Analysis of polysaccharide in the cyst wall of Pneumocystis carinii and therapeutic strategy for pneumocystosis using beta-1, 3-glucan biosynthesis inhibitor in vivo.

卡氏肺孢子虫囊壁多糖分析及体内β-1,3-葡聚糖生物合成抑制剂治疗肺孢子虫病的策略。

• 批准号: 02670171
• 负责人: YAMADA Minoru
• 金额: $ 1.47万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670171/
• 关键词: Pneumocystis carinii; pellicle; beta-1, 3-glucan biosynthesis inhibitor; Therapy; Prophylaxis; Aculeacin A; Glucan; Aculeacin A and trimethoprim-sulfamethoxazole; Zymolyase

In vivo activities of a beta-1, 3-glucan biosynthesis inhibitor, aculeacin A, against P. carinii and P. carinii pneumonia were investigated using the rat model. Intraperitoneal administration of aculeacin A at 25 mg/kg or 10 mg/kg, or even at 2 mg/kg per day for 2 weeks from 5 Weeks of steroid treatment, affected cyst wall formation, inhibited cyst maturation, and prevented severe pneumonia in steroid-treated rats. Administration of aculeacin A at 10 mg/kg, or even at 2 mg/kg per day earlier, during the initial phase of infection, was more effective suggesting that this drug can be used prophilactically. Simultaneous administration of aculeacin A (0.4 mg/kg) and trimethoprim-sulfamethoxazole (1mg/kg as a dose of sulfamethoxazole) from 5 weeks of steroid treatment showed therapeutic effects against rat pneumocystosis. This data suggested that dosages of both drugs were reduced, though distinct synergy of use of both drugs was not given in this case.Thus it is hoped that studies of beta-1, 3-glucan biosynthetic inhibitors will not only help in the understanding of the biochemical pathways of the organisms, but also lead to improved human pneumocystosis chemotherapy.

采用大鼠肺炎模型，研究了β-1，3-葡聚糖生物合成抑制剂Aulein A对卡氏肺孢子虫和卡氏肺孢子虫肺炎的体内抑制作用。激素治疗5周后，以25 mg/kg或10 mg/kg，甚至每天2 mg/kg的剂量连续给药2周，均可影响囊壁形成，抑制囊壁成熟，预防重症肺炎。在感染初期给药10 mg/kg，甚至每天2 mg/kg更有效，这表明该药物可用于亲蜂房使用。激素治疗5周后，同时给予阿库莱星A(0.4 mg/kg)和新诺明-磺胺甲恶唑(1 mg/kg)，对大鼠肺孢子虫病有明显的治疗作用。这一数据表明，这两种药物的剂量都有所减少，尽管在这种情况下，两种药物的使用没有明显的协同作用。因此，希望对β-1，3-葡聚糖生物合成抑制剂的研究不仅有助于了解生物的生化途径，而且有助于改进人类肺孢子虫病的化疗。

项目成果

松本 芳嗣: "グルカン合成阻害薬aculeacin AとST合剤の併用による実験的ラット・ニュ-モシスチスカリニ肺炎の予防" 寄生虫学雑誌. 41. 116 (1992)

Yoshitsugu Matsumoto：“联合使用葡聚糖合成抑制剂 aculeacin A 和 ST 组合对大鼠卡氏肺孢子虫肺炎的实验预防”，寄生虫学杂志 41. 116 (1992)。

山田 稔: "ニュ-モシスチス・カリニ肺炎の治療薬としてのグルカン合成阻害薬,aculeacinA" 寄生虫学雑誌. (1991)

Minoru Yamada：“Aculeacin A，一种葡聚糖合成抑制剂，作为卡氏肺囊虫肺炎的治疗剂”《寄生虫学杂志》（1991 年）。

松本 芳嗣: "グルカン合成阻害薬,aculeacin Aによるニュ-モシスチス・カリニ肺炎予防効果とその作用機作に関する考察" 寄生虫学雑誌(発表予定). 41. (1992)

Yoshitsugu Matsumoto：“葡聚糖合成抑制剂 aculeacin A 对卡氏肺囊虫肺炎的预防作用及其作用机制的研究”《寄生虫学杂志》41（待出版）。

Y. Matsumoto: "Yeast glucan of Pneumocystis carinii cyst wall : An excellent target for chemotherapy" Journal of Protozoology. 38(6). 6S-7S

Y. Matsumoto：“卡氏肺孢子虫囊壁的酵母葡聚糖：化疗的绝佳靶点”《原生动物学杂志》。

Yoshitsugu Matsumoto: "Yeast glucan of Pneumocystis carinii cyst wall;An excellent target for chemotherapy" Journal of Protozoology. 38. 6S-7S (1992)

Yoshitsugu Matsumoto：“卡氏肺孢子虫囊壁的酵母葡聚糖；化疗的绝佳靶点”《原生动物学杂志》。