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Effect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro

Colebrook, A L; Jenkins, David; Jones, M K; Tatarczuch, L; Lightowlers, M W

Description

Surgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the...[Show more]

dc.contributor.authorColebrook, A L
dc.contributor.authorJenkins, David
dc.contributor.authorJones, M K
dc.contributor.authorTatarczuch, L
dc.contributor.authorLightowlers, M W
dc.date.accessioned2015-12-13T22:50:23Z
dc.date.available2015-12-13T22:50:23Z
dc.identifier.issn0031-1820
dc.identifier.urihttp://hdl.handle.net/1885/80752
dc.description.abstractSurgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the effectiveness of CsA as a scolicidal agent by testing the toxic effect of CsA at higher doses over various time-periods. Experiments were performed on activated and unactivated protoscoleces cultured in nutrient medium or sheep hydatid cyst fluid. All activated protoscoleces were killed following culture in 100 μg/ml of CsA for 3 days and 50 or 20 μg/ml for 5 days. The lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15 days in culture with 100 or 50 μg/ml of CsA. Pulse treatment of protoscoleces with 50, 20 or 10 μg/ml of CsA for 5 min or 72 h killed all parasites by day 10 and day 5 respectively. Untreated protoscoleces remained greater than 95% viable for the duration of experiments. Changes in protoscolex ultrastructure induced by treatment with 10 μg/ml of CsA over 10 days in in vitro culture was assessed by TEM. Protoscolex alterations observed in treated parasites included an increase in cellular vacuolization, swelling of mitochondria, rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of the extracellular matrix and an increase in lipid globules. The untreated protoscoleces, by comparison, had few changes during the 10-day culture period with the exception of large amounts of extracellular glycogen observed in the protoscoleces at culture days 7 and 10. From these results, CsA is clearly an effective scolicidal agent in vitro that may have potential application as a new therapeutic agent in the treatment of human hydatid disease.
dc.publisherCambridge University Press
dc.sourceParasitology
dc.subjectKeywords: cyclosporin A; glycogen; lipid; article; cell culture; cell damage; cell survival; cell swelling; cell ultrastructure; cell vacuole; controlled study; drug efficacy; drug pulse therapy; echinococcosis; Echinococcus granulosus; extracellular matrix; hydati Cyclosporin A; Echinococcus granulosus; Hydatid; Scolicidal agent
dc.titleEffect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume129
dc.date.issued2004
local.identifier.absfor070708 - Veterinary Parasitology
local.identifier.ariespublicationMigratedxPub9017
local.type.statusPublished Version
local.contributor.affiliationColebrook, A L, University of Melbourne
local.contributor.affiliationJenkins, David, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationJones, M K, University of Melbourne
local.contributor.affiliationTatarczuch, L, University of Melbourne
local.contributor.affiliationLightowlers, M W, University of Melbourne
local.bibliographicCitation.startpage497
local.bibliographicCitation.lastpage504
local.identifier.doi10.1017/S0031182004005773
dc.date.updated2016-02-24T09:49:42Z
local.identifier.scopusID2-s2.0-5644269099
CollectionsANU Research Publications

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