Influence of a cyclic combination chemotherapeutic protocol on primary haemostasis in dogs suffering from malignant lymphoma

The purpose of this study was to examine the influence of cyclic combination chemotherapy on primary haemostasis in dogs with malignant lymphoma. Seventeen dogs receiving cytostatic treatment for high-grade lymphoma were included in the study. The dogs were treated with a Madison–Wisconsin derived protocol, which included asparaginase, vincristine, doxorubicin and prednisolone. At different time points during the first 4 weeks of induction, platelet count, capillary bleeding time, analysis of the platelet function using the platelet function analyser PFA-100, and platelet aggregation by the Born-method were measured.The most obvious changes were found for median values of the platelet count, which increased significantly from 210,000/μL before induction to 349,000/μL during the second week of induction (P = 0.0010). Median platelet count subsequently decreased by the fourth week of treatment (Friedman-test: P < 0.0001). None of the parameters of platelet function (capillary bleeding time, automatic platelet function analysis, aggregation maximum) showed significant changes with time (P > 0.05, Friedman-test). The results did not suggest that significant platelet dysfunction was induced by the chemotherapeutic protocol used in the study.     

Increase in minimal residual disease in peripheral blood before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy

Background: We developed previously a minimal residual disease (MRD) monitoring system in dogs with lymphoma by exploring a highly sensitive real‐time PCR system. Objectives: To identify the change in MRD before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy. Animals: Twenty dogs with multicentric high‐grade B‐cell lymphoma. Methods: MRD levels in peripheral blood mononuclear cells (PBMCs) were measured by real‐time PCR amplifying the rearranged immunoglobulin heavy chain gene. MRD measurement and clinical assessment were performed every 2–4 weeks for 28–601 days after completion of chemotherapy. An increase in MRD was defined as an increase by more than 0.5, calculated by log₁₀[copy number of MRD per 10⁵ PBMCs], based on the uncertainty level observed in a canine lymphoma cell line. Results: During the follow‐up period, 15 dogs relapsed in 28–320 days (median, 120 days) after completion of chemotherapy. An increase in MRD was detected 2 weeks or more before relapse in 14 of the 15 dogs, but an increase in MRD before relapse could not be detected in the remaining 1 dog. The time from increased MRD to clinical relapse was 0–63 days (median, 42 days). In contrast, no increase in MRD was detected in 5 dogs that did not experience clinical relapse. Conclusion and Clinical Importance: An increase in MRD can be detected before clinical relapse in dogs with lymphoma. Application of early reinduction therapy based on an increase in MRD before clinical relapse may improve treatment outcome in canine lymphoma.     

Marked MMP-2 transcriptional up-regulation in mononuclear leukocytes invading the subarachnoidal space in aseptic suppurative Steroid-Responsive Meningitis–Arteritis in dogs

Canine Steroid-Responsive Meningitis–Arteritis (SRMA) is a suitable animal model for studies on the development of neutrophilic pleocytosis in aseptic meningitis. Samples of dogs in the acute phase of SRMA (n = 16) were examined for gene expression of matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2. Results were compared to those of dogs under glucocorticosteroid treatment for SRMA (n = 16) and dogs with other inflammatory and neoplastic diseases of the central nervous system (CNS) (n = 19). Samples included mononuclear (PBMCs) and polymorphonuclear cells (PBPMNs) of peripheral blood and cerebrospinal fluid white blood cells (CSF WBCs). In the acute phase of SRMA CSF WBCs showed mRNA expression for MMP-2 and -9 and TIMP-1 and -2, highlighting a contribution of these cells to the overall content of MMPs and TIMPs in CSF. MMP-2 mRNA levels in CSF WBCs were significantly up-regulated in comparison to PBMC expression levels, suggesting that MMP-2 is relevant for PBMC invasion into the subarachnoidal space and that the expression is influenced by migratory activity through the blood–CSF-barrier.     

The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: A preliminary study of autocrine and paracrine loops

Vascular Endothelial Growth Factor (VEGF) and its receptor KDR are involved in the regulation of angiogenesis and are up-regulated in a number of tumours in humans and in particular, breast cancer. We therefore evaluated the prognostic potential of the angiogenetic process in feline and canine mammary carcinomas by the immunohistochemical assessment of VEGF expression and micro vessel density (MVD) quantification and examined the interplay between VEGF and KDR. These variables were related to some relevant clinicopathological parameters and to overall survival (OS). VEGF and KDR expression were evaluated in epithelial, stromal and endothelial compartments in order to identify autocrine and/or paracrine loops. In dogs an increased VEGF expression did not show any statistical correlation with the clinicopathological parameters examined and was not correlated to a poorer prognosis. MVD was found to be significantly correlated to the histologic type (P = 0.04), tumour grading (P = 0.02), and to the OS (P = 0.01). In cats VEGF expression was significantly correlated to tumor grading (P = 0.01) and OS (P = 0.03), while no significant associations were found between MVD and the other parameters. VEGF and KDR were found to be detected on the epithelial, and/or endothelial and/or stromal cells of the carcinomas in both species, suggesting indications for some possible autocrine and paracrine loops. Our results encourage further studies on the possible prognostic role of VEGF and MVD in canine and feline mammary tumours and on the role of growth factors and their receptors in promoting tumour proliferation and an “angiogenetic shift”. The VEGF/KDR system may play a role in malignant transformation and tumor progression.     

The effect of maropitant on intraoperative isoflurane requirements and postoperative nausea and vomiting in dogs: a randomized clinical trial

ObjectiveTo establish if preoperative maropitant significantly reduced intraoperative isoflurane requirements and reduced clinical signs associated with postoperative nausea and vomiting (PONV) in dogs.Study designRandomized clinical trial.AnimalsTwenty-four healthy, client-owned dogs undergoing routine ovariohysterectomy.MethodsPremedication involved acepromazine (0.03 mg kg⁻¹) combined with methadone (0.3 mg kg⁻¹) intramuscularly 45 minutes before anaesthetic induction with intravenous (IV) propofol, dosed to effect. Meloxicam (0.2 mg kg⁻¹) was administered intravenously. Dogs were randomly assigned to administration of saline (group S; 0.1 mL kg⁻¹, n = 12) or maropitant (group M; 1 mg kg⁻¹, n = 12) subcutaneously at time of premedication. Methadone (0.1 mg kg⁻¹ IV) was repeated 4 hours later. Anaesthesia was maintained with isoflurane in oxygen, dosed to effect by an observer unaware of group allocation. The dogs were assessed hourly, starting 1 hour postoperatively, using the short form of the Glasgow Composite Pain Score (GCPS), and for ptyalism and signs attributable to PONV [score from 0 (none) to 3 (severe)] by blinded observers. Owners completed a questionnaire at the postoperative recheck.ResultsOverall mean ± standard deviation end-tidal isoflurane percentage was lower in group M (1.19 ± 0.26%) than group S (1.44 ± 0.23%) (p = 0.022), but was not significantly different between groups at specific noxious events (skin incision, ovarian pedicle clamp application, cervical clamp application, wound closure). Cardiorespiratory variables and postoperative GCPS were not significantly different between groups. Overall, 50% of dogs displayed signs attributable to PONV, with no difference in PONV scores between groups (p = 0.198). No difference in anaesthetic recovery was noted by owners between groups.ConclusionsMaropitant reduced overall intraoperative isoflurane requirements but did not affect the incidence of PONV.Clinical relevanceMaropitant provided no significant benefits to dogs undergoing ovariohysterectomy with this anaesthetic and analgesic protocol, although clinically significant reductions in isoflurane requirements were noted.     

Entamoeba infections in different populations of dogs in an endemic area of Lahore,Pakistan

Entamoeba histolytica, a protozoan parasite that affects humans and other primates all over the world. It is a common waterborne pathogen in endemic areas that have fecal oral transmission cycle. The aim of the present study was to examine the prevalence of E. histolytica and other Entamoeba species cysts in three different dog populations. Fecal samples from 600 dogs were collected and processed to detect Entamoeba cysts using the triple fecal test (light microscopy) and fecal antigens of E. histolytica were detected using a fecal antigen ELISA (TechLab E. histolytica II). Because it is impossible to differentiate E. histolytica from Entamoeba dispar and E. moshkovskii, using light microscopy we referred to all cysts morphologically consistent with E. histolytica as E. histolytica/dispar/moskovskii to reflect this uncertainty. Samples from 197 household dogs without clinical signs, 122 samples from household dogs exhibiting clinical signs of diarrhea, dysentery and vomiting and 281 stray dogs with no specific clinical signs were examined. Entamoeba histolytica-like cysts were observed in 94 (15.6%, 95% CI = ±3.88) by triple fecal test microscopy and E. histolytica antigens were demonstrated in 66 (11%, 95% CI = ±4.41) by fecal antigen ELISA in 600 fecal samples. Significant differences (P ≤ 0.05) in prevalence were found between the three populations. Twenty (10.1%, 95% CI = ±7.86) and 11 (5.6%, 95% CI = ±7.70) of 197 fecal samples from household dogs without clinical signs were positive by microscopy and by antigen ELISA, respectively. Twenty-nine (23.8%, 95% CI = ±6.58) and 23 (18.8%, 95% CI = ±7.81) of 122 the fecal samples from household dogs with clinical signs were positive by microscopy and by antigen ELISA, respectively. Forty-five (16.01%, 95% CI = ±5.62) and 32 (11.3%, 95% CI = ±6.38) of 281 fecal samples from stray dogs were positive by microscopy and by fecal antigen ELISA, respectively. Dogs from the youngest age group (6 months to 1 year) were more likely to be E. histolytica antigen positive than were dogs from the other two older age groups, with a significant difference (P ≤ 0.05) between all age groups. Statistically, no significant (P ≥ 0.05) difference of prevalence was seen in male and female dogs. The local dogs had the highest prevalence rate of E. histolytica antigens (36 of 246, 14.2%, 95% CI = ±6.32) followed by imported breeds (11 of 115, 9.5%, 95% CI = ±10.4) and crossbred (19 of 239, 8.3%, 95% CI = ±7.47), indicating a significant (P ≤ 0.05) trend of positivity between various breeds of dogs. These findings suggest that dogs may play an important role in the epidemiology of this pathogen.     

Preference among 7 bait flavors delivered to domestic dogs in Arizona: Implications for oral rabies vaccination on the Navajo Nation

Less than 20% of the domestic dogs on tribal lands in the United States are vaccinated against rabies. One method to increase vaccination rates may be the distribution of oral rabies vaccines (ORVs). ONRAB^® (Artemis Technologies, Inc., Ontario, Canada) is the primary ORV used in Canada to vaccinate striped skunks and raccoons. To investigate the potential use of ONRAB^® ORV baits to vaccinate feral domestic dogs against rabies on tribal lands and beyond, we performed a flavor preference study. A total of 7 bait flavors (bacon, cheese, dog food, hazelnut, sugar-vanilla, peanut butter, and sardine) were offered in pairs to 13 domestic dogs. Each dog was offered all possible combinations of bait pairs over a period of 10 days, with each bait offered 6 times. The proportion of times each bait was consumed first by individual dogs was calculated and comparisons among dogs were conducted using the MIXED procedure in SAS (SAS Institute, Cary, NC). Pairwise comparisons between baits were performed using “contrast” statements with sugar-vanilla flavor as the default for comparison. Type 3 tests of fixed effects showed a significant treatment effect (F_6,72 = 9.74, P < 0.0001). Sugar-vanilla was selected first during 14% of the offerings and exhibited the least preference among all bait types (F_1,72 = 22.46, P < 0.0001). Dog food was selected first 56% of the time, and more frequently than all other bait types (F_1,72 = 13.09, P = 0.0005).     

Breed-related differences in altered BRCA1 expression,phenotype and subtype in malignant canine mammary tumors

BRCA1 is a high-penetrance breast cancer susceptibility gene and BRCA1-associated breast cancer has a high familial prevalence that is more common among certain populations of humans. A similar high prevalence also exists for canine mammary tumors (CMTs) and the objective of this study was to determine the breed-related differences in malignant CMTs. Comparative analyses of the expression of various prognostic factors for CMTs, including BRCA1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) were conducted on 139 malignant CMT cases from five breeds with the highest prevalence of CMTs in Korea.Significant breed-related differences were observed in the expression of BRCA1 (P = 0.003), histological grade (P = 0.038), and extensive lymphatic invasion (P = 0.042). The Shih Tzu breed had the highest proportion of dogs with malignant CMT and strong overexpression of BRCA1. Cytoplasmic and membranous expression of BRCA1 was associated with the ER negative (P = 0.004), PR negative (P = 0.046), and triple negative (ER, PR, and HER-2 negative; P = 0.016) phenotype and the basal-like molecular subtype (P = 0.019) in Shih Tzu dogs. Since these features are similar to BRCA1-related human breast cancer, dogs with BRCA1-associated CMT, particularly Shih Tzu dogs, may serve as a suitable spontaneous model, although additional molecular studies are needed.     

Resveratrol decreases oxidative burst capacity and alters stimulated leukocyte cytokine production in vitro

IntroductionResveratrol, a naturally-occurring phytophenol, has been shown to bolster immune surveillance and reverse immunosenescence in a dose dependent manner in rodents and humans. Although safety and pharmacokinetic studies have been completed in dogs, the immunomodulatory effects of resveratrol in dogs has not yet been investigated. The objective of this study was to determine the effect of resveratrol on canine innate immune system function in vitro. The hypothesis was that similar to other species, low concentrations of resveratrol would stimulate while high concentrations would depress innate immune system function.MethodsWhole blood was collected from six healthy, adult, client-owned dogs and was incubated with resveratrol at final concentrations of 6000 ng ml⁻¹, 3000 ng ml⁻¹, 1000 ng ml⁻¹, or control solution for 4 h. Following incubation, phagocytosis and oxidative burst were evaluated using flow cytometry, and LPS-, lipoteichoic acid (LTA) – and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay.ResultsPhagocytosis was not altered by resveratrol at any concentration compared to control. However, while the number of PMNs capable of performing oxidative burst did not change, the robustness of the reaction following stimulation with Escherichia coli and PMA was reduced in a dose dependent manner. In addition, LPS-, LTA-, PG, and PBS-stimulated TNF production was increased following incubation with all concentrations of resveratrol compared to control, and this effect was dose dependent. LTA-stimulated IL-6 was increased with resveratrol compared to control. Furthermore, LTA-stimulated IL-10 was decreased with 6000 ng ml⁻¹ and 3000 ng ml⁻¹ concentrations of resveratrol and PG-stimulated IL-10 production was decreased with all concentrations of resveratrol compared to control. The LPS-, LTA-, and PG-stimulated TNF:IL-10 ratio was increased with 6000 ng ml⁻¹ of resveratrol compared to control and lower resveratrol concentrations.ConclusionWhile resveratrol was sparing to PMN phagocytosis, it reduced the robustness of PMN oxidative burst. Resveratrol also increased pro-inflammatory and decreased anti-inflammatory leukocyte cytokine production capacity in vitro. These data suggest that resveratrol supplementation may depress oxidative burst reactions while promoting pro-inflammatory leukocyte cytokine production and decreasing anti-inflammatory cytokine production. Based on these findings, further in vivo study regarding the effects of resveratrol on PMN oxidative burst capability and leukocyte cytokine production capacity are indicated prior to routine supplementation.     

Influence of age on bronchoscopic findings in healthy beagle dogs

The aims of this study were to evaluate the effect of age on bronchoscopic features and bronchoalveolar lavage fluid (BALF) cellularity in dogs. Thirty healthy beagle dogs from three age groups were included: young dogs (10 months to 4.5 years of age; n = 8), middle-aged dogs (5–8 years old; n = 13) and older dogs (>8 years; n = 9). Haematology, thoracic radiography, bronchoscopy and bronchoalveolar lavage were performed; bronchoscopic findings were scored and BALF total and differential cell counts were determined. The total bronchoscopic score was higher in older dogs; these dogs had more irregular bronchial mucosa, more prominent mucosal vessels and bronchiectasis. Younger dogs had a higher percentage of neutrophils in BALF compared with middle-aged and old dogs and a higher percentage of lymphocytes in BALF compared with middle-aged dogs. The results show that age has an effect on bronchoscopic features of airways and the composition of BALF in the dog.     

Computed tomographic morphology and clinical features of extrahepatic portosystemic shunts in 172 dogs in Japan

Canine extrahepatic congenital portosystemic shunts (EH-cPSS) are classified into several anatomical types, depending on the origin and termination of the shunt vessel. The aim of this retrospective study was to determine the proportion and clinical features of each anatomical shunt type in a population of dogs presented to a veterinary teaching hospital in Japan. Dogs diagnosed with EH-cPSS using computed tomographic (CT) portography were included (n = 172) and shunts were classified based on previous reports. Clinical data were collected from case records and analysed statistically. The most common anatomical type was the spleno-phrenic shunt (n = 64), followed by the spleno-azygos (n = 38), right gastric-caval (n = 29), spleno-caval (n = 21), right gastric-caval with caudal loop (n = 9), right gastric-phrenic (n = 6), colono-caval (n = 3), spleno-phrenic and azygos (n = 1), and porto-caval (n = 1) shunts. Spleno-phrenic and spleno-azygos shunts were diagnosed more frequently in older dogs than right gastric-caval and spleno-caval shunts (P < 0.05). The portal vein/aortic (PV/Ao) ratio was significantly larger in dogs with spleno-phrenic shunts than in dogs with spleno-azygos, right gastric-caval or spleno-caval shunts (P < 0.05). The PV/Ao ratio was significantly larger in dogs with spleno-azygos shunts than in dogs with right gastric-caval shunts. Dogs with spleno-phrenic shunts had significantly lower serum alkaline phosphatase activities than those with right gastric-caval or spleno-caval shunts. Dogs with spleno-phrenic shunts had significantly lower fasting ammonia concentrations than those with spleno-caval shunts.     

Grade is an independent prognostic factor for feline mammary carcinomas: A clinicopathological and survival analysis

Feline mammary carcinomas (FMC) are highly infiltrative tumours which show a strong tendency for local recurrence and metastasis. Histological type assessment of these tumours is not sufficiently discriminatory in predicting prognosis and in this study the prognostic significance of the Elston and Ellis method of histological grading was evaluated. Ninety-two feline mammary carcinomas from 84 cats were graded and 64 queens were included in a follow-up study.Grade was significantly related to tumour size (P = 0.006), clinical stage (P = 0.005), lymphovascular invasion (P < 0.0001), mitotic index (P < 0.0001), Ki67 index (P = 0.001), overall survival (P = 0.0001) and disease-free survival (P < 0.0001). Cox regression analysis identified grade as an independent prognostic factor. Multivariable analysis also showed regional lymph node metastasis and lymphovascular emboli as independent prognostic factors related to overall survival and to disease-free-survival, respectively. The study demonstrated that histological grading can be used as a prognostic factor to evaluate the biological behaviour of FMC.     

Weekly variability of plasma and serum NT-proBNP measurements in normal dogs

ObjectivesTo determine the weekly variability of serum and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in healthy dogs.Animals, materials and methodsFifty-three normal dogs were examined prospectively. Serum (n = 25) or plasma (n = 28) samples were obtained for NT-proBNP assay at one week interval for 3 consecutive weeks.ResultsMedian serum or plasma NT-proBNP concentration did not change over 3 consecutive weeks. Twenty-two of 53 dogs (42%) had at least one NT-proBNP value >500 pmol/L, including 14 dogs with at least one serum NT-proBNP concentration >500 pmol/L and 8 dogs with at least one plasma NT-proBNP concentration >500 pmol/L during the 3-week sampling period. The difference between the maximum and minimum NT-proBNP value obtained over the 3-week sampling period was <100 pmol/L in 40% of dogs, between 100 and 200 pmol/L in 40% of dogs, and >200 pmol/L in 20% of dogs. Of the 19 dogs with a value >500 pmol/L on either week 1 or 2, 11 dogs (58%) had a subsequent NT-proBNP value <500 pmol/L on either week 2 or 3.ConclusionsThere is a high degree of variability in weekly serum and plasma NT-proBNP values in healthy dogs. Individual variability should be considered when interpreting NT-proBNP results in dogs.     

Comparative speed of efficacy against Ctenocephalides felis of two oral treatments for dogs containing either afoxolaner or fluralaner

A study was designed to compare the efficacy of NexGard^® and Bravecto™, 2 recently introduced oral ectoparasiticides containing isoxazolines, against fleas (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to 28.6 kg, were included in this parallel group design, randomized, and controlled efficacy study. On Day −1, the 24 dogs were allocated to 3 study groups: untreated control; Nexgard^® treated and Bravecto™ treated. The treatments were administered on Days 0, 28 and 56 for Nexgard^® (labelled for monthly administration), and once on Day 0 for Bravecto™ (labelled for a 12 week use). Flea infestations were performed weekly with 100 adult unfed C. felis on each dog from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post-infestation and removed and counted 24 h post-infestation. The arithmetic mean flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post-infestation, indicating vigorous flea challenges on all assessment days. Both the Nexgard^® and Bravecto™ treated groups had statistically significantly (p < 0.05) less fleas compared to the untreated group on all assessment time points and days. Significantly fewer fleas were recorded for NexGard^® treated dogs compared to Bravecto™ treated dogs at 6 h post-infestation on Day 56, 63, 70, 77 and 84 and at 12 h post-infestation on Days 70 and 84. No statistically significant (p < 0.05) differences were recorded between the treated groups at 24 h post-infestation. Efficacies recorded 6 h post-infestation for Nexgard^® ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1% (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies recorded for Bravecto™ ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post-infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post-infestation. Efficacies observed at 24 h were 100% for both products during the study except 99.6% on Day 84 for Bravecto™.     

Follow-up of 100 dogs with acute diarrhoea in a primary care practice

This study aimed to examine the aetiology of acute diarrhoea and the relapse rate in 100 client-owned dogs presented to a first-opinion clinic. History, physical examination, faecal testing and owner questionnaire data were collected at initial presentation (T₀) and at either the time of relapse or at a recheck performed within 3 months. All dogs received treatment according to their clinical signs. Of 96 dogs that completed the study, 37 (38.5%) relapsed during the study period, 21 (21.9%) relapsed within 3 months, and 16 others (16.6%) at 3 months to 1 year after initial examination. Dogs that had undergone a change in housing location within 1 month prior to presentation and dogs <1 year old were significantly more likely to have positive parasitological analyses (P = 0.02 and P = 0.001, respectively). Pica was a risk factor for relapse (P = 0.0002).     

Expression of trefoil factor genes in the duodenum and colon of dogs with inflammatory bowel disease and healthy dogs

Trefoil factors (TFF) are small peptides produced by goblet cells, which are crucial for epithelial restitution. In humans with inflammatory bowel disease (IBD), TFF expression is up-regulated as part of an unspecific repair mechanism. The goal of this study was to assess TFF gene expression in the gastrointestinal tract from dogs with IBD compared to healthy controls. Preliminary assessment by PCR revealed TFF1 and 3 expression in the small and large intestine, whereas TFF2 was amplified only in the stomach. Subsequent RT-qPCR (with relative quantification against 3 reference genes) on endoscopic duodenal (IBD n = 22, healthy controls n = 18) and colonic (IBD n = 12, controls n = 11) biopsies revealed that TFF1 expression was significantly up-regulated in the duodenum from IBD dogs (Mann–Whitney p = 0.001), whereas TFF3 expression was significantly lower in IBD colon compared to controls (t-test p = 0.018).This study demonstrates evidence for dysregulation of TFF gene expression in canine IBD. Up-regulation of TFF1 could signify ectopic expression as a compensatory repair-mechanism, whereas down-regulation of TFF3 could contribute to defective epithelial barrier function, respectively. Whether this is a cause or consequence of IBD could not be established.     

Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency

ObjectiveTo examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC).AnimalsThirteen Boxer dogs with ARVC.Materials and methodsTissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing.ResultsIn cardiomyopathic Boxer dogs, myocardial calstabin2 mRNA and protein were significantly decreased as compared to healthy control dogs (calstabin2 protein normalized to tetrameric cardiac ryanodine receptor (RyR2) complex: affected, 0.51 ± 0.04; control, 3.81 ± 0.22; P < 0.0001). Calstabin2 deficiency in diseased dog hearts was associated with a significantly increased open probability of single RyR2 channels indicating intracellular Ca²⁺ leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations.ConclusionsCalstabin2 deficiency is a potential mechanism of Ca²⁺ leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.     

Quadricuspid aortic valve and associated abnormalities in the dog: Report of six cases

ObjectivesTo describe the clinical and echocardiographic findings in dogs with quadricuspid aortic valve (QAV).BackgroundQAV is a rare canine congenital heart disease which has been reported only three times in the young dog.Animals, materials and methodsSix dogs (0.3- to 13-year-old) with QAV diagnosed by two-dimensional echocardiography were retrospectively evaluated. Medical records, echocardiograms, and follow-ups were reviewed.ResultsAccording to aortic cusp morphology, QAV was classified as type A (n = 1), type B (n = 4) or type C (n = 1). QAV was associated with at least one other heart disease in all of the dogs including, ventricular septal defect (n = 1), enlarged left coronary ostium (n = 4), degenerative mitral valve disease (MVD, n = 1) and patent ductus arteriosus (PDA, n = 3). Mild to moderate aortic regurgitation was also detected in all dogs by continuous-wave and color-flow Doppler echocardiography. QAV was diagnosed in four asymptomatic dogs referred for evaluation of a heart murmur. The remaining two dogs had QAV and PDA with evidence of mild exercise intolerance and moderately retarded growth. The PDA was surgically corrected in both dogs and at the time of writing, 1–2.5 years after the initial diagnosis, none of the six animals shows evidence of clinical signs.ConclusionQAV is a cause of aortic insufficiency. It may incidentally be found by two-dimensional echocardiography in dogs of various ages in association with other congenital or acquired cardiac abnormalities.     

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs

To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg^?1) as a positive control, followed by TDB (52.5 μg h^?1) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL^?1 (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1 h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect.