Associação entre resposta clínica e eventos adversos ao metilfenidato e genes dopaminérgicos e serotoninérgicos em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade

Introdução: Poucos estudos sobre a farmacogenética do Transtorno de Déficit de Atenção/Hiperatividade (TDAH) foram conduzidos até o momento, apesar da extensa literatura sobre a participação de genes na etiologia do TDAH. Os estudos farmacogenéticos podem auxiliar na identificação a priori dos indivíduos que se beneficiarão de determinados tratamentos e dos que possivelmente apresentarão intolerância aos agentes farmacológicos. A maior parte dos estudos, até o momento, avaliou genes do sistema dopaminérgico e resultou em achados tanto positivos quanto negativos. Métodos: em um estudo naturalístico avaliamos os efeitos dos polimorfismos dos genes candidatos dopaminérgicos (DRD4, DAT1) e serotoninérgicos (HTR1B, HTR2A e 5-HTT) na resposta ao tratamento em 111 pacientes para os quais foi prescrito metilfenidato. As medidas de desfecho (Swanson, Nolan, and Pelham scale - versão IV – anexo I, Children Global Assessment Scale – anexo II, Barkley’s Stimulants Side Effects Rating Scale – anexo III) foram aplicadas no momento de avaliação e um mês após a intervenção. Resultados: Participaram do estudo 111 famílias de crianças e adolescentes eurobrasileiros de ambos os sexos que apresentavam TDAH segundo o DSM-IV. Estes pacientes foram consecutivamente triados no Programa de Déficit de Atenção/Hiperatividade do Hospital de Clínicas de Porto Alegre entre janeiro de 2003 e maio de 2004. Não foi detectada associação significativa entre os polimorfismos dos genes dopaminérgicos e serotoninérgicos avaliados e a resposta ao metilfenidato ou presença de eventos adversos. Conclusão: Os achados deste estudo quanto aos genes dopaminérgicos são negativos, concordando com três outros estudos disponíveis na literatura. Este foi o primeiro estudo a avaliar o efeito dos genes serotoninérgicos isolados na resposta ao metilfenidato e na presença de eventos adversos. Não foi encontrada nenhuma associação significativa. Os resultados dos estudos existentes são de difícil comparação devido à grande variabilidade metodológica existente entre os estudos. Assim, ensaios controlados multicêntricos prospectivos com maiores tamanhos amostrais são necessários para desvendar o papel dos genes candidatos na resposta ao tratamento para o TDAH.

Validação de formulário de notificação de eventos adversos a plantas medicinais e fitoterápicos

Pós-graduação em Ciências Farmacêuticas - FCFAR

Geração de vacinas antitumorais de células dendríticas humanas sensibilizadas com RNA de células tumorais pré-tratadas com agentes antineoplásicos

O câncer colorretal (CCR) é a terceira causa mais comum de câncer no mundo em ambos os sexos e a segunda causa em países desenvolvidos. Seu tratamento convencional é baseado na cirurgia associada à radioterapia e à quimioterapia em dose máxima tolerável, para tentativa de eliminação massiva das células tumorais. Tal abordagem, no entanto, pode causar efeitos colaterais importantes, entre eles as alterações hematopoiéticas e a supressão da resposta imune. As vacinas de células dendríticas mostram-se como opção terapêutica promissora para muitos tipos de câncer, havendo diferentes protocolos de preparação e sensibilização dessas células para dirigir a resposta antitumoral específica. Alguns agentes antineoplásicos em doses ultrabaixas mostraram modular positivamente as células dendríticas (DCs) e, na célula tumoral, promover alterações na transcrição de vários genes imunologicamente relevantes. Considerando que, em estudos prévios, tais mudanças transcricionais resultaram em aumento de imunogenicidade das células tumorais, hipotetizamos que o RNA das células pré-tratadas deve ser mais eficiente do que o RNA das células originais para preparação de vacinas de células dendríticas. Assim, objetivamos avaliar se o tratamento de células do tumor de cólon humano (HT-29) com PAC ou 5-FU/LEUCO torna seu RNA mais eficiente para preparação dessas vacinas. Para essa investigação, DCs humanas geradas a partir de monócitos de sangue periférico foram transfectadas com RNA total das células tumorais pré-tratadas e, a seguir, testadas quanto à capacidade de apresentação de antígenos e indução de células T citolíticas específicas. Apesar da baixa viabilidade celular pós eletroporação, os resultados obtidos sugerem que o tratamento de células tumorais com concentrações não tóxicas de 5-FU ou PAC promove alteração de expressão... (Resumo completo, clicar acesso eletrônico abaixo)

Efeito das baixas concentrações de agentes antineoplásicos sobre linfócitos humanos de sangue periférico

Our previous studies have shown that low concentrations (noncytotoxics) of antineoplastic agents modulate positively the dendritic cells, favoring their in vitro maturation and improving their antigen presenting function. The effects on colorectal cancer cells (HCT-116) were also investigated and we have observed an increased immunogenicity and susceptibility to cytotoxic T cells. Thereby, this study aimed to investigate the effect of 5-fluorouracil (5-FU) an azacitidine (AZA), in minimum effective and noncytotoxic concentrations on lymphocytes of healthy donors. In this study we have analyzed the cytotoxic effect of drugs at these concentrations as well as the proliferative ability of lymphocytes. In vitro production of IL-10 and IFN-γ has been also evaluated. We have observed that low concentrations of those chemotherapeutic agents are not cytotoxic for lymphocytes. However, the minimum effective concentrations (5-FU: 0,410±0,088 e AZA: 0,757±0,233; p<0, 05) have reduced the cell number. Proliferative activity of allogeneic lymphocytes in a mixed reaction (MLR) was not affected by the treatment. The cytokine production was not affected by the treatments, either. In conclusion, low concentrations of 5-FU and AZA has no deleterious effects on human peripheral blood lymphocytes and seems to be safe for combinatory administration with DC vaccines

Efeitos do metotrexate subaracnoideo sobre a medula espinal e as meninges de coelhos

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

Uso de rastreadores de eventos adversos a medicamentos para farmacovigilância no âmbito hospitalar

Eventos adversos a medicamentos (EAM) ainda são uma das principais limitações nos serviços de cuidados com a saúde, causando risco aos pacientes, além de grande impacto econômico. Assim, fazem-se necessários métodos de identificação de eventos adversos mais eficazes que a tradicional notificação espontânea, a qual revela apenas 5% do total de eventos. A utilização de critérios rastreadores (ou trigger tools), elaborados pelo Institute for Healthcare Improvement, tem se mostrado como a alternativa mais válida e eficiente para a triagem dos EAM. Com o objetivo principal de identificar os principais eventos adversos e medicamentos envolvidos, uma seleção de três critérios rastreadores foi utilizada, a saber: INR (razão normalizada internacional) > 6, WBC (contagem de leucócitos) < 3000/mm³ ou registros de episódios de sedação excessiva, letargia ou queda. Informações sobre os rastreadores foram coletadas e analisadas a partir dos prontuários de pacientes internados no Hospital Estadual Américo Brasiliense internados, de novembro de 2011 a janeiro de 2012 e maio a julho de 2012, a fim de se confirmar a ocorrência de evento adverso. Foram analisados prontuários referentes a 3318 hospitalizações, nas quais foram detectados 69 eventos adversos, 49 dos quais foram causados por apenas quatro das 12 classes de medicamentos envolvidos em algum EAM: anticoagulantes orais, relacionados ao rastreador INR>6 (eficácia = 0,75), sedativos e antipsicóticos, relacionados ao rastreador de sedação excessiva, letargia ou queda (eficácia = 0,52), e antivirais, relacionados ao rastreador WBC<3000 (eficácia = 0,48). Quando os rastreadores eram acionados e não estavam relacionados a EAM, os fatores de confusão mais recorrentes foram: torpor secundário ao quadro clínico, acidentes não relacionados ao medicamento e pacientes propositalmente em regime de sedação. Apesar de valores-limite menos radicais poderem aumentar a ...

Importância do polimorfismo OGG1 Ser326Cys no estudo dos efeitos para a saúde que resultam da exposição ocupacional a genotóxicos: o caso da exposição a antioneoplásicos

O ensaio cometa é um dos ensaios de avaliação de genotoxicidade mais promissores de avaliação do risco humano, sendo recomendado para a monitorização de populações com exposição crónica a agentes genotóxicos. Os laboratórios são ambientes profissionais em que os trabalhadores podem encontrar-se expostos a agentes químicos. As drogas antineoplásicas são agentes químicos que são considerados carcinogénicos e, desta forma, medidas de protecção especiais devem ser adoptadas. O objectivo desta comunicação é contribuir para o desenvolvimento de um programa de biomonitorização que inclui a avaliação de genotoxicidade relacionada com biomarcadores de susceptibilidade genética.

Competição larval em Chrysomya megacephala (F.) (Diptera: Calliphoridae): efeitos de diferentes níveis de agregação larval sobre estimativas de peso, fecundidade e investimento reprodutivo

In insects that utilize patchy and ephemeral resources for feeding and egg laying, the outcome of larval competition for food resources depends on the amount of resources and the spatial distribution of immatures among patches of food. In the present study, the results of larval competition for food in Chrysomya megacephala, in traits such as female weight, fecundity and reproductive investment, were different in situations where the level of larval aggregation (proportion of competitors per amount of food) was the same, but with densities of competitors and amounts of food proportionally different. These results are indicative that the larval competition may depend both on the larval density and the amount of food, in different situations with the same proportion of larvae per gram of food.

Educação a distância e efeitos em cadeia

This article is divided into two parts. The first presents two abstract arguments that constitute the starting point for the development of the second part, which is directed towards discussing some aspects of the distance learning policies, i.e., the role of public authorities in encouraging and shaping this type of education. First of all, it is intended to establish some assumptions to understand the emergence of this phenomenon and some of its conditioning factors and consequences; then to suggest some analytical tools to allow us to reflect on public policy in this area.

Efeitos da cobertura do solo com filme de polietileno azul no consumo de água da cultura da alface cultivada em estufa

The covering of the soil is an agricultural practice that intends to control the harmful herbs, to reduce the losses of water by evaporation of the soil, and to facilitate the harvest and the commercialization, once the product is cleaner and healthier. However, when the soil is covered important microclimatic parameters are also altered, and consequently the germination of seeds, the growth of roots, the absorption of water and nutrients, the metabolic activity of the plants and the carbohydrates storage. The current trial intended to evaluate the effect of soil covering with blue colored film on consumptive water-use in a lettuce crop (Lactuca sativa, L.). The experiment was carried out in a plastic greenhouse in Araras - São Paulo State, Brazil from March 3rd, 2001 to May 5th, 2001. The consumptive water-use was measured through two weighing lysimeter installed inside the greenhouse. Crop spacing was 0.25 m x 0.25 m and the color of the film above soil was blue. Leaf area index (IAF), was measured six times (7; 14; 21; 28; 35; 40 days after transplant) and the water-use efficiency (EU) was measured at the end. The experimental design was subdivided portions with two treatments, bare soil and covered soil. The average consumptive water-use was 4.17 mm day-1 to the bare soil treatment and 3.11 mm day-1 to the covered soil treatment. The final leaf area index was 25.23 to the bare soil treatment and 24.39 to the covered soil treatment, and there was no statistical difference between then.

Efeitos da temperatura do ar, linhagem e período do dia nas freqüências de ocorrências e tempos de expressão comportamental de matrizes pesadas

Behavioral adjustments may occur fast and with less cost than the physiological adaptations. Considering the social behavior is suggestive that the frequency and the intensity of aggressive interactions, the total social cohesion and the extent of vicious attitudes may be used to evaluate welfare. This research presents an analysis of the interactions between the experimental factors such as temperature, genetic and time of the day in the behavior of female broiler breeders under controlled environment in a climatic chamber in order to enhance the different reaction of the birds facing distinct environmental conditions. The results showed significant differences between the behaviors expressed by the studied genetics presenting the need of monitoring them in real-time in order to predict their welfare in commercial housing, due to the complexity of the environmental variables that interfere in the well being process. The research also concluded that the welfare evaluation of female broiler breeders needs to consider the time of the day during the observation of the behaviors.

Determinação em tempo real da magnitude de danos físicos por impacto em linhas de beneficiamento e em condições de laboratório e seus efeitos na qualidade de tomate

Tomatoes are one of the most important vegetable crops grown in Brazil and are among the crops that have one of the highest post-harvest losses indexes in the country. The present work aimed at evaluating impact damage observed in packing lines of fresh tomatoes as well as to determine, under laboratory conditions, quality alterations of tomato fruits submitted to impact damage in different surface types. Critical points evaluation was accomplished using an instrumented sphere. Critical transference points found showed variations in acceleration levels from 30 to 129 G (m s-2). Tests carried out under laboratory conditions showed that padded surfaces reduced up to 31% impact damage. Incidence of severe internal physical damage was evaluated by a subjective scale and increased by 79% on hard surfaces for the highest fall drop. On the other hand, it was observed an effective reduction in physical damage on fruits when padded surfaces were used. When a 10-cm drop was performed, the maximum reduction measured was 10% for hard surfaces and 5% for previously padded surfaces. For quality parameters, it was observed for high drops on hard surfaces, highest values for weight loss, total acidity, lower values for vitamin C and Soluble Solids.

Estudo dos efeitos de temporada de treinamento físico sobre a Performance de uma equipe de handebol feminino sub-21

Handball is a sport that demands endurance associated with fast and powerful actions such as jumps, blocks, sprints and throws. The aim of this study was to evaluate the effects of a 38-week systematic physical training applied to a women's under 21 handball team on upper and lower limb power, 30m sprints speed and endurance. The periodization applied was an adaptation of the Verkhoshansky theory, and aimed at two performance peaks during the season with six data collections. The median and range values for three kg medicine ball throwing was: 2.98m (2.15-3.50); 2.84m (2.43-3.20); 2.90m (2.60-3.38); 3.10 (2.83-3.81); 2.84 (2.55-3.57) and 3.34 (2.93-3.83). Regarding the three-pass running test: 5.60m (4.93-6.58); 5.37m (5.04-6.38); 5.36m (4.93-6.12); 5.65m (4.80-6.78); 5.63m (5.00-6.40) and 5.83m (5.14-6.05). Regarding the 30-m sprint test: 5.8m/s (5.45-6.44); 6,64 m/s (6,24-7,09); 5.65m/s (5.17-5.95); (there was not IV moment for this test); 6.19 m/s (5.57-6.26) and 5.83 (5.14-6.05).Regarding the 30-m sprint endurance test until 10% decrease: 4 sprints (4-6); 5 sprints (4-9); 4,5 sprints (4-16); (there was not IV moment for this test); 6 sprints (4-12) and 5 sprints (4-5). Significant differences (p<0.05) were observed in three kg medicine ball throwing and three-pass running tests at least in one of the performance peak planned, with no significant differences in 30-m sprint speed or endurance tests. The applied physical training was efficient at improving the specific physical fitness in the performance peaks, as well as giving support for better physical training adjustment for the upcoming season.

Adesão de linhagem selvagem de Streptococcus thermophilus em superfície de aço inoxidável e efeitos da higienização na sua remoção

A wild strain of Streptococcus thermophilus isolated from pasteurized milk was evaluated using an experimental model with respect to its adhesion onto stainless steel surfaces and its behaviour when submitted to cleansing and sanification. In milk, the adhesion of the microorganism on to stainless steel surfaces was studied after 6 hours of contact at 45°C with agitation, and after a cleansing process involving cleaning stages with alkaline and acid detergents followed by sanification, in order to evaluate the resistance of the adhered cells. The microorganism adhered to stainless steel surfaces producing a cell load of 10(4) CFU/cm². After alkaline cleansing, no adhered cells were detected but 6 CFU/cm² were still detected on the surfaces after acid cleansing. Cleansing, followed by sanification with sodium hypochlorite, was sufficient to reduce the load of wild S. thermophilus on the stainless steel surfaces to non-detectable levels. The experimental model proved adequate for the study indicating that the wild microorganism S. thermophilus produces biofilms on stainless steel surfaces. Alkaline cleansing remove more that 99.9% of the adhered cells. The few cells adhered on the surface are removed by acid cleansing demonstrating the need to use different steps and types of detergent for efficient cleansing. The best results for the removal of these biofilms are obtained by using alkaline cleansing followed by acid cleaning, this procedure being more efficient when complemented by sanification with sodium hypochlorite.

Efeitos da constrição pupilar na perimetria de freqüência dupla em olhos normais

Purpose: To study the effects of pupillary constriction on frequency doubling perimetry in a group of normal subjects. Methods: Eighteen healthy volunteers participated in the study. Only one eye per patient (right eye) underwent frequency doubling perimetry (Full Threshold C-20 strategy). For the second session, one drop of 2% pilocarpine was administered to the volunteers' right eye and the examination was repeated after 60 minutes. Results: Sixty minutes after administration of 2% pilocarpine, there was a significant reduction of the pupillary diameter from 4.22 ± 0.17 mm to 1.55 ± 0.51 mm (p<0.05). There was a significant reduction of the mean retinal sensibility after pupillary constriction. The threshold sensitivity of the central 5º worsened by 5.67 ± 2.49 dB; the area between 2.5º and 10º worsened by 4.49 ± 2.73 dB; and the area between 10º and 20º worsened by 5.10 ± 3.55 dB (p<0.01). A reduction of 4.06 ± 2.67 dB was observed in the mean deviation, as well as an increase of 0.64 ± 0.94 dB in the pattern standard deviation (p<0.01). No differences were observed regarding the number of fixation losses, false-positive and false-negatives responses, and duration of the examination. Conclusion: Changes in pupillary diameter may produce significant declines in threshold sensitivities of the 20º visual field tested by frequency doubling perimetry. These results suggest that is important to maintain a constant pupillary diameter in seriate examinations.