Studies for mechanisms and treatments of deep seated mycosis. --An establishment of animal models of recurrent pulmonary aspergillosis and analysis of its' pathogenicity --

1)肺曲霉病复发模型的建立与分析我们建立了以环磷酰胺代替醋酸可的松诱导的肺曲霉复发大鼠模型。在这个新模型中，实现了疾病的快速和均匀复发，并且在实验的各个点上，组织病理学结果与肺的活曲霉计数有很好的相关性。通过血清和尿液中曲霉抗原的检测也可以很容易地估计复发的临床过程。2)抗原检测在人类病例中的临床评价。我们已经认识到抗原检测对上述模型中曲霉感染的早期诊断的有用性。然后从假定或证明有曲霉感染的人类临床病例中提取血清和尿液样本。我们可以得出结论，抗原检测对曲霉病的诊断也是有用的。3)利用急性和复发性肺曲霉病大鼠模型，在体内评价新的抗真菌药物或新的治疗方法，如细胞因子和MDPs。在这些研究中，我们发现乌司他丁与抗真菌药物联合使用具有抗曲霉活性。

1) An establishment and analysis of recurrent model of pulmonary aspergillosisWe have established a new rat model of recurrent pulmonary aspergillus, induced by cyclophosphamide in stead of cortisone acetate. In this new model, rapid and uniform recurrence of the disease was achieved, and histopathological findings were correlate well with viable aspergillus counts of the lung at various points of the experiments.The clinical course of the recurrence was also easily estimated by the detection of aspergillus antigens in sera and urines.2) Clinical evaluation of the usefulness of antigen detection in human cases.We have recognized the usefulness of antigen detection for early diagnosis of aspergillus infection in the above model. Then serum and urine samples obtained from human clinical cases who were supposed or proven to have aspergillus infection. And we can conclude that antigen detection is useful to diagnose of aspergillosis also in human cases.3) Acute and recurrent rat models of pulmonary aspergillosis were also used for in vivo evaluations of new antifungal agents or new approaches of treatment, such as cytokines and MDPs. In these studies, we found anti-aspergillus activity of ulinastatine with combination of antifungal agents.