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1.
Artigo em Inglês | MEDLINE | ID: mdl-34568514

RESUMO

Acne keloidalis nuchae (AKN) is a progressive inflammatory condition that affects posterior neck and occiput. Treatment options include antibiotics, steroids, lasers, radiotherapy and surgery. We present three patients with advanced 'tumor-stage' AKN that underwent radical local excision followed by either immediate or delayed skin resurfacing, and briefly review existing literature.

2.
Am J Nephrol ; 51(11): 891-902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33130676

RESUMO

BACKGROUND: Chronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile. Further, we aimed to elucidate potential mechanisms driving renal recovery. METHODS: Unilateral RVD was induced in 14 pigs. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified by multidetector CT imaging. Pigs then received a single intrarenal injection of KTP-ELP-VEGF or vehicle. CT quantification of renal hemodynamics was repeated 4 weeks later, and then pigs were euthanized. Ex vivo renal microvascular (MV) density and media-to-lumen ratio, macrophage infiltration, and fibrosis were quantified. In parallel, THP-1 human monocytes were differentiated into naïve macrophages (M0) or inflammatory macrophages (M1) and incubated with VEGF, KTP-ELP, KTP-ELP-VEGF, or control media. The mRNA expression of macrophage polarization and angiogenic markers was quantified (qPCR). RESULTS: Intrarenal KTP-ELP-VEGF improved RBF, GFR, and MV density and attenuated MV media-to-lumen ratio and renal fibrosis compared to placebo, accompanied by augmented renal M2 macrophages. In vitro, exposure to VEGF/KTP-ELP-VEGF shifted M0 macrophages to a proangiogenic M2 phenotype while M1s were nonresponsive to VEGF treatment. CONCLUSIONS: Our results support the efficacy of a new renal-specific biologic construct in recovering renal function and suggest that VEGF may directly influence macrophage phenotype as a possible mechanism to improve MV integrity and function in the stenotic kidney.


Assuntos
Proteínas Recombinantes de Fusão/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Obstrução da Artéria Renal/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Animais , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Modelos Animais de Doenças , Elastina/administração & dosagem , Elastina/genética , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/fisiologia , Masculino , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Peptídeos/administração & dosagem , Peptídeos/genética , Proteínas Recombinantes de Fusão/genética , Obstrução da Artéria Renal/etiologia , Circulação Renal/efeitos dos fármacos , Sus scrofa , Fator A de Crescimento do Endotélio Vascular/genética
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