RESUMEN
OBJECTIVE: Tolerability and safety of 0.1% tacrolimus ointment in treating nickel-induced allergic contact dermatitis (ACD) were evaluated. METHODS: Patients allergic to nickel applied nickel patches to each upper inner aspect of the arm for 4 to 8 hours daily. Tacrolimus was applied to patch site on one arm and vehicle to patch site on the other, twice daily. Physician's Global Assessment, signs and symptoms of ACD, pruritus scores, and adverse events were evaluated. RESULTS: After 8 weeks, dermatitis in 45% of patients was clear or almost clear (Physician's Global Assessment) with tacrolimus; and 1% with vehicle (P < .001). Significant results were achieved as early as day 8. Tacrolimus was superior in ACD signs and symptoms improvement and pruritus reduction (P < .001). Adverse events were similar between treatments. LIMITATIONS: This model, involving one agent, may not be generalizable for other agents. CONCLUSIONS: Tacrolimus ointment 0.1% is well tolerated and significantly more effective than vehicle in treating chronically exposed, nickel-induced ACD.
Asunto(s)
Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/etiología , Inmunosupresores/administración & dosificación , Níquel/efectos adversos , Tacrolimus/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pomadas , Estudios ProspectivosRESUMEN
We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, including our own series of indole piperidine compounds. On the basis of these results, a number of site-directed mutations (SDM) were designed that were intended to verify the proposed docking models. From these it was clear that further refinements would be necessary in the model. This was aided by the publication of a crystal structure of bovine rhodopsin, and a new receptor model was built by homology to this structure. This latest model enabled us to define ligand-docking hypotheses that were in complete agreement with the results of the SDM experiments.