A natural cell-penetrating nanopeptide combined with pentavalent antimonial as experimental therapy against cutaneous leishmaniasis.

The inadequacy of available treatments for leishmaniasis has presented up to 40% therapeutic failure. This fact suggests an urgency in the discovery of new drugs or alternative approaches for treating this disease. The objective of this study was to evaluate the antileishmanial activity of combined therapy between crotamine (CTA) from Crotalus durissus terrificus and the pentavalent antimonial Glucantime® (GLU). The assays were in vitro performed measuring the inhibition of Leishmania amazonensis amastigotes, followed by the evaluation of cellular production of cytokines and nitrites. After that, analytical methods were performed in order to characterize the molecules involved in the study by Mass Spectrometry, molecular affinity through an in silico assay and Surface Plasmon Resonance. In vivo experiments with BALB/c mice were performed by analyzing parasitemia, lesion size and immunological mediators. In the in vitro experiments, the pharmacological association improved the inhibition of the amastigotes, modulated the production of cytokines and nitric oxide. The therapy improved the effectiveness of the GLU, demonstrating a decreased parasitemia in the infected tissues. Altogether, the results suggest that the combined approach with CTA and GLU may be a promising alternative for the treatment of cutaneous leishmaniasis.

Tumor growth activity of duloxetine in Ehrlich carcinoma in mice.

OBJECTIVE: The objective of this study was to analyze whether duloxetine influences tumor growth in Ehrlich carcinoma. The mice were administered 5 or 30 mg/kg of duloxetine or saline solution. All animals were inoculated with tumor cells. The tumor progression was evaluated by body weight, abdominal circumference, ascites volume and tumor cell count. The effect of duloxetine on immune response was evaluated by lymphoid cells, nitric oxide (NO) production, arginase and superoxide dismutase (SOD) activity and the spleen immunophenotyping. RESULTS: There was no difference between the groups regarding weight, abdominal circumference, ascites volume and number of tumor cells. Duloxetine increased the cells of the inguinal lymph node. There was no difference in the number of cells in the bone marrow and spleen. Ascites SOD activity was greater in Duloxetine groups. There were no differences in the levels of NO, nitrite, and arginase. The number of antibody for CD3 (CD3+), CD4+, CD8+ and CD28+ cells was lower in the duloxetine groups. In conclusion, duloxetine has no direct effect on tumor growth and does not alter immunity. The drug increased the SOD that fights free radicals and led the migration of lymphocytes, suggesting that duloxetine could be used in tumor-bearing individuals.