| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Although candidiasis is the most commonly observed systemic mycosis in a compromised host, constituting a significant percentage of all infections, the mechanisms of host defense against the infection have not been fully understood. Two major types of defense mechanisms, one non-specific and one-speci-fic, have been considered responsible for the resistance to candidiasis. In this study, firstly it was aimed to develop useful model for the study of fungal infections and analyses of effector cells which play an important defensive role against fungal infections. Secondly, actual analitic studies of various effectors in these newly developed models using various BRMs(biological response modifiers).
Throughout the present studies, it was confirmed that intravenous or intraperitoneal infection models in mice is still useful ones for the test of the effectiveness of various BRMs as well as antifungal chemotherapeutics. However, itwas found that in these intravenous or intraperitoneal Candida
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albicans infection models,infection is too early to manifest complicated host defense mechanisms: therefore, those systemic candemia models are not always suitable for studies of the progressive development of host resistance to the infection. The other problem is that when mice are infected with Candida by the i.v. or i.p. route, the organisms grow in the connecting tubles or in the pelvis of the kidneys even after the host defense mechanisms in other organs have fully marshalled their forces to eradicate the Candida cells The host defense against C. albicans is assumed to be diminished in the kidney due to its functional or structural characteristics. However, compared to these progressive candemia models, in mouse thigh lesion model reported by the present studies, a mouse does not die from the infection, and the host defense mechanisms can fully develop and operate without being impaired by other factors. Therefore, this model was considered to be useful for the study histopathological mechanisms of infections. Further studies, however, also indicated that mouse thigh lesion model has also disadvantages and is not suitable for the test of antifungal activity of chemotherapeutic agents, because even amphotericin B, flucytosine or ketoconazole does not exhibited any activities in this model. Our studies using these models also showed the possibilities that different effector cells play an important role in different infection models for the eradication of fungal elements.
Active roles of interferons and interleukins produced by BRMs against fungal infections are also confirmed. Less
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