Examination of drugs effective for Ieishmaniasis

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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.