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1.
Clin Exp Dermatol ; 41(6): 667-70, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27378586

RESUMO

Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS.


Assuntos
Dermoscopia/métodos , Técnica Direta de Fluorescência para Anticorpo/métodos , Penicilamina/efeitos adversos , Dermatopatias/induzido quimicamente , Adulto , Quelantes/efeitos adversos , Quelantes/uso terapêutico , Tecido Elástico/patologia , Feminino , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/patologia , Humanos , Penicilamina/administração & dosagem , Penicilamina/uso terapêutico , Doenças Raras , Pele/patologia , Dermatopatias/patologia
2.
Cell Death Dis ; 6: e1644, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25675304

RESUMO

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.


Assuntos
Albuminas/farmacologia , Proteínas de Ligação a Calmodulina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Proteínas de Ligação a Calmodulina/genética , Linhagem Celular , Proteínas do Citoesqueleto/genética , Feminino , Humanos , Imuno-Histoquímica , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Masculino , Proteínas de Membrana/genética , Microscopia Confocal , Proteínas do Tecido Nervoso/genética , RNA Interferente Pequeno/genética , Ratos , Proteínas Repressoras/genética
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