Morphological changes of endothelial cells and pharmaceutical actions of drugs and poisons using the cells.
Morphological changes of endothelial cells and pharmaceutical actions of drugs and poisons using the cells.
批准号:
14570383
负责人:
TAKAYASU Tatsunori
金额:
$2.24万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003
中文摘要
药物和毒药的毒性表现为人体的致死剂量。本研究以人内皮细胞(HUVEC)为研究对象,探讨了致死剂量与细胞死亡剂量之间的关系。用药物和毒物混合培养液的形态学变化判断HUVEC的死亡。使用甲基苯丙胺(MA)、可卡因、苯巴比妥(PB)、百草枯(PQ)的细胞死亡剂量分别为5、5、5和0.1 mM。其他57种药物和毒物用同样的方法进行筛选。毒性最大的是亚砷酸钠(0.01mM),毒性最小的是甲醇(2M)。根据文献,MA、可卡因、PB、PQ的人体致死剂量(含推定值)分别为1.3 ~ 20mg /kg、7 ~ 10mg /kg、14 ~ 200mg /kg、14 ~ 40mg/kg。为了比较致死剂量和细胞死亡剂量的值,单位取mg/L和mg/kg。MA、可卡因、PB和PQ的浓度分别为0.007 ~ 0.1、0.002 ~ 0.003、0.06 ~ 0.9和0.05 ~ 0.16 mm。在MA中,可卡因和PB的人致死剂量与HUVEC细胞死亡相比为1/6 ~ 1/700。在PQ中,人的剂量与HUVEC细胞死亡水平相同。用同样的方法,绘制了49种物质的人体致死剂量与HUVEC细胞死亡之间的关系。绘制关系线时,相关系数(r)为0.310,说明相关性较差。综上所述,在所检测的61种药物和毒物中,HUVEC的形态学变化与人的致死剂量关系不大。致死剂量与人内皮细胞死亡之间的关系有待进一步研究。
英文摘要
Toxicity of drugs and poisons shows as lethal dose in human. In this study, relationship between the lethal dose and dose of the cell death was examined using human endothelial cells(HUVEC). Death of HUVEC judged with morphological changes in culture fluids mixed with drugs and poisons. Doses of the cell death using methamphetamine(MA), cocaine, phenobarbital(PB), paraquat(PQ) showed 5,5,5 and 0.1 mM, respectively. The other 57 drugs and poisons were screened with the same method. The most poisonous substance was arsenite sodium (0.01mM) and the least poisonous one was methanol(2M). By the references, lethal doses of human(including presumption values) in MA, cocaine, PB and PQ were 1.3-20,7-10,14-200 and 14-40mg/kg, respectively. To compare the values between lethal dose and dose of cell death, the unit made mg/L of mg/kg. The concentrations of MA, cocaine, PB and PQ were 0.007-0.1,0.002-0.003,0.06-0.9 and 0.05-0.16mM, respectively. In MA, cocaine and PB lethal doses of human showed 1/6 to 1/700 comparing to cell death of HUVEC. In PQ, however, the dose of human was same level as cell death of HUVEC. In the same manner, 49 substances were plotted between lethal dose of human and the cell death of HUVEC. When the relation line was made, the correlation coefficient(r) was 0.310, indicating poor relationship. In conclusion, morphological changes of HUVEC showed poor relationship to lethal dose of human in total 61 drugs and poisons examined. Further examination needs to determine the relationship between lethal dose and endothelial cell death in human.
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Y.Ishida, T.Takayasuら計6名: "The pathogenic roles of tumor necrosis factor receptor p55 in acetaminophen-induced liver injury in mice."J.Leukoc.Biol.. 75・1. 59-67 (2004)
Y.Ishida、T.Takayasu 等 6 人:“肿瘤坏死因子受体 p55 在对乙酰氨基酚诱导的小鼠肝损伤中的致病作用”。J.Leukoc.Biol.. 75・1 (2004)。
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T.Ohshima, T.Takayasu.: "Drug analysis in forensic specimens : distribution of body fluids and organs. In "Recent Research Development in Drug Metabolism.""Transworld Reserach Network. 16 (2002)
T.Ohshima、T.Takayasu.:“法医标本中的药物分析:体液和器官的分布。在“药物代谢的最新研究进展”中。”Transworld 研究网络。
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高安達典, 大島 徹: "ガソリン・灯油 in"薬毒物分析実践ハンドブック""じほう. 8 (2002)
Tatsunori Takayasu、Toru Oshima:《药物和毒物分析实用手册》中的汽油和煤油 Jiho. 8 (2002)
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***, T.Ohshima: "Gasoline and ***"Handbook of Practical Analysis of Drugs and Poisons in Human Specimens -chromatographic methods-. 140-148 (2002)
***,T.Ohshima:“汽油和***”人体样本中药物和毒物的实用分析手册 - 色谱方法 -。
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高安達典: "血管内皮細胞を用いた薬毒物による形態変化-予備的検討"法中毒. 22・2. 140-141 (2004)
Tatsunori Takayasu:“使用血管内皮细胞的药物毒物引起的形态变化 - 初步研究”法律成瘾 22・2(2004)。
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共 10 条
Comprehensive analysis for biological toxicity with synthetic narcotic MDMA
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批准号:23590845
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.33万
-
财政年份:2011
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负责人:TAKAYASU Tatsunori
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依托单位:
Molecular-toxic and -pathological analyses for a synthetic narcotic, MDMA
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批准号:20590673
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.08万
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财政年份:2008
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负责人:TAKAYASU Tatsunori
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依托单位:
Molecular toxicological analysis in abused-drug cocaine-induced liver injury-A study with knockout mice.
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批准号:18590630
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.55万
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财政年份:2006
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负责人:TAKAYASU Tatsunori
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依托单位:
海外基金