RESUMEN
The selective serotonin re-uptake inhibitor (SSRI) fluoxetine is widely used in the treatment of depression in children and fertile women, but its effect on developing tissues has been sparsely investigated. The aim of this study was to investigate if enamel organs and ameloblast-derived cells express serotonin receptors that are affected by peripherally circulating serotonin or fluoxetine. Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old mice and ameloblast-like cells (LS8 cells) express functional serotonin receptors, the rate-limiting enzyme in serotonin synthesis (Thp1), as well as the serotonin transporter (5HTT), indicating that enamel organs and ameloblasts are able to respond to serotonin and regulate serotonin availability. Fluoxetine and serotonin enhanced the alkaline phosphatase activity in the cell culture medium from cultured LS8 cells, whereas the expression of enamelin (Enam), amelogenin (Amel), and matrix metalloproteinase-20 (MMP-20) were all significantly down-regulated. The secretion of vascular endothelial growth factor (VEGF), monocyte chemotactic protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10) was also reduced compared with controls. In conclusion, enamel organs and ameloblast-like cells express functional serotonin receptors. Reduced transcription of enamel proteins and secretion of vascular factors may indicate possible adverse effects of fluoxetine on amelogenesis.
Asunto(s)
Ameloblastos/efectos de los fármacos , Órgano del Esmalte/efectos de los fármacos , Fluoxetina/farmacología , Receptores de Serotonina/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Fosfatasa Alcalina/análisis , Fosfatasa Alcalina/efectos de los fármacos , Amelogenina/análisis , Amelogenina/efectos de los fármacos , Animales , Técnicas de Cultivo de Célula , Línea Celular , Quimiocina CCL2/análisis , Quimiocina CCL2/efectos de los fármacos , Quimiocina CXCL10/análisis , Quimiocina CXCL10/efectos de los fármacos , Medios de Cultivo , Proteínas del Esmalte Dental/análisis , Proteínas del Esmalte Dental/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , L-Lactato Deshidrogenasa/análisis , L-Lactato Deshidrogenasa/efectos de los fármacos , Metaloproteinasa 20 de la Matriz/análisis , Metaloproteinasa 20 de la Matriz/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Receptores de Serotonina/análisis , Serotonina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/análisis , Proteínas de Transporte de Serotonina en la Membrana Plasmática/efectos de los fármacos , Agonistas de Receptores de Serotonina/farmacología , Espectrofotometría Atómica , Triptófano Hidroxilasa/análisis , Triptófano Hidroxilasa/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention.
Asunto(s)
Alcoholismo/terapia , Atención Ambulatoria/métodos , Prestación Integrada de Atención de Salud , Trastorno Depresivo Mayor/terapia , Evaluación de Programas y Proyectos de Salud , Alcoholismo/complicaciones , Canadá , Servicios Comunitarios de Salud Mental , Trastorno Depresivo Mayor/complicaciones , Implementación de Plan de Salud , Humanos , Proyectos Piloto , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effects of two different fluoride concentrations on the expression of enamel proteins, alkaline phosphatase (ALP), cytokines and interleukins by an ameloblast-derived cell line. METHODS: Murine ameloblast-derived cells (LS-8), mouse odontogenic epithelia, were exposed to 1 or 5ppm sodium fluoride (NaF) (0.46 and 2.25ppm F, respectively) for 1, 3 and 7 days. The effect of NaF on the mRNA expression of enamel proteins was quantified; the secretion of cytokines, and interleukins, and the alkaline phosphatase (ALP) activity, into the cell culture medium was measured and compared to untreated controls. The effect on cell growth after 1- and 3-days in culture was measured using BrdU incorporation. RESULTS: Fluoride at 2.25ppm reduced mRNA expression of the structural enamel matrix proteins amelogenin (amel), ameloblastin (ambn), enamelin (enam), and the enamel protease matrix metallopeptidase-20 (MMP-20). Similarly several vascularisation factors (vascular endothelial growth factor (VEGF), monocyte chemoattractant proteins (MCP-1) and interferon inducible protein 10 (IP-10), was also reduced by 2.25ppm fluoride. ALP activity and proliferation were stimulated by 0.46ppm fluoride but inhibited by 2.25ppm fluoride. CONCLUSIONS: These results indicate that fluoride may impact on the expression of structural enamel proteins and the protease responsible for processing these proteins during the secretory stage of amelogenesis and go some way to explaining the mineralization defect that characterises fluorotic enamel.