A study was designed to compare use of an numerical rating scale (NRS) and a visual analogue scale (VAS) for subjective assessment of lameness, using sheep as a model. The NRS consisted of 5 divisions, 0, 1, 2, 3, and 4; 4 of these divisions (1-4) described lameness. The VAS used a 100-mm horizontal line with vertical bars at either end; one end was labeled 'sound' and the other was labeled 'could not be more lame.' Two independent observers graded lameness in 62 sheep, and between- and within-observer differences were assessed for each scoring system to compare the NRS with the VAS. Results indicated no significant differences between the 2 observers scoring lameness, using either the VAS or the NRS. The scores obtained, using the VAS, were not normally distributed, although differences between scores for the 2 observers were. The NRS scores followed a normal distribution pattern. Investigation of repeated measurement for the same sheep, using both scales, revealed no significant difference between either. A comparison of the NRS and VAS scores made by each observer indicated that although correlation was good (observer 1; r = 0.94; observer 2; r = 0.95), there was not perfect agreement. The maximal NRS score of 4 was associated with VAS values > 68 mm, indicating that the NRS divisions did not reflect equal increases in lameness. The VAS and NRS scores for each observer were highly reproducible, although they were more variable for sheep that were regarded as moderately lame. Results indicate that although the NRS and VAS compared favorably with respect to repeatability, reproducibility, and use by 2 observers, the VAS is inherently more sensitive. In addition, the NRS and VAS should not be used interchangeably.

Dexamethasone pharmacokinetics was studied in 10 healthy dogs receiving high-dose administration of dexamethasone (dosage, 0.1 mg/kg of body weight, IV), alone or combined with ACTH dosage, 0.5 U/kg, IV), or low-dose administration of dexamethasone (dosage, 0.01 mg/kg, IV) in an incomplete cross-over design. Serum samples were obtained at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 720, 1,080, 1,440, 1,920, 2,400, and 2,880 minutes after dexamethasone administration; dexamethasone was measured by radioimmunoassay validated for use in dogs. Dexamethasone pharmacokinetics was adequately described by a two-compartment first-order open model. Comparison of pharmacokinetics for the low- and high-dose protocols revealed dose dependence; area under the curve, mean residence time, clearance, and volume of distribution increased significantly when dexamethasone dosage increased, The elimination rate constant was significantly (P < 0.05) less, and the elimination half-life significantly greater for the high-dose protocols; however, the distribution rate constant and distribution half-life were not significantly different when high-dose protocols were compared with the low-dose protocol. Dose-dependent increases in volume of distribution and clearance may be related to saturation of protein-binding sites. Concurrent administration of ACTH did not affect dexamethasone disposition.

A simple and humane model of inflammation, induced by the intradermal injection of 0.3 mL of sterile 2% carrageenan, was characterized in calves by measuring the volume of skin swelling plus histological analysis of skin biopsies. Carrageenan produced a biphasic increase in skin swelling, with an early edematous response followed by a more chronic cellular infiltrate. The swelling and sensitivity to pressure observed in the early response were suitable for testing the antiedematous and analgesic activity of a new nonsteroidal anti-inflammatory drug (NSAID), oxindanac. Pretreatment with intravenous oxindanac at doses from 0.5 to 8.0 mg/kg reduced the volume of swelling and this reached statistical significance (p < 0.05) at 2 mg/kg. The ED50 and ED90 values for inhibition of the peak swelling volume (4 h) were estimated to be 1 mg/kg and 2 mg/kg, respectively. These compare with an ED90 of 2.0 mg/kg for inhibition of serum TxB2 production, an index of platelet cyclo-oxygenase activity. The dose of oxindanac required for antiedematous activity correlated, therefore, with maximal inhibition of serum TxB2. The analgesic activity of oxindanac reached no clear maximum response, but statistically significant difference (p < 0.05) from placebo was reached with doses of 2 mg/kg and above. It is concluded that intradermal carrageenan produced a simple, humane and useful model for dose estimation of a new NSAID in calves.

The sodium-dependent transporter system responsible for L-glutamine uptake by brush border membrane vesicles prepared from equine jejunum was characterized. Vesicle purity was ascertained by a 14- to 17-fold increase in activity of the brush border enzyme markers. Glutamine uptake was found to occur into an osmotically active space with negligible membrane binding. The sodium-dependent velocity represented approximately 80% of total uptake and demonstrated overshoots. Kinetic studies of sodium-dependent glutamine transport at concentrations between 5 micromolar and 5 mM revealed a single saturable high-affinity carrier with a Michaelis constant of 519 +/- 90 micromolar and a maximal transport velocity of 3.08 +/- 0.97 nmol/mg of protein/10 s. Glutamine uptake was not affected by changes in environmental pH. Lithium could not substitute for sodium as a contransporter ion. 2-Methylaminoisobutyric acid inhibited the sodium-dependent carrier only minimally, but marked inhibition (> 90%) was observed in the presence of histidine, alanine, cysteine, and nonradioactive glutamine. Kinetic analysis of the sodium-independent transporter revealed it to have a Michaelis constant = 260 +/- 47 micromolar and a maximal transport velocity of 0.32 t 0.06 nmol/mg of protein/10 s. We conclude that glutamine transport in equine jejunal brush border membrane vesicles occurs primarily via the system B transporter and, to a lesser extent, by a sodium-independent carrier.

To investigate the determinants of glomerular ultrafiltration, renal micropuncture studies were performed in 9 cats. Mean single nephron glomerular filtration rate (SNGFR), directly measured in outer cortical nephrons, was 29.4 +/- 3.0 nl/min. This was similar to the estimated value for SNGFR (31.3 +/- 4.6 nl/min) obtained by dividing left kidney total glomerular filtration rate (1.41 +/- 0.12 ml/min/kg of body weight) by left glomerular count (175,200 +/- 13,600 glomeruli/kidney). In micropuncture studies performed at mean renal perfusion pressure of 101.3 +/-1.0 mm of Hg, the glomerular capillary hydrostatic pressure was 58.0 +/- 1.4 mm of Hg. The glomerular transcapillary hydrostatic pressure gradient (40.0 +/- 1.8 mm of Hg) exceeded colloid osmotic pressure at the efferent end of the glomerular capillaries (28.4 +/- 2.1 mm of Hg) in all cats studied, indicating existence of positive effective filtration pressure throughout the glomerular capillary bed. These results indicate that glomerular capillary pressure is sufficiently high to prevent forces from reaching filtration pressure equilibrium in feline outer cortical nephrons. Thus, the value of SNGFR in feline nephrons depends on the glomerular transcapillary hydrostatic pressure gradient and the glomerular ultrafiltration coefficient.

Concentration of sulfamethazine was measured in plasma and tissues (fat, liver, kidney, spleen, lungs, and skeletal muscle) of pigs given the drug IV and PC. The plasma concentration vs time curve was best described by a 2-compartment model, with a distribution half-life of 0.46 hour and an elimination half-life of 16.9 hours. Bioavailability after oral administration was 85.8 +/- 5.3%. The tissue and plasma sulfamethazine concentration vs time data ,ere used to develop a multicompartment pharmacokinetic model of sulfamethazine disposition in pigs. Plasma and tissue concentrations of sulfamethazine in pigs were measured at various intervals after multiple oral doses of sulfamethazine, and were compared to concentrations predicted by the model. Model predictions for tissue concentrations of sulfamethazine after addition of the drug to feed (110 micrograms/g of feed for 98 days; 550 micrograms/g for 30 days) were compared to results from other studies. The model accurately predicted the number of days for sulfamethazine concentration to fall below 0.1 Kg of tissue/g (0.1 ppm. the tolerated concentration) in various tissues.

A rebreathing method for measurement of pulmonary diffusing capacity for carbon monoxide (DL(CO)) and functional residual capacity (FRC) was evaluated in conscious horses. Horses were manually ventilated through an endotracheal tube, using a custom-made syringe filled with a gas mixture containing 18-carbon monoxide (18CO) and helium (He). The 18CO and He concentrations were continuously monitored by use of a mass spectrometer connected to the rebreathing circuit. Values for DL(CO), and FRC were calculated from changes in the concentration of these 2 gases. In 11 Thoroughbreds, mean (+/- SD) DL(CO) was 330.3 +/- 56.9 ml.min-1.mm of Hg-1, and FRC was 20.21 +/- 3.35 L. Body weight normalization yielded mean (+/- SD) values of 0.652 +/- 0.114 ml.min-1.mm of Hg-1.kg-1 for DL(CO), and 39.9 +/- 6.4 ml.kg-1 for FRC.

Twelve resected canine gallbladders (in vitro) and the gallbladder in each of 14 dogs (in vivo) were ultrasonographically examined. Gallbladder volume was calculated from ultrasonographically measured geometric dimensions, using 4 volumetric model formulas: cone, ellipse, biplanar ellipse, and prolate ellipse. Calculated volume was compared with true gallbladder volume, as measured by water displacement. AU examined models for calculation of gallbladder volume were closely associated with true gallbladder volume (P < 0.005), and all models provided accurate predictions of true gallbladder volume (r2 > 0.80). Calculated volumes can be corrected mathematically by use of the regression coefficient and constant for each model. Body weight was not significantly associated with gallbladder volume in any of the models considered. Use of ultrasonography to accurately measure gallbladder volume could be combined with synthetic cholecystokinin-stimulated gallbladder emptying to provide information about biliary function and patency in icteric animals. Such information could aid the clinical decision between surgical or medical treatment. Correction of calculated volumes would not be necessary in association with induced emptying studies, because volume change is more important than absolute volume.

Single doses (2.2 mg/kg of body weight) of phenylbutazone (PBZ) were administered IV to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of PBZ and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing PBZ disposition. Median volume of distribution at steady-state was 0.274 L/kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of PBZ for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of PBZ to adult horses.