The use of dietary supplements as an alternative treatment for joint-related pathologies such as osteoarthritis (OA) is increasing. However, there is little scientific evidence to support the intended use. The aim of this study was to evaluate the anti-inflammatory effects of creatine- and amino acid-based supplements in primary cultured canine chondrocytes (CnCs) as an in-vitro model of OA and compare the effects to more commonly used agents, such as the non-steroidal anti-inflammatory drug (NSAID), carprofen, and the joint supplement, glucosamine (GS). CnCs were stimulated with interleukin-1β (IL-1β) and the subsequent release of prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNFα) was measured using an enzyme-linked immunosorbent assay (ELISA). Changes in oxylipins were also assessed using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). All compounds examined were able to significantly reduce the release of PGE2 and TNFα and were associated with reductions in cyclooxygenase-2 (COX-2) expression and nuclear factor-kappaB (NF-κB) phosphorylation. The creatine- and amino acids-based supplements also altered the profile of oxylipins produced. All compounds examined were less effective at reducing the release of PGE2 than carprofen. Carprofen significantly increased release of TNFα from CnCs, however, while the other agents reduced TNFα release. This study suggests that creatine- and amino acid-based supplements may have a beneficial role in preventing inflammation within the joint and that further studies are warranted.

OBJECTIVE To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration. ANIMALS 9 healthy adult horses. PROCEDURES In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1. RESULTS For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

OBJECTIVE To assess whether IV regional limb perfusion (IVRLP) and intraosseous regional limb perfusion (IORLP) of ceftiofur sodium resulted in clinically relevant drug concentrations in the synovial fluid of the tibiotarsal-tarsometatarsal joint of chickens (ie, an avian model) and to determine whether one of those techniques was superior to the other. ANIMALS 12 healthy adult hens. PROCEDURES Birds were randomly assigned to receive ceftiofur sodium (2 mg/kg) by the IVRLP (n = 4), IORLP (4), or IM (control; 4) route once daily for 6 consecutive days. Blood and tibiotarsal-tarsometatarsal synovial fluid samples were collected 15 minutes after ceftiofur administration on predetermined days for quantification of ceftiofur concentration. Plasma and synovial fluid ceftiofur concentrations were compared among the 3 groups. RESULTS All 4 birds in the IVRLP group developed mild to moderate bruising around the injection site, but this bruising did not prohibit completion of the prescribed treatment regimen. No adverse effects were observed in any of the other birds. The mean plasma and synovial fluid ceftiofur concentrations exceeded the therapeutic threshold for most common bacterial pathogens (> 1.0 μg/mL) at all sample acquisition times for all 3 groups. The mean synovial fluid ceftiofur concentration for the IVRLP group was significantly greater than that for the IORLP and control groups at all sample acquisition times. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that IVRLP may be a safe and effective technique for antimicrobial administration to birds with joint infections, contaminated wounds, pododermatitis, and other musculoskeletal infections of the distal aspect of a limb.

OBJECTIVE To investigate the effect of high doses of orally administered levothyroxine sodium (LT4) on serum concentrations of triiodothyronine (T3) and thyroxine (T4) in euthyroid horses. ANIMALS 12 healthy adult horses. PROCEDURES 10 horses initially received water (vehicle) or 240 mg (5X treatment) or 480 mg (10× treatment) of LT4, and blood samples were collected at baseline (0 hours) and 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, and 120 hours after treatment to measure serum T3 and T4 concentrations. Three horses then received 480 mg of LT4 for 14 days, and T4 concentration was measured on days 0, 14, 21, 28, and 35. Changes in T3 and T4 concentrations were compared over time and among treatments. RESULTS One-time administration of LT4 resulted in variable but significant increases in both T3 and T4 concentrations for up to 120 hours; however, T3 and T4 concentrations rarely exceeded reference intervals with either treatment. Prolonged administration of 480 mg of LT4 resulted in a 15-fold increase in T4 concentration after 14 days, but concentration returned to day 0 values within 21 days after LT4 administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE In euthyroid horses, administration of a high dose of LT4 resulted in mild increases in thyroid hormone concentrations; however, prolonged administration of high doses of LT4 resulted in markedly increased thyroid hormone concentrations that returned to pretreatment values within 3 weeks after discontinuation of LT4 administration. These results indicated complex kinetics of LT4 and suggested a possible saturation of T4 excretion in euthyroid horses.

OBJECTIVE To evaluate the efficacy of maropitant and loperamide for the prevention and reduction of adverse gastrointestinal effects associated with administration of paclitaxel to dogs with cancer. ANIMALS 168 dogs with cancer. PROCEDURES The study comprised 2 phases. For phase 1, dogs in the intervention group were administered maropitant and loperamide followed by paclitaxel. Outcomes were compared with those for a control group that received only maropitant and paclitaxel. For phase 2, all dogs of phase 1 that did not receive maropitant and loperamide and that had adverse gastrointestinal effects were enrolled; they received maropitant and loperamide and another dose of paclitaxel. RESULTS In phase 1, significantly fewer dogs in the intervention group had adverse effects. For dogs that had adverse effects, the intervention group had a lower severity of lack of appetite and lethargy. Also, adverse effects for dogs in the intervention group were of significantly shorter duration than for the control group. In phase 2, significant reductions in adverse effects were observed after administration of maropitant and loperamide. In those dogs that still had adverse effects after administration of maropitant and loperamide, there was a significant reduction in severity of signs of nausea and lethargy. CONCLUSIONS AND CLINICAL RELEVANCE A combination of maropitant and loperamide was found to be safe for use and effective for reducing or preventing signs of paclitaxel-induced gastrointestinal effects in dogs.

OBJECTIVE To evaluate accuracy of articular surfaces determined by use of 2 perpendicular CT orientations, micro-CT, and laser scanning. SAMPLE 23 cat cadavers. PROCEDURES Images of antebrachia were obtained by use of CT (voxel size, 0.6 mm) in longitudinal orientation (CTLO images) and transverse orientation (CTTO images) and by use of micro-CT (voxel size, 0.024 mm) in a longitudinal orientation. Images were reconstructed. Craniocaudal and mediolateral length, radius of curvature, and deviation of the articular surface of the distal portion of the radius of 3-D renderings for CTLO, CTTO, and micro-CT images were compared with results of 3-D renderings acquired with a laser scanner (resolution, 0.025 mm). RESULTS Measurement of CTLO and CTTO images overestimated craniocaudal and mediolateral length of the articular surface by 4% to 10%. Measurement of micro-CT images underestimated craniocaudal and mediolateral length by 1%. Measurement of CTLO and CTTO images underestimated mediolateral radius of curvature by 15% and overestimated craniocaudal radius of curvature by > 100%; use of micro-CT images underestimated them by 3% and 5%, respectively. Mean ± SD surface deviation was 0.26 ± 0.09 mm for CTLO images, 0.30 ± 0.28 mm for CTTO images, and 0.04 ± 0.02 mm for micro-CT images. CONCLUSIONS AND CLINICAL RELEVANCE Articular surface models derived from CT images had dimensional errors that approximately matched the voxel size. Thus, CT cannot be used to plan conforming arthroplasties in small joints and could lack precision when used to plan the correction of a limb deformity or repair of a fracture.

OBJECTIVE To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS 8 purpose-bred, 2-year-old Beagles. PROCEDURES A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 μg/kg) or MED mixed with 400 μg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 μg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole–treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.

The objectives of this study were to describe the frequency of antimicrobial resistance (AMR) in Escherichia coli and Campylobacter spp. isolates in fecal samples from beef cow-calf herds and to examine the associations between herd management practices, reported antimicrobial use, and AMR. Baseline prevalence data are needed to evaluate the effectiveness of antimicrobial stewardship programs. A pooled fecal sample, representing 20 cows, was collected from each of 107 herds during pregnancy testing. In the 305 recovered E. coli isolates (maximum 3 per herd), resistance to ≥ 1 antimicrobial was identified in 12 isolates [4%, 95% confidence interval (CI): 2% to 7%] from 105 herds (11%, 95% CI: 7% to 19%). The most common resistances identified in E. coli isolates were to tetracycline (3%) and to both streptomycin and sulfisoxazole (3%). Only 1 E. coli isolate was resistant to an antimicrobial of very high importance to human health - amoxicillin/clavulanic acid. However, 2 E. coli isolates had intermediate susceptibility to ciprofloxacin. Resistance to 1 antimicrobial was identified in 16 of 87 Campylobacter spp. isolates (18%, 95% CI: 11% to 28%) from 87 herds. Resistance to tetracycline was reported in 15% of Campylobacter spp. isolates and to nalidixic acid in 3.4%. Herds in which cows were treated with florfenicol were more likely to have E. coli resistance to ≥ 2 antimicrobials (OR 7.1, 95% CI: 1.1 to 57, P = 0.03). Herds with calf mortality of > 5% were more likely to have E. coli with resistance to streptomycin and sulfisoxazole [odds ratio (OR): 7.8, P = 0.03]. The results of this study are consistent with previous reports from western Canada and provide a starting point for designing an ongoing antimicrobial surveillance program.

OBJECTIVE To evaluate the lipidomic profile of surfactant obtained from horses with asthma at various clinical stages and to compare results with findings for healthy horses exposed to the same conditions. SAMPLE Surfactant samples obtained from 6 horses with severe asthma and 7 healthy horses. PROCEDURES Clinical evaluation of horses and surfactant analysis were performed. Samples obtained from horses with severe asthma and healthy horses before (baseline), during, and after exposure to hay were analyzed. Crude surfactant pellets were dried prior to dissolution in a solution of isopropanol:methanol:chloroform (4:2:1) containing 7.5mM ammonium acetate. Shotgun lipidomics were performed by use of high-resolution data acquisition on an ion-trap mass spectrometer. Findings were analyzed by use of an ANOVA with a Tukey-Kramer post hoc test. RESULTS Results of lipidomic analysis were evaluated to detect significant differences between groups of horses and among exposure statuses within groups of horses. Significantly increased amounts of cyclic phosphatidic acid (cPA) and diacylglycerol (DAG) were detected in surfactant from severely asthmatic horses during exposure to hay, compared with baseline and postexposure concentrations. Concentrations of cPA and DAG did not change significantly in healthy horses regardless of exposure status. CONCLUSIONS AND CLINICAL RELEVANCE cPA 16:0 and DAG 36:2 were 2 novel lipid mediators identified in surfactant obtained from asthmatic horses with clinical disease. These molecules were likely biomarkers of sustained inflammation. Further studies are needed to evaluate a possible correlation with disease severity and potential alterations in the plasma lipidomic profile of horses with asthma.

This study aimed to determine the effect of a single injection of paracetamol on the sevoflurane minimum alveolar concentration (MAC) response to noxious mechanical stimulation. Seven healthy adult beagles were enrolled in a prospective, randomized, blinded, crossover experimental study. Anesthesia was induced with propofol [11.6 ± 2.4 mg/kg body weight (BW)] and maintained with sevoflurane. The MAC was determined before (MAC-1) and after (MAC-2) treatment with 15 mg/kg BW of intravenous (IV) paracetamol or saline over 15 minutes. Samples for plasma paracetamol determination were collected immediately after IV treatment administration and following MAC-2 determination (123 ± 27 minutes after starting paracetamol administration). The MAC-1 was similar between treatments (1.7% ± 0.4%). There were no differences between control and paracetamol groups at MAC-2 (2.0% ± 0.4% and 1.7% ± 0.5%, respectively; P = 0.285). Paracetamol plasma concentrations after paracetamol administration were 34.5 ± 9.9 μg/mL, decreasing at the end of the procedure (8.5 ± 4.2 μg/mL). In conclusion, 15 mg/kg BW of IV paracetamol did not significantly reduce sevoflurane MAC in healthy dogs.