Therapeutic potential of biogenic silver nanoparticles in murine cutaneous leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In the last years, silver nanoparticles have appeared as novel antimicrobial agents. In this work, we evaluated the therapeutic potential of silver nanoparticles prepared by two different processes: 1) chemical synthesis (Chem-AgNP); and 2) biosynthesis from the fungus Fusarium oxysporum (Bio-AgNP), in the treatment of cutaneous leishmaniasis. When tested in vitro against Leishmania amazonensis promastigotes, Bio-AgNP was 4-fold more potent than Chem-AgNP (IC50 = 25 uM and 100 uM, respectively). In vivo studies in mice infected in the ear showed that bi-weekly intralesional injections with only 6.5 ug/Kg of body weight of Bio-AgNP during 4 weeks were equally effective as 300-fold higher doses of the reference drug amphotericin B, and more effective than 3-fold higher doses of Chem-AgNP. Contrary to the hepato- and nephrotoxicity that resulted from amphotericin B treatment, and the slight hepatotoxicity produced by Chem-AgNP, no changes in serum levels of AST, ALT and creatinine were detected with Bio-AgNP. Together, these findings show that the biogenic synthesis resulted in enhanced in vitro and in vivo antileishmanial activities, and safer silver nanoparticles as compared with the chemical synthesis.208997Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Análisis de polimorfismo de nucleótido simple en el gen FASN y su relación con características de producción en pollos

El objetivo de este trabajo es evaluar la posible asociación entre un polimorfismo de nucleótido simple (SNP) del gen FASN y cada uno de los siguientes caracteres productivos: Consumo de Alimento (CA), Ganancia de Peso (GP) y Peso Vivo Final (PVF). Durante la experiencia en el Instituto Nacional de Tecnología Agropecuaria (INTA), se organizaron y criaron 229 pollos de familias de hermanos enteros y de medios hermanos paternos. Cada una de las aves fue alojada en jaulas individuales con agua y alimentada con pellet ad libitum. El peso corporal se registró a los 54 días de edad y luego se determinó semanalmente y en forma individual el consumo de alimento y el peso durante 21 días. Los genotipos del gen FASN fueron identificados por amplificación por PCR y digeridos por la endonucleasa Hae III. La información fenotípica fue analizada en forma independiente por ANOVA con un modelo aleatorio. No se ha demostrado que los SNP evaluados en este trabajo afecten los caracteres analizados

Galectins in the regulation of platelet biology

Platelets are anucleated blood cells derived from megakaryocytes, and although they are essential for proper hemostasis, their function extends to physiologic processes such as tissue repair, wound remodeling, and antimicrobial host defense, or pathologic conditions such as thrombosis, atherosclerosis, chronic inflammatory diseases, and cancer. Recently, we demonstrated that two structurally divergent members of the galectin family, galectin-1 and galectin-8, are potent platelet agonists. The emergence of galectins as soluble mediators capable of triggering platelet activation opens a new field of research that will provide further insights into the mechanisms linking inflammatory responses to thrombus formation and could expand our view of the role of platelets much beyond hemostasis to their pathophysiologic role during inflammation and cancer. The present article details the various protocols and reagents currently used in our laboratory to study the role of galectins in human platelet function.Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Engineered human Tmpk fused with truncated cell-surface markers: versatile cell-fate control safety cassettes

Cell-fate control gene therapy (CFCGT)-based strategies can augment existing gene therapy and cell transplantation approaches by providing a safety element in the event of deleterious outcomes. Previously, we described a novel enzyme/prodrug combination for CFCGT. Here, we present results employing novel lentiviral constructs harboring sequences for truncated surface molecules (CD19 or low-affinity nerve growth factor receptor) directly fused to that CFCGT cDNA (TmpkF105Y). This confers an enforced one-to-one correlation between cell marking and eradication functions. In-vitro analysis demonstrated the full functionality of the fusion product. Next, low-dose 3'-azido-3'-deoxythymidine (AZT) administration to non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice injected with transduced clonal K562 cells suppressed tumor growth; furthermore, one integrated vector on average was sufficient to mediate cytotoxicity. Further, in a murine xenogeneic leukemia-lymphoma model we also demonstrated in-vivo control over transduced Raji cells. Finally, in a proof-of-principle study to examine the utility of this cassette in combination with a therapeutic cDNA, we integrated this novel CFCGT fusion construct into a lentivector designed for treatment of Fabry disease. Transduction with this vector restored enzyme activity in Fabry cells and retained AZT sensitivity. In addition, human Fabry patient CD34(+) cells showed high transduction efficiencies and retained normal colony-generating capacity when compared with the non-transduced controls. These collective results demonstrated that this novel and broadly applicable fusion system may enhance general safety in gene- and cell-based therapies.Fil: Scaife, Matthew. University of Toronto; CanadáFil: Pacienza, Natalia Alejandra. University Health Network. Ontario Cancer Institute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Au, B. C. Y.. University Health Network. Ontario Cancer Institute; CanadáFil: Wang, J. C. M.. University Health Network. Ontario Cancer Institute; CanadáFil: Devine, S.. University of Toronto; CanadáFil: Scheid, E.. Mc Master University; CanadáFil: Lee, C. J.. University Health Network. Ontario Cancer Institute; CanadáFil: Lopez Perez, O.. University Health Network. Ontario Cancer Institute; CanadáFil: Neschadim, A.. University of Toronto; CanadáFil: Fowler, D. H.. National Institutes of Health; Estados UnidosFil: Foley, R.. Mc Master University; CanadáFil: Medin, J. A.. University of Toronto; Canadá. University Health Network. Ontario Cancer Institute; Canad