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作者： YU Hong Nigel BARRASS Sonya GALES Eva LENZ dan weston lan WILSONB Tony PARRY Helen POWELL Dale THURMAN QIAO Jun-wen QIN Qiu-ping REN Jin Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica Global Safety Assessment

Paracetamol(acetaminophen,APAP) was administered orally in a rising dose protocol to 2 male and 2 female Cynomolgus monkeys to determine the Maximum Tolerated dose(MTD) for subsequent toxicology *** the subsequent repeat dose study involving 6 monkeys,no dose-limiting toxicity was seen at up to 900 mg·kg~(-1)·d~(-1) APAP for 14 *** analysis showed that plasma exposure rose,albeit less than proportionally,with increasing *** were some fluctuations in clinical chemistry and haematology parameters,but these were not dose-related, and there were no compound-related findings observed *** monkeys at 900 mg·kg~(-1)·d~(-1) had a 5 cm, gas filled segment in their large intestine that was considered *** profiling of the urine showed parent and glucuronidated APAP,but the cysteinyl conjugate which would be anticipated if the monkey has similar metabolism to rats and man was notably *** opens the possibility that metabolism in the cynomolgus monkey differs from that in the other species,and shows that the cynomolgus monkey is a poor model for investigating paracetamol-mediated toxicity in humans.

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Evaluation of paracetamol toxicity in the cynomolgus monkey

Evaluation of paracetamol toxicity in the cynomolgus monkey

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2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

Paracetamol(acetominophen,APAP) was administered orally in a rising dose protocol to 2 male and 2 female Cynomolgus monkeys to determine the Maximum Tolerated dose(MTD) for subsequent toxicology *** the subsequent repeat dose study involving 6 monkeys,no dose-limiting toxicity was seen at up to 900 mg·kg·d APAP for 14 *** analysis showed that plasma exposure rose,albeit less than proportionally,with increasing *** were some fluctuations in clinical chemistry and haematology parameters,but these were not dose-related, and there were no compound-related findings observed *** monkeys at 900 mg·kg·d had a 5 cm, gas filled segment in their large intestine that was considered *** profiling of the urine showed parent and glucuronidated APAP,but the cysteinyl conjugate which would be anticipated if the monkey has similar metabolism to rats and man was notably *** opens the possibility that metabolism in the cynomolgus monkey differs from that in the other species,and shows that the cynomolgus monkey is a poor model for investigating paracetamol-mediated toxicity in humans.

关键词： acetominophen toxicity

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Evaluation of paracetamol toxicity in the cynomolgus monkey

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中国药理学与毒理学杂志 2013年第3期 544-544页

作者： YU Hong Nigel BARRASS Sonya GALES Eva LENZ dan weston Ian WILSONB Tony PARRY Helen POWELL Dale THURMAN QIAO Jun-wen QIN Qiu-ping REN Jin Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica Global Safety Assessment AstraZeneca R&D BostonMAUSA and UK

Paracetamol(acetominophen,APAP) was administered orally in a rising dose protocol to 2 male and 2 female Cynomolgus monkeys to determine the Maximum Tolerated dose(MTD) for subsequent toxicology *** the subsequent repeat dose study involving 6 monkeys,no dose-limiting toxicity was seen at up to 900 mg·kg-1.d-1 APAP for 14 *** analysis showed that plasma exposure rose,albeit less than proportionally,with increasing *** were some fluctuations in clinical chemistry and haematology parameters,but these were not dose-related,and there were no compound-related findings observed *** monkeys at 900 mg·kg-1.d-1 had a 5 cm,gas filled segment in their large intestine that was considered *** profiling of the urine showed parent and glucuronidated APAP,but the cysteinyl conjugate which would be anticipated if the monkey has similar metabolism to rats and man was notably *** opens the possibility that metabolism in the cynomolgus monkey differs from that in the other species,and shows that the cynomolgus monkey is a poor model for investigating paracetamol-mediated toxicity in humans.

关键词： acetominophen toxicity

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Using Bayesian multitemporal classification to monitor tropical forest cover changes in Kalimantan,Indonesia

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International Journal of Digital Earth 2022年第1期15卷 2061-2077页

作者： Inggit Lolita Sari Christopher J.weston Glenn J.Newnham Liubov Volkova Faculty of Science School of Ecosystem and Forest SciencesThe University of MelbourneCreswickAustralia Research Center for Remote Sensing National Research and Innovation Agency (BRIN)JakartaIndonesia CSIRO Land and Water Clayton SouthAustralia

Significant areas of native forest in Kalimantan,on the island of Borneo,have been cleared for the expansion of plantations of oil palm and *** this study multisource remote sensing was used to develop a time series of land cover maps that distinguish native forest from *** a study area in east Kalimantan,Landsat images were combined with either ALOS PALSAR or Sentinel-1 images to map four land cover classes(native forest,oil palm plantation,rubber plantation,non-forest).Bayesian multitemporal classification was applied to increase map accuracy and maps were validated using a confusion matrix;final map overall accuracy was>90%.Over 18 years from 2000 to 2018 nearly half the native forests in the study area were converted to either non-forest or plantations of either rubber or oil palm,with the highest losses between 2015 and *** upwards from 2008 large areas of degraded or cleared forests,mapped as non-forest,were converted to oil palm *** of native forests to plantation mainly occurred in lowland and wetland forest,while significant forest regrowth was detected in degraded *** maps will help Indonesia with strategies and policies for balancing economic growth and conservation.

关键词： Multitemporal classification Bayesian networks Landsat ALOS PALSAR sentinel-1 Indonesia

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饥饿诱导肿瘤细胞自噬对细胞周期的影响

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癌症 2008年第8期27卷 788-794页

作者：葛军娜黄丹肖田王尊李小兰肖徽陶德定龚建平华中科技大学同济医学院附属同济医院胃肠外科湖北武汉430030 华中科技大学同济医学院附属同济医院分子医学中心肿瘤研究所湖北武汉430030

背景与目的:无血清饥饿方法可以诱发细胞自噬,同时也可以引起细胞周期阻滞。虽然研究者们对细胞自噬与细胞周期已经进行了深入的研究,但是对于两者之间的关系还是知之甚少。本研究旨在通过研究细胞周期素(Cyclin)在饥饿诱导的细胞发生... 详细信息

背景与目的:无血清饥饿方法可以诱发细胞自噬,同时也可以引起细胞周期阻滞。虽然研究者们对细胞自噬与细胞周期已经进行了深入的研究,但是对于两者之间的关系还是知之甚少。本研究旨在通过研究细胞周期素(Cyclin)在饥饿诱导的细胞发生自噬时表达的变化,来探讨自噬对细胞周期的影响。方法:对照组:d-Hanks液代替培养基饥饿诱导处于对数生长期的HeLa细胞,收获饥饿0、3、6、12h的细胞。实验组:用d-Hanks液开始饥饿的同时加入3-甲基腺嘌呤(3-methyladenine,3-MA),收获饥饿0、3、6、12h的细胞,用流式细胞术和Western blot法检测细胞周期素和特异性标记自噬的兔抗人微管相关蛋白1轻链3Ⅱ(microtubule-associated protein 1 light chain 3,LC-3)。结果:饥饿3h对照组HeLa细胞中有LC-3表达,并随饥饿时间延长而逐渐增加。Cyclin E、Cyclin D3在饥饿3h开始减少,在饥饿6h降低至最低水平,而Cyclin A、Cyclin B1在饥饿6h开始下降。实验组HeLa细胞在饥饿3h时LC-3的表达水平较低,随饥饿时间的延长LC-3表达基本不变化,Cyclin D3、Cyclin E、Cyclin A、Cyclin B1表达的下降速度也较对照组减慢。结论:自噬参与饥饿诱导的Cyclin降解的水解过程,Cyclin D3、Cyclin E水解比Cyclin A、Cyclin B1出现早,降解速度快。

关键词： HeLa细胞自噬细胞周期素细胞周期 3-甲基腺嘌呤流式细胞术

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