Eugene A. Averkin's research while affiliated with Oregon State University and other places

Methyl-5(6)-phenylsulfinyl-2-benzimidazole carbamate (Oxfendazole) (Syntex Research, Syntex (U.S.A.), Inc., Palo Alto, Calif. 94304) a new potent anthelminthic, was tested at nine dosage levels against gastrointestinal and lungworm helminths in naturally infected lambs. A modified least significance difference test (P= 0.05) was used on log transformed data to test for differences in the average efficacies of the various dose groups as the primary basis for selecting the optimum field dosage level. Five (5.0) mg/kg provided high (⩾90%) efficacy against parasitic stages of the following helminths: Chabertia ovina, Cooperia spp., Dictyocaulus filaria, Haemonchus contortus, Moniezia sp., Nematodirus spp., Oesophagostomum venulosum, Ostertagia spp., Trichostrongylus spp. and Trichuris ovis.Limited numbers of Bunostomum trigonocephalum and Capillaria spp. precluded definitive conclusions regarding efficacy against these parasites. Efficacy against Strongyloides papillosus was erratic at all dosage levels. Toxicity attributable to Oxfendazole was not observed.

Oxfendazole was administered to pregnant cows at 2.5 and 5 mg/kg body weight to determine the anthelmintic efficacy against naturally acquired larvae which became inhibited at the early 4th stage. The experimental design included three groups of orally-treated cows, that is, 10 placebo treated control cows, 11 cows treated with 2.5 mg/kg of oxfendazole and 10 cows treated with 5.0 mg/kg of oxfendazole. Oxfendazole at 2.5 mg/kg body weight was 82 and 94% effective against EL-4 and adult O. ostertagi, respectively. At 5 mg/kg, Oxfendazole was 95 and 99% effective against EL-4 And adult O. ostertagi, respectively. The results suggested the use of a field dosage level of 5 mg/kg body weight oxfendazole where inhibited larvae may be encountered.

1. Human hepatic "acid" beta-galactosidase preparations, which had been purified approximately 250-fold, were examined for activities toward 4-methylumbelliferyl beta-galactosylceramide, lactosylceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosyl-glucosylceramide(GM1-ganglioside) and galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside). 2. The enzyme was active toward the synthetic substrate, GM1-ganglioside and asialo GM1-ganglioside but was inactive toward galactosylceramide. Under our assay conditions, optimized for lactosylceramidase II, the preparations were as active toward lactosylceramide as toward GM1-ganglioside or its asialo derivative. The apparent Km values for the three natural substrates were similar. When determined by the assay system of Wehger, D.A., Sattler, M., Clark, C. and McKelvey, H. (1974) Clin. Chim Acta 56, 199-206, lactosylceramide-cleaving activity was 0.2% of that determined by our assay system. This confirmed our previous suggestion that the Wenger assay system determines exclusively the activity of lactosylceramidase I, which is probably identical with galactosylceramide beta-galactosidase. 3. Crude sodium taurocholate was far more effective than pure taurocholate in stimulating hydrolysis of the three glycosphingolipids by the beta-galactosidase. However, crude taurocholate could largely be replaced by smaller amounts of sodium taurodeoxycholate, suggesting that the unique activating capacity of the crude taurocholate might be due to taurodeoxycholate present as the major impurity. 4. Cl- was generally stimulatory for hydrolysis of the natural glycosphingolipids by our enzyme preparation. Effects of additional oleic acid and Triton X-100 were generally minor in either direction. 5. When the enzyme preparation was diluted with water, activity toward the synthetic substrate declined rapidly while those toward the natural substrates were essentially stable. Activity toward the synthetic substrate remained much more stable when the enzyme was diluted with 0.1 M sodium citrate/phosphate buffer, pH 5.0. 6. These observations provide insight into the complex relationship among the human hepatic beta-galactosidases.