Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome

Nos últimos anos, o Ministério da Saúde do Brasil e a Organização Mundial da Saúde tem apoiado a investigação de novas tecnologias que possam contribuir para a vigilância, novos tratamentos e controle da leishmaniose visceral no país. Assim, o objetivo deste trabalho foi isolar compostos de plantas do bioma Caatinga, e investigar a toxicidade destes compostos contra as formas promastigotas e amastigotas de Leishmania infantum chagasi, principal parasita responsável pela leishmaniose visceral na América do Sul, e avaliar a sua capacidade para inibir a enzima acetil-colinesterase (AChE). Após a exposição aos compostos em estudo, foram realizados testes utilizando a forma promastigota que expressa luciferase e ELISA in situ para medir a viabilidade das formas promastigotas e amastigota, respectivamente. O ensaio colorimétrico MTT foi realizado para determinar a toxicidade destas substâncias utilizando células monocíticas murina RAW 264.7. Todos os compostos foram testados in vitro para as sua propriedade anti-colinesterásica. Um cumarina, escoparona, foi isolada a partir de hastes de Platymiscium floribundum, e os flavonóides, rutina e quercetina, foram isolados a partir de grãos de Dimorphandra gardneriana. Estes compostos foram purificados, utilizando cromatografia em coluna gel eluída com solventes orgânicos em misturas de polaridade crescente, e identificados por análise espectral. Nos ensaios leishmanicidas, os compostos fenólicos mostraram eficácia contra as formas extracelulares promastigotas, com EC50 para escoporona de 21.4µg/mL e para quercetina e rutina 26 e 30.3µg/mL, respectivamente. Os flavonóides apresentaram resultados comparáveis à droga controle, a anfotericina B, contra as formas amastigotas com EC50 para quercetina e rutina de 10.6 e 43.3µg/mL, respectivamente. Os compostos inibiram a enzima AChE com halos de inibição variando de 0,8 a 0,6cm, indicando um possível mecanismo de ação para a atividade leishmanicida.

Proposal of non-invasive experimental model to induce scoliosis in rats

Background: In the literature, there are several experimental models that induce scoliosis in rats; however, they make use of drugs or invasive interventions to generate a scoliotic curve. Objectives: To design and apply a non-invasive immobilization model to induce scoliosis in rats. Methods: Four-week old male Wistar rats (85 +/- 3.3 g) were divided into two groups: control (CG) and scoliosis (SG). The animals in the SG were immobilized by two vests (scapular and pelvic) made from polyvinyl chloride (PVC) and externally attached to each other by a retainer that regulated the scoliosis angle for twelve weeks with left convexity. After immobilization, the abdominal, intercostal, paravertebral, and pectoral muscles were collected for chemical and metabolic analyses. Radiographic reports were performed every 30 days over a 16-week period. Results: The model was effective in the induction of scoliosis, even 30 days after immobilization, with a stable angle of 28 +/- 5 degrees. The chemical and metabolic analyses showed a decrease (p<0.05) in the glycogenic reserves and in the relationship between DNA and total protein reserves of all the muscles analyzed in the scoliosis group, being lower (p<0.05) in the convex side. The values for the Homeostatic Model Assessment of Insulin Resistance indicated a resistance condition to insulin (p<0.05) in the scoliosis group (0.66 +/- 0.03), when compared to the control group (0.81 +/- 0.02). Conclusions: The scoliosis curvature remained stable 30 days after immobilization. The chemical and metabolic analyses suggest changes in muscular homeostasis during the induced scoliosis process.

GeoHealth: A Georeferenced System for Health Data Analysis in Primary Care

The Primary Care Information System (SIAB) concentrates basic healthcare information from all different regions of Brazil. The information is collected by primary care teams on a paper-based procedure that degrades the quality of information provided to the healthcare authorities and slows down the process of decision making. To overcome these problems we propose a new data gathering application that uses a mobile device connected to a 3G network and a GPS to be used by the primary care teams for collecting the families' data. A prototype was developed in which a digital version of one SIAB form is made available at the mobile device. The prototype was tested in a basic healthcare unit located in a suburb of Sao Paulo. The results obtained so far have shown that the proposed process is a better alternative for data collecting at primary care, both in terms of data quality and lower deployment time to health care authorities.

Growth, body composition and hematology of juvenile pacu (Piaractus mesopotamicus) fed increasing levels of ractopamine

The effects of four levels of dietary ractopamine (RAC) on growth, body composition and hematology of pacu, Piaractus mesopotamicus juveniles (103.6+/-3.3g) were studied. Fish were housed into 12 circular tanks of 1 m(3) - 15 fish per tank - and fed for 60 days with practical diets supplemented with 0; 10; 20 or 40mg RAC per kg of diet, in a totally randomized design trial (n=3). Fish fed diets containing up to 40mg RAC/kg diet for 60 days did not have improved growth or body composition parameters. There were no significant differences in hematocrit, hemoglobin and mean corpuscular hemoglobin. Plasma glucose and triglycerides were significantly smaller in fish fed with RAC; however no significant differences between RAC levels were detected. The inclusion of up to 40mg RAC/kg of diet did not improve growth and body composition, but influenced some hematological and biochemical parameters of juvenile pacu.

Caspase-mediated cleavage of the exosome subunit PM/Scl-75 during apoptosis

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75, is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal part of the protein at Asp369 (IILD369↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally, the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed.