A associação entre genes do sistema noradrenégico e a resposta clínica ao tratamento com metilfenidato em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade : um estudo de farmacogenética

Introdução O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) está associado a um impacto negativo em diversas esferas da vida dos indivíduos afetados e de suas famílias. Os prejuízos causados por este transtorno são minimizados de forma significativa pelo tratamento medicamentoso, principalmente pelo uso do metilfenidato (MFD), cujo mecanismo de ação não é completamente conhecido. Estudos pré-clínicos têm apontado para o sistema noradrenérgico como um dos principais alvos da ação do MFD. Há um número reduzido de estudos que avaliaram a associação de genes do sistema noradrenérgico à melhora dos sintomas do TDAH e à ocorrência de efeitos adversos com o tratamento com MFD. Objetivos O presente estudo tem por objetivo avaliar a associação de polimorfismos localizados nos genes para o receptor adrenérgico α2A (ADRA2A), para a enzima dopamina-β-hidroxilase (DBH) e para o transportador de noradrenalina (NET1) e a resposta clínica (em termos de melhora sintomatológica, melhora do funcionamento global e ocorrência de efeitos adversos) ao tratamento com MFD em crianças e adolescentes com TDAH. Métodos 14 Crianças e adolescentes diagnosticados com TDAH foram tratados com MFD e reavaliados no 1o e no 3o mês de uso da medicação. Nos três momentos, os pais relataram a ocorrência de sintomas de desatenção, hiperatividade-impulsividade e oposição através da Escala Swanson, Nolan e Pelham - versão IV (SNAP-IV) e de efeitos colaterais à medicação através da Escala de Efeitos Adversos de Barkley (SERS). O médico assistente avaliou o funcionamento global da criança através da Escala de Avaliação Global de Crianças (CGAS). Foram avaliados os polimorfismos ADRA2A MspI, DBH TaqI e HhaI e NET1 BslI. Suas associações às medidas clínicas descritas foram analisadas através do método da análise de variância (ANOVA) para medidas repetidas ou através do modelo de efeitos mistos. Foi avaliada ainda a associação da interação entre os polimorfismos DBH TaqI, DBH HhaI e NET1 BslI e a redução dos sintomas através da ANOVA. Resultados Foram incluídos nas análises 106 indivíduos. Foi detectado um efeito significativo da interação entre a presença do alelo G no polimosfismo ADRA2A MspI e o tratamento com MFD ao longo do tempo sobre os sintomas de desatenção após 1 mês (n=106; F1,104 =8.51; P=0.004) e 3 meses (n=106; F2,198 =4.30; P=0.015) de tratamento. Não houve associação entre este polimorfismo e os demais desfechos avaliados. Paradoxalmente, indivíduos homozigotos para o alelo A2 no polimorfismo DBH TaqI apresentaram menor redução dos sintomas de hiperatividade-impulsividade após 1 mês (n=83; F=7.13; P=0.009) e maior redução destes sintomas após 3 meses (n=80; F=3.01; P=0.05) de tratamento com MFD do que indivíduos sem este genótipo. Não houve associação entre este polimorfismo e os demais desfechos avaliados. Não foram detectadas associações significativas dos polimorfismos DBH HhaI e NET1 BslI e melhora de sintomas, melhora do funcionamento global ou ocorrência de efeitos adversos durante o tratamento com MFD (P>0.05). Não foi demonstrado efeito da interação entre os polimorfismos avaliados sobre a resposta ao tratamento com MFD (P>0.05). Conclusão Este estudo demonstrou de forma consistente a participação do polimorfismo MspI do gene ADRA2A na redução de sintomas de desatenção com o tratamento com MFD durante o período de acompanhamento. As evidências clínicas encontradas corroboram dados bioquímicos, neurobiológicos e farmacológicos existentes e indicam a necessidade de mais estudos sobre a participação do sistema noradrenérgico no mecanismo de ação do MFD. Esforços conjuntos entre os diversos grupos de pesquisa devem ser postos em prática para que novas metodologias possam ser empregadas no tratamento do TDAH.

A concordância verbal na comunidade de São Miguel dos Pretos, Restinga Seca, RS

Este trabalho tem o objetivo de analisar a concordância verbal de 1a, 2a e 3a pessoas do plural na comunidade de remanescentes de escravos São Miguel dos Pretos, localizada em Restinga Seca, RS. A amostra é composta por 24 informantes homens e mulheres, cujas idades variam entre 15 e 90 anos. Existe a proposta de duas análises: a concordância verbal padrão versus a concordância verbal não-padrão das pessoas do plural e a presença versus a ausência das desinências DNP4 (nós plantamos), DNP5 (vocês plantam) e DNP6 (eles plantam). Consideram-se as variáveis sociais faixa etária, gênero e informante no estudo da concordância padrão. Constata-se que os falantes da comunidade quilombola estão adquirindo a concordância verbal padrão, uma vez que os resultados por faixa etária são de 40% para a geração mais nova e de 16% para a geração mais velha. A análise feita sobre a presença das desinências apresenta 73% de emprego de DNP4 e 80% de DNP6. Sobre este estudo, destacam-se as variáveis lingüísticas saliência fônica e posição do sujeito: confirma-se que as formas verbais mais salientes e que o sujeito anteposto ao verbo estão associados ao aumento da concordância. Também percebe-se que há um processo de aquisição das desinências número-pessoais DNP4 (jovens 77%, adultos 79% e velhos 66%) e DNP6 (pesos relativos de 0,64 para jovens, de 0,56 para adultos e de 0,38 para velhos), pois há um aumento do seu uso a cada geração, indicando a existência de um processo de mudança geracional. Os resultados encontrados se diferem das comunidades negras de Helvécia, Rio de Contas e Cinzento (BA) e aproximam-se dos encontrados em comunidades urbanas ou em comunidades cujos falantes têm maior grau de escolaridade.

Fundamentação numérica da Análise em Portugal em Anastácio da Cunha, Gomes Teixeira e Vicente Gonçalves

Neste trabalho estudamos a fundamentação numérica da Análise em Portugal, centrando particularmente este estudo nos trabalhos de José Anastácio da Cunha, Francisco Gomes Teixeira e Vicente Gonçalves. Num capítulo introdutório apresentamos uma perspectiva cronológica da procura de uma fundamentação rigorosa para a matemática, com o intuito de enquadrar historicamente as obras destes matemáticos Portugueses e reconhecer possíveis influências prestadas por trabalhos de outros autores. Relacionado com Anastácio da Cunha, analisamos os aspectos fundamentais da sua obra Principios Mathematicos, procurando evidenciar os resultados mais importantes avançados pelo autor, bem como as suas preocupações axiomáticas que não eram usuais no século XVIII, em que se insere a sua obra. Neste trabalho foi igualmente efectuada uma análise às quatro edições do Curso de Analyse Infinitesimal — Calculo Integral de Francisco Gomes Teixeira, particularmente centrada na definição do conceito de número irracional. Finalmente, analisamos o Curso de Álgebra Superior de Vicente Gonçalves, particularmente as duas últimas edições. A 2a edição do referido Curso foi objecto de duras críticas por parte de Neves Real e um dos objectivos deste trabalho foi o de procurar analisar essas críticas e verificar até que ponto influenciaram a reformulação de alguns aspectos da 3a edição.

Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos

GURGEL, Bruno Cesar de vasconcelos.Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos. 2003.97f. Dissertaçao (Mestrado) - Universidade Estadual de Campinas. Faculdade de Odontologia de Piracicaba. Piracicaba, 2003. Disponivel em: . Acesso em: 04 out. 2010.

Life cycle and behaviour of the predaceous mite Cunaxatricha tarsospinosa (Acari: Prostigmata: Cunaxidae)

Life cycle and behaviour of Cunaxatricha tarsospinosa Castro & Den Heyer from rubber trees in Brazil were studied, with Tenuipalpus heveae Baker offered as prey. The study was conducted at 25.4 +/- A 0.2A degrees C, 83 +/- A 5% RH and 12:12 h L:D photophase. The egg stage was the longest immature stage, lasting 17.1 +/- A 1.3 days (mean +/- A SE); total juvenile development was completed in 33.2 +/- A 2.8 days. Lifetime fecundity was 12.0 +/- A 2.2 eggs. Intrinsic rate of population increase was low, suggesting that T. heveae may not be a good prey for the predator. All specimens of C. tarsospinosa collected in the field for this study were females, no males were found. Concurrently, only females were obtained in the laboratory. This seems to be the first report of thelytokous parthenogenesis for cunaxids. Similar to earlier reports for some Cunaxinae and Coleoscirinae, prey were captured when predators were actively searching for them.

Movement of Spodoptera frugiperda Adults (Lepidoptera: Noctuidae) in Maize in Brazil

The fall armyworm, Spodoptera frugiperda (J. E. Smith), is one of the most important maize pests in the Americas and particularly in South America. With the adoption of genetically modified plants expressing Bacillus thuringiensis toxins for lepidopterous pest control, there is a need for establishing strategies to delay the development of insect resistance (e.g. refuge areas). Thus, information on target insects' dispersal is essential to improve pest management techniques. The objective of this work was to evaluate the dispersal capacity of S. frugiperda adults using mark-release-recapture techniques. Insects were marked using red oil-soluble dye in the larval artificial diet. Marked adults were released twice in each growing season (dry and wet) in southeastern Brazil in 2006 and 2007. Recapture of marked insects was performed using light and pheromone traps. Males are more attracted to light traps than females and the recapture rate was higher in the dry season than in the rainy season. The most adequate model to explain the relationship between flight distance and number of recaptured insects is y = a(2)/ (1+ (2a(1.8)+ bx))((2.6)), where y is the distance and x is the number captured. The maximum recapture distances were 806 m for males and 608 m for females. Therefore, strategies for establishment of refuges should take such distances into consideration.

Latent heat loss of dairy cows in an equatorial semi-arid environment

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise comparativa do desempenho de um Controlador Fuzzy acoplado a um PID Neural sintonizado por um Algoritmo Genético com Controladores Inteligentes Convencionais

On this paper, it is made a comparative analysis among a controller fuzzy coupled to a PID neural adjusted by an AGwith several traditional control techniques, all of them applied in a system of tanks (I model of 2nd order non lineal). With the objective of making possible the techniques involved in the comparative analysis and to validate the control to be compared, simulations were accomplished of some control techniques (conventional PID adjusted by GA, Neural PID (PIDN) adjusted by GA, Fuzzy PI, two Fuzzy attached to a PID Neural adjusted by GA and Fuzzy MISO (3 inputs) attached to a PIDN adjusted by GA) to have some comparative effects with the considered controller. After doing, all the tests, some control structures were elected from all the tested techniques on the simulating stage (conventional PID adjusted by GA, Fuzzy PI, two Fuzzy attached to a PIDN adjusted by GA and Fuzzy MISO (3 inputs) attached to a PIDN adjusted by GA), to be implemented at the real system of tanks. These two kinds of operation, both the simulated and the real, were very important to achieve a solid basement in order to establish the comparisons and the possible validations show by the results

Modelagem e medições de ondas de rádio para predição de perda de propagação em ambientes urbanos

In this dissertation new models of propagation path loss predictions are proposed by from techniques of optimization recent and measures of power levels for the urban and suburban areas of Natal, city of Brazilian northeast. These new proposed models are: (i) a statistical model that was implemented based in the addition of second-order statistics for the power and the altimetry of the relief in model of linear losses; (ii) a artificial neural networks model used the training of the algorithm backpropagation, in order to get the equation of propagation losses; (iii) a model based on the technique of the random walker, that considers the random of the absorption and the chaos of the environment and than its unknown parameters for the equation of propagation losses are determined through of a neural network. The digitalization of the relief for the urban and suburban areas of Natal were carried through of the development of specific computational programs and had been used available maps in the Statistics and Geography Brazilian Institute. The validations of the proposed propagation models had been carried through comparisons with measures and propagation classic models, and numerical good agreements were observed. These new considered models could be applied to any urban and suburban scenes with characteristic similar architectural to the city of Natal

Crescimento e produção de genótipos de bananeiras em clima subtropical

O presente trabalho teve como objetivo avaliar as características de crescimento e o potencial produtivo de genótipos de bananeira em Botucatu/SP. Foram avaliadas características de crescimento, tais como altura de planta, circunferência do pseudocaule, número de folhas e número de dias entre o florescimento e a colheita. Estas medidas foram realizadas na emissão da inflorescência. Foram mensuradas também as características de produção, como peso do cacho, número de frutos, peso médio dos frutos, produtividade, número de pencas; peso, número, comprimento e diâmetro dos frutos da 2a penca. O delineamento adotado foi o inteiramente casualisado, com 11 tratamentos (genótipos), cinco repetições e duas plantas úteis por parcela experimental. Os genótipos que apresentaram melhor desempenho agronômico, dentro de cada grupo genômico, foram 'Grand Naine'(AAA), 'Thap Maeo' (AAB) e 'Fhia 01' (AAAB).

Sistema de secagem solar para frutos tropicais e modelagem da secagem de banana em um secador de coluna estática

In this study were projected, built and tested an electric solar dryer consisting of a solar collector, a drying chamber, an exhaust fan and a fan to promote forced hot air convection. Banana drying experiments were also carried out in a static column dryer to model the drying and to obtain parameters that can be used as a first approximation in the modeling of an electric solar dryer, depending on the similarity of the experimental conditions between the two drying systems. From the banana drying experiments conducted in the static column dryer, we obtained food weight data as a function of aqueous concentration and temperature. Simplified mathematical models of the banana drying were made, based on Fick s and Fourier s second equations, which were tested with the experimental data. We determined and/or modeled parameters such as banana moisture content, density, thin layer drying curves, equilibrium moisture content, molecular diffusivity of the water in banana DAB, external mass transfer coefficient kM, specific heat Cp, thermal conductivity k, latent heat of water evaporation in the food Lfood, time to heat food, and minimum energy and power required to heat the food and evaporate the water. When we considered the shrinkage of radius R of a banana, the calculated values of DAB and kM generally better represent the phenomenon of water diffusion in a solid. The latent heat of water evaporation in the food Lfood calculated by modeling is higher than the latent heat of pure water evaporation Lwater. The values calculated for DAB and KM that best represent the drying were obtained with the analytical model of the present paper. These values had good agreement with those assessed with a numeric model described in the literature, in which convective boundary condition and food shrinkage are considered. Using parameters such as Cp, DAB, k, kM and Lfood, one can elaborate the preliminary dryer project and calculate the economy using only solar energy rather than using solar energy along with electrical energy

Estudo da secagem do pedúnculo do caju em sistemas convencional e solar: modelagem e simulação do processo

This work aims to study the drying of cashew-nut pulp with different lay-out of dryers using conventional and solar energy. It concerns with the use of exceeding of the regional raw material and the suitable knowledge for the applicability of the drying systems as pathway for food conservation. Besides, it used renewable sources as solar energy to dry these agroindustrial products. Runs were carried out using a conventional tray-dryer with temperature, air velocity control and cashew slice thickness of 55°C, 65°C, 75°C; 3.0; 4.5, 6.0 m s-1; 1.0; 1.5 and 2.0 cm, respectively, in order to compare the studied systems. To evaluate the conventional tray-dryer, it was used a diffusional model of 2nd Fick´s law, where the drying curves were quite well fitted to an infinite flat plate design. For the drying runs where the room temperature had no control, it was developed a phenomenological-mathematical model for the solar dryer with indirect radiation under natural and forced convection based on material and energy balances of the system. Besides, it was carried out assays in the in natura as well as dehydrated, statistic analysis of the experimental drying data, sensorial analysis of the final dry product and a simplified economical analysis of the systems studied

Yersinia enterocolitica O : 3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo

The mechanisms by which arthritis-provoking pathogens such as Yersinia enterocolitica interact with the human immune system to produce inflammatory synovitis are not well known. One of the immunomodulating mechanisms used against these pathogens is the polyclonal activation of lymphocytes. In this study, we investigated the extent of the B-lymphocyte activation induced in mice by a strain of Y. enterocolitica O:3 (FCF 526) isolated from a patient with arthritis, and compared it with two other strains, a virulent one (FCF 397[+]) isolated from a patient without arthritis and its plasmidless isogenic pair (FCF397[-]). Also we investigated the production of autoantibodies in mice infected with these different strains. SPF Swiss mice were infected intravenously with a suspension of Y. enterocolitica . Spleen cells were taken on days 7, 14, 21 and 28 after infection and the number of cells secreting nonspecific and specific antibodies of IgG 1 , IgG 2a , IgG 2b , IgG 3 , IgM and IgA isotypes were determined by the ELISPOT technique. The presence of autoantibodies in mouse serum was investigated by the dot-blot assay. The pattern of infection of the three bacterial strains were almost the same. We observed a general increase in the number of nonspecific Ig-secreting cells with all three strains, and the greatest increases observed were in the IgG 2a and IgG 3 isotypes. Only a small fraction of the immunoglobulins detected were antibacterial, suggesting that the rest resulted from polyclonal B cell activation. The strain isolated from the patient with arthritis (FCF526) induced the greatest production of autoantibodies, coinciding with the period in which the greatest activation of nonspecific B lymphocytes was seen. There were no signs of arthritis or inflammation in the joints of the infected animals. Based on our results, we were unable to determine whether there is an association between the arthritogenic capability of Y. enterocolitica and polyclonal activation of B cells.

Immobilization of streptavidin in sol-gel films: Application on the diagnosis of hepatitis C virus

Recent advances have accelerated the development of biosensors for the analysis of specific gene sequences. In this kind of biosensor, a DNA probe is immobilized on a transducer and the hybridization with the target DNA is monitored by suitable methodology. In the present work, the streptavidin (STA) was encapsulated in thin films siloxane-poly(propylene oxide) hybrids prepared by sol-gel method and deposited on the graphite electrode surface by dip-coating process. Biotinylated 18-mer probes were immobilized through STA and a novel amperometric DNA biosensor for the detection and genotyping of the hepatitis C virus (genotypes 1, 2A/C, 2B and 3) is described. The HCV RNA from serum was submitted to reverse transcriptase-linked polymerase chain reaction (RT-PCR) and biotin-labeled cDNA was obtained. Thus, the cDNA was hybridized to the target-specific oligonucleotide probe immobilized on the graphite electrode surface and following the avidin-peroxidase conjugate was added. The enzymatic response was investigated by constant potential amperometry at -0.45 V versus Ag/AgCl using H2O2 and KI solutions. HCV RNA negative and positive controls and positive samples of sera patients were analyzed and the results were compared to commercial kit. The proposed methodology appeared to be suitable and convenient tool for streptavidin immobilization and diagnose of HCV disease. (c) 2006 Elsevier B.V. All rights reserved.

Anxiogenic-like effects of mCPP microinfusions into the amygdala (but not dorsal or ventral hippocampus) in mice exposed to elevated plus-maze

Serotonin (5-HT) can either increase or decrease anxiety-like behaviour in animals, actions that depend upon neuroanatomical site of action and 5-HT receptor subtype. Although systemic studies with 5-HT(2) receptor agonists and antagonists suggest a facilitatory role for this receptor subtype in anxiety, somewhat inconsistent results have been obtained when such compounds have been directly applied to limbic targets such as the hippocampus and amygdala. The present study investigated the effects of the 5-HT(2B/2C) receptor agonist mCPP bilaterally microinjected into the dorsal hippocampus (DH: 0, 0.3 1.0 or 3.0 nmol/0.2 mu l), the ventral hippocampus (VH: 0, 0.3, 1.0 or 3.0 nmol/0.2 mu l) or the amygdaloid complex (0, 0.15, 0.5, 1.0 or 3.0 nmol/0.1 mu l) in mice exposed to the elevated plus-maze (EPM). Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that mCPP microinfusions into the DH or VH failed to affect any behavioural measure in the EPM. However, when injected into the amygdaloid complex, the dose of 1.0 nmol of this 5HT(2B/2C) receptor agonist increased behavioural indices of anxiety without significantly altering general activity levels. This anxiogenic-like effect of mCPP was selectively and completely blocked by local injection of a behaviourally-inactive dose of SDZ SER-082 (10 nmol/0.1 mu l), a preferential 5-HT(2C) receptor antagonist. These data suggest that 5HT(2C) receptors located within the amygdaloid complex (but not the dorsal or ventral hippocampus) play a facilitatory role in plus-maze anxiety in mice. (c) 2007 Elsevier B.V. All rights reserved.