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吸入性伊曲康唑纳米混悬液在接种烟曲霉的幼鹌鹑模型肺部感染中的活性与安全性

Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

作者信息

Wlaź Piotr, Knaga Sebastian, Kasperek Kornel, Wlaź Aleksandra, Poleszak Ewa, Jeżewska-Witkowska Grażyna, Winiarczyk Stanisław, Wyska Elżbieta, Heinekamp Thorsten, Rundfeldt Chris

机构信息

Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland,

出版信息

Mycopathologia. 2015 Aug;180(1-2):35-42. doi: 10.1007/s11046-015-9885-2. Epub 2015 Mar 20.

DOI:10.1007/s11046-015-9885-2
PMID:25790942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4498244/
Abstract

Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

摘要

肺部曲霉菌病在鹦鹉、猎鹰及其他圈养鸟类中时有报道。吸入是烟曲霉的主要感染途径,可导致急性和慢性疾病状态。伊曲康唑(ITRA)是鸟类常用的抗真菌药物,但其给药需要反复口服,且安全范围较窄。为研究吸入性ITRA的疗效,将六组每组十只的幼鹌鹑(日本鹌鹑)经气管内接种5×10⁶个孢子(3组)或5×10⁷个孢子(3组)。接种后2小时开始,动物每天暴露于雾化的ITRA纳米混悬液(10%混悬液或4%混悬液)中30分钟,持续6天。对照组在相同时间段内暴露于雾化盐水中。评估存活率和临床评分,并对动物进行大体病理学检查。在对照动物中,曲霉菌病导致全身性疾病,无肺部或气囊肉芽肿。动物死于多器官衰竭。吸入10%的ITRA纳米混悬液可阻止低剂量孢子暴露鹌鹑的致死性并预防与疾病相关的症状,而接种高剂量孢子鹌鹑的病程则有所延缓。吸入4%的ITRA纳米混悬液效果较差。两种吸入方式耐受性良好,大体病理学检查未发现局部毒性迹象。数据表明,吸入10%的ITRA纳米混悬液能够减轻鹌鹑急性烟曲霉感染。较低浓度的ITRA可能仅对慢性肺部曲霉菌病有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/e98770145782/11046_2015_9885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/0f0da8226e8c/11046_2015_9885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/220bf7188033/11046_2015_9885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/e98770145782/11046_2015_9885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/0f0da8226e8c/11046_2015_9885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/220bf7188033/11046_2015_9885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/4498244/e98770145782/11046_2015_9885_Fig3_HTML.jpg

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