Guidelines of the Brazilian Association of Studies on Alcohol and Other Drugs (ABEAD) for diagnoses and treatment of psychiatric comorbidity with alcohol and other drugs dependence

Recently, several studies have focused on comorbity psychiatric disorders with alcohol and other substance dependence. The Brazilian Association of Studies on Alcohol and Other Drugs proposed the Brazilian Guidelines project. This study review diagnostic and therapeutic criteria to the most prevalent psychiatric comorbidities. Randomized clinical trials, epidemiological, animal studies and other forms of research are reviewed. The main psychiatric comorbidities are studied based on guidelines adopted by other countries and the literature data resumed. Epidemiological aspects, diagnoses, integrated treatment and service organization, as well as specific psychotherapic and pharmacological treatment are discussed. The Brazilian Association of Studies on Alcohol and Other Drugs Guidelines reassures the importance of adequate diagnoses and treatment regarding alcoholic and drug dependent patients suffering of comorbid psychiatric disorders.O diagnóstico e tratamento de comorbidade psiquiátrica e dependência de álcool e outras substâncias tem sido objeto de inúmeros estudos nos últimos anos. A Associação Brasileira de Estudos do Álcool e Outras Drogas desenvolveu o projeto Diretrizes. Este trabalho visa o desenvolvimento de critérios diagnósticos e terapêuticos atualizados para as comorbidades psiquiátricas mais prevalentes. Ensaios clínicos randomizados, estudos epidemiológicos, com animais e outros estudos são revisados. As principais comorbidades psiquiátricas são estudadas e os dados de literatura resumidos, tendo como referência diretrizes adotadas em outros países. São abordados aspectos epidemiológicos, critérios diagnósticos, tratamento integrado e organização de serviço especializado, assim como especificidades do tratamento psicoterápico e farmacológico. As Diretrizes da Associação Brasileira de Estudos do Álcool e Outras Drogas reforçam a importância da abordagem adequada do dependente químico portador de comorbidade psiquiátrica.Universidade Federal de Santa Catarina Núcleo de PsiquiatriaInstituto de Psiquiatria de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP) Unidade de Pesquisa em Álcool e DrogasSanta Casa de Misericórdia de São Paulo Unidade de Álcool e DrogasUniversidade de São Paulo Faculdade de Medicina Hospital das ClinicasCentro de Atendimento Médico e SocialHospital de Clínicas de Porto AlegreHospital Israelita Albert EinsteinSanta Casa do Rio de Janeiro Setor de Dependência QuímicaUniversidade Gama FilhoUNIFESP, Unidade de Pesquisa em Álcool e DrogasSciEL

Avaliação da função macrofágica na hanseníase virchowiana: marcadores de superfície, receptores TLR e NLR e mediadores inflamatórios

Macrophages play a major role in the elimination of M. leprae (ML). These cells participate in pathogen recognition and activation of the immune system. However in the lepromatous leprosy macrophages become targets, serving as habitat for the bacillus that protects itself from the action of the immune system. This study aimed to evaluate the macrophage function in lepromatous leprosy patients (LLP) in term of surface molecules expression and cytokine and H2O2 production. Moreover, considering the possible involvement of inflammasome complex in macrophage response against ML, inflammasome genes expression was evaluated. ML induced surface expression of activation markers CD40 and ICAM in healthy controls (HC) and LLP macrophages in a similar way, as well as TLRs involved in ML recognition (TLR1 and TLR2). Pro-inflammatory cytokines TNF and IL-1β showed a different behavior. ML was able to induce TNF in HC and LLP, but not IL-1β. Similarly, ML induced significant production of H2O2 in HC but not in LLP macrophages. No difference was found in the production of anti-inflammatory molecules IL-10 and IL1RA in HC and LLP macrophages stimulated with ML. When inflammasome genes expression was analyzed an up-regulation of IL1B gene was observed in both HC and LLP macrophages stimulated with ML. Together, our data indicate that the deficiency in the production of IL-1β and H2O2 in lepromatous leprosy patients combined with IL1B gene expression induction by M. leprae suggested that even if surface recognition of ML and general activation of macrophages are apparently normal, the bacteria is able to inhibits the pathways leading to I IL-1β and H2O2 production, possibly affecting inflammasome activationOs macrófagos desempenham um papel importante na eliminação do M. Leprae (ML). Estas células participam do reconhecimento de patógenos e ativação do sistema imune, no entanto na hanseníase virchowiana elas se tornam alvos, servindo de habitat para o bacilo, que ali se protege da ação do sistema imune. Assim, este estudo teve por objetivo avaliar a função macrofágica de pacientes com hanseníase virchowiana (LLP) em termos de expressão de marcadores de superfície e produção de mediadores inflamatórios. Além disso, considerando o possível envolvimento dos inflamassomas na resposta dos macrófagos ao ML, foi avaliada a expressão de genes do complexo do inflamassoma. Para tanto, macrófagos diferenciados a partir de monócitos sanguíneos de LLP e indivíduos saudáveis (HC) foram cultivados com ML. A expressão dos marcadores de ativação CD40 e ICAM, e dos receptores do tipo Toll envolvidos no reconhecimento do ML, TLR1 e TLR2, foi avaliada por citometria de fluxo. A produção de citocinas pró (TNF e IL-1β) e anti-inflamatórias (IL-10 e IL-1RA) foi determinada por ELISA e a produção de H2O2 foi avaliada por ensaio colorimétrico. A expressão relativa dos genes NLRP1, NLRP3, NLRC4, CASP1, IL1B e IL18 foi avaliada por PCR em tempo real. ML induziu expressão semelhante de CD40 e ICAM em HC e LLP, assim como dos TLR1 e TLR2. TNF e IL-1β mostraram comportamento diferente, sendo que o ML estimulou uma produção significativa de TNF em HC e LLP, mas não induziu a secreção de IL-1β. H2O2 não foi significativamente induzida pelo ML em LLP. Nenhuma diferença foi encontrada para as citocinas anti-inflamatórias entre HC e LLP. A análise da expressão de genes relacionados aos inflamassomas mostrou que ML é capaz de induzir o gene da IL-1β, mas não dos receptores analisados. Os dados aqui reportados mostrando deficiência na secreção de IL-1β em macrófagos estimulados com ML e a baixa quantidade de H2O2 produzida ...Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Peripersonal space in social context is modulated by action reward, but differently in males and females

The peripersonal space (PPS) is a multisensory representation of the near-body region of space where objects appear at hand. It also represents a buffer zone protecting the body from external threats and as such it contributes to the organization of social interactions. However, how the combination of embodied objects processing and constraints inherent to social interactions contributes to PPS representation remains an open issue. By using a cooperative task where two male (N = 22) or female (N = 18) participants, sharing the same action space, were requested to select a number of stimuli on a touch-screen table, we investigated the effect of non-uniform distribution of reward-yielding stimuli on selection strategy and perceptual judgments of reachability, used as a proxy of PPS representation. The probability to select a reward-yielding stimulus (50% of the stimuli) was 75% in the proximal space of one of the two confederates. Results showed that participants initially prioritized stimuli in their proximal space and were progressively influenced by the spatial distribution of reward-yielding stimuli, thus invading their confederate’s action space when associated with higher probability of reward. The distribution of reward-yielding stimuli led to an increase of reachability threshold, but only when biased towards the participants’ distal space. Although the invasion of others’ PPS was more pronounced in male participants, the biased distribution of reward-yielding stimuli altered the reachability threshold similarly in males and females. As a whole, the data revealed that reward expectations in relation to motor actions influence both PPS exploration and representation in social context, but differently in males and females.This work was funded by the French National Research Agency (ANR-11-EQPX-0023) and also supported by European funds through the program FEDER SCV-IrDIVE. M-F G was supported by a Ph.D. grant from the University of Lille and Région Hauts-de-France

Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of lepros