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Hypothermic Endpoint for an Intranasal Invasive Pulmonary Aspergillosis Mouse Model

机译:鼻内侵袭性肺曲霉病小鼠模型的低温终点

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Immunocompromised mice were infected intranasally with Aspergillus fumigatus as part of a vaccine efficacy study. Although body temperature was measured throughout the study, a formal evaluation of its usefulness as an endpoint criterion was not performed. We retrospectively evaluated survival data and temperature records to determine whether body temperature can be used as an objective predictor of death and included in the humane endpoint criteria for this mouse model. CF1 mice were immunosup-pressed with either cortisone acetate or by treatment with antiGRl (a neutrophil-depleting antibody) and then intranasally challenged with A. fumigatus. Body temperature was measured by using an infrared noncontact thermometer a maximum of 3 times daily untildeath or euthanasia. A surface body temperature below 29.0 °C was correlated with a poor chance of survival, and using this cutoff point with signs of morbidity (hunched, ruffled fur, respiratory distress) reliably indicates mice for euthanasia withoutnegatively affecting data collection. Using 2 subsequent readings of less than 31.0 °C as an endpoint would have led to premature euthanasia of only one mouse (2.2%). As a single reading, a body temperature of 28.8 °C had a sensitivity of 92.2% and specificity of 90.9%. Hypothermia proved to be a useful addition to the humane endpoint criteria for this mouse model, and veterinary and research groups should discuss their study needs in relation to animal welfare to best determine the most appropriatemeans of including this parameter.
机译:作为疫苗功效研究的一部分,免疫力低下的小鼠经鼻内烟熏曲霉感染。尽管在整个研究过程中都对体温进行了测量,但并未对其作为终点标准的有用性进行正式评估。我们回顾性评估了生存数据和温度记录,以确定体温是否可以用作死亡的客观预测指标,并包括在此小鼠模型的人道终点标准中。 CF1小鼠用醋酸可的松或通过抗GR1(一种中性粒细胞消耗抗体)进行免疫抑制,然后用烟曲霉鼻内攻击。每天最多使用3次红外非接触式温度计测量体温,直到死亡或安乐死为止。低于29.0°C的体表温度与较差的存活机会相关,并且使用此临界点并带有发病迹象(弯腰,皮毛褶皱,呼吸窘迫)可靠地表明小鼠处于安乐死状态,而对数据收集没有负面影响。使用两个低于31.0°C的后续读数作为终点将仅导致一只小鼠(2.2%)的过早安乐死。作为单次读数,体温为28.8°C,灵敏度为92.2%,特异性为90.9%。体温过低证明是对该小鼠模型的人道终点标准的有用补充,兽医和研究小组应讨论其与动物福利有关的研究需求,以最好地确定包括该参数的最合适的方法。

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