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An investigational drug (2-picoline, 6-amino-4-nitro-, 1-oxide) was evaluated to characterize the anti-coccidial spectrum of the compound. Two concentrations of the drug (125 and 250 ppm) were evaluated for bioactivity; weight gain, survival, dropping, and lesion scores were the response variables utilized to ascertain activity. The activities of the picoline derivative were compared with monensin, maduramicin, and a narasin/nicarbazin (1:1) combination. The investigational drug had significant activity against Eimeria tenella and Eimeria necatrix, and the 250-ppm level was significantly more active than 125 ppm. At 250 ppm, the E. tenella activity of the picoline derivative was comparable to both monensin (120 ppm) and the 50-ppm narasin/nicarbazin combination, significantly less effective than maduramicin (6 ppm), and significantly more efficacious than 30 ppm narasin/nicarbazin. At the same level (250 ppm), the picoline derivative had significantly less E. necatrix activity than monensin (120 ppm), maduramicin (6 ppm), and narasin/nicarbazin (50 ppm), and significantly greater activity than 30 ppm narasin/nicarbazin. At best, only extremely weak Eimeria acervulina, Eimeria brunetti, and Eimeria maxima activities were noted with the investigational drug; higher concentrations of the picoline derivative may achieve greater anti-coccidial activity against these species. The efficacy of narasin/nicarbazin compared favorably with monensin and maduramicin; the 50-ppm level of the combination appeared significantly more efficacious than 30-ppm.

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Sporozoites of Eimeria tenella, an important pathogen of poultry, were killed in vitro in a time- and concentration-dependent manner by exposure to diluted concentrations of normal human milk. Sodium cholate (bile salt stimulator) potentiated the anti-coccidial activity. The anti-coccidial activity was not found in the milk of lower mammals (cow, sheep, goat, dog). The component in human milk showing the activity was initially hypothesized to be a bile salt-stimulated lipase. However, testing of purified lipase (with or without sodium cholate) indicated no anti-coccidial activity. Consequently, we theorize that the active component may be a free fatty acid.

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The activities of five anticoccidials were compared against Eimeria species in/of chickens, in controlled in vivo and in vitro laboratory studies. Two more recent and potent market entries (maduramicin and halofuginone) were compared with three older polyether antibiotic anticoccidials (monensin, lasalocid and salinomycin). Halofuginone, lasalocid, maduramicin, monensin and salinomycin were evaluated at 3, 125, 5, 120 and 66 ppm, respectively, of active drug in the diets. At these levels, all five drugs demonstrated significant activity against Eimeria tenella, E. maxima, E. necatrix, E. brunetti and E. acervulina (in vivo). Monensin was least effective against E. tenella, and one of the lesser efficacious drugs against E. necatrix, maduramicin, was least effective against E. maxima. In studies of single Eimeria species infections, comparable weight gains were noted for the drugs. In the mixed Eimeria species infections, however, birds treated with maduramicin had significantly higher weight gains than did birds medicated with monensin. Unlike in vivo potencies, titration in vitro indicated that monensin was most potent (active at 10(-6) mcg ml-1), and maduramicin and lasalocid least potent (inactive at less than or equal to 10(-3) mcg ml-1).

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Alborixin, a polyether antibiotic with ionophore properties, was evaluated to determine the effect of the drug on weight gain of chickens and to define the anticoccidial spectrum of activity. The 50-ppm concentration in the diet was identified as the maximum level that did not significantly reduce weight gain beyond that of monensin (standard drug); consequently, the drug was evaluated for anticoccidial activity at this dilution. At the 50-ppm level, alborixin demonstrated broad-spectrum anticoccidial activity; however, the drug lacked Eimeria necatrix efficacy. Monensin and maduramycin were significantly more efficacious than alborixin as a treatment for several species of Eimeria. Higher concentrations of alborixin (greater than 50 ppm) appear essential to achieve broad-spectrum and comparable anticoccidial activity, however, these levels substantially depressed weight gains. Alborixin is similar to many other polyethers in that weight gains are adversely affected at drug levels essential for solid broad-spectrum anticoccidial activity.

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Thirty dogs (20 treated, 10 controls) with naturally-acquired generalized demodicosis were utilized to evaluate the bio-activity and safety of a liquid concentrate formulation of amitraz, with or without the addition of a nonionic detergent. The detergent was added to the treatment mixture to enhance wetting and thereby reduce the number of treatments required to return diseased animals to a normal state. Three--six miticide treatments were topically applied to dogs at 14-day intervals, at a concentration of 250 parts per million active drug. The liquid concentrate with or without detergent, was equally effective and safe as a dermatotherapy for demodicosis; addition of the nonionic detergent grossly improved the wetting characteristics of the treatment mixture; however, it did not alter the biological activity or the safety of the therapy.

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Fifty-two dogs naturally parasitized with Demodex canis and having the generalized form of the disease were utilized to evaluate the efficacy and safety of single or multiple topical treatments with a liquid concentrate formulation of amitraz. Ten dogs (5 treated, 5 controls) were utilized to evaluate a single treatment. A single topical treatment with the miticide did not significantly reduce the incidence of dogs with mites, however, significant clinical improvement resulted. Side-effects were not observed after treatment. Forty-two dogs (26 treated, 16 controls) were utilized to evaluate multiple topical treatments with the liquid concentrate. A series of 3-6 treatments was applied topically at 14-day intervals. The dogs treated with the miticide received an average of 4.5 topical treatments. All (100%) of the dogs responded clinically, and the mean rate of improvement at four weeks post-treatment was 99.1%. Most dogs (96.2%) were cleared of mites after 3-6 treatments, and Mitaban did not cause any dermatologic, ocular, or other clinical side-effects. Multiple treatments with the liquid concentrate were highly efficacious and safe for treatment of generalized demodicosis. Control dogs did not improve clinically and retained mite populations.

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