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
Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient’s prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination., Martin Petras, Dagmar Kalenska, Matej Samos, Tomas Bolek, Miroslava Sarlinova, Peter Racay, Erika Halasova, Oliver Štrbák, Jan Stasko, Ludovit Musak, Michaela Skorvanova, Eva Baranovicova., and Obsahuje bibliografii
We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106±12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334±12 vs. 125±32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2±7.2 vs. 7.3±2.2 vs. 8.3±5.5 min, p=0.003), cessation of LVMA (11.3±5.6 vs. 4.4±0.4 vs. 7.4±2.9 min, p=0.027) and cessation of microcirculation (25.3±12.6 vs. 13.4±2.4 vs. 23.2±8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA., R. Skulec, D. Astapenko, R. Cerna Parizkova, B. Furst, M. Bilska, T. Parizek, T. Hovanec, N. Pinterova, J. Knor, J. Dudakova, A. Truhlar, V. Radochova, Z. Zadak, V. Cerny., and Obsahuje bibliografii
The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury., M. Barančík, L. Grešová, M. Barteková, I. Dovinová., and Obsahuje bibliografii
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. In addition to the genetic, epigenetic and immunological components, various other factors, e.g. unhealthy dietary habits, play a role in the MS pathogenesis. Dietary intervention is a highly appealing approach, as it presents a simple and relatively low risk method to potentially improve outcomes in patients with brain disorders in order to achieve remission and improvement of clinical status, well-being and life expectancy of patients with MS. The importance of saturated fat intake restriction for the clinical status improvement of MS patients was pointed for the first time in 1950s. Recently, decreased risk of first clinical diagnosis of CNS demyelination associated with higher intake of omega-3 polyunsaturated fatty acids particularly originating from fish was reported. Only few clinical trials have been performed to address the question of the role of dietary intervention, such is e.g. low saturated fat diet in MS treatment. This review summarizes current knowledge about the effect of different dietary approaches (diets low in saturated fat and dietary supplements such as fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, seeds oils, high fiber diet, vitamin D, etc.) on neurological signs, patient’s well-being, physical and inflammatory status. So far the results are not conclusive, therefore much more research is needed to confirm and to understand the effectiveness of these dietary interventions in the long term and well defined studies., A. Penesová, Z. Dean, B. Kollár, A. Havranová, R. Imrich, M. Vlček, Ž. Rádiková., and Obsahuje bibliografii