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Biomedical subjects

E T Lyons

Publications and source records attributed to E T Lyons.

At least 127 records · Page 7Linked to original sources

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.

Animals↗

Critical tests of the antiparasitic activity of thiabendazole and trichlorfon sequentially administered to horses via stomach tube.

Thirteen critical tests were conducted in horses naturally infected with helminths and bots. Single doses of thiabendazole (44 mg/kg of body weight) and trichlorfon (40 mg/kg of body weight) powder formulations were administered as suspensions sequentially given via stomach tube to evaluate the efficacy of the combination against the large parasites of horses. Parasite removal efficacies were 100% against 2nd instar Gasterophilus intestinalis and 2nd and 3rd instar Gasterophilus nasalis and 82 to 100% against 3rd instar G intestinals. There were complete removals of mature and immature Parascaris equorum and mature Oxyuris equi. Removal efficacies against Strongylus vulgaris were 89 to 100% and against Strongylus edentatus, 82 to 100%. Of 2 horses infected with Strongylus equinus, removals were 72 and 100%. Seven of the 13 horses treated had transient, semi-liquid feces during the posttreatment hours 1 through 24.

Administration, Oral↗

Thelazia lacrymalis in horses in Kentucky and observations on the face fly (Musca autumnalis) as a probable intermediate host.

Eyes from 114 (30.3%) of 376 dead horses, examined from 3 April 1975 to 3 April 1976, were naturally infected with adult Thelazia lacrymalis; 1 horse was also infected with 1 male Thelazia skrijabini. Adult T. lacrymalis from dead horses were successfully transferred mechanically to the eyes of 3 of 4 Shetland ponies raised helminth-free. Larvae from gravid female T. lacrymalis underwent development in experimentally infected, laboratory-raised face flies (Musca autumnalis) and third-stage larvae ranging from 1.82 to 2.94 mm in total length were recovered at 12 to 15 days postexposure. A total of 866 naturally occurring face flies were collected from the head region of horses. Twelve of the face flies harbored larval stages of Thelazia spp. One of the larvae resembled third-stage T. lacrymalis that were recovered from the experimentally infected, laboratory-raised face flies. Introduction of 3 third-stage larvae from 1 face fly onto the cornea of a pony raised helminth-free resulted in the recovery of 1 male T. skrjabini 242 days later. In addition to the eyeworm larvae, other parasites recovered from the face flies included Heterotylenchus autumnalis, hypopi of astigmatid mites and a first instar beetle (Coleoptera: Rhipiphoridae). Data from these investigations indicate the likelihood that face flies are an intermediate host for T. lacrymalis and probably other species of Thelazia in this part of the country.

Animals↗

Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.

Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.

Administration, Oral↗

Critical tests of anthelmintic activity of a paste formulation of thiabendazole in horses.

Critical tests of the activity on large strongyles, ascarids, mature pinworms, and bots were carried out in 11 horses intraorally treated with a paste formulation of thiabendazole. The dose level of 44 mg/kg was administered to 3 horses, and the dose level of 88 mg/kg to 8 horses. Removals of Strongylus vulgaris and mature Oxyuris equi were 100% at the 2 dose levels, and efficacy against Strongylus edentatus varied from 95 to 99% and 89 to 100% for the 44- and the 88-mg/kg dose levels, respectively. Strongylus equinus was completely removed from the 1 infected horse treated at the dose level of 88 mg/kg. Activity of the smaller dose against Parascaris equorum was 46%, and that of the larger dose varied from 32 to 100%. The drug was inactive on Gasterophilus intestinalis and Gasterophilus nasalis.

Administration, Oral↗

Studies on the development and chemotherapy of larvae of Parascaris equorum (Nematoda: Ascaridoidea) in experimentally and naturally infected foals.

Experimentally induced infections of Parascaris equorum in worm-free pony foals required 14 to 17 days for migration of the larvae through the liver and lungs, and 79 to 110 days to become gametogenically functional. Treatment of experimentally infected or naturally exposed foals during the parenteral phase of development, using levamisole at 8 mg/kg, a mixture of levamisole at 8 mg/kg plus piperazine at 88 mg base equivalent/kg, or dl-tetramisole at 10 mg/kg, was quite efficacious in (1) reducing the number of P. equorum larvae recovered from the small intestines of the foals at necropsy, or (2)delaying the appearance of ascarid eggs in the feces of treated foals beyond the time period observed for the untreated foals. Three formulations of dichlorvos at doses of 10, 20, 30, or 40 mg/kg, and 2 formulations of trichlorfon at 20 or 40 mg/kg, were not effective when treatment was given on or before the 14th day after infective eggs were administered. Treatment with a gel formulation of dichlorvos at 20 mg/kg 17 to 28 days after experimental infection was 100% effective in removing ascarid larvae from the small intestines of poly foals.

Animals↗

Methyl 5(6)-phenylsulfinyl-2-benzimidazolecarbamate, a new, potent anthelmintic.

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.

Animals↗

Activity of organophosphorus compounds against oral stages of gasterophilus intestinalis and Gasterophilus nasalis.

Controlled tests of the efficacy of bot-active compounds, dichlorvos, trichlorfon, trichlorfon butonate, and carbon disulfide on the larvae of Gasterophilus intestinalis and Gasterophilus nasalis during their migratory period in the tissue of the mouth of horses and ponies were completed on experimentally induced and naturally acquired infections. Against the experimental parasitisms in pony foals, the resin-pellet formulation of dichlorvos given on the feed at the dose level of 37 mg/kg, 2 formulations of trichlorfon given by stomach tube at the dose level of 40 mg/kg, another of trichlorfon given on the feed, and trichlorfon butonate given intragastrically at the dose level of 43 mg/kg were 100% efficacious. Against naturally acquired parasitisms in horses, a broad-spectrum gel formulation of dichlorvos given intraorally at the dose level of 36 mg/kg was quite efficacious, whereas liquid carbon disulfide given by stomach tube at the dose level of 2.4 ml/45.45 kg was ineffective.

Administration, Oral↗

Occurrence of second and third instars of Gasterophilus intestinalis and Gasterophilus nasalis in stomachs of horses in Kentucky.

The occurrence of 2nd and 3rd instars of Gasterophilus intestinalis and Gasterophilus nasalis was determined in 476 horses during the 22-year period from 1951 to 1973. Overall, G intestinalis infected 98.7% of the horses and averaged 168/horse; whereas G nasalis infected 80.7% of the horses and averaged 52/horse. Aggregate average total numbers for G intestinalis ranged from a low of 50 in September to a high of 229 in March, and for G nasalis, from a low of 14 in September to a high of 82 in February. Horses were infected by 2nd or 3rd instars of both species on a year-round basis. Differentiation between the instars provided insight into the dynamics of the infections. For G intestinalis, the data indicated (1) 2nd instars from the previous year's generation of flies continue to arrive in the stomach until April; (2) arrival of the current year's crop of 2nd instars starts in July; and (3) 3rd instars from the previous year's generation of flies are not voided in appreciable numbers until August, when numbers of the current year's crop of 3rd instars appear in the stomach. For G nasalis, the data indicated (1) arrival in the stomach of the current year's generation of 2nd instars starts in July and terminates in January and (2) 3rd instars from the previous year's generation of flies are voided over a period beginning in March and extending into August, when the current year's crop of 3rd instars begin to appear. Acquisition of infections of horses with G intestinalis is nearly a year-round process, except for April, because of the persistence of viable larvae in eggs for a prolonged period after development and fly activity has ceased in the fall. In contrast, infection with G nasalis is interrupted between December and May, because eggs hatch naturally after a short period of development, and fly activity ceases in the fall.

Animals↗

Critical tests of suspension, paste, and pellet formulations of cambendazole in the horse.

Three formulations of cambendazole were evaluated for anthelmintic activity by critical testing method in 21 horses. Cambendazole suspension was administered via stomach tube at the dose rate of 10 mg/kg to 3 horses and at the dose rate of 20 mg/kg to 3 horses. Cambendazole paste was given intraorally to 8 horses, and the pellet formulation was fed to 7 horses at the dose rate of 20 mg/kg. Anthelmintic activity of cambendazole was similar for all dose rates and formulations. Gasterophilus intestinalis, Gasterophilus nasalis, Draschia megastoma, Anoplocephala perfoliata, and Anoplocephala magna appeared to be refractory. The 3 formulations removed (1) 100% of Parascaris equorum and mature Oxyuris equi, (2) 82 to 100% of Strongylus vulgaris, (3) 80 to 100% of Strongylus edentatus, (4) 85 to 99% of small strongyles, and (5) 79 to 100% of immature Oxyuris equi. Probstmayria vivipara was present in only 1 horse and removal was 99%. There was some evidence of activity on Habronema muscae. Toxicosis was not observed.

Administration, Oral↗