To determine the effect of oral administration of prednisolone on thyroid function, 12 healthy Beagles were given 1.1 mg of prednisolone/kg of body weight every 12 hours for 22 days after 8 days of diagnostic testing of the dogs before treatment with prednisolone. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) response tests were performed before treatment (days 1 and 8 of the study) and during treatment (days 21 and 28 of the study). Blood samples were collected daily at 8 AM and 2 and 8 PM to rule out normal daily hormone fluctuations as the cause of a potential decrease in serum triodothyronine (T3), thyroxine (T4), and free T4 (fT4) concentrations. Serum T3, T4, and fT4 concentrations before treatment and 1 day and 21 days after the first prednisolone dose were compared by analyses of variance. Post-TSH and -TRH serum T3 and T4 concentrations before and during treatment were compared, using the Student t test for paired data. Oral administration of prednisolone significantly (P < 0.005) decreased serum T3, T4, and fT4 concentrations in the 8 AM and 2 and 8 PM samples obtained 1 day and 21 days after the first prednisolone dose. Serum T4 and fT4 concentrations in 8 AM and 2 PM samples were significantly (P < 0.05) lower 21 days after the first prednisolone dose than they were at 1 day after the first dose. Before treatment, serum T4 concentration in the 2 PM samples was significantly (P < 0.05) higher than serum T4 concentration in 8 AM and 8 PM samples. Oral administration of prednisolone significantly (P < 0.01) decreased serum T3 and T4 concentrations 6 hours after TSH and TRH injections. Significant difference in the mean incremental change in serum T3 and T4 concentrations was not observed when comparing before- and during prednisolone treatment values for the TRH response test. However, for the TSH response test, the mean incremental changes in serum T3 and T4 concentrations were significantly (P < 0.01) lower during prednisolone treatment. Despite the decreased TSH response incremental change in serum T4 concentration during oral treatment with prednisolone, the lowest value observed fell within the before-treatment range. In addition, during treatment, baseline serum T3 and T4 concentrations after TSH administration increased, on average, 3.7 and 8.4 times, respectively.

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Full-thickness skin wounds were created on the dorsum of both metacarpi in 8 horses. Three topical treatment regimens were studied. All wounds were bandaged with a nonadherent dressing, which was held in place with a snug elastic wrap. Group-A wounds were treated with a proprietary topical wound medication that consisted of a spray and an ointment. Group-B wounds were treated with the same regimen, except the putative active ingredients in the ointment were omitted. Group-C wounds were treated with a dry nonadherent bandage only. Wound dressings were changed every day and the limbs were photographed every other day until the wounds were healed. Specimens of normal skin and biopsy specimens of healed wounds were examined histologically and were assayed for hydroxyproline content. Wound healing measurements quantitated for each wound were number of days to healing, maximal wound size attained, day wound contraction commenced, day epithelium first noticed, rate of wound contraction, final wound size, and fraction of the wound that healed by contraction. The cosmetic appearance of the healed wounds was also graded. Significant differences were not noticed in hydroxyproline content, histologic appearance, or any of the wound healing measurements between treatment groups. The cosmetic appearance of healed group-A and -B wounds was significantly better than the appearance of group-C wounds. The topical treatment regimens studied neither enhanced nor inhibited wound healing in this study.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after sc and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after sc dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after sc dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 microgram/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for sc dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after sc dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 microgram/ml for IV, sc, and oral administration, respectively. On the basis of maintaining enrofloxacin serum concentrations at 4 times the minimal inhibitory concentration for Pasteurella multocida, oral dosing resulted in the longest maximal time interval between doses of 15.4 hours vs 9.9 hours and 7.4 hours for IV and SC injections, respectively. Because enrofloxacin is widely dispersed in the rabbit's body, it is estimated from the data in this study that in vivo inhibitory concentrations of enrofloxacin for Pasteurella multocida may be maintained at oral dosage regimens equivalent to 5 mg/kg (q 12 h).

Eight ponies were allotted to 2 groups of 4. Group-1 ponies (1-4) were given 0.2 g of indole/kg of body weight orally and group-2 ponies (5 to 8) were given 0.1 g of indole/kg. Various physical, hematologic, and physiologic measurements were obtained after administration of indole. Intravascular hemolysis and hemoglobinuria were detected in both groups within 24 hours of dosing. Hemolysis was reflected by decreases in PCV, hemoglobin concentration, and RBC count, and an increase in indirect bilirubin. Erythrocyte fragility appeared to increase in both groups at 8 hours after dosing and peaked at 16 hours after dosing. At 72 hours after dosing, the RBC fragility value was less than predose measurements. Heinz body formation was noticed in group-2 ponies, but not in group 1. Plasma indole concentrations increased in both groups from the nondetectable predose concentrations. Group-1 values were 203% of group-2 values. In group 2, plasma indole was nondetectable by 12 hours, whereas low concentrations could still be measured in the group-1 ponies at 24 hours. Ponies in group 1 died or were euthanatized between 24 and 72 hours after dosing, whereas group-2 ponies were euthanatized between 48 and 120 hours. At necropsy, all body fat, mucous membranes, and elastic tissue were stained yellow. Hemoglobinuric nephrosis was the most prominent microscopic lesion. Results of this study indicated that indole, a metabolite of the amino acid tryptophan, causes acute intravascular hemolysis in ponies.

The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid. On the basis of our findings, we conclude that topically administered indomethacin is effective in reducing protein concentrations in secondary AH and is rapidly eliminated from the eye.

An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses weredeveloped. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use ofhigh-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol. Absorption of the 2 doses of dl-alpha-tocopherol acetate indicated a dose response; the area under the curve at 24 hours (AUC24) was 4.3 micrograms.h/ml for the 45-IU/kg dose and 32.2 micrograms.h/ml (P < 0.01) for the 90-IU/kg dose. Maximal absorption was apparent when vitamin E was naturally consumed in grain, compared with administration of identical preparations by stomach tube or paste. In the same horses, dl-alpha-tocopherol and dl-alpha-tocopherol acetate plus polyethylene glycol had statistically similar absorption curves and both had significantly greater AUC24, compared with dl-alpha-tocopherol acetate; values for the 3 compounds were 23.6, 25.8, and 12.6 micrograms.h/ml, respectively. The AUC24 varied betweenindividual horses, but time of peak value was consistently observed between 6 and 9 hours. On the basis of the data from this study, the recommended technique for performing the oral vitamin E absorption test in horses would be administration of 90 IU of the free form of dl-alpha-tocopherol/kg, mixed in 1 L of grain to horses from which food has been withheld for 12 hours, followed by allowing the horses ad libitum access to hay immediately after administration of the vitamin E. Three baseline serum alpha-tocopherol values should be obtained within 24 hours prior to the test, with the last sample being obtained just prior to administration of the test dose of vitamin E. Heparinized plasma also may be used for this testing procedure. alpha-Tocopherol concentration should be measured at 3, 6, 9, 12, and 24 hours after vitamin E administration.

Urethral pressure profiles (UPPs) were recorded in ten adult healthy male cats before and after administration of either phenoxybenzamine, diazepam, nifedipine or xylazine. A significant decrease (p < 0.05) in urethral pressure at the level of the prostate was observed following treatment with all drugs. Xylazine produced a significant decrease in urethral pressure 4 to 7 cm from the tip of the penis in healthy male cats. None of the drugs used decreased urethral pressure in the zones of pure striated muscle or pure smooth muscle in these cats, making current recommendations for pharmacological management of urethral spasm suspect. Further studies are necessary to evaluate clinical cases of urethral spasm and to study the effects of these drugs on the urethral pressure of cats suffering from this spasm.

Effects of topical administration of a single dose of 2% pilocarpine on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and, diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was found to be 10.1 (+/- 0.5) mm. Topical treatment with pilocarpine resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 4 hours after treatment. Mean reduction of IOP was 15.2% in the treated eye and 9.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction in pupil diameter was 28.5% in the treated eye and 14.2% in the nontreated eye. Topically administered pilocarpine results in reduction of IOP and pupil diameter in treated and contralateral eyes, which supports the use of pilocarpine for treatment of glaucoma in cats.

The vaccine efficacy of a genetically engineered deletion mutant strain of pseudorabies virus, strain 783, was compared with that of the conventionally attenuated Bartha strain. Strain 783 has deletions in the genes coding for glycoprotein I and thymidine kinase. In experiment 1, which had a 3-month interval between vaccination and challenge exposure, strain 783 protected pigs significantly (P < 0.05) better against virulent virus challenge exposure than did the Bartha strain. The growth of pigs vaccinated with strain 783 was not arrested, whereas that of pigs vaccinated with the Bartha strain was arrested for 7 days. Of 8 pigs given strain 783, 4 were fully protected against challenge exposure; none of the pigs given strain Bartha was fully protected. In experiment 2, which had a 3-week interval between vaccination and challenge exposure, the growth of pigs vaccinated with strain 783 was arrested for 3.5 days, whereas that of pigs vaccinated with the Bartha strain was arrested for 6 days. In experiment 3, pigs with moderate titer of maternal antibodies were vaccinated twice IM or once intranasally with either strain 783 or Bartha and were challenge-exposed 3 months after vaccination. Pigs given strain 783 twice IM were significantly (P < 0.05) better protected than were the other pigs. They had growth arrest of only 6 days, compared with 9 days for pigs of other groups, and shed less virus after challenge exposure. Results of this study indicate that the vaccine based on the deletion mutant strain 783 is more efficacious than is the Bartha strain of pseudorabies virus.