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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
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
落迦(金幣+5): 還是不太通 2011-05-31 19:52:58
| Canis familiaris, the domestic dog, is a major preclinical animal species for drug development. 家犬是臨床前藥物研發(fā)中常用的主要實驗動物。 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]. 這一實驗動物種類在安全性和有效性研究中都有廣泛的應(yīng)用，包括調(diào)控毒理學(xué)和心血管遙測技術(shù)研究中的應(yīng)用，因而可用作轉(zhuǎn)錄安全性和人劑量預(yù)測的模型。 |
4樓2011-05-31 11:51:45
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
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- 金幣: 12916.1
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- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
★ ★
sltmac(金幣+2): 謝謝應(yīng)助~~ 2011-05-31 15:23:37
落迦(金幣+10, 翻譯EPI+1): 謝謝關(guān)注 2011-05-31 19:52:20
sltmac(金幣+2): 謝謝應(yīng)助~~ 2011-05-31 15:23:37
落迦(金幣+10, 翻譯EPI+1): 謝謝關(guān)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]. 當(dāng)有關(guān)性別二態(tài)性毒性現(xiàn)象在臨床快速出現(xiàn)時，對在藥物不良反應(yīng)中的性別差異話題漸漸引起了更多的注意。Much of these data rule out some obvious gender differences (such as body weight and body fat) [6,7] as major causal factors. 這些資料中的大多數(shù)都將某些明顯的性別差異（諸如體重和脂肪含量）作為主要起因。However, it is possible that hormonal signaling underlies these basic differences which are poorly understood at the moment. 然而，激素信號是這些基礎(chǔ)差異的基礎(chǔ)，可能這些事實在那時還認(rèn)識不足。 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，急需在分子水平進行基礎(chǔ)研究，以理解和在將來防止藥物不良反應(yīng)中的性別差異。 |
2樓2011-05-31 11:44:26
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
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- 蟲號: 1184404
- 注冊: 2011-01-06
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3樓2011-05-31 11:45:25
8814402
至尊木蟲 (職業(yè)作家)
- 翻譯EPI: 509
- 應(yīng)助: 18 (小學(xué)生)
- 貴賓: 0.381
- 金幣: 12916.1
- 散金: 47
- 紅花: 16
- 帖子: 4183
- 在線: 357.8小時
- 蟲號: 1184404
- 注冊: 2011-01-06
- 專業(yè): 藥物學(xué)其他科學(xué)問題
【答案】應(yīng)助回帖
落迦(金幣+15): 5 2011-05-31 19:54:01
|
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， 在當(dāng)前研究中，我們研究主要藥物代謝器官組織（包括心臟）中的基因表達，以確定性別差異是否存在，如果存在，進一步研究其在藥物研發(fā)中的潛在意義。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.另一個要考慮的是，臨床前動物研究與調(diào)控毒理學(xué)不同，傾向于主導(dǎo)性地使用雄性動物，這樣研究就會存在性別差異問題，并在臨床中帶到人上，這一問題正在被忽略。 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. 本研究中我們研究了家犬心臟（心室和心房）以及主要藥物代謝有關(guān)器官組織如腎（髓質(zhì)和皮質(zhì)）肝和小腸的基因表達，并通過通路分析工具來評估是否存在重要的性別差異。 |
5樓2011-05-31 14:40:00
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