Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease.

AIM: Elderly patients have an increased incidence of ischaemic dilated cardiomyopathy often related to diffuse coronary artery disease. Trimetazidine protects ischaemic myocardium by improving the myocardial energy utilisation during myocardial ischaemia. Aim of the present study was to evaluate the effects of trimetazidine on left ventricular (LV) function in elderly patients with ischaemic heart disease and reduced LV function. METHODS: Forty seven elderly patients (40 males and 7 females, mean age 78+/-3 years) were randomised to receive, in addition to standard therapy, either trimetazidine or placebo and were evaluated by echocardiography at baseline and after 6 months. RESULTS: Trimetazidine and placebo had no effect on either blood pressure or heart rate (SBP 2+/-5 vs 4+/-6 mmHg, DBP -1+/-6 vs 3+/-4 mmHg, HR -3+/-7 vs 5+/-9 bpm, trimetazidine and placebo compared to baseline, respectively). At the end of the study patients randomised to trimetazidine showed a significant greater left ventricular function and smaller left ventricular diastolic and systolic diameters and volume indices compared to patients receiving placebo (LVEF: 34.4+/-2.3% vs 27+/-2.8%, p<0.0001; LVEDD: 58.6+/-1.9 mm vs 64+/-1.7 mm, p<0.0001; LVESD: 44.5+/-1.1 vs 50+/-0.8 mm, p<0.0001). A significant smaller wall motion score index was detected in trimetazidine-treated patients compared to those allocated to placebo (1.24+/-0.12 vs 1.45+/-0.19, p<0.01), the percentage change in LVEF compared to baseline was also significantly greater in trimetazidine-treated patients. Diastolic function significantly improved in the trimetazidine group while it remained unchanged in the placebo group. At follow-up evaluation, patients receiving trimetazidine showed a greater improvement in angina and NYHA class than patients allocated to placebo. Quality of life significantly improved in all patients treated with trimetazidine while remained unchanged in those allocated to placebo. CONCLUSION: In elderly patients with ischaemic cardiomyopathy trimetazidine in addition to standard medical therapy has a beneficial effect on LV systolic and diastolic function, and improves quality of life.     

Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease

Human holobiomes are networks of mutualistic interactions between human cells and complex communities of bacteria and fungi that colonize the human body. The immune system must tolerate colonization with commensal bacteria and fungi but defend against invasion by either organism. Molecular ecological surveys of the human prokaryotic microbiota performed to date have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information regarding the eukaryotic composition of the microbiota. In this review, we describe the ecology and the human niches of our fungal “fellow travelers” in both health and disease, discriminating between passengers, colonizers, and pathogens based on the interaction of these fungi with the human immune system. We conclude by highlighting the need to reconsider the etiology of many fungal and immune‐related diseases in the context of the crosstalk between the human system and its resident microbial communities.     

IL‐4‐induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells

Human Th17 cells have a limited proliferative capacity compared to other T‐cell subsets. We have shown that human Th17 cells display impaired IL‐2 production due to IL‐4‐induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17 cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B‐cell traslocation gene) antiproliferative protein family, which prevents cell‐cycle progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher levels of Tob1 than Th1 cells in both resting and TCR‐activated conditions. Accordingly, the expression of positive regulators of the cell cycle (cyclin A, B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells correlated with both RAR (retinoic acid receptor)‐related orphan receptor C (RORC) and IL4I1 levels. However, RORC was not directly involved in the regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a substantial decrease of Tob1 expression. These data suggest that IL4I1 upregulation in human Th17 cells limits their TCR‐mediated expansion not only by blocking the molecular pathway involved in the activation of the IL‐2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle.     

Nigral involvement and nigrostriatal dysfunction in Huntington's disease: Evidences from an MRI and SPECT study

BackgroundHuntington disease (HD) is pathologically characterized by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies investigated the neuronal loss and the functional role of the substantia nigra in modulating clinical features in HD.Methods12 patients and 12 age-matched controls underwent SPECT scans with ¹²³I-FP-CIT and a 1.5 T MRI scan with inversion recovery technique. The association between both clinical and neuropsychological features and striatal uptake and volume of substantia nigra was explored.ResultsStriatal (p < 0.05), caudate (p < 0.05), and putaminal (p < 0.01) uptake was significantly lower in patients with respect to controls. Further, the volume of substantia nigra was reduced in HD when compared to controls (p < 0.01). No relationship between the volume of SN and tracer striatal uptake was found as well as between clinical and neuropsychological features with the SPECT and MRI results.ConclusionsOur results confirm that the degeneration of nigrostriatal pathway may occur in symptomatic HD patients. If confirmed by larger studies, the lack of any kind of correlation between clinical and neuropsychological features with striatal uptake and volume of substantia nigra suggests that motor and cognitive aspects in HD are not directly related to nigrostriatal degeneration.     

Testosterone and heart failure

Testosterone deficiency is a generalized phenomenon seen in the course of chronic heart failure (CHF). Reduction in circulating testosterone level is a predictor of deterioration of functional capacity over time, underscoring the role of testosterone deficiency in CHF. Anabolic hormones are determinants of exercise capacity and circulating levels of anabolic hormones strongly determine muscle mass and strength. Testosterone deficiency is involved in the pathophysiology of CHF, contributing to some features of this syndrome, such as the reduced muscle mass, abnormal energy handling, fatigue, dyspnea and, finally, cachexia. This review summarizes current knowledge on the role of testosterone deficiency in the pathophysiology of CHF, gaining insights from the potential implications of testosterone as supplementation therapy.