Do the spatial characteristics of myocardial scar tissue determine the risk of ventricular arrhythmias?

Sudden cardiac death is one of the main causes of mortality in patients with structural heart disease. Although an implantable cardioverter de?brillator signi?cantly reduces the mortality rate, many patients never receive a shock. Identi?cation of high-risk patients would reduce the costs associated with this therapy and prevent the deleterious effect of inappropriate discharges. As scar tissue is the substrate of ventricular arrhythmias in patients with structural heart disease, scar characterization could allow strati?cation of the risk. The objective of this article is to review the role of scar characteristics in the pathogenesis of ventricular arrhythmias in patients with structural heart disease.

Assembling models of embryo development: Image analysis and the construction of digital atlases

Digital atlases of animal development provide a quantitative description of morphogenesis, opening the path toward processes modeling. Prototypic atlases offer a data integration framework where to gather information from cohorts of individuals with phenotypic variability. Relevant information for further theoretical reconstruction includes measurements in time and space for cell behaviors and gene expression. The latter as well as data integration in a prototypic model, rely on image processing strategies. Developing the tools to integrate and analyze biological multidimensional data are highly relevant for assessing chemical toxicity or performing drugs preclinical testing. This article surveys some of the most prominent efforts to assemble these prototypes, categorizes them according to salient criteria and discusses the key questions in the field and the future challenges toward the reconstruction of multiscale dynamics in model organisms.

A simple regional-scale model for forecasting sorghum yield across North-Eastern Australia

Sorghum is the main dryland summer crop in NE Australia and a number of agricultural businesses would benefit from an ability to forecast production likelihood at regional scale. In this study we sought to develop a simple agro-climatic modelling approach for predicting shire (statistical local area) sorghum yield. Actual shire yield data, available for the period 1983-1997 from the Australian Bureau of Statistics, were used to train the model. Shire yield was related to a water stress index (SI) that was derived from the agro-climatic model. The model involved a simple fallow and crop water balance that was driven by climate data available at recording stations within each shire. Parameters defining the soil water holding capacity, maximum number of sowings (MXNS) in any year, planting rainfall requirement, and critical period for stress during the crop cycle were optimised as part of the model fitting procedure. Cross-validated correlations (CVR) ranged from 0.5 to 0.9 at shire scale. When aggregated to regional and national scales, 78-84% of the annual variation in sorghum yield was explained. The model was used to examine trends in sorghum productivity and the approach to using it in an operational forecasting system was outlined. (c) 2005 Elsevier B.V. All rights reserved.

Human aquaporins:regulators of transcellular water flow

Background - Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistent with their expression in most tissues, AQPs are associated with diverse physiological and pathophysiological processes. Scope of review - AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volume regulation (CVR) is particularly notable. This review examines the regulatory role of AQPs in transcellular water flow, especially in CVR. We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema. Major conclusions - AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapid movement of water across diverse cell membranes and playing regulatory roles in CVR. Gating mechanisms have been proposed for human AQPs, but have only been reported for plant and microbial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow. General significance - Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins.

Endothelial cell-derived Pentraxin 3 limits the vasoreparative therapeutic potential of Circulating Angiogenic Cells

AIMS: Circulating Angiogenic Cells (CACs) promote revascularization of ischemic tissues although their underlying mechanism of action and the consequences of delivering varying numbers of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation.

METHODS & RESULTS: CACs at low (2x10(5)cells/ml) and mid (2x10(6)cells/ml) cellular densities significantly enhanced endothelial cell (EC) tube formation in vitro, while high density CACs (2x10(7)cells/ml) significantly inhibited this angiogenic process. In vivo, Matrigel-based angiogenesis assays confirmed mid-density CACs as pro-angiogenic and high density CACs as anti-angiogenic. Secretome characterization of CAC-EC conditioned media identified pentraxin 3 (PTX3) as only present in the high density CAC-EC co-culture. Recombinant PTX3 inhibited endothelial tube formation in vitro and in vivo Importantly, our data revealed that the anti-angiogenic effect observed in high density CAC-EC co-cultures was significantly abrogated when PTX3 bioactivity was blocked using neutralizing antibodies or PTX3 siRNA in endothelial cells. We show evidence for an endothelial source of PTX3, triggered by exposure to high density CACs. In addition, we confirmed that PTX3 inhibits FGF2-mediated angiogenesis, and that the PTX3 N-terminus, containing the FGF-binding site, is responsible for such anti-angiogenic effects.

CONCLUSIONS: Endothelium, when exposed to high density CACs, releases PTX3 which markedly impairs the vascular regenerative response in an autocrine manner. Therefore, CAC density and accompanying release of angiocrine PTX3 are critical considerations when using these cells as a cell therapy for ischemic disease.

Mediterranean diet: the impact on cardiovascular risk and metabolic syndrome in HIV patients, in Lisbon, Portugal

Introduction - Metabolic syndrome (MS) is common in HIV-infected individuals and it is associated with higher cardiovascular risk (CVR). Mediterranean diet has been associated with a better metabolic control and lower CVR. Materials and methods - From December 2013 to May 2014, individuals between 18 and 65 years of age, who attended the outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the frequency of intake. Higher scores represent higher adherence. CVR was assessed using D.A.D tool (classified as low, moderate or high risk). We excluded individuals with opportunistic disease, hospitalized in the past three months or with renal disease diagnosis. All participants gave written informed consent. Results - In the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523) Caucasian, with a mean age of 46.5±8.9 years. Patients were divided in two groups: naïve (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528). Mean length of HIV diagnosis was 6.7±6.5 years (naïve) and 13.3±6.1 years (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of the patients, respectively. MS was present in 33.9% (n=179) of patients in ART group and 16.3% (n=7) in naïve group. Presence of MS was associated with ART group (OR=2.7; p=0.018). MS was also associated with older age in this group (p=0.000). Overall, mean MedDietScore was 27.3±5.5. Higher score was associated with older age (r=0.319; p=0.000). Naïve patients presented a trend to higher adherence to Mediterranean diet (65.1% vs 51.7% in naïve group; p=0.090). No relation between MS and Mediterranean diet was found. Higher CVR was associated with the presence of MS in the ART group (p=0.001). In this group, individuals with moderate CVR presented higher rates of adherence to Mediterranean diet (p=0.036) when compared to low and high CVR score. Conclusions - In this cross-sectional study, naïve individuals presented a trend to higher adherence to Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was found in individuals with moderate CVR score. We think that this might suggest that this group of patients adopt this diet only in the presence of metabolic alterations or perceived CVR. Prospective studies in HIV patients are required to determine the impact of adherence to Mediterranean diet on the reduction of CVR.

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity

Objective- This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. Methods- Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. Results- Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 �g/ml) nor native LDL (100 �g/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 �M), and MnTBAP (a free radical scavenger, 50��M). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2 .- levels were determined in IMA versus CA VSMC. Conclusions- Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects.

Inibição de linhagens do complexo Fusarium Graminearum por compostos naturais e sintéticos

Quando produtos alimentícios e especiarias são contaminados por micotoxinas é quase impossível detoxificar utilizando processos usuais da indústria de alimentos ou durante o preparo doméstico. Por isso, controlar o crescimento do fungo e a produção de toxinas é uma demanda para garantir a segurança alimentar. Os agrotóxicos são rotineiramente utilizados como estratégia para proteger as plantas de doenças provocadas pela contaminação fúngica. No entanto, eles estão associados a efeitos adversos ao sistema nervoso central e periférico, têm ação imunodepressora e são cancerígenos. Em virtude disso, o objetivo deste trabalho foi estudar a inibição do desenvolvimento, do potencial toxigênico e da expressão gênica de linhagens do Complexo Fusarium graminearum por compostos naturais comparativamente aos fungicidas azoxistrobina e trifloxistrobina. Do farelo de arroz, foram extraídos o γ-orizanol e os ácidos fenólicos (EFF). Das sementes de nim foram extraídos os ácidos fenólicos (EFN), totalizando três extratos naturais. A capacidade antioxidante dos extratos foi verificada pelo consumo do radical livre DPPH• , capacidade de captura do radical ABTS●+, redução do ferro e inibição da oxidação enzimática. Os mecanismos de inibição de três linhagens de F. graminearum foram avaliados através da determinação de compostos estruturais (glicosamina e ergosterol) e da atividade de enzimas do metabolismo primário (α- amilase e proteases). Foram determinadas as micotoxinas de Fusarium: deoxinivalenol (DON), 15 acetildeoxinivalenol (15AcDON), 3 acetildeoxinivalenol (3AcDON), nivalenol (NIV) e zearalenona (ZEA). A expressão dos genes Tri1 e Tri5 foi determinada a fim de verificar se ocorria modificação da expressão gênica nas linhagens do Complexo F. graminearum ocasionada pela presença dos antifúngicos. O EFF apresenta atividade antioxidante destacada em relação aos demais extratos naturais para inibir a iniciação do processo, a propagação do radical livre e a catálise enzimática. A presença dos compostos naturais mostrou efeito promissor como antifúngico para as linhagens, sendo que a concentração necessária para inibir 50% do crescimento radial das colônias (MIC50) foi 0,9 g/kg para γ-orizanol; 0,032 g/kg para EFF e 0,037 g/kg para EFN, portanto, os extratos fenólicos são mais eficazes para inibição de F. graminearum do que o γ-orizanol. Os extratos naturais afetaram as atividades das enzimas α-amilase e proteases. Também ocorreu a redução da formação de componentes estruturais (glicosamina e ergosterol). Os extratos naturais se destacaram pela capacidade de inibição de micotoxinas produzidas pela biomassa fúngica, com destaque para o EFN sobre a produção de DON, 15AcDON, 3AcDON e ZEA. Sendo assim, é possível dizer que há uma relação direta entre a atividade antioxidante na inibição do fungo e na manifestação do seu potencial toxigênico. Além disso, esse estudo contribuiu com a elucidação do mecanismo de ação dos antifúngicos naturais estudados. Ocorre modificação na expressão gênica quando a linhagem é submetida ao tratamento com antifúngico, havendo uma relação direta entre a expressão do gene Tri5 e a produção de DON.

Semiology versus laboratory approaches: comparison between interarm blood preassure differences and APOB/APOA ratio

Nowadays complementary diagnostic methods are replacing clinical examination and semiology is loosing space in our clinical practice. One of our main concerns in clinical practice is to assess Cardiovascular risk (CVR). And previous studies reported an increased CVR with a divergence of 10mmhg or more measured between both arms-interarm blood pressure difference (IAD)