amplitude or upstroke velocity of transmembrane APs, it delivers highly accurate information on AP duration and configuration, including early afterdepolarizations as well as relative changes in transmembrane diastolic and systolic potential changes. Based on available data, the MAP probably reflects the transmembrane voltage of cells within a few millimeters of the exploring electrode. Thus MAP recordings offer the opportunity to study a variety of electrophysiological phenomena in the in situ heart (including effects of cycle length changes and antiarrhythmic drugs on AP duration)., S.-G. Yang, O. Kittnar., and Obsahuje bibliografii a bibliografické odkazy
Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies., B. Aldhoon ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Bone metabolism is regulated by interaction between two skeletal cells – osteoclasts and osteoblasts. Function of these cells is controlled by a number of humoral factors, including neurohormones, which ensure equilibrium between bone resorption and bone formation. Influence of neurohormones on bone metabolism is often bimodal and depends on the tissue, in which the hormone is expressed. While hypothalamic beta-1 and beta-2-adrenergic systems stimulate bone formation, beta-2 receptors in bone tissue activate osteoclatogenesis and increases bone resorption. Chronic stimulation of peripheral beta-2 receptors is known to quicken bone loss and alter the mechanical quality of the skeleton. This is supported by the observation of a low incidence of hip fractures in patients treated with betablockers. A bimodal osteo-tropic effect has also been observed with serotonin. While serotonin synthetized in brain has osteo-anabolic effects, serotonin released from the duodenum inhibits osteoblast activity and decreases bone formation. On the other hand, both cannabinoid systems (CB1 receptors in the brain and CB2 in bone tissue) are unambiguously osteoprotective, especially with regard to the aging skeleton. Positive (protective) effects on bone have also been shown by some hypophyseal hormones, such as thyrotropin (which inhibits bone resorption) and adrenocorticotropic hormone and oxytocin, both of which stimulate bone formation. Low oxytocin levels have been shown to potentiate bone loss induced by hypoestrinism in postmenopausal women, as well as in girls with mental anorexia. In addition to reviewing neurohormones with anabolic effects, this article also reviews neurohormones with unambiguously catabolic effects on the skeleton, such as neuropeptide Y and neuromedin U. An important aim of research in this field is the synthesis of new molecules that can stimulate osteo-anabolic or inhibiting osteo-catabolic processes., I. Žofková, P. Matucha., and Obsahuje bibliografii
In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/β-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure., I. Zofkova, J. Blahos., and Obsahuje bibliografii
The reactions of human organism to changes of internal or external environment termed as stress response have been at the center of interest during recent decades. Several theories were designed to describe the regulatory mechanisms which maintain the stability of vital physiological functions under conditions of threat or other environmental challenges. However, most of the models of stress reactivity were focused on specific aspects of the regulatory outcomes - physiological (e.g. neuroendocrine), psychological or behavioral regulation. Recently, a novel complex theory based on evolutionary and developmental biology has been introduced. The Adaptive Calibration Model of stress response employs a broad range of the findings from previous theories of stress and analyzes the responsivity to stress with respect to interindividual differences as a consequence of conditional adaptation - the ability to modify developmental trajectory to match the conditions of the social and physical environment. This review summarizes the contributions of the most important models in the field of stress response and emphasizes the importance of complex analysis of the psycho-physiological mechanisms. Moreover, it outlines the implications for nonpharmacological treatment of stress-related disorders with the application of biofeedback training as a promising tool based on voluntary modification of neurophysiological functions., I. Tonhajzerova, M. Mestanik., and Obsahuje bibliografii