OBJECTIVE To determine the pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs. ANIMALS 6 healthy adult dogs. PROCEDURES Each dog received a single dose of trazodone (approx 8 mg/kg) per rectum. Trazodone tablets were crushed into a powder, mixed with 5 mL of tap water, and injected into the rectum via a red rubber catheter. Sedation scores were assigned, and blood samples were collected for determination of plasma trazodone concentration at predetermined times before and after drug administration. Pharmacokinetic parameters were estimated by noncompartmental analysis. RESULTS Plasma trazodone concentration remained below the detection limit for 1 dog even though it became moderately sedate. Median (interquartile [25th to 75th percentile] range [IQR]) maximum plasma trazodone concentration and volume of distribution and clearance corrected for bioavailability were 1.00 μg/mL (0.66 to 1.40 μg/mL), 10.3 L/kg (7.37 to 14.4 L/kg), and 639 mL/kg/h (594 to 719 mL/kg/h), respectively. Median time to maximum plasma trazodone concentration and elimination half-life were 15 minutes (range, 15 to 30 minutes) and 12 hours (IQR, 7.99 to 12.7 hours), respectively. All dogs became mildly or moderately sedate, and the extent of sedation was maximal at a median of 30 minutes (IQR, 30 to 60 minutes) after trazodone administration. No adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Rectal administration of trazodone may be a viable option for sedation and treatment of anxiety in dogs for which administration of sedatives and anxiolytics by other routes is contraindicated. Further research is necessary to better elucidate the pharmacokinetics and efficacy of trazodone following rectal administration and determine optimal dosing.

OBJECTIVE To determine whether cell-free DNA (cfDNA) was detectable in CSF samples from dogs, whether CSF sample volume impacted CSF cfDNA concentration measurement, and whether CSF cfDNA concentration was associated with CNS disease category or CSF RBC count (RBCC), nucleated cell count (NCC), or protein concentration, which could aid in the diagnosis of neurologic diseases in dogs. SAMPLE 80 CSF samples collected from dogs with (n = 60) and without (20) clinical neurologic disease between February 2017 and May 2018. PROCEDURES Results for CSF RBCC, NCC, protein concentration, and cfDNA concentration were compared across CSF groups established on the basis of whether they were obtained from dogs with (case groups) or without (control group) clinical signs of neurologic disease In addition, 5 paired CSF samples representing large (3.0-mL) and small (0.5-mL) volumes, were used to evaluate whether sample volume impacted measurement of CSF cfDNA concentration. RESULTS cfDNA was detected in 76 of the 80 (95%) CSF samples used to evaluate parameters across disease categories and in all 5 of the paired samples used to evaluate whether sample volume impacted cfDNA quantification. There were no substantial differences in cfDNA concentrations identified between groups (on the basis of disease category or sample volume), and the CSF cfDNA concentration did not meaningfully correlate with CSF RBCC, NCC, or protein concentration. CONCLUSIONS AND CLINICAL RELEVANCE Although results indicated that the CSF cfDNA concentration could not be used to differentiate between categories of neurologic disease in dogs of the the present study, further investigation is warranted regarding the use of CSF analysis, including sequencing specific cfDNA mutations, for diagnosing and monitoring neurologic disease in dogs.

OBJECTIVE To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). ANIMALS 15 MDs with ICRPs and 5 dogs with non–ICRP-related large bowel diarrhea (controls). PROCEDURES Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro–MMP-2 and pro–MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed. RESULTS Activities of pro–MMP-2 and pro–MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro–MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity. CONCLUSIONS AND CLINICAL RELEVANCE Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.

OBJECTIVE To assess the effect of transrectal palpation (TRP) performed with the fetal membrane slip (FMS) technique for early pregnancy diagnosis on the proportion and type of associated pregnancy losses (PLs) in dairy cattle. ANIMALS 580 healthy pregnant cattle. PROCEDURES Data for artificially inseminated females with 1 or 2 viable embryos detected by transrectal ultrasonography (TRUS) at approximately 30 days of gestation were retrospectively assessed. Cattle were assigned to 1 of 2 groups on the basis of whether they did or did not undergo TRP once between 34 and 41 days of gestation (palpation and control group, respectively). At approximately 45 and 60 days of gestation, all cattle were reevaluated by TRUS; PL was categorized as type I (FMS detectable by TRP and TRUS-confirmed evidence of embryo or fetus degeneration and a functional corpus luteum) or type II (FMS undetectable by TRP and no TRUS-confirmed evidence of an embryo or fetus or of a functional corpus luteum). RESULTS Of the 580 healthy pregnant cattle, 271 underwent TRP and 309 did not. In the palpation and control groups, PL occurred in 40 (14.8%) and 47 (15.2%) cattle, respectively. Among the palpation group's PLs, 17 (43%) were type I and 23 (58%) were type II. Among the control group's PLs, 27 (57%) were type I and 20 (43%) were type II. The prevalance and type of PL did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE TRP with the FMS technique for early pregnancy diagnosis did not increase the prevalence of PL in dairy cattle or alert the proportion of type I versus type II PL.

OBJECTIVE To evaluate the time and number of laser beam passes required to make full-thickness skin incisions and extent of laser-induced tissue artifacts following use of a CO(2) laser at various settings. SAMPLE 24 skin specimens from six 5-month-old porcine carcasses. PROCEDURES 4 full-thickness skin specimens were harvested from the flank regions of each carcass within 30 minutes after euthanasia and randomly assigned to 4 treatment groups. Three 5-cm-long incisions were made in each specimen with a CO(2) laser (beam diameter, 0.4 mm) set to deliver a continuous wave of energy alone (groups 1 and 2) or in superpulse mode (groups 3 and 4) at 10 (groups 1 and 3) or 20 (groups 2 and 4) W of power. The time and number of passes required to achieve a full-thickness incision were recorded, and extent of laser-induced tissue artifact (as determined by histologic evaluation) was compared among the 4 groups. RESULTS Mean time required to make a full-thickness skin incision for groups 2 and 4 (power, 20 W) was significantly less than that for groups 1 and 3 (power, 10 W). Mean number of passes was lowest for group 2 (continuous wave at 20 W). Extent of laser-induced tissue artifact was greatest for group 4 (superpulse mode at 20 W). CONCLUSIONS AND CLINICAL RELEVANCE Results provided preliminary information regarding use of CO(2) lasers to make skin incisions in veterinary patients. In vivo studies are necessary to evaluate the effect of various CO(2) laser settings on tissue healing and patient outcome.

OBJECTIVE To determine whether a dose-response relationship exists between short-term oral prednisone administration and common clinicopathologic variables, cardiovascular biomarkers, and systolic arterial blood pressure (SAP) in healthy dogs. ANIMALS 8 healthy Beagles. PROCEDURES Dogs underwent five 5-day experiments (no prednisone treatment [control condition] and prednisone administration at 0.5, 1, 2, and 4 mg/kg, PO, q 24 h), with a 9-day washout period between protocols. Analyses performed before and after treatments included a CBC, serum biochemical analysis, and determination of SAP, fractional excretion of electrolytes, urine protein-to-creatinine ratio, glomerular filtration rate (GFR), serum N-terminal pro B–type natriuretic peptide (NT-proBNP) and plasma cortisol concentrations, and plasma renin activity. Linear mixed-effects modeling was used to compare changes in variables from baseline (day 1 for the same experiment) among treatment conditions. RESULTS Changes in serum glucose concentration and GFR were significantly greater after administration of prednisone at 4 mg/kg than for the control condition. Fractional excretion of sodium was decreased from baseline when dogs received 0.5, 1, or 4 mg of prednisone/kg, compared with results for the control condition. Several expected changes in clinicopathologic values were observed after prednisone administration at any dose. Changes in serum NT-proBNP concentration, plasma renin activity, and SAP did not differ from changes for the control condition at any prednisone dose. CONCLUSIONS AND CLINICAL RELEVANCE Oral prednisone administration did not affect SAP, NT-proBNP concentration, or measures of renin-angiotensin-aldosterone system activation in healthy laboratory-housed dogs but was associated with relative increases in GFR and serum glucose concentration.

Achyranthes japonica Nakai (A. japonica) is a medicinal herb found widely distributed throughout Korea. The biological activities of A. japonica are well-documented and include anti-fungal, anti-inflammatory, and immunity enhancement. The objective of the present study was to investigate the immune-related activities of A. japonica extract in dogs. The extract was acquired by ethanol extraction and purified by filtration. To examine the effect of A. japonica extract on immune cell viability, human lymphocytes, such as Jurkat T-cells and Ramos B-cells, were exposed to the extract. After treatment with the extract, the number of Ramos B-cells was increased, whereas Jurkat T-cells remained unaffected. Griess assay revealed decreased nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage Raw 264.7 cells after exposure to A. japonica extract. To evaluate the in-vivo effect in dogs, feed containing A. japonica extract was provided to 8 dogs for 2 months. Blood samples were collected before, during, and after consumption of the feed. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples and the number of T-cells and B-cells were assessed using flow cytometry with anti-dog fluorescein isothiocyanate (FITC)-conjugated CD3 and anti-dog phycoerythrin (PE)-conjugated CD21 antibodies, respectively. We observed a significant increase in the average number of B-cells in the PBMCs during ingestion of the feed containing A. japonica. In addition, enzyme-linked immunosorbent assay (ELISA) revealed a decrease in the levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in 3 out of 8 dogs and increased levels of interleukin-10 (IL-10), an anti-inflammatory cytokine, in 4 out of 8 dogs. Taken together, we believe that these changes indicate that A. japonica extract is beneficial in improving the immunity of dogs by stimulating B-cells and inducing production of anti-inflammatory responses.

OBJECTIVE To determine the thermal antinociceptive effects of butorphanol tartrate and butorphanol tartrate in a sustained-release 25% poloxamer 407 (P407) gel formulation (But-P407) in parrots. ANIMALS 13 orange-winged Amazon parrots (Amazona amazonica). PROCEDURES First, butorphanol tartrate (5 mg/kg) or saline (0.9% NaCl) solution was administered IM to birds in a randomized complete crossover design. The temperature prompting a foot withdrawal response to a thermal stimulus (ie, the thermal threshold) was determined 30 minutes before (baseline) and at various points after treatment administration. Second, But-P407 (12.5 mg/kg) or P407 was administered SC in a similar crossover design. Thermal threshold was determined before and at various points after treatment administration. Third, But-P407 (12.5 mg/kg) or saline solution was administered SC and evaluated as in the second trial. Sedation was scored immediately before each time point in all 3 trials. RESULTS In the first trial, a significant increase in thermal threshold was noted 30 minutes after butorphanol tartrate (vs saline solution) administration. No sedation was noted. In the second and third trials, no significant difference was identified between results for But-P407 and those for either control treatment (saline solution or P407). Mild sedation was noted in the second trial following But-P407 administration. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a small but significant thermal antinociceptive effect of butorphanol tartrate lasting between 30 minutes and 1.5 hours in orange-winged Amazon parrots. No antinociceptive effect of butorphanol tartrate was demonstrated when delivered in P407. Further research is needed to evaluate the potential analgesic effects of But-P407.

OBJECTIVE To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica). ANIMALS 8 orange-winged Amazon parrots (4 males and 4 females). PROCEDURES Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV. RESULTS Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.

OBJECTIVE To determine whether a customized unilateral intervertebral anchored fusion device combined with (vs without) an intervertebral spacer would increase the stability of the L1-L2 motion segment following complete intervertebral diskectomy in canine cadaveric specimens. SAMPLE Vertebral columns from T13 through L3 harvested from 16 skeletally mature Beagles without thoracolumbar disease. PROCEDURES Complete diskectomy of the L1-2 disk was performed in each specimen. Unilateral stabilization of the L1-L2 motion segment was performed with the first of 2 implants: a unilateral intervertebral anchored fusion device that consisted of a locking compression plate with or without an intervertebral spacer. The resulting construct was biomechanically tested; then, the first implant was removed, and the second implant was applied to the contralateral side and tested. Range of motion in flexion and extension, lateral bending, and torsion was compared among intact specimens (prior to diskectomy) and constructs. RESULTS Compared with intact specimens, constructs stabilized with either implant were as stable in flexion and extension, significantly more stable in lateral bending, and significantly less stable in axial rotation. Constructs stabilized with the fusion device plus intervertebral spacer were significantly stiffer in lateral bending than those stabilized with the fusion device alone. No significant differences in flexion and extension and rotation were noted between implants. CONCLUSIONS AND CLINICAL RELEVANCE Findings did not support the use of this customized unilateral intervertebral anchored fusion device with an intervertebral spacer to improve unilateral stabilization of the L1-L2 motion segment after complete L1-2 diskectomy in dogs.