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The topic of sex differences in adverse responses to drugs is gaining much attention at the moment, as data in regards to gender dimorphic toxicity in the clinic are rapidly emerging [4,5]. Much of these data rule out some obvious gender differences (such as body weight and body fat) [6,7] as major causal factors. However, it is possible that hormonal signaling underlies these basic differences which are poorly understood at the moment. Hence, there is a compelling need for basic research at the molecular level, in order to comprehend and thus perhaps prevent these sex differences in adverse responses in the future. Canis familiaris, the domestic dog, is a major preclinical animal species for drug development. The species is used in a wide range of studies involving safety and efficacy, including regulatory toxicology studies and cardiovascular telemetry studies [1] and thereby in translational safety and dose-prediction models to human [2]. Therefore, in the current study, we investigate gene expression in the major drug metabolizing tissues (in addition to heart tissues) to see whether any sex differences occur - and if so - to investigate the potential implications for drug development. Another issue to consider is that apart from regulatory toxicology studies, preclinical animal studies tend to be predominantly male [3] and the concern is that sex differences, which may translate to humans in the clinic, are being overlooked. In this study we investigated gene expression profiles in dog heart tissues (ventricle and atrium), along with the major drug metabolizing tissues of the kidney (medulla and cortex), liver and small bowel (gut ileum) and used pathway analysis tools to evaluate whether major sex differences were occurring. |
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8814402
至尊木虫 (职业作家)
- 翻译EPI: 509
- 应助: 18 (小学生)
- 贵宾: 0.381
- 金币: 12916.1
- 散金: 47
- 红花: 16
- 帖子: 4183
- 在线: 357.8小时
- 虫号: 1184404
- 注册: 2011-01-06
- 专业: 药物学其他科学问题
【答案】应助回帖
落迦(金币+5): 还是不太通 2011-05-31 19:52:58
| Canis familiaris, the domestic dog, is a major preclinical animal species for drug development. 家犬是临床前药物研发中常用的主要实验动物。 The species is used in a wide range of studies involving safety and efficacy, including regulatory toxicology studies and cardiovascular telemetry studies [1] and thereby in translational safety and dose-prediction models to human [2]. 这一实验动物种类在安全性和有效性研究中都有广泛的应用，包括调控毒理学和心血管遥测技术研究中的应用，因而可用作转录安全性和人剂量预测的模型。 |
4楼2011-05-31 11:51:45
8814402
至尊木虫 (职业作家)
- 翻译EPI: 509
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- 专业: 药物学其他科学问题
【答案】应助回帖
★ ★
sltmac(金币+2): 谢谢应助~~ 2011-05-31 15:23:37
落迦(金币+10, 翻译EPI+1): 谢谢关注 2011-05-31 19:52:20
sltmac(金币+2): 谢谢应助~~ 2011-05-31 15:23:37
落迦(金币+10, 翻译EPI+1): 谢谢关注 2011-05-31 19:52:20
| The topic of sex differences in adverse responses to drugs is gaining much attention at the moment, as data in regards to gender dimorphic toxicity in the clinic are rapidly emerging [4,5]. 当有关性别二态性毒性现象在临床快速出现时，对在药物不良反应中的性别差异话题渐渐引起了更多的注意。Much of these data rule out some obvious gender differences (such as body weight and body fat) [6,7] as major causal factors. 这些资料中的大多数都将某些明显的性别差异（诸如体重和脂肪含量）作为主要起因。However, it is possible that hormonal signaling underlies these basic differences which are poorly understood at the moment. 然而，激素信号是这些基础差异的基础，可能这些事实在那时还认识不足。 Hence, there is a compelling need for basic research at the molecular level, in order to comprehend and thus perhaps prevent these sex differences in adverse responses in the future.因此，急需在分子水平进行基础研究，以理解和在将来防止药物不良反应中的性别差异。 |
2楼2011-05-31 11:44:26
8814402
至尊木虫 (职业作家)
- 翻译EPI: 509
- 应助: 18 (小学生)
- 贵宾: 0.381
- 金币: 12916.1
- 散金: 47
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- 帖子: 4183
- 在线: 357.8小时
- 虫号: 1184404
- 注册: 2011-01-06
- 专业: 药物学其他科学问题
3楼2011-05-31 11:45:25
8814402
至尊木虫 (职业作家)
- 翻译EPI: 509
- 应助: 18 (小学生)
- 贵宾: 0.381
- 金币: 12916.1
- 散金: 47
- 红花: 16
- 帖子: 4183
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- 虫号: 1184404
- 注册: 2011-01-06
- 专业: 药物学其他科学问题
【答案】应助回帖
落迦(金币+15): 5 2011-05-31 19:54:01
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Therefore, in the current study, we investigate gene expression in the major drug metabolizing tissues (in addition to heart tissues) to see whether any sex differences occur - and if so - to investigate the potential implications for drug development.因此， 在当前研究中，我们研究主要药物代谢器官组织（包括心脏）中的基因表达，以确定性别差异是否存在，如果存在，进一步研究其在药物研发中的潜在意义。Another issue to consider is that apart from regulatory toxicology studies, preclinical animal studies tend to be predominantly male [3] and the concern is that sex differences, which may translate to humans in the clinic, are being overlooked.另一个要考虑的是，临床前动物研究与调控毒理学不同，倾向于主导性地使用雄性动物，这样研究就会存在性别差异问题，并在临床中带到人上，这一问题正在被忽略。 In this study we investigated gene expression profiles in dog heart tissues (ventricle and atrium), along with the major drug metabolizing tissues of the kidney (medulla and cortex), liver and small bowel (gut ileum) and used pathway analysis tools to evaluate whether major sex differences were occurring. 本研究中我们研究了家犬心脏（心室和心房）以及主要药物代谢有关器官组织如肾（髓质和皮质）肝和小肠的基因表达，并通过通路分析工具来评估是否存在重要的性别差异。 |
5楼2011-05-31 14:40:00
