Intoxicação por êxtase: bases toxicológicas para o tratamento

Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.Os jovens estão cada vez mais usando o 3,4-metilenodioximetanfetamina, conhecido como êxtase, pois acreditam que não causa danos. Entretanto, existem muitos relatos de efeitos adversos, incluindo a intoxicação aguda, abuso potencial e possíveis efeitos neurotóxicos. Portanto, profissionais da área da saúde necessitam reconhecer prontamente os sintomas da intoxicação a fim de iniciar o tratamento o mais breve possível. A droga é usada via oral durante várias horas de festas com danças. Agudamente, o êxtase aumenta a liberação do serotonina e diminui sua recaptação, levando a hipertensão, hipertermia, trismo e vômitos. Há discussão se as doses recreacionais causam danos permanentes aos neurônios serotonérgicos em humanos. Os usuários apresentam risco elevado de desenvolver distúrbios psicopatológicos, além disso, o uso prolongado pode induzir a dependência, caracterizada pela tolerância e ressaca. A intoxicação aguda necessita de tratamento de emergência, para se evitar reações adversas e complicações graves. Não há antidotos específicos para tratar a intoxicação aguda. Medidas de suporte e tratamento médico para cada uma das complicações devem ser executados, mantendo-se em mente que os sintomas a serem tratados originam-se principalmente do sistema nervoso central e do sistema cardiovascular

Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer

BACKGROUND: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. METHODS: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. RESULTS: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. CONCLUSIONS: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer