With the fastest 10% of samples being reported within 35 minutes (haematology) and 1 hour 5 minutes (biochemistry) of request, our study showed that delays can be attributable to laboratory TAT. Given the limited ability to further improve laboratory processes, the solutions to improving TAT need to come from a collaborative and integrated approach that includes strategies before samples reach the laboratory and downstream review of results.
Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabeled artemisinin and dihydroartemisinin have measured uptake in Plasmodium falciparum-infected erythrocytes. Uptake is much greater in infected than in uninfected erythrocytes, but the relative contributions of transport, binding, and metabolism to this process still await definition. In this study, we characterized mechanisms by which [14 C]artemisone is taken up into uninfected and P. falciparum-infected human erythrocytes in vitro. Radiolabeled artemisone rapidly enters uninfected erythrocytes without much exceeding extracellular concentrations. Unlabeled artemisone does not compete in this process. Radiolabeled artemisone is concentrated greatly by a time-and temperature-dependent mechanism in infected erythrocytes. This uptake is abrogated by unlabeled artemisone. In addition, the uptake of artemisone into three subcellular fractions, and its distribution into these fractions, is examined as a function of parasite maturation. These data are relevant to an understanding of the mechanisms of action of this important class of drugs.
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