Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT

Influence of semi-solid casting and equal channel pressing on microstructure of a hypoeutectic Al-Si alloy

The aim of this work was to develop understanding of microstructural evolution of the alloy casted in semi-solid condition using a cooling slope and conventional casting followed by ECAP in a 120 die. Feed materials were prepared by cooling slope casting and conventional casting for ECAP process. The microstructures and Vickers hardness of the worked materials extruded by two routes (A and B) were evaluated. The primary α-Al phase tends to be elongated after processing by route A. However, its morphology was similar in nature to the microstructure of the as-cast sample after processing by route B. The Si particles become fragmented during ECAP processing and are more nearly globular in shape and uniform in size than in the as-cast sample. The microstructure of the semi-solid cast ECAPed samples was more homogenous than that of the conventional cast ECAPed sample followed by ECAP for both routes. The hardness of semi-solid cast ECAP samples was also higher than that of conventional cast ECAPed samples for both routes

Effects of Amino Acids on Malarial Heme Crystallization

To gain insight into the mechanism of malarial hemozoin formation and to explore various biological groups for screening novel antimalarial drugs, we examined the effects of amino acids on the formation of β-hematin (BH), which is a synthetic heme crystal structurally identical to hemozoin, in vitro. Our results showed that BH formation was significantly inhibited by basic amino acids (arginine, lysine, and histidine), probably due to the abilities of these amino acids to complex with heme. The results suggest an involvement in the improvement of the blood-schizonticidal activity of 8-quinolinamine when conjugated with basic amino acids. In addition, cysteine also inhibited BH formation, possibly due to its ability to reduce heme iron or decompose heme in acidic conditions. In contrast, BH formation was enhanced by amino acids with high hydrophobicity values (leucine, isoleucine, valine, methionine, and phenylalanine), with the exception of tryptophan at high temperature but was not affected in Tween-induced BH formation under normal physiological conditions. The present results can lead to further research on the development of new antimalarials by conjugating these amino acids, especially basic amino acids, with other substances, or by forming complex or small peptides that could have special effects on BH formation