A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil.

BACKGROUND: The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high rate of failure. Miltefosine has proven efficacy for CL caused by L. braziliensis, with a cure rate (CR) of 75%. A combined treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) and miltefosine could increase CR and decrease healing time. METHODS: A randomized, double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M + GM) vs miltefosine and placebo (M + P) vs Sbv in 133 patients with CL caused by L. braziliensis in Bahia, Brazil. RESULTS: The final CR at 180 days after the initiation of treatment was 44.4% in the Sbv group, 76.6% in the M + P group (P = .003 vs Sbv), and 75.6% in the M + GM group (P = .004 vs Sbv). The median healing time for cure was 102 days for the Sbv group and 60 days for both miltefosine groups (P = .0009). During the 6-month follow-up period, 4 relapses were documented: 1 in the Sbv group, 1 in the M + P group, and 2 in the M + GM group. Mild adverse events occurred in 65% of patients from the Sbv group, 76% and 79% from the M + P and M + GM groups respectively. CONCLUSIONS: Miltefosine is more effective than Sbv for the treatment of CL caused by L. braziliensis in Brazil and accelerates the healing time. Association with GM-CSF does not improve therapeutic outcome. CLINICAL TRIALS REGISTRATION: NCT03023111.

Adverse effects of p-TSA-doped polypyrrole particulate exposure during zebrafish (Danio rerio) development.

Nanomaterials have been attracting attention due to the wide range of applications in nanomedicine. Polypyrrole (PPy), a conductive polymer, has been employed in the biomedical field due to its stimulus-responsive properties, although in vivo studies to assess its potential undesirable effects are limited. This study evaluated the effects of PPy doped with p-toluene sulfonic acid ((p-TSA); PPy/p-TSA) exposure (at 25, 100, 250 and 500 µg/mL) during six consecutive days on mortality, hatching, spontaneous movement, heart rate, morphology and locomotion behavior of zebrafish embryos/larvae. Additionally, PPy/p-TSA envelopment of developing embryo chorions and gene expression of a hypoxia-related marker in this context were also evaluated. No significant mortality was found; however, altered heart rate and early hatching was identified in all exposed groups at 48 hours post-fertilization (hpf). Surprisingly, with the 500 µg/mL dose, hatching initiated as early as 24 hpf. PPy/p-TSA adhered to and enveloped the chorion of embryos in a time- and dose-dependent fashion; morphological changes in body length and ocular distance were found with higher concentrations. PPy/p-TSA-exposed animals showed locomotor behavioral alterations compatible with hypoactivity. A significant increase in the turn angle with a concomitant reduction in meander was also verified at higher concentrations. Taken together, these results emphasize the adverse effects of PPy/p-TSA on zebrafish development and behavior. Some effects of PPy/p-TSA exposure were dose-dependent, and indicate specific adverse effects of PPy/p-TSA on zebrafish development and behavior.