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Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for α-1-antitrypsin, human matrix metalloproteinase 9 (MMP9), human tissue inhibitor of metalloproteinases 1 (TIMP-1), metallothionein and urokinase type plasminogen activator receptor (uPAR). We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP), 20 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH). Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.Key words: endemic pemphigus foliaceus; autoimmune blistering skin diseases; matrix metalloproteinase 9; tissue inhibitor of metalloproteinases 1; urokinase type plasminogen activator receptor; α-1-antitrypsin IntroductionMultiple theories have been proposed regarding the pathophysiology of cutaneous autoimmune blistering skin diseases (ABDs). Some involve plasminogen activation, desmoglein compensation, acetylcholine receptor antibodies, and intracellular signal control of autoantibodies [1]. Moreover, human autoantibodies and the presence of complement are primary factors in producing the blisters of human autoimmune skin blistering diseases and are thought to exert their pathogenic effect via proteases [2,3]. Few studies have tested for proteases and protease inhibitors in lesional skin from patients affected by ABDs [4,5]. We decided to investigate enzymes that could be modulated by ions that have been postulated as triggers for ABDs. We also aimed to investigate enzymes that are related to xenobiotics, based on our previous findings of metals and metalloids in skin biopsies of patients with a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El-Bagre-EPF) that are exposed to significant mercury pollution [5]. Thus, we utilized immunohistochemistry (IHC) to test for anti-human-α-1-antitrypsin, anti-human matrix metalloproteinase 9 (MMP9), anti-human tissue inhibitor of metalloproteinases 1 (TIMP1), urokinase type plasminogen activator receptor (uPAR) and for metallothionein in patients affected by autoimmune skin blistering diseases.

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"Sócrates: Puedo contarte una tradición de los antiguos, que conocían la verdad.Si nosotros pudiésemos descubrirla por nosotros mismos, ¿nos seguiríamos preocupando aún de lo que los hombres hayan pensado antes que nosotros?" ResumenEste artículo da una primera aproximación al papel que puede jugar la investigación en medicina, en el proceso de aprendizaje, dentro del desarrollo de profesionales autorregulados y autónomos. Para ello se propone partir de una reflexión pedagógica de aspectos referentes a la situación actual de la educación en medicina, posteriormente analizar ciertos roles y propósitos de la investigación al interior de las Facultades de Medicina, su interacción con los medios docentes y finalmente evaluar las estrategias educativas actuales para generar aprendizaje autónomo y herramientas de metacognición. Dentro del análisis se integran los resultados de entrevistas a profundidad aplicadas a estudiantes y docentes de diferentes facultades de medicina, cuyo objetivo fue explorar los aspectos mencionados. La investigación permite que el estudiante aborde al conocimiento desde cuatro perspectivas: desarrollar habilidades de metacognición, pensamiento complejo, apartarse de la concepción pasiva-tradicional y aprender a aprender.

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