A New VMAT-2 Inhibitor NBI-641449 in the Treatment of Huntington Disease.

AIMS: To evaluate the effectiveness of a new VMAT-2 inhibitor NBI-641449 in controlling hyperkinetic movements of Huntington disease (HD) and to investigate its possible therapeutic effects. METHODS: We applied three different doses of NBI-641449 (1, 10, 100 mg/kg/day) for 2 weeks in 4-month-old YAC128 mice and wild-type (WT) mice. Rotarod performance and locomotive activities were tested during the administration of the drug. The concentration of dopamine (DA) and its metabolites was quantified in the striatal tissues by high-performance liquid chromatography (HPLC). Neuron survival in striatum and huntingtin protein aggregates were assessed with immunostaining. Expression levels of endoplasmic reticulum (ER) stress proteins were detected by immunoblotting. RESULTS: Rotarod performance was significantly improved after treatment with low or middle dose of NBI-641449 in YAC128 mice. Open field test showed that NBI-641449 treatment could attenuate the increased horizontal activity (HACTV), total vertical movement, moving time, and moving distance in YAC128 mice. High dose of NBI-641449 might cause sedative effects in WT and YAC128 mice. HPLC showed that NBI-641449 caused a dose-dependent decrease of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid levels in the striatum. NeuN and DARPP-32 immunostaining revealed that NBI-641449 had no significant effect on the neuron survival in the striatum. However, NBI-641449 treatment reduced the huntingtin protein aggregates in the cortex of YAC128 mice. In addition, the levels of ER stress proteins were increased in YAC128 mice, which can be suppressed by NBI-641449. CONCLUSIONS: These findings suggest that this new VMAT-2 inhibitor NBI-641449 may have therapeutic potential for the treatment of HD.

Cápsulas de óleo de peixe: percepção da dosagem e finalidade de consumo / Capsules of fish oil: the perception of strength and purpose of consumption

O objetivo desse estudo foi conhecer o perfil do consumidor de cápsulas de óleo de peixe compradas em farmácias de manipulação, localizadas no Estado do Rio de Janeiro tendo como referencial a finalidade de consumo. O projeto foi desenvolvido no município do Rio de Janeiro e município de Duque de Caxias que apresentaram maior número de farmácias de manipulação regularizadas no Conselho Regional de Farmácia do Rio de Janeiro (CRF-RJ). Como estratégia para obtenção de informações sobre o consumo, utilizou-se o banco de dados Pharma, programa de gerenciamento de farmácias de manipulação, e entrevistas realizadas com os consumidores. A população pesquisada foi majoritariamente feminina, na faixa etária de 15 a 24 anos, solteiras e cursando nível superior. Em relação aos objetivos de consumo de cápsulas de óleo de peixe na amostra pesquisada, verificou-se que a maioria dos consumidores (41,32%) utilizou o produto visando a diminuição dos níveis de colesterol e 32,6% desta população a obtenção de ação antioxidante com fins estéticos. Concluiu-se que o consumidor não possui conhecimento a respeito das dosagens adequadas farmacologicamente a finalidade de consumo desse produto. Somente 3,94% da população estudada conhecia a dosagem adequada para alcançar os respectivos objetivos terapêuticos. Pode-se observar que a maioria dos consumidores de cápsulas de óleo de peixe da amostra pesquisada utilizou o produto baseando-se em informações de amigos, internet, revistas e televisão. Dos sujeitos da pesquisa do sexo masculino, somente 6,06% consultou um médico enquanto que esta frequência foi de 16,66% na população do sexo feminino. Este estudo visou ainda fornecer subsídios para a formulação de propostas de controle para a utilização de alimentos funcionais e fundamentar parâmetros que garantam a proteção à saúde da população pelos órgãos competentes, através da venda segura de suplementos alimentares no Brasil.

The aim of this study was to identify consumer capsules of fish oil purchased in pharmacies, located in Rio de Janeiro referencing the purpose of consumption. The project was developed in Rio de Janeiro and Duque de Caxias with the highest number of pharmacies in regularized by the Regional PharmacyConcil (CRF-RJ). We used information from the database Pharma is a management program for pharmacies, and interviews with consumers. The research population was predominantly female, aged 15 to 24, unmarried and studying in higher education. For the purposes of consumption in the sample surveyed, it was found that most consumers (41.32%) used the capsules of fish oil in order to reduce the levels of cholesterol and 32.6% of this population had the goal of consumption to obtain an antioxidant for cosmetic purposes. One of the possible conclusions is the ignorance of consumers regarding appropriate dosages pharmacologically the goal of consumption of this product. Only 3.94% of the women knew the correct dosage to achieve their therapeutic goals, while 96.06% did not know the proper dosage. This study found that most consumers of capsules of fish oil from our sample used the product based on information from friends, internet, magazines and television. Among men surveyed, only 6.06% consulted a doctor while this rate was 16.66% for female audience. This result represents a risk to the health of consumers by undermining the goals of consumption when the dosage of functional food is not eaten as recommended pharmacological. This study also aimed to provide information for formulating proposals for the control and use of functional foods and establish parameters that ensure the protection of health of the population by the competent bodies, through the sale of dietary supplements safe in Brazil.