In this study, we investigated whether β-glucan from Saccharomyces cerevisiae exerts beneficial effects on mucosal immunity in an ovine ruminal explant (ORE) model. Once the ORE model was established, viability was assessed through histological change, E-cadherin expression, CK-18 and Ki-67 distribution. Then, the OREs were co-cultured with β-glucan, following which, gene and protein expression levels of sheep β-defensin-1 (SBD-1), pro-inflammatory interleukin (IL)-6, and anti-inflammatory IL-10 were detected using quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin staining, qPCR, and immunohistochemistry showed that the overall ORE structure was intact after 96 hours in culture, but explants cultured for more than 24 hours showed epithelial degradation. Therefore, we performed the follow-up test within 24 hours. qPCR and ELISA revealed that the gene and protein expression levels of SBD-1, IL-6, and IL-10 in the OREs significantly increased (P < 0.05) after treatment with β-glucan compared with controls. This study identified the feasibility and optimal conditions of ORE culture and demonstrated that β-glucan activates SBD-1, IL-6, and IL-10 secretion in OREs to promote mucosal immunity.

OBJECTIVE To evaluate the effect of suture caliber on the tensile strength of tenorrhaphies performed with a locking-loop technique in cadaveric canine tendons SAMPLE 60 superficial digital flexor tendons (SDFTs) from 30 cadaveric adult dogs. PROCEDURES Transverse tenotomy was performed, and SDFTs were repaired with a locking-loop technique and polypropylene suture of 5 randomly assigned calibers: size-0, 2-0, 3-0, 4-0, or 5-0 (n = 12 SDFTs/suture caliber). Tendon constructs were tested to failure. Yield, peak, and failure forces and causes of failure were compared between groups. RESULTS Mean ± SD failure force for the constructs was significantly greater with large-caliber suture (size-0: 73.5 ± 3.1 N; size 2-0: 54.4 ± 7.1 N; size 3-0: 28.7 ± 4.9 N; size 4-0: 18.7 ± 3.4 N; and size 5-0: 8.8 ± 2.8 N). The likelihood of construct failure by suture pullout through the tendon substance increased with large-caliber suture (size-0: 12/12), whereas the likelihood of construct failure by suture breakage increased with small-caliber suture (2-0: 10/12; 3-0, 4-0, and 5-0: 12/12 each). CONCLUSIONS AND CLINICAL RELEVANCE Large-caliber suture had greater tensile strength for tenorrhaphies performed with a locking-loop technique in cadaveric canine tendons. Prior to the use of large-caliber suture in patients requiring tenorrhaphy, however, in vivo studies are required to confirm the results obtained here.

OBJECTIVE To determine the effects of coadministration of naltrexone, a human opioid abuse deterrent, on the pharmacokinetics and pharmacodynamics of a methadone-fluconazole combination administered orally to dogs. Animals: 12 healthy Beagles. PROCEDURES Dogs (body weight, 10.7 to 13.9 kg) were randomly allocated to 2 groups in a parallel design study. All dogs received fluconazole (100 mg [7.19 to 9.35 mg/kg], PO). Twelve hours later (time 0), dogs were administered methadone (10 mg [0.72 to 0.93 mg/kg]) plus fluconazole (50 mg [3.62 to 4.22 mg/kg]; methadone-fluconazole) or methadone (10 mg [0.72 to 0.93 mg/kg]) plus fluconazole (50 mg [3.60 to 4.67 mg/kg]) and naltrexone (2.5 mg [0.18 to 0.23 mg/kg]; methadone-fluconazole-naltrexone), PO, in a gelatin capsule. Blood samples were collected for pharmacokinetic analysis, and rectal temperature and sedation were assessed to evaluate opioid effects at predetermined times up to 24 hours after treatment. RESULTS Most dogs had slight sedation during the 12 hours after drug administration; 1 dog/group had moderate sedation at 1 time point. Mean rectal temperatures decreased significantly from baseline (immediate pretreatment) values from 2 to ≥ 12 hours and 2 to ≥ 8 hours after methadone-fluconazole and methadone-fluconazole-naltrexone treatment, respectively. Geometric mean maximum observed concentration of methadone in plasma was 35.1 and 33.5 ng/mL and geometric mean terminal half-life was 7.92 and 7.09 hours after methadone-fluconazole and methadone-fluconazole-naltrexone treatment, respectively. Naltrexone was sporadically detected in 1 dog. The active naltrexone metabolite, β-naltrexol, was not detected. The inactive metabolite, naltrexone glucuronide, was detected in all dogs administered methadone-fluconazole-naltrexone. CONCLUSIONS AND CLINICAL RELEVANCE Opioid effects were detected after oral administration of methadone-fluconazole or methadone-fluconazole-naltrexone. Further studies assessing additional opioid effects, including antinociception, are needed.

The objective of this study was to evaluate the effect of intra-abdominal pressure (IAP) on cardiorespiratory parameters during pneumoperitoneum with carbon dioxide in domestic rabbits. Six juvenile female New Zealand white rabbits were assigned to randomized sequences of IAP (0, 4, 8 mmHg) in a crossover study. The following parameters were measured at each IAP: direct arterial blood pressure (ABP); cardiac output, (CO), cardiac index, and stroke volume index (CI, SVI); heart rate; end-tidal carbon dioxide (ETCO(2)); arterial blood gases (PaCO(2), PaO(2)); peak inspiratory pressure (PIP); and peripheral oxygen saturation (SpO(2)). Between IAPs, the abdomen was desufflated for a 5-minute washout period. Mixed linear regression models were used for statistical analysis. Heart rate, SpO(2), and ABP were not significantly affected by IAP, although there was a positive increase in ABP with IAP. Partial pressure of carbon dioxide (PaCO(2)) was increased at an IAP of 8 mmHg and ETCO(2) and PIP were greater with each IAP applied. Cardiac output and CI were significantly decreased with IAP and, although SVI showed the same trend, it was not statistically significant. In conclusion, pneumoperitoneum with carbon dioxide causes an increase in ETCO(2), PaCO(2), and PIP, whereas cardiac output and CI decrease. These cardiorespiratory changes should be considered when determining the optimal IAP for laparoscopic procedures in rabbits.

OBJECTIVE To evaluate the effect of presurgical storage conditions on leakage pressures of enterotomy sites closed with unidirectional barbed suture material in fresh, chilled, and frozen-thawed cadaveric canine jejunal specimens. SAMPLE 36 grossly normal jejunal segments obtained from 4 dog cadavers. PROCEDURES 9 jejunal segments were harvested immediately from each euthanized dog and randomly assigned to be tested within 4 hours after collection (fresh segments), stored at 4°C for 24 hours before testing (chilled segments), or stored at −20°C for 7 days and thawed at 21°C for 6 hours before testing (frozen-thawed segments). For leakage pressure testing, a 3-cm-long antimesenteric enterotomy was performed and repaired with 3-0 unidirectional barbed suture material in a simple continuous pattern in each segment. Time to complete the enterotomy, initial leakage pressure, maximum intraluminal pressure, and leakage location were recorded for each segment. RESULTS Mean ± SD initial leakage pressure for fresh, chilled, and frozen-thawed segments was 52.8 ± 14.9 mm Hg, 51.8 ± 11.9 mm Hg, and 33.3 ± 7.7 mm Hg, respectively. Frozen-thawed segments had significantly lower mean initial leakage pressure, compared with findings for fresh or chilled segments. Time to complete the enterotomy, maximum intraluminal pressure, and leakage location did not differ among groups. CONCLUSIONS AND CLINICAL RELEVANCE Leak pressure testing of cadaveric jejunal segments that are fresh or chilled at 4°C for 24 hours is recommended for enterotomy studies involving barbed suture material in dogs. Freezing and thawing of cadaveric jejunal tissues prior to investigative use is not recommended because leak pressure data may be falsely low.

OBJECTIVE To characterize antimicrobial prescribing patterns of clinicians and clinical services at a large animal veterinary teaching hospital and identify factors associated with antimicrobial prescribing. ANIMALS All large animals (ie, equids, bovids, sheep, goats, camelids, swine, and cervids) evaluated at the New Bolton Center hospital at the University of Pennsylvania from 2013 through 2018. PROCEDURES In a cross-sectional study design, data on antimicrobial use by clinicians and clinical services were collected from administrative and billing records. Multivariable regression modeling was performed to identify factors associated with antimicrobial prescribing patterns. RESULTS Antimicrobials and critically important antimicrobials of the highest priority were dispensed in 42.1% (9,853/23,428) and 24.0% (2,360/9,853) of visits, respectively, and these proportions differed significantly among clinicians. Per visit, the median (interquartile [25th to 75th percentile] range) number of animal-defined daily doses dispensed was 3.6 (0.8 to 11.1) and the mean (SD) number of antimicrobial classes dispensed was 2.0 (1.3). Patient species, age, affected body system, and duration of hospitalization as well as submission of specimens for bacterial culture were significantly associated with prescribing patterns. CONCLUSIONS AND CLINICAL RELEVANCE The frequency and quantity of antimicrobials prescribed differed significantly among clinicians within and across services, even for animals with clinical signs affecting the same body system. Patient- and visit-level factors explained some but not all of the heterogeneity in prescribing patterns, suggesting that other clinician-specific factors drove such practices. More research is needed to better understand antimicrobial prescribing patterns of clinicians, particularly in situations for which no antimicrobial use guidelines have been established.

OBJECTIVE To evaluate histologic changes and gene expression patterns in body and limb wounds in horses in response to bacterial inoculation. SAMPLE Wound biopsy specimens from 6 horses collected on days 7, 14, 21, and 27 after excisional wounds (20 wounds/horse) were created over the metacarpal and metatarsal region and lateral thoracic region (body) and then inoculated or not inoculated on day 4 with Staphylococcus aureus and Pseudomonas aeruginosa. PROCEDURES Specimens were histologically scored for the amount of inflammation, edema, angiogenesis, fibrosis organization, and epithelialization. Quantitative PCR assays were performed to quantify gene expression of 10 inflammatory, proteolytic, fibrotic, and hypoxia-related markers involved in wound healing. RESULTS Except for gene expression of interleukin-6 on day 27 and tumor necrosis factor-α on day 14, bacterial inoculation had no significant effect on histologic scores and gene expression. Gene expression of interleukin-1β and -6, serum amyloid A, and matrix metalloproteinase-9 was higher in limb wounds versus body wounds by day 27. Gene expression of cellular communication network factor 1 was higher in limb wounds versus body wounds throughout the observation period. CONCLUSIONS AND CLINICAL RELEVANCE The lack of clear markers of wound infection in this study reflected well-known difficulties in detecting wound infections in horses. Changes consistent with protracted inflammation were evident in limb wounds, and gene expression patterns of limb wounds shared similarities with those of chronic wounds in humans. Cellular communication network factor warrants further investigation and may be useful in elucidating the mechanisms underlying poor limb wound healing in horses.

This study investigated oxidative stress biomarkers at 3 different oxygen concentrations in dogs under general anesthesia to determine whether high-concentration oxygen increases oxidative stress. Six healthy beagles were randomly assigned to receive 3 anesthesia protocols (inhalation of 40%, 60%, and 100% oxygen) during 3 hours of general anesthesia with sevoflurane, with at least one week in between each protocol. For each experiment, blood samples were collected at 0, 3, 6, and 24 hours after inhalation of oxygen. Derivatives of reactive oxygen metabolites, biochemical antioxidant potential, superoxide dismutase, and 8-hydroxydeoxyguanosine in the blood did not significantly differ among the 3 groups at any time point. This study is the first comparing high concentrations of oxygen with low concentrations of oxygen for anesthesia in dogs. According to our findings, 100% oxygen may not alter the oxidative stress level in dogs during general anesthesia with sevoflurane for 3 hours.

OBJECTIVE To determine the accuracy of tidal volume (VT) delivery among 5 different models of large-animal ventilators when tested at various settings for VT delivery, peak inspiratory flow (PIF) rate, and fresh gas flow (FGF) rate. SAMPLE 4 different models of pneumatically powered ventilators and 1 electrically powered piston-driven ventilator. PROCEDURES After a leak flow check, each ventilator was tested 10 times for each experimental setting combination of 5 levels of preset VT, 3 PIF rates, and 4 FGF rates. A thermal mass flow and volume meter was used as the gold-standard method to measure delivered VT. In addition, circuit systems of rubber versus polyvinyl chloride breathing hoses were evaluated with the piston-driven ventilator. Differences between preset and delivered VT (volume error [ΔVT]) were calculated as a percentage of preset VT, and ANOVA was used to compare results across devices. Pearson correlation coefficient analyses and the coefficient of determination (r2) were used to assess potential associations between the ΔVT and the preset VT, PIF rate, and FGF rate. RESULTS For each combination of experimental settings, ventilators had ΔVT values that ranged from 1.2% to 22.2%. Mean ± SD ΔVT was 4.8 ± 2.5% for the piston-driven ventilator, compared with 6.6 ± 3.2%, 10.6 ± 2.9%, 13.8 ± 2.97%, and 15.2 ± 2.6% for the 4 pneumatic ventilators. The ΔVT increased with higher PIF rates (r2 = 0.69), decreased with higher FGF rates (r2 = 0.62), and decreased with higher preset VT (r2 = 0.58). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the tested ventilators all had ΔVT but that the extent of each of ΔVT varied among ventilators. Close monitoring of delivered VT with external flow and volume meters is warranted, particularly when pneumatic ventilators are used or when very precise VT delivery is required.

OBJECTIVE To evaluate the thermal antinociceptive effects of hydromorphone hydrochloride after IM administration to orange-winged Amazon parrots (Amazona amazonica). ANIMALS 8 healthy adult parrots (4 males and 4 females). PROCEDURES In a randomized crossover study, each bird received hydromorphone (0.1, 1, and 2 mg/kg) and saline (0.9% NaCl) solution (1 mL/kg; control) IM, with a 7-day interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before and after treatment administration. Adverse effects were also monitored. The TFWT, agitation-sedation score, and proportion of birds that developed adverse effects were compared among treatments over time. RESULTS Compared with the mean TFWT for the control treatment, the mean TFWT was significantly increased at 0.5, 1.5, and 3 hours and 1.5, 3, and 6 hours after administration of the 1- and 2-mg/kg hydromorphone doses, respectively. Significant agitation was observed at 0.5, 1.5, and 3 hours after administration of the 1 - and 2-mg/kg hydromorphone doses. Other adverse effects observed after administration of the 1- and 2-mg/kg doses included miosis, ataxia, and nausea-like behavior (opening the beak and moving the tongue back and forth). CONCLUSIONS AND CLINICAL RELEVANCE Although the 1- and 2-mg/kg hydromorphone doses appeared to have antinociceptive effects, they also caused agitation, signs of nausea, and ataxia. Further research is necessary to evaluate administration of lower doses of hydromorphone and other types of stimulation to better elucidate the analgesic and adverse effects of the drug in psittacine species.