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Objective: To explore the antileishmanial effect of tioxolone and its niosomal form against Leishmania tropica. Methods: Tioxolone niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. The cytotoxicity of tioxolone and its niosomal form was measured by MTT assay, leishmanicidal activity against promastigote and amastigote by MTT assay, apoptosis by flow cytometry, IL-12, IL-10 and metacaspase gene expression levels by q-PCR. Results: Span/Tween 40 and Span/Tween 60 niosomes had good physical stability as depicted in their size distribution curves and high encapsulation efficiency (>99%). The release profile of the entrapped compounds showed Fickian's model of tioxolone delivery based on diffusion through lipid bilayers. With the IC50 value for amastigote as (24.5±2.1) μg/mL and selectivity index as 10.5, the Span/Tween 60 niosome (NT2) had a superior effect to other drugs. The CC50 value and IC50 of promastigote value for NT2 were (257.5±24.5) μg/mL and (164.8±20.6) μg/ mL, respectively. The flow cytometric analysis showed that tioxolone and niosomal forms induced apoptosis of Leishmania tropica promastigotes in a dose-dependent manner. NT2 increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene. Conclusions: Niosomes of tioxolone play an immunomodulatory role in increasing Th1 cytokine profile and inhibiting the Th2 cytokine profile. It could be used for treatment of anthroponotic cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomalencapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P=0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 µg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning. [ABSTRACT FROM AUTHOR]

There is no effective treatment modality available against different forms of leishmaniasis. Therefore, the aim of this study was to improve the penetration and efficacy of selenium and glucantime coupled with niosomes and compared them with their simple forms alone on in vitro susceptibility assays. In this study, the niosomal formulations of selenium and in combination with glucantime were prepared. The size and morphology of the niosomal formulations were characterized and the effectivity of the new formulation was also evaluated using in vitro MTT assay, intra-macrophage model, and gene expression profile. From the results obtained, no cytotoxicity effect was observed for niosomal and simple forms of drugs, as alone or in combination. Niosomal formulations of the drugs significantly showed more inhibitory effects (P=0.001) than the simple drugs when the selectivity index was considered. The gene expression levels of Interleukin (IL-10) significantly decreased, while the level of IL-12 and metacaspase significantly increased (P=0.001). The results of the present study showed that selenium plus glucantime niosome possess a potent anti-leishmanial effect and enhanced their lethal activity as evidenced by the in vitro experiments. [ABSTRACT FROM AUTHOR]

Abstract: Background: The age of onset of vitiligo is before 20 years in approximately in 50% of patients, and its incidence decreases with increasing age. In this study, our aim was to analyze the epidemiological and clinical factors of patients with late-onset vitiligo and compare these to patients with early-onset vitiligo. Methods: Eight hundred and twenty-five consecutive patients with vitiligo were examined from March 2003 through May 2006. The patients were divided into late-onset (disease onset > 50 years of age) and early-onset groups. Results: There were 54 (6.5%) patients diagnosed with late-onset vitiligo; 48.1% of these patients were female. Of those with early-onset vitiligo, 63.9% were female and 36.1% were male (p =0.02). Positive family history was present in 27.8% and 40.4% of the late- and early-onset groups, respectively. The most common first sites of involvement were the limbs in both groups. Generalized vitiligo (vitiligo vulgaris) was the most common presentation in both groups. Koebner phenomenon was detected in 79.6% of late- and 64.9% of early-onset vitiligo patients (p =0.02). Leukotrichia was present in 77.8% of late- and 52.7% of patients with early-onset vitiligo (p <0.001). Mucosal involvement was observed in 59.3% and 47% of late- and early-onset vitiligo patients, respectively (p =0.08). Associated diseases were seen in 18.5% of late- and in 23.1% of early-onset vitiligo patients. Conclusion: In patients with late-onset vitiligo, male gender, Koebner phenomenon, leukotrichia, and mucosal involvement were more common than in patients with early-onset vitiligo. [Copyright &y& Elsevier]