These factors are presumably made in the body but are absent from media because they are yet unknown; even if known, some factors may be labile in culture or too costly for routine Perifosine FDA addition. Finally, because most of the small nutritive solutes in Table 1 are inexpensive and not overtly toxic to cell cultures, it may have been reasonable to include them at higher than necessary levels in standard media.Table 1Concentrations of nutrients in RPMI 1640 and human plasma. Human plasma values represent measured means from indicated studies. Where available, data is from fasting donors without vitamin supplementation. Nutrients listed as ��essential�� …

How does provision of nutrients at supraphysiological concentrations affect malaria parasite cultivation and our understanding of parasite physiology? The answer depends, in part, on knowing which nutrients are essential for parasite cultivation, as was examined initially by [7] and also tallied in Table 1. Interestingly, subsequent studies found that some of these essential nutrients can be removed without detriment to parasite growth [9, our unpublished studies]. This might reflect either differences in experimental protocols or changes in parasite phenotypes over the intervening decades of in vitro propagation, as discussed further below.To explore possible effects of high nutrients concentrations, we recently compared parasite growth rates in the standard synthetic formulation (RPMI 1640 medium supplemented with hypoxanthine and a lipid source) to that in pooled human serum from healthy American donors.

We found that cultures of common laboratory parasite clones expanded at 60�C90% faster rates in the synthetic medium than in pooled serum [10]. One explanation for preferential growth in RPMI 1640 is that these clones have been cultivated in this medium for many years and may therefore have adapted to faster growth in synthetic formulations. Another possibility is that use of media with supraphysiological nutrient concentrations may produce artificially high parasite expansion rates. This may seem desirable to experimentalists who demand large amounts of parasite material for their research, but it also confuses our understanding of in vivo parasite behavior.

Because a primary motivation of basic malaria research is to identify parasite targets for therapeutic intervention, another important question is whether in vitro studies using RPMI 1640 can faithfully determine which parasite activities Cilengitide are essential for in vivo survival and growth. A key target that illustrates this problem is the plasmodial surface anion channel (PSAC). This ion channel localizes to the host erythrocyte membrane and is conserved in malaria parasites that infect rodents, birds, and primates [11, 12]. Similar channels are absent from other parasites and mammals [13, 14].