Long-term treatment with 3, 4-methylenedioxymethamphetamine caused retina damage in C57BL/6 mice / Tratamento a longo prazo com 3, 4-metilenedioximetanfetamina causando dano na retina em camundongos C57BL/6

ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.

RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.

Intoxicación aguda por MDMA Serie de casos / ACUTE INTOXICATION BY MDMA (ECTASY) REPORT OF 4 CONSECUTIVE PATIENTS

Drugs are a rising problem with today teens. One of these up and coming substances is ectasy. Properly known as MDMA (methyldioxymethamphetamine), is most commonly used at clubes, raves, and atmospheres where there are a lot of people and loud music. MDMA commonly known as ectasy, is a psychoactive drug used as a recreational drug. Desidered effects of its abuse include empathy, euphoria and heightened sensations. When taken by mouth effects begin after 30-45 minutes and lasts 3-5 hours. Adverse effects of MDMA use include addiction, memory problems, paranoia, difficulty sleeping, blurred vision, sweating and a rapid heartheat. Use may also lead to depression and fatigue. Deaths have been reported due to increased body temperature and dehydration. MDMA influences in neurotransmitters serotonin. MDMA generally is illegal in most countries. In general, MDMA users begin reporting effects within 30 to 50 minutes of consumption. The most serious short-term physical health risks of MDMA are hyperthermia and dehydration. Cases of life-threatening or fatal hyponatremia (excessively low sodium concentration in the blood) have developed in MDMA users attemping to prevent dehydration by consuming excessive amount of water without replenishing electrolytes. MDMA overdose intoxication symptoms vary widely due to the involvement of multiple organ system. In most fatalities MDMA was not the only drug involved. Acute toxicity is mainly caused by serotonin syndrome and sympthomimetic effects. MDMA´s toxicity in overdose may be exacerbated by caffeine, with which it is frequently cut (mixed with to increase volume). Caffeine provokes adverse interactions with MDMA ectasy. Polydipsia is another mechanism of hyponatremia after ectasy ingestion. During april 2016, four patients comming from an electronic party were assisted at the Emergentology service from the "Juan Fernandez" hospital from the city of Buenos Aires. The clinical features of these patients are described, and the treatment and the evolution observed, are documented.

effect of pentoxifylline on bcl-2 gene expression changes in hippocampus after long-term use of ecstasy in Wistar rats

3,4- Methylenedioxymethamphetamine [MDMA or "Ecstasy"] is a psychoactive and hallucinogenic drug of abuse. MDMA has been shown to produce neurotoxicity both in animals and humans. Recently, the vasodilator drugs such as pentoxifylline is one of the new strategies which have been considered as neuroprotector. In this study effect of pentoxifylline on bcl-2 gene expression changes in hippocampus of rat following long- term use of ecstasy was investigated. 30 male Wistar rats weighing 250-300g were randomly divided into 5 groups: control [normal], sham [MDMA injection], experimental 1[MDMA and then PTX injections], experimental 2[PTX injection and after 1 week, MDMA injection] and vehicle [saline injection] groups. All drugs were injected intraperitoneally. Two weeks later, the hippocampi were removed for studying the changes in bcl-2 gene expression. We used quantitative real time PCR for detection of bcl-2 gene expression in treated groups and then compared them to control samples. The results showed the gene dosage ratio of 0.49, 0.78 and 1.17 for sham, experimental 1 and experimental 2 groups, respectively. The results also showed the bcl-2gene expression declined in sham group as compared to the experimental groups. Furthermore, we observed a significant difference in the bcl-2 gene expression between sham and experimental 2 groups. We conclude that quantitative real time PCR could be used as a direct method for the detection of bcl-2 gene expression in tested and normal samples

Neuroprotective properties of Melissa offtcinalis l. extract against ecstasy-induced neurotoxicity

The aim of the present study was to investigate the neuroprotective effects of Melissa officinalis, a major antioxidant plant, against neuron toxicity in hippocampal primary culture induced by 3,4-methylenedioxymethamphetamine [MDMA] or ecstasy, one of the most abused drugs, which causes neurotoxicity. 3-[4,5-dimethyl2 thiazoyl]2,5-diphenyketrazolium bromide [MTT] assay was used to assess mitochondrial activity, reflecting cell survival. Caspase-3 activity assay and Hoechst / propiedium iodide [PI] staining were done to show apoptotic cell death. A high dose of ecstasy caused profound mitochondrial dysfunction, around 40% less than the control value, and increased apoptotic neuronal death to around 35% more than the control value in hippocampal neuronal culture. Co-treatment with Melissa officinalis significantly reversed these damages to around 15% and 20% respectively of the MDMA alone group, and provided protection against MDMA-induced mitochondrial dysfunction and apoptosis in neurons. Melissa officinalis has revealed neuroprotective effects against apoptosis induced by MDMA in the primary neurons of hippocampal culture, which could be due to its free radical scavenging properties and monoamine oxidase [MAO] inhibitory effects

"Extase" (3,4 metilenodioximetanfetamina, MDMA): uma droga velha e um problema novo? / \"Ecstasy\" (3,4 methylenedioxymethamphetamine, MDMA): an old drug and a new problem?

O uso recreacional da MDMA ou, como tem sido popularmente chamado, êxtase, tem sido identificado em vários dos pacientes que buscam tratamento para dependências de drogas nas clínicas de Säo paulo. Embora a MDMA näo seja uma nova droga, pois foi sintetizada no começo do século, a maioria dos profissionais de saúde näo tem conhecimento de seus efeitos físicos e psíquicos e das possíveis complicaçöes que podem ocorrer com seu uso. O objetivo desta revisäo é: 1) traçar um histórico da MDMA desde a sua síntese até seu uso recente como droga de abuso em vários países; 2) discutir seus principais efeitos químicos e toxicológicos; 3) apresentar os possíveis efeitos adversos da MDMA em humanos; 4) discutir o perfil de uso em outros países e seus possíveis padröes em nosso meio. Foi feita revisäo de literatura baseada no MEDLINE no período de 1985 a 1995