The dopamine (DA) transporter DAT1 is a major target bound by cocaine in brain. We examined the influence of functional genetic variants in DAT1 on cocaine addiction. Repeat polymorphisms, including a 30-bp variable-number tandem repeat (VNTR) in intron 8 (Int8 VNTR) with two common alleles, were genotyped in cocaine-dependent abusers (n ؍ 699) and in controls with no past history of drug abuse (n ؍ 866) from Sã o Paulo, Brazil. Positive association was observed with allele 3 of the Int8 VNTR and cocaine abuse (allele odds ratio ؍ 1.2, 95% confidence interval ؍ 1.01-1.37, P ؍ 0.036; 3͞3 homozygote odds ratio ؍ 1.45, 95% confidence interval ؍ 1.18 -1.78, P ؍ 0.0008). Population stratification was assessed and did not affect the results. Haplotypic analyses using additional polymorphisms indicated that the Int8 VNTR is responsible for the observed association. Functional analyses in reportergene constructs, demonstrated that allele 3 mediates significant (P < 0.05) but small reduced expression compared with the ''protective'' allele 2. This difference increased when 1 and 10 M cocaine was added to the cell culture (Ϸ40% reduction of the 3 allele expression versus the 2 allele). The 3 allele also demonstrated Ϸ3-fold-increased expression over the 2 allele in response to KCl plus forskolin challenge. We demonstrate a robust association between cocaine dependence and a VNTR allele in SLC6A3, conferring a small but detectible effect, and we show that this VNTR may be functional. This study suggests that DAT1 gene variation may play a role in cocaine dependence etiology.addiction ͉ genetics ͉ SLC6A3
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ObjetivoAvaliar o perfil sociodemográfico e o padrão de uso da cocaína entre usuários de drogas hospitalizados. Métodos Estudo transversal com dependentes químicos maiores de 18 anos, internados em alguns hospitais psiquiátricos da região metropolitana da Grande São Paulo, Brasil, com condições clínicas de responder a questionário padronizado e que concordaram em participar do estudo. Foram selecionados seis hospitais psiquiátricos que recebiam, por procura espontânea, pacientes da rede pública e privada de toda a região da Grande São Paulo. A coleta de informações foi feita por meio de entrevistas estruturadas, aplicada individualmente por psicóloga treinada. Para análise estatística utilizou-se do teste t de Sudent e Qui-quadrado, e o nível de significância foi fixado em 5%. Resultados Encontrou-se maior taxa (38,4%) de usuários de crack e pequena prevalência (1,6%) de usuários de drogas injetáveis. Os dependentes de cocaína fumada apresentavam baixa escolaridade, encontravam-se mais freqüentemente desempregados, haviam morado nas ruas, usavam maiores quantidades de droga e tinham sido presos em maior número de vezes do que aqueles que usavam outras vias de administração da droga. Conclusões Os resultados sugerem que o uso de drogas é um grave problema de saúde pública na Grande São Paulo, mostrado pelo número de internações hospitalares por dependência. Os usuários de crack apresentam pior condição socioeconômica e maior envolvimento com a violência e a criminalidade.
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Background: The frequency of ESBL producing Klebsiella pneumoniae bloodstream infections (BSI) is high in Brazilian hospitals, however little is known regarding what role, if any, resistance plays in the expected outcome in hospitals with a high prevalence of these pathogens.
Our study shows that S aureus bacteremia has a high mortality, especially when the lung is the source of infection and when shock develops; resistance to methicillin may be another risk factor for poor outcome.
The Brazilian Portuguese version of the HAT-QoL is valid, reliable, and may contribute to evaluating the impact of HIV infection on the quality of life of patients in Brazil.
Our study shows that S aureus bacteremia has a high mortality, especially when the lung is the source of infection and when shock develops; resistance to methicillin may be another risk factor for poor outcome.
Hepatitis C virus (HCV) causes infectious hepatitis worldwide. It is transmitted mainly by blood products and sharing of intravenous paraphernalia during illicit drug use. High prevalence rates have been described among specific groups considered to be at higher risk for HCV infection, including prison inmates. The objectives of this study were: to determine the HCV seroprevalence among inmates of Casa de
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