OBJECTIVE To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in guinea pigs (Cavia porcellus). ANIMALS 8 healthy adult guinea pigs (4 sexually intact females and 4 sexually intact males). PROCEDURES In a crossover study, hydromorphone (0.3 mg/kg) was administered once IM (epaxial musculature) or IV (cephalic catheter) to each guinea pig at a 1-week interval (2 treatments/guinea pig). Blood samples were collected before and at predetermined intervals after drug administration via a vascular access port. Plasma hydromorphone concentrations were determined by liquid chromatography–tandem mass spectrometry. Noncompartmental analysis of data was used to calculate pharmacokinetic parameters. RESULTS Mean ± SD clearance and volume of distribution for hydromorphone administered IV were 52.8 ± 13.5 mL/min/kg and 2.39 ± 0.479 L/kg, respectively. Mean residence time determined for the IV and IM administration routes was 0.77 ± 0.14 hours and 0.99 ± 0.34 hours, respectively. The maximum observed plasma concentration following IM administration of hydromorphone was 171.9 ± 29.4 ng/mL. No sedative effects were observed after drug administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetic data indicated that hydromorphone at a dose of 0.3 mg/kg may be administered IV every 2 to 3 hours or IM every 4 to 5 hours to maintain a target plasma concentration between 2 and 4 ng/mL in guinea pigs. Hydromorphone had high bioavailability after IM administration. Further research is necessary to evaluate the effects of other doses and administration routes and the analgesic effects of hydromorphone in guinea pigs.

The aim of this study was to assess the genetic variability of Mycoplasma hyopneumoniae within various swine production flows. Four M. hyopneumoniae positive production flows, composed of 4 production stages, were selected for this study. Laryngeal and/or bronchial swabs were collected from each production stage within a flow, for a period of 4 months up to 3 years. A multiple-locus variable-number tandem repeat analysis was performed to assess the genetic variation of M. hyopneumoniae within and across production flows through the identification of variable-number tandem repeat (VNTR) types. A maximum of 6 M. hyopneumoniae VNTR types were identified in a single flow, in which VNTR types appeared to be flow specific. An identical VNTR type was detected across several production stages for up to 3 years. In this study, minimal M. hyopneumoniae genetic variation was evidenced within and across production flows.

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.

OBJECTIVE To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS I0 healthy purpose-bred sexually intact female hounds. PROCEDURES Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.

OBJECTIVE To determine the effects of 2 augmentation techniques on the mechanical properties of titanium cannulated bone screws. SAMPLE 33 titanium cannulated bone screws (outer diameter, 6.5 mm; guide channel diameter, 3.6 mm). PROCEDURES 11 screws were allocated to each of 3 groups. The guide channel of each screw was filled with polymethyl methacrylate bone cement alone (OCS group) or in combination with a 3.2-mm-diameter orthopedic pin (PCS group) or remained unmodified (control group) before mechanical testing. Each screw underwent a single-cycle 3-point bending test to failure with a monotonic loading rate of 2.5 mm/min. Failure was defined as an acute decrease in resistance to load of ≥ 20% or a bending deformation of 15 mm. Mechanical properties were determined for each screw and compared among the 3 groups. RESULTS All screws in the control and OCS groups and 1 screw in the PCS group broke during testing; a 15-mm bending deformation was achieved for the remaining 10 screws in the PCS group. Maximum load and load at failure differed significantly among the 3 groups. Stiffness and load at yield for the PCS group were significantly greater than those for the control and OCS groups but did not differ between the control and OCS groups. CONCLUSIONS AND CLINICAL RELEVANCE Use of bone cement and an orthopedic pin to fill the guide channel of cannulated screws significantly increased the strength of the construct, but ex vivo and in vivo studies are necessary before this augmentation technique can be recommended for clinical patients.

The objective of this study was to document tidal variations in tracheal height during normal respiration in 19 healthy adult (> 1 y old) small-breed dogs (< 10 kg) using fluoroscopy and radiography. Each dog underwent tracheal fluoroscopic examination on inspiration and expiration while in a standing position (F-S) and in right lateral recumbency (F-RL), followed by radiographic projections obtained in right lateral recumbency. The percent variation in tracheal height during maximal inspiration and expiration was determined at 3 different locations [cervical region (CR), thoracic inlet (TI), and intrathoracic (IT) region]. When all imaging procedures and sites of measurement were considered, tracheal height varied during physiologic inspiration and expiration from 0% to 21.1%, with a mean of 4.5%. The mean percent variation in tracheal height was not significantly different among imaging modalities (F-S versus F-RL versus radiography) (P = 0.16) or measurement sites (CR versus TI versus IT) (P = 0.89). The body condition score (BCS) (P = 0.96), age (P = 0.95), and breed (P = 0.19) did not significantly influence the mean percent variation in tracheal height. The average variation in tracheal height during maximal physiological inspiration and expiration is small (< 6%) in most healthy adult small-breed dogs as assessed by fluoroscopy and radiography, although tracheal height may vary by as much as 21.1% in some healthy individuals. Inspiratory and expiratory radiographs acquired in right lateral recumbency provide an accurate assessment of tracheal height as an alternative to fluoroscopy.

OBJECTIVE To determine the change in mean hepatic apparent diffusion coefficient (ADC) and hepatic fat fraction (HFF) during body weight gain in cats by use of MRI. ANIMALS 12 purpose-bred adult neutered male cats. PROCEDURES The cats underwent general health and MRI examination at time 0 (before dietary intervention) and time 1 (after 40 weeks of being fed high-energy food ad libitum). Sequences included multiple-echo gradient-recalled echo MRI and diffusion-weighted MRI with 3 b values (0, 400, and 800 s/mm2). Variables (body weight and the HFF and ADC in selected regions of interest in the liver parenchyma) were compared between time points by Wilcoxon paired-sample tests. Relationships among variables were assessed with generalized mixed-effects models. RESULTS Median body weight was 4.5 and 6.5 kg, mean ± SD HFF was 3.39 ± 0.89% and 5.37 ± 1.92%, and mean ± SD hepatic ADC was 1.21 ± 0.08 × 10−3 mm2/s and 1.01 ± 0.2 × 10−3 mm2/s at times 0 and 1, respectively. Significant differences between time points were found for body weight, HFF, and ADC. The HFF was positively associated with body weight and ADC was negatively associated with HFF. CONCLUSIONS AND CLINICAL RELEVANCE Similar to findings in people, cats had decreasing hepatic ADC as HFF increased. Protons associated with fat tissue in the liver may reduce diffusivity, resulting in a lower ADC than in liver with lower HFF. Longer studies and evaluation of cats with different nutritional states are necessary to further investigate these findings.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the most significant zoonotic pathogens that poses a threat to humans. Previous studies have identified that Salmonella-secreted effector K3 (SseK3) is a novel translated and secreted protein of S. Typhimurium. The objective of this study was to determine whether deletion of the sseK3 gene can attenuate the virulence of S. Typhimurium. To do this, we constructed an sseK3 deletion mutant using the double-exchange allele of the suicide plasmid pRE112ΔsseK3 and assessed the virulence and intracellular proliferation of the mutant. The sseK3 deletion mutant exhibited adhesion and invasion properties similar to those of wild-type (WT) S. Typhimurium, although the virulence and intracellular proliferation of the mutant were significantly reduced compared to that of the WT strain. Furthermore, the observed increase in the median lethal dose (LD(50)) reflects a decrease in the pathogenicity of the sseK3 deletion mutant in a murine model. In summary, we concluded that disruption of sseK3 can attenuate the intracellular proliferation and reduce the virulence of S. Typhimurium.

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 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.