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Schistosoma mansoni: salicylanilides as topical prophylactic against cercarial penetration of mice
Authors:R E Miller  W A Reid
Affiliation:1. School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, Malaysia;2. Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Subang Jaya, Selangor, Malaysia;3. Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia;4. Colloids and Interface Science Centre (CISC), Centre of Excellence (COE), RRIM Sungai Buloh Research Station, Malaysian Rubber Board (MRB), Sungai Buloh, Selangor, Malaysia;5. ULTI Pharmaceuticals, Hamilton, New Zealand;6. Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia;1. Department of Radiology, Ospedali Riuniti, Ancona, Italy;2. Department of Radiology, Azienda Ospedaliero Universitaria Ferrara, Ospedale Sant’ Anna Cona, Ferrara, Italy;3. Department of Diagnostic and Interventional Neuroradiology, Foch Hospital, Suresnes, France;4. Department of Cardiology, Foch Hospital, Suresnes, France;5. Division of Neurology, Stroke Center, Foch Hospital, University Versailles Saint-Quentin en Yvelines, Suresnes, France;1. Department of Food Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan;2. Quality Assurance Section, Gemfont Corporation, Taipei 10062, Taiwan;3. Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan;4. Department of Medical Imaging and Radiological Sciences, and Center for Infectious Disease and Cancer Research, and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;5. Department of Gastroenterology, Palo Alto Medical Foundation, Mountain View, CA 94040, USA;6. Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;7. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;1. Vascular Anomalies & Malformations Program (VAMP) at the Division of Vascular Surgery, Department of Surgery, Rutgers Robert Wood Johnson Medical School, Robert Wood Johnson University Hospital, Bristol-Myers Squibb Children''s Hospital, New Brunswick, NJ;2. Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
Abstract:Salicylanilide and 37 of its analogs were applied topically to mice as candidate chemoprophylactic agents against Schistosoma mansoni cercarial penetration. The compounds were solubilized in absolute methanol, dimethyl sulfoxide, or isopropanol at concentrations not exceeding 1.25% W/V. The tails of the mice of each experimental group were treated by immersion for 5 min in the test compound solution or in the vehicle. The treated tails of 5 mice from each group were washed for 30 min in flowing tap water 3-4 hr after compound application. Tails of all mice were then exposed to approximately 100 cercariae by tail immersion for 1 hr, 24 hr after treatment. The portal veins were perfused 49 days after exposure and worm burdens were determined. The protective capacity of each compound was calculated by comparing the reduction of the mean worm burdens of the compound treated mice to the worm burdens of those treated with only the vehicle and expressing the resulting value as percentage protection. Of the 38 compounds tested, 20 provided 98% or better protection if the treated tails were not washed before exposure to cercariae. Of these 20 active compounds, 16 provided 98% or better protection from infection by S. mansoni cercariae even after the mouse tails were subjected to the 30 min wash.
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