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    Title: Nephrotoxicity assessments of acetaminophen during zebrafish embryogenesis
    Authors: Peng, Hsi-Chu;Wang, Yun-Hsin;Wen, Chi-Chung;Wang, Wei-Hua;Cheng, Chien-Chung;Chen,Yau-Hung
    Contributors: 淡江大學數學學系;淡江大學化學學系
    Keywords: Acetaminophen;Fluorescent;Kidney;Nephrotoxicity;Transgenic;Zebrafish;共變量測量誤差;柯斯模型;半母數最大概似估計;剖面概似函數
    Date: 2010-05
    Issue Date: 2011-05-20 09:42:19 (UTC+8)
    Publisher: Philadelphia: Elsevier Inc.
    Abstract: We used a green fluorescent kidney line, Tg(wt1b:GFP), as a model to access the acetaminophen (AAP)-induced nephrotoxicity dynamically. Zebrafish (Danio rerio) embryos at different developmental stages (12–60 hpf) were treated with different dosages of AAP (0–45 mM) for different time courses (12–60 h). Results showed that zebrafish embryos exhibited no evident differences in survival rates and morphological changes between the mock-treated control (0 mM) and 2.25 mM AAP-exposure (12–72 hpf) groups. In contrast, after higher doses (22.5 and 45 mM) of exposure, embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tube, pronephric duct, and a cystic and atrophic glomerulus. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AAP increased. Interestingly, under the same exposure time course (12 h) and dose (22.5 mM), embryos displayed higher percentages of severe defects at earlier developmental stage of exposure (12–24 hpf), whereas embryos displayed higher percentages of mild defects at later exposure (60–72 hpf). With an exposure time course less than 24 h of 45 mM AAP, no embryo survived by the developmental stage of 72 hpf. These results indicated that AAP-induced nephrotoxicity depended on the exposure dose, time course and developmental stages. Immunohistochemical experiments showed that the cells' morphologies of the pronephric tube, pronephric duct and glomerulus were disrupted by AAP, and consequently caused cell death. Real-time RT-PCR revealed embryos after AAP treatment decreased the expression of cox2 and bcl2, but increased p53 expression. In conclusion, AAP-induced defects on glomerulus, pronephric tube and pronephric duct could be easily and dynamically observed in vivo during kidney development in this present model.
    對於具共變量誤差之存活資料,假設給定測量共變量,真實共變量之條件分佈已知下,本文研究柯斯正比風險模型的半母數最大概然估計。我們證明了回歸係數估計的漸進常態性和有效性,剖面概似函數的微分可為其共變異矩陣之一致性估計,以及概然函數比檢定的漸進卡方性。我們也對於半母數最大概然估計及剖面概似函數的計算提出一高效的演算法。模擬試驗成功說明了所提估計方法的數值表現。
    Relation: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 151(4), pp.480-486
    DOI: 10.1016/j.cbpc.2010.02.004
    Appears in Collections:[數學學系暨研究所] 期刊論文
    [化學學系暨研究所] 期刊論文

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