OBJECTIVE: To determine the pharmacokinetics of a single oral dose of trazodone and its effect on the activity of domestic pigeons (Columba livia). ANIMALS: 6 healthy adult male domestic pigeons. PROCEDURES: During the first of 3 experiments, birds received orally administered trazodone at doses ranging from 3 to 30 mg/kg to determine the dose for subsequent experiments. During the second experiment, each bird received 1 dose of trazodone (30 mg/kg, PO). Blood was collected for determination of plasma trazodone concentration before and at predetermined times for 24 hours after drug administration. Pharmacokinetic parameters were calculated by noncompartmental analysis. During experiment 3, birds were instrumented with ultralightweight accelerometers and received orally administered trazodone (30 mg/kg) or an equal volume of water twice at a 48-hour interval. Activity of birds was monitored for 24 hours after administration of each treatment. RESULTS: No adverse effects were observed. Mean ± SD terminal half-life of trazodone was 5.65 ± 1.75 hours. Plasma trazodone concentrations remained > 0.130 μg/mL for approximately 20 hours. Trazodone did not affect the activity of birds during the first 2 and 15 hours after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that oral administration of 1 dose (30 mg/kg) of trazodone to healthy pigeons was safe and resulted in plasma drug concentrations that were similar to those considered therapeutic in humans and dogs for up to 20 hours. Further research is necessary to characterize the pharmacokinetics for repeated doses as well as the clinical effects of trazodone in birds with behavior problems.

OBJECTIVE To characterize abdominal lymphatic drainage in cats after thoracic duct ligation (TDL) and cisterna chyli ablation (CCA). ANIMALS 7 purpose-bred research cats. PROCEDURES Baseline CT lymphangiography was performed. A popliteal lymph node was injected with iohexol, and images were acquired at 5-minute intervals for 15 minutes. Cats underwent TDL and CCA; methylene blue was used to aid in identifying lymphatic vessels. The CT lymphangiography was repeated immediately after and 30 days after surgery. All cats were euthanized and necropsied. RESULTS Results of baseline CT lymphangiography were unremarkable for all 7 cats. Only 5 cats completed the study. Leakage of contrast medium at the level of the cisterna chyli was seen on CT lymphangiography images obtained from all cats immediately after surgery. Evaluation of 30-day postoperative CT lymphangiography images revealed small branches entering the caudal vena cava in 2 cats, leakage of contrast medium into the caudal vena cava with no visible branches in 1 cat, and no contrast medium in the caudal vena cava in 2 cats. Contrast medium did not flow beyond the level of the cisterna chyli in any cat. Gross examination during necropsy revealed that all cats had small lymphatic vessels that appeared to connect to local vasculature identified in the region of the cisterna chyli. CONCLUSIONS AND CLINICAL RELEVANCE Abdominal lymphaticovenous anastomoses formed after TDL and CCA in cats. This would support use of these procedures for treatment of cats with idiopathic chylothorax, although additional studies with clinically affected cats are warranted.

Septic arthritis is an important disease in horses, necessitating aggressive and prolonged therapy. In order to guide therapy, reliable methods of detecting the eradication of infection are needed. Therefore, the objective of this study was to investigate detection of eradication of infection in an experimental model of equine septic arthritis using standard diagnostic techniques. For this purpose, 17 adult horses were assigned to 3 experimental groups. The middle carpal joint of each horse was injected with Escherichia coli (Septic group, n = 8), lipopolysaccharide (LPS) (LPS group, n = 6), or sterile saline (Control group, n = 3) at day 0. Contralateral joints were not injected. Standard therapy was applied to all joints except non-injected joints in the Control group at day 1. Sequential samples of synovial fluid (SF) were collected for bacterial culture using 3 culture media [Columbia blood agar (CBA), brain heart infusion broth (BHI), and Signal blood culture medium] and for cytological evaluation [percentage neutrophils (PN), total nucleated cell count (TNCC), and total protein (TP)]. Escherichia coli-specific polymerase chain reaction (PCR) was carried out to detect E. coli DNA in synovial fluid. Culture and PCR were positive for E. coli in all joints injected with E. coli at day 1 and 1 joint was positive on BHI at day 4. Based on the results of bacterial culture, PCR, and TNCC, the elimination of infection in our experimental model occurred by day 4 post-infection in 6 out of 7 cases. Total protein (TP) and PN remained elevated at clinical threshold used for diagnosis of septic arthritis until day 14. In our experimental model of E. coli-induced arthritis, we conclude that TP and PN may not be good indicators for detecting the eradication of bacterial infection caused by E. coli from infected and subsequently treated joints.

With acrylic external-fixation frames for fracture repair the acrylic columns can be contoured to allow greater versatility in the placement of transfixation pins, thus minimizing damage to the surrounding soft tissue and making mandibular and transarticular fixation easier. However, contouring affects the stiffness and ultimate strength of the construct under axial compression. In this study, polymethylmethacrylate columns 21 mm in diameter angled at 0°, 30°, 45°, 60°, or 90° with clamps were constructed. For each angulation group, pins 3.2-mm long were placed in 6 columns, 2 pins at each end, 1.5 cm from each other, and 6 columns had no pins. Each column was allowed to polymerize for a minimum of 10 min, then was placed in a biomechanical-testing machine, the load cell at the bottom end of the column and the actuator on top, with a preload of 10 to 12 N to prevent slippage. The columns underwent axial loading at a rate of 8 mm/s until catastrophic failure occurred. Data on force and deformation were collected every 0.025 s. Both stiffness and ultimate strength of the column decreased significantly (P < 0.01), up to 77% and 70%, respectively, with each increase of angulation. The columns with pins were significantly less stiff (P < 0.05) than those without pins at angulations of 45° and 60°. However, the columns with pins did not show significant differences in ultimate strength from the columns without pins at any of the angulations. The point of failure was always at the angle of the column, demonstrating that in axial compression the weakest point is not the pin-acrylic interface when pins are eccentrically located within the column.

Canine osteosarcoma is a devastating disease with an overall poor prognosis. Radiation therapy and bisphosphonates are currently used in combination for palliative treatment, despite a paucity of literature that investigates their combined use. The objectives of this study were to assess the in vitro effects of radiation therapy and bisphosphonates on canine osteosarcoma cells when used in combination. Canine osteosarcoma cell lines D17 and Dharma were treated with radiation and pamidronate or zoledronate, both alone and in combination. The effects of these treatments were assessed using clonogenic survival and cell viability assays. Dose-dependent decreases in clonogenic survival and cell viability were observed for both radiation and bisphosphonate treatment. Combination index analysis revealed antagonistic interactions when radiation and bisphosphonates were used in combination at specific doses for both D17 and Dharma osteosarcoma cells. Further investigation of the combined effects of radiation and bisphosphonates for the palliative treatment of canine osteosarcoma is warranted.

OBJECTIVE To determine pharmacokinetics and pharmacodynamics after oral administration of a single dose of clopidogrel to horses. ANIMALS 6 healthy adult horses. PROCEDURES Blood samples were collected before and at various times up to 24 hours after oral administration of clopidogrel (2 mg/kg). Reactivity of platelets from each blood sample was determined by optical aggregometry and phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Concentrations of clopidogrel and the clopidogrel active metabolite derivative (CAMD) were measured in each blood sample by use of liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were determined with a noncompartmental model. RESULTS Compared with results for preadministration samples, platelet aggregation in response to 12.5μM ADP decreased significantly within 4 hours after clopidogrel administration for 5 of 6 horses. After 24 hours, platelet aggregation was identical to that measured before administration. Platelet aggregation in response to 25μM ADP was identical between samples obtained before and after administration. Phosphorylation of VASP in response to ADP (20μM) and prostaglandin E1 (3.3μM) was also unchanged by administration of clopidogrel. Time to maximum concentration of clopidogrel and CAMD was 0.54 and 0.71 hours, respectively, and calculated terminal-phase half-life of clopidogrel and CAMD was 1.81 and 0.97 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Clopidogrel or CAMD caused competitive inhibition of ADP-induced platelet aggregation during the first 24 hours after clopidogrel administration. Because CAMD was rapidly eliminated from horses, clopidogrel administration may be needed more frequently than in other species in which clopidogrel causes irreversible platelet inhibition.

OBJECTIVE To compare laryngeal impedance, in terms of air flow and pressure, following arytenoid corniculectomy (COR) versus 3 other airway interventions (left-sided laryngoplasty with ipsilateral ventriculocordectomy [LLP], LLP combined with COR [LLPCOR], and partial arytenoidectomy [PA]) performed on cadaveric equine larynges with simulated left recurrent laryngeal neuropathy (RLN) and to determine whether relative laryngeal collapse correlated with the interventions performed. SAMPLE 28 cadaveric equine larynges. PROCEDURES Each larynx in states of simulated left RLN alone and with airway interventions in the order LLP, LLPCOR, COR, and PA was evaluated in a box model construct that replicated upper airway flow mechanics consistent with peak exercise in horses. Results for impedance, calculated from airflow and pressure changes, were compared between states for each larynx. Multivariable mixed-effects analysis controlling for repeated measures within larynx was performed to calculate the predicted mean impedance for each state. RESULTS Results indicated that tracheal adapter diameter, individual larynx properties, airway intervention, and relative laryngeal collapse affected laryngeal impedance. The LLP and LLPCOR interventions had the lowest impedance, whereas the COR and PA interventions did not differ substantially from the simulated left RLN state. Residual intraclass correlation of the model was 27.6 %. CONCLUSIONS AND CLINICAL RELEVANCE Although impedance was higher for the simulated left RLN with the COR intervention state than with the LLP intervention state, given the clinical success of PA for treating RLN in horses and the similar results for the COR and PA intervention states in the present study, the use of COR warrants further investigation. The residual interclass correlation suggested that individual laryngeal variation affected impedance and may have a clinical effect.

OBJECTIVE To determine the effects of oral omeprazole administration on the fecal and gastric microbiota of healthy adult horses. ANIMALS 12 healthy adult research horses. PROCEDURES Horses were randomly assigned to receive omeprazole paste (4 mg/kg, PO, q 24 h) or a sham (control) treatment (tap water [20 mL, PO, q 24 h]) for 28 days. Fecal and gastric fluid samples were collected prior to the first treatment (day 0), and on days 7, 28, 35, and 56. Sample DNA was extracted, and bacterial 16S rRNA gene sequences were amplified and sequenced to characterize α and β diversity and differential expression of the fecal and gastric microbiota. Data were analyzed by visual examination and by statistical methods. RESULTS Composition and diversity of the fecal microbiota did not differ significantly between treatment groups or over time. Substantial variation in gastric fluid results within groups and over time precluded meaningful interpretation of the microbiota in those samples. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that omeprazole administration had no effect on fecal microbiota composition and diversity in this group of healthy adult horses. Small sample size limited power to detect a difference if one existed; however, qualitative graphic examination supported that any difference would likely have been small and of limited clinical importance. Adequate data to evaluate potential effects on the gastric microbiota were not obtained. Investigations are needed to determine the effects of omeprazole in horses with systemic disease or horses receiving other medical treatments.

Drugs applied on human cancer cells can influence the rate of cell proliferation. The present study investigates the use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) colorimetric assay to evaluate canine tumor cell proliferation after exposure to the injectable anesthetic, propofol. Primary (CIPp) and metastatic (CIPm) canine tubular adenocarcinoma cell lines were incubated with cell culture medium (control) or propofol (1, 5, and 10 μg/mL). The MTT assays were performed after 6 and 12 hours of exposure. Measurements of absorbance were obtained for each condition with a spectrophotometer and compared with controls using a 3-way analysis of variance (P < 0.05). An increased cell proliferation rate was observed in CIPp exposed to 5 and 10 μg/mL of propofol for 6 hours and 1, 5, and 10 μg/mL for 12 hours. No significant changes were observed in CIPm after 6 hours of exposure. All propofol concentrations decreased the cell proliferation rate in CIPm after 12 hours of exposure. The MTT assays showed that exposure of CIPp to propofol for 6 and 12 hours increased cell proliferation. A decrease in the CIPm proliferation rate was observed when propofol exposure lasted for 12 hours. Further studies are warranted to better understand the role of propofol on cancer cell proliferation.

Osteoarthritis, the leading cause of chronic joint pain, is studied through different animal models, but none of them is ideal in terms of reliability and translational value. In this pilot study of female rats, 3 surgical models of osteoarthritic pain, i.e., destabilization of the medial meniscus (DMM), cranial cruciate ligament transection (CCLT), and the combination of both surgical models (COMBO) and 1 chemical model [intra-articular injection of monosodium iodoacetate (MIA)] were compared for their impact on functional pain outcomes [static weight-bearing (SWB) and punctate tactile paw withdrawal threshold (PWT)] and spinal neuropeptides [substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), and somatostatin (SST)]. Six rats were assigned to each model group and a sham group. Both the chemical model (MIA) and surgical COMBO model induced functional alterations in SWB and PWT, with the changes being more persistent in the surgical combination group. Both models also produced an increase in levels of pro-nociceptive and anti-nociceptive neuropeptides at different timepoints. Pain comparison with the MIA model showed the advantage of a surgical model, especially the combination of the DMM and CCLT models, whereas each surgical model alone only led to temporary functional alterations and no change in neuropeptidomics.