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
Compression of the rostral ventrolateral medulla oblongata (RVLM) by an abnormally located artery is regarded as one possible cause of arterial hypertension. There exists a limited set of data suggesting that increased sympathetic activity in patients with RVLM compression may lead to arterial hypertension. Accordingly, we decided to assess the sympathetic activity in patients with severe arterial hy pertension and to investigate any correlation with the presence of RVLM compression. Sixty-four patients with severe arterial hypertension were enrolled in our study. Sympathetic activity was evaluated using 24-hour urinary norepinephrine as measured by high-pressure liquid chromatography with electrochemical detection. The presence of RVLM compression was assessed with magnetic resonance imaging. Neurovascular compression of the RVLM was identified in 40 patients, 27 of whom presented left-sided compression. Twenty-four hour urinary norepinephrine averaged 263.6± 135.9 nmol in patients with neurovascular compression - 255.6±137.3 nmol in those with left-sided compression and 251.6±138.5 nmol in patients without RVLM compression. We did not identify any increase in urinary norepinephrine in patients with severe arterial hypertension and neurovascular compression of the RVLM. Our results do not support the hypothesis that neurovascular compression of RVLM may exhibit a sympathetically mediated increase in blood pressure., M. Solař ... [et al.]., 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
Pulse dye densitometry (PDD) enables the evaluation of hemodynamic state as well as liver function. A repeated examination, even after a short pause (or under stress condition), enables to follow safely the dynamics of liver pathology. From presented parameters we have evaluated as reliable the C5-clearance, an expression of equilibrium state in the two compartment liver system. Furthermore, T-index expresses ratio of C5 value to cardiac output, it is a sensitive indicator of the blood pole, i.e. sinusoidal uptake, which is in very good correlation with staging of hepatopathies. The isolated h constant in correlation to T-index is valuable For functional grading. The Japanese automatic analyzer of indocyanine green (ICG) dilution and elimination curves, after incorporation of a two compartment mathematical mode l, becomes more useful for complex hepatological diagnostics. Non-invasive PDD is becoming of uppermost importance to clinic al interest, yielding comparable results as other complicated and invasive examinations and may be, therefore, repeated in short time intervals for different indications with minimal stress of examined patient., J. A. Tichý ... [et al.]., and Obsahuje seznam literatury
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
During the last thirty years since the discovery of endothelin-1, the therapeutic strategy that has evolved in the clinic, mainly in the treatment of pulmonary arterial hypertension, is to block the action of the peptide either at the ETA subtype or both receptors using orally active small molecule antagonists. Recently, there has been a rapid expansion in research targeting ET receptors using chemical entities other than small molecules, particularly monoclonal antibody antagonists and selective peptide agonists and antagonists. While usually sacrificing oral bio-availability, these compounds have other therapeutic advantages with the potential to considerably expand drug targets in the endothelin pathway and extend treatment to other pathophysiological conditions. Where the small molecule approach has been retained, a novel strategy to combine two vasoconstrictor targets, the angiotensin AT1 receptor as well as the ETA receptor in the dual antagonist sparsentan has been developed. A second emerging strategy is to combine drugs that have two different targets, the ETA antagonist ambrisentan with the phosphodiesterase inhibitor tadalafil, to improve the treatment of pulmonary arterial hypertension. The solving of the crystal structure of the ETB receptor has the potential to identify allosteric binding sites for novel ligands. A further key advance is the experimental validation of a single nucleotide polymorphism that has genome wide significance in five vascular diseases and that significantly increases the amount of big endothelin-1 precursor in the plasma. This observation provides a rationale for testing this single nucleotide polymorphism to stratify patients for allocation to treatment with endothelin agents and highlights the potential to use personalized precision medicine in the endothelin field., A. P. Davenport, R. E. Kuc, C. Southan, J. J. Maguire., and Seznam literatury
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