Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Effects from RF spoiling disequilibrium in the background offsets of phase-contrast velocity imaging

To investigate how disequilibrium of spoiling affects background offset errors in phase-contrast velocity images

Theory and Applications of X-ray Standing Waves in Real Crystals

Theoretical aspects of x-ray standing wave method for investigation of the real structure of crystals are considered in this review paper. Starting from the general approach of the secondary radiation yield from deformed crystals this theory is applied to different concreat cases. Various models of deformed crystals like: bicrystal model, multilayer model, crystals with extended deformation field are considered in detailes. Peculiarities of x-ray standing wave behavior in different scattering geometries (Bragg, Laue) are analysed in detailes. New possibilities to solve the phase problem with x-ray standing wave method are discussed in the review. General theoretical approaches are illustrated with a big number of experimental results.Comment: 101 pages, 43 figures, 3 table

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Оценка качества образования на основе компетентностного подхода

В работе представлен практический опыт оценки качества образования в новом формате компетентностного подход

Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium

OBJECTIVE: To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). DESIGN: Five cross-sectional studies. SETTING: Studies were conducted in five regions of Germany from 1997 to 2006. PARTICIPANTS: The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalent T2DM. RESULTS: We found significant multiplicative interactions between gender and the individual variables–—social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. CONCLUSIONS: Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women

In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI

To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33±8years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363±37ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42±0.28cm2. In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p=0.034). Average T1 time of the RV myocardium was 1,016±61ms, and average T1 of the left-ventricular (LV) was 956±25ms (p<0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV