Examination of drugs effective for Ieishmaniasis

检查对利什曼病有效的药物

• 批准号: 07557209
• 负责人: HASHIGUCHI Yoshihisa
• 金额: $ 4.35万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557209/
• 关键词: antimalarial drug; Mephaquin; Artesunate; antileishmanial drug; cutaneous leishmaniasis; PCR; nucleotide sequence; electron-microscopic pathology; メフロキシ; Mefloquine; Artesunate; リーシュマニア症; メファキン; プラスモトリム; P-糖タンパク質遺伝子; IL-8遺伝子; AP-PCR; Nest

In leishmaniasis, antimonials such as Glucantime and Pentostum are the first choice of treatment for a wide range of clinical forms of the disease in the world. However , these drugs have several disadvatages including severe side effects when they are administered intramuscularly or intravenously to the patients. Therefore, it is necessary to develop urgently more effective and cost-efficient drugs for the treatment.In this study, we tried to search for some drugs, which are non-side effective and easy handling even in rural areas without any sophisticated equipments. Based on our field trial with swveral drugs, it was found that both of the paromomycin ointment and the lotion of Glucnatime mixed with mercury chrome were highly effective for cutaneous lesions caused by Leishmania (Viannia) panamensis and L.(V.) guyanensis. On the other hand, antimalarial drugs, mefloquine and artesunate, were used as oral therapy for cutaneous leismaniasis. These drugs gave a satisfactory result for patients caused by the two species mentioned above, L.(V.) panamensis and L.(V.) guyanensis. In order to get some information on the action machanisms of the drugs in patients treated. skin blopsy materisls were examined electron-microscopically.For diagnosis of patient and/or evaluation of drug effectiveness, PS-PCR (polymorphism specific-polymerase chain reaction) and PCR tergeting mini-exone gene were also developed in addition to AP-PCR.An in vitro experimental model using Lamdr2 gene was established to study mechanisms of drug-resistance at molecular level. In animals infected with Leishmania, an anti-tumor drug, ONO4007 was tested. The results obtained suggested that the drug would be useful for leishmaniasis treatment, when it was used in combination with other anti-leishmanial drugs, such as antimonials, mefloquine and artesunate.

在利什曼病中，世界上各种临床形式的利什曼病都是首选的治疗药物，如葛兰素史克和潘多司坦。然而，这些药物有几个缺点，包括严重的副作用，当它们被肌肉或静脉注射给患者时。因此，迫切需要开发更有效、更经济的治疗药物。在本研究中，我们试图寻找一些即使在没有任何尖端设备的农村地区也能非副作用有效且易于操作的药物。根据我们的现场药物试验，发现帕罗霉素软膏和葡萄糖与铬汞混合洗剂对由美洲利什曼原虫和L.(V.)Guyanensis。另一方面，甲氟喹和青蒿琥酯等抗疟药物被用于皮肤利什曼病的口服治疗。这些药物对上述两种病原菌L.(V.)Panamens和L.(V.)Guyanensis。以了解药物在治疗患者中的作用机制。在AP-PCR的基础上，建立了PS-PCR(多态特异性聚合酶链式反应)和以mini-exOne为靶点的基因检测方法，建立了Lamdr2基因的体外实验模型，从分子水平研究耐药机制。在感染利什曼原虫的动物身上，一种抗肿瘤药物ONO4007进行了测试。结果提示，该药与其他抗利什曼药物如锑、甲氟喹、青蒿琥酯合用时，可用于治疗利什曼病。

项目成果

Y.Hashiguchi(ed.): "Kyowa Printing Co." Estudios sobre la Leishmaniasis en el Nuevo Mundo y su Transmision con Especial Referencia al Ecuador.No.3. 175 (1997)

Y.Hashiguchi（主编）：《协和印刷公司》

橋口義久: "世界の感染症アフリカトリパノソーマ症,オンコセルカ症,シャーガス症,バベシア症,リーシュマニア症,リンパ管フィラリア症" 菜根出版, (1997)

Yoshihisa Hashiguchi：“世界传染病非洲锥虫病、盘尾丝虫病、恰加斯病、巴贝虫病、利什曼病、淋巴丝虫病”Nane Publishing，（1997）

Y.Hashiguchi: "Estudios sobre la Leishmaniasis en el Nuevo Mundo y su Transmision con Especial Referencia al Ecuador" Kyowa Printing Co., 147 (1996)

Y.Hashiguchi：“Estudios sobre la Leishmaniasis en el Nuevo Mundo y su Transmission con Especial Referencia al Ecuador”Kyowa Printing Co.，147 (1996)

橋口義久: "寄生虫学・衛生動物学の進展のためのブレーンストーミングリーシュマニア症対策の現状と将来-そのbreak throughを夢みて-" 長崎大学熱帯医学研究所出版, ((印刷中))

桥口义久：“寄生虫学和卫生动物学的进步集思广益：利什曼病对策的现状和未来 - 梦想突破 -”长崎大学热带医学研究所出版，（（出版中））

橋口義久: "皮膚リーシュマニア症" 皮膚科の臨床. 38・4. 547-556 (1996)

桥口义久：“皮肤利什曼病”临床皮肤病学 38・4（1996）。