Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/36881 |
Resumo: | 2020-11-06 |
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Clemmer, L.Martins, Y. C.Zanini, G. M.Frangos, J. A.Carvalho, L. J. M.2019-11-06T12:20:31Z2019-11-06T12:20:31Z2011CLEMMER, L. et al. Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain. Antimicrobial Agents and Chemotherapy, v. 55, n. 4, p. 1383-1390, Apr. 2011.0066-4804https://www.arca.fiocruz.br/handle/icict/3688110.1128/AAC.01277-101098-6596engAmerican Society for MicrobiologyArtemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the braininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2020-11-06La Jolla Bioengineering Institute. San Diego, CA, USA.La Jolla Bioengineering Institute. San Diego, CA, USA.La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. San Diego, CA, USA.La Jolla Bioengineering Institute. San Diego, CA, USA.The murine model of cerebral malaria (ECM) caused by Plasmodium berghei ANKA (PbA) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human CM therapeutics. However, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. A first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ECM. We evaluated the efficacy of artemisinin, artemether, artesunate, and quinine given intraperitoneally once a day, and combinations with mefloquine, in suppressing PbA infection in mice with moderate parasitemia. Artemether, artesunate, and quinine were then evaluated for efficacy in rescuing PbA-infected mice with ECM, strictly defined by using objective criteria based on the presentation of clinical signs of neurological involvement, degree of hypothermia, and performance in a set of six motor behavior tests. Artemether at 25 mg/kg presented the fastest parasite killing ability in 24 h and fully avoided recrudescence in a 5-day treatment protocol. Artemether and artesunate were equally effective in rescuing mice with late-stage ECM (46 and 43% survival, respectively), whereas quinine had a poor performance (12.5% survival). Artemether caused a marked decrease in brain leukocyte accumulation 24 h after the first dose. In conclusion, artemether and artesunate are effective in rescuing mice with late-stage ECM and decrease brain inflammation. In addition, the described protocols for more strict clinical evaluation and for rescue treatment provide a framework for studies of CM adjunctive therapies using this mouse model.Cerebral malariaArtemetherArtesunateinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/36881/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALve_Clemmer_L_etal_INI_2011.pdfve_Clemmer_L_etal_INI_2011.pdfapplication/pdf1826723https://www.arca.fiocruz.br/bitstream/icict/36881/2/ve_Clemmer_L_etal_INI_2011.pdf29deb7d48ed37f68727cd72c0cbde0fdMD52TEXTve_Clemmer_L_etal_INI_2011.pdf.txtve_Clemmer_L_etal_INI_2011.pdf.txtExtracted texttext/plain46736https://www.arca.fiocruz.br/bitstream/icict/36881/3/ve_Clemmer_L_etal_INI_2011.pdf.txt3b3aee5598555317a91cf1b6f09113e8MD53icict/368812021-02-10 19:38:19.134oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-02-10T22:38:19Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
title |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
spellingShingle |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain Clemmer, L. Cerebral malaria Artemether Artesunate |
title_short |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
title_full |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
title_fullStr |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
title_full_unstemmed |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
title_sort |
Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain |
author |
Clemmer, L. |
author_facet |
Clemmer, L. Martins, Y. C. Zanini, G. M. Frangos, J. A. Carvalho, L. J. M. |
author_role |
author |
author2 |
Martins, Y. C. Zanini, G. M. Frangos, J. A. Carvalho, L. J. M. |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Clemmer, L. Martins, Y. C. Zanini, G. M. Frangos, J. A. Carvalho, L. J. M. |
dc.subject.en.pt_BR.fl_str_mv |
Cerebral malaria Artemether Artesunate |
topic |
Cerebral malaria Artemether Artesunate |
description |
2020-11-06 |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011 |
dc.date.accessioned.fl_str_mv |
2019-11-06T12:20:31Z |
dc.date.available.fl_str_mv |
2019-11-06T12:20:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
CLEMMER, L. et al. Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain. Antimicrobial Agents and Chemotherapy, v. 55, n. 4, p. 1383-1390, Apr. 2011. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/36881 |
dc.identifier.issn.pt_BR.fl_str_mv |
0066-4804 |
dc.identifier.doi.none.fl_str_mv |
10.1128/AAC.01277-10 |
dc.identifier.eissn.none.fl_str_mv |
1098-6596 |
identifier_str_mv |
CLEMMER, L. et al. Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain. Antimicrobial Agents and Chemotherapy, v. 55, n. 4, p. 1383-1390, Apr. 2011. 0066-4804 10.1128/AAC.01277-10 1098-6596 |
url |
https://www.arca.fiocruz.br/handle/icict/36881 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
American Society for Microbiology |
publisher.none.fl_str_mv |
American Society for Microbiology |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Fundação Oswaldo Cruz (FIOCRUZ) |
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FIOCRUZ |
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