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BACKGROUND Schistosomiasis--infection with helminth parasites in the genus Schistosoma, including S. mansoni--is a widespread, devastating tropical disease affecting more than 200 million people. No vaccine is available, and praziquantel, the only drug extensively utilized, is currently administered more than 100 million people yearly. Because praziquantel(More)
Despite the widespread use of chemotherapy and other control strategies over the past 50years, transmission rates for schistosomiasis have changed little. Regardless of the approach used, future control efforts will require a more complete understanding of fundamental parasite biology. Schistosomes undergo complex development involving an alteration of(More)
Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-kappaB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands(More)
Studies of mutations affecting lifespan in Caenorhabditis elegans show that mitochondrial generation of reactive oxygen species (ROS) plays a major causative role in organismal aging. Here, we describe a novel mechanism for regulating mitochondrial ROS production and lifespan in C. elegans: progressive mitochondrial protein modification by the(More)
Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends almost exclusively on praziquantel. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a quantitative high-throughput screen, were shown(More)
Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic portal circulation of their human host up to 30 years without being eliminated by the host immune attack. Production of an antioxidant "firewall," which would neutralize the oxidative assault generated by host immune defenses, is one proposed survival mechanism of the(More)
Schistosomiasis is a parasitic disease affecting over 200 million people currently treated with one drug, praziquantel. A possible drug target is the seleno-protein thioredoxin-glutathione reductase (TGR), a key enzyme in the pathway of the parasite for detoxification of reactive oxygen species. The enzyme is a unique fusion of a glutaredoxin domain with a(More)
Peroxiredoxins are a large family of peroxidases that have important antioxidant and cell signaling functions. Genes encoding two novel 2-cysteine peroxiredoxin proteins were identified in the expressed sequence tag data base of the helminth parasite Schistosoma mansoni, a causative agent of schistosomiasis. The recombinant proteins showed peroxidase(More)
The efficacy of Ferulsinaic acid (FA) to modulate the antioxidant enzymes and to reduce oxidative stress induced-diabetic nephropathy (DN) was studied. Rats were fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin; 5, 50 and(More)
OBJECTIVE Establishing Caenorhabditis elegans as a model for glucose toxicity-mediated life span reduction. RESEARCH DESIGN AND METHODS C. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products(More)