The aim of the study was to describe the process of neuron death in the cerebral cortex caused by embryonic carbofuran exposure. 81 mouse foetuses from 27 breeding mice were used in the study. Carbofuran was administered by gavage from the 6ᵗʰ to the 15ᵗʰ day of gestation to two groups: one at 0.0208 and the other at 0.0417 mg/kg b.w. On the 17ᵗʰ day, the mice were sacrificed and the foetuses were taken to measure the ROS (malondialdehyde/MDA and superoxide dismutase/SOD) activity in brain tissue, the number of apoptotic embryonic cerebral cortex neurons using a TUNEL assay, and necrotic cells using HE staining. Examination of p53 and caspase 3 expression was done by immunohistochemistry. Data were analysed using analysis of variance (ANOVA) and Duncan’s test. Increased activity of cerebral ROS characterised by significant elevation of the MDA level (P < 0.05), decreased SOD (P < 0.01), increased p53 and caspase 3 expression, and cerebral cortical neuron death either by necrosis or apoptosis (P < 0.05) were found. At the low dose carbofuran increased expression of p53, caspase 3, and apoptosis. At the high dose it increased levels of MDA and necrosis. Increased expression of p53 and caspase 3 and apoptosis indicated that carbofuran may cause apoptosis through the intrinsic pathway. The increased apoptosis grants an opportunity to prevent and treat the effect of ROS due to gestational carbofuran exposure.

OBJECTIVE To determine the impact of mechanical ventilation (MV) and perfusion conditions on the efficacy of pulse-delivered inhaled nitric oxide (PiNO) in anesthetized horses. ANIMALS 27 healthy adult horses. PROCEDURES Anesthetized horses were allocated into 4 groups: spontaneous breathing (SB) with low (< 70 mm Hg) mean arterial blood pressure (MAP; group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Dobutamine was used to maintain MAP > 70 mm Hg. Data were collected after a 60-minute equilibration period and at 15 and 30 minutes during PiNO administration. Variables included Pao2, arterial oxygen saturation and content, oxygen delivery, and physiologic dead space-to-tidal volume ratio. Data were analyzed with Shapiro-Wilk, Mann-Whitney U, and Friedman ANOVA tests. RESULTS Pao2, arterial oxygen saturation, arterial oxygen content, and oxygen delivery increased significantly with PiNO in the SB-L, SB-N, and MV-N groups; were significantly lower in group MV-L than in group MV-N; and were lower in MV-N than in both SB groups during PiNO. Physiologic dead space-to-tidal volume ratio was highest in the MV-L group. CONCLUSIONS AND CLINICAL RELEVANCE Pulmonary perfusion impacted PiNO efficacy during MV but not during SB. Use of PiNO failed to increase oxygenation in the MV-L group, likely because of profound ventilation-perfusion mismatching. During SB, PiNO improved oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted. Use of PiNO was most effective in horses with adequate perfusion.

OBJECTIVE To evaluate and quantify the kinematic behavior of canine mandibles before and after bilateral rostral or unilateral segmental mandibulectomy as well as after mandibular reconstruction with a locking reconstruction plate in ex vivo conditions. SAMPLE Head specimens from cadavers of 16 dogs (range in body weight, 30 to 35 kg). PROCEDURE Specimens were assigned to undergo unilateral segmental (n = 8) or bilateral rostral (8) mandibulectomy and then mandibular reconstruction by internal fixation with locking plates. Kinematic markers were attached to each specimen in a custom-built load frame. Markers were tracked in 3-D space during standardized loading conditions, and mandibular motions were quantified. Differences in mandibular range of motion among 3 experimental conditions (before mandibulectomy [ie, with mandibles intact], after mandibulectomy, and after reconstruction) were assessed by means of repeated-measures ANOVA. RESULTS Both unilateral segmental and bilateral rostral mandibulectomy resulted in significantly greater mandibular motion and instability, compared with results for intact mandibles. No significant differences in motion were detected between mandibles reconstructed after unilateral segmental mandibulectomy and intact mandibles. Similarly, the motion of mandibles reconstructed after rostral mandibulectomy was no different from that of intact mandibles, except in the lateral direction. CONCLUSIONS AND CLINICAL RELEVANCE Mandibular kinematics in head specimens from canine cadavers were significantly altered after unilateral segmental and bilateral rostral mandibulectomy. These alterations were corrected after mandibular reconstruction with locking reconstruction plates. Findings reinforced the clinical observations of the beneficial effect of reconstruction on mandibular function and the need for reconstructive surgery after mandibulectomy in dogs.

OBJECTIVE To assess effects of nitrogen and helium on efficacy of an alveolar recruitment maneuver (ARM) for improving pulmonary mechanics and oxygen exchange in anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses were anesthetized twice in a randomized crossover study. Isoflurane-anesthetized horses in dorsal recumbency were ventilated with 30% oxygen and 70% nitrogen (treatment N) or heliox (30% oxygen and 70% helium; treatment H) as carrier gas. After 60 minutes, an ARM was performed. Optimal positive end-expiratory pressure was identified and maintained for 120 minutes. Throughout the experiment, arterial blood pressures, heart rate, peak inspiratory pressure, dynamic compliance (C(dyn)), and Pao(2) were measured. Variables were compared with baseline values and between treatments by use of an ANOVA. RESULTS The ARM resulted in significant increases in Pao(2) and C(dyn) and decreases in the alveolar-arterial gradient in the partial pressure of oxygen in all horses. After the ARM and during the subsequent 120-minute phase, mean values were significantly lower for treatment N than treatment H for Pao2 and C(dyn). Optimal positive end-expiratory pressure was consistently 15 cm H(2)O for treatment N, but it was 10 cm H(2)O (4 horses) and 15 cm H(2)O (2 horses) for treatment H.

OBJECTIVE To compare effects of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for anesthetic induction on cardiorespiratory and acid-base variables before and during isoflurane-maintained anesthesia in healthy dogs. ANIMALS 6 dogs. PROCEDURES Dogs were anesthetized with sevoflurane and instrumented. After dogs recovered from anesthesia, baseline values for cardiorespiratory variables and cardiac output were determined, and arterial and mixed-venous blood samples were obtained. Tiletamine-zolazepam (5 mg/kg), alfaxalone (4 mg/kg), propofol (6 mg/kg), or ketamine-diazepam (7 and 0.3 mg/kg) was administered IV in 25% increments to enable intubation. After induction (M0) and at 10, 20, 40, and 60 minutes of a light anesthetic plane maintained with isoflurane, measurements and sample collections were repeated. Cardiorespiratory and acid-base variables were compared with a repeated-measures ANOVA and post hoc t test and between time points with a pairwise Tukey test. RESULTS Mean ± SD intubation doses were 3.8 ± 0.8 mg/kg for tiletamine-zolazepam, 2.8 ± 0.3 mg/kg for alfaxalone, 6.1 ± 0.9 mg/kg and 0.26 ± 0.04 mg/kg for ketamine-diazepam, and 5.4 ± 1.1 mg/kg for propofol. Anesthetic depth was similar among regimens. At M0, heart rate increased by 94.9%, 74.7%, and 54.3% for tiletamine-zolazepam, ketamine-diazepam, and alfaxalone, respectively. Tiletamine-zolazepam caused higher oxygen delivery than propofol. Postinduction apnea occurred in 3 dogs when receiving alfaxalone. Acid-base variables remained within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs in which a light plane of anesthesia was maintained with isoflurane, cardiovascular and metabolic effects after induction with tiletamine-zolazepam were comparable to those after induction with alfaxalone and ketamine-diazepam.

OBJECTIVE To evaluate the lipidomic profile of surfactant obtained from horses with asthma at various clinical stages and to compare results with findings for healthy horses exposed to the same conditions. SAMPLE Surfactant samples obtained from 6 horses with severe asthma and 7 healthy horses. PROCEDURES Clinical evaluation of horses and surfactant analysis were performed. Samples obtained from horses with severe asthma and healthy horses before (baseline), during, and after exposure to hay were analyzed. Crude surfactant pellets were dried prior to dissolution in a solution of isopropanol:methanol:chloroform (4:2:1) containing 7.5mM ammonium acetate. Shotgun lipidomics were performed by use of high-resolution data acquisition on an ion-trap mass spectrometer. Findings were analyzed by use of an ANOVA with a Tukey-Kramer post hoc test. RESULTS Results of lipidomic analysis were evaluated to detect significant differences between groups of horses and among exposure statuses within groups of horses. Significantly increased amounts of cyclic phosphatidic acid (cPA) and diacylglycerol (DAG) were detected in surfactant from severely asthmatic horses during exposure to hay, compared with baseline and postexposure concentrations. Concentrations of cPA and DAG did not change significantly in healthy horses regardless of exposure status. CONCLUSIONS AND CLINICAL RELEVANCE cPA 16:0 and DAG 36:2 were 2 novel lipid mediators identified in surfactant obtained from asthmatic horses with clinical disease. These molecules were likely biomarkers of sustained inflammation. Further studies are needed to evaluate a possible correlation with disease severity and potential alterations in the plasma lipidomic profile of horses with asthma.

OBJECTIVE To determine the effect of orally administered melatonin on the intraocular pressure (IOP) of ophthalmologically normal dogs. ANIMALS 20 ophthalmologically normal dogs (40 eyes). PROCEDURES In a randomized crossover study, each dog received a 7-day regimen of melatonin (0.1 to 0.2 mg/kg, PO, q 12 h) and a placebo (150 mg of lactose powder in a capsule, PO, q 12 h), with a 7-day washout period between treatment regimens. Rebound tonometry was used to measure the IOP in both eyes of each dog 5 times at 2-hour intervals on days 0 (before administration of the first dose), 2, 4, and 7 (after administration of the last dose) of each treatment period. Repeated-measures ANOVA was used to evaluate the effects of treatment, day, and IOP measurement time within day on IOP. RESULTS Intraocular pressure was not significantly associated with treatment but was associated with day and the interaction between day and IOP measurement time within day. The mean ± SD IOP was 14.26 ± 2.95 and 14.34 ± 2.69 mm Hg for the melatonin and placebo regimens, respectively. Within each treatment period, the mean IOP tended to decrease from day 0 to 7 as well as within each day, which was attributed to the dogs becoming acclimated to the study protocol and natural diurnal variations in IOP. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of melatonin (0.1 to 0.2 mg/kg, q 12 h for 7 d) did not significantly affect the IOP of ophthalmologically normal dogs.

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.

OBJECTIVE To determine whether the lactate threshold of dogs could be determined by a visual method and to assess the extent of agreement and bias among treadmill velocities for the lactate threshold as determined by visual (LTv) and polynomial (LTp) methods, glucose threshold as determined by visual (GTv) and polynomial (GTp) methods, and heart rate deflection point (HRdp) as a method for estimating the aerobic capacity of dogs. ANIMALS 18 healthy adult Beagles. PROCEDURES Each dog underwent a standardized incremental treadmill exercise test once. The test ended when the dog began to show signs of fatigue. Plasma lactate and glucose concentrations and heart rate (HR) were plotted against exercise intensity (treadmill velocity) for the duration of the test, and the LTv, GTv, and HRdp were determined visually. The LTp and GTp were determined by means of a second-order polynomial function. One-way ANOVA, Pearson correlation, Bland-Altman analyses, and ordinary least products regression were used to assess the extent of agreement and bias among the various threshold velocities. RESULTS Mean velocity did not differ significantly among the thresholds evaluated. There was a strong positive correlation between the LTv velocity and the velocity for GTv (r = 0.91), LTp (r = 0.96), GTp (r = 0.94), and HRdp (r = 0.95). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that LTv could be determined for dogs undergoing intense exercise on a treadmill, and the treadmill velocity corresponding to the LTv was associated with the velocity for the other hallmarks of endurance. Thus, that method may be useful for prescription and evaluation of conditioning programs for dogs.

OBJECTIVE To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs. ANIMALS 5 purpose-bred hound-cross dogs. PROCEDURES A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA. RESULTS Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant. CONCLUSIONS AND CLINICAL RELEVANCE In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.