RESUMEN
BACKGROUND: The oral sphingosine-1-phosphate receptor modulator fingolimod (FTY720) was recently approved for the treatment of relapsing-remitting multiple sclerosis. To date, data about a possible recurrence of disease activity after discontinuation of fingolimod treatment are scarce. OBJECTIVE: To describe a patient who discontinued fingolimod treatment after a local malignant melanoma was diagnosed. Three months after cessation, he had a striking rebound of multiple sclerosis activity. DESIGN: Case report and review of literature. SETTING: Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Munich, Germany. PATIENT: A 45-year-old man diagnosed as having relapsing-remitting multiple sclerosis. MAIN OUTCOME MEASURES: Multiple sclerosis disease activity including annual relapse rate, Expanded Disability Status Scale score, and number of gadolinium-enhancing lesions on magnetic resonance imaging before, during, and after treatment with fingolimod. RESULTS: Three months after discontinuation of treatment with fingolimod, the patient experienced a severe relapse, with Expanded Disability Status Scale score progression from 2.5 to 4.5. On brain and spinal magnetic resonance imaging, he showed a rebound of disease activity, with a drastic increase of gadolinium-enhancing lesions (>20). CONCLUSIONS: Two aspects relevant to any newly approved multiple sclerosis treatment with immunomodulatory properties are highlighted with this case: first, possible rebound of disease activity after discontinuation; second, the occurrence of a tumor as a possible treatment-related complication.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Melanoma/complicaciones , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Glicoles de Propileno/uso terapéutico , Esfingosina/análogos & derivados , Encéfalo/patología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Clorhidrato de Fingolimod , Humanos , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/patología , Recurrencia , Esfingosina/uso terapéutico , Resultado del TratamientoRESUMEN
Tissue engineering of autologous cartilage transplants is suggested as a new approach in reconstruction of external auricular deformities. 1.6-Hexanediol (HD), 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 6-hydroxyhexanoic acid (HHA) are matrices of the open-pored polyurethane three-dimensional scaffold. Since these bioresorbable materials may interact with the human organism, cytotoxic effects on human chondrocytes and lymphocytes and genotoxic effects on human lymphocytes were monitored. Staining with propidium iodide and fluorescence diacetate as well as the EZ4U proliferation assay served for the detection of cytotoxic effects of the materials on human chondrocytes. Trypan blue staining was used to monitor cytotoxicity on lymphocytes. Genotoxic effects on lymphocytes in terms of strand breaks, alkali labile sites and incomplete excision repair were determined by the alkaline single cell microgel electrophoresis (Comet) assay. Cytotoxic effects in chondrocytes and lymphocytes as well as genotoxic effects in lymphocytes were dose-dependent with threshold values of 5mg/mL HD, 0.5mg/mL DBU and 0.03 mg/mL HHA showing no effects. These data suggest that these matrices could be safely used for scaffolds made of polyurethane unless these compounds are not released at a rate giving higher concentrations at the site of implantation or in body fluids, respectively.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/toxicidad , Caproatos/toxicidad , Cartílago Articular , Glicoles/toxicidad , Mutágenos , Ingeniería de Tejidos/efectos adversos , Andamios del Tejido/efectos adversos , Supervivencia Celular , Condrocitos/efectos de los fármacos , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidroxiácidos , Linfocitos/efectos de los fármacos , MasculinoRESUMEN
Customizing auricles with biodegradable polyurethane colonized with autologous chondrocytes as an approach for tissue engineering cartilage transplants has been suggested for the reconstruction of the external ear to repair auricular deformities. Dextrose, triethanolamine and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) are matrices of an open-pored polyurethane three-dimensional scaffold. After release from the polymer, these compounds can be absorbed into the human organism. Therefore, cytotoxic effects on human chondrocytes and lymphocytes and genotoxic effects on human lymphocytes were determined. Propidium iodide and fluoresceine diacetate staining as well as quantitative proliferations testing with EZ4U served to detect cytotoxic effects on chondrocytes. In lymphocytes cytotoxicity was checked by trypan blue staining and the alkaline single cell microgel electrophoresis (Comet) assay was used to study genotoxic effects. Dose-dependent cytotoxicity and genotoxicity of the matrices could be shown. Concentrations up to 4.25mg/ml for dextrose, 0.15 mg/ml for PEG-PPG-PEG and 0.9 mg/ml for triethanolamine did not show cytotoxic effects in chondrocytes or genotoxic effects in lymphocytes. These data suggest that dextrose, triethanolamine and PEG-PPG-PEG could be safely used if scaffolds made of open-pored polyurethane do not release these compounds at a rate giving higher concentrations at the site of implantation or in body fluids, respectively.