Olmesartan/amlodipine: a review of its use in the management of hypertension

Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy

Synaptic GluN2B/CaMKII-α signaling induces synapto-nuclear transport of ERK and Jacob

A central pathway in synaptic plasticity couples N-Methyl-D-Aspartate-receptor (NMDAR)-signalling to the activation of extracellular signal-regulated kinases (ERKs) cascade. ERK-dependency has been demonstrated for several forms of synaptic plasticity as well as learning and memory and includes local synaptic processes but also long-distance signalling to the nucleus. It is, however, controversial how NMDAR signals are connected to ERK activation in dendritic spines and nuclear import of ERK. The synapto-nuclear messenger Jacob couples NMDAR-dependent Ca2+-signalling to CREB-mediated gene expression. Protein transport of Jacob from synapse to nucleus essentially requires activation of GluN2B-containing NMDARs. Subsequent phosphorylation and binding of ERK1/2 to and ERK-dependent phosphorylation of serine 180 in Jacob encodes synaptic but not extrasynaptic NMDAR activation. In this study we show that stimulation of synaptic NMDAR in hippocampal primary neurons and induction of long-term potentiation (LTP) in acute slices results in GluN2B-dependent activation of CaMKII-α and subsequent nuclear import of active ERK and serine 180 phosphorylated Jacob. On the contrary, no evidence was found that either GluN2A-containing NMDAR or RasGRF2 are upstream of ERK activation and nuclear import of Jacob and ERK

The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders.

Over the last decade, an increasing number of reports underscored the importance of epigenetic regulations in brain plasticity. Epigenetic elements such as readers, writers and erasers recognize, establish, and remove the epigenetic tags in nucleosomes, respectively. One such regulation concerns DNA-methylation and demethylation, which are highly dynamic and activity-dependent processes even in the adult neurons. It is nowadays widely believed that external stimuli control the methylation marks on the DNA and that such processes serve transcriptional regulation in neurons. In this mini-review, we cover the current knowledge on the regulatory mechanisms controlling in particular DNA demethylation as well as the possible functional consequences in health and disease

Определение деформаций провода обмоток трансформатора собственным магнитным полем

Приводится рассмотрение продольных и поперечных деформаций проводника обмотки трансформатора, вызванных током короткого замыкания. Приводятся полезные соотношения, позволяющие оценить удлинения и сдвиг проводников в обмотке при известном токе. Приводится пример расчета распределения пондеромоторных сил для проводников обмотки трансформатора круглого и прямоугольного сечения

Ca2+ sensor proteins in dendritic spines: a race for Ca2+

Dendritic spines are believed to be micro-compartments of Ca2+ regulation. In a recent study, it was suggested that the ubiquitous and evolutionarily conserved Ca2+ sensor, calmodulin (CaM), is the first to intercept Ca2+ entering the spine and might be responsible for the fast decay of Ca2+ transients in spines. Neuronal calcium sensor (NCS) and neuronal calcium-binding protein (nCaBP) families consist of Ca2+ sensors with largely unknown synaptic functions despite an increasing number of interaction partners. Particularly how these sensors operate in spines in the presence of CaM has not been discussed in detail before. The limited Ca2+ resources and the existence of common targets create a highly competitive environment where Ca2+ sensors compete with each other for Ca2+ and target binding. In this review, we take a simple numerical approach to put forth possible scenarios and their impact on signaling via Ca2+ sensors of the NCS and nCaBP families. We also discuss the ways in which spine geometry and properties of ion channels, their kinetics and distribution, alter the spatio-temporal aspects of Ca2+ transients in dendritic spines, whose interplay with Ca2+ sensors in turn influences the race for Ca2+

Application of image recognition theory in non-destructive radiation testing of materials quality used in extreme conditions

Для обнаружения дефектов материалов и деталей космических аппаратов используетсярадиационный метод неразрушающего контроля. Обработка изображений, получаемых этим методом, проводится с помощью специальных алгоритмов. В работе обоснована возможность использования нейросетевого метода и предложен алгоритм на его основе для распознавания образов.The radiation method of nondestructive testing is used for the detection of defects in materials and components of spacecraft. Processing of the images, obtained by this method, is carried out using specialized algorithms. In the paper the possibility of using neural networks method is considered and the algorithm for image recognition based on it is suggested

Constraining recent lead pollution sources in the North Pacific using ice core stable lead isotopes

Trends and sources of lead (Pb) aerosol pollution in the North Pacific rim of North America from 1850 to 2001 are investigated using a high-resolution (subannual to annual) ice core record recovered from Eclipse Icefield (3017 masl; St. Elias Mountains, Canada). Beginning in the early 1940s, increasing Pb concentration at Eclipse Icefield occurs coevally with anthropogenic Pb deposition in central Greenland, suggesting that North American Pb pollution may have been in part or wholly responsible in both regions. Isotopic ratios (208Pb/207Pb and 206Pb/207Pb) from 1970 to 2001 confirm that a portion of the Pb deposited at Eclipse Icefield is anthropogenic, and that it represents a variable mixture of East Asian (Chinese and Japanese) emissions transported eastward across the Pacific Ocean and a North American component resulting from transient meridional atmospheric flow. Based on comparison with source material Pb isotope ratios, Chinese and North American coal combustion have likely been the primary sources of Eclipse Icefield Pb over the 1970–2001 time period. The Eclipse Icefield Pb isotope composition also implies that the North Pacific mid-troposphere is not directly impacted by transpolar atmospheric flow from Europe. Annually averaged Pb concentrations in the Eclipse Icefield ice core record show no long-term trend during 1970–2001; however, increasing 208Pb/207Pb and decreasing 206Pb/207Pb ratios reflect the progressive East Asian industrialization and increase in Asian pollutant outflow. The post-1970 decrease in North American Pb emissions is likely necessary to explain the Eclipse Icefield Pb concentration time series. When compared with low (lichen) and high (Mt. Logan ice core) elevation Pb data, the Eclipse ice core record suggests a gradual increase in pollutant deposition and stronger trans-Pacific Asian contribution with rising elevation in the mountains of the North Pacific rim

Attraction to Sad Music: The Role of Imagery, Absorption, and Rumination

Previous studies have identified links between attraction to negative emotion in music with the traits of absorption and rumination. However, no studies have examined the possible interdependencies and influences of these traits. We sought to determine whether a cognitive processing path that leads to attraction to sad music could be identified. We argued that auditory imagery might be an interesting competency to add to the investigation because of the links between imagery and absorption. Participants completed validated surveys measuring the three target cognitive measures, as well as a Like Sad Music Scale. Mediation analysis revealed that absorption mediated imagery in response to sad music, as predicted, and rumination predicted attraction to sad music independently of the other traits. Suggestions for expanding the cognitive process path are proposed, including further investigation of the possible central role of absorption. (PsycINFO Database Record (c) 2018 APA, all rights reserved