Objective-To determine the effect of caprine arthritis-encephalitis virus (CAEV) infection on expression of interleukin-16 (IL-16). Animals-6 goats experimentally infected with CAEV and 6 age-matched healthy uninfected control goats. Procedure-Peripheral blood mononuclear cells (PBMCs) and synovial membrane cells from infected and control goats cultured with or without phytohemagglutinin were analyzed for IL-16 mRNA by use of a reverse transcriptase-polymerase chain reaction assay with goat-specific primers, after cloning and sequencing of a 384-bp fragment of the goat IL-16 gene. Synovial fluid, serum, and culture supernatants of PBMCs and synovial cells of control and CAEV-infected goats were analyzed for IL-16 by use of an ELISA. Results-The 384-bp product was 86% homologous to the corresponding human IL-16 nucleotide sequence. Higher expression of IL-16 mRNA in PBMCs (unstimulated or stimulated with phytohemagglutinin) was detected in samples from CAEV-infected goats, compared with control goats, but the difference was not significant. Synovial membrane cells infected in vitro had higher expression than uninfected control cells. Higher IL-16 concentration was detected in synovial fluid, serum, and culture supernatants of PBMCs of infected goats than in samples from control goats. Conclusions and Clinical Relevance-Infection with CAEV increases expression of IL-16, a proinflammatory and chemotactic cytokine. This cytokine appears to be constitutively expressed at low concentrations in normal uninfected PBMCs and synovial membrane cells. Increased production of IL-16 in CAEV infection may partly be responsible for increased lymphoid cell infiltrations observed in arthritic joints and other tissues of CAEV-infected goats.

Objective-To evaluate a model for atopic dermatitis (AD) and to measure the effect of sensitization in Beagles genetically predisposed to produce high serum concentrations of allergen specific IgE. Animals-22 laboratory Beagles. Procedure-Seventeen dogs were sensitized from birth to 3 allergens (recombinant birch pollen, Dermatophagoides pteronyssinus, and D farinae). Five nonsensitized dogs from the same litters served as controls. Clinical scoring, regular intradermal testing, measurement of serum concentrations of allergen-specific IgE, and collection of biopsy specimens of skin at 23, 32, and 43 weeks of age were performed. Serial tissue sections were stained for identification of IgE+ cells, mast cells and their subtypes, T-cells, Langerhans cells, and major histocompatibility complex class-II+ cells. At the age of 15 months, dogs were continuously exposed to 2 µg of mite allergen/ g of dust. Results-Sensitized dogs had positive intradermal test reactions and significantly higher serum concentrations of allergen specific IgE, compared with nonsensitized dogs. In sensitized and nonsensitized dogs, a significantly higher number of mast cells was found at predilection sites, compared with the control biopsy site. The number of mast cells at predilection sites increased with age. Sensitization significantly increased the number of epidermal Langerhans cells by 23 weeks of age. The number of epidermal Langerhans cells significantly increased in nonsensitized dogs by 32 weeks of age. Clinical scoring only revealed mild transient erythema in some dogs. Conclusion and Clinical Relevance-Increases in concentrations of serum allergen-specific IgE and exposure to allergens is not sufficient to induce clinical signs of AD in genetically predisposed dogs.

Objective-To compare cardiopulmonary responses during anesthesia maintained with halothane and responses during anesthesia maintained by use of a total intravenous anesthetic (TIVA) regimen in horses. Animals-7 healthy adult horses (1 female, 6 geldings). Procedure-Each horse was anesthetized twice. Romifidine was administered IV, and anesthesia was induced by IV administration of ketamine. Anesthesia was maintained for 75 minutes by administration of halothane (HA) or IV infusion of romifidine, guaifenesin, and ketamine (TIVA). The order for TIVA or HA was randomized. Cardiopulmonary variables were measured 40, 60, and 75 minutes after the start of HA or TIVA. Results-Systolic, diastolic, and mean carotid arterial pressures, velocity time integral, and peak acceleration of aortic blood flow were greater, and systolic, diastolic, and mean pulmonary arterial pressure were lower at all time points for TIVA than for HA. Pre-ejection period was shorter and ejection time was longer for TIVA than for HA. Heart rate was greater for HA at 60 minutes. Minute ventilation and alveolar ventilation were greater and inspiratory time was longer for TIVA than for HA at 75 minutes. The PaCO2 was higher at 60 and 75 minutes for HA than for TIVA. Conclusions and Clinical relevance-Horses receiving a constant-rate infusion of romifidine, guaifenesin, and ketamine maintained higher arterial blood pressures than when they were administered HA. There was some indication that left ventricular function may be better during TIVA, but influences of preload and afterload on measured variables could account for some of these differences.

Objective-To determine significant molecular and cellular factors responsible for differences in secondintention healing in thoracic and metacarpal wounds of horses. Animals-6 adult mixed-breed horses. Procedure-A full-thickness skin wound on the metacarpus and another such wound on the pectoral region were created, photographed, and measured, and tissue was harvested from these sites weekly for 4 weeks. Gene expression of type-I collagen, transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-1, and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by quantitative in situ hybridization. Myofibroblasts were detected by immunohistochemical labeling with α-smooth muscle actin (α-SMA). Collagen accumulation was detected by use of picrosirius red staining. Tissue morphology was examined by use of H&E staining. Results-Unlike thoracic wounds, forelimb wounds enlarged during the first 2 weeks. Myofibroblasts, detected by week 1, remained abundant with superior organization in thoracic wounds. Type-I collagen mRNA accumulated progressively in both wounds. More type-I collagen and TGF-β1 mRNA were seen in forelimb wounds. Volume of MMP-1 mRNA decreased from day 0 in both wounds. By week 3, TIMP-1 mRNA concentration was greater in thoracic wounds. Conclusions and Clinical Relevance-Greater collagen synthesis in metacarpal than thoracic wounds was documented by increased concentrations of myofibroblasts, type-I collagen mRNA, TGF-β1 mRNA, and decreased collagen degradation (ie, MMP-1). Imbalanced collagen synthesis and degradation likely correlate with development of exuberant granulation tissue, delaying healing in wounds of the distal portions of the limbs. Factors that inhibit collagen synthesis or stimulate collagenase may provide treatment options for horses with exuberant granulation tissue.

Objective-To assess effects of exercise on a treadmill with changes in gastric volume and pH in the proximal portion of the stomach of horses. Animals-3 healthy adult horses. Procedure-A polyester bag of approximately 1,600 mL was placed into the proximal portion of the stomach of each horse via a nasogastric tube. Changes in bag volume, determined by an electronic barostat, were recorded before, during, and after a training session on a treadmill with and without prior withholding of food. In separate experiments, pH in the proximal portion of the stomach was continuously recorded during exercise for fed and food-withheld conditions. Finally, changes in intra-abdominal and intragastric pressure were simultaneously recorded during a training session. Results-Bag volume rapidly decreased to nearly zero during trotting and galloping. Conversely, a return to walking resulted in a sharp increase in volume and a return to pre-exercise values. Intragastric and intraabdominal pressures increased almost in parallel with walking, trotting, galloping, and galloping on a slope. Gastric pH decreased rapidly to < 4 at the beginning of walking, continued to decrease during trotting and galloping, and remained low until a return to walking. Conclusions and Clinical Relevance-Increased intra-abdominal pressure during intense exercise in horses causes gastric compression, pushing acidic contents into the proximal, squamous-lined region of the stomach. Increased duration of acid exposure directly related to daily duration of exercise may be the reason that squamous lesions tend to develop or worsen when horses are in intensive training programs.

Objective-To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats. Animals-6 healthy adult cats with a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. Procedure-CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay. Results-Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng·h/ml. Conclusions and Clinical Relevance-Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats.

Objective-To determine whether intrathecal (IT) or IV administration of oxytocin will diminish amplitude of the reflex-evoked muscle action potential (REMP) in the digastricus muscle during electrical stimulation of the tooth pulp in anesthetized dogs, thus suggesting an analgesic effect for oxytocin. Animals-6 male Beagles that were 2 to 6 years old. Procedure-Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin by both the IT and IV routes of administration. Noninvasive dental dolorimetry was used to assess changes in pain threshold following administration of treatments. Effectiveness of analgesia was determined on the basis of change in REMP amplitude in the digastricus muscle. Results-Morphine administered IV significantly inhibited REMP amplitude, compared with IV administration of saline solution or oxytocin. There was not a significant change in REMP amplitude between saline solution and oxytocin administered IV. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution or oxytocin. Intrathecal administration of oxytocin significantly increased REMP amplitude, compared with IT administration of saline solution or morphine. Conclusions and Clinical Relevance-Although IV administration of oxytocin did not have an effect on REMP amplitude, compared with IV administration of saline solution, IT administration of oxytocin had the opposite effect of morphine and increased REMP amplitude of the digastricus muscle. These data do not support the use of oxytocin as an analgesic agent in dogs.

Objective-To characterize matrix metalloproteinase (MMP)-2 and -9 in CSF of clinically normal dogs. Sample Population-Samples of CSF collected from 23 dogs. Procedure-Dogs were anesthetized, CSF samples were collected, and dogs were then euthanatized. Each CSF sample was evaluated immediately for RBC count, WBC count, and protein and glucose concentrations, and cytologic examination also was performed. Samples were considered normal when protein concentration was < 25 mg/dL and CSF contained < 6 WBCs/μL and < 25 RBCs/μL. Samples were stored at -70°C. Sections of brain tissue were collected and processed for histologic examination. The MMPs were evaluated by use of gelatin zymography and a polyclonal antibody-based sandwich ELISA. Results-Mean WBC count for CSF samples was < 1 WBC/μL (range, 0 to 3 WBCs/mL). Mean protein concentration was 12 mg/dL (range, 8 to 17 mg/dL). Mean RBC count was 3.65 RBCs/μL (range, 0 to 21 RBCs/μL). All CSF samples generated a clear band on zymography gels that corresponded to the human commercial standard of proenzyme MMP-2. Other major clear bands were not detected on zymography gels. Bands correlating to MMP-9 were not detected in any samples. The ELISA results revealed a mean +/- SD proenzyme MMP-2 concentration of 5.61 +/- 1.92 ng/mL (range, 3.36 to 10.83 ng/mL). Conclusions and Clinical Relevance-The proenzyme form of MMP-2 is detectable in CSF of clinically normal dogs, whereas MMP-9 is not detectable. Additional investigation of MMPs in CSF from dogs with various diseases of the nervous system is indicated.

Objective-To determine the effect of a commercially available nasal strip on airway mechanics in exercising horses. Animals-6 horses (5 Standardbreds and 1 Thoroughbred). Procedure-Horses exercised on a treadmill at speeds corresponding to 100 and 120% of maximal heart rate with and without application of a commercially available nasal strip. Concurrently, tracheal pressures, airflow, and heart rate were measured. Peak inspiratory and expiratory tracheal pressures, airflow, respiratory frequency, and tidal volume were recorded. Inspiratory and expiratory airway resistances were calculated by dividing peak pressures by peak flows. Endoscopic examination of the narrowest point of the nasal cavity (ie, nasal valve) was performed in 1 resting horse before, during, and after application of a nasal strip. Results-During exercise on a treadmill, peak tracheal inspiratory pressure and inspiratory airway resistance were significantly less when nasal strips were applied to horses exercising at speeds corresponding to 100 and 120% of maximal heart rate. Application of the nasal strip pulled the dorsal conchal fold laterally, expanding the dorsal meatus. Conclusions and Clinical Relevance-The commercially available nasal strip tented the skin over the nasal valve and dilated that section of the nasal passage, resulting in decreased airway resistance during inspiration. The nasal strip probably decreases the amount of work required for respiratory muscles in horses during intense exercise and may reduce the energy required for breathing in these horses.

Objective-To evaluate postexposure prophylaxis (PEP) in dogs experimentally infected with rabies. Procedure-29 Beagles. Procedure-Dogs were sedated and inoculated in the right masseter muscle with a salivary gland homogenate from a naturally infected rabid dog (day 0). Six hours later, 5 dogs were treated by administration of 2 murine anti-rabies glycoprotein monoclonal antibodies (mAb) and commercial vaccine; 5 received mAb alone; 5 received purified, heat-treated, equine rabies immune globulin (PHT-ERIG) and vaccine; 5 received PHT-ERIG alone; 4 received vaccine alone; and 5 control dogs were not treated. The mAb or PHTERIG was administered at the site of rabies virus inoculation. Additional vaccine doses for groups mAb plus vaccine, PHT-ERIG plus vaccine, and vaccine alone were administered IM in the right hind limb on days 3, 7, 14, and 35. Results-All control dogs and dogs that received only vaccine developed rabies. In the PHT-ERIG and vaccine group, 2 of 5 dogs were protected, whereas none were protected with PHT-ERIG alone. Use of mAb alone resulted in protection in 4 of 5 dogs. Administration of mAb in combination with vaccine provided protection in all 5 dogs. Conclusions and Clinical Relevance-Current national guidelines recommend euthanasia or a 6- month quarantine for unvaccinated animals exposed to rabies. Findings from this study document that vaccine alone following severe exposure was unable to provide protection from rabies. However, vaccine combined with mAb resulted in protection in all treated dogs, revealing the potential use of mAb in PEP against rabies in naïve dogs.