Objective: To identify proteins with differential expression between healthy dogs and dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament (CCL) disease. Sample: Serum and synovial fluid samples obtained from dogs with stifle joint osteoarthritis before (n = 10) and after (8) surgery and control dogs without osteoarthritis (9) and archived synovial membrane and articular cartilage samples obtained from dogs with stifle joint osteoarthritis (5) and dogs without arthritis (5). Procedures: Serum and synovial fluid samples were analyzed via liquid chromatography–tandem mass spectrometry; results were compared against a nonredundant protein database. Expression of complement component 3 in archived tissue samples was determined via immunohistochemical methods. Results: No proteins had significantly different expression between serum samples of control dogs versus those of dogs with stifle joint osteoarthritis. Eleven proteins (complement component 3 precursor, complement factor I precursor, apolipoprotein B-100 precursor, serum paraoxonase and arylesterase 1, zinc-alpha-2-glycoprotein precursor, serum amyloid A, transthyretin precursor, retinol-binding protein 4 precursor, alpha-2-macroglobulin precursor, angiotensinogen precursor, and fibronectin 1 isoform 1 preproprotein) had significantly different expression (> 2.0-fold) between synovial fluid samples obtained before surgery from dogs with stifle joint osteoarthritis versus those obtained from control dogs. Complement component 3 was strongly expressed in all (5/5) synovial membrane samples of dogs with stifle joint osteoarthritis and weakly expressed in 3 of 5 synovial membrane samples of dogs without stifle joint arthritis. Conclusions and Clinical Relevance: Findings suggested that the complement system and proteins involved in lipid and cholesterol metabolism may have a role in stifle joint osteoarthritis, CCL disease, or both.

Objective: To evaluate associations between economic and performance outcomes with the number of treatments after an initial diagnosis of bovine respiratory disease (BRD) in commercial feedlot cattle. Animals: 212,867 cattle arriving in a Midwestern feedlot between 2001 and 2006. Procedures: An economic model was created to estimate net returns. Generalized linear mixed models were used to determine associations between the frequency of BRD treatments and other demographic variables with economic and performance outcomes. Results: Net returns decreased with increasing number of treatments for BRD. However, the magnitude depended on the season during which cattle arrived at the feedlot, with significantly higher returns for cattle arriving during fall and summer than for cattle arriving during winter and spring. For fall arrivals, there were higher mean net returns for cattle that were never treated ($39.41) than for cattle treated once ($29.49), twice ($16.56), or ≥ 3 times (−$33.00). For summer arrivals, there were higher least squares mean net returns for cattle that were never treated ($31.83) than for cattle treated once ($20.22), twice ($6.37), or ≥ 3 times ($−42.56). Carcass traits pertaining to weight and quality grade were deemed responsible for differences in net returns among cattle receiving different numbers of treatments after an initial diagnosis of BRD. Conclusions and Clinical Relevance: Differences in economic net returns and performance outcomes for feedlot cattle were determined on the basis of number of treatments after an initial diagnosis of BRD; the analysis accounted for the season of arrival, sex, and weight class.

Objective-To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). Animals-6 healthy mixed-breed dogs. Procedures-Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. Results-Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). Conclusions and Clinical Relevance-On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Objective-To determine the effect of biopsy collection depth on the postprandial activation of mammalian target of rapamycin (mTOR) signaling factors, particularly protein kinase B, ribosomal protein S6 kinase, ribosomal protein S6, and eukaryotic initiation factor 4E binding protein 1 in middle-aged horses. Animals-6 healthy Thoroughbred mares (mean +/- SD age, 13.4 +/- 3.4 years). Procedures-Horses were fed a high-protein feed at 3 g/kg. Sixty minutes after horses were fed, the percutaneous needle biopsy technique was used to collect biopsy specimens from the gluteus medius muscle at 6, 8, and 10 cm below the surface of the skin. Muscle specimens were analyzed for the activation of upstream and downstream mTOR signaling factors, myosin heavy chain (MHC) isoform composition, and amino acid concentrations. Results-A 21% increase in MHC IIA isoform expression and a 21% decrease in MHC IIX isoform expression were identified as biopsy depth increased from 8 to 10 cm below the surface of the skin; however, no significant change was evident in the degree of MHC I expression with muscle depth. Biopsy depth had no significant effect on the phosphorylation of any of the mTOR signaling factors evaluated. Conclusions and Clinical Relevance-Postprandial mTOR signaling could be compared between middle-aged horses when biopsy specimens were collected between 6 and 10 cm below the surface of the skin. Optimization of muscle biopsy techniques for evaluating mTOR signaling in horses will facilitate the design of future investigations into the factors that regulate muscle mass in horses.

Objective-To determine kinematic changes to the hoof of horses at a walk after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness (baseline) values after perineural anesthesia. Animals-6 clinically normal Quarter Horses. Procedures-For each horse, a sole-pressure model was used to induce 3 grades of lameness in the right forelimb, after which perineural anesthesia was administered to eliminate lameness. Optical kinematics were obtained for both forelimbs with the horse walking before (baseline) and after induction of each grade of lameness and after perineural anesthesia. Linear acceleration profiles were used to identify hoof events, and each stride was divided into hoof-contact, break-over, initial-swing, terminal-swing, and total-swing segments. Kinematic variables were compared within and between limbs for each segment by use of mixed repeated-measures ANOVA. Results-During the hoof-contact and terminal-swing segments, the hoof of the left (nonlame) forelimb had greater sagittal-plane orientation than did the hoof of the right (lame) forelimb. For the lame limb following lameness induction, the break-over duration and maximum cranial acceleration were increased from baseline. After perineural anesthesia, break-over duration for the lame limb returned to a value similar to that at baseline, and orientation of the hoof during the terminal-swing segment did not differ between the lame and nonlame limbs. Conclusions and Clinical Relevance-Subclinical unilateral forelimb lameness resulted in significant alterations to hoof kinematics in horses that are walking, and the use of hoof kinematics may be beneficial for the detection of subclinical lameness in horses.

Objective-To assess the effects of oxygen insufflation rate, respiratory rate, and tidal volume on fraction of inspired oxygen (Fio2) in cadaveric canine heads attached to a lung model. Sample-16 heads of canine cadavers. Procedures-Each cadaver head was instrumented with a nasal insufflation catheter through which oxygen was delivered. The trachea was attached to a sample collection port connected by means of corrugated tubing to a lung model. Eight treatment combinations that varied in respiratory rate (10 or 20 breaths/min), tidal volume (10 or 15 mL/kg), and oxygen insufflation rate (50 or 100 mL/kg/min) were applied to each head in a replicated Latin square design. Gas samples were manually collected, and inspired oxygen concentrations were analyzed. The Fio2 and end-tidal CO2 concentration were determined and compared among sample groups. Results-Estimated least squares mean Fio2 for various treatment combinations ranged from 32.2% to 60.6%. The Fio2 was significantly increased at the higher insufflation rate (estimated marginal least squares mean, 48.7% vs 38.6% for 100 and 50 mL/kg/min, respectively), lower respiratory rate (48.9% vs 38.3% for 10 and 20 breaths/min, respectively), and smaller tidal volume (46.8% vs 40.0% for 10 and 15 mL/kg, respectively). Conclusions and Clinical Relevance-Fio2 in the model was affected by oxygen insufflation rate, respiratory rate, and tidal volume. This information may potentially help clinicians interpret results of blood gas analysis and manage canine patients receiving oxygen insufflation via a nasal catheter.

Objective-To compare the recovery rates of Campylobacter fetus subsp venerealis (Cfv) from preputial scrapings of infected bulls with passive filtration on selective medium versus nonselective medium, with and without transport medium. Samples-217 preputial scrapings from 12 bulls (4 naturally and 8 artificially infected with Cfv). Procedures-Preputial scrapings were collected in 2 mL of PBS solution and bacteriologically cultured directly on Skirrow medium or passively filtered through 0.65-μm filters onto blood agar, with or without 24 hour preincubation in modified Weybridge transport enrichment medium (TEM). After 72 hours, plates were examined for Cfv and bacterial and fungal contamination or overgrowth. Results-Passive filtration of fresh preputial scrapings onto blood agar yielded significantly higher recovery rates of Cfv (86%) than direct plating on Skirrow medium (32%), whereas recovery from TEM was poor for both media (35% and 40%, respectively). Skirrow cultures without TEM were significantly more likely to have fungal contamination than were cultures performed with any other technique, and fungal contamination was virtually eliminated by passive filtration onto blood agar. Bacterial contamination by Pseudomonas spp was significantly more common with Skirrow medium versus passive filtration on blood agar, regardless of TEM use. Conclusions and Clinical Relevance-The use of transport medium and the choice of culture medium had significant effects on Cfv recovery and culture contamination rates from clinical samples. Both factors should be considered when animals are tested for this pathogen.

Objective-To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses. Animals-6 healthy rabbits. Procedures-A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed. Results-The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively. Conclusions and Clinical Relevance-Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed.

Objective: To evaluate metaphylactic RNA interference to prevent equine herpesvirus type 1 (EHV-1) infection in experimental herpesvirus myeloencephalopathy in horses and to determine whether horses infected with a neuropathogenic strain of the virus that develop equine herpesvirus myeloencephalopathy (EHM) have differences in viremia. Animals: 13 seronegative horses. Procedures: EHV-1 strain Ab4 was administered intranasally on day 0, and small interfering RNAs (siRNAs [EHV-1 specific siRNAs {n = 7} or an irrelevant siRNA {6}]) were administered intranasally 24 hours before and 12, 24, 36, and 48 hours after infection. Physical and neurologic examinations, nasal swab specimens, and blood samples were collected for virus isolation and quantitative PCR assay. Data from the study were combined with data from a previous study of 14 horses. Results: No significant difference was detected in clinical variables, viremia, or detection of EHV-1 in nasal swab specimens of horses treated with the EHV-1 targeted siRNAs (sigB3-siOri2) versus controls. No significant differences in viremia were detected between horses that developed EHM and those that did not. Conclusions and Clinical Relevance—Administration of siRNAs targeted against EHV-1 around the time of EHV-1 infection was not protective with this experimental design. Horses infected with the neuropathogenic EHV-1 strain Ab4 that developed EHM did not have a more pronounced viremia.

Objective: To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration. Animals: 6 healthy cats. Procedures: In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis. Results: Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%. Conclusions and Clinical Relevance: The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.