Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Detalhes bibliográficos
Autor(a) principal: Orjuela-Sánchez, Pamela
Data de Publicação: 2013
Outros Autores: Ong, Peng Kai, Zanini, Graziela M., Melchior, Benoit, Martins, Yuri C., Meays, Diana, Frangos, John A., Carvalho, Leonardo J. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12685
Resumo: La Jolla Bioengineering Institute. San Diego, California, USA.
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spelling Orjuela-Sánchez, PamelaOng, Peng KaiZanini, Graziela M.Melchior, BenoitMartins, Yuri C.Meays, DianaFrangos, John A.Carvalho, Leonardo J. M.2016-02-02T16:06:26Z2016-02-02T16:06:26Z2013ORJUELA-SANCHEZ, Pamela et al. Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria. Antimicrobial Agents and Chemotherapy, v. 57, n. 11, p. 5462-5471, Nov. 2013.1098-6596https://www.arca.fiocruz.br/handle/icict/1268510.1128/AAC.00488-13engAmerican Society for MicrobiologyTransdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malariainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLa Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA.La Jolla Bioengineering Institute. San Diego, California, USA / Fundação Oswaldo cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Cerebral malaria (CM) is associated with low nitric oxide (NO) bioavailability, cerebrovascular constriction, occlusion, and hypoperfusion. Administration of exogenous NO partially prevents the neurological syndrome and associated vascular pathology in an experimental CM (ECM) mouse model. In this study, we evaluated the effects of transdermal glyceryl trinitrate in preventing ECM and, in combination with artemether, rescuing late-stage ECM mice from mortality. The glyceryl trinitrate and/or artemether effect on survival and clinical recovery was evaluated in C57BL/6 mice infected with P. berghei ANKA. NO synthase (NOS) expression in mouse brain was determined by Western blots. Mean arterial pressure (MAP) and pial arteriolar diameter were monitored using a tail-cuff blood pressure system and a cranial window preparation, respectively. Preventative administration of glyceryl trinitrate at 0.025 mg/h decreased ECM mortality from 67 to 11% and downregulated inducible NOS expression in the brain. When administered as adjunctive rescue therapy with artemether, glyceryl trinitrate increased survival from 47 to 79%. The adjunctive therapy caused a sustained reversal of pial arteriolar vasoconstriction in ECM mice, an effect not observed with artemether alone. Glyceryl trinitrate induced a 13% decrease in MAP in uninfected mice but did not further affect MAP in hypotensive ECM mice. Glyceryl trinitrate, when combined with artemether, was an effective adjunctive rescue treatment for ECM. This treatment ameliorated pial arteriolar vasospasm and did not significantly affect MAP. These results indicate that transdermal glyceryl trinitrate has potential to be considered as a candidate for adjunctive therapy for CM.Cerebral MalariaTherapyTransdermal Glyceryl TrinitrateMalária CerebralTerapiaNitroglicerinaTransdérmicoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12685/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALleonardo3_carvalho_etal_IOC_2013.pdfleonardo3_carvalho_etal_IOC_2013.pdfapplication/pdf1589877https://www.arca.fiocruz.br/bitstream/icict/12685/2/leonardo3_carvalho_etal_IOC_2013.pdf7e3c5586b089840035cd67a91ffe7045MD52TEXTleonardo3_carvalho_etal_IOC_2013.pdf.txtleonardo3_carvalho_etal_IOC_2013.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
title Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
spellingShingle Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
Orjuela-Sánchez, Pamela
Cerebral Malaria
Therapy
Transdermal Glyceryl Trinitrate
Malária Cerebral
Terapia
Nitroglicerina
Transdérmico
title_short Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
title_full Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
title_fullStr Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
title_full_unstemmed Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
title_sort Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria
author Orjuela-Sánchez, Pamela
author_facet Orjuela-Sánchez, Pamela
Ong, Peng Kai
Zanini, Graziela M.
Melchior, Benoit
Martins, Yuri C.
Meays, Diana
Frangos, John A.
Carvalho, Leonardo J. M.
author_role author
author2 Ong, Peng Kai
Zanini, Graziela M.
Melchior, Benoit
Martins, Yuri C.
Meays, Diana
Frangos, John A.
Carvalho, Leonardo J. M.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Orjuela-Sánchez, Pamela
Ong, Peng Kai
Zanini, Graziela M.
Melchior, Benoit
Martins, Yuri C.
Meays, Diana
Frangos, John A.
Carvalho, Leonardo J. M.
dc.subject.en.pt_BR.fl_str_mv Cerebral Malaria
Therapy
Transdermal Glyceryl Trinitrate
topic Cerebral Malaria
Therapy
Transdermal Glyceryl Trinitrate
Malária Cerebral
Terapia
Nitroglicerina
Transdérmico
dc.subject.decs.pt_BR.fl_str_mv Malária Cerebral
Terapia
Nitroglicerina
Transdérmico
description La Jolla Bioengineering Institute. San Diego, California, USA.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-02-02T16:06:26Z
dc.date.available.fl_str_mv 2016-02-02T16:06:26Z
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 ORJUELA-SANCHEZ, Pamela et al. Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria. Antimicrobial Agents and Chemotherapy, v. 57, n. 11, p. 5462-5471, Nov. 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12685
dc.identifier.issn.none.fl_str_mv 1098-6596
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.00488-13
identifier_str_mv ORJUELA-SANCHEZ, Pamela et al. Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria. Antimicrobial Agents and Chemotherapy, v. 57, n. 11, p. 5462-5471, Nov. 2013.
1098-6596
10.1128/AAC.00488-13
url https://www.arca.fiocruz.br/handle/icict/12685
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/12685/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/12685/2/leonardo3_carvalho_etal_IOC_2013.pdf
https://www.arca.fiocruz.br/bitstream/icict/12685/3/leonardo3_carvalho_etal_IOC_2013.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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