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自动化生物气溶胶暴露系统:临床前平台开发及在非人灵长类动物中的呼吸剂量学应用

The automated bioaerosol exposure system: preclinical platform development and a respiratory dosimetry application with nonhuman primates.

作者信息

Hartings Justin M, Roy Chad J

机构信息

Hartings Consulting, Inc., USA.

出版信息

J Pharmacol Toxicol Methods. 2004 Jan-Feb;49(1):39-55. doi: 10.1016/j.vascn.2003.07.001.

DOI:10.1016/j.vascn.2003.07.001
PMID:14670693
Abstract

INTRODUCTION

Well-characterized inhalation exposure systems are critical for preclinical testing and pathogenesis studies. The automated bioaerosol exposure system (ABES) provides a microprocessor-driven inhalation platform that provides exquisite data acquisition and control over all aspects of inhalation exposures. Because this represents a new technology, the development and characteristics of the ABES are thoroughly discussed. In addition to control over homeostatic and aerosol conditions, the ABES incorporates a dosimetry function based on respiratory performance of the test animal during inhalation.

METHODS

To test the system, rhesus macaques were initially sham-exposed using the ABES in a head-only inhalation configuration. The ABES was subsequently used under biosafety level (BSL)-III conditions in a vaccine efficacy challenge using aerosolized staphylococcal enterotoxin B (SEB) toxin, again using the real-time dosimetry function of the system.

RESULTS

Sham exposure results indicated significant departures from corresponding whole-body plethysmography (WBP) respiratory function estimates taken before the inhalation procedure. The results of the SEB exposure demonstrated the utility of using the ABES to generate consistently accurate and precise inhalation dose.

DISCUSSION

Taken together, the results of the sham and toxin challenge experiments demonstrate that the dosimetry function of the ABES improves the precision and accuracy of inhaled dose delivery and calculation as compared to predictive WBP conducted before the exposure. The ABES represents a highly adaptable platform for the design of inhalation systems to suit the requirements of a variety of animal models.

摘要

引言

特征明确的吸入暴露系统对于临床前测试和发病机制研究至关重要。自动化生物气溶胶暴露系统(ABES)提供了一个由微处理器驱动的吸入平台,可对吸入暴露的各个方面进行精确的数据采集和控制。由于这代表了一项新技术,因此对ABES的开发和特性进行了全面讨论。除了控制体内平衡和气溶胶条件外,ABES还基于测试动物在吸入过程中的呼吸性能纳入了剂量测定功能。

方法

为了测试该系统,最初使用ABES以仅头部吸入配置对恒河猴进行假暴露。随后,在生物安全三级(BSL-III)条件下,使用雾化的葡萄球菌肠毒素B(SEB)毒素在疫苗效力挑战中再次使用该系统的实时剂量测定功能。

结果

假暴露结果表明,与吸入程序前进行的相应全身体积描记法(WBP)呼吸功能估计值有显著差异。SEB暴露结果证明了使用ABES产生始终准确和精确的吸入剂量的效用。

讨论

综合来看,假暴露和毒素挑战实验的结果表明,与暴露前进行的预测性WBP相比,ABES的剂量测定功能提高了吸入剂量递送和计算的精度和准确性。ABES代表了一个高度适应性强的平台,可用于设计吸入系统以满足各种动物模型的要求。

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