Tu1261 Short Term Relief of Rectal Pain With Diazepam Cream: A Novel New Approach

Abstract

Toxoplasmsis is one of the most common foodborne gastrointestinal and congenital illnesses in United States. Two billion people globally are estimated to be infected with Toxoplasma with severe and unknown consequences. Safe and effective preventive or therapeuticmeasures are needed to impact the disease. Diclazuril, an herbicide related compound, specifically targets chlorophyll complex in the organisms which is not present in man and animals. We hypothesized that Diclazuril to be safe and effective against gastrointestinal Toxoplasmosis in our murine pregnancy model. Methods: Programmed pregnant mice were infected with escalating doses of organisms from Type II strain (most common strain from man in U.S) and treated with varied doses of Diclazuril, or sham. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of experiment. Results: Infected dams developed anemia (Controls vs infected-dams p<0.05) and ascities with moderate to severe GI related complications in organisms' dose dependent manner. Diclazuril dose dependently protected dams from ascities and anemia. Infected dams showed splenomegaly, with massive infiltration of epithelioid cells and loss of germinal structure with significant increases in weight and length of splenic tissues and improved in dams treated with Diclazuril. Infected dams exhibited moderate (score 0 to 4 scale=3+0.02) to severe hepatitis (3.5+0.01) with influx of inflammatory and plasma cells, dysplastic and necrotized hepatocytes in organisms' dose escalatingmanner. Diclazuril treatment dose dependently protected dams from hepatitis, also in organisms' dose related manner (respectively infected-treated versus infected-shamtreated controls P<0.001, P<0.01 and P<0.05). Colonic tissues significantly shortened in length with infiltration of lymphocytes, and macrophages in mucosal structure which improved in Diclazuril treated dams. Diclazuril protected fetuses but had no effect on abdominal pain related behavior. Conclusions: Diclazuril treatment dose dependently protected dams from mild to moderate gastrointestinal complications and their fetuses against adverse effects of Toxoplasmosis. This is the first report describing of Diclazuril safety and efficacy in pregnancy and gastrointestinal Toxoplasmosis. Supported by NIH-NIDCR (HO) and KSTC (TT).