Early retinopathy in the Bernese Mountain Dog in France: preliminary observations

The objective of the study was to describe a form of early retinopathy in the Bernese Mountain Dog in France. Sixty-two Bernese Mountain Dogs (38 males and 24 females), whose ages ranged from 2 months to 9 years, were examined over a period of 3 years. Visual behavior, pupillary light reflexes, menace responses and ocular fundi were evaluated in all animals. Electroretinography (ERG) was performed on six of the affected dogs after dark adaptation. Fluorescein angiography (FA) was performed on one affected dog. Whenever possible, the pedigrees of the affected dogs were evaluated. A histological examination of the retina was performed on one of the affected dogs. Eight dogs (seven males and one female) were diagnosed with retinopathy with an early onset of clinical signs. (Four dogs were aged between 3 months and 1 year, two dogs were aged 2 and 3.5 years, and one dog was 7 years old.) Night vision was impaired in most of the dogs. Retinopathy was characterized ophthalmoscopically by a bilateral, symmetrical horizontal zone of tapetal hyper-reflectivity adjacent to and above the optic disc, and sometimes by peri-papillary hyper-reflectivity. ERG changes included a reduction in b-wave amplitude varying from one case to another. Fluoroscein angiography demonstrated an ischemic-type alteration with epitheliopathy opposite the hyper-reflective zone. Pedigree examinations suggested a familial predisposition. The histological examination indicated photoreceptor degeneration that was more pronounced in the central tapetal zone. In France, retinopathy in the Bernese Mountain Dog involves an early retinal degeneration that produces specific manifestations of the ocular fundus, night visual impairment or blindness, and has familial transmission.     

Serological evidence of Anaplasma spp., Borrelia burgdorferi and Ehrlichia canis in dogs from the Republic of Korea by rapid diagnostic test kits

BackgroundEmergent and re-emergent canine tick-borne infections are attracting increasing attention worldwide. The rise in pet ownership and the close relationship between dogs and their owners are the most concerning factors because dogs may act as competent reservoirs for human tick-transmitted infectious agents.ObjectivesThis study contributes to the epidemiological surveillance of canine tick-transmitted infections with zoonotic risk in the Republic of Korea (ROK) by investigating the seroprevalence of the pathogens, Anaplasma spp., Borrelia burgdorferi, and Ehrlichia canis.MethodsFour hundred and thirty whole blood samples from domestic dogs were collected in seven metropolitan cities and nine provinces in the ROK and tested using SensPERT Ab test kits (VetAll Laboratories®) to detect seroreactive animals.ResultsThe seroprevalence rates identified were 9.8% (42/430) for Anaplasma spp., 2.8% (12/430) for B. burgdorferi, and 1.4% (6/430) for E. canis. The risk factors evaluated in this study that could be associated with the development of a humoral immune response, such as sex, age, and history of tick exposure, were similar. There was only one exception for dogs seroreactive to Anaplasma spp., where the risk factor “tick exposure” was statistically significant (p = 0.047).ConclusionsThis serological survey exhibited the widespread presence of Anaplasma spp., B. burgdorferi, and E. canis throughout the ROK. Hence, dogs may play a key role as the sentinel animals of multiple zoonotic infectious agents in the country.     

Gain‐of‐function mutation in PTPN11 in histiocytic sarcomas of Bernese Mountain Dogs

Histiocytic sarcoma (HS) is an aggressive malignant neoplasm of dendritic cell origin that is common in certain breeds of dogs. High prevalence of fatal, disseminated HS has been described in Bernese Mountain Dogs (BMDs). Support for genetic predisposition to develop HS has been presented in several studies, but to date, causative genetic events have not been reported. In addition, no driver mutations have been identified in tumours. Recently, E76K gain‐of‐function mutation in SHP2 encoded by the PTPN11 gene has been described in human histiocytic malignancies. In our study, we identified the PTPN11^E76K in HS of BMDs. Amplification of exon 3 of the PTPN11 gene followed by Sanger sequencing was used to detect the mutation and estimate the prevalence in HS from 30 BMDs, 13 Golden Retrievers and 10 other dog breeds. The overall prevalence of PTPN11^E76K in HS of BMDs was 36.67% compared with 8.69% in other breeds. No mutation was identified in normal tissues from 10 BMDs with HS that carried the mutation and 12 control dogs with no neoplastic disease, including 6 BMDs. Increased immunoreactivity for AKT, phosphorylated ERK1/2 and phosphorylated AKT in a small subset of BMDs with PTPN11^E76K suggests that a gain‐of‐function might be mediated by the ERK and AKT pathways. These data suggest PTPN11^E76K as an important driver mutation of HS in BMDs. This information may not only aid in unravelling the tumourigenic events associated with HS in BMDs, but also help in identifying more promising therapeutic strategies.     

Spirochetemia caused by Borrelia turicatae infection in 3 dogs in Texas

Spirochetemia was diagnosed in 2 Siberian Huskies and a Rottweiler from the northwestern region of Texas between June 1999 and October 2001. Clinical findings were nonspecific; tick exposure was documented in 2 of the dogs. Hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1 with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia (n=2). One anemic dog had a positive Coombs' test. In 1 dog, Western blot analysis of serum yielded multiple positive bands with B turicatae lysate, indicating the spirochetemia most likely was due to B turicatae infection. In 2 dogs, spirochetes were cultured from the blood and identified using DNA analysis as Borrelia turicatae; 1 of these dogs also was seropositive for Ehrlichia canis and B burgdorferi. In 2 cases, spirochetemia was more prominent in blood smears prepared immediately after sample collection than in smears prepared from EDTA blood. Two dogs recovered with doxycycline treatment; 1 dog declined clinically despite treatment and was euthanized. B turicatae is the agent of tick-borne (endemic) relapsing fever in humans and is distinct from B burgdorferi, the agent of Lyme disease; however, serologic cross-reactivity may occur. B turicatae is transmitted by the soft tick, Ornithodoros turicata, and infection should be considered in dogs with spirochetemia and possible exposure to the tick vector.     

ACVIM consensus update on Lyme borreliosis in dogs and cats

An update of the 2006 American College of Veterinary Internal Medicine (ACVIM) Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment, and Prevention was presented at the 2016 ACVIM Forum in Denver, CO, followed by panel and audience discussion and a drafted consensus statement distributed online to diplomates for comment. The updated consensus statement is presented below. The consensus statement aims to provide guidance on the diagnosis, treatment, and prevention of Lyme borreliosis in dogs and cats.     

Complement C3 participates in the development of goose fatty liver potentially by regulating the expression of FASN and ETNK1

Non-alcoholic fatty liver disease ( NAFLD ) occurs in humans, domestic animals and poultry. Different from upregulation of complement C3 in human NAFLD, C3 expression is inhibited in goose fatty liver ( GFL ), implying a specific role of C3 in GFL. This study was mainly focused on uncovering the uniqueness of goose liver cells in the regulation of C3 expression and identifying the downstream genes of C3 to improve understanding on the specific role of C3 in GFL. The results showed that C3 expression was inhibited in the liver, muscle and fat tissues of the overfed versus control (normally fed) geese. Oleate and insulin could inhibit C3 expression in goose primary hepatocytes but induce it in mouse primary hepatocytes. A total of 1,123 differentially expressed genes ( DEGs ) were affected by C3 overexpression and were mainly enriched in immune response/inflammation and catabolism-related KEGG pathways. Additionally, the representative downstream genes (FASN and ETNK1) of C3 could mediate the role of C3 in the development of GFL. In conclusion, the suppression of C3 in GFL is at least partially attributed to hyperinsulinemia, hyperlipidemia and uniqueness of goose liver cells. Complement C3 does not only affect hepatic steatosis but also affect inflammation/immune response in GFL.     

Suppurative, nonseptic polyarthropathy in dogs

The goals of this study were to determine the historical, physical examination, and clinicopathologic findings in dogs with suppurative, nonseptic polyarthropathy and to identify concurrent disorders associated with this syndrome. Medical records of 52 dogs with cytologic evidence of suppurative inflammation in two or more joints were examined retrospectively. Age of dogs was 4.8 years (median, range: 0.5-12 years). There was no clear breed or sex predilection, but most were large-breed dogs (body weight > or = 20 kg [44.4 lbs] in 40/52). Body temperature was 103.0 degrees F (39.4 degrees C) (median, range: 100.0-105.9 degrees F), with 29 of 52 dogs having a body temperature > or = 103 degrees F (39.4 degrees C). Lameness was identified in 42 of 52 dogs. Erosive changes were found in only 1 of 37 dogs that had radiography performed. A clear underlying disease process was not identified in 34 of 52 dogs. Seven dogs had evidence of infectious or inflammatory processes at extra-articular sites; 4 dogs were diagnosed with systemic lupus erythematosus (SLE); 2 dogs had gastrointestinal disease; 2 dogs had been vaccinated within 1 month before onset of polyarthritis; 1 dog had cancer; 1 dog had polyarthritis and meningitis; and 1 dog had erosive polyarthritis. Of the 44 dogs tested, 25 had antibodies to Borrelia burgdorferi, detected by an ELISA assay, which was significantly greater than the general hospital population (P = .007). Antibodies against Rickettsia rickettsiae and Ehrlichia canis were not definitively identified in the sera of any dog tested in this study (45 and 44 dogs, respectively). We conclude that an underlying disease process is not identified in most cases of suppurative polyarthropathy in dogs and that intestinal disease, neoplasia, and SLE are uncommon causes of polyarthritis. While seropositivity against the causative agent of Lyme disease was common and possibly a cause of polyarthritis in some dogs of our study, evidence of other vector-borne infection was not identified.     

鸡与哺乳动物补体活性与C3含量的比较

本文研究了不同动物血清补体水平及其补体C3含量的差异.采取成年鸡、猪、羊、牛、豚鼠五种动物的新鲜血清,测定其补体总活性;生化合成C3α链N端21肽,免疫家兔,制备抗鸡C3抗体,用来测定不同动物血清中C3含量.结果表明,抗鸡C3抗体能够与各种哺乳动物血清中的补体C3发生特异性反应,可以用来测定各种动物血清中的C3含量,测定结果为鸡血清中的C3含量为0.34士0.005 mg/mL、猪1.47±0.008 mg/mL、山羊1.70±0.005mg/mL、牛1.78±0.007 mg/mL、豚鼠4.18±0.008 mg/mL,其中鸡血清中补体总活性和C3含量都远远低于哺乳动物,差异极显著(P＜0.01).     

补体C3基因多态性与相关疾病研究进展

在补体各成分中,补体第三组分(C3)在血清中含量最高,是补体系统的核心.C3在功能上不仅处于补体经典途径、甘露糖结合凝集素途径和补体旁路途径三条激活途径的汇合点,还是C3b依赖的阳性反馈环路的基础;而且C3裂解片段及其结合蛋白复杂多样,在免疫防御、免疫调控以及免疫病理中发挥着重要的作用.当C3基因发生突变或缺失时会造成C3缺陷性疾病,常伴发免疫性疾病及反复细菌感染,患者对病原菌感染的易感性显著增加.论文概述了C3基因结构及其多态性以及其与机体易感性的关联性.     

ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis, treatment, and prevention

The purpose of this report is to offer a consensus opinion of ACVIM diplomates on the diagnosis, treatment, and prevention of Borrelia burgdorferi infections in dogs (canine Lyme disease). Clinical syndromes known to commonly be associated with canine Lyme disease include polyarthritis and glomerulopathy. Serological test results can be used to document exposure to B. burgdorferi but not prove illness. Although serum enzyme-linked immunosorbent assay/indirect fluorescent antibody assay titers can stay positive for months to years after treatment, quantitative C6 peptide antibody paired tests need more study. Serological screening of healthy dogs is controversial because it can lead to overdiagnosis or overtreatment of normal dogs, most of which never develop Lyme disease. However, serological screening can provide seroprevalence and sentinel data and stimulate owner education about tick infections and control. Although it is unknown whether treatment of seropositive healthy dogs is beneficial, the consensus is that seropositive dogs should be evaluated for proteinuria and other coinfections and tick control prescribed. Tick control can include a product that repels or protects against tick attachment, thereby helping to prevent transmission of coinfections as well as Borrelia spp. Seropositive dogs with clinical abnormalities thought to arise from Lyme disease generally are treated with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer treatment as well as medications and diets for protein-losing nephropathy. The ACVIM diplomates believe the use of Lyme vaccines still is controversial and most do not administer them. It is the consensus opinion that additional research is needed to study predictors of illness, "Lyme nephropathy," and coinfections in Lyme endemic areas.     

肌注PHA对犬血清中补体C3、C4的影响

为研究植物凝集素(PHA)对各犬血清中补体C3、C4浓度的影响,试验分成4个组:低剂量组(0.05 mg/kg)、中剂量组(0.10 mg/kg)、高剂量组(0.20 mg/kg)、对照组,对犬进行肌肉注射。在注射前和注射后的7 d、14 d对各组犬进行采血测定其血清中补体的含量,并进行统计分析。结果:中剂量组可显著提高机体的补体水平(P<0.05),并在高水平维持较长时间;低剂量组和高剂量组作用不显著(P>0.05)。     

鸡与哺乳动物补体活性与C_3含量的比较

本文研究了不同动物血清补体水平及其补体C3含量的差异。采取成年鸡、猪、羊、牛、豚鼠五种动物的新鲜血清,测定其补体总活性;生化合成C3α链N端21肽,免疫家兔,制备抗鸡C3抗体,用来测定不同动物血清中C3含量。结果表明,抗鸡C3抗体能够与各种哺乳动物血清中的补体C3发生特异性反应,可以用来测定各种动物血清中的C3含量,测定结果为:鸡血清中的C3含量为0.34±0.005 mg/mL、猪1.47±0.008 mg/mL、山羊1.70±0.005mg/mL、牛1.78±0.007 mg/mL、豚鼠4.18±0.008 mg/mL,其中鸡血清中补体总活性和C3含量都远远低于哺乳动物,差异极显著(P<0.01).     

多房棘球绦虫钙网蛋白的表达及其与补体组分C1q的相互作用分析

为表达多房棘球绦虫钙网蛋白EmCRT,并对其进行初步鉴定及结构与补体结合功能分析.本研究以多房棘球绦虫囊cDNA为模板,通过PCR扩增目的基因,克隆至pcDNA3.3-Myc载体,构建重组质粒pcDNA3.3-Myc-EmCRT;PCR、酶切及测序鉴定其正确后,以脂质体转染法转染Hela细胞,运用Western blo...     

芩连液与白虎汤对气分证家兔补体经典途径活化的影响比较

为比较经方白虎汤与自拟方芩连液的分子疗效区别,以静脉注射内毒素建立了具有高热证候的气分证家兔模型,并用白虎汤和自拟方芩连液分别进行治疗,通过ELISA检测比较治疗前后血清总补体(CH50)的含量变化,并采用实时荧光定量PCR技术检测了肝组织中补体第三成分(C3)基因和C-反应蛋白(CRP)基因的表达变化。结果表明,在气分证家兔模型中,补体系统以经典途径活化。白虎汤的治疗能同时保证C3基因和CRP基因的高表达起到治愈作用,而芩连液仅以提高CRP的表达量发挥一定的保护作用。研究表明白虎汤对动物气分证的疗效优于芩连液。     

Evaluation of 2 ELISAs to determine Borrelia burgdorferi seropositivity in horses over a 12-month period

The blacklegged tick (Ixodes scapularis), which transmits Borrelia burgdorferi, the causative agent of Lyme disease, has undergone rapid range expansion in Ontario. In horses, Lyme disease remains an enigmatic disease, with limited understanding of the pathogenesis and many issues pertaining to selection and interpretation of laboratory tests. We evaluated B. burgdorferi seropositivity in naturally exposed horses over a 12-mo period and compared paired samples with 2 common serologic tests. Serum samples were collected in 2017, ~1 y after initial testing, from a cohort of 22 horses that were seropositive in a 2016 seroprevalence study. Samples were tested using a C6 ELISA and a multiplex ELISA targeting outer surface proteins A, C, and F. 1 y after initial testing, 14 of 22 (64%) horses remained seropositive; 7 (32%) were positive on the multiplex ELISA, 2 (9%) on C6 ELISA, and 5 (23%) on both tests. Repeatability was 100% for the C6 ELISA, and 95% for the multiplex ELISA, with no significant difference between paired sample multiplex titer values. Our results indicate strong intra-test reliability, although further investigation is required to determine the clinical significance of serologic testing.     

Breed‐specific variation of hematologic and biochemical analytes in healthy adult Bernese Mountain dogs

Background: Hematology and serum biochemistry reference intervals in dogs may be affected by internal factors, such as breed and age, and external factors, such as the environment, diet, and lifestyle. In humans, it is well established that geographic origin and age may have an impact on reference intervals and, therefore, more specific reference intervals are sought for subpopulations. Objective: The objective of this study was to validate and transfer standard laboratory reference intervals for healthy Bernese Mountain dogs and to create new intervals for analytes where the established laboratory reference intervals were rejected. Methods: The procedure was performed using the human Clinical and Laboratory Standards Institute‐approved model modified for veterinary use. Thirty‐two dogs were included in the study using a direct a priori method, as recommended. Results: While 23 of the standard laboratory reference intervals were readily validated, 7 of the analytes (eosinophils, MCHC, alkaline phosphatase [ALP], γ‐glutamyltransferase, total bilirubin, amylase, and cholesterol) required new reference intervals according to the standard. These were calculated using the robust method. In particular, the new reference range for ALP was wide compared with the established laboratory reference interval. No clinical causes were found for differences in the results of these analytes. Conclusion: We found significant differences in 7 hematologic and serum biochemical analytes for which a breed‐specific variation appears to be the most plausible explanation. Breed‐specific reference intervals for Bernese Mountain dogs will help avoid misinterpretation of laboratory results in the diagnostic process.     

Serum cystatin C concentration can be used to evaluate glomerular filtration rate in small dogs

Serum cystatin C levels (CysC) are used in human medicine to document progressive kidney failure. Although CysC are not thought to be useful for the diagnosis of kidney dysfunction in dogs, there has been no specific consideration of body weight as a confounding issue. The aim of this study was to assess that the utility of CysC for the diagnosis of decreased glomerular filtration rate (GFR) in smaller vs. larger dogs. In clinically healthy dogs, serum creatinine (Cre) and CysC correlate directly with body weight; we found that dogs weighing <20 kg had significantly lower CysC than those weighing ≥20 kg (0.27 ± 0.07 vs. 0.34 ± 0.05 mg/l, respectively, P<0.001). In dogs weighing <20 kg, CysC had superior diagnostic accuracy for the detection of mildly decreased plasma iohexol clearance (PCio) (<1.8 ml/min/kg) compared with Cre (sensitivity 100% vs. 80.9% and specificity 100% vs. 85.7%); this was not true for dogs weighing ≥20 kg. Additionally, using a cut-off PCio of <1.8 ml/min/kg, the area under receiver-operating characteristics curve (AUC) of CysC was significantly higher than that of Cre in dogs weighing <20 kg (P<0.05); this was not true for dogs weighing ≥20 kg (P=0.695). In conclusion, CysC is a useful marker for the detection of a mild decreasing GFR compared with Cre in dogs weighing <20 kg.