Objective-To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis. Animals-8 purpose-bred mixed-breed dogs. Procedures-n a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward. Results-Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments. Conclusions and Clinical Relevance-HDA had no apparent effect on sodium urate–induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.

Objective-To objectively describe morphometric features of the craniocervical junction region of Cavalier King Charles Spaniels (CKCSs) and non-CKCS dogs with suspected Chiari-like malformation (CLM) and identify associations between these features and the presence of other malformations in this region. Animals-216 CKCSs and 58 non-CKCS dogs. Procedures-Magnetic resonance and computed tomographic images of the head and craniocervical junction region of patients evaluated because of suspected CLM were assessed for cerebellar compression (CC), ventral spinal cord compression at the C1-C2 articulation (medullary kinking), and dorsal spinal cord compression at the C1-C2 articulation (dorsal compression). A compression index was calculated for each of these 3 locations in each dog. Multiple logistic regression analysis was performed to determine whether breed (CKCS vs non-CKCS) and compression index values were associated with the presence of other craniocervical junction abnormalities. Results-All 274 dogs had CC; medullary kinking was identified in 187 (68.2%) and dorsal compression was identified in 104 (38.0%). Atlantooccipital overlapping (AOO) was identified in 76 (27.7%) dogs. Breed of dog (CKCS vs non-CKCS) and value of CC index were the only significant predictors of AOO. The CKCSs had an almost 5-fold decrease in risk of AOO, compared with the non-CKCS dogs, and the risk of AOO nearly doubled for every 10% increase in CC index. Conclusions and Clinical Relevance-The anatomic abnormality responsible for CC was AOO in a substantial percentage of dogs suspected to have CLM. The CC index value may be used to help differentiate subtypes of craniocervical junction abnormalities in dogs.

Objective-To evaluate respiratory mechanical function and bronchoalveolar lavage (BAL) cytologic results in healthy alpacas. Animals-16 client-owned adult alpacas. Procedures-Measurements of pulmonary function were performed, including functional residual capacity (FRC) via helium dilution, respiratory system resistance via forced oscillatory technique (FOT), and assessment of breathing pattern by use of respiratory inductive plethysmography (RIP) in standing and sternally recumbent alpacas. Bronchoalveolar lavage was performed orotracheally during short-term anesthesia. Results-Mean +/- SD measurements of respiratory function were obtained in standing alpacas for FRC (3.19 +/- 0.53 L), tidal volume (0.8 +/- 0.13 L), and respiratory system resistance at 1 Hz (2.70 +/- 0.88 cm H2O/L/s), 2 Hz (2.98 +/- 0.70 cm H2O/L/s), 3 Hz (3.14 +/- 0.77 cm H2O/L/s), 5 Hz (3.45 +/- 0.91 cm H2O/L/s), and 7 Hz (3.84 +/- 0.93 cm H2O/L/s). Mean phase angle, as a measurement of thoracoabdominal asynchrony, was 19.59 +/- 10.06°, and mean difference between nasal and plethysmographic flow measurements was 0.18 +/- 0.07 L/s. Tidal volume, peak inspiratory flow, and peak expiratory flow were significantly higher in sternally recumbent alpacas than in standing alpacas. Cytologic examination of BAL fluid revealed 58.52 +/- 12.36% alveolar macrophages, 30.53 +/- 13.78% lymphocytes, 10.95 +/- 9.29% neutrophils, 0% mast cells, and several ciliated epithelial cells. Conclusions and Clinical Relevance-Pulmonary function testing was tolerated well in nonsedated untrained alpacas. Bronchoalveolar lavage in alpacas yielded samples with adequate cellularity that had a greater abundance of neutrophils than has been reported in horses.

Objective: To determine the distribution of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) in skin (including hair follicles and sweat and sebaceous glands) of clinically normal dogs and dogs with atopic dermatitis (AD) and to compare results with those for positive control samples for CB1 (hippocampus) and CB2 (lymph nodes). Sample: Skin samples from 5 healthy dogs and 5 dogs with AD and popliteal lymph node and hippocampus samples from 5 cadavers of dogs. Procedures: CB1 and CB2 were immunohistochemically localized in formalin-fixed, paraffin-embedded sections of tissue samples. Results: In skin samples of healthy dogs, CB1 and CB2 immunoreactivity was detected in various types of cells in the epidermis and in cells in the dermis, including perivascular cells with mast cell morphology, fibroblasts, and endothelial cells. In skin samples of dogs with AD, CB1 and CB2 immunoreactivity was stronger than it was in skin samples of healthy dogs. In positive control tissue samples, CB1 immunoreactivity was detected in all areas of the hippocampus, and CB2 immunoreactivity was detected in B-cell zones of lymphoid follicles. Conclusions and Clinical Relevance: The endocannabinoid system and cannabimimetic compounds protect against effects of allergic inflammatory disorders in various species of mammals. Results of the present study contributed to knowledge of the endocannabinoid system and indicated this system may be a target for treatment of immune-mediated and inflammatory disorders such as allergic skin diseases in dogs.

Objective: To compare anatomic features of cross-sectional specimens with those of MRI images of the heads of loggerhead sea turtles (Caretta caretta). Animals: 5 cadavers of juvenile female loggerhead sea turtles. Procedures: Spin-echo T1-weighted and T2-weighted MRI scans were obtained in sagittal, transverse, and dorsal planes with a 0.2-T magnet and head coil. Head specimens were grossly dissected and photographed. Anatomic features of the MRI images were compared with those of gross anatomic sections of the heads from 4 of these turtles. Results: In the MRI images, anatomic details of the turtles' heads were identified by the characteristics of signal intensity of various tissues. Relevant anatomic structures were identified and labeled on the MRI images and corresponding anatomic sections. Conclusions and Clinical Relevance: The MRI images obtained through this study provided valid information on anatomic characteristics of the head in juvenile loggerhead sea turtles and should be useful for guiding clinical evaluation of this anatomic region in this species.

Objective: To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. Animals: 12 healthy adult horses (10 mares and 2 geldings). Procedures: Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed. Results: All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses. Conclusions and Clinical Relevance: Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.

Objective: To evaluate the role of the semitendinosus muscle in stabilization of the canine stifle joint. Sample: Left stifle joints collected from cadavers of 8 healthy Beagles. Procedures: Left hind limbs, including the pelvis, were collected. To mimic the tensile force of the quadriceps, gastrocnemius, and semitendinosus muscles, wires were placed under strain between the ends of each muscle. A sensor was used to measure the tensile force in each wire. Specimens were tested in the following sequence: cranial cruciate ligament (CrCL) intact, CrCL transected, released (tensile force of semitendinosus muscle was released in the CrCL-transected stifle joint), and readjusted (tensile force of semitendinosus muscle was reapplied in the CrCL-transected stifle joint). Specimens were loaded at 65.3% of body weight, and tensile force in the wires as well as the cranial tibial displacement were measured. Results: Tensile force for the CrCL-transected condition increased significantly, compared with that for the CrCL-intact condition. Mean ± SD cranial tibial displacement for the CrCL-transected condition was 2.1 ± 1.3 mm, which increased to 7.2 ± 2.3 mm after release of the tensile force in the semitendinosus muscle. Conclusions and Clinical Relevance: Results supported the contention that the semitendinosus muscle is an agonist of the CrCL in the stifle joint of dogs. Moreover, the quadriceps and gastrocnemius muscles may be antagonists of the CrCL. These findings suggested that the risk of CrCL rupture may be increased by diseases (such as cauda equina syndrome) associated with a decrease in activity of the semitendinosus muscle.

Objective-To establish the maximum tolerated dose of Clostridium novyi-NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. Animals-6 client-owned dogs. Procedures-A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C novyi-NT spores IV. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. Results-The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C novyi-NT infection; both required surgical intervention. Clostridium novyi-NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). Conclusions and Clinical Relevance-Results indicated that C novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin.

The Streptococcus suis 103 gene product is an immunogenic and protective lipoprotein that is a component of an ATP-binding cassette transporter implicated in zinc uptake. Belonging to the same transcriptional unit and downstream of the 103 gene is a gene that encodes a homologue of the pneumococcal histidine triad (Pht) protein Pht309. In an intraperitoneal mouse model the virulence of a mutant lacking the 103 gene was more than 50 times lower than that of the wild-type (WT) parent strain, S. suis serotype 2 strain P1/7. In addition, the immunogenicity of this mutant was dramatically decreased. In striking contrast, the virulence and immunogenicity of a P1/7 mutant lacking the Pht309 gene were similar to those of the parent strain. These results demonstrate that the 103 lipoprotein is strongly involved in S. suis virulence and support the hypothesis that this lipoprotein might be an excellent candidate for vaccines aiming to achieve broad protection against streptococci.