SUMMARY
The apicomplexan parasite Plasmodium falciparum causes malignant malaria. The mechanism of parasite egress from infected erythrocytes that disseminate parasites in the host at the end of each asexual cycle is unknown [1]. Two new stages of the egress program are revealed: 1) swelling of the parasitophorus vacuole accompanied by shrinkage of the erythrocyte compartment and 2) poration of the host cell membrane seconds before erythrocyte rupture due to egress. Egress was inhibited in dehydrated cells from patients with sickle cell disease, in accord with experimental dehydration of normal cells [2], suggesting that vacuole swelling involves intake of water from the erythrocyte compartment. Erythrocyte membrane poration occurs in relaxed cells, thus excluding involvement of osmotic pressure in this process. Poration does not depend on cysteine protease activity because protease inhibition blocks egress [3–5] but not poration, and poration is required for the parasite cycle because the membrane sealant P1107 interferes with egress. We suggest the following egress program: parasites initiate water influx into the vacuole from the erythrocyte cytosol to expand the vacuole for parasite separation and vacuole rupture upon its critical swelling. Separated parasites leave the erythrocyte by breaching its membrane, weakened by putative digestion of erythrocyte cytoskeleton [3–5] and membrane poration.
Abstract-Diazinon and chlorpyrifos are two organophosphorous pesticides widely found in municipal, agricultural, and urban storm water discharges. Because they are often found concurrently, their relationship with respect to joint toxicity is of interest, particularly in regard to interpreting the results of toxicity identification evaluations (TIEs) that point to metabolically activated organophosphorous pesticide(s) as causes of toxicity. Joint toxicity was evaluated using static tests that incorporated 48-to 96-h exposure periods using laboratory water, natural water, and urban storm water. Chemical concentrations were verified analytically. Mortalities were measured at 24-h intervals and joint toxicity was calculated on the basis of toxic units (TUs) for every time interval (1 TU ϭ median lethal concentration [LC50]). Forty-eight-hour LC50 values ranged between 0.26 and 0.58 g/L for diazinon and between 0.058 and 0.079 g/L for chlorpyrifos. The 96-h values were approximately 65% of their respective 48-h values. Under the assumption of strict additivity, the LC50 (as TUs) of the mixture should be the sum of the respective fractions of diazinon and chlorpyrifos and should total unity. These values were calculated for a total of 12 time intervals. The TUs associated with the mixtures in laboratory water ranged between 0.89 and 1.46, with an average of 1.13. The values for the natural and storm water samples were similar to those obtained with laboratory water. These data confirmed the results of TIEs that suggested that diazinon and chlorpyrifos exhibit additive toxicity when present together.
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