13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.
13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.
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DOI：
10.1371/journal.pone.0012451
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发表时间：
2010-08-27
期刊：
影响因子：
3.7
通讯作者：
Bishai WR
中科院分区：
文献类型：
--
作者：
Jassal MS;Nedeltchev GG;Lee JH;Choi SW;Atudorei V;Sharp ZD;Deretic V;Timmins GS;Bishai WR
病原体特异性代谢途径可通过呼吸试验检测，该试验基于引入稳定的同位素标记底物并使用便携式红外光谱仪检测呼出气中的标记产物。我们测试了分枝杆菌尿素酶活性是否可以在这种呼吸测试形式中作为新的生物标志物和肺结核诊断的基础。致敏新西兰白色家兔接受牛分枝杆菌或结核分枝杆菌的支气管镜感染。感染后约2个月，当出现显著空洞性肺病理学时，用25 mg/kg异烟肼（INH）治疗家兔。[13C]在选定的时间点将尿素直接滴注到插管兔的肺中，分析呼出气样品，并测定δ 13 CO2形成的动力学。接种前获得的样品用作家兔模型中背景13 CO2转化的对照样品。在给药后15分钟内，在受感染家兔的呼出气中很容易检测到[13 C]-尿素通过分枝杆菌尿素酶活性代谢转化产生的13 CO2。分析显示，在疾病早期和INH治疗前，13 CO2形成率迅速增加。INH治疗后，所有可评价的家兔均显示13 CO2形成率降低。尿素呼气试验可为结核病和治疗反应提供有用的诊断和生物标志物测定。未来的工作将测试M的特异性。使用肺靶向干粉吸入制剂，联合口服脲酶抑制剂和饱和口服剂量的未标记尿素，这将阻止来自脲酶阳性胃肠道微生物的δ 13 CO2信号，治疗结核病。
Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/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, and the kinetics of δ13CO2 formation were determined. Samples obtained prior to inoculation served as control samples for background 13CO2 conversion in the rabbit model. 13CO2, from metabolic conversion of [13C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of 13CO2 formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of 13CO2 formation. Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the δ13CO2 signal from urease-positive gastrointestinal organisms.
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OPC-67683，一种硝基二氢 - 米达佐尔衍生物，在体外和小鼠中针对结核病有前途的作用。
影响因子：
15.8
作者：
Matsumoto, Makoto;Hashizume, Hiroyuki;Tomishige, Tatsuo;Kawasaki, Masanori;Tsubouchi, Hidetsugu;Sasaki, Hirofumi;Shimokawa, Yoshihiko;Komatsu, Makoto
通讯作者：
Komatsu, Makoto
DOI：
10.1164/rccm.200210-1125oc
发表时间：
2003-05-15
影响因子：
24.7
作者：
Jindani, A;Doré, CJ;Mitchison, DA
通讯作者：
Mitchison, DA
影响因子：
9.4
作者：
DAMATO, JJ;COLLINS, MT;MCCLATCHY, JK
通讯作者：
MCCLATCHY, JK
影响因子：
3.2
作者：
Donald, P. R.;Diacon, A. H.
通讯作者：
Diacon, A. H.
影响因子：
3.9
作者：
Grandjean L;Moore DA
通讯作者：
Moore DA