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J Exp Med ; 216(9): 2057-2070, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31270247


Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

Pharm Biol ; 56(1): 51-59, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29275696


CONTEXT: Actinobacteria are a precious source of novel bioactive metabolites with potential pharmaceutical applications. OBJECTIVES: Representatives of 11 genera of rare Actinobacteria were selected for the evaluation of antioxidant activity. MATERIAL AND METHODS: Fermentation broths of the Actinobacteria were extracted and dosage of 10 to 2000 µg/mL were applied for in vitro antioxidant-related bioassays. Cytotoxicity was assessed at the concentration of 2.5-20 µg/mL. RESULTS: In the DPPH scavenging activity, 15 out of 52 extracts showed 17.0-26.8% activity in quantitative evaluation. Metabolites of five prominent antioxidant producing strains protected the DNA (pUC19) against UV-induced photolyzed H2O2-oxidative degradation. The potent antioxidant extracts inhibited two oxidative enzymes of xanthine oxidase in the range of 17.5-45.2% (three extracts had IC50 less than allopurinol) and lipoxygenase in the range of 36-55% (all five extracts had IC50 values less than daidzein). All these extracts could also protect eythrocytes from iron-induced hemolysis with ED50 values in a range of 0.014-1.25 mg/mL. Growth restoration of the yeast cells lacking the sod1 gene was observed by the antioxidant metabolite of Saccharothrix ecbatanensis UTMC 537 at the concentration of 1 mg/mL. CONCLUSIONS: The presence of nonidentical metabolites might be responsible for antioxidant and enzyme inhibitory activities of S. ecbatanensis, newly described actinobacterium in family Pseudonocardiaceae. The scavenging of the free electrons, protection of DNA and model yeast cells against oxidative stress, in addition to the inhibition of the oxidating enzymes are the main mechanisms of the antioxidant effect of the introduced resource in this study.

Actinobacteria/metabolismo , Antioxidantes/metabolismo , Oxidantes/antagonistas & inibidores , Oxidantes/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Artemia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos