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CONTEXT: Cutaneous leishmaniasis (CL) is a public health problem in several endemic countries. Recent studies on mouse model and also a few clinical experiments showed that the type of immune response generated at the site of infection and especially balance between regulatory and effector T-cells determines the outcome of the disease toward self-limiting or long-lasting lesions. AIMS: The aim of this study was to evaluate the role of natural regulatory T cells (nTregs) in early and late cutaneous lesions of human Leishmania major (L. major) infection. SETTINGS AND DESIGN: Skin biopsies were collected from parasitologically proven lesions of 28 CL patients, divided into two groups of early and late lesions. The causative agents were identified to be L. major. MATERIALS AND METHODS: Quantitative real-time reverse transcription polymerase chain reaction (PCR) and immunofluorescent staining of biopsies were used to assess the Foxp3 mRNA expression and frequency of nTregs in two groups. Mann-Whitney U test was used to determine the significance of deference between the two groups. RESULTS: Mean relative expressions of Foxp3 mRNA were 0.53 ± 0.23 and 1.26 ± 0.99 in early and late lesions, respectively, which was significantly upper in chronic lesions (P = 0.007). Parallel results were obtained in tissue staining method. CONCLUSIONS: Increased in gene expression and protein staining of nTreg markers in chronic biopsy samples indicates a role for these cells in chronic L. major induced leishmaniasis and supports the effectiveness of regulatory T cell-based immunotherapy for treatment of chronic CL.
RESUMO
BACKGROUND: Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin-angiotensin-aldosterone and sympathetic system on the heart besides its antioxidant and anti-inflammatory effects. HYPOTHESIS: We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF. METHODS: A placebo-controlled double-blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10 mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N-terminal pro-B-type natriuretic peptide (NT-Pro BNP), high-sensitivity C-reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks. RESULTS: Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups. CONCLUSIONS: Oral melatonin decreased NT-Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.