Real-time evaluation of longitudinal peak systolic strain (speckle tracking measurement) in left and right ventricles of athletes

<p>Abstract</p> <p>Background</p> <p>Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.</p> <p>Methods</p> <p>32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.</p> <p>Results</p> <p>In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS ^{medium-apical}-23.87 ± 4.94; ^{basalfreewall}-25.04 ± 4.12 at rest) and controls (RV LPSS^{medium-apical}-25.21 ± 4.97; ^{basalfreewall}-28.69 ± 4.62 at rest) than in the LV of both (athletes LV LPSS ^{medium-apical}-18.14 ± 4.16; ^{basallateralwall}-16.05 ± 12.32; controls ^{medium-apical}-18.81 ± 2.64; ^{basallateralwall}-19.74 ± 3.84) With the HG test a significant enhancement of the LPSS(with P < .05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.</p> <p>Conclusion</p> <p>ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation.</p

Epistasis between COMT and MTHFR in Maternal-Fetal Dyads Increases Risk for Preeclampsia

Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C→T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor “T” allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Fungal G-protein-coupled receptors::mediators of pathogenesis and targets for disease control

G-protein signalling pathways are involved in sensing the environment, enabling fungi to coordinate cell function, metabolism and development with their surroundings, thereby promoting their survival, propagation and virulence. G-protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in fungi. Despite the apparent importance of GPCR signalling to fungal biology and virulence, relatively few GPCR–G-protein interactions, and even fewer receptor-binding ligands, have been identified. Approximately 40% of current pharmaceuticals target human GPCRs, due to their cell surface location and central role in cell signalling. Fungal GPCRs do not belong to any of the mammalian receptor classes, making them druggable targets for antifungal development. This Review Article evaluates developments in our understanding of fungal GPCR-mediated signalling, while substantiating the rationale for considering these receptors as potential antifungal targets. The need for insights into the structure–function relationship of receptor–ligand interactions is highlighted, which could facilitate the development of receptor-interfering compounds that could be used in disease control

Calagem e adubação fosfatada promovem crescimento inicial e produção de hipericina em erva-de-São-João Liming and phosphate fertilization promote initial growth and hipericin production in St. John's wort

A erva-de-São-João é uma planta medicinal empregada no tratamento antidepressivo. A hipericina é considerada um dos compostos que contribui para o efeito medicinal da planta. Uma vez que a concentração e a quantidade do princípio ativo pode ser afetada pela nutrição das plantas, este trabalho teve por objetivo avaliar os efeitos do pH do solo e da adubação fosfatada sobre o crescimento inicial e a produção de hipericina em erva-de-São-João. O experimento foi realizado em Lages, SC, de julho a dezembro de 2003, em casa de vegetação. Utilizou-se delineamento experimental inteiramente casualizado (fatorial 4 x 3), correspondendo a quatro valores de pH (4,1; 5,5; 6,0 e 6,5) e três doses de P (0, 50 e 100 mg kg-1 de solo), com quatro repetições. Foram cultivadas duas plantas por vaso, em um Cambissolo Húmico Álico. Avaliou-se a produção de massa seca, a altura e o número de ramificações da parte aérea, o número de glândulas escuras nas folhas e a concentração e a quantidade total de hipericina na parte aérea. A produção de massa seca da parte aérea aumentou com a adição de P e, em maior magnitude, com a calagem. A altura das plantas somente foi influenciada pela calagem. O número de ramificações e de glândulas escuras e a concentração de hipericina aumentaram com a aplicação de P apenas na ausência de calagem, e com a calagem na ausência de P. Os maiores conteúdos de hipericina por vaso foram verificados nos tratamentos com pH 6,0 e 6,5 e doses de P de 50 e 100 mg kg-1 de solo.<br>St. Jonh's wort is a medicinal plant used for anti-depressive treatment. Hypericin is considered one of the compounds that contribute to the medicinal effect of the plant. Since the concentration and the total quantity of active ingredients may be affected by plant nutrition, this work was conducted to investigate the effects of soil pH and phosphorus (P) addition to the soil on initial growth and hypericin production of St. John's wort. The experiment was carried out in Lages, SC, from July until December of 2003, in a greenhouse. It followed a completely randomized factorial design (4 x 3), with four levels of pH (4.1, 5.5, 6.0, and 6.5) and three doses of P (0, 50, and 100 mg kg-1 of soil), and four replicates. Two plants were cultivated per pot, under a Humic Inceptisol. Plants were harvested and assessed for aerial dry matter production, height, number of lateral shoots, number of dark glands in the leaves, aerial hypericin content and aerial total hypericin production. The aerial dry matter production increased with P addition and, in a larger amount, with liming. The plant height was only affected by the liming. The number of lateral shoots and dark glands in the leaves as well as the hipericin concentration only increased with P application in the soil without liming, and with liming in the soil that did not receive P. The highest total hypericin production per pot was achieved in the treatments with pH values of 6.0 and 6.5 and P doses of 50 and 100 mg kg-1 of soil