RESUMEN
The purpose of this study was to compare the cytotoxic effects of the fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin. Human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0 mg/mL) for 4 or 24 hours. Cell proliferation and viability were assessed with the MTT assay, neutral red uptake, and bromo deoxy uridine incorporation. In both cell lines, ofloxacin inhibited cell proliferation and viability. These effects were time and dose dependent. Concentrations of ofloxacin ranging from 0.4 to 2.4 mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability. In contrast, netilmicin induced no toxic effect. The differences between ofloxacin and netilmicin were highly statistically significant (p < 0.001). This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is compromised.
Asunto(s)
Conjuntiva/citología , Epitelio Corneal/citología , Netilmicina/farmacocinética , Administración Tópica , Aminoglicósidos/administración & dosificación , Aminoglicósidos/farmacocinética , Bromodesoxiuridina , División Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/metabolismo , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Formazáns , Humanos , Netilmicina/administración & dosificación , Rojo Neutro , Ofloxacino/administración & dosificación , Sales de TetrazolioRESUMEN
OBJECTIVES: In the present work, a method to induce experimental allergic encephalomyelitis (EAE) in female SJL/J mice was developed and validated in our laboratory. Although the latter is a popular animal model to mimic human multiple sclerosis, it remains to be clarified if: (1) the measurement of circulating antibodies against myelin antigens can be used as an index to predict the development of clinical EAE, as well as the severity of disease, and (2) the genetic susceptibility of this strain is associated with altered hypothalamo-pituitary-adrenal (HPA) function. METHODS AND RESULTS: We observed that SJL/J mice display a strong humoral response to immunization with myelin basic protein (MBP), as assessed by the titration of circulating anti-MBP antibodies. However, there was no apparent correlation between the presence and amount of circulating antibodies and the occurrence or severity of disease. Concerning the responsiveness of the HPA axis, we observed that circulating corticosterone levels are not modified at all during the induction of EAE, whereas an increase is observed at a later stage of the disease. CONCLUSIONS: The above profile is strongly reminiscent of the HPA axis response to the induction of EAE in Lewis rats, suggesting that the susceptibility of SJL/J mice to EAE may similarly be caused, at least in part, by blunted HPA reactivity to immune challenges.