In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Endoscopic-assisted lumbosacral foraminotomy in the dog

OBJECTIVE: To determine if endoscopic-assisted foraminotomy significantly increased the area of the L7-S1 intervertebral foramen and if, over 12 weeks, stenosis would occur. STUDY DESIGN: Prospective, experimental study. ANIMAL POPULATION: Six clinically normal, 22-29 kg, adult dogs. METHODS: Using endoscopic assistance, unilateral L7-S1 foraminotomy was performed. Computed tomography of L7-S1 was performed preoperatively, immediately postoperatively, and at 12 weeks. Parasagittal foramen area (PFA) measurements were obtained at the entry, middle, and exit zones of the treated and control foramen for each period. Objective and subjective data were compared among dogs by time period and treatment status. RESULTS: Endoscopic-assisted foraminotomy resulted in a significant increase in the mean PFA of the entry and middle zones immediately postoperatively. The exit zone was not significantly larger at any time. The foramen remained significantly larger at 12 weeks only in the middle zone; however, some decrease in the surgically created foramen enlargement occurred at all 3 levels. The procedure was well tolerated but dogs did have transient, mild delay of functional return postoperatively. CONCLUSIONS: Endoscopic-assisted foraminotomy in dogs can be performed for certain foraminal regions, allowing enhanced visibility of the spinal canal. The foramen can be surgically enlarged at the entry and middle zones using this technique; however, some reduction of the foraminal enlargement occurs by 12 weeks. The clinical implications of this reduction cannot be determined from this study. CLINICAL RELEVANCE: Endoscopic-assisted foraminotomy could be used to improve intraoperative visualization in dogs with foraminal stenosis as a component of degenerative lumbosacral stenosis.     

放牧绵羊瘤胃液挥发性脂肪酸的变化规律及其受蠕虫感染的影响

选用敖汉细毛羊的育成母羊和成年母羊进行了3年试验.第1年试验在同一饲养水平下设对照组、常规驱虫组和缓释胶囊驱虫组;第2年和第3年又在常规饲养和改进饲养2种饲养方案下进行驱虫试验.所有试验羊在以披碱草、羊草和冰草为主的同类草场上放牧,每年进行3次驱虫处理.试验表明:放牧绵羊瘤胃液中挥发性脂肪酸(VFA)浓度随季节呈动态变化.其挥发性脂肪酸总量(TVFA)在青草期内较高;在枯草期内较低.放牧绵羊瘤胃发酵水平较低,特别在冬春季节内瘤胃发酵处于最低水平,发酵质量不高.另外,绵羊瘤胃液pH值随季节变动幅度较小.但发现在枯草期内的瘤胃液pH值高于青草期,特别在冬春季节内较高.蠕虫感染严重的时期内,蠕虫会影响绵羊瘤胃发酵水平,使瘤胃液VFA浓度降低;但常规驱虫法与缓释胶囊驱虫法间差异不显著.改进饲养与常规饲养方案对绵羊瘤胃液挥发性脂肪酸总量无显著影响.     

In vitro antimicrobial activity of a commercial ear antiseptic containing chlorhexidine and Tris–EDTA

Minimum bactericidal concentrations (MBCs) of a commercial ear antiseptic containing chlorhexidine 0.15% and Tris–EDTA (Otodine^®) were determined by broth microdilution for 150 isolates representing the most common pathogens associated with canine otitis. The microorganisms were classified into three groups according to their levels of susceptibility. The most susceptible group included Staphylococcus pseudintermedius, Malassezia pachydermatis, Streptococcus canis and Corynebacterium auriscanis, which were generally killed by 1 : 64 dilution of the antiseptic product (MBC = 23/0.8 μg/mL of chlorhexidine/Tris–EDTA). The most resistant organism was Proteus mirabilis, which survived up to 1 : 8 dilution of the product (MBC = 375/12 μg/mL). Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus displayed intermediate MBCs ranging between 188/6 and 47/1.5 μg/mL. Interestingly, S. pseudintermedius was more susceptible than S. aureus, and no significant difference was observed between meticillin‐resistant and meticillin‐susceptible isolates within each species, indicating that antiseptic use is unlikely to co‐select for meticillin resistance. Although the concentrations required for killing (MBCs) varied considerably with microorganism type, the combination of chlorhexidine 0.15% and Tris–EDTA was active against all the pathogens most commonly involved in canine otitis.     

Presumptive primary central nervous system T cell lymphoma in a deer (Capreolus capreolus)

This report describes the morphological and immunohistochemical findings in an approximately 7-year old wild European roe deer (Capreolus capreolus) with an infiltrative primary central nervous system T cell lymphoma. The roebuck had lost its timidity and was shot by a hunter. It was submitted for necropsy to exclude rabies. Gross examination revealed besides a verminous pneumonia no abnormal findings. Histologically, there was a highly cellular, not well demarcated, unencapsulated, and infiltrative neoplasm within basal parts of the brain. Tumour cells were round, up to 15μm in diameter and loosely arranged in sheets with a multifocally predominant perivascular infiltration. Immunohistochemically, tumour cells were positive for CD3 antigen. Whilst secondary lymphomas of the central nervous system emerge by metastatic seeding of tumour cells, primary lymphomas originate within the neuroparenchyma. This is the first report of a primary central nervous system lymphoma in an European roe deer.     

INADVERTENT INTRATHECAL ADMINISTRATION OF DIATRIZOATE MEGLUMINE AND DIATRIZOATE SODIUM DURING MYELOGRAPHY IN A DOG

A dog undergoing diagnostic myelography inadvertently received 0.5 ml diatrizoate meglumine (66%) and (10%) diatrizoate sodium via intrathecal injection. This resulted in post-operative seizures requiring extended sedation of the patient. The clinical course and management of this patient are presented. Complications associated with the inappropriate administration of a hyperosmolar contrast agent into the subarachnoid space and the results of similar accidents in humans are also discussed. The dog in the report recovered with no evidence of long trem neurological dam