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.

OBJECTIVE To investigate the pharmacokinetics of metformin hydrochloride in healthy dogs after IV and oral bolus administrations and determine the oral dose of metformin that yields serum concentrations equivalent to those thought to be effective in humans. ANIMALS 7 healthy adult mixed-breed dogs. PROCEDURES Each dog was given a single dose of metformin IV (mean ± SD dose, 24.77 ± 0.60 mg/kg) or PO (mean dose, 19.14 ± 2.78 mg/kg) with a 1-week washout period between treatments. For each treatment, blood samples were collected before and at intervals up to 72 hours after metformin administration. Seventy-two hours after the crossover study, each dog was administered metformin (mean dose, 13.57 ± 0.55 mg/kg), PO, twice daily for 7 days. Blood samples were taken before treatment initiation on day 0 and immediately before the morning drug administration on days 2, 4, 6, and 7. Serum metformin concentrations were determined by means of a validated flow injection analysis–tandem mass spectrometry method. RESULTS After IV or oral administration to the 7 dogs, there was high interindividual variability in mean serum metformin concentrations over time. Mean ± SD half-life of metformin following IV administration was 20.4 ± 4.1 hours. The mean time to maximum serum concentration was 2.5 ± 0.4 hours. Mean systemic clearance and volume of distribution were 24.1 ± 7.8 mL/min/kg and 44.8 ± 23.5 L/kg, respectively. The mean oral bioavailability was 31%. CONCLUSIONS AND CLINICAL RELEVANCE The study data indicated that the general disposition pattern and bioavailability of metformin in dogs are similar to those reported for cats and humans

OBJECTIVE To evaluate dynamic movement of the diaphragm of clinically normal dogs by use of fluoroscopy and to obtain quantitative data of diaphragmatic excursion during spontaneous breathing. ANIMALS 8 healthy male Beagles with no history of respiratory tract disease. PROCEDURES Fluoroscopy was performed during stabilized respiratory conditions. The beam center was located at the level of the diaphragm, and diaphragmatic motion was recorded during 3 respiratory cycles in dogs positioned in left lateral, right lateral, and dorsal recumbency. Extent of excursion of the diaphragmatic cupula and both crura, difference in excursion between the left and right crura, and ratios of the excursions of the diaphragmatic cupula and left and right crura to the length of the eighth thoracic vertebra were determined. RESULTS Diaphragmatic crural excursion was symmetric for dogs in right lateral recumbency, and the crural excursion was approximately three-quarters of the vertebral length; however, crural excursion appeared to be asymmetric for dogs in left lateral recumbency. Mean ± SD difference in excursion between the right and left crura was 22.68 ± 8.68% for left lateral recumbency, 16.63 ± 9.22% for right lateral recumbency, and 18.11 ± 12.96% for dorsal recumbency. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the fluoroscopic view of a dog positioned in right lateral recumbency may allow better evaluation of the symmetry of diaphragmatic excursion, compared with results for other recumbency positions. This study provided quantitative data on the excursion of diaphragmatic movement observed by use of fluoroscopy in clinically normal Beagles.

OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses. ANIMALS 12 healthy adult horses. PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to assess platelet activation (including ADP- and collagen-induced aggregation and closure times, flow-cytometric variables of platelet-leukocyte aggregates, platelet membrane P-selectin and phosphatidylserine expression, and microparticle release), von Willebrand factor (vWF) concentration, and cofactor activity. In addition, thrombelastography was used to evaluate fibrin formation in tissue factor–activated whole blood and plasma and to assess tissue plasminogen activator–induced plasma fibrinolysis. For each treatment, values obtained before and 72 hours after start of administration were compared by use of Wilcoxon signed rank tests. RESULTS Yunnan Baiyao treatment had no significant effect on any hemostatic variable, compared with results for the placebo treatment. CONCLUSIONS AND CLINICAL RELEVANCE Administration of Yunnan Baiyao at a dosage typically used in clinical practice had no effect on in vitro measures of platelet or vWF function and no enhancement of fibrin-clot formation or stability. Any hemostatic actions of Yunnan Baiyao may require higher dosages or result from cell-surface interactions at sites of vascular and tissue injury not examined in this study.

OBJECTIVE To develop a noninvasive biomarker-based detection system specific for Mycobacterium bovis for monitoring infection in wild animals. SAMPLE Serum samples from 8 experimentally infected yearling white-tailed deer (Odocoileus virginianus) and 3 age-matched control deer and from 393 Minnesota Department of Natural Resources hunter-harvested white-tailed deer in northwest Minnesota. PROCEDURES 8 yearling deer were inoculated with 2 × 10(8) CFUs of virulent M bovis strain 1315 (day 0), and sera were obtained on days 0, 19, 48, and 60; sera were obtained from 3 uninoculated control deer on those same days. Sera from these deer and 9 M bovis-positive hunter-harvested deer were tested for 3 Mycobacterium-specific biomarkers (MB1895c, MB2515c, and polyketide synthase 5) by use of an indirect ELISA. That same ELISA was used to test sera obtained from 384 exposed noninfected deer in northwest Minnesota from 2007 through 2010, concurrent with an outbreak of tuberculosis involving cattle and deer in that region. RESULTS ELISA results revealed that tuberculosis infection could be detected as early as 48 days after inoculation in experimentally infected deer. Results for 384 deer sera revealed that prevalence of tuberculosis decreased over the 4-year period. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the prevalence of tuberculosis in Minnesota deer decreased after 2009 but tuberculosis may have persisted (as subclinical disease) at extremely low levels, as indicated by the presence of low concentrations of circulating biomarkers. Biomarker-based diagnostic tests may offer a specific approach for early identification of M bovis infection.

OBJECTIVE To evaluate biomechanical properties of intact feline mandibles, compared with those for mandibles with an experimentally created osteotomy that was stabilized with 1 of 2 internal fixation configurations. SAMPLE 20 mandibles from 10 adult feline cadavers. PROCEDURES An incomplete block study design was used to assign the mandibles of each cadaver to 2 of 3 groups (locking plate with locking screws [locking construct], locking plate with nonlocking screws [nonlocking construct], or intact). Within each cadaver, mandibles were randomly assigned to the assigned treatments. For mandibles assigned to the locking and nonlocking constructs, a simple transverse osteotomy was created caudal to the mandibular first molar tooth after plate application. All mandibles were loaded in cantilever bending in a single-load-to-failure test while simultaneously recording load and actuator displacement. Mode of failure (bone or plate failure) was recorded, and radiographic evidence of tooth root and mandibular canal damage was evaluated. Mechanical properties were compared among the 3 groups. RESULTS Stiffness, bending moments, and most post-yield energies for mandibles with the locking and nonlocking constructs were significantly lower than those for intact mandibles. Peak bending moment and stiffness for mandibles with the locking construct were significantly greater than those for mandibles with the nonlocking construct. Mode of failure and frequency of screw damage to tooth roots and the mandibular canal did not differ between the locking and nonlocking constructs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both fixation constructs were mechanically inferior to intact mandibles. The locking construct was mechanically stronger than the nonlocking construct.

OBJECTIVE To evaluate the effect of bilateral ventriculocordectomy via ventral laryngotomy on laryngeal airway resistance (LAR) in canine cadaver larynges. SAMPLE 6 clinically normal canine cadaver larynges. PROCEDURES LAR was determined for each specimen before (baseline) and after bilateral ventriculocordectomy with the epiglottis open and closed. After ventral laryngotomy was performed, the vocal cords were sharply excised, and the incised mucosal edges were apposed with 4-0 glycomer 631 suture in a simple continuous pattern. The thyroid cartilage was apposed with 3-0 polypropylene suture in a simple continuous pattern. RESULTS With the epiglottis closed, baseline median LAR was 27.6 cm H2O/L/s (range, 21.2 to 30.6 cm H2O/L/s), which did not differ significantly from the median LAR after bilateral ventriculocordectomy (24.7 cm H2O/L/s [range, 20.6 to 27.7 cm H2O/L/s]). With the epiglottis open, baseline median LAR was 7.3 cm H2O/L/s (range, 5.4 to 7.8 cm H2O/L/s), which did not differ significantly from the median LAR after bilateral ventriculocordectomy (7.2 cm H2O/L/s [range, 6.6 to 7.6 cm H2O/L/s]). CONCLUSIONS AND CLINICAL RELEVANCE Bilateral ventriculocordectomy did not affect LAR with an open epiglottis in canine cadaver larynges. Therefore, it may not be an effective treatment for laryngeal paralysis. It also did not affect LAR with a closed epiglottis, which may indicate protection against aspiration pneumonia.

OBJECTIVE To evaluate the correlation between the density of native gastric Helicobacter spp and the presence of gastric lesions in dogs. ANIMALS 80 dogs of various breeds, sexes, and ages. PROCEDURES Gastroscopic and histologic examinations were performed for all dogs. Helicobacter spp were detected by combining evaluation of urease activity and results of bacteriologic culture, microscopic observation, and a 16S rRNA PCR assay. The density of Helicobacter-like organisms was evaluated with light microscopy by use of Warthin-Starry modified stain. Correlations were evaluated by use of the Spearman correlation analysis. RESULTS Gastritis was found in 55 of 80 dogs and classified as mild (n = 31), moderate (16), or severe (8). Of these 55 dogs, only 8 had clinical signs. Histologic examination revealed some degree of lymphocytic-plasmacytic infiltrate, mild eosinophilia, and neutrophilic inflammation in the lamina propria. Seventy-six dogs had positive results for Helicobacter spp. Helicobacter pylori DNA was not detected. Low density and homogeneous distribution of Helicobacter spp were observed in all gastric zones. CONCLUSIONS AND CLINICAL RELEVANCE A significant correlation between density of Helicobacter spp and gastroscopic or histologic lesions was not detected. These findings supported the contention that there is no correlation between general Helicobacter spp density or numbers and gastritis in dogs.

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.