Objective—To evaluate the elimination pharmacokinetics of a single IM injection of a long-acting ceftiofur preparation (ceftiofur crystalline-free acid [CCFA]) in healthy adult helmeted guineafowl (Numida meleagris). Animals—14 healthy adult guineafowl. Procedures—1 dose of CCFA (10 mg/kg) was administered IM to each of the guineafowl. Blood samples were collected intermittently via jugular venipuncture over a 144-hour period. Concentrations of ceftiofur and all desfuroylceftiofur metabolites were measured in plasma via high-performance liquid chromatography. Results—No adverse effects of drug administration or blood collection were observed in any bird. The minimal inhibitory concentration (MIC) for many bacterial pathogens of poultry and domestic ducks (1 μg/mL) was achieved by 1 hour after administration in most birds and by 2 hours in all birds. A maximum plasma concentration of 5.26 μg/mL was reached 19.3 hours after administration. Plasma concentrations remained higher than the MIC for at least 56 hours in all birds and for at least 72 hours in all but 2 birds. The harmonic mean ± pseudo-SD terminal half-life of ceftiofur was 29.0 ± 4.93 hours. The mean area under the curve was 306 ± 69.3 μg•h/mL, with a mean residence time of 52.0 ± 8.43 hours. Conclusions and Clinical Relevance—A dosage of 10 mg of CCFA/kg, IM, every 72 hours in helmeted guineafowl should provide a sufficient plasma drug concentration to inhibit growth of bacteria with an MIC ≤ 1 μg/mL. Clinical use should ideally be based on bacterial culture and antimicrobial susceptibility data and awareness that use of CCFA in avian patients constitutes extralabel use of this product.

Objective—To evaluate expression of matrix metalloproteinase (MMP)-2 and -9 and membrane-type 1 MMP (MT1-MMP) in melanocytomas and malignant melanomas of dogs, analyze in vitro production of MMPs by canine melanoma cell lines and primary dermal fibroblasts, and investigate mutual communication between tumor cells and fibroblasts and the influence of collagen on MMP regulation. Sample—35 biopsy specimens from melanocytic tumors and primary dermal fibroblasts of dogs and 3 canine melanoma cell lines (CML-1, CML-10c2, and CML-6M). Procedures—MMP-2, MMP-9, and MT1-MMP were detected in tumor samples by use of unohistochemical analysis. In vitro production was analyzed via reverse transcriptase-PCR assay, immunocytochemical analysis, zymography, and immunoblotting. Results—MMP-9 was overexpressed in malignant melanomas, compared with expression in melanocytomas, whereas no significant differences in MMP-2 and MT1-MMP immunostaining were detected. Stromal cells also often had positive staining results. In vitro, all 3 melanoma cell lines and dermal fibroblasts had evidence of MMP-2 and MT1-MMP, but only melanoma cells had evidence of MMP-9. Coculture of CML-1 or CML-10c2 cells and dermal fibroblasts induced an increase in expression of the active form of MMP-2. Culture of melanoma cells on type I collagen increased the activation state of MT1-MMP. Conclusions and Clinical Relevance—MMP-9 expression was increased in malignant melanomas of dogs. Stromal cells were a source for MMPs. Stromal cells, in combination with matrix components such as type I collagen, can interact with tumor cells to regulate MMP production. Information about MMP production and regulation could help in the development of new treatments.

Objective—To compare in vitro axial compression, abaxial compression, and torsional stiffnesses of intact and plated radii from small- and large-breed dogs. Sample—Radii from 18 small-breed and 9 large-breed skeletally mature dogs. Procedures—3 groups were tested: large-breed dog radii plated with 3.5-mm limited-contact dynamic compression plates (LCDCPs), small-breed dog radii plated with 2.0-mm dynamic compression plates (DCPs), and small-breed dog radii plated with 2.0/2.7-mm cut-to-length plates (CTLPs). The axial compression, abaxial compression, and torsional stiffnesses of each intact radius were determined under loading with a material testing machine. An osteotomy was performed, radii were plated, and testing was repeated. The stiffness values of the plated radii were expressed as absolute and normalized values; the latter was calculated as a percentage of the stiffness of the intact bone. Absolute and normalized stiffness values were compared among groups. Results—The absolute stiffnesses of plated radii in axial and abaxial compression were 52% to 83% of the intact stiffnesses in all fixation groups. No difference was found in torsion. There was no difference in normalized stiffnesses between small-breed radii stabilized with CTLPs and large-breed radii stabilized with LCDCPs; however, small-breed radii stabilized with DCPs were less stiff than were any other group. Conclusions and Clinical Relevance—Plated radii of small-breed dogs had normalized stiffnesses equal to or less than plated radii of large-breed dogs. The complications typically associated with plating of radial fractures in small-breed dogs cannot be ascribed to an overly stiff bone-plate construct.

Objective—To determine selected cardiopulmonary values and baroreceptor response in conscious green iguanas (Iguana iguana) and to evaluate the use of blood gas analysis and pulse oximetry in this species. Animals—15 healthy juvenile green iguanas. Procedures—Baseline cardiopulmonary values were determined in 15 conscious iguanas breathing room air. Effects of 100% O2 inspiration were also measured (n = 6), and the baroreceptor reflex was characterized by exponential sigmoidal curve fitting analysis. Results—Conscious iguanas had a mean ± SD resting heart rate of 52 ± 8 beats/min, respiratory rate of 28 ± 6 breaths/min, and systolic, mean, and diastolic arterial blood pressures of 69 ± 10 mm Hg, 62 ± 12 mm Hg, and 56 ± 13 mm Hg, respectively. Mean arterial pH at 37°C was 7.29 ± 0.11, Pao2 was 81 ± 10 mm Hg, and Paco2 was 42 ± 9 mm Hg; corrected for a body temperature of 30°C, mean arterial pH at 37°C was 7.382 ±0.12, Pao2 was 54 ± 15 mm Hg, and Paco2 was 32 ± 7 mm Hg. Inspiration of 100% O2 did not change heart and respiratory rates but increased Pao2 to 486 ± 105 mm Hg (corrected value, 437 ± 96 mm Hg). A baroreceptor reflex was evident, with mean heart rates ranging from 30 ± 3 beats/min to 63 ± 5 beats/min and mean arterial blood pressures ranging from 42 ± 3 mm Hg to 58 ± 3 mm Hg. Conclusions and Clinical Relevance—This study provided needed information on cardiopulmonary values in healthy green iguanas, the application and limitation of arterial and venous blood gas analysis, and the accuracy of pulse oximetry.

Objective—To determine the analgesic and systemic effects of thoracic epidural administration of ketamine, lidocaine, or both in conscious dogs. Animals—6 adult mixed-breed dogs. Procedures—Each dog received 2% lidocaine hydrochloride without epinephrine (3.8 mg/kg), 5% ketamine hydrochloride (3.0 mg/kg), or both in randomized order with = 1 week between treatments. Drugs were administered in a total volume of 0.25 mL/kg through a thoracic epidural catheter implanted via the lumbosacral approach. Heart rate, blood pressure, respiratory rate, rectal temperature, analgesia, sedation, and ataxia were determined before treatment (baseline [time 0]) and at 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, and 180 minutes after administration. Results—The main areas of analgesia for the 3 treatments were the thorax and forelimbs bilaterally. Median duration of analgesia was shorter after administration of ketamine (30 minutes) than after administration of lidocaine (40 minutes) and lidocaine plus ketamine (90 minutes). All treatments caused moderate motor blockade, and only the ketamine and lidocaine plus ketamine treatments caused mild sedation. Significant decreases in systolic and mean arterial blood pressure were observed only with the lidocaine plus ketamine treatment. Conclusions and Clinical Relevance—Thoracic epidural administration of lidocaine plus ketamine resulted in longer duration of analgesia of the thorax and forelimbs bilaterally in conscious dogs, compared with administration of ketamine or lidocaine alone. Additional studies are needed to determine whether this technique adequately relieves postoperative pain after thoracic surgical procedures and whether it causes respiratory depression in dogs.

Objective-To determine the effects of once-daily oral administration of N-acetyl-d-glucosamine (NAG) on plasma and urine glycosaminoglycan (GAG) concentrations in cats with idiopathic cystitis (IC). Animals-19 cats with IC and 10 clinically normal cats. Procedures-Cats with IC were randomly assigned to receive 250 mg of NAG in capsule form orally once daily for 28 days (n = 12) or a placebo (capsule containing cellulose) orally once daily for the same period (7). In cats with IC, plasma and urine GAG concentrations and urine creatinine concentration were measured on days 0 (immediately before first dose), 7, 14, 21, 28, and 56. For purposes of comparison, those variables were measured in 10 clinically normal cats on day 0. Results-Mean +/- SEM urine GAG-to-creatinine concentration ratios (day 0 data) for cats with IC and clinically normal cats differed significantly (3.11 +/- 0.62 μg/mL and 14.23 +/- 3.47 μg/mL, respectively). For cats with IC, mean plasma GAG concentration in NAG-treated cats (39.96 +/- 5.34 micrograms/mL) was higher than that in placebo-treated cats (24.20 +/- 3.35 micrograms/mL) on day 21. In the NAG-treated cats, plasma GAG concentration on days 21 (39.96 +/- 5.34 micrograms/mL) and 28 (39.91 +/- 6.74 micrograms/mL) differed significantly from the day 0 concentration (27.46 +/- 3.90 micrograms/mL). Conclusions and Clinical Relevance-Cats with IC have lower urinary GAG-to-creatinine concentration ratios than did clinically normal cats. Administration of NAG (250 mg, PO, q 24 h) significantly increased plasma GAG concentrations in cats with IC after 21 days of treatment.

Objective—To evaluate the ability of 2-D time-of-flight (ToF) magnetic resonance angiography (MRA) to depict intracranial vasculature and compare results obtained with 3.0- and 7.0-T scanners in dogs. Animals—5 healthy Beagles. Procedures—2-D ToF-MRA of the intracranial vasculature was obtained for each dog by use of a 3.0-T and a 7.0-T scanner. Quantitative assessment of the images was obtained by documentation of the visibility of major arteries comprising the cerebral arterial circle and their branches and recording the number of vessels visualized in the dorsal third of the brain. Qualitative assessment was established by evaluation of overall image quality and image artifacts. Results—Use of 3.0- and 7.0-T scanners allowed visualization of the larger vessels of the cerebral arterial circle. Use of a 7.0-T scanner was superior to use of a 3.0-T scanner in depiction of the first- and second-order arterial branches. Maximum-intensity projection images had a larger number of vessels when obtained by use of a 7.0-T scanner than with a 3.0-T scanner. Overall, image quality and artifacts were similar with both scanners. Conclusions and Clinical Relevance—Visualization of the major intracranial arteries was comparable with 3.0- and 7.0-T scanners; the 7.0-T scanner was superior for visualizing smaller vessels. Results indicated that ToF-MRA is an easily performed imaging technique that can be included as part of a standard magnetic resonance imaging examination and should be included in the imaging protocol of dogs suspected of having cerebrovascular disease.

Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle. Animals—33 healthy Angus calves approximately 7 to 8 months of age. Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry. Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells. Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.

The present study investigated whether the 14-3-3 η and γ proteins, which are potent matrix metalloprotease (MMP) stimulators, are detectable in the synovial fluid of dogs with cranial cruciate ligament rupture (CCLR). Synovial fluid samples from 7 dogs with unilateral CCLR and control samples from 4 dogs without a history of any joint inflammation or any other abnormalities underwent Western blot analysis for the 14-3-3 η, γ, and σ proteins as well as MMP-1 and MMP-3. Craniocaudal and lateral radiographic projections of the stifle joint were evaluated for the presence and severity of 13 specific radiographic markers of osteoarthritis and graded numerically. The Spearman method was used to detect any correlation between the 14-3-3-η level in the synovial fluid and the radiograph-based grade. The η isoform was present only in the samples from the dogs with CCLR. The levels of 14-3-3-γ, MMP-1, and MMP-3 were significantly higher in the samples from the dogs with CCLR than in the control samples (P < 0.05). However, there was no significant difference between the CCLR and control samples in the level of the σ isoform. The Spearman method showed a significant correlation between the 14-3-3-η level in the synovial fluid and the presence of either patellar osteophytes or lateral or medial (or both) condylar periarticular osteophytes (P < 0.05). The MMP stimulatory effect of the 14-3-3 η and γ isoforms may be the reason for the high levels of MMP-1 and MMP-3 observed. Thus, 14-3-3 proteins, especially the η isoform, may be important markers of osteoarthritis caused by CCLR.

The objective of this study was to experimentally infect calves with bovine viral diarrhea virus (BVDV) isolated from free-ranging white-tailed deer. Twelve colostrum-deprived male Holstein calves were used. Eight were inoculated intranasally with a BVDV type 1a isolated from free-ranging white-tailed deer, and the other four were inoculated with the cell culture medium only and served as a control group. Whole blood, saliva, and nasal and rectal secretions were collected on days 0, 3, 7, 10, 14, 17, and 21 after inoculation for virus isolation and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). On days 14 and 21, 4 calves in the infected group and 2 in the control group were euthanized; multiple tissue samples were collected for histopathologic study. Histopathologic changes included thymic atrophy and lymphoid depletion of the Peyer's patches in all 8 infected calves. The RT-PCR gave positive results with the buffy coat of all 8 infected calves, the nasal samples of 7, and the saliva samples of 2. Virus neutralization testing of the serum gave positive results for 4 of the 8 infected calves, and enzyme-linked immunosorbent assay of the serum gave positive results for 3. All of the samples from the control calves yielded negative results.