Tropical and Subtropical Parasitic Diseases: Targets for a New Approach to Virtual Screening.

Computational techniques are widely used to reduce costs associated with new drug development with the ability to bind a specific molecular target. These studies need a Brookhaven protein data bank structure sample of the enzyme interaction with an inhibitor of adequate size. In this context, a new computational methodology is postulated to be used when there are no published samples fulfilling this requirements. In this study, 7 compounds, which showed anti-T. cruzi, L. donovani and L. infantum properties, and proved to be inhibitors of their Fe-SOD enzymes, have been theoretically evaluated against related parasites Fe-SOD enzymes, which have been proposed as targets for antiparasitic drugs. This methodology may be applied to similar cases and also to generate starting structures to be used with different CADD methods.

Selenoprotein P-expression, functions, and roles in mammals.

Selenoprotein P (Sepp1) is a secreted protein that is made up of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. Sepp1 isoforms of varying lengths occur but quantitation of them has not been achieved. Hepatic synthesis of Sepp1 affects whole-body selenium content and the liver is the source of most plasma Sepp1. ApoER2, a member of the lipoprotein receptor family, binds Sepp1 and facilitates its uptake into the testis and retention of its selenium by the brain. Megalin, another lipoprotein receptor, facilitates uptake of filtered Sepp1 into proximal tubule cells of the kidney. Thus, Sepp1 serves in homeostasis and distribution of selenium. Mice with deletion of Sepp1 suffer greater morbidity and mortality from infection with Trypanosoma congolense than do wild-type mice. Mice that express only the N-terminal domain of Sepp1 have the same severity of illness as wild-type mice, indicating that the protective function of Sepp1 against the infection resides in the N-terminal (redox) domain. Thus, Sepp1 has several functions. In addition, plasma Sepp1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.

The effect of zinc supplementation on parasitic reinfestation of Guatemalan schoolchildren.

One hundred thirty children (65-95 mo old) from a low-socioeconomic neighborhood of Guatemala City participated in a randomized, double-blind, controlled trial of zinc supplementation. One group received 10 mg Zn/d (n = 65) and the other group received a placebo (n = 65); 90 +/- 9.2 doses were given over 120-150 d. Stools were examined for prevalence and intensity of helminths and prevalence of protozoa at the beginning and end of the study. The initial prevalence was 42% for helminths and 18% for protozoa, with no differences between groups. Mebendazole was administered to all children, and protozoal infections were treated specifically at the beginning of the study. The reinfection rates were 17% (11 of 65) for helminths and 12.3% (8 of 65) for protozoa in the zinc group and 15% (10 of 65) and 10.7% (7 of 65), respectively, in the placebo group (P > 0.05). Analysis by specific parasites revealed no treatment effect. We conclude that neither plasma or hair zinc status nor oral zinc supplementation had an effect on parasite status in children.