Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.FAPESPCNP

Identificação de biomarcadores para qualidade da carne de animais Nelore e Brangus

Na última década, a origem da carne bovina começou a ser questionada e, por conseguinte, passou a ser valorizada por consumidores esclarecidos. Essa valorização tende a aumentar nos próximos anos, seja para garantir aspectos sanitários, nutritivos, sensoriais e até mesmo de indicação geográfica ou terroir. O presente projeto tem como objetivo desenvolver biomarcadores para caracterização fenotípica da carne

Pesquisa e percepção pública sobre biossegurança de OGM: subsídios para decisões estratégicas na America Latina.

O projeto LAC-Biosafety é um consórcio entre Brasil, Colômbia, Costa Rica e Peru, sob a coordenação do Centro Internacional de Agricultura Tropical. Suas atividades de pesquisa visam complementar informações técnicas de biossegurança ambiental para as culturas de algodão, arroz, batata, mandioca e milho, buscando harmonização de propostas de pesquisa em nível regional. Ao mesmo tempo busca subsidiar o conhecimento do impacto socioeconômico de algumas dessas culturas. Merece destaque a maneira inovadora de detectar a percepção pública sobre o tema para caracterizar e atender às necessidades de comunicação adequadas com os consumidores. Esse componente do projeto vem ao encontro de expectativas regionais e nacionais, bem como dos valores e diretrizes estratégicas da Embrapa quando propõe o aprimoramento dos canais de diálogo com seus públicos alvo sobre a biossegurança de culturas agrícolas de vulto socioeconômico. As informações técnicas geradas preencherão vazios de informação e apoiarão órgãos nacionais competentes na tomada de decisão. A Embrapa será o agente facilitador do acesso à informação científica e facilitador do diálogo na sociedade. Essas ações do projeto também atendem às prioridades recém estabelecidas na conferência da FAO (Guadalajara, março 2010) sobre biotecnologias na agricultura de países em desenvolvimento. Futuramente espera-se que o projeto possa se consolidar como elemento aglutinador dos pesquisadores e comunicadores da Embrapa envolvidos nesta área.Disponível em: Acesso em: 21 fev. 2011

Compound A, a Dissociated Glucocorticoid Receptor Modulator, Inhibits T-bet (Th1) and Induces GATA-3 (Th2) Activity in Immune Cells

Background: Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has antiinflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively. Results: Using Western analysis and reporter gene assays, we show in murine T cells that, similar to GCs, CpdA inhibits T-bet activity via a transrepressive mechanism. Different from GCs, CpdA induces GATA-3 activity by p38 MAPK-induction of GATA-3 phosphorylation and nuclear translocation. CpdA effects are reversed by the GR antagonist RU38486, proving the involvement of GR in these actions. ELISA assays demonstrate that modulation of T-bet and GATA-3 impacts on cytokine production shown by a decrease in IFN-c and an increase in IL-5 production, respectively. Conclusions: Taken together, through their effect favoring Th2 over Th1 responses, particular dissociated GR ligands, fo

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

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