OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days. ANIMALS Twelve 2- to 14-day old healthy Arabian and Arabian-pony cross neonatal foals. PROCEDURES A 1.27-cm strip of cream containing 7.3 mg of diclofenac sodium (n = 6 foals) or an equivalent amount of placebo cream (6 foals) was applied topically to a 5-cm square of shaved skin over the anterolateral aspect of the left tarsometatarsal region every 12 hours for 7 days. Physical examination, CBC, serum biochemistry, urinalysis, gastric endoscopy, and ultrasonographic examination of the kidneys and right dorsal colon were performed before and after cream application. Venous blood samples were collected at predefined intervals following application of the diclofenac cream, and plasma diclofenac concentrations were determined by liquid chromatography–mass spectrometry. RESULTS No foal developed any adverse effects attributed to diclofenac application, and no significant differences in values of evaluated variables were identified between treatment groups. Plasma diclofenac concentrations peaked rapidly following application of the diclofenac cream, reaching a maximum of < 1 ng/mL within 2 hours, and declined rapidly after application ceased. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of the 1% diclofenac sodium cream to foals as described appeared safe, and low plasma concentrations of diclofenac suggested minimal systemic absorption. Practitioners may consider use of this medication to treat focal areas of pain and inflammation in neonatal foals.

This study aimed to evaluate the digital Brix and optical serum total protein (STP) refractometers for measuring concentrations of serum immunoglobulin G (IgG) in alpacas and compare them to IgG concentrations measured by the reference method of radial immunodiffusion (RID) assay. The appropriate cutoff point for Brix and STP refractometers and the transmission infrared (TIR) spectroscopy method was determined for low IgG concentrations (< 10 g/L). Serum samples were collected from alpacas (N = 169) and tested by both refractometers. The correlation between Brix % and STP was high [correlation coefficient (r) = 0.99]. However, the correlation coefficients between Brix % and STP with serum RID-IgG concentrations were only 0.56 and 0.55, respectively. Twenty-one (12.4%) of 169 alpaca serum samples had IgG concentrations of < 10 g/L. Using receiver operator characteristic curve (ROC) analysis, the optimal cutoff points for the TIR assay, digital Brix, and optical STP refractometers for assessing low IgG (RID < 10 g/L) were 13 g/L, 8.8%, and 50 g/L, respectively. The TIR assay showed higher sensitivity (Se = 95.2%) and specificity (Sp = 96.8%) than either the digital Brix (Se = 90.5% and Sp = 65.5%) or optical STP (Se = 81% and Sp = 73.7%) refractometers for assessing alpacas with low IgG. In conclusion, the Brix and STP refractometers lack accuracy in measuring alpaca IgG concentrations, but may be useful for screening animals for low serum IgG. However, the TIR assay with a cutoff point of 13 g/L was more appropriate for identifying low IgG than either refractometer. Another study that focuses on neonatal crias is recommended in order to evaluate the usefulness of these assays for field diagnosing of failure of transfer of passive immunity (FTPI).

The objective of this study was to compare the protection against challenge with porcine circovirus 2 (PCV2) induced by an experimental vaccine based on open reading frame (ORF) 2 of PCV2 DNA plus an adjuvant (aluminum hydroxide, cobalt oxide, or liposome) and a commercial PCV2 subunit vaccine. A total of 35 colostrum-fed, cross-bred, conventional piglets were randomly divided into 7 groups. The commercial vaccine was more efficacious against PCV2 challenge than the 4 experimental vaccines according to immunologic, virologic, and pathological outcomes. The pigs inoculated with the experimental vaccine containing the liposome adjuvant had significantly higher levels (P < 0.05) of neutralizing antibodies and interferon-γ-secreting cells, and significantly lower levels (P < 0.05) of PCV2 viremia than the pigs inoculated with the other experimental vaccines. The pigs inoculated with the experimental vaccines containing either the liposome adjuvant or the cobalt oxide adjuvant had significantly lower lymphoid lesion scores (P < 0.05) than the pigs in the group inoculated with the PCV2 DNA vaccine dissolved in phosphate-buffered saline. Liposome proved to be a potent adjuvant that efficiently enhanced both humoral and cellular immune responses induced by the PCV2 DNA vaccine.

OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide. ANIMALS 6 healthy adult cats. PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m2) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments. Plasma samples were obtained at various time points for up to 8 hours after administration. Samples were treated with semicarbazide hydrochloride to trap the 4-OHCP in stable form, which allowed for cyclophosphamide and trapped 4-OHCP to be simultaneously measured by use of tandem mass spectrometry. Pharmacokinetic parameters were determined from drug concentration-versus-time data for both cyclophosphamide and 4-OHCP. RESULTS Cyclophosphamide was tolerated well regardless of route of administration. Pharmacokinetic parameters for 4-OHCP were similar after oral, IV, and IP administration. Area under the concentration-time curve for cyclophosphamide was lower after oral administration than after IV or IP administration. CONCLUSIONS AND CLINICAL RELEVANCE Cyclophosphamide can be administered interchangeably to cats as oral, IV, and IP formulations, which should provide benefits with regard to cost and ease of administration to certain feline patients.

OBJECTIVE To use MRI and CT to compare the amount of tissue damage (soft tissue and bone) to the heads of goats after administration of a nonpenetrating or penetrating captive bolt. ANIMALS Cadavers of twelve 1- to 5-year-old mixed-breed goats that had been euthanized with an overdose of pentobarbital as part of an unrelated study. PROCEDURES Cadavers were randomly assigned to receive a nonpenetrating (n = 6) or penetrating (6) captive bolt. The head of 1 cadaver was imaged via CT and MRI. The muzzle of a device designed to administer either a penetrating or nonpenetrating captive bolt was then placed flush on the dorsal midline of each head at the level of the external occipital protuberance (poll) and aimed downward toward the cranialmost portion of the intermandibular space, and the assigned bolt was administered. Heads were removed, and CT and MRI of each head were performed. After imaging, each skull was transected along the sagittal plane to permit gross evaluation of central nervous tissue and obtain digital photographic images. In addition, 1 head that received a nonpenetrating captive bolt was further evaluated via blunt dissection and removal of adnexa from the external surface of the calvarium. RESULTS MRI, CT, and dissection of skulls revealed severe skeletal and soft tissue damage after impact with the penetrating and nonpenetrating captive bolts. CONCLUSIONS AND CLINICAL RELEVANCE The nonpenetrating captive bolt appeared to cause damage similar to that of the penetrating captive bolt in the cranium and soft tissues of the head in caprine cadavers. This damage suggested that administration of a nonpenetrating captive bolt as described here may be an acceptable method of euthanasia in goats.

OBJECTIVE To determine effects of transforming growth factor (TGF)-β and interleukin (IL)-1β on inflammatory markers in cultured canine chondrocytes to clarify the role of these cytokines in osteoarthritis of dogs. SAMPLE Pooled chondrocytes isolated from the stifle joints of 4 adult dogs. PROCEDURES Chondrocytes were isolated, cultured, and frozen at −80°C. Pooled cells were incubated in medium with or without TGF-β (1 or 10 ng/mL) and subsequently stimulated with IL-1β (10 ng/mL). Concentrations of nitric oxide (NO) and prostaglandin (PG) E were measured in culture supernatants. Gene expression of matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-2, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2 was quantified by use of real-time quantitative PCR assays. RESULTS Stimulation with IL-1β increased gene expression of all inflammatory markers, except for TIMP-2. Incubation with TGF-β resulted in a significant decrease in MMP-3 and TIMP-2 mRNA concentrations but had no effect on PGE and NO concentrations. For cells treated with TGF-β followed by IL-1β, concentrations of PGE and NO were lower, compared with concentrations for IL-1β control cells. Furthermore, IL-1β–induced gene expression of iNOS, MMP-3, and COX-2 was downregulated. However, the IL-1β–induced downregulation of TIMP-2 gene expression was partially restored by pretreatment with TGF-β. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IL-1β increased the expression of inflammatory genes and mediators, and TGF-β largely attenuated the IL-1β–mediated inflammatory response. Therefore, TGF-β might be a novel target for use in the prevention and treatment of cartilage breakdown in dogs with osteoarthritis.

OBJECTIVE To determine accuracy for a technique of needle redirection at a single craniolateral site for injection of 3 compartments of the equine stifle joint, describe the external needle position, and identify the location of the needle tip within each joint compartment. SAMPLE 24 equine cadaver stifle joints. PROCEDURES Stifle joints were placed in a customized stand. After the needle was placed, external needle position was measured and recorded. Each joint compartment (medial and lateral compartments of the femorotibial joint and the femoropatellar joint) was injected with a solution containing iodinated contrast medium, water, and dye. Radiography, assessment of intra-articular location of the needle tip, and gross dissection were performed to determine success of entering each joint compartment. Student t tests and an ANOVA were used to compare mean values. RESULTS Overall accuracy was 19 of 24 (79.1%), and accuracy for individual joint compartments was at least 21 of 24 (87.5%). Mean depth of needle insertion to access each compartment of the stifle joint was 5.71 cm. Mean angle of insertion (relative to the long axis of the tibia) was 82.1°, 80.3°, and 18.5° for the medial compartment of the femorotibial joint, lateral compartment of the femorotibial joint, and femoropatellar joint, respectively, and 28° medial, 7.3° lateral, and 1.3° lateral for the medial compartment of the femorotibial joint, lateral compartment of the femorotibial joint, and femoropatellar joint, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that this was an accurate technique for successful injection of the 3 equine stifle joint compartments.

OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.

OBJECTIVE To determine the ability of an accelerometer within a commercially available portable media device (PMD) to measure changes in postural stability of standing horses during various stance conditions and to compare these results with data obtained by use of a stationary force platform. ANIMALS 7 clinically normal horses. PROCEDURES A PMD was mounted on a surcingle; the surcingle was placed immediately caudal to the highest point of the shoulders (withers). Each horse was examined while standing on a stationary force platform system in a normal square stance, forelimb base-narrow stance, and normal square stance at 5 and 10 minutes after sedation induced by IV administration of xylazine hydrochloride. A minimum of 5 trials were conducted for each stance condition. Ranges of craniocaudal and mediolateral motion as well as SDs were collected for the PMD and force platform system. Analyses were performed with mixed-model ANOVAs, and correlation coefficients were calculated. RESULTS Stance condition significantly altered craniocaudal accelerations measured by use of the PMD, all craniocaudal and mediolateral displacements of the center of pressure, and velocities measured by use of the stationary force platform. For both the PMD and force platform, SDs were significantly affected by stance condition in both craniocaudal and mediolateral directions. Correlation coefficients between the systems for all variables were low to moderate (r = 0.18 to 0.58). CONCLUSIONS AND CLINICAL RELEVANCE Body-mounted PMDs should be investigated for use in assessment of postural stability in horses with neuromuscular abnormalities.

OBJECTIVE To determine repeatability of gait variables measured by use of extremity-mounted inertial measurement units (IMUs) in nonlame horses during trotting under controlled conditions of treadmill exercise. ANIMALS 10 horses. PROCEDURES Six IMUs were strapped to the metacarpal, metatarsal, and distal tibial regions of each horse. Data were collected in a standardized manner (3 measurements/d on 3 d/wk over a 3-week period) while each horse was trotted on a treadmill. Every measurement consisted of a minimum of 20 strides from which a minimum of 10 strides was selected for analysis. Spatial and temporal variables were derived from the IMUs. Repeatability coefficients based on the within-subject SD were computed for each gait analysis variable at each week. RESULTS Most of the temporal and spatial variables had high repeatability (repeatability coefficients < 10), and the repeatability coefficients were consistent among the 3 weeks of data collection. Some spatial variables, specifically the symmetry variables (which were calculated from other variables), had somewhat higher repeatability coefficients (ie, lower repeatability) only in the last week. CONCLUSIONS AND CLINICAL RELEVANCE With the exceptions of some symmetry variables, which may reflect individual variations during movement, the extremity-mounted IMUs provided data with high repeatability for nonlame horses trotting under controlled conditions of treadmill exercise. Repeatability was achieved for each instrumented limb segment with regard to the spatial relationship between 2 adjacent segments (joint angles) and the temporal relationship among all segments (limb phasing). Extremity-mounted IMUs could have the potential to become a method for gait analysis in horses.