| Project/Area Number |
14572148
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
HISHINUMA Takanori Tohoku University, Hospital, Associate professor, 病院, 助教授 (20199003)
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| Co-Investigator(Kenkyū-buntansha) |
AIBA Setsuya Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80159269)
TOMIOKA Yoshihisa Josai Internatioanl University, Center for International Studies and Education, Research Associate, 国際文化教育センター, 助手 (00282062)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | leukotriene / LTE4 / LC-MS / asthma / atopic dermatitis / psoriasis / thromnboxane / diagnosis / LC / MS / アトピー / MS-MS / 微量定量 |
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| Research Abstract |
Liquid chromatography/tandem mass spectrometric method (LC/MS/MS) was developed for the quantitation of leukotriene E4(LTE4) in human urine. After addition of deuterium labeled internal standard to urine, these subjects were extracted by solid-phase extraction using Empore C18 disk cartridge. The reconstituted extracts were analysed by LC/MS/MS in the selected reaction monitoring (SRM) mode monitoring. Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid by the action of 5-lipoxygenase. The cysteinyl LTs (LTC4, LTD4 and LTE4) are inflammatory mediators and are known to play a part in the pathogenesis of inflammatory diseases. They increase vascular permeability and dilate skin blood vessels. Thus, a potential role for enhanced LT production in the pathogenesis of AD has been suggested. Urinary LTE4 levels are a useful index of whole-body cysteinyl LT production in vivo because LTE4 is a stable urinary metabolite of LTC4 and LTD4.
Atopic dermatitis (AD) is a chroni
… More
c inflammatory skin disease frequently seen in patients with a personal or family history of respiratory allergy. Many observations have indicated that IgE-mediated mechanisms play a part in the pathogenesis of AD. I used LC/MS-MS to determine urinary LTE4 levels in patients with AD and healthy volunteers, and examined the relationship between urinary LTE4 and total serum IgE levels. I clarified theincreased LTE4 excretion in patients with AD compared with healthy volunteers, and a significant correlation between urinary LTE4 and total serum IgE levels in patients with AD.
The present findings suggest that cysteinyl LTs play a crucial part in the pathogenesis of AD. Beneficial effects of 5-lipoxygenase inhibitors and receptor antagonists may be expected in the treatment of AD. Moreover, the diagnosis of AD is primarily based on skin tests and measurements of total IgE and specific IgE in serum. Measurement of urinary LTE4, which is simple and non-invasive, may be useful in evaluating the serum IgE level and assessing the pathological symptoms in AD.
Furthermore, to compare the relation to AD with LTE4, I developed microdetermination method of 11-dehydro thromboxane B2(11-dehydro TXB2, a urinary metabolite of thromboxane A2). Less
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