カニクイザルを用いた大腸菌由来リポポリサッカライド(LPS)投与による播種性血管内凝固症候群(DIC)モデル作成及びその病態解析

• Material Type: 博士論文
• Title: カニクイザルを用いた大腸菌由来リポポリサッカライド(LPS)投与による播種性血管内凝固症候群(DIC)モデル作成及びその病態解析
• Author/Editor: 蓑毛, 博文
• Author Heading: 蓑毛, 博文 ミノモ, ヒロフミ
• Publication, Distribution, etc.: Japanese Pharmacological Society
• Publication Date: 2017
• Publication Date (W3CDTF): 2017
• Alternative Title: Establishment of Disseminated Intravascular Coagulation (DIC) Model by a Single iv Administration of E. coli-derived Lipopolysaccharide (LPS) to Cynomolgus Monkeys and Evaluation of its Pathophysiological Status
• Periodical title: Journal of Pharmacological Sciences
• No. or year of volume/issue: 133 2
• Volume: 133
• Issue: 2
• Pages: 88-95
• Degree grantor/type: 鹿児島大学
• Date Granted: 2017-09-29
• Dissertation Number: 甲総研第433号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: Thrombomodulin; LPS; DIC
• Target Audience: 一般
• Note (General): 博士論文全文, 最終試験結果の要旨, 論文審査の要旨, 博士論文要旨; We prepared a DIC model by administrating LPS to cynomolgus monkeys, and investigated its potential for evaluations of new medicines for DIC therapy. Peripheral blood mononuclear cells (PBMC) collected from cynomolgus monkeys were incubated with LPS (8 types), and TNF-α levels in the media were measured. LPS from E. coli (K-235) was most appropriate in terms of larger increases and smaller variation in TNF-α levels. PBMC from rats, cynomolgus monkeys or humans were incubated with LPS (K-235), and the TNF-α response to LPS was investigated. The response was comparable between cynomolgus monkeys and humans but small in rats. In an in vivo experiment, LPS (K-235) was administered once intravenously to cynomolgus monkeys with or without recombinant human thrombomodulin (rhTM) to investigate any changes in coagulation and fibrinolysis biomarkers and the suppressive effect of rhTM. The liver, kidney, and lung were examined histopathologically. Almost all of the changes resembled the pathophysiological status of human DIC and were suppressed by co-administration of rhTM. The DIC model resembling human DIC was established by LPS (K-235) treatment in cynomolgus monkeys, and therapeutic effect of rhTM was noted, suggesting that this model is useful in evaluations of the efficacy of new medicines for DIC therapy.
• Format (IMT): application/pdf
• Source: Diss_蓑毛_博文_ISK433_2017 （fulltext）; https://ir.kagoshima-u.ac.jp/record/13967/files/Diss_%E8%93%91%E6%AF%9B_%E5%8D%9A%E6%96%87_ISK433_2017.pdf
• Access Restrictions: インターネット公開
• Rights (production): © 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
• Related Material: Journal of Pharmacological Sciences; https://www.sciencedirect.com/journal/journal-of-pharmacological-sciences
• Is Version Of (URI): URI; https://doi.org/10.1016/j.jphs.2017.01.005
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ