Examination of drugs effective for Ieishmaniasis

在利什曼病中，葡聚糖和戊酮等锑类药物是世界上多种临床形式该病的首选治疗药物。然而，这些药物有几个缺点，包括严重的副作用，当他们给病人肌肉或静脉注射。因此，迫切需要开发更有效和更具成本效益的治疗药物。在这项研究中，我们试图寻找一些即使在没有先进设备的农村地区也没有副作用，有效且易于操作的药物。通过对几种药物的实地试验，发现帕罗霉素软膏和葡糖苷混汞铬洗剂对巴拿马利什曼原虫和古延利什曼原虫引起的皮肤病变均有较好的疗效。另一方面，抗疟药物甲氟喹和青蒿琥酯被用于皮肤雷斯曼病的口服治疗。这些药物对由上述两种病原菌引起的患者，即巴拿马和古雁两种病原菌，疗效满意。为了了解药物对治疗患者的作用机制。电镜下观察皮肤斑点状物质。为了诊断患者和/或评估药物的有效性，除了AP-PCR之外，还开发了PS-PCR（多态性特异性聚合酶链反应）和靶向mini-外显子基因的PCR。利用Lamdr2基因建立体外实验模型，从分子水平研究其耐药机制。在感染利什曼原虫（一种抗肿瘤药物）的动物身上，ONO4007进行了测试。获得的结果表明，当它与其他抗利什曼病药物（如锑、甲氟喹和青蒿琥酯）联合使用时，这种药物将对治疗利什曼病有用。

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.