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1.
J Clin Microbiol ; 55(11): 3210-3218, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28814586

RESUMO

Aspergillus fumigatus is the main species responsible for aspergillosis in humans. The diagnosis of aspergillosis remains difficult, and the rapid emergence of azole resistance in A. fumigatus is worrisome. The aim of this study was to validate the new MycoGENIE A. fumigatus real-time PCR kit and to evaluate its performance on clinical samples for the detection of A. fumigatus and its azole resistance. This multiplex assay detects DNA from the A. fumigatus species complex by targeting the multicopy 28S rRNA gene and specific TR34 and L98H mutations in the single-copy-number cyp51A gene of A. fumigatus The specificity of cyp51A mutation detection was assessed by testing DNA samples from 25 wild-type or mutated clinical A. fumigatus isolates. Clinical validation was performed on 88 respiratory samples obtained from 62 patients and on 69 serum samples obtained from 16 patients with proven or probable aspergillosis and 13 patients without aspergillosis. The limit of detection was <1 copy for the Aspergillus 28S rRNA gene and 6 copies for the cyp51A gene harboring the TR34 and L98H alterations. No cross-reactivity was detected with various fungi and bacteria. All isolates harboring the TR34 and L98H mutations were accurately detected by quantitative PCR (qPCR) analysis. With respiratory samples, qPCR results showed a sensitivity and specificity of 92.9% and 90.1%, respectively, while with serum samples, the sensitivity and specificity were 100% and 84.6%, respectively. Our study demonstrated that this new real-time PCR kit enables sensitive and rapid detection of A. fumigatus DNA and azole resistance due to TR34 and L98H mutations in clinical samples.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/isolamento & purificação , Azóis/farmacologia , Aspergilose Pulmonar Invasiva/diagnóstico , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Aspergillus fumigatus/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Reação em Cadeia da Polimerase Multiplex/métodos , RNA Ribossômico 28S/genética , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
2.
Int J Biochem Cell Biol ; 38(4): 629-37, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16343977

RESUMO

The grape-derived polyphenol resveratrol is anti-proliferative for human liver myofibroblasts, which may be beneficial for the treatment of liver fibrosis. However, its mechanism of action is ill understood. Here, we have studied how resveratrol interfered with signaling pathways used by epidermal or platelet-derived growth factors to induce the proliferation of these cells. We found that resveratrol inhibited epidermal growth factor or platelet-derived growth factor-induced DNA synthesis. Resveratrol did not, however, decrease epidermal growth factor receptor autophosphorylation or activation of extracellular regulated kinases, but strongly inhibited the phosphorylation of Akt and of its substrate forkhead related transcription factor. This suggested that resveratrol inhibited epidermal growth factor-induced mitogenic signaling through inhibition of the phosphatidylinositol 3-kinase /Akt pathway. The phosphatidylinositol 3-kinase inhibitor LY 294002, also, inhibited epidermal growth factor-dependent DNA synthesis and Akt phosphorylation but did not decrease extracellular regulated kinases phosphorylation. In contrast, resveratrol inhibited platelet-derived growth factor-stimulated receptor autophosphorylation and every subsequent signaling step. Resveratrol did not directly inhibit phosphatidylinositol 3-kinase activity measured on immunoprecipitates from epidermal growth factor-stimulated myofibroblasts, but it strongly reduced the autophosphorylation of the phosphatidylinositol 3-kinase downstream target phospho-inositide-dependent kinase-1 that phosphorylates Akt. We, thus, show that resveratrol has growth factor-specific effects: it inhibits platelet-derived growth factor signaling via reduced receptor activation, whereas it reduces epidermal growth factor-dependent DNA synthesis via inhibition of the phosphatidylinositol 3-kinase/Akt pathway, possibly through inhibition of phospho-inositide-dependent kinase-1 activity.


Assuntos
Inibidores Enzimáticos/farmacologia , Fibroblastos/metabolismo , Fígado/metabolismo , Mioblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Vitis/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Fatores de Crescimento de Fibroblastos/farmacologia , Fibroblastos/citologia , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Fígado/citologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Mioblastos/citologia , Fenóis/química , Fenóis/farmacologia , Fenóis/uso terapêutico , Fator de Crescimento Derivado de Plaquetas/farmacologia , Polifenóis , Resveratrol , Estilbenos/química , Estilbenos/uso terapêutico
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