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Effects of albendazole,artesunate,praziquantel and miltefosine,on Opisthorchis viverrini cercariae and mature metacercariae

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Asian Pacific Journal of Tropical Medicine 2017年第2期10卷 120-126页

作者： Phornphitcha Pechdee Monticha Chaiyasaeng Chanisala Sereewong Jukkrid Chaiyos Apiporn Suwannatrai Sutee Wongmaneeprateep Smarn Tesana Food-Borne Parasite Research Group Department of ParasitologyFaculty of MedicineKhon Kaen University Department of Fisheries Faculty of AgricultureKhon Kaen University

Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(***) for alternative approach to interrupting its cycle for developing a field-based control ***:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on *** cercariae and mature metacercariae were *** concentrations(LC_(50) and LC_(95)) of these drugs were *** metacercariae previously exposed to various concentrations of the drugs were administered to *** were harvested 30 d post infection and worm recovery rates ***,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h ***:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,***_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated *** adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to *** cercariae but lesser efficacy to *** should be further studied with the eventual aim of developing a field-based control program.

关键词： Albendazole Artesunate Praziquantel miltefosine Opisthorchis viverrini Cercariae

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miltefosine的类似物及光敏探针的合成和表征

Miltefosine的类似物及光敏探针的合成和表征

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作者：黄飞武汉大学

学位级别：硕士

miltefosine（HePC,十六烷基磷酸胆碱）是烷基溶血磷脂类似物的一种,是人工合成的小分子抗癌药物,目前应用于临床治疗皮肤癌、乳癌等,并被制成口服药剂。近年来,miltefosine治疗利什曼病的良好疗效也越来越引起人们的注视。在印度它已... 详细信息

miltefosine（HePC,十六烷基磷酸胆碱）是烷基溶血磷脂类似物的一种,是人工合成的小分子抗癌药物,目前应用于临床治疗皮肤癌、乳癌等,并被制成口服药剂。近年来,miltefosine治疗利什曼病的良好疗效也越来越引起人们的注视。在印度它已经被注册用于口服治疗内脏利什曼病,治愈率达97%。 miltefosine取得了很好的临床成功,但是,它的胃肠毒性和溶血副作用却限制了它的运用。因此,发展出更新、更安全的药物显得相当重要。基于这一点,我们设计和合成了一系列miltefosine的类似物,以希望得到新一代的抗癌药物。长链醇作为烷基磷酸胆碱的主要组成部分,其结构的变化也直接影响了miltefosine的物理和化学性质。在合成长链羧酸类似物的基础上,我们合成了一系列含醚键的长链醇。进而,我们合成了12—丙氧基十二烷基磷酸胆碱和12—乙氧基十二烷基磷酸胆碱,在结构上模拟了十六烷基磷酸胆碱。由于醚键的引入,增强了miltefosine长链端的亲水性,使得它更容易透过细胞膜,进而降低miltefosine发挥药效所需的最小浓度,有可能减小其毒副作用。 miltefosine类似物结构与生物活性相关性的研究显示,磷脂结构并不是必须的。因此,我们大胆地舍弃了磷酸基团,代之以结构更稳定的碳酸基团,合成出一系列烷基碳酸酯胆碱。我们认为这些烷基碳酸酯胆碱类似物不会被一些生物体内的磷脂代谢酶水解,且更容易在细胞膜上富集。尽管miltefosine临床治疗肿瘤和利什曼病取得了很好的效果,但其作用机理尚不清楚。已经提出的抗癌机理包括:调节细胞膜的透过性和细胞膜磷脂的组分;调节磷脂的代谢;改变生殖信号的传导途径;诱导细胞凋亡等。因此,得到其确切的作用靶标是澄清其机理的出发点。光亲合标记是研究药物和靶标相互作用的有效方法,目前已被生物化学和分子生物学广泛用于研究生物体系的空间邻近组分,它为分子空间邻近结构提供了最直接的证据。我们设计和合成了miltefosine的光标记类似物,希望通过光亲合

关键词： miltefosine 光亲合标记光亲合标记探针四氟苯基叠氮烷基磷酸胆碱

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Cutaneous leishmaniasis in Louisiana-one-year follow-up:A case report

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World Journal of Clinical Infectious Diseases 2021年第1期11卷 19-26页

作者： Ashaur Azhar Hillary E Connell Christopher Haas Jelena Surla Devin Reed Sanjay Kamboj Gordon L Love Yussef Bennani Department of Medicine Section of Infectious DiseasesLouisiana State University Health Sciences CenterSchool of MedicineNew OrleansLA 70112United States Department of Medicine Louisiana State University Health Sciences CenterSchool of MedicineNew OrleansLA 70112United States Department of Dermatology Louisiana State University Health Sciences CenterSchool of MedicineNew OrleansLA 70112United States Jack Perry Strong Professor and Chair Department of PathologyLouisiana State University Health Sciences CenterSchool of MedicineNew OrleansLA 70112United States

Reports of leishmaniasis are scarce in North *** is considered to be one of the neglected tropical *** is seen in immigrants from endemic areas to United *** are not readily available in the United *** or inadequately treated cutaneous leishmaniasis not only causes localized disfigurement but can advance to more permanent and devastating mucosal disfigurement and perforation,if caused by a species that can also cause mucocutaneous *** SUMMARY A 42-year-old human immunodeficiency virus negative male immigrant from Honduras presented to the emergency department of our facility in Louisiana with a 2-mo history of a left lower extremity *** started as a painless blister that progressed in size and developed into other smaller lesions tracking up the thigh and became tender and *** looked nontoxic and *** was *** tests,except inflammatory markers,were within normal *** cellulitis of the leg was treated with 6 d of vancomycin that also relieved the *** biopsy was obtained,and histopathology was suspicious for *** chain reaction/deoxyribonucleic acid sequencing done by centers for disease control and prevention confirmed the diagnosis as Leishmania *** was no involvement of nasooropharyngeal mucosa,confirmed by *** patient was treated with miltefosine for 28 *** follow-up after approximately 11 mo revealed a healed skin *** Cutaneous leishmaniasis should be in the differential diagnosis of skin ulcers of travelers from endemic *** regarding diagnosis and treatment of leishmaniasis needs to be enhanced.

关键词： Cutaneous leishmaniasis Neglected diseases Leishmania(Viannia)panamensis miltefosine Leishmania Case report

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