182 resultados para haemonchus placei


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The production of sheep, both in Brazil and worldwide, has shown significant growth in the last years but still has some obstacles to its development, among them are the low indexes caused by parasites, with emphasis on haemoncose. Among the control methods used in the fight against worms are the anthelmintics, and one of the most active principles in this traditional treatment is ivermectin. While being the tool of choice in the treatment of parasitic diseases, improper use of the same led to the emergence of resistant isolates, not only to ivermectin, as several other active principles of antiparasitic drugs

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Pós-graduação em Ciência Animal - FMVA

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Pós-graduação em Medicina Veterinária - FCAV

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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[ES] Los problemas asociados al uso de antihelmínticos en el control de las nematodosis gastrointestinales, tales como la presencia de residuos en alimentos de origen animal o la aparición de resistencias han estimulado el estudio del control inmunológico de numerosas parasitosis.

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Eliminadas las páginas en blanco

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Monepantel is the first drug of a new family of anthelmintics, the amino acetonitrile derivatives (AAD), presently used to treat ruminants infected with gastrointestinal nematodes such as Haemonchus contortus. Monepantel shows an excellent tolerability in mammals and is active against multidrug-resistant parasites, indicating that its molecular target is absent or inaccessible in the host and is different from those of the classic anthelmintics. Genetic approaches with mutant nematodes have suggested acetylcholine receptors of the DEG-3 subfamily as the targets of AADs, an enigmatic clade of ligand-gated ion channels that is specific to nematodes and does not occur in mammals. Here we demonstrate direct interaction of monepantel, its major active metabolite monepantel sulfone, and other AADs with potential targets of the DEG-3 subfamily of acetylcholine receptors. H. contortus DEG-3/DES-2 receptors were functionally expressed in Xenopus laevis oocytes and were found to be preferentially activated by choline, to permeate monovalent cations, and to a smaller extent, calcium ions. Although monepantel and monepantel sulfone did not activate the channels by themselves, they substantially enhanced the late currents after activation of the channels with choline, indicating that these AADs are type II positive allosteric modulators of H. contortus DEG-3/DES-2 channels. It is noteworthy that the R-enantiomer of monepantel, which is inactive as an anthelmintic, inhibited the late currents after stimulation of H. contortus DEG-3/DES-2 receptors with choline. In summary, we present the first direct evidence for interaction of AADs with DEG-3-type acetylcholine receptors and discuss these findings in the context of anthelmintic action of AADs.