Uptake of benzimidazoles by Trichuris suis in vivo in pigs.
Uptake of benzimidazoles by Trichuris suis in vivo in pigs.
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DOI：
10.1016/j.ijpddr.2014.03.003
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发表时间：
2014-08
影响因子：
4
通讯作者：
Thamsborg, Stig Milan
中科院分区：
文献类型：
--
作者：
Hansen, Tina V. A.;Friis, Christian;Nejsum, Peter;Olsen, Annette;Thamsborg, Stig Milan
在猪体内证实了体外猪鞭虫对FBZ的低摄取。OXF和FBZSO 2的血浆和蠕虫浓度之间的高度相关性。FBZ的血浆和蠕虫浓度之间无相关性。血-肠细胞途径对于FBZ代谢物到达T.猪。FBZ可以输入T。从血液-肠上皮细胞途径和肠内容物中分离。人们认识到，单剂量苯并咪唑（BZ）对猪鞭虫线虫和人类密切相关的鞭虫线虫的临床疗效仅为差至中等。最近的体外研究表明，芬苯达唑（FBZ）在T。SUIS可能是其疗效差的原因。本研究的目的是通过测量FBZ及其代谢产物奥芬达唑（OXF）和FBZ砜（FBZSO 2）在T.从FBZ处理的猪和猪的血浆中分离的suis。FBZ在T. SUIS为66.6pmol/mg干蠕虫组织，约为先前体外研究中测量值的一半。血药浓度与T. OXF（r = 0.93，P = 0.0007）和FBZSO 2（r = 0.85，P = 0.007）在猪蠕虫中呈高度阳性，但FBZ与OXF和FBZSO 2之间无相关性。这项研究表明，低摄取FBZ观察T。猪在体外，也发生在体内。猪血浆中OXF和FBZSO_2浓度与T. suis（以及FBZ缺乏这种相关性）表明代谢物通过血液-肠上皮细胞界面到达蠕虫，而FBZ主要通过宿主的肠腔到达蠕虫。
The low uptake of FBZ by Trichuris suis in vitro was confirmed in vivo in pigs. High correlation between plasma and worm concentrations of OXF and FBZSO2. No correlation between plasma and worm concentrations of FBZ. The blood–enterocyte pathway seems important for FBZ-metabolites to reach T. suis. FBZ may enter T. suis from the blood–enterocyte pathway and the intestinal content. It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for its poor efficacy. The aim of this study was to investigate this hypothesis by measuring the concentrations of FBZ and its metabolites, oxfendazole (OXF) and FBZ sulphone (FBZSO2), in T. suis isolated from FBZ treated pigs and in plasma of the pigs. The highest concentration of FBZ measured in T. suis was 66.6 pmol/mg dry worm tissue which was approximately half of what was measured in a previous in vitro study. The correlation between drug concentrations in plasma and in T. suis worms was highly positive for OXF (r = 0.93, P = 0.0007) and FBZSO2 (r = 0.85, P = 0.007), but no correlation was found for FBZ. This study shows that the low uptake of FBZ observed for T. suis in vitro, also takes place in vivo. The high and significant correlations between OXF and FBZSO2 concentrations in plasma of the pigs and T. suis (and the lack of this correlation for FBZ) suggests that the metabolites reach the worms via the blood–enterocyte interface while FBZ primarily reaches the worms via the intestinal lumen of the host.
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影响因子：
2.6
作者：
Hennessy, D. R.;Bauer, C.;Roepstorff, A.
通讯作者：
Roepstorff, A.
影响因子：
2.4
作者：
JENKINS, T
通讯作者：
JENKINS, T
影响因子：
11.8
作者：
Knopp, Stefanie;Mohammed, Khalfan A.;Utzinger, Juerg
通讯作者：
Utzinger, Juerg
DOI：
10.1016/j.trstmh.2008.12.010
发表时间：
2009-05-01
影响因子：
2.2
作者：
Olsen, Annette;Namwanje, Harriet;Thamsborg, Stig M.
通讯作者：
Thamsborg, Stig M.
影响因子：
3.8
作者：
Hansen, Tina V. A.;Nejsum, Peter;Thamsborg, Stig Milan
通讯作者：
Thamsborg, Stig Milan