Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy, and future strategies.
Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy, and future strategies.
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利什曼病化疗：生化机制、临床疗效和未来策略。
DOI：
--
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
J. Berman
中科院分区：
文献类型：
--
作者：
J. Berman
20世纪80年代，皮肤、粘膜和内脏利什曼病的治疗取得了重大进展。五价锑的安全疗法以戊巴比妥形式（Wellcome基金会，伦敦; 20 mg锑/[kg.d]，持续20-30天）对这些疾病的初始治愈率大于90%。生化研究表明，至少有三个寄生虫特异性特征与化疗药物的作用机制有关：（1）糖酵解酶和脂肪酸催化剂的一些酶组织成细胞器（糖体）发生在利什曼原虫中，而不是在哺乳动物细胞中。由于锑抑制无鞭毛体通过糖酵解酶的葡萄糖分解和脂肪酸分解，锑的作用机制可能与糖体结构或功能的改变有关。(2)嘌呤类似物可以在无鞭毛体中通过嘌呤生物合成的补救途径比在哺乳动物细胞中更大程度地利用，并且别嘌呤醇和别嘌呤醇核糖核苷通过这些手段代谢成推测有毒的核苷酸。(3)无鞭毛体甾醇的生物合成类似于假丝酵母等真菌，主要的脱甲基甾醇是麦角甾烷系列，酮康唑抑制其合成。初步的临床研究表明，嘌呤类和甾醇类抑制剂可能具有临床实用性，作为口服药物治疗皮肤利什曼病。已提出了可能的治疗策略的经典和实验代理。
The 1980s have seen significant advances in the treatment of cutaneous, mucosal, and visceral leishmaniasis. Safe regimens of pentavalent antimony in the form of Pentostam (Wellcome Foundation, London; 20 mg of antimony/[kg.d] for 20-30 days) have produced initial cure rates of greater than 90% in these diseases. Biochemical investigations have demonstrated at least three parasite-specific features relevant to the mechanism of action of chemotherapeutic agents: (1) Organization of glycolytic enzymes and some enzymes of fatty acid catabolism into organelles (glycosomes) occurs in Leishmania but not in mammalian cells. Since antimony inhibits both amastigote catabolism of glucose via glycolytic enzymes and catabolism of fatty acids, the mechanism of action of antimony may relate to alteration of glycosomal structure or function. (2) Purine analogues can be utilized by the salvage pathway of purine biosynthesis in amastigotes to a greater extent than in mammalian cells, and allopurinol and allopurinol ribonucleoside are metabolized into presumably toxic nucleotides by these means. (3) Amastigote sterol biosynthesis is akin to that of such fungi as Candida in that the major demethylated sterol is of the ergostane series and in that ketoconazole inhibits its synthesis. Preliminary clinical studies suggest that the purines and the sterol inhibitors may have clinical utility as oral agents against cutaneous leishmaniasis. Possible treatment strategies for the classic and experimental agents have been proposed.
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利什曼病和疟疾：流行病学分析的新工具。
DOI：
10.1126/science.3535070
发表时间：
1986
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Wirth,DF;Rogers,WO;BarkerJr,R;Dourado,H;Suesebang,L;Albuquerque,B
通讯作者：
Albuquerque,B
硝呋莫司治疗皮肤粘膜利什曼病的进一步试验。
DOI：
10.1016/0035-9203(81)90086-9
发表时间：
1981
影响因子：
2.2
作者：
Guerra,MF;Marsden,PD;Cuba,CC;Barretto,AC
通讯作者：
Barretto,AC
福霉素 B 的磷酸化和抗利什曼原虫活性。
DOI：
10.1016/0006-291x(81)91976-8
发表时间：
1981
影响因子：
3.1
作者：
Carson,DA;Chang,KP
通讯作者：
Chang,KP
通过比较核 DNA 限制性片段模式揭示利什曼原虫属的进化。
DOI：
10.1073/pnas.84.2.484
发表时间：
1987
影响因子：
11.1
作者：
Beverley,SM;Ismach,RB;Pratt,DM
通讯作者：
Pratt,DM