Morphologic Effects of Artemisinin in Plasmodium Falciparum

Yoshimasa MaenoInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Tetsuhiko ToyoshimaInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Hisashi FujiokaInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Yoshihiro ItoInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Steven R. MeshnickInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Achille BenakisInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Wilbur K. MilhousInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Masamichi AikawaInstitute of Pathology, Case Western Reserve University, Department of Epidemiology, School of Public Health, University of Michigan, Department of Pharmacology, University of Geneva, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Cleveland, Ohio, Switzerland

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Ultrastructural changes induced in Plasmodium falciparum by artemisinin were studied in vitro. Electron microscopic autoradiography was performed on infected erythrocytes that were exposed in vitro to 3H-dihydroartemisinin and 14C-artemisinin. These drugs consistently were located in food vacuoles and mitochondria. Two hours after administration, changes were observed in parasite mitochondria, rough endoplasmic reticulum, and nuclear envelope. At four hours, in addition to the earlier changes, nuclear membranes and, to a lesser extent, some plasma membranes formed myelin figures. In addition, there was a disappearance of ribosomes, and a destruction of food vacuole membranes. These changes may lead to the total disorganization of the parasites. Approximately 30% of the parasites manifested these alterations.

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