RESUMEN
Topical steroids are effective in treating bullous pemphigoid (BP). Autoantibodies against BP180 are related to disease activity, but correlation of these autoantibodies with response to topical steroid therapy has not yet been clearly evaluated. We investigate the usefulness of close and early monitoring of autoantibodies against BP180 and BP230 for assessment of response to therapy and early detection of therapeutic failure in BP patients treated topically. In eight BP patients under treatment with topical or systemic steroid therapy we retrospectively evaluated clinical course and autoantibodies against BP180 and BP230 as well as indirect immunofluorescence titres (IIF). Data were included at diagnosis, during hospitalization and follow-ups. Autoantibodies against BP180 parallel disease activity in all topically and as well as systemically treated patients. Autoantibodies against BP230 correlated in five out of eight patients. Autoantibodies directed against BP180 and, to a lesser degree, against BP230 correlate with the clinical course of topically treated BP patients. Monitoring autoantibodies against BP180 is a useful tool to evaluate the efficacy of topical therapy in BP.
Asunto(s)
Corticoesteroides/administración & dosificación , Autoanticuerpos/sangre , Autoantígenos/inmunología , Distonina/inmunología , Inmunoglobulina G/sangre , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Penfigoide Ampolloso/sangre , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/inmunología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Colágeno Tipo XVIIAsunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Neoplasias de Cabeza y Cuello/metabolismo , Hemangioma Capilar/tratamiento farmacológico , Proteínas de Neoplasias/biosíntesis , Propranolol/administración & dosificación , Receptores Adrenérgicos beta 2/biosíntesis , Neoplasias Cutáneas/tratamiento farmacológico , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Hemangioma Capilar/metabolismo , Hemangioma Capilar/patología , Humanos , Lactante , Masculino , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
The aim of this study was to analyze the influence of cholinergic and anticholinergic drugs on epidermal physiology using organotypic cocultures (OTCs). Blocking of all acetylcholine receptors (AChRs) by combined treatment with mecamylamine and atropine or treatment with strychnine (blocking alpha9nAChR) for 7-14 days resulted in a complete inhibition of epidermal differentiation and proliferation. Blockage of nicotinic (n)AChR with mecamylamine led to a less pronounced delay in epidermal differentiation and proliferation than blockage of muscarinic (m)AChR with atropine, evidenced by reduced epithelial thickness and expression of terminal differentiation markers like cytokeratin 2e or filaggrin. In OTCs treated with atropine, mecamylamine, or strychnine, we could demonstrate intracellular lipid accumulation in the lower epidermal layers, indicating a severely disturbed epidermal barrier. In addition, we observed prominent acantholysis in the basal and lower suprabasal layers in mecamylamine-, atropine-, and strychnine-treated cultures, accompanied by a decreased expression of cell adhesion proteins. This globally reduced cell adhesion led to cell death via intrinsic activation of apoptosis. In contrast, stimulation of nAChR and mAChR with cholinergic drugs resulted in a significantly thickened epithelium, accompanied by an improved epithelial maturation. In summary, we show that epidermal AChR are crucially involved in the regulation of epidermal homeostasis.
Asunto(s)
Acetilcolina/fisiología , Epidermis/fisiología , Receptores Muscarínicos/fisiología , Receptores Nicotínicos/fisiología , Apoptosis , Atropina/farmacología , Biomarcadores/análisis , Biomarcadores/metabolismo , Adhesión Celular , Diferenciación Celular , Proliferación Celular , Agonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/farmacología , Proteínas del Citoesqueleto/análisis , Proteínas del Citoesqueleto/metabolismo , Cadherinas Desmosómicas/análisis , Cadherinas Desmosómicas/metabolismo , Células Epidérmicas , Epidermis/química , Proteínas Filagrina , Homeostasis , Humanos , Proteínas de Filamentos Intermediarios/análisis , Queratina-2/análisis , Metabolismo de los Lípidos , Lípidos/análisis , Mecamilamina/farmacología , Técnicas de Cultivo de Órganos , Receptores Muscarínicos/efectos de los fármacos , Receptores Nicotínicos/efectos de los fármacos , Estricnina/farmacología , Uniones Estrechas/química , Uniones Estrechas/ultraestructuraRESUMEN
Detection of micrometastases in the regional tumor-draining lymph nodes is critical for staging and prognosis in melanoma patients. We applied a quantitative multiple-marker RT-PCR assay to improve the detection of occult melanoma cells in the sentinel lymph node (SLN). From 139 patients with primary cutaneous melanoma who underwent sentinel lymphadenectomy, a total of 235 SLN were assessed for Melan-A and tyrosinase expression by real-time quantitative RT-PCR. Twenty-three patients (17%) were positive by histopathology and expressed messenger RNA of one or two markers. Of the patients with histopathologically negative SLN 39 (28%) were reclassified by positive RT-PCR. Patients were examined for tumor recurrences during a median follow-up period of 29 mo. Tumor recurrences were demonstrated in eight patients (35%) with histopathologically positive SLN, in four patients (10%) with submicroscopic tumor cells detected exclusively by real-time RT-PCR, and in none of the patients negative by both methods. The differences in recurrence rates were statistically significant (p=0.01). These data indicate that real-time quantitative RT-PCR for the detection of minimal residual melanoma in SLN improves the prediction of disease-free survival.