BIOLOGICAL APPLICATIONS OF THERMOSPRAY LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY

热喷雾液相色谱/质谱的生物学应用

• 批准号: 3878151
• 负责人: A L YERGEY
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3878151
• 关键词: 25 hydroxycholecalciferol; Cushing's syndrome; adolescence (12-20); adrenalectomy; anorexia nervosa; blood chemistry; calcium metabolism; cholecalciferol; circadian rhythms; clinical biomedical equipment; cortisol; excretion; growth factor; high performance liquid chromatography; human subject; hydroxysteroids; isotope dilution method; mass spectrometry; middle childhood (6-11); protein structure; radiotracer; small cell lung cancer; stable isotope; tissue /cell culture; urinalysis; vitamin metabolism

Continuing use of stable isotope dilution liquid chromatography/mass spectrometry (LC/MS) have produced a number of significant findings: 1) Measurement of cortisol levels and cortisol production rates a) the value of urinary free cortisol in anorexia nervosa (n=5) averages 97+/-46 (mu)g/day vs normal values of 42+/-17 (mu)g/day. Morning serum cortisol levels in the anorexia nervosa patients averaged 32+/-12 (mu)g/dl (normal 10-20 (mu)g/dl). These data suggest that, despite high calcium intakes, significant abnormalities in calcium metabolism exist in adolescents with this eating disorder [See project ZOI HD 01400-08 LTPBI. 2) The earlier findings of daily FPR being significantly lower than accepted values has raised issues of appropriate therapies. Bioavailability studies using oral hydrocortisone and a tri-dutero tracer to determine the appearance of cortisol in plasma indicate absorption of 56+/-10% in 4 patients with adrenal insufficiency. These data may be used to determine appropriate oral replacement levels of cortisol. 3) Measurement of the endogenous production rate of 25-OH vitamin D3 (25OH-D) has been accomplished using 6, 19, 19(- 2)H3-25-OH-vitamin D3 as a tracer. Using a single pool model and bolus infusion of tracer at -5% of the plasma pool level of preliminary results yield a value for the half life of 25D of 11+/-1 days (n=5). Earlier studies using radio-labelled tracers have yielded values of the half life of 25OH-D of about 20 days in humans and have suggested that, in rats, the value varies with dietary fiber. We undertook the measurement of the half life of 25OH-D in humans along with the investigation of the effects of dietary fiber on calcium absorption and 25OH-D metabolism. Preliminary results show a) half life that is reduced by about 50% from earlier results, and b) no perturbation of the 25OH-D metabolism by high levels of dietary fiber.

继续使用稳定的同位素稀释液色谱/质量 光谱法（LC/MS）产生了许多重要发现： 1）测量皮质醇水平和皮质醇生产率a） 神经性厌食（n = 5）中无尿皮质醇的值平均97 +/- 46 （MU）g/天与正常值为42 +/- 17（mu）g/day。早晨血清皮质醇 神经性厌食症患者的水平平均为32 +/- 12（MU）G/DL（正常 10-20（MU）G/DL）。这些数据表明，尽管钙摄入量很高，但 钙代谢的明显异常存在于 这种饮食失调[请参阅ZOI HD项目01400-08 LTPBI。 2）较早 每日FPR的发现显着低于所接受的值 提出了适当疗法的问题。使用口腔的生物利用度研究 氢化可的松和三核示踪剂，以确定 血浆中的皮质醇表明4例患者的吸收56 +/- 10％ 肾上腺功能不全。这些数据可用于确定适当的口头 皮质醇的替代水平。 3）内源性生产的测量 使用6、19、19（ - 2）H3-25-OH-VITAMIN D3作为示踪剂。使用单个泳池模型和推注 在初步结果的血浆池水平的-5％输注示踪剂 产生25天11 +/- 1天的半寿命的值（n = 5）。较早 使用无线电标记的示踪剂的研究产生了半衰期的值 在人类约20天的25OH-D中，并建议在大鼠中 饮食纤维的价值各不相同。我们进行了一半的测量 人类25oH-d的寿命，并调查 饮食纤维吸收钙和25OH-D代谢。初步的 结果表明a）半衰期从早期降低了约50％ 结果，b）高水平的25OH-D代谢没有扰动 饮食纤维。