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 the degree of histomorphometric damage in dorsal colon and pelvic flexure biopsy specimens (DCBSs and PFBSs, respectively) obtained from horses with large colon volvulus (LCV) and assess the accuracy of predicting short-term outcome for those horses on the basis of DCBS or PFBS characteristics. ANIMALS 18 horses with ≥ 360° LCV that underwent large colon resection. PROCEDURES During surgery, biopsy specimens from the dorsal colon resection site and the pelvic flexure (when available) were collected from each horse. Interstitial-to-crypt (I:C) ratio (ratio of the lamina propria space occupied by the interstitium to that occupied by crypts), hemorrhage within the lamina propria (mucosal hemorrhage score [MHS] from 0 to 4), and percentage losses of glandular and luminal epithelium were determined in paired biopsy specimens and compared to determine optimal cutoff values for calculating the accuracy of DCBS and PFBS characteristics to predict short-term outcome (survival or nonsurvival after recovery from surgery). RESULTS Paired biopsy specimens were obtained from 17 of the 18 horses. The I:C ratio and percentage glandular epithelial loss differed between DCBSs and PFBSs. For DCBSs, an I:C ratio ≥ 0.9 and MHS ≥ 3 each predicted patient nonsurvival with 77.8% accuracy. For PFBSs, an I:C ratio ≥ I and MHS ≥ 3 predicted patient nonsurvival with 70.6% and 82.4% accuracy, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Although different, histomorphometric measurements for either DCBSs or PFBSs could be used to accurately predict short-term outcome for horses with LCV that underwent large colon resection, and arguably PFBSs are easier to collect.

The endocannabinoid (eCB) system modulates the degree of injury caused by inflammation, while enhancing the activity of phagocytes that promote resolution of inflammation and tissue repair. In-vitro studies with the monoacylglycerol lipase (MAGL) inhibitor JZL184 have suggested that increased eCB signaling might enhance the ability of the host immune system to clear invading pathogens. Although the neurochemical effects of JZL184 on the eCB system in rodents are well-known, its immuneregulating effects are less clear, especially in chickens. The primary objective of this study was to explore whether modulating the eCB system affects immune responses in chickens. To do this, we administered JZL184 [10 and 40 mg/kg body weight (BW), intraperitoneal injection] into chickens prior to a challenge with avian pathogenic Escherichia coli (APEC) O78. Bacteria were isolated from livers, blood, air sacs, and hearts at 8, 28, and 56 h post-infection and the gross lesions in air sacs, livers, and hearts were also examined. Serum levels of JZL184 were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which indicated that the drug was distributed systemically. The number of birds positive for airsacculitis after APEC O78 challenge was marginally higher in groups treated with JZL184 than in the control group (P = 0.064). Rather than augmenting host defense and enhancing pathogen clearance, these results suggested that JZL184 might have immunosuppressive effects that exacerbated APEC O78 infection in chickens.

The objective of this study was to evaluate the association between ketonemia and serum paraoxonase-1 (PON1), malondialdehyde (MDA), and other blood components in tail and mammary veins of dairy cows. Forty-two Holstein dairy cows with decreased feed intake were divided into HIGH (≥ 1.2 mM; n = 31) and LOW (< 1.2 mM; n = 11) groups based on the β-hydroxybutyrate concentration in plasma collected from the tail vein. The HIGH group had a significantly greater plasma non-esterified fatty acid (NEFA) concentration, but significantly lower serum PON1 activity and phospholipid concentration, and a tendency to have a lower cholesterol ester concentration than the LOW group. Serum PON1 activity was not correlated with the MDA concentration but was positively correlated with serum concentrations of cholesterol esters and phospholipids, and negatively correlated with the plasma NEFA concentration. These results suggest that serum PON1 activity is reduced by hyperketonemia and the relevance of PON1 to MDA seems to not be direct, though it is involved.

A prospective study of 65 research beagles kept in a rabies-free environment was undertaken to determine the duration of immunity after they received licensed rabies vaccines. The eventual goal was to extend mandated rabies booster intervals to 5 or 7 years and help reduce the risk of vaccine-associated adverse events. Three groups of dogs were vaccinated with 1 of 2 commercial rabies vaccines or saline at 12 and 15 weeks of age. Beginning 5 years 5 months later, vaccinated and unvaccinated dogs were challenged with virulent rabies virus and observed for 90 days over a series of 3 trials. Humoral and cellular immune responses were examined by serology and flow cytometry. Brain tissue from all challenged dogs was tested for rabies virus. Challenge trial 1 was confounded due to insufficiently virulent virus. In trials 2 and 3 virulent challenge provided 100% mortality in controls. Vaccinate survival was 80% (4/5) after 6 years 7 months, 50% (6/12) after 7 years 1 month, and 20% (1/5) after 8years 0 months. Antibody responses 12 days post-challenge correlated strongly with survival. In a separate non-challenge trial, administration of either a recombinant or a killed rabies vaccine demonstrated memory antibody responses 6 years 1 month after initial vaccination compared with unvaccinated controls. Our data demonstrated that i) duration of immunity to rabies in vaccinated dogs extends beyond 3 years; ii) immunologic memory exists even in vaccinated dogs with serum antibody titer < 0.1 IU/mL; and iii) non-adjuvanted recombinant rabies vaccine induces excellent antibody responses in previously vaccinated dogs 14 days after administration.

OBJECTIVE To compare the torsional mechanical properties of 2 external skeletal fixators (ESFs) placed with 2 intramedullary pin (IP) and transfixation pin (TP) size combinations in a model of raptor tibiotarsal bone fracture. SAMPLE 24 ESF-synthetic tibiotarsal bone model (polyoxymethylene) constructs. PROCEDURES Synthetic bone models were fabricated with an 8-mm (simulated fracture) gap. Four types of ESF-synthetic bone model constructs (6/group) were tested: a FESSA with a 1.6-mm IP and 1.6-mm TPs, a FESSA with a 2.0-mm IP and 1.1-mm TPs, an acrylic connecting bar with a 1.6-mm IP and 1.6-mm TPs, and an acrylic connecting bar with a 2.0-mm IP and 1.1-mm TPs. Models were rotated in torsion (5°/s) to failure or the machine angle limit (80°). Mechanical variables at yield and at failure were determined from load deformation curves. Effects of overall construct type, connecting bar type, and IP and TP size combination on mechanical properties were assessed with mixed-model ANOVAs. RESULTS Both FESSA constructs had significantly greater median stiffness and median torque at yield than both acrylic bar constructs; FESSA constructs with a 1.6-mm IP and 1.6-mm TPs had greatest stiffness of all tested constructs and lowest gap strain at yield. No FESSA constructs failed during testing; 7 of 12 acrylic bar constructs failed by fracture of the connecting bar at the interface with a TP. CONCLUSIONS AND CLINICAL RELEVANCE Although acrylic bar ESFs have been successfully used in avian patients, the FESSA constructs in this study were mechanically superior to acrylic bar constructs, with greatest benefit resulting from use with the larger TP configuration.

The objective of this study was to evaluate the efficacy of a modified-live virus (MLV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against a heterologous PRRSV-2 challenge in late-term pregnancy gilts under experimental conditions. Eighteen gilts were randomly assigned to vaccinated-challenged, unvaccinated-challenged, and unvaccinated-unchallenged groups (n = 6 gilts per group). Pregnant gilts in the vaccinated-challenged and unvaccinated-unchallenged groups were able to carry their pregnancies to full term and farrowed after 114 to 115 days of gestation. In contrast, pregnant gilts in the unvaccinated-challenged group did not reach full term and farrowed early, after 104 to 108 days of gestation. Pregnant gilts vaccinated with the PRRSV-2 MLV vaccine exhibited a reduction in PRRSV-2 viremia. At the time of challenge with PRRSV-2, vaccinated gilts had relatively low levels of neutralizing antibody titers (≤ 1:16 titer), whereas the number of interferon-γ-secreting cells (IFN-γ-SC) was consistently at protective levels (IFN-γ-SC, ≥ 150 per million). Induction of cell-mediated immunity, as measured by PRRSV-2-specific IFN-γ-SC, correlated with a reduction in PRRSV-2 viremia. Duration of immunity was a minimum of 19 wk. Taken together, the results presented here suggest that vaccination of gilts with a PRRSV-2 MLV vaccine can protect against a heterologous PRRSV-2 challenge and improve the reproductive performance of late-term pregnancy gilts.

OBJECTIVE To determine values of F-wave parameters for the tibial nerve in clinically normal Miniature Dachshunds and those with thoracolumbar intervertebral disk herniation (IVDH). ANIMALS 53 Miniature Dachshunds (10 clinically normal and 43 with various clinical grades of thoracolumbar IVDH). PROCEDURES F-waves were elicited in the interosseous muscles of 1 hind limb in each dog by stimulation of the tibial nerve. F-wave parameters were measured for 32 stimuli/dog, and mean values were calculated. Linear regression was performed to assess correlations between F-wave parameters and clinical severity of IVDH. RESULTS For clinically normal dogs, mean ± SD values of shortest F-wave latency, mean F-wave conduction velocity, mean F-wave duration, and ratio of the mean F-wave amplitude to M response amplitude were 8.6 ± 0.6 milliseconds, 83.7 ± 6.1 m/s, 6.6 ± 1.5 milliseconds, and 9.8 ± 8.5%, respectively. F-wave persistence was 100%. Mean F-wave duration was positively correlated with clinical grade of IVDH. Linear regression yielded the following regression equation: F-wave duration (milliseconds) = 6.0 + 2.7 × IVDH grade. One dog with grade 2 IVDH had a mean F-wave duration shorter than that of all 5 dogs with grade 1 IVDH; 1 dog with grade 3 IVDH had a longer duration than that of all 10 dogs with grade 4 IVDH. CONCLUSIONS AND CLINICAL RELEVANCE Mean F-wave duration was correlated with the severity of inhibitory motor tract dysfunction in the spinal cord of dogs. F-wave examination may be useful for objective functional evaluation of upper motor neurons in the spinal cord.

OBJECTIVE To determine the efficacy and duration of effect for liposomal bupivacaine following perineural administration to the medial and lateral palmar digital nerves of horses. ANIMALS 9 nonlame mares. PROCEDURES For each horse, 2 mL of liposomal bupivacaine (13.3 mg/mL; total dose, 53.2 mg or approx 0.11 mg/kg) or sterile saline (0.9% NaCl) solution was injected adjacent to the medial and lateral palmar digital nerves at the level of the distal aspect of the proximal sesamoid bones of a randomly selected forelimb. Twenty-one days later, the opposite treatment was administered in the contralateral forelimb. A digital algometer was used to measure the mechanical nociceptive threshold (MNT) immediately before and at predetermined times for 48 hours after injection of each treatment. The mean MNT was compared between the 2 treatments at each measurement time. RESULTS The mean MNT for the liposomal bupivacaine-treated limbs was significantly greater (ie, the limb was less sensitive) than that for the saline-treated limbs between 30 minutes and 4 hours after treatment injection. Following liposomal bupivacaine administration, 1 horse developed mild swelling at the injection sites that resolved without treatment within 24 hours. No other adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that liposomal bupivacaine is another option for perineural anesthesia in horses. Further research is necessary to determine the optimal dose and better elucidate the duration of effect for the drug when used for palmar digital nerve blocks in horses.

Recumbency affects respiratory mechanics and oxygenation in anesthetized horses. Changes in pleural and abdominal pressures that can impair ventilation have not been described in all recumbencies. The objective of this study was to determine the effects of patient positioning on transdiaphragmatic pressure and selected hemodynamic variables. Horses were maintained under total intravenous general anesthesia with nasal oxygen supplementation. Transnasal balloon catheters in the stomach and thoracic esophagus were used to measure intrathoracic and gastric pressures in standing horses and in anesthetized horses positioned in right and left lateral recumbency, dorsal recumbency, reverse Trendelenburg position, and Trendelenburg position. Transdiaphragmatic pressure was calculated as the difference between gastric and intrathoracic pressures. Measurements of oxygen saturation (SpO(2)), heart rate, systolic, diastolic and mean arterial pressures, and respiratory rate were obtained every 5 minutes. When compared to dorsal recumbency, gastric expiratory pressure is decreased in the standing position. Thoracic expiratory pressure is decreased in standing and reverse Trendelenburg. Transdiaphragmatic expiratory pressure and SpO(2) are decreased in Trendelenburg. Heart rate is increased in reverse Trendelenburg. Systolic, diastolic, and mean arterial pressures are decreased in reverse Trendelenburg and increased in left lateral and right lateral recumbency. We found that there is wide variation in respiratory pressures between horses and positions and they are not predictive of associated changes in hemodynamic variables.