Convenção-Quadro para o Controle do Tabaco: adesão e implantação na América Latina / WHO Framework Convention on Tobacco Control: adherence and establishment in Latin America

OBJETIVO:Traçar o panorama de adesão mundial à Convenção-Quadro para o Controle do Tabaco (CQCT) e descrever a implantação das medidas preconizadas pela CQCT em países latino-americanos. MÉTODOS: Este estudo descritivo baseou-se em análise de dados secundários para determinar o status de adesão, no ano de 2015, dos países das seis regiões definidas pela Organização Mundial da Saúde (OMS) à CQCT. Depois disso, realizou-se um mapeamento da implantação, até o ano de 2012, das medidas preconizadas pela CQCT no total de Estados Partes e particularmente em 12 Estados Partes latino-americanos. Finalmente, Brasil, Chile, Colômbia, México e Venezuela foram avaliados quanto ao grau de implantação da CQCT (incipiente, intermediária e avançada). Foram consideradas neste passo medidas englobadas por quatro eixos - redução da demanda por tabaco, redução da oferta de tabaco, redução dos danos ao ambiente e à saúde das pessoas causados pelo tabaco e apoio ao abandono do tabaco. RESULTADOS: Até agosto de 2015, 180 países haviam ingressado no rol de Estados Partes da CQCT. Considerando os 126 países que enviaram relatórios de progresso global da implantação no ciclo de 2012, as medidas mais prevalentes adotadas referiam-se à proteção contra a exposição à fumaça do tabaco (83,0% para o total de países e 100% para o conjunto de países latinoamericanos). Entre os cinco países selecionados para análise detalhada, as medidas destinadas à redução da demanda e da oferta do tabaco foram as mais frequentes. As medidas relacionadas à redução de danos ao ambiente foram raras. Brasil e México apresentaram a situação mais avançada de implantação entre os países estudados. CONCLUSÕES: A América Latina apresentou uma alta proporção de Estados Partes que implantaram as medidas preconizadas pela CQCT. A heterogeneidade da situação de implantação nos cinco países selecionados sugere que as políticas de controle de tabaco são condicionadas por particularidades nacionais.

OBJECTIVE: To draw an overview of the adherence of countries around the world to the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) and to describe the establishment of WHO FCTC recommended measures in Latin American countries. METHODS: This descriptive study was based on analysis of documents and secondary data to determine the status of countries from the six WHO regions regarding adherence to the FCTC. After that, the establishment of recommended measures until the year 2012 was mapped in all States Parties and particularly in 12 Latin American States Parties. Finally, the degree to which FCTC measures had been established in Brazil, Chile, Colombia, Mexico, and Venezuela was assessed (incipient, intermediate, or advanced). This step took into consideration the measures covered by four domains - reduction in the demand for tobacco, reduction in the offer of tobacco, reduction in damage to the environment and to the health of people caused by tobacco, and support for quitting the use of tobacco. RESULTS: Until August 2015, 180 countries had joined as States Parties to the FCTC. Considering the 126 countries that submitted global progress reports in the 2012 cycle, the most prevalent measures adopted referred to the protection against exposure to tobacco smoke (83.0% for all countries and 100% for the group of Latin American countries). Among the five countries selected for detailed analysis, the measures referring to the reduction of demand and offer of tobacco were the most frequent. Measures focused on reducing environmental damage were rare. Brazil and Mexico had the most advanced FCTC status among the studied countries. CONCLUSIONS: Latin America presented a high proportion of States Parties with established FCTC recommended measures. The heterogeneity of the FCTC status in the five selected countries suggests that the implementation of tobacco control policies depends on specific aspects of each country.

Sistema endocanabinoide y desarrollo de esteatosis hepática / A role for the endocannabinoid system in hepatic steatosis

The endocannabinoid system (SEC) is an important modulator of several metabolic functions. This system is composed by cannabinoid receptors type 1 and 2 (RCB1 and RCB2), their endogenous ligands, known as endocannabinoids, and the enzymes involved in their synthesis and degradation. A deregulated SEC originates metabolic alterations in several tissues, resulting in the typical manifestations of the metabolic syndrome. Liver steatosis of different origins constitutes a physiopathological condition where an altered hepatic SEC is observed. In this condition, there is an increased expression of RCB1 and/or higher endocannabinoid levels in different hepatic cells, which may exert an autocrine/paracrine hyperstimulation of RCB1/RCB2. Activation of RCB1 stimulate the expression of several hepatocyte lipogenic factors, thus leading to increased de novo fatty acids synthesis and consequently to an abnormal accumulation of triglycerides. The effect of RCB2 activity on hepatic function is still controversial because, on one side its stimulation has an interesting protective effect on alcoholic liver disease while, on the other, it may enhance the development of hepatic steatosis in experimental models of diet-induced obesity. In this review we discuss the proposed mechanisms by which SEC is involved in the etiology of hepatic steatosis, as well as the therapeutic possibilities involving peripheral RCB1/RCB2 antagonism/agonism, for the treatment of this condition.

The endocannabinoid system and its role in schizophrenia: a systematic review of the literature / O sistema endocanabinoide e seu papel na esquizofrenia: uma revisão sistemática da literatura

OBJECTIVE: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. METHODS: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. RESULTS: Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. CONCLUSIONS: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.

OBJETIVO: A esquizofrenia é um transtorno psiquiátrico cujos mecanismos permanecem apenas parcialmente elucidados. As atuais propostas relativas à base biológica, tais como a hipótese dopaminérgica, não explicam por completo a diversidade de seus sintomas, o que indica que outros processos podem estar envolvidos. Este artigo tem como objetivo revisar indícios que sustentem o envolvimento do sistema endocanabinoide (SECB), um grupo de neurotransmissoresalvo dos compostos da Cannabis sativa, nesse transtorno. MÉTODOS: Revisão sistemática dos artigos originais, publicados em inglês e indexados no PubMed até abril de 2012. RESULTADOS: A maioria dos estudos empregou métodos neuroquímicos ou de neuroimagem genéticos e histológicos - tanto in vivo quanto post-mortem - para investigar se os componentes do SECB estão comprometidos nos pacientes. De modo geral, os dados mostram mudanças nos receptores canabinoides em determinadas regiões cerebrais, bem como a alteração dos níveis de endocanabinoides no líquido cefalorraquidiano e/ou no sangue. CONCLUSÕES: Ainda que a disfunção do SECB tenha sido descrita, os resultados dos estudos não são totalmente consistentes. São necessários mais dados para definir melhor o papel desse sistema na esquizofrenia.

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits / Del cannabis al sistema endocannabinoide: re-enfocando la atención hacia los potenciales beneficios clínicos

Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the 'holy grail' of endocannabinoid research.

La cannabis sativa es una especie herbácea usada en uno de los remedios herbarios más viejos conocidos al ser humano. Durante los últimos cuatro mil anos, se ha usado para el tratamiento de numerosas enfermedades, pero debido a sus propiedades psicoactivas, su uso medicinal actual se halla muy restringido. En este estudio, se busca resaltar los adelantos hechos durante los últimos cuarenta anos en cuanto a entender los mecanismos responsables de los efectos del cannabis sobre el cuerpo humano, y cómo éstos pueden utilizarse potencialmente en la práctica clínica. Durante este tiempo, se han aislado los ingredientes activos primarios en el cannabis, se han descubierto receptores canna-binoides específicos, y se han identificado por lo menos cinco neurotransmisores endógenos (endo-cannabinoides). Juntos, éstos forman la estructura de un complejo sistema de senalización endocannabinoide, el cual tiene una amplia distribución en el cuerpo y desempena un papel en la regulación de numerosos procesos fisiológicos dentro del organismo. Por tanto, se piensa que los ligandos cannabinoides despliegan un considerable potencial terapêutico. Así, el dinamismo para desarrollar compuestos que puedan ser dirigidos a sistemas neuronales en dosis suficientemente bajas como para eliminar los efectos cognitivos secundarios, sigue siendo el "santo grial" de la investigación de los endocannabinoides.

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

The psychiatric side-effects of rimonabant / Os efeitos-colaterais psiquiátricos do rimonabanto

OBJECTIVE: Experimental evidence has suggested that drugs that enhance cannabinoid type-1 (CB1) receptor activity may induce anxiolytic and antidepressant effects, whilst the opposite has been reported with antagonists. Thus, the objective of the present review is to discuss the potential psychiatric side-effects of CB1 receptor antagonists, such as rimonabant, which has been recently marketed in several countries for the treatment of smoking cessation, obesity and associated metabolic disorders. METHOD: Literature searches were performed in PubMed and SciELO databases up to February 2009. The terms searched were "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes", "smoking cessation" and "side-effects". RESULTS: Clinical trials have revealed that rimonabant may promote weight loss in obese patients, although it may also induce symptoms of anxiety and depression. DISCUSSION: Patients taking CB1 receptor antagonists should be carefully investigated for psychiatric side-effects. These drugs should not be prescribed for those already suffering from mental disorders. Nevertheless, the development of new compounds targeting the endocannabinoid system for the treatment of several conditions would be necessary and opportune.

OBJETIVO: Evidência experimental sugere que drogas que aumentam a atividade dos receptores canabinóides tipo 1 (CB1) podem induzir efeitos ansiolíticos ou antidepressivos, enquanto que o oposto tem sido relatado com antagonistas. Assim, o objetivo da presente revisão é discutir os potenciais efeitos-colaterais psiquiátricos de antagonistas do receptor CB1, como o rimonabanto, que foi recentemente liberado para comercialização em diversos países para o tratamento do tabagismo, obesidade e de desordens metabólicas associadas. MÉTODO: Foi realizada uma busca na literatura no PubMed e Scielo até fevereiro de 2009, com os termos "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes" , "smoking cessation" e "side effects". RESULTADOS: Ensaios clínicos revelaram que o rimonabanto pode produzir perda de peso em pacientes obesos, embora também possa induzir sintomas de ansiedade e depressão. DISCUSSÃO: Pacientes tomando antagonistas do receptor CB1 devem ser cuidadosamente examinados quanto aos efeitos-colaterais psiquiátricos. Estas drogas não devem ser prescritas a indivíduos que já sofrem de transtornos mentais. Entretanto, o desenvolvimento de novos compostos que atuem no sistema endocanabinóide para o tratamento das mais diversas condições parece necessário e oportuno.

Unconventional neurotransmitters, neurodegeneration and neuroprotection

Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.