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xiaowanzi9新蟲 (正式寫手)
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| Organs affected by doxycycline administration in both rats and Cynomolgus monkeys were the stomach and thyroid. In rats, both the glandular and non-glandular stomachs were affected. Effects in the rat non-glandular stomach included spongiosis at the limiting ridge, submucosal inflammation, hyperkeratosis and increased incidence of epithelial hyperplasia but these findings are not discussed further here as the non-glandular stomach does not have a counterpart in humans. From clinical experience, doxycycline is known to be irritant to the gastric and oesophageal mucosas. At 600 mg/kg/day in the 13 week rat study, focal erosion in the glandular stomach was of sufficient severity to cause or contribute to death in 2 animals but it was not observed at lower doses. Other changes in the glandular stomach included increased mucus producing cells/mucus production, observed in both rats and monkeys, and submucosal inflammation and eosinophilic chief cells, observed only in rats. In rats, other parts of the gastrointestinal tract (small and large intestines) were also affected, which may have been due to changes in intestinal flora. At doses ≥400 mg/kg/day (13 week study), diffuse mucosal hyperplasia was observed in both the duodenum and caecum and, additionally, villus hypertrophy was observed in the caecum. The NOEL for gastrointestinal lesions was 25 mg/kg/day in rats (ERAUC 2) and 30 mg/kg/day in monkeys (ERAUC 2.5 based on the 1 year study). |
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xiaowanzi9
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3樓2014-10-20 11:40:52
ssssllllnnnn 
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真強必勝: 金幣+3, 謝謝 2014-10-20 10:55:21
xiaowanzi9: 金幣+25, 翻譯EPI+1, ★★★★★最佳答案, 謝謝你 2014-10-20 11:03:53
真強必勝: 金幣+3, 謝謝 2014-10-20 10:55:21
xiaowanzi9: 金幣+25, 翻譯EPI+1, ★★★★★最佳答案, 謝謝你 2014-10-20 11:03:53
| 在大鼠和獼猴，受使用多西環(huán)素影響的器官是胃和甲狀腺。在大鼠中，胃的腺體和非腺體腺部分都受到影響。在大鼠胃的非腺體部分的影響包括海綿層水腫，主要限于脊、粘膜下炎癥、角化過度和上皮增生發(fā)病率增加等。但因為人沒有胃非腺體所對應的結構，因此這里對這些發(fā)現(xiàn)不做進一步論述。根據(jù)臨床經(jīng)驗，多西環(huán)素是胃和食管粘膜已知的刺激物。在600毫克/千克/天持續(xù)13周的大鼠研究中，在2只動物，腺胃的侵蝕足夠嚴重，可以引起動物死亡或是動物死亡的原因。但較低劑量時并未觀察到。在腺胃其他的變化包括，粘液分泌細胞增多/粘液生產(chǎn)增多，這在大鼠和猴中都出現(xiàn)；以及粘膜下炎癥和嗜酸性主細胞，僅見于大鼠觀察。在大鼠，胃腸道的其他部分（小腸和大腸）也受到影響，這可能是由于改變了腸道菌群。在劑量≥400毫克/千克/天（13周研究）時，在十二指腸和盲腸均出現(xiàn)彌漫性粘膜增生。此外，盲腸出現(xiàn)絨毛肥大。未觀察到胃腸損傷效應的劑量分別是：大鼠（ERAUC2）25毫克/千克/天、猴（ERAUC2.5根據(jù)1年的研究）30毫克/公斤/天的。 |
2樓2014-10-20 10:14:18
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