Urotensin II-Induced Increase in Myocardial Distensibility Is Modulated by Angiotensin II and Endothelin-1

Endogenous regulators, such as angiotensin-II (AngII), endothelin-1 (ET-1) and urotensin-II (U-II) are released from various cell types and their plasma levels are elevated in several cardiovascular diseases. The present study evaluated a potential crosstalk between these systems by investigating if the myocardial effects of U-II are modulated by AngII or ET-1. Effects of U-II (10(-8), 10(-7), 10(-6) M) were tested in rabbit papillary muscles in the absence and in the presence of losartan (selective AT, receptor antagonist), PD-145065 (nonselective ET-1 receptors antagonist), losartan plus PD-145065, AngII or ET-1. U-II promoted concentration-dependent negative inotropic and lusitropic effects that were abolished in all experimental conditions. Also, U-II increased resting muscle length up to 1.008 +/- 0.002 L/L(max). Correcting it to its initial value resulted in a 19.5 +/- 3.5 % decrease of resting tension, indicating increased muscle distensibility. This effect on muscle length was completely abolished in the presence of losartan and significantly attenuated by PD-145065 or losartan plus PD-145065. This effect was increased in the presence of AngII, resulting in a 27.5 +/- 3.9 % decrease of resting tension, but was unaffected by the presence of ET-1. This study demonstrated an interaction of the U-II system with the AngII and ET-1 systems in terms of regulation of systolic and diastolic function

Rodent models of heart failure: an updated review

Heart failure (HF) is one of the major health and economic burdens worldwide, and its prevalence is continuously increasing. The study of HF requires reliable animal models to study the chronic changes and pharmacologic interventions in myocardial structure and function and to follow its progression toward HF. Indeed, during the past 40 years, basic and translational scientists have used small animal models to understand the pathophysiology of HF and find more efficient ways of preventing and managing patients suffering from congestive HF (CHF). Each species and each animal model has advantages and disadvantages, and the choice of one model over another should take them into account for a good experimental design. The aim of this review is to describe and highlight the advantages and drawbacks of some commonly used HF rodents models, including both non-genetically and genetically engineered models, with a specific subchapter concerning diastolic HF models

Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17%) more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury

A qualitative study of independent fast food vendors near secondary schools in disadvantaged Scottish neighbourhoods

Background: Preventing and reducing childhood and adolescent obesity is a growing priority in many countries. Recent UK data suggest that children in more deprived areas have higher rates of obesity and poorer diet quality than those in less deprived areas. As adolescents spend a large proportion of time in school, interventions to improve the food environment in and around schools are being considered. Nutrient standards for school meals are mandatory in the UK, but many secondary pupils purchase foods outside schools at break or lunchtime that may not meet these standards. Methods: Qualitative interviews were conducted with fast food shop managers to explore barriers to offering healthier menu options. Recruitment targeted independently-owned shops near secondary schools (pupils aged c.12-17) in low-income areas of three Scottish cities. Ten interviews were completed, recorded, and transcribed for analysis. An inductive qualitative approach was used to analyse the data in NVivo 10. Results: Five themes emerged from the data: pride in what is sold; individual autonomy and responsibility; customer demand; profit margin; and neighbourhood context. Interviewees consistently expressed pride in the foods they sold, most of which were homemade. They felt that healthy eating and general wellbeing are the responsibility of the individual and that offering what customers want to eat, not necessarily what they should eat, was the only way to stay in business. Most vendors felt they were struggling to maintain a profit, and that many aspects of the low-income neighbourhood context would make change difficult or impossible. Conclusions: Independent food shops in low-income areas face barriers to offering healthy food choices, and interventions and policies that target the food environment around schools should take the neighbourhood context into consideration

Concentrações séricas de proteínas totais em ovinos alimentados com dietas contendo urucum em níveis crescentes de inclusão.

O presente estudo foi conduzido com o objetivo de se determinar as concentrações séricas de proteínas totais em ovinos alimentados com dietas contendo urucum integral em níveis crescentes de inclusão (0,0%; 9,72%; 22,07% e 34,32%) em função dos tempos de coleta pós-prandial. Foram utilizados dezesseis ovinos, machos, castrados alojados em gaiolas metabólicas recebendo dietas compostas de feno de pasto nativo, milho, farelo de soja e urucum integral. A coleta de sangue foi feita por pução na veia jugular em quatro tempos pré-estabelecidos (zero, duas, cinco e oito horas pós-prandial). Utilizou-se delineamento inteiramente casualizado em esquema de parcelas subdivididas, tendo nas parcelas os níveis de inclusão de urucum integral e nas sub-parcelas os tempos de coleta com quatro repetições. As médias obtidas foram comparadas pelo teste SNK (P<0,05). Não houve interação significativa entre os níveis de inclusão de urucum integral e os tempos de coleta de sangue. A inclusão de urucum integral as dietas apresenta restrições quanto sua utilização para ovinos. Abstract: This study was conducted in order to determine serum concentrations of total protein in sheep fed diets containing annatto integral in increasing levels of inclusion (0.0%, 9.72%, 22.07% and 34 32%) as a function of collection time post-prandial. We used sixteen sheep, castrated male housed in metabolic cages and fed diets composed of native grass hay, corn, soybean meal and whole annatto. Blood collection was done by netting in the jugular vein in four pre-set times (zero, two, five and eight hours postprandial). We used a randomized design in split plots, and plots the levels of annatto full inclusion in the sub-plots and the collection times with four replications. The averages were compared by SNK test (P <0.05). No significant interaction between the inclusions of annatto and full time for blood collection. The inclusion of full annatto diets has restrictions on its use for sheep

Mechanical and structural characterization of tibial prosthetic interfaces before and after aging under simulated service conditions

Prosthesis interface is one of the most important components to promote individual's health and comfort, as it establishes direct contact with the skin and transfers loads generated during gait. The aim of this study was to mechanically characterize, three commercial interfaces (block copolymer, silicone gel and silicone elestomer), under static and dynamic conditions, before and after undergoing a process of chemical aging in synthetic sweat for periods up to 90 days. Static mechanical compression tests were performed on the materials, as well as fatigue tests to assess their static and dynamic mechanical behaviors, respectively. For the second, a sinusoidal load was applied with an appropriate range of deformation for each material. Several analytical techniques were also used to characterize the materials, namely Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), and morphology characterization by Scanning Electron Microscopy (SEM). All the tested materials have strong viscoelastic behavior, showing a linear response for small deformations, followed by a nonlinear behavior for higher deformation. The block copolymer and the silicone gel are affected by aging in synthetic sweat in a similar way, with a significant increase of their rigidity after 30 days, followed by a progressive reduction. The silicone elastomer displays a continuous increase of rigidity along the 90 days of storage, being the most sensitive to aging affects. It also exhibits the lowest stiffness value, being suitable for uses that require maximum comfort. All materials demonstrate chemical and structural stability under service simulated conditions. (C) 2014 Elsevier Ltd. All rights reserved

Three-dimensional localization of nanoscale battery reactions using soft X-ray tomography.

Battery function is determined by the efficiency and reversibility of the electrochemical phase transformations at solid electrodes. The microscopic tools available to study the chemical states of matter with the required spatial resolution and chemical specificity are intrinsically limited when studying complex architectures by their reliance on two-dimensional projections of thick material. Here, we report the development of soft X-ray ptychographic tomography, which resolves chemical states in three dimensions at 11 nm spatial resolution. We study an ensemble of nano-plates of lithium iron phosphate extracted from a battery electrode at 50% state of charge. Using a set of nanoscale tomograms, we quantify the electrochemical state and resolve phase boundaries throughout the volume of individual nanoparticles. These observations reveal multiple reaction points, intra-particle heterogeneity, and size effects that highlight the importance of multi-dimensional analytical tools in providing novel insight to the design of the next generation of high-performance devices

In vitro characterisation of solid drug nanoparticle compositions of efavirenz in a brain endothelium cell line

The antiretroviral drug efavirenz displays many desirable pharmacokinetic properties such as a long half‐life enabling once daily dosing but suffers from central nervous system safety issues. Various nanotechnologies have been explored to mitigate some of the limitations with efavirenz. While there has been progress in increasing the bioavailability, there has been no attempt to assess the impact of increased exposure to efavirenz on central nervous system safety. The uptake of aqueous and solid drug nanoparticle (SDN) formulations of efavirenz was assessed in the human cerebral microvessel endothelial cells/D3 brain endothelial cell line. The mechanisms of uptake were probed using a panel of transport and endocytosis inhibitors. The cellular accumulation of an efavirenz aqueous solution was significantly reduced by amantadine, but this was not observed with SDNs. The uptake of efavirenz SDNs was reduced by dynasore, but concentrations of the efavirenz aqueous solution were not affected. These data indicate that efavirenz is a substrate for transporters in brain endothelial cells (amantadine is an inhibitor of organic cation transporters 1 and 2), and formation of SDNs may bypass this interaction in favour of a mechanism involving dynamin‐mediated endocytosis