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Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro

Overview of attention for article published in Veterinary Parasitology, May 2015
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Title
Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug-resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in vitro
Published in
Veterinary Parasitology, May 2015
DOI 10.1016/j.vetpar.2015.04.025
Pubmed ID
Authors

Ali Raza, Steven R. Kopp, Abdul Jabbar, Andrew C. Kotze

Abstract

P-glycoproteins (P-gps) play an important role in the sensitivity of nematodes to anthelmintic drugs. They have been implicated in a number of anthelmintic resistances, particularly for macrocyclic lactone drugs. Hence, inhibition of nematode P-gps has been suggested as a means of reversing some types of anthelmintic resistance. The present study aimed to investigate the ability of the most-recently developed group of P-gp inhibitors (the so-called 'third generation' of inhibitors) including tariquidar, zosuquidar and elacridar, to increase the sensitivity of Haemonchus contortus larvae to various anthelmintics (ivermectin, levamisole and thiabendazole) in vitro. We compared these compounds to some older P-gp inhibitors (e.g. verapamil and valspodar). Larval migration and development assays were used to measure the sensitivity of larvae to anthelmintics alone, or in combination with P-gp inhibitors. Significant increases in sensitivity to ivermectin were observed with zosuquidar and tariquidar in larval migration assays (synergism ratios up to 6-fold). Several of the inhibitors increased the sensitivity of both the drug-resistant and -susceptible isolates (e.g. tariquidar with ivermectin in migration assays, zosuquidar with ivermectin in larval development assays), while others had significant effects on the resistant isolate only (e.g. zosuquidar with ivermectin in migration assays, verapamil with ivermectin in development assays). This suggests that some of the inhibitors interact with P-gps representing intrinsic pathways present across nematode populations with quite different drug sensitivities, while other inhibitors interact with P-gps of significance only to resistant nematodes, and hence most likely representing an acquired resistance mechanism. The study highlights the potential of the third generation of P-gp inhibitors for increasing the sensitivity of nematodes to anthelmintics.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 2 3%
Belgium 1 2%
Indonesia 1 2%
Unknown 55 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 19%
Student > Master 9 15%
Student > Bachelor 7 12%
Student > Ph. D. Student 6 10%
Student > Doctoral Student 4 7%
Other 15 25%
Unknown 7 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 16 27%
Veterinary Science and Veterinary Medicine 13 22%
Biochemistry, Genetics and Molecular Biology 7 12%
Medicine and Dentistry 3 5%
Psychology 2 3%
Other 7 12%
Unknown 11 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 May 2015.
All research outputs
#22,759,802
of 25,374,647 outputs
Outputs from Veterinary Parasitology
#2,775
of 3,451 outputs
Outputs of similar age
#239,313
of 279,161 outputs
Outputs of similar age from Veterinary Parasitology
#52
of 76 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,451 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 76 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.