Morrow J D, Guzzo C, Lazarus G, Oates J A, Roberts L J
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
J Invest Dermatol. 1995 Jun;104(6):937-40. doi: 10.1111/1523-1747.ep12606209.
Symptoms of mastocytosis have been attributed to the overproduction of both histamine and prostaglandin (PG) D2. Recently, we developed an assay for the major urinary metabolite of PGD2 (PGD-M), 9 alpha,11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid, and demonstrated that urinary excretion of this compound is markedly increased in patients with mastocytosis. It had been shown previously that measurement of the urinary excretion of histamine metabolites provides a more sensitive biochemical diagnostic indicator of systemic mastocytosis than does measurement of unmetabolized histamine. Therefore, we examined the correlation between the urinary excretion of the histamine metabolite, NT-methylhistamine, and PGD-M in urine samples from patients with mastocytosis. Urinary excretion of NT-methylhistamine and PGD-M was measured in 46 urine samples from 17 patients with histologically documented mastocytosis. Both compounds were quantified by mass spectrometry. In all urine collections showing an increase above normal (2 SD above the mean) in the excretion of NT-methylhistamine, the fold increase above normal in the urinary excretion of PGD-M was substantially greater. Further, in some urine samples from four patients whose excretion of NT-methylhistamine was consistently normal, the excretion of PGD-M was increased above normal by as much as 300%. These data indicate that quantification of the urinary excretion of PGD-M is a more sensitive biochemical diagnostic indicator of mastocytosis than is the quantification of NT-methylhistamine.
肥大细胞增多症的症状被认为是由于组胺和前列腺素（PG）D2的过度产生所致。最近，我们开发了一种检测PGD2主要尿代谢物（PGD-M），即9α,11β-二羟基-15-氧代-2,3,18,19-四去甲前列腺素-5-烯-1,20-二酸的方法，并证明该化合物的尿排泄量在肥大细胞增多症患者中显著增加。此前已有研究表明，与未代谢的组胺测量相比，组胺代谢物的尿排泄量测量为系统性肥大细胞增多症提供了更敏感的生化诊断指标。因此，我们研究了肥大细胞增多症患者尿液样本中组胺代谢物N-甲基组胺的尿排泄量与PGD-M之间的相关性。对17例经组织学证实为肥大细胞增多症患者的46份尿液样本进行了N-甲基组胺和PGD-M的尿排泄量测量。两种化合物均通过质谱法定量。在所有显示N-甲基组胺排泄量高于正常水平（高于平均值2个标准差）的尿液样本中，PGD-M的尿排泄量高于正常水平的倍数显著更大。此外，在4例N-甲基组胺排泄量始终正常的患者的一些尿液样本中，PGD-M的排泄量比正常水平高出多达300%。这些数据表明，与N-甲基组胺的定量相比，PGD-M尿排泄量的定量是肥大细胞增多症更敏感的生化诊断指标。
