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1.
Transpl Infect Dis ; 19(3)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28295973

RESUMO

Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date, no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection. Pathology, culture, and molecular speciation showed the nodule was caused by cutaneous A. rosae. He had been on voriconazole as antifungal prophylaxis, but was found to have a subtherapeutic voriconazole level. He was switched to posaconazole based on published in vitro data showing its superior efficacy in Alternaria treatment. Susceptibility testing showed that the A. rosae isolate was indeed susceptible to posaconazole. His cutaneous lesion remained stable, but he died from respiratory failure secondary to lobar pneumonia. At lung autopsy, A. rosae was not identified in the lungs. We believe this to be the first published report, to our knowledge, of A. rosae infection in humans.


Assuntos
Alternaria/patogenicidade , Alternariose/microbiologia , Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feoifomicose/microbiologia , Mielofibrose Primária/terapia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Aciclovir/uso terapêutico , Idoso , Alternaria/isolamento & purificação , Antibioticoprofilaxia/métodos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Evolução Fatal , Doença Enxerto-Hospedeiro/tratamento farmacológico , Mãos/diagnóstico por imagem , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Levofloxacino/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Testes de Sensibilidade Microbiana , Seios Paranasais/diagnóstico por imagem , Pneumonia/complicações , Prednisona/uso terapêutico , Insuficiência Respiratória/complicações , Esporos Fúngicos/isolamento & purificação , Esporos Fúngicos/patogenicidade , Transplante Homólogo/efeitos adversos , Triazóis/uso terapêutico , Voriconazol/uso terapêutico
2.
Endocrinology ; 158(2): 293-303, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27870582

RESUMO

Islet endothelial cells produce paracrine factors that support ß-cell function and growth. Endothelial dysfunction underlies diabetic microvascular complications; thus, we hypothesized that in diabetes, islet endothelial cells become dysfunctional, which may contribute to ß-cell secretory dysfunction. Islets/islet endothelial cells were isolated from diabetic B6.BKS(D)-Leprdb/J male (db/db) mice, treated with or without the glucose-lowering agent phlorizin, or from C57BL/6J mice fed a high-fat diet for 18 weeks and appropriate controls. Messenger RNA (mRNA) and/or the protein levels of the cell adhesion molecule E-selectin (Sele), proinflammatory cytokine interleukin-6 (Il6), vasoconstrictor endothelin-1 (Edn1), and endothelial nitric oxide synthase (Nos3; Nos3) were evaluated, along with advanced glycation end product immunoreactivity. Furthermore, an islet endothelial cell line (MS-1) was exposed to diabetic factors (glucose, palmitate, insulin, and tumor necrosis factor-α) for six days. Conditioned media were collected from these cells, incubated with isolated islets, and glucose-stimulated insulin secretion and insulin content were assessed. Islet endothelial cells from db/db mice exhibited increased Sele, Il6, and Edn1 mRNA levels, decreased Nos3 protein, and accumulation of advanced glycation end products. Phlorizin treatment significantly increased Nos3 protein levels but did not alter expression of the other markers. High-fat feeding in C57BL/6J mice resulted in increased islet Sele, Il6, and Edn1 but no change in Nos3. Exposure of islets to conditioned media from MS-1 cells cultured in diabetic conditions resulted in a 50% decrease in glucose-stimulated insulin secretion and 30% decrease in insulin content. These findings demonstrate that, in diabetes, islet endothelial cells show evidence of a dysfunctional phenotype, which may contribute to loss of ß-cell function.


Assuntos
Endotélio/fisiopatologia , Insulina/metabolismo , Ilhotas Pancreáticas/fisiopatologia , Animais , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/metabolismo , Glucose , Secreção de Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Florizina
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