RESUMEN
Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was â¼14%, â¼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey.
Asunto(s)
Drogas Ilícitas/inmunología , Drogas Ilícitas/orina , Inmunoensayo , Detección de Abuso de Sustancias/métodos , Adulto , Anfetamina/inmunología , Anfetamina/orina , Cromatografía Liquida , Cocaína/inmunología , Cocaína/orina , Dronabinol/inmunología , Dronabinol/orina , Etanol/inmunología , Etanol/orina , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metanfetamina/inmunología , Metanfetamina/orina , Persona de Mediana Edad , N-Metil-3,4-metilenodioxianfetamina/inmunología , N-Metil-3,4-metilenodioxianfetamina/orina , Oxicodona/inmunología , Oxicodona/orina , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. METHODS: We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. RESULTS: We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. CONCLUSIONS: Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroimmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals.
Asunto(s)
Asma/inmunología , Inflamación/inmunología , Leucocitos/efectos de los fármacos , Pulmón/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/farmacología , Células Th2/efectos de los fármacos , Animales , Células de la Médula Ósea , Líquido del Lavado Bronquioalveolar/citología , Movimiento Celular/efectos de los fármacos , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Recuento de Leucocitos , Pulmón/citología , Masculino , Mastocitos/efectos de los fármacos , Ratones , N-Metil-3,4-metilenodioxianfetamina/inmunología , Células Th2/fisiología , Tráquea/efectos de los fármacosRESUMEN
Methamphetamine and ecstasy are addictive drugs that cause major health problems in young people. Here we report on the development of high-affinity monoclonal antibodies to methamphetamine and its analogues, which may constitute powerful tools for antibody-based therapy. Six haptens, methamphetamine and ecstasy analogues, were synthesized, linked to a carrier protein and injected into mice. Several specific monoclonal antibodies were subsequently obtained following fusion of splenocytes from the immunized animals, with Sp2/O cells. Antibody specificity was fully investigated by competition ELISA, using a series of analogues, to identify specific amphetamine and/or ecstasy-specific antibodies. Antibody affinity was estimated to be in the range of 10(8) M(-1) with an enantiomeric hapten. Finally, two characteristic hybridoma clones (DAS-M243-6H5 and DAS-M278-4B12), secreting specific and potent mAbs were isolated. The development of drug-specific antibodies as in this study may provide promising therapeutic insight into how to neutralize methamphetamine in vivo during acute intoxication.
Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Metanfetamina/inmunología , Animales , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Monoclonales/uso terapéutico , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Haptenos/química , Humanos , Hibridomas/inmunología , Drogas Ilícitas/inmunología , Drogas Ilícitas/toxicidad , Inmunoterapia , Técnicas In Vitro , Metanfetamina/análogos & derivados , Metanfetamina/toxicidad , Ratones , Ratones Endogámicos BALB C , N-Metil-3,4-metilenodioxianfetamina/inmunología , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Trastornos Relacionados con Sustancias/terapiaRESUMEN
The purpose of the present study was to examine the role of serotonin release in methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rats. We examined the effect of pretreatment with the selective serotonin reuptake inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para-chlorophenylalanine on MDMA-induced suppression of interleukin-1beta and tumour necrosis factor (TNF)-alpha secretion following an in vivo lipopolysaccharide challenge. Although paroxetine blocked MDMA-induced serotonin depletion in the cortex and hypothalamus, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced TNF-alpha secretion. Similarly, although para-chlorophenylalanine caused a 90% depletion in cortical and hypothalamic serotonin content, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced interleukin-1beta or TNF-alpha secretion. In conclusion, although MDMA is a potent releaser of serotonin, the suppressive effects of MDMA on lipopolysaccharide-induced proinflammatory cytokine secretion cannot be attributed to its serotonin-releasing properties.