13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis 英文参考文献.docVIP

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13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis 英文参考文献.doc

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13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis 英文参考文献

13[C]-UreaBreathTestasaNovelPoint-of-Care BiomarkerforTuberculosisTreatmentandDiagnosis MandeepS.Jassal1,2,GuenoG.Nedeltchev1,Jong-HeeLee1,SeongWonChoi3,ViorelAtudorei4, ZacharyD.Sharp4,VojoDeretic5,GrahamS.Timmins3,WilliamR.Bishai1* 1Center for Tuberculosis Research, JohnsHopkins University School ofMedicine,Baltimore, Maryland, United States of America, 2Division ofPediatric Pulmonology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3Division of Pharmaceutical Sciences, University of New Mexico, Albuquerque,NewMexico,UnitedStatesofAmerica,4DepartmentofEarthandPlanetarySciences,UniversityofNewMexico,Albuquerque,NewMexico,UnitedStatesof America,5DepartmentofMolecularGeneticsandMicrobiology,UniversityofNewMexico,Albuquerque,NewMexico,UnitedStatesofAmerica Abstract Background: Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeledsubstratesanddetectionoflabeledproductsinexhaledbreathusingportableinfraredspectrometers. Methodology/PrincipalFindings:Wetestedwhethermycobacterialureaseactivitycouldbeutilizedinsuchabreathtest format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwentbronchoscopicinfectionwitheither MycobacteriumbovisorMycobacteriumtuberculosis.Rabbitsweretreated with 25mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [13C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed,andthekineticsofd13CO2formationweredetermined.Samplesobtainedpriortoinoculationservedascontrol samples for background 13CO2 conversion in the rabbit model. CO2, from metabolic conversion of [ C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15minutes of administration.Analysesshowedarapidincreaseintherateof13CO2fo