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A method was developed, using a 0.25% agar matrix, to incorporate varying concentrations of linoleate and correlate cercarial transformation and eicosanoid production in vitro. Schistosoma mansoni cercariae were stimulated to penetrate over a wide range of linoleate concentrations; however, the transformation process occurred over a narrow range. Approximately 25% of cercariae penetrated the agar matrix in controls (no linoleate) and 0.003 mM linoleate. Penetration rates rose gradually until, at linoleate concentrations of 0.3 mM or greater, penetration approached 100%. The transformation process did not begin until the linoleate concentration in agar reached 2.0 mM (3.8%), and achieved maximum (91%) at 3.0 mM. A concentration of 9.0 mM linoleate gave 100% penetration and transformation rates, but penetration was superficial and cercariae were not viable. Cercarial eicosanoid production was concentration-related. Various eicosanoid classes were associated with cercarial penetration and transformation. Penetration rates were correlated with increasing leukotriene (LT, R = 0.9541) and hydroxyeicosatetraenoic acid (HETE, R = 0.8363) levels, while transformation rates correlated with increasing prostaglandin levels (R = 0.9225). Correlating eicosanoid production with penetration and transformation rates strengthened the hypothesis that successful cercarial penetration and transformation are dependent on both skin essential fatty acid levels and resulting cercarial eicosanoid production.

Abstract. N, N-diethyl-m-toluamide (DEET) is a common and fairly safe active ingredient in many insect repellents. Our recent studies showed that when applied to the skin, DEET has a potent anti-parasitic effect against Schistosoma mansoni. However, the beneficial effects of DEET lasted only for a few minutes, presumably due to its rapid absorption through the skin. In this study, we evaluated different carrier formulations that prolong the activity of DEET in the skin. Among the various formulations analyzed, DEET incorporated into liposomes (LIPODEET) appeared to prolong the activity of DEET for more than 48 hr after a single application. Furthermore, LIPODEET was found to be minimally absorbed through the skin and loss due to washing off was limited. These findings thus suggest LIPODEET is a safe and long-acting formulation of DEET that is quite effective against schistosomiasis. N, N-diethyl-m-toluamide (DEET) is a relative safe, broad spectrum insect repellent that is used extensively against both human and animal pests worldwide.1,2 Although chemical research has produced a number of DEET analogs and other related compounds, none have consistently enjoyed as widespread use as DEET. 3 Even though DEET is highly effective, the duration of action of DEET appears to be short lived. Once applied to the skin, DEET has an insect repellent activity ranging from 30 min to 6 hr, 4,5 whereas its antiparasitic effect is even shorter.6 To obtain a longer duration of activity, there is a need to reapply DEET, often repeatedly with concentrations as high as 70%. 5 This is due to the fact that DEET is absorbed through the skin relatively quickly and is thus rapidly cleared from the skin.7,8 Therefore, any agent that retards the absorption of DEET through the skin will potentially prolong the repellency, or in this case the anti-parasitic action of DEET in the superficial layers of the skin. Furthermore, a reduced absorption will potentially decrease any systemic toxicity associated with DEET. We therefore tested various formulations that prolonged the effect of DEET against schistosomiasis in the skin. MATERIALS AND METHODSRadio-labeling of snails and collection of radiolabeled cercariae. Biomphalaria glabrata species of snails infected with S. mansoni were obtained from Dr. Fred Lewis (Biomedical Research Institute, Rockville, MD). The infected snails were maintained under controlled conditions of light at 85-87ЊF. Snails were checked individually for the presence of the parasite by observing the emergence of cercariae from them by exposing to a bright light source for 1 hr. Once determining that the snails are releasing cercariae, they were radiolabeled with 35 S-methionine as described previously. 9 Snails suspended in distilled water (0. 5 ml/snail) were exposed to 35 S-methionine (Tran 35 S-label, specific activity ϭ 1,047 Ci/mmol, catalog # 51006; ICN Pharmaceuticals, Inc., Irvine, CA) at a concentration of 20 Ci/ml at 37ЊC in the dark. After 16 hr of exposure to the radioisotope, the snails were rinsed, moved to ...