Comparison of the effects of methadone and butorphanol combined with acepromazine for canine gastroduodenoscopy

ObjectiveTo evaluate the feasibility of gastroduodenoscopy in dogs premedicated with acepromazine in combination with butorphanol or methadone.Study designProspective, randomized, double-blinded clinical trial.AnimalsA group of 40 client-owned dogs.MethodsDogs were randomly allocated to one of two groups and give intramuscular acepromazine 0.02 mg kg^–1 combined with either butorphanol 0.3 mg kg^–1 (group ACEBUT) or methadone 0.2 mg kg^–1 (group ACEMET). General anaesthesia was induced with propofol and ketamine and maintained with sevoflurane (2.3%) in oxygen. Cardiopulmonary variables were recorded at 5 minute intervals during anaesthesia. Feasibility of the entire gastroduodenoscopy was evaluated with a visual analogue scale (VAS) from 0 (best) to 100 (worst) (primary outcome of the study). Lower oesophageal sphincter dilatation and duodenal intubation were scored. Pylorus diameter was measured with standard endoscopic inflatable balloons. Overall cardiovascular stability was assessed during anaesthesia, using a VAS (0-100), as was the presence of fluid in the oesophagus, regurgitation, need for mechanical ventilation, and intraoperative and postoperative rescue analgesia (secondary outcomes of the study). Differences between treatments were analysed with Mann–Whitney U, Student t test, Fisher exact test or mixed model analysis of variance as appropriate. Subsequently, feasibility VAS of the gastroduodenoscopy was assessed for noninferiority between groups. The noninferiority margin was set as –10.ResultsAll gastroduodenoscopies were successfully completed in both groups using an endoscope tip diameter of 12.8 mm in all but one dog. Feasibility of gastroduodenoscopy was evaluated as 2.9 ± 5.6 in group ACEBUT and 5.1 ± 5.8 in group ACEMET. No significant differences between groups were detected in any measured or assessed variables, and noninferiority was confirmed.Conclusion and clinical relevanceIn our study population, the effects of methadone and butorphanol when combined with acepromazine were comparable.     

犬慢性肾衰竭进程中肠道菌群代谢物短链脂肪酸水平的变化及其对肾功能的影响

本研究旨在评估短链脂肪酸在慢性肾衰竭患犬和健康犬中的水平,探究短链脂肪酸变化的原因及其对肾功能的影响。选取22例轻度慢性肾衰患犬（M-CRF组）、29例重度慢性肾衰患犬（S-CRF组）和26例健康对照犬（HC组）,用16S rDNA测序技术分析肠道菌群多样性,气相色谱法检测粪中短链脂肪酸浓度。通过粪菌移植和补充丁酸钠给5/6肾摘除犬,观察肠道菌群及丁酸钠对肾功能影响。结果显示：1）S-CRF组肠道菌群多样性指标观察物种数及Simpson指数低于HC组（P<0.05）,PCoA分析显示,S-CRF组肠道菌群与M-CRF、HC组有差异。2）LEfSe分析显示,S-CRF组和HC组间大量差异菌群,拟杆菌科、拟杆菌属及假单胞菌科等7个菌种富集于S-CRF组,普氏杆菌科、梭菌科、普氏杆菌属及普拉梭菌属等11个菌种富集于HC组。CCA分析发现富集于S-CRF组菌种丰度与肾功能指标呈正相关。3）S-CRF组粪中乙酸、丙酸及丁酸浓度均显著低于HC组和M-CRF组,M-CRF组丁酸浓度显著低于HC组（P<0.05）,且丁酸浓度与血中胱抑素C（Cys-c）、肌酐（Cr）及尿素氮（BUN）等肾功能指标呈负相关（r值分别为-0.451、-0.583和-0.514,P<0.01）。4）与慢性肾衰模型组（5/6 Nx组）比较,慢性肾衰犬给与丁酸钠8周后,血清Cr和BUN显著降低（P<0.05）;粪菌移植8周后,血清Cr和BUN显著升高（P<0.05）,丁酸钠可回调血清Cr和BUN水平。综上表明,慢性肾衰竭患犬肠道菌群多样性降低,菌群结构及丰度改变,粪中短链脂肪酸浓度降低,这些变化可加剧肾功能障碍。为犬慢性肾衰竭的防治提供新的理论依据。     

Abnormal bone mineralization in a puppy fed an imbalanced raw meat homemade diet diagnosed and monitored using dual-energy X-ray absorptiometry

A 4-month-old male Old English Sheepdog was presented for evaluation of a raw meat-based homemade diet after a 1-month history of progressive lameness. Marked dietary deficiencies were detected, which included calcium, phosphorus and vitamin D. Hypovitaminosis D and hypocalcaemia were diagnosed by serum analysis. Evidence of severe diffuse osteopenia was noted on survey radiographs. Dual-energy X-ray absorptiometry (DEXA) was used to quantify bone mineral content and density and compare to published reference ranges. The puppy's initial bone mineralization was markedly subnormal, with bone mineral density 66% lower than expected, and bone mineral content 40% lower than expected. Subsequent DEXA scans were performed at intervals during the puppy's recovery to document the rate of bone re-mineralization and guide therapeutic recommendations. Marked improvement was achieved within 4 months through exercise control and feeding of a diet appropriately formulated for large breed puppy growth and development. This report reinforces the necessity of thorough dietary history and highlights the potential for malnutrition in pets fed homemade and raw meat-based diets. Use of DEXA has rarely been reported in clinical cases, yet can be a valuable tool for diagnosing and monitoring cases with abnormal bone mineralization. Further studies using DEXA to track bone mineralization in healthy puppies are encouraged to develop a more robust reference range of bone mineralization in growing dogs of varying sizes, weights and ages.     

Prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma

Currently, antimicrobial-resistant staphylococci, particularly methicillin-resistant Staphylococcus pseudintermedius (MRSP), are frequently isolated from canine superficial pyoderma in Japan. However, little is known regarding the nasal prevalence of MRSP in pet dogs. Here, we determined the prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma. Of the 125 nares and 108 affected sites of pet dogs with superficial pyoderma, 107 (13 species) and 110 (eight species) staphylococci strains, respectively, were isolated. The isolation rate of S. pseudintermedius from pyoderma sites (82/110 strains, 74.5%) was significantly higher than that from nares (57/107 strains, 53.3%) (P<0.01). Notably, the prevalence of MRSP (18/57 strains, 31.6%) in nares was equivalent to that in pyoderma sites (28/82 strains, 34.1%). Furthermore, the phenotypes and genotypes of antimicrobial resistance in MRSP strains from nares were similar to those from pyoderma sites. Our findings revealed that the prevalence of antimicrobial-resistant staphylococci in the nares of pet dogs with superficial pyoderma is the same level as that in affected sites. Therefore, considerable attention should be paid to the antimicrobial resistance of commensal staphylococci in companion animals.     

Characterization of a novel nicotinamide adenine dinucleotide-cytochrome b5 reductase mutation associated with canine hereditary methemoglobinemia

Hereditary methemoglobinemia associated with nicotinamide adenine dinucleotide-cytochrome b5 reductase (b5R) deficiency is a rare autosomal recessive disorder in animals. Recently, nonsynonymous b5R gene (CYB5R3) variants have been reported to be associated with canine and feline hereditary methemoglobinemia. However, the underlying molecular mechanisms of canine and feline methemoglobinemia caused by these nonsynonymous variants have not yet been reported. Previously, we reported a Pomeranian dog family with hereditary methemoglobinemia, carrying CYB5R3 mutation of an A>C transition at codon 194 in exon 7, replacing an isoleucine residue with leucine (p.Ile194Leu). In this study, we investigated the enzymatic and structural properties of the soluble form of wild-type and Ile194Leu canine b5Rs to characterize the effects of this missense mutation. Our results showed that the kinetic properties of the mutant enzyme were not affected by this amino acid substitution. The secondary structure of the wild-type and Ile194Leu b5Rs detected by circular dichroism showed a similar pattern. However, the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin hydrolysis. Moreover, the thermostability and unfolding measurements indicated that the mutant enzyme was more sensitive to temperature-dependent denaturation than the wild-type b5R. We concluded from these results that unstable mutant enzyme properties with normal enzymatic activity would be associated with hereditary methemoglobinemia in the Pomeranian dog family.     

Pseudorabies virus infection in hunting dogs in Oita,Japan: Report from a prefecture free from Aujeszky’s disease in domestic pigs

We isolated two pseudorabies virus (PRV) isolates (designated OT-1 and OT-2) from two hunting dogs exhibiting neurological manifestations after eating the flesh of wild boar hunted in Oita prefecture, Kyushu Island, Japan. The isolates corresponded to a previously reported PRV (MY-1 strain) isolated from a hunting dog in neighboring Miyazaki prefecture, and it clustered into genotype II based on the glycoprotein C sequence. Our results suggest that this common PRV strain may have been maintained in wild boars on Kyushu Island even though domestic pigs in this area have attained an Aujeszky’s disease-free status.     

Expression of P-glycoprotein and breast cancer resistance protein in three cases of canine lymphoma showing drug resistance

In canine lymphoma, drug resistance is the major factor hindering treatment. In this study, we performed immunohistochemical examination of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which are considered as transporters related to multidrug resistance in three recurrent canine lymphomas. All cases were negative for both transporters before anticancer drug administration, but became positive after this administration. The expression was confirmed in capillary endothelial cells, such as in brain capillaries acting as the blood-brain barrier (BBB). It is suggested that both transporters expressed on capillary endothelial cells in lymphoma tissue may inhibit the spread of anticancer drugs into tumor tissues from blood, the same as the BBB. Therefore, capillary endothelial cells could act as a blood-tumor barrier, which might be involved in drug resistance in canine lymphoma.