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A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.
Zhang, Rou; Suwanarusk, Rossarin; Malleret, Benoit; Cooke, Brian M; Nosten, Francois; Lau, Yee-Ling; Dao, Ming; Lim, Chwee Teck; Renia, Laurent; Tan, Kevin Shyong Wei; Russell, Bruce.
Afiliação
  • Zhang R; Department of Microbiology, Yong Loo Lin School of Medicine.
  • Suwanarusk R; Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
  • Malleret B; Department of Microbiology, Yong Loo Lin School of Medicine Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
  • Cooke BM; Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
  • Nosten F; Shoklo Malaria Research Unit, Mae Sot, Tak Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.
  • Lau YL; Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur.
  • Dao M; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge.
  • Lim CT; Biomedical Engineering, National University of Singapore.
  • Renia L; Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
  • Tan KS; Department of Microbiology, Yong Loo Lin School of Medicine.
  • Russell B; Department of Microbiology, Yong Loo Lin School of Medicine.
J Infect Dis ; 213(1): 100-4, 2016 Jan 01.
Article em En | MEDLINE | ID: mdl-26136472
ABSTRACT
Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Plasmodium vivax / Compostos de Espiro / Malária Falciparum / Indóis / Antimaláricos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Plasmodium vivax / Compostos de Espiro / Malária Falciparum / Indóis / Antimaláricos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article