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The avermectins and the milbemycins are structurally related classes of 16-membered macrocyclic lactones (ML) that have a broad spectrum of activity. Most studies on the mode of action of ML have used the avermectin, ivermectin (IVM). IVM activates glutamate-gated chloride channels that contain alpha-type subunits, resulting in a hyperpolarization of the(More)
In vertebrates, the function of P-glycoprotein (PGP) is to protect against toxic compounds through active efflux of the toxin from target tissues. In clinical oncology, the overexpression of PGP confers drug resistance. The function(s) of PGP in nematode physiology or in conferring drug resistance is less understood. The objective of this study was to(More)
ABC systems are one of the largest described protein superfamilies. These systems have a domain organization that may contain 1 or more transmembrane domains (ABC_TM1F) and 1 or 2 ATP-binding domains (ABC_2). The functions (e.g., import, export and DNA repair) of these proteins distinguish the 3 classes of ABC systems. Mining and PCR-based cloning were used(More)
Isometamidium chloride (Samorin) is therapeutic in rainbow trout (Oncorhynchus mykiss) during preclinical and chronic cryptobiosis. However, the toxic mechanism of isometamidium on Cryptobia salmositica has not been elucidated. The objective of the present study was to examine the in vitro effects of isometamidium on C. salmositica. Under in vitro(More)
Treatment with ivermectin (IVM) is known to cause a loss of polymorphism at certain loci of the beta-tubulin, gamma-aminobutyric-acid-receptor, glutamate-gated-chloride-channel and ATP-binding-cassette (ABC) transporter genes of IVM-resistant Haemonchus contortus. The genetic variation of four ABC-transporter homologues from Onchocerca volvulus was(More)
Widespread use of ivermectin (IVM) as part of the Onchocerciasis Control Program (OCP) in West Africa could influence the evolution of the human filarial parasite Onchocerca volvulus. Use of IVM, in some areas for 15 years, may have restricted genetic diversity of O. volvulus, resembling effects attributed to a population bottleneck. Large population-based(More)
A series of compounds (triphenylmethanes, thiazines, xanthenes, benzidines, phenanthridiniums, napthalamines, and diamidines) were screened for in vitro toxicity against Cryptobia salmositica. Isometamidium chloride (Samorin) was cryptobiacidal at low concentrations and was examined for therapeutic and prophylactic activities against C. salmositica in(More)
The effect of ivermectin and moxidectin on the motility of Brugia malayi adults and microfilariae and on the fertility of B. malayi females was examined. Motility was reduced in adults after exposure to both drugs and worms were non-motile and dead within eight days. The motility of microfilariae was significantly reduced at all drug concentrations and(More)
An antigen-capture enzyme-linked immunosorbent assay (ELISA) was developed to detect and measure isometamidium chloride in the plasma of Oncorhynchus tshawytscha and O. mykiss. Isometamidium-ovalbumin conjugate and anti-isometamidium antibodies were used to coat polystyrene plates. The peroxidase saturation technique was used to optimize the coating antigen(More)
Whole cell lysates of pathogenic and nonpathogenic strains of Cryptobia salmositica were subjected to subcellular fractionation using differential and isopycnic centrifugation in sucrose. The glycolytic enzymes hexokinase, fructose-1,6-biphosphate aldolase, triosephosphate isomerase, glucosephosphate isomerase and glyceraldehyde-3-phosphate-dehydrogenase(More)