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.     

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.     

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     

The prevalence of Cryptosporidium spp. oocysts in wild mammals in the Kruger National Park, South Africa

This study determined the prevalence of Cryptosporidium spp. oocysts in faecal samples from elephant (Loxodonta africana), buffalo (Syncerus caffer) and impala (Aepyceros melampus) in the Kruger National Park (KNP) and an adjacent game reserve in South Africa. Two of the study areas were in close proximity to rural communities on the western KNP boundary and the third study area was located in the centre of the KNP. Fresh stool samples (n=445) were collected and tested using an immunofluorescent antibody test (IFA) for Cryptosporidium parvum. A total of 278 of these were randomly selected (approximately 90 samples per wildlife species) and tested with the modified Ziehl Neelsen staining technique (ZN) for Cryptosporidium spp. The prevalence of Cryptosporidium spp. was highest in elephants (25.8% [95% confidence interval: 17.3, 35.9]), compared to buffalo (5.5% [1.8, 12.4]) and impala (4.3% [1.2, 10.5]). C. parvum showed similar patterns, being most prevalent in elephants (4.2% [1.5, 8.8]), compared to buffalo (1.4% [0.2, 5.1]) and impala (1.9% [0.4, 5.3]). 29 samples, including ZN positive and IFA positive samples, were retested using a real time PCR (rtPCR) technique. Of the 28 ZN-positive samples, 14 (50%) were positive with rtPCR and of the 9 IFA-positive samples 6 (67%) were confirmed positive by rtPCR. The prevalence of Cryptosporidium oocysts was significantly higher in both of the two study areas adjacent to the western KNP boundary compared to the area in the centre of the KNP (OR=3.2 [1.2, 9.0]; P=0.024). Our study demonstrates for the first time the presence of Cryptosporidium spp. in wildlife in South Africa. The transmission of this parasite between wildlife, domestic animals and humans is a plausible hypothesis and represents a potential risk for immunodeficient human populations.     

Histomorphometry of fragmented medial coronoid process in dogs: a comparison of affected and normal coronoid processes

OBJECTIVE: To determine if fatigue microdamage is associated with fragmented medial coronoid process (FMCP). STUDY DESIGN: Prospective study. ANIMALS: Thirty-eight dogs were admitted for subtotal coronoid ostectomy as treatment for FMCP. Surgical specimens of medial coronoid process (MCP) were retrieved from treated dogs. Normal MCP were collected from 5 age- and breed-matched dogs and 2 age-matched research beagles that were euthanatized for reasons other than elbow disease. METHODS: MCP specimens from affected elbows were classified into 4 groups based on disease severity. Specimens were bulk-stained for microdamage using 1% basic fuchsin, embedded in polymethylmethacrylate and sectioned at 130 microm. Specimens were evaluated using epifluorescent microscopy (425-440 excitation, 475 nm barrier filter) for diffuse damage (D.DX), osteocyte loss, and porosity. Cartilage thickness was evaluated using bright field microscopy. Qualitative observations were also made. RESULTS: MCP specimens from affected elbows had increased D.Dx, increased osteocyte loss, and greater porosity than normal groups. Specimens classified as severe FMCP (Classes 3, 4) had the most fatigue microdamage. Some Class 1 specimens, defined as having no visible fissuring of the articular cartilage (AC), had large microcracks in trabecular bone. CONCLUSIONS: Accumulation of subchondral fatigue microdamage, is associated with MCP fragmentation. Fissuring occurs in the subchondral bone before gross fibrillation of articular cartilage develops. CLINICAL RELEVANCE: Accumulation of fatigue microdamage in the MCP is important in the pathogenesis of FMCP. The underlying cause of this microdamage accumulation must be identified before treatment plans that will prevent further osteoarthritis of the elbow joint can be designed.     

Femoral bone adaptation to unstable long-term cemented total hip arthroplasty in dogs

OBJECTIVE: To evaluate femoral adaptation after unstable long-term cemented total hip arthroplasty (cTHA) in dogs. STUDY DESIGN: Clinical study. ANIMALS: Four dogs. METHODS: Paired femurs were examined from client-owned dogs that were donated to a retrieval program after death from causes unrelated to their cTHA. Mean (+/-SEM) dog age was 10.0+/-1.5 years and implant duration was 6.0+/-1.4 years. Implanted femurs had radiographic changes associated with implant loosening and gross mechanical instability at femur retrieval. Femurs were evaluated at 3 levels relative to implant length. Cortical area and medullary area were measured at each level, and cortical porosity was assessed at each level in 4 quadrants and in 3 regions. Implanted femurs were compared with the contralateral non-implanted femurs. RESULTS: Cortical area and cortical porosity were increased at all levels in femurs with unstable implants. Implanted femurs had increased porosity in all quadrants and regions at the proximal 2 levels, and increased porosity in only the cranial quadrant and mid-cortical area at the distal level, when compared with contralateral non-implanted femurs. Corresponding medullary areas were not different. CONCLUSIONS: Significant histomorphometric changes occur in femurs after unstable cTHA. The patterns of periosteal bone formation and endosteal bone resorption support mechanisms of stress shielding and wear debris-mediated osteolysis as factors that may contribute to femoral adaptation and implant loosening. CLINICAL RELEVANCE: Despite popularity and excellent return to function with cTHA, aseptic loosening remains a serious long-term complication. Substantial net bone loss and unfavorable environment with unstable cTHA may make revision surgery less successful.