A prediction algorithm for drug response in patients with mesial temporal lobe epilepsy based on clinical and genetic information

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide121FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/07559-

Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin

Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation-results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.publishersversionpublishe

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet coun

Structural assessment, toxicity, and increased antimicrobial activity

Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.publishersversionpublishe

Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis

Plantio direto, adubação verde e suplementação com esterco de aves na produção orgânica de berinjela.

Sob manejo orgânico, foram avaliados, em Seropédica, RJ, os sistemas de plantio direto da berinjela(Solanum melongena) nas palhadas de Crotalaria juncea (crotalária), Pennisetum glaucum (milheto, cv. BRS 1501)e vegetação espontânea (pousio), em comparação com o plantio convencional (aração e gradagem ou enxada rotativa). Simultaneamente, foram avaliados três tipos de cultivo: berinjela em monocultura, em consórcio com crotalária e em consórcio com caupi (Vigna unguiculata, cv. Mauá). Não houve diferença entre os sistemas de plantio direto e convencional quanto à produção comercial da berinjela. A palhada da crotalária foi mais eficiente que a do milheto e do pousio para cobertura morta do solo e conseqüentemente o controle de plantas espontâneas foi maior. O cultivo simultâneo com as leguminosas não acarretou redução da produtividade da berinjela.Em um segundo estudo, foram comparados plantio direto (palhadas de crotalária e da vegetação espontânea) e plantio convencional, combinados com doses crescentes de cama de aviário (0, 100, 200 e 400 kg ha-1 de N)aplicada em cobertura. Em termos de aporte de biomassa, a crotalária foi novamente superior à vegetação espontânea.A berinjela respondeu à adubação orgânica, com produtividade máxima de 50,6 t ha-1 , correspondendo à maior dose empregada, contra 36,9 t ha-1 referentes ao controle