OBJECTIVE To evaluate pharmacokinetics of cefazolin after IV injection of cefazolin (22 mg/kg) and after simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg) to dogs. ANIMALS 12 adult Beagles. PROCEDURES Dogs (6/group) were assigned to receive a single injection of cefazolin (IV group; 22 mg/kg, IV) or simultaneous injections (IV + IM group; 22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period by use of ultrafiltration probes for pharmacokinetic analysis. RESULTS Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.2, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. Mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half-life, and time to maximum concentration was 74.99 and 154.16 h·μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, and 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Therefore, simultaneous IV and IM administration of cefazolin 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

OBJECTIVE To determine manubrium heart scores (MHSs) from measurements of cardiac short-axis length (cSAL) and long-axis length (cLAL) relative to the corresponding manubrium length (ML) on thoracic radiographic views of dogs and assess correlation of MHSs with vertebral heart scores (VHSs). ANIMALS 120 clinically normal large-breed dogs (LBDs) and small-breed dogs (SBDs). PROCEDURES On right lateral views (RLVs) and ventrodorsal views (VDVs) for each dog, cSAL and cLAL were measured and expressed as a ratio; the cSAL:ML ratio (short-MHS), cLAL:ML ratio (long-MHS), and cSAL-and-cLAL:ML ratio (overall-MHS) were also calculated. The VHS was determined from the RLV. Correlation of VHS with MHS was assessed. RESULTS On RLVs and VDVs, mean cSAL:cLAL ratios were 0.77 (SD, 0.05) and 0.72 (SD, 0.05), respectively, in 60 LBDs and 0.81 (SD, 0.06) and 0.78 (SD, 0.06), respectively, in 60 SBDs. In LBDs, mean short-MHS, long-MHS, and overall-MHS were 2.1 (SD, 0.22), 2.7 (SD, 0.24), and 4.8 (SD, 0.5), respectively, on RLVs and 2.3 (SD, 0.26), 3.2 (SD, 0.34), and 5.4 (SD, 0.6), respectively, on VDVs. In SBDs, mean short-MHS, long-MHS, and overall-MHS were 2.4 (SD, 0.39), 2.9 (SD, 0.50), and 5.3 (SD, 0.83), respectively, on RLVs and 2.5 (SD, 0.44), 3.2 (SD, 0.51), and 5.8 (SD, 0.92), respectively, on VDVs. Mean VHSs were 10.73 (SD, 0.52) and 10.27 (SD, 0.81) in LBDs and SBDs, respectively. A significant correlation was identified between VHS and each MHS in LBDs. CONCLUSIONS AND CLINICAL RELEVANCE In the dogs evaluated, radiographic cardiac dimensions and MHSs were correlated. Validity of the MHS for cardiac dimension assessment in other healthy dogs and dogs with cardiac disease warrants investigation.

To investigate the effects of a xylazine infusion during isoflurane anesthesia on global perfusion parameters and gastrointestinal oxygenation and microperfusion, 8 adult warmblood horses were sedated with xylazine and anesthesia induced with midazolam and ketamine. Horses were mechanically ventilated during anesthesia. After 3 h of stable isoflurane anesthesia (FEIso 1.3 Vol %), a xylazine infusion with 1 mg/kg body weight (BW) per hour was started for 1 h and then stopped. Before, during, and after xylazine infusion, heart rate (HR), arterial blood pressure (MAP), cardiac output (CO), central venous pressure (CVP), and pulmonary artery pressure (PAP) were measured and systemic vascular resistance (SVR) was calculated. Arterial blood gases were taken and oxygen delivery (DO2) and alveolar dead space (VDalv) were calculated. Further intestinal oxygen and microperfusion were measured using white light spectroscopy and laser Doppler flowmetry. Surface probes were placed via median laparotomy on the stomach, the jejunum, and the colon. Wilcoxon rank-sum test was used to compare values over time (P < 0.05). During xylazine infusion, MAP, CVP, PAP, SVR, and VDalv increased significantly, whereas CO, DO2, and intestinal microperfusion decreased. Intestinal oxygenation remained unchanged. All parameters returned to pre-xylazine values within 1 h after stopping xylazine infusion. A xylazine infusion during constant isoflurane anesthesia in horses impairs global and intestinal perfusion without changing tissue oxygenation in normoxic healthy horses. Further studies are necessary, however, to evaluate whether a possible reduction of isoflurane concentration by xylazine infusion will ameliorate these negative effects.

Sulfur-induced polioencephalomalacia (PEM) is an important disease affecting cattle in certain geographical regions. However, the pathogenesis of brain damage is not completely understood. We previously observed that excess dietary sulfur may influence thiamine status and altered thiamine metabolism may be involved in the pathogenesis of sulfur-induced PEM in cattle. In this study, we evaluated the activities of thiamine-dependent enzymes [α-ketogluterate dehydrogenase (α-KGDH) and pyruvate dehydrogenase (PDH)] and cytochrome c oxidase (COX) in the cerebral cortex of sulfur-induced PEM-affected cattle (n = 9) and clinically normal cattle (n = 8, each group) exposed to low or high dietary sulfur [LS = 0.30% versus HS = 0.67% sulfur on a dry matter (DM) basis]. Enzyme activities in PEM brains were measured from the brain tissue regions and examined using ultraviolent (UV) light illumination to show fluorescence or non-fluorescence regions. No gross changes under regular or UV light, or histopathological changes indicative of PEM were detected in the brains of cattle exposed to LS or HS diets. The PDH, α-KGDH, and COX activities did not differ between LS and HS brains, but all enzymes showed significantly lower (P < 0.05) activities in UV-positive region of PEM brains compared with LS and HS brains. The UV-negative regions of PEM brain had similar PDH activities to LS and HS brains, but the activities of α-KGDH and COX were significantly lower than in LS and HS brains. The results of this study suggest that reduced enzyme activities of brain PHD, α-KGDH, and COX are associated with the pathogenesis of sulfur-induced PEM.

OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge. ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group). PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group. RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group. CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.

OBJECTIVE To determine effects of transforming growth factor (TGF)-β and interleukin (IL)-1β on inflammatory markers in cultured canine chondrocytes to clarify the role of these cytokines in osteoarthritis of dogs. SAMPLE Pooled chondrocytes isolated from the stifle joints of 4 adult dogs. PROCEDURES Chondrocytes were isolated, cultured, and frozen at −80°C. Pooled cells were incubated in medium with or without TGF-β (1 or 10 ng/mL) and subsequently stimulated with IL-1β (10 ng/mL). Concentrations of nitric oxide (NO) and prostaglandin (PG) E were measured in culture supernatants. Gene expression of matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-2, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2 was quantified by use of real-time quantitative PCR assays. RESULTS Stimulation with IL-1β increased gene expression of all inflammatory markers, except for TIMP-2. Incubation with TGF-β resulted in a significant decrease in MMP-3 and TIMP-2 mRNA concentrations but had no effect on PGE and NO concentrations. For cells treated with TGF-β followed by IL-1β, concentrations of PGE and NO were lower, compared with concentrations for IL-1β control cells. Furthermore, IL-1β–induced gene expression of iNOS, MMP-3, and COX-2 was downregulated. However, the IL-1β–induced downregulation of TIMP-2 gene expression was partially restored by pretreatment with TGF-β. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IL-1β increased the expression of inflammatory genes and mediators, and TGF-β largely attenuated the IL-1β–mediated inflammatory response. Therefore, TGF-β might be a novel target for use in the prevention and treatment of cartilage breakdown in dogs with osteoarthritis.

OBJECTIVE To assess 3-D geometry of the humerus of dogs and determine whether the craniocaudal canal flare index (CFI) is associated with specific geometric features. SAMPLE CT images (n = 40) and radiographs (38) for 2 groups of skeletally mature nonchondrodystrophic dogs. PROCEDURES General dimensions (length, CFI, cortical thickness, and humeral head offset), curvature (shaft, humeral head, and glenoid cavity), version (humeral head and greater tubercle), and torsion were evaluated on CT images. Dogs were allocated into 3 groups on the basis of the craniocaudal CFI, and results were compared among these 3 groups. The CT measurements were compared with radiographic measurements obtained for another group of dogs. RESULTS Mean ± SD humeral head version was −75.9 ± 9.6° (range, −100.7° to −59.4°). Mean mechanical lateral distal humeral angle, mechanical caudal proximal humeral angle, and mechanical cranial distal humeral angle were 89.5 ± 3.5°, 50.2 ± 4.5°, and 72.9 ± 7.8°, respectively, and did not differ from corresponding radiographic measurements. Mean humeral curvature was 20.4 ± 4.4° (range, 9.6° to 30.5°). Mean craniocaudal CFI was 1.74 ± 0.18 (range, 1.37 to 2.10). Dogs with a high craniocaudal CFI had thicker cranial and medial cortices than dogs with a low craniocaudal CFI. Increased body weight was associated with a lower craniocaudal CFI. Radiographic and CT measurements of craniocaudal CFI and curvature differed significantly. CONCLUSIONS AND CLINICAL RELEVANCE CT-based 3-D reconstructions allowed the assessment of shaft angulation, torsion, and CFI. Radiographic and CT measurements of shaft curvature and CFI may differ.

Porcine infectious anemia caused by Mycoplasma suis is a global disease and results in serious economic losses. To determine the prevalence of M. suis infection in eastern China, a cross-sectional serologic study was conducted with 3458 porcine serum samples randomly obtained from January 2014 to August 2016. The samples were tested with a blocking enzyme-linked immunosorbent assay developed in our laboratory. The seroprevalence was 33.3% in the complete sample set and was 25.9%, 37.8%, and 37.8% in 2014, 2015, and 2016, respectively. The seroprevalence was distinctly higher in summer (39.9%) and autumn (42.0%) than in spring (28.9%) and winter (23.3%). Shanghai was the region with the highest seroprevalence (54.2%) and Jiangsu the region with the lowest (23.0%). The seroprevalence was markedly higher in boars (47.1%), multiparous sows (47.0%), and replacement gilts (39.2%) than in piglets (24.2%), fattening pigs (17.2%), and nursery pigs (12.5%). These data demonstrate that the prevalence of M. suis infection is increasing yearly in eastern China.

OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.

In order to study the ability of Lactobacillus casei to ameliorate murine enteritis, 18 mice were randomly divided into 3 groups: the enteritis group, intervention group, and control group. The interleukin (IL)-6 and transforming growth factor-β (TGF)-β content in mouse peripheral blood and duodenum was detected using an enzyme-linked immunosorbent assay (ELISA). The number of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) and CD4+IL-17A+ Th17 cells in the mesenteric lymph nodes (MLN) and spleen were detected using flow cytometry, and quantitative reverse transcription polymerase chain reaction (PCR) and western blot analysis were used to measure Foxp3 and retinoid-related orphan receptor-γ (RORγt) mRNA and protein expression in the MLN. Histological changes in the duodenum were observed. Results indicate that in the intervention group, IL-6 content in mouse peripheral blood and duodenum was significantly lower than in the enteritis group (P < 0.05), while TGF-β content was significantly increased compared to the enteritis group (P < 0.05). For the intervention group, the percentages of CD4+CD25+Foxp3+ Tregs in spleen and MLN were increased (P < 0.05), while the percentages of CD4+IL-17A+ Th17 cells were decreased compared to the enteritis group (P < 0.05). The expression of Foxp3 mRNA and protein in the intervention group was higher than in the enteritis group, while RORγt mRNA and protein were significantly lower (P < 0.05). After mice in the enteritis group were treated with L. casei, duodenal inflammation was relieved. This study demonstrated that L. casei could have possible implications for the enterotoxigenic Escherichia coli (ETEC) induced intestinal inflammation by regulating the ratio imbalance of Th17/Treg cells.