Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica

BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985 and 2007. RESULTS: There were still many unanswered questions regarding the pharmacology of ecstasy and the pathophysiology of its toxic effects. The fundamental mechanism of action is insufficient to explain all effects induced by the drug. The exact mechanism responsible for mediating the toxic effects of MDMA on 5-HT neurons remain to be elucidated. DISCUSSION: There is limited information in published literature about the underlying pharmacology and mechanism of action that could account for the neurotoxic and other phathophysiological effect of MDMA.CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase) é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável

Aneurisma infectado de artéria braquial após endocardite infecciosa de valva mitral Infected aneurysm of brachial artery after mitral valve infective endocarditis

Apresentamos um caso de aneurisma infectado de artéria braquial em paciente com endocardite infecciosa por Streptococcus bovis. Homem de 49 anos de idade se apresentou com febre, dispnéia e sopro regurgitativo em foco mitral com irradiação para axila. O ecocardiograma demonstrou vegetação em valva mitral nativa. Após troca valvar mitral com implante de prótese biológica, observou-se massa pulsátil de cinco centímetros de diâmetro em fossa antecubital direita. Foi feito o diagnóstico de aneurisma infectado de artéria braquial, e o tratamento cirúrgico foi realizado com sucesso. O objetivo desse relato de caso é apresentar uma complicação pouco comum após endocardite infecciosa.<br>We present a case of brachial artery infected aneurysm in a patient with infective endocarditis caused by Streptococcus bovis. A 49-year-old man presented with fever dyspnea and a pansystolic murmur with irradiation to axilla. The echocardiogram revealed vegetation in native mitral valve. After mitral valve replacement with bioprosthesis, it was observed pulsatile mass of five centimeters in diameter at antecubital fossa of right upper limb. It was made the diagnosis of infected aneurysm of the brachial artery, and the surgery was performed successfully. The aim of this case report is to show a rare complication after infective endocarditis

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos Experimental model of myocardial infarction induced by isoproterenol in rats

OBJETIVO: Avaliar e validar, em nosso meio, o modelo de infarto do miocárdio induzido por isoproterenol em ratos por meio de análises de parâmetros hematológicos, bioquímicos, de marcadores do estresse oxidativo e histopatológicos. MÉTODOS: Trinta ratos jovens, machos, da linhagem Wistar (145 a 230 g), foram alocados aleatoriamente em dois grupos: grupo Simulado, submetido à falsa indução de infarto do miocárdio, e grupo Infarto, submetido à indução do infarto do miocárdio com isoproterenol. As aplicações, para indução do infarto, foram realizadas durante dois dias consecutivos, com intervalo de 24 horas entre elas. Após 24 horas da última aplicação, os ratos de ambos os grupos foram anestesiados e sacrificados para realização de coleta de sangue para hemograma e análise bioquímica (TGO, TGP, troponina I, ureia e creatinina) e coleta de fragmento do miocárdio para avaliação de marcadores do estresse oxidativo (atividade da catalase e concentração de glutationa) e exame histopatológico. RESULTADOS: Não houve mortalidade no grupo Simulado, enquanto a mortalidade no grupo Infarto foi de 25%. A indução do infarto do miocárdio com isoproterenol causou elevação das contagens de leucócitos e neutrófilos, dos níveis de TGO, troponina I e ureia, reduziu a atividade da catalase e os níveis teciduais de glutationa e causou alterações histopatológicas. Não acarretou alterações nas concentrações de hemoglobina, TGP e creatinina. CONCLUSÕES: O modelo de infarto do miocárdio induzido por isoproterenol em ratos foi adequadamente reproduzido em nosso laboratório, acarretando alterações em parâmetros hematológicos, bioquímicos, de marcadores de estresse oxidativo e histopatológicos.<br>OBJECTIVE: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological parameters. METHODS: Thirty young, male, Wistar rats (145 to 230 g) were randomly allocated in two groups: Sham group, which underwent a virtual myocardial infarction induction, and the Infarction group, which underwent a myocardial infarction induction with isoproterenol. The administrations for the infarction induction were performed during two consecutive days and a 24-hour interval between them. Twenty-four hours after the last administration, rats from both groups were anesthetized and sacrificed for blood sample collection to evaluate complete blood count (CBC) and biochemical parameters (SGOT, SGPT, troponin I, urea and creatinin), obtain myocardial fragments for oxidative stress markers analyses (catalase activity and glutathione concentrations) as well as histopathological examinations. RESULTS: There were no death cases in the Sham group, while the mortality rate in the Infarction group was 25%. Myocardial infarction induction with isoproterenol raised leukocytes and neutrophils counts, SGOT, troponin I and urea concentrations, reduced catalase enzyme activity and glutathione concentrations in the myocardium and let to histopathological concentrations as well. It did not exert alterations in terms of hemoglobin, SGPT and creatinin concentrations. CONCLUSIONS: The isoproterenol-induced myocardial infarction essay in rats was adequately reproduced in our laboratory, causing alterations in hematological, biochemical, oxidative stress markers and histopathological parameters

Antimicrobial Efficacy of Propolis-Containing Varnish in Children: A Randomized and Double-Blind Clinical Trial

Dental caries is a sugar-dependent condition common in childhood, which causes microbiological imbalance in dental biofilm. The present study evaluated the antimicrobial efficacy of a 2.5% Brazilian Red Propolis (BRP) dental varnish to prevent caries in children. Seventy-five children with high caries risk, aged between 36 and 71 months and with no caries, were assigned to three groups to receive varnish treatment containing 2.5% BRP, 1% chlorhexidine, or 5% fluoride. The varnish was applied to the occlusal surfaces of the deciduous second molars on the first day of treatment (D1), after 90 days (D90), and 180 days of the start of treatment (D180). Saliva was collected to assess S. mutans before each varnish application and 180 days at the end of treatment (D360). Values were expressed in log10 (CFU/mL). Statistics were performed by applying repeated measures of variance analysis, Tukey's multiple comparisons test, and paired t-test. In the first dilution (1 : 10), there was microbial load reduction at the following periods: BRP in D0-D90 (p<0.05) and D0-D180 (p<0.01); fluoride in D0-D90 (p<0.001); and chlorhexidine in D0-D180 (p<0.05). In the second dilution (1 : 100), there was microbial load reduction in the groups at the following periods: BRP in D0-D90 (p<0.05) and D0-D180 (p<0.01); fluoride in D0-D180 (p<0.05), and chlorhexidine in D0-180 (p<0.01) and D0-360 (p<0.05). The 2.5% BRP dental varnish was effective in decreasing S. mutans colonies in saliva when used within 90 days

Dose-response evaluation of a copaiba-containing varnish against streptococcus mutans in vivo

Introduction: Dental caries is the most prevalent disease in humans and its incidence is particularly high during childhood. The use of medicinal plants is a common practice in Brazil. Objective: To evaluate the optimal antimicrobial concentration of Copaifera langsdorffii (copaiba) oil-resin, in the form of dental varnish, against Streptococcus mutans (S. mutans) in children. Methods: Twenty-four children, caries-free, aged until 6 years old, were selected to participate in this study. The varnish was applied to the occlusal surfaces of all deciduous molars. The antimicrobial activity was analyzed in saliva, whose collection was conducted in two phases: before applying the copaiba varnish and after use to verify the instantaneous effectiveness of Copaifera langsdorffii dental varnish in the reduction of S. mutans. The microbiological analysis was repeated twice, establishing dilutions of 1:10 mL and 1:100 mL. Results: Comparisons between different times within the same dilution were carried out by repeated measures analysis of variance (ANOVA) associated with Tukey’s multiple comparisons test. Comparisons of conditions prior to and after treatment were performed using the t test for paired samples and it indicated that the 1% formulation promoted a more significant decrease in the number of S. mutans colonies (p = 0,0026). Conclusion: Copaiba oil-resin, in the form of dental varnish, has antimicrobial activity against S. mutans in all the concentrations studied. Further studies to identify the long-term activity and anticaries effect of this varnish are required to establish its use in caries prevention. Keywords: Dental caries, Saliva, Streptococcus mutan

Clinical and Microbiological Evaluation of Brazilian Red Propolis Containing-Dentifrice in Orthodontic Patients: A Randomized Clinical Trial

Aim. To evaluate the efficacy of dentifrice containing brazilian red propolis (BRP) in adolescents under orthodontic treatment. Materials and Methods. This is a randomized, double-blind, clinical trial. A total of 92 participants free from caries were randomized into 2 groups; the first received fluoride dentifrice, and the second received fluoride dentifrice incorporated with BRP. The gingival bleeding index (GBI) was recorded, and saliva was collected on the baseline (D0) and after 28 days (D28) for microbiological analysis. Data from GBI and Colony Forming Units (CFU) (log10) were expressed as mean and standard deviation. Results. The two groups reduced GBI significantly, with no difference in the intergroup analysis. In the intragroup analysis, it was observed that G2 (p<0.001) had a significant reduction for Gram-negative bacteria, while there was significance (p<0.001) in the intergroup analysis when compared with G1. For S. mutans bacteria, it was observed that only G2 had a statistically significant reduction (p<0.001), and there was significant reduction (p=0.006) in the intergroup analysis of the G2 group when compared with G1. Conclusions. Dentifrice containing BRP demonstrated better clinical and microbiological activity. Future studies are needed to better identify effects to establish the use of dentifrice containing propolis in biofilm control

Clinical and Antimicrobial Evaluation of Copaifera langsdorffii Desf. Dental Varnish in Children: A Clinical Study

Background. The objective of this study was to evaluate the clinical and microbiological efficacies of (C. langsdorffii) dental varnish in children at high risk of dental caries.. Methods. This is a longitudinal, randomized, controlled clinical trial. Ninety high-risk caries-free children (ICDAS II = 0) were recruited and randomly divided into three groups: C. langsdorffii, chlorhexidine, or fluoride. The varnishes were applied on the second deciduous molars for three times: baseline (D0), after 90 days (D90), and after 180 days (D180). Saliva was collected on D0, D90, D180, and D360 to evaluate S. mutans reduction. Statistics were carried out by ANOVA, Tukey’s test, and the paired t-test. Results. Copaiba varnish demonstrated significant S. mutans reduction: D360 versus D0 p<0.0001, D180 versus D0 p<0.001, D360 versus D90 p<0.001, D180 versus D90 p<0.001, and D360 versus D180 p<0.05. Chlorhexidine varnish significantly reduced S. mutans at D180 versus D0 p<0.05. Fluoride reduced at D180 versus D0 p<0.001. Conclusions. Three annual applications of this varnish showed substantial antimicrobial activity against S. mutans and caries prevention for up to 12 months