A vaccine against S. pyogenes: Design and experimental immune response

Streptococcus pyogenes causes severe invasive infections: the post-streptococcal sequelae of acute rheumatic fever (RF) and rheumatic heart disease (RHD), acute glomerulonephritis, and uncomplicated pharyngitis and pyoderma. Efforts to produce a vaccine against S. pyogenes began several decades ago, and different models have been proposed. Here, we describe the methodology used in the development of a new vaccine model, consisting of both T and B protective epitopes constructed as synthetic peptides and recombinant proteins. Two adjuvants were tested in an experimental inbred mouse model: a classical Freund`s adjuvant and a new adjuvant (AFCo1) that induces mucosal immune responses and is obtained by calcium precipitation of a proteoliposome derived from the outer membrane of Neisseria meningitides B. The StreptInCor vaccine epitope co-administrated with AFCo1 adjuvant induced mucosal (IgA) and systemic (IgG) antibodies as preferential Th1-mediated immune responses. No autoimmune reactions were observed, suggesting that the vaccine epitope is safe. (c) 2009 Elsevier Inc. All rights reserved.

Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

In a multi-target complex network, the links (L-ij) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K-i, K-m, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

Estudio de superaleaciones base Ni para su utilización en componentes de turbinas.

[ES]La industria aeronáutica se ha convertido en los últimos tiempos en uno de los sectores más innovadores. Una de las características de este sector es que exige una amplia gama de materiales con propiedades únicas como las superaleaciones en base Ni MARM247 y C1023, que son materiales nuevos que parecen tener un comportamiento ideal para su uso en turbinas. El objetivo de este proyecto es obtener en un mismo documento todos los datos posibles, tanto teóricos como empíricos de estos materiales. El proyecto se puede dividir en dos partes: investigación de la mayor cantidad de información y realizar algunos ensayos con muestras.

Physical research in dynamized systems

The concept of dynamized medicines is commonly used in homeopathy. As a medical practice, homeopathy is based on clinical observations and experimental assays. In spite of the lack of a credible scientific explanation for its action mechanisms, clinical evidence has been collected since 200 years ago. This paper discusses the most important physical models related to dynamized systems, as well as some perspectives and consequences in studying such systems. While early theories dealt with structural changes in single solvent molecules, modern theories consider collective effects and self-organizing properties. The concept of information was recently introduced to model the capability of a dynamized system to interact with a biological organism, without a molecular agent being needed. The features and limitations of theoretical approaches, as well as experimental results are discussed. (C) 2002 Published by Elsevier B.V. Ltd.

Boron transport in Eucalyptus. 2. Identification in silico of a putative boron transporter for xylem loading in eucalypt

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comportamento fotofísico do antraceno em sistemas micro-heterogêneos argila-surfactantes-íons metálicos

Argilas constituem uma classe de complexos micro-heterogêneos e podem ser utilizados como substrato para adsorção. O seu comportamento de sorção em fase sólida intensificada pela presença de surfactantes, argilas organofílicas, é um importante fenômeno explorado pela tecnologia ambiental para a remoção de compostos orgânicos policíclicos (hidrocarbonetos aromáticos policíclicos, HPA) da água, introduzidos no ambiente por fontes antropogênicas. Este trabalho tem por objetivo estudar o comportamento fotofísico do antraceno, como modelo de HPA, em sistemas micro-heterogêneos argila-surfactantes-íons metálicos (M(II)= Cd(II), Cu(II), Hg(II), Ni(II) e Pb(II); surfactantes: CTACl; SDS; TR-X100). Os estudos foram conduzidos pelo monitoramento na mudança das propriedades de fluorescência estática e na supressão da emissão do antraceno utilizado como sonda fluorescente. Como supressores foram utilizados os cátions metálicos: Cd(II), Cu(II), Hg(II), Ni(II) e Pb(II). O perfil do espectro de fluorescência e os resultados dos ensaios de supressão da fluorescência da sonda permitiram inferir na localização do sítio de solubilização do antraceno nos sistemas micro-heterogêneos estudados e na conseqüente organização dos mesmos.

Suplementação de acidificantes em rações de leitões desmamados: Desempenho e digestibilidade

In two experimental assays it was evaluated the diet acidifier supplementation effect on performance (assay 1) and on nutrient apparent digestibility coefficients (assay 2). During 42 days in assay 1, 120 piglets weaned at 21-days years old were allotted in8eight experimental block design with3three pigs per experimental unit. The treatments were a control and4four acidified diets. In assay 2,0ten piglets with an average weight of 16,4 kg were allotted in two experimental block design receiving two treatments under five replications (control diet without acidifier or supplied with 1,0% fumaric acid). On performance study the fumaric acid inclusion in the diet permitted a feed intake increase from 0 to 15 days, and weight gain from 0 to 32 days and from 0 to 42 days. In assay 2, the diet 1,0% of fumaric acid inclusion did not modified the apparent digestibility coefficients of dry matter and moreover diet chemical compounds. The similar apparent digestibility coefficient of dietetic nutrients with the acidifier inclusio, probabl, occurred due to the short period of evaluation. The fumaric acid inclusion in weaned piglet diets improved performance of piglets.

Avaliação do pH, temperatura e imunoistoquímica de proteínas envolvidas na maciez da carne de ovinos

Pós-graduação em Medicina Veterinária - FMVZ

Projeto e construção de câmaras reverberantes em escala reduzida para o estudo das características de perda de transmissão de divisórias confeccionadas a partir de materiais regionais

Projetar e construir câmaras reverberantes, em modelo reduzido, para a determinação da perda de transmissão de materiais usados para o controle de ruído nas áreas industriais e da construção civil foi o foco principal deste trabalho. Por outro lado, buscou-se estabelecer uma metodologia de análise e interpretação dos parâmetros acústicos a partir da teoria dos modelos em escala reduzida, de tal modo que se possa inferir a perda de transmissão dos materiais estudados. A necessidade desta construção ocorre devido aos estudos dos desempenhos acústicos dos materiais serem realizados em câmaras reverberantes (em escala real), disponíveis apenas em algumas regiões do Brasil, dificultando e encarecendo os testes de desempenho dos materiais para pesquisadores de outras regiões. Assim, de modo a se ter um custo baixo, foi realizada a construção das câmaras reverberantes, em escala reduzida de 1:6, sendo o objetivo principal o estudo da perda de transmissão de divisórias desenvolvidas com material regional, estabelecendo comparação entre os seus desempenhos, e ao mesmo tempo permitir a sua utilização em aulas práticas de acústica. Apesar das câmaras terem sido construídas em escala reduzida, o fator de escala (1:6) não foi considerado e as medições foram realizadas nas freqüências reais das bandas de oitava delimitadas entre 125 Hz e 8 kHz. As divisórias foram ensaiadas para a determinação dos parâmetros acústicos, tendo por base as normas ISO 140 e 354. Finalmente, a partir dos resultados encontrados, foi possível comprovar a eficiência dos materiais utilizados para a obtenção de divisórias que podem ser usadas para o isolamento de ruído em ambientes construídos e/ou enclausuramentos industriais. Além dos ensaios experimentais, foram realizados cálculos analíticos segundo as equações da Análise Estatística Energética (SEA) para efeito de comprovação e validação dos resultados.

Rainwater toxicity and contamination study from So Paulo Metropolitan Region, Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Plasma corticosterone levels in mouse models of pain

Background: Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs. Aims/Methods: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone. Results: Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice. Conclusion: Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.

Binding of antioxidant flavone isovitexin to human serum albumin investigated by experimental and computational assays

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sensitivity of edge detection methods for quantifying cell migration assays

Quantitative imaging methods to analyze cell migration assays are not standardized. Here we present a suite of two–dimensional barrier assays describing the collective spreading of an initially–confined population of 3T3 fibroblast cells. To quantify the motility rate we apply two different automatic image detection methods to locate the position of the leading edge of the spreading population after 24, 48 and 72 hours. These results are compared with a manual edge detection method where we systematically vary the detection threshold. Our results indicate that the observed spreading rates are very sensitive to the choice of image analysis tools and we show that a standard measure of cell migration can vary by as much as 25% for the same experimental images depending on the details of the image analysis tools. Our results imply that it is very difficult, if not impossible, to meaningfully compare previously published measures of cell migration since previous results have been obtained using different image analysis techniques and the details of these techniques are not always reported. Using a mathematical model, we provide a physical interpretation of our edge detection results. The physical interpretation is important since edge detection algorithms alone do not specify any physical measure, or physical definition, of the leading edge of the spreading population. Our modeling indicates that variations in the image threshold parameter correspond to a consistent variation in the local cell density. This means that varying the threshold parameter is equivalent to varying the location of the leading edge in the range of approximately 1–5% of the maximum cell density.

Design and interpretation of cell trajectory assays

Cell trajectory data is often reported in the experimental cell biology literature to distinguish between different types of cell migration. Unfortunately, there is no accepted protocol for designing or interpreting such experiments and this makes it difficult to quantitatively compare different published data sets and to understand how changes in experimental design influence our ability to interpret different experiments. Here, we use an individual based mathematical model to simulate the key features of a cell trajectory experiment. This shows that our ability to correctly interpret trajectory data is extremely sensitive to the geometry and timing of the experiment, the degree of motility bias and the number of experimental replicates. We show that cell trajectory experiments produce data that is most reliable when the experiment is performed in a quasi 1D geometry with a large number of identically{prepared experiments conducted over a relatively short time interval rather than few trajectories recorded over particularly long time intervals.

Association between postmenopausal osteoporosis and experimental periodontitis

To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.