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1.
J Eur Acad Dermatol Venereol ; 23(1): 42-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18702625

RESUMO

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a chronic cutaneous disorder of keratinization for which there is no known cure. Current therapies are often ineffective, painful, or unappealing. OBJECTIVE: To investigate the efficacy and safety of diclofenac sodium 3% gel for the treatment of DSAP. METHODS: Seventeen adult patients with a diagnosis of DSAP applied diclofenac sodium 3% gel to a target area (forearm) twice daily for 3 months up to a maximum of 6 months in an open-label, multicentre pilot study. Target area lesion counts were performed monthly, and global lesion counts were performed at baseline and at weeks 12 and 24. A treatment satisfaction questionnaire was completed at weeks 12 and 24. RESULTS: Thirteen patients completed 12 weeks of treatment and 10 completed 24 weeks. Among patients who completed 12 weeks, there was a mean decrease of 4% in target area lesions, while a mean increase of 12% was noted in global lesions. Among patients who completed 24 weeks, there was a mean increase of 19% in global lesions, but only a 10% increase noted in the target area. Seven of 13 patients had a decrease in target area lesions at week 12 and 3 of 10 patients at week 24. Questionnaire responses indicated 6 out of 10 patients would use the medication again. CONCLUSION: Target area DSAP lesions in the majority of patients treated with diclofenac sodium 3% gel (both 12 and 24 weeks) progressed to a lesser extent as compared to the global lesion count.


Assuntos
Diclofenaco/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Poroceratose/tratamento farmacológico , Adulto , Diclofenaco/administração & dosagem , Géis , Humanos , Projetos Piloto , Inquéritos e Questionários
2.
J Invest Dermatol ; 117(6): 1601-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11886529

RESUMO

Human keratinocyte motility plays an important role in the re-epithelialization of human skin wounds. The wound bed over which human keratinocytes migrate is rich in extracellular matrices, such as fibrin, fibronectin, and collagen, and serum factors, such as platelet-derived growth factor and transforming growth factor beta 1. Extracellular matrices and the serum factors bind to cell surface receptors and initiate a cascade of intracellular signaling events that regulate cell migration. In this study, we identified an intracellular signaling pathway that mediates collagen- driven motility of human keratinocytes. Pharmaco logic inhibition of the activation of p38-alpha and p38-beta mitogen-activated protein kinase activation potently blocked collagen-driven human keratinocyte migration. Transfection of the same keratinocytes with the kinase-negative mutants of p38-alpha or p38-beta mitogen-activated protein kinase markedly inhibited keratinocyte migration on collagen. Attachment of keratinocytes to collagen activated p38 mitogen- activated protein kinase, as well as p44/p42 ERKs. Interestingly, activation of the p38 mitogen-activated protein kinase cascade by overexpressing the constitutively active MKK3 and MKK6, MKK3b(E) and MKK6b(E), could neither initiate migration in the absence of collagen nor enhance collagen-driven migration. This study provides evidence that the p38-MAPK/SAPK pathway is necessary, but insufficient, for mediating human keratinocyte migration on collagen.


Assuntos
Movimento Celular/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno , Queratinócitos/citologia , Queratinócitos/enzimologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Linhagem Celular Transformada , Movimento Celular/efeitos dos fármacos , Colágeno Tipo I/farmacologia , Derme/citologia , Matriz Extracelular/metabolismo , Humanos , MAP Quinase Quinase 3 , MAP Quinase Quinase 4 , MAP Quinase Quinase 6 , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Tirosina Quinases/metabolismo , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno
3.
J Biol Chem ; 275(32): 24429-35, 2000 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-10821839

RESUMO

Dystrophic epidermolysis bullosa (DEB) is an inherited mechano-bullous disorder of skin caused by mutations in the type VII collagen gene. The lack of therapy for DEB provides an impetus to develop gene therapy strategies. However, the full-length 9-kilobase type VII collagen cDNA exceeds the cloning capacity of current viral delivery vectors. In this study, we produced a recombinant type VII minicollagen containing the intact noncollagenous domains, NC1 and NC2, and part of the central collagenous domain using stably transfected human 293 cell clones and purified large quantities of the recombinant minicollagen VII from culture media. Minicollagen VII was secreted as correctly-folded, disulfide-bonded, helical trimers resistant to protease degradation. Purified minicollagen VII bound to fibronectin, laminin-5, type I collagen, and type IV collagen. Furthermore, retroviral-mediated transduction of the minigene construct into DEB keratinocytes (in which type VII collagen was absent) resulted in persistent synthesis and secretion of a 230-kDa recombinant minicollagen VII. In comparison with parent DEB keratinocytes, the gene-corrected DEB keratinocytes demonstrated enhanced cell-substratum adhesion, increased proliferative potential, and reduced cell motility, features that reversed the DEB phenotype toward normal. We conclude that the use of the minicollagen VII may provide a strategy to correct the cellular manifestations of gene defects in DEB.


Assuntos
Colágeno/química , Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Queratinócitos/fisiologia , Linhagem Celular , Movimento Celular , Clonagem Molecular , Colágeno/biossíntese , DNA Complementar , Epidermólise Bolhosa Distrófica/terapia , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Humanos , Queratinócitos/citologia , Dobramento de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Retroviridae , Deleção de Sequência , Transfecção
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