OBJECTIVE To determine effects of restriction feeding of a moderate-protein, high-fiber diet on loss of body weight (BW), voluntary physical activity, body composition, and fecal microbiota of overweight cats. ANIMALS 8 neutered male adult cats. PROCEDURES After BW maintenance for 4 weeks (week 0 = last week of baseline period), cats were fed to lose approximately 1.5% of BW/wk for 18 weeks. Food intake (daily), BW (twice per week), body condition score (weekly), body composition (every 4 weeks), serum biochemical analysis (weeks 0, 1, 2, 4, 8, 12, and 16), physical activity (every 6 weeks), and fecal microbiota (weeks 0, 1, 2, 4, 8, 12, and 16) were assessed. RESULTS BW, body condition score, serum triglyceride concentration, and body fat mass and percentage decreased significantly over time. Lean mass decreased significantly at weeks 12 and 16. Energy required to maintain BW was 14% less than National Research Council estimates for overweight cats and 16% more than resting energy requirement estimates. Energy required for weight loss was 11% more, 6% less, and 16% less than American Animal Hospital Association recommendations for weight loss (80% of resting energy requirement) at weeks 1 through 4, 5 through 8, and 9 through 18, respectively. Relative abundance of Actinobacteria increased and Bacteroidetes decreased with weight loss. CONCLUSIONS AND CLINICAL RELEVANCE Restricted feeding of a moderate-protein, high-fiber diet appeared to be a safe and effective means for weight loss in cats. Energy requirements for neutered cats may be overestimated and should be reconsidered.

OBJECTIVE To evaluate the plasma disposition of mycophenolic acid (MPA) and its derivatives MPA glucuronide and MPA glucoside after twice-daily infusions of mycophenolate mofetil (MMF) in healthy cats for 3 days and to assess the effect of MMF administration on peripheral blood mononuclear cell (PBMC) counts and CD4+-to-CD8+ ratios. ANIMALS 5 healthy adult cats. PROCEDURES MMF was administered to each cat (10 mg/kg, IV, q 12 h for 3 days). Each dose of MMF was diluted with 5% dextrose in water and then administered over a 2-hour period with a syringe pump. Blood samples were collected for analysis. A chromatographic method was used to quantitate concentrations of MPA and its metabolites. Effects of MMF on PBMC counts and CD4+-to-CD8+ ratios were assessed by use of flow cytometry. RESULTS All cats biotransformed MMF into MPA. The MPA area under the plasma concentration–time curve from 0 to 14 hours ranged from 14.6 to 37.6 mg·h/L and from 14.4 to 22.3 mg·h/L after the first and last infusion, respectively. Total number of PBMCs was reduced in 4 of 5 cats (mean ± SD reduction, 25.9 ± 15.8% and 26.7 ± 19.3%) at 24 and 48 hours after the end of the first infusion of MMF, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Plasma disposition of MPA after twice-daily IV infusions for 3 days was variable in all cats. There were no remarkable changes in PBMC counts and CD4+-to-CD8+ ratios.

OBJECTIVE To determine effects for 2 IV regional limb perfusion (IVRLP) protocols involving tiludronate on lameness of horses with navicular syndrome. ANIMALS 15 horses with bilateral forelimb navicular syndrome. PROCEDURES Shoeing and anti-inflammatory injection into the distal interphalangeal joint (DIPJ) of both forelimbs (day 0) were performed on all horses. On day 14, horses received 1 of 3 IVRLPs consisting of 0.1 mg of tiludronate/kg (low-dose tiludronate [LDT]; n = 5), 0.2 mg of tiludronate/kg (high-dose tiludronate [HDT]; 5), or saline (0.9% NaCl) solution (placebo; 5); treatments were repeated at days 24 and 34. Lameness severity of both forelimbs was evaluated via subjective evaluation and force plate analysis before and after shoeing on day 0 and at days 14, 34, 60, and 120. Mean subjective lameness score and peak vertical ground reaction force (PVGRF) for the more severely lame forelimb (LFL) and both (combined) forelimbs (CFL) were compared over time. RESULTS For all horses, mean PVGRF for the LFL and CFL was increased at 14 days. No difference in mean subjective lameness score or mean PVGRF was detected within groups at any time. Mean PVGRF of the CFL was higher for the HDT group than the LDT and placebo groups only at 120 days. CONCLUSIONS AND CLINICAL RELEVANCE Use of the tiludronate IVRLP protocols described here provided no further improvement in lameness over therapeutic shoeing and anti-inflammatory injection of the DIPJ in horses with navicular syndrome. However, HDT-treated horses were objectively less lame than LDT- or placebo-treated horses at 120 days.

OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times were obtained for predetermined sites of the DIPJ before (T1preGd) and after (T1postGd) intra-articular gadolinium administration. Corresponding cartilage sites underwent macroscopic, histologic, and immunohistochemical evaluation, and cartilage glycosaminoglycan concentration and water content were determined. Median T1preGd and T1postGd were correlated with macroscopic, histologic, and biochemical data. Mixed generalized linear models were created to evaluate the effects of cartilage site, articular surface, and macroscopic and histologic scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median T1postGd was lower than the median T1preGd for normal and diseased cartilage. Both T1preGd and T1postGd were correlated with macroscopic and histologic scores, whereby T1preGd increased and T1postGd decreased as osteoarthritis progressed. There was topographic variation of T1preGd and T1postGd within the DIPJ. Cartilage glycosaminoglycan concentration and water content were significantly correlated with T1preGd and macroscopic and histologic scores but were not correlated with T1postGd. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dGEMRIC relaxation times varied for DIPJs with various degrees of osteoarthritis. These findings may help facilitate early detection of osteoarthritis.

OBJECTIVE To create a bioactive synovium scaffold by infusing decellularized synovial-derived extracellular matrix (synECM) with synovial-derived mesenchymal stem cells (synMSCs). SAMPLE Synovium from the femoropatellar and medial femorotibial joints of equine cadavers. PROCEDURES The synMSCs were cultured in monolayer and not treated or cotransduced to enhance expression of green fluorescent protein (GFP) and human bone morphogenetic protein (BMP)-2. The synECM was decellularized with 0.1% peracetic acid and then seeded with synMSCs (0.5 × 10(6) cells/0.5 mL) by use of a 30% serum gradient. Samples were evaluated on days 0, 3, 7, and 14. Cell migration, differentiation, and distribution into the synECMs were determined by cell surface marker CD90, viability, histologic morphology, and fluorescence microscopy results and expression of GFP, BMP-2, hyaluronan (HA), and proteoglycan (PG). RESULTS At day 14, synMSCs were viable and had multiplied 2.5-fold in the synECMs. The synECMs seeded with synMSCs had a significant decrease in CD90 expression and significant increases in HA and PG expression. The synECMs seeded with synMSCs cotransduced with GFP, or BMP-2 had a significant increase in BMP-2 expression. CONCLUSIONS AND CLINICAL RELEVANCE The synECM seeded with synMSCs or synMSCs cotransduced with GFP, or BMP-2 yielded a bioactive synovial scaffold. Expression of BMP-2 by synMSCs cotransduced to enhance expression of BMP-2 or GFP and an accompanying increase in both HA and PG expression indicated production of anabolic agents and synoviocyte differentiation in the scaffold. Because BMP-2 can promote repair of damaged cartilage, such a bioactive scaffold could be useful for treatment of injured cartilage.

OBJECTIVE To determine whether stored (cooled or frozen-thawed) jejunal segments can be used to obtain dependable leak pressure data after enterotomy closure. SAMPLE 36 jejunal segments from 3 juvenile pigs. PROCEDURES Jejunal segments were harvested from euthanized pigs and assigned to 1 of 3 treatment groups (n = 12 segments/group) as follows: fresh (used within 4 hours after collection), cooled (stored overnight at 5°C before use), and frozen-thawed (frozen at −12°C for 8 days and thawed at room temperature [23°C] for 1 hour before use). Jejunal segments were suspended and 2-cm enterotomy incisions were made on the antimesenteric border. Enterotomies were closed with a simple continuous suture pattern. Lactated Ringer solution was infused into each segment until failure at the suture line was detected. Leak pressure was measured by use of a digital transducer. RESULTS Mean ± SD leak pressure for fresh, cooled, and frozen-thawed segments was 68.3 ± 23.7 mm Hg, 55.3 ± 28.1 mm Hg, and 14.4 ± 14.8 mm Hg, respectively. Overall, there were no significant differences in mean leak pressure among pigs, but a significant difference in mean leak pressure was detected among treatment groups. Mean leak pressure was significantly lower for frozen-thawed segments than for fresh or cooled segments, but mean leak pressure did not differ significantly between fresh and cooled segments. CONCLUSIONS AND CLINICAL RELEVANCE Fresh porcine jejunal segments or segments cooled overnight may be used for determining intestinal leak pressure, but frozen-thawed segments should not be used.

OBJECTIVE To validate that dogs become hypocoagulable following rattlesnake envenomation and to determine whether thromboelastographic abnormalities are correlated with envenomation severity for dogs bitten by rattlesnakes native to southern California. ANIMALS 14 dogs with observed or suspected rattlesnake envenomation (envenomated dogs) and 10 healthy control dogs. PROCEDURES For each dog, a citrate-anticoagulated blood sample underwent kaolin-activated thromboelastography. For each envenomated dog, a snakebite severity score was assigned on the basis of clinical findings, and prothrombin time, activated partial thromboplastin time, and platelet count were determined when the attending clinician deemed it necessary and owner finances allowed. RESULTS For 12 of 14 envenomated dogs, the thromboelastographically determined clot strength was below the 25th percentile for the clot strength of control dogs, which was indicative of a hypocoagulable state. No envenomated dog had thromboelastographic results indicative of a hypercoagulable state. One envenomated dog had a prolonged prothrombin time, but the activated partial thromboplastin time and all thromboelastographic variables were within the respective reference ranges for that dog. Seven of 13 envenomated dogs were thrombocytopenic (platelet count, ≤ 170,000 platelets/μL). Snakebite severity score was negatively correlated with platelet count but was not correlated with any thromboelastographic variable. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs generally become hypocoagulable following rattlesnake envenomation. Thromboelastography might provide an objective measure of the coagulation status of envenomated dogs and aid in the identification of dogs that are in a hypocoagulable state and in need of antivenin treatment prior to the onset of progressive clinical signs.

OBJECTIVE To determine reference intervals for total nucleated cell count, total protein concentration, pH, RBC count, and percentages of neutrophils, lymphocytes, and large mononuclear cells in synovial fluid samples (SFSs) obtained from the carpal and tarsal joints of healthy swine. ANIMALS 54 healthy commercial finisher pigs that had no evidence of lameness or gross joint swelling. PROCEDURES Each pig was anesthetized, and SFSs were collected from 1 carpal and 1 tarsal joint for fluid analysis, cytologic evaluation, bacterial culture, and PCR analyses for common swine joint pathogens. Each pig was euthanized after SFS collection, and synovial tissue samples were collected for histologic assessment. If necessary, postmortem SFSs were collected. RESULTS Overall, 37 of 50 tarsal and 46 of 53 carpal SFSs met inclusion criteria of sufficient volume, no gross blood contamination, and negative results of bacterial culture and PCR analyses, and were from joints with histologically normal synovial tissues. For the carpal and tarsal joints, upper reference limits were as follows: total nucleated cell count, 3,281 cells/μL and 2,368 cells/μL, respectively; total protein concentration, 3.6 g/dL and 3.6 g/dL, respectively; pH, 7.2 and 7.0, respectively; RBC count, 0.8 × 10(6) cells/μL and 0.1 × 10(6) cells/μL, respectively; and percentage of neutrophils, 46.5% and 33.7%, respectively; percentage of lymphocytes, 40.6% and 56.3%, respectively; and percentage of large mononuclear cells, 92.0% and 95.3%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results have provided reference intervals for selected variables in SFSs obtained from the carpal and the tarsal joints of healthy swine, which should be useful in diagnostic investigations of swine lameness and arthritis.

OBJECTIVE To evaluate efficacy of an alveolar recruitment maneuver (ARM) with positive end-expiratory pressures (PEEPs) in anesthetized horses ventilated with oxygen or heliox (70% helium and 30% oxygen). ANIMALS 6 healthy adult horses. PROCEDURES In a randomized crossover study, horses were anesthetized and positioned in dorsal recumbency. Volume-controlled ventilation was performed with heliox or oxygen (fraction of inspired oxygen [Fio2] > 90%). Sixty minutes after mechanical ventilation commenced, an ARM with PEEP (0 to 30 cm H2O in steps of 5 cm H2O every 5 minutes, followed by incremental steps back to 0 cm H2O) was performed. Peak inspiratory pressure, dynamic lung compliance (Cdyn), and Pao2 were measured during each PEEP. Indices of pulmonary oxygen exchange and alveolar dead space were calculated. Variables were compared with baseline values (PEEP, 0 cm H2O) and between ventilation gases by use of repeated-measures ANOVAs. RESULTS For both ventilation gases, ARM significantly increased pulmonary oxygen exchange indices and Cdyn. Mean ± SD Cdyn (506 ± 35 mL/cm H2O) and Pao2-to-Fio2 ratio (439 ± 36) were significantly higher and alveolar-arterial difference in Pao2 (38 ± 11 mm Hg) was significantly lower for heliox, compared with values for oxygen (357 ± 50 mL/cm H2O, 380 ± 92, and 266 ± 88 mm Hg, respectively). CONCLUSIONS AND CLINICAL RELEVANCE An ARM in isoflurane-anesthetized horses ventilated with heliox significantly improved pulmonary oxygen exchange and respiratory mechanics by decreasing resistive properties of the respiratory system and reducing turbulent gas flow in small airways.