Ivermectin as an antiparasitic agent in cattle

In experimental trials on cattle, ivermectin given SC at 200 micrograms/kg had 95% or better efficacy against adult and immature GI and pulmonary nematodes, including inhibited fourth-stage larvae of Ostertagia ostertagi. Studies of efficacy against ectoparasites revealed nearly 100% efficacy against sucking lice, psoroptic and sarcoptic mange mites and cattle grubs. Safety trials revealed no adverse effects with the recommended dosage, including bulls and pregnant cows. A few grub-infested cattle died from acute esophagitis associated with a host-parasite reaction after ivermectin injection.     

The activity of closantel as an equine antiparasitic agent

Eighteen pony foals were experimentally infected with 500 third stage larvae of Strongylus vulgaris at 2 weeks, and at 2, 4, 6 and 8 months after birth. For the duration of the study, all foals were kept in the same pasture with their mothers to allow natural infection with other parasites by exposure to a contaminated environment. Twelve of the foals were utilized in groups of 3 and treated orally five times at two month intervals starting at one month of age with closantel at doses of 5, 10, 20 or 40 mg kg-1. Ten months after birth the foals were necropsied to determine the parasitic burdens in the gastrointestinal tracts and the cranial mesenteric arteries. The results indicate a high antiparasitic activity of closantel against larval stages of Gasterophilus intestinalis and S. vulgaris, as well as against adult S. vulgaris, S. edentatus, Anoplocephala perfoliata and Triodontophorus spp., when used at doses of 20 or 40 mg kg-1.     

Critical test and safety evaluations of an oral paste preparation of mebendazole and trichlorfon in horses

Critical tests were done on 24 naturally parasitized horses to compare the antiparasitic activity of an oral paste preparation of mebendazole and trichlorfon with that of the marketed powder formulation. Each formulation was administered at the recommended dosages of 8.8 mg of mebendazole and 40 mg of trichlorfon/kg of body weight. Efficacy of the paste formulation ranged from 97.7% to 100% against 2nd- and 3rd-stage Gasterophilus spp, adult Strongylus vulgaris, S edentatus, Parascaris equorum, small strongyles; and larval and adult forms of Oxyuris equi. Adverse effects were generally limited to slight softening of the feces. Mild and transient restlessness or sweating were also observed in 2 of 12 horses treated with the paste formulation. The toxic effects of the paste, administered at 2.2 times the therapeutic dose, were examined in 6 horses and compared with the effects of a nonmedicated paste, administered in similar volumes to 6 other horses. Drug-related changes were not detected in clinical chemical analyses, hematologic values, or liver function tests. Transient clinical signs of organophosphate toxicosis (primarily the passage of loose feces) and prolonged inhibition of erythrocyte cholinesterase activity were evident within 1 hour after drug treatment. These effects were similar to those reported for the 2.2 X dose of marketed powder formulation.     

Methods in the evaluation of antiparasitic drugs in the horse.

The critical test is the primary method used for the efficacy evaluation of drugs against the major internal parasites (bots, ascarids, large strongyles, small strongyles, and pinworms) of the horse. The critical test determines: (1) spectrum of activity, (2) effectiveness of removal, (3) pattern of discharge, and (4) physical condition of each species of these parasites. General characteristics of the major parasitisms of the horse are discussed briefly. Criteria of the critical test also are considered including: (1) number of tests, (2) strain variation and drug resistance, (3) selection of test horses, (4) diagnosis of parasitic species, (5) numbers of parasites, (6) minimal efficacy requirements, and (7) other parasitic species. The controlled test principally is used on a selected basis for the small nematodes in the proximal portion of the digestive tract which cannot be properly evaluated by the critical test, or for other limited objectives. Clinical trials are discussed briefly but are invaluable supplements to the critical and controlled tests in the total assessment of a drug as a new product or for continued effectiveness in clinical use. Experimental procedures used in the conduct of drug evaluations should not be rigidly prescribed but should reflect input by the individual investigatior.     

Critical tests of morantel-trichlorfon paste formulation against internal parasites of the horse

Critical tests were completed on six horses to evaluate the antiparasitic activity of a paste formulation mixture of morantel citrate and trichlorfon, administered intraorally at the dose rate of 6 mg morantel base kg-1 and trichlorfon at 30 mg kg-1. Aggregate average removals were: 78% for two horses infected with 2nd instar Gasterophilus intestinalis; 100% for one infected with 2nd instar G. nasalis; 96% for six infected with 3rd instar G. intestinalis; 100% for four infected with 3rd instar G. nasalis; 100% for five infected with Parascaris equorum; 100% for one infected with mature Oxyuris equi; 100% for five infected with Strongylus vulgaris; 72% for five infected with S. edentatus; and partial removal (25%) of Anoplocephala perfoliata infection from one infected animal. Pre- and post-treatment EPG and LPG data indicated a reduction of 97% of the mature small strongyle infections. Evidence of toxicosis was not observed in any of the horses.     

Dental dolorimetry for the evaluation of an analgesic agent in the horse

A monopolar electrode was implanted surgically in the canine tooth dentine layer to evaluate pain threshold responses of horses. A constant-current stimulator was used to deliver a known electrical current to the tooth pulp nerve. A single stimulus of 2-ms duration, repeated at greater than or equal to 20-s intervals, was used to elicit a head lift response. The lowest current level that produced 3 positive head lift responses was recorded as the pain threshold of the horse. The testing technique, dental dolorimetry, was easily performed. Tooth pulp pain thresholds (TPPT) were established on 8 nonmedicated adult male horses. Electrodes were nonreactive and remained functional for up to 98 days. Base-line TPPT values were consistent with repeated measurements on the same day and measurements on subsequent test days. The quantity of electrical current necessary to elicit the TPPT was increased after administration of xylazine HCl as a test analgesic.     

Interpretation of laryngeal function tests in the horse

Idiopathic left-sided laryngeal paralysis was present in 14 of 169 horses on a thoroughbred horse farm (8.3 per cent). In nine animals, it was evident only after exercise and arytenoid abduction and adduction were normal at rest. Asynchronous movement of the arytenoid cartilages was observed in 94 horses at rest (55.6 per cent), 86 of which were considered to be normal after exercise. Conversely, synchronous movement of the arytenoids was noted when at rest in six of the 14 animals diagnosed as having laryngeal hemiplegia after exercise. An abnormal inspiratory noise during exercise was detectable in 11 of these 14 horses, but not in the remainder. An abnormal noise on inspiration was also produced by nine horses in which laryngeal hemiplegia was not diagnosed.     

Efficacy and safety of mitomycin C as an agent to treat corneal scarring in horses using an in vitro model

Objective Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in vitro model. Procedure An in vitro model of equine corneal fibroblast (ECF) developed was used. The ECF or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta‐1 (TGFβ1) under serum‐free conditions. The MMC dose for the equine cornea was defined with dose‐dependent trypan blue exclusion and (3‐4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays after applying MMC to the cultures once for 2 min. The efficacy of MMC to control corneal scarring in horses was determined by measuring mRNA and protein expression of corneal scarring markers (alpha‐smooth muscle actin and F‐actin) with western blotting, immunocytochemistry and/or quantitative real‐time polymerase chain reactions. Results A single 2‐min treatment of 0.02% or less MMC did not alter ECF phenotype, viability, or cellular proliferation whereas 0.05% or higher MMC doses showed mild‐to‐moderate cellular toxicity. The TGFβ1 at 1 ng/mL showed significant myofibroblast formation in ECF under serum‐free conditions. A single 2‐min, 0.02% MMC treatment 24 h (early) after TGFβ1 stimulation significantly reduced conversion of ECF to myofibroblasts, however, a single 0.02% MMC treatment 11 days after TGFβ1 stimulation showed moderate myofibroblast inhibition. Conclusions That MMC safely and effectively reduced scarring in ECF by reducing the degree of transdifferentiation of corneal fibroblasts to myofibroblasts in vitro. Further clinical in vivo investigations are warranted using MMC in horses.     

Critical Tests on Thiabendazole as an Anthelmintic in Sheep

The results of critical tests on thiabendazole given at three dose levels, 50 mg/kg, 80 mg/kg and 100 mg/kg, to groups of naturally parasitized lambs are reported. While the compound appeared to be efficient at all levels, the best results were obtained at 100 mg/kg. The total percentage removals of all worms present in the gut at these three dosage levels were 79.1 per cent at the 50 mg/kg level, 96.3 per cent at the 80 mg/kg level and 99.5 per cent at the 100 mg/kg level.