Diethylcarbamazine mediated potentiation of emodepside induced paralysis requires TRP-2 in adult Brugia malayi.
Diethylcarbamazine mediated potentiation of emodepside induced paralysis requires TRP-2 in adult Brugia malayi.
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DOI：
10.1016/j.ijpddr.2022.10.002
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发表时间：
2022-12
影响因子：
4
通讯作者：
Martin, Richard J.
中科院分区：
文献类型：
--
作者：
Kashyap, Sudhanva S.;McHugh, Mark A.;Robertson, Alan P.;Martin, Richard J.
人类和兽医的丝虫线虫感染是热带国家的一个主要健康问题。它们通过叮咬的昆虫和蚊子传播。淋巴丝虫病是一组由丝虫属引起的丝虫感染。和班氏乌氏杆菌感染了全球超过1.2亿人。受感染者四肢肿胀，毁容，导致无法工作和被社会排斥。控制和预防这些感染涉及大规模药物管理的驱虫剂，包括乙胺嗪（DEC）的组合。DEC对微丝蚴有作用，但对蠕虫作用不明显。SLO-1（BK）通道激活剂emodepside可以杀死许多丝虫物种的成虫。然而，依莫地塞对B的体内功效是次优的。马来人，可能是由于淋巴系统中的生物利用度降低。在B中表达不同的slo-1剪接变体。马来语也会影响对依莫地昔的敏感性。本研究探讨了DEC对成年雌性B中emodepside介导的麻痹的增强作用。马来语。蠕虫运动性测量表明，DEC和emodepside的共同应用增加emodepside的效力4倍。甚至在蠕虫从DEC的初始效应恢复（脱敏）后，emodepside效应的增强仍然存在。RNAi敲低表明DEC介导的emodepside增强需要TRP-2通道的存在。我们的研究表明，添加DEC可以增强emodepside的效果，其中生物利用度或对特定物种的活性可能较低。
Human and veterinary filarial nematode infections are a major health concern in tropical countries. They are transmitted by biting insects and mosquitoes. Lymphatic filariasis, a group of filarial infections caused by Brugia spp. and Wucheria bancrofti affect more than 120 million people worldwide. Infected individuals develop swollen limbs and disfigurement, leading to an inability to work and ostracization from society. Control and prophylaxis for these infections involve mass drug administration combinations of anthelmintics including diethylcarbamazine (DEC). DEC has actions on microfilariae, but its effects on adult worms are less pronounced. The SLO-1 (BK) channel activator, emodepside, kills adults of many filarial species. However, the in vivo efficacy of emodepside is suboptimal against B. malayi, possibly due to reduced bioavailability in the lymphatic system. Expressing different slo-1 splice variants in B. malayi also affects sensitivity to emodepside. This study explores the potentiation of emodepside mediated paralysis by DEC in adult female B. malayi. Worminator motility measurements show that co-application of DEC and emodepside increases the potency of emodepside 4-fold. The potentiation of the emodepside effect persists even after the worms recover (desensitize) from the initial effects of DEC. RNAi knock-down demonstrates that the DEC-mediated potentiation of emodepside requires the presence of TRP-2 channels. Our study demonstrates that the addition of DEC could enhance the effect of emodepside where bioavailability or activity against a specific species may be low.
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DOI：
10.1056/nejmoa1706854
发表时间：
2018-11-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
King CL;Suamani J;Sanuku N;Cheng YC;Satofan S;Mancuso B;Goss CW;Robinson LJ;Siba PM;Weil GJ;Kazura JW
通讯作者：
Kazura JW
影响因子：
2
作者：
Kruedewagen, Eva Maria;Remer, Carolin;Stanneck, Dorothee
通讯作者：
Stanneck, Dorothee
影响因子：
4
作者：
Zahner, H;Taubert, A;von Samson-Himmelstjerna, G
通讯作者：
von Samson-Himmelstjerna, G
影响因子：
3.8
作者：
Kulke D;von Samson-Himmelstjerna G;Miltsch SM;Wolstenholme AJ;Jex AR;Gasser RB;Ballesteros C;Geary TG;Keiser J;Townson S;Harder A;Krücken J
通讯作者：
Krücken J
DOI：
10.1016/0169-4758(90)90227-u
发表时间：
1990-04-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
LACEY, E
通讯作者：
LACEY, E