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BackgroundNumerous studies in veterinary species have recently linked vitamin D status with non-skeletal health disorders. Previous studies have indicated that dogs cannot produce endogenous vitamin D via cutaneous production and rely solely on dietary intake of vitamin D. The seasonal variation of vitamin D seen in humans due to changes in UV exposure therefore is unlikely to be replicated in these animals.ObjectivesThe objective of this study was to investigate the natural variation in 25-hydroxyvitamin-D concentration in dogs subject to seasonal UV exposure.MethodsThis longitudinal study followed 18 healthy dogs fed a standardized diet over one year, with blood samples obtained monthly. Two key vitamin D metabolites, 25-hydroxyvitamin-D2 and 25-hydroxyvitamin-D3, were assessed by liquid chromatography tandem mass spectrometry in serum samples. Various other biochemical parameters were also measured. Seasonality was assessed using Cosinor statistical analysis.ResultsAlthough the dogs were subject to seasonally varying UV radiation, 25-hydroxyvitamin-D and related biomarkers (including calcium and parathyroid hormone) remained stable over time and did not follow a seasonal pattern. 25-hydroxyvitamin-D was not positively correlated to exposure to UV radiation. Nonetheless, variation in 25-hydroxyvitamin-D concentration between individual dogs was detected.ConclusionsGiven the standardization of diet, we concluded that the seasonal stability of 25-hydroxyvitamin-D concentration (vitamin D status) was likely a direct result of lack of cutaneous vitamin D production in this species and highlights the importance of dietary intake. The variation in 25-hydroxyvitamin-D concentration between animals warrants further investigatio

ObjectivesTo investigate the relationship between total and ionised calcium concentrations in dogs with ionised hypercalcaemia and to evaluate how albumin influences this relationship.MethodsInitially, a reference interval for ionised and total calcium was established using a large population of healthy adult dogs. Our teaching hospital clinical database was searched to identify adult dogs with ionised hypercalcaemia between 2012 and 2017, a time frame when the same sample handling and analysis protocols were in place as for the healthy reference interval population. The relationship between ionised and total calcium concentrations was then compared in the ionised hypercalcaemia population.ResultsBased on biochemical analysis of 351 healthy adult dogs, a reference interval of 1.18 to 1.53 mmol/L for ionised calcium and 2.24 to 2.85 mmol/L for total calcium was established. Using these reference intervals, 63 dogs with ionised hypercalcaemia were identified, of which 23 did not have a total hypercalcaemia. Only seven of the 23 dogs with ionised hypercalcaemia and total calcium below the upper limit of the reference interval had hypoalbuminemia. The majority of dogs with ionised hypercalcemia and normal total calcium had a modest increase in ionised calcium.Clinical SignificanceIf relying on total calcium alone, more than one third of dogs with ionised hypercalcaemia will be classified as normocalcaemic and the majority of these dogs had normal serum albumin.

Background Protein-losing enteropathy (PLE) because of chronic inflammatory enteropathy (CIE) in dogs is often treated with a combination of glucocorticoids and second-line immunosuppressant (SLI). This combined approach might not be necessary in all dogs. Hypothesis/objectives To describe diagnostic features and outcomes of dogs with PLE treated with glucocorticoids alone (group P) or with glucocorticoids and SLI (group S). Animals Thirty-one dogs with PLE. Material and methods Retrospective analysis of signalment data from diagnostic procedures, treatment, and outcome of dogs with CIE/PLE (from 2015 to 2017), using the hospital's digital case database. Dogs with hypoalbuminemia and CIE were included. Because of a stepwise treatment algorithm, dogs were allocated to group P or S. Time to serum albumin concentrations ≥20 g/L and survival data were collected. Dogs were additionally categorized by their albumin and cobalamin serum concentrations. Multivariate and univariate analysis as well as Pearson's correlation and Kaplan-Maier survival analysis were performed. Results Seventeen dogs were included in group P and 14 in group S. World Small Animal Veterinary Association score of the duodenum was different between groups (P = .05), but none of the other examined data. Median time until serum albumin reached >20 g/L was 13 days. Median survival time after start of treatment was 85 days (range, 13-463 days) in group P and 166 days (range, 8-390 days) in group S. Conclusion and clinical importance No routine diagnostic test was predictive of clinical response, treatment group, or outcome. Glucocorticoid treatment alone can be appropriate in dogs with PLE.

OBJECTIVES: Calcium is the most abundant mineral in the body and plays a critical role in a wide range of physiological processes. Low concentrations of ionised calcium, the most metabolically available form of calcium, have been linked to an increased risk of adverse clinical outcomes in dogs. Magnesium plays an important role in parathyroid hormone function. The objective of this study was to define the prevalence and aetiology of hypomagnesaemia in a hospitalised cohort of dogs with ionised hypocalcaemia (IHC).METHODS: A total magnesium reference interval was established using serum biochemistry results from 346 clinically healthy dogs. The clinical records of dogs with IHC were reviewed, and concurrent serum magnesium concentrations were recorded alongside clinical signs and underlying aetiology. The prevalence, clinical presentation and aetiology of hypomagnesaemia were examined in the IHC population.RESULTS: Two hundred and ninety-five IHC dogs were identified. Hypomagnesaemia was identified in 22%. Total magnesium concentration was significantly higher in dogs with renal disease. The most common cause of concurrent hypomagnesaemia and IHC was gastrointestinal diseases.CONCLUSION: Low concentrations of serum magnesium occur in approximately one fifth of all dogs with IHC. Further studies are required to clarify the link between magnesium status, IHC and clinical outcome.

BACKGROUND: Congenital portosystemic shunt (cPSS) is one of the most common congenital disorders diagnosed in dogs. Hepatic encephalopathy (HE) is a frequent complication in dogs with a cPSS and is a major cause of morbidity and mortality. Despite HE been a major cause of morbidity in dogs with a cPSS, little is known about the cellular changes that occur in the central nervous system of dogs with a cPSS.OBJECTIVES: The objective of this study was to characterise the histological changes in the cerebral cortex and cerebellum of dogs with cPSS with particular emphasis on astrocyte morphology.METHODS: Eight dogs with a confirmed cPSS were included in the study.RESULTS: Six dogs had substantial numbers of Alzheimer type II astrocytes and all cases had increased immunoreactivity for glial fibrillary acidic protein in the cerebral cortex, even if there were minimal other morphological changes.CONCLUSIONS: This study demonstrates that dogs with a cPSS have marked cellular changes in the cerebral cortex and cerebellum. The cellular changes that occur in the cerebral cortex and cerebellum of dogs with spontaneously arising HE are similar to changes which occur in humans with HE, further validating dogs with a cPSS as a good model for human HE.

BACKGROUND: Current tests for diagnosing liver disease in dogs are sub-optimal. MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR-122 could have utility in identifying dogs with liver disease.OBJECTIVE: Establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease.ANIMALS: Stored serum from 120 healthy dogs, 100 dogs with non-liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed.METHODS: Retrospective study. Medical records of dogs with liver disease, non-liver disease and healthy dogs were reviewed. Serum miR-122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements.RESULTS: In healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR-122 were 110 (90% CI 80-114), 594 (505-682), and 3312 (2925-5144) copies/μL, respectively. There was no difference between healthy dogs and dogs with non-liver disease (median ± IQR: healthy dogs 609 [327-1014] copies/μL; non-liver disease 607 [300-1351] copies/μL). miR-122 was higher in dogs with liver disease (11 332 [4418-20 520] copies/μL, P < .001 compared to healthy dogs). miR-122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86-0.99]). The upper limit of normal for healthy dogs (3312 copies/μL) had a sensitivity of 77% and specificity of 97% for identifying liver disease.CONCLUSION AND CLINICAL IMPORTANCE: Liver disease can be sensitively and specifically diagnosed in dogs by measurement of miR-122.

Background Melatonin is a hormone produced and secreted primarily by the pineal gland and mainly metabolised in the liver. Increased melatonin concentrations have been reported in human cirrhosis and hepatic encephalopathy (HE), a syndrome of neurological dysfunction. The pathogenesis of canine HE is incompletely understood. Melatonin has been hypothesised as a contributor to the development of HE. The aim of this study was to investigate whether serum melatonin concentrations are increased in canine congenital portosystemic shunting (cPSS), with and without HE. Methods Medical records were retrospectively reviewed, for which archived (−80°C) serum samples were available. A canine competitive ELISA was used to measure melatonin in two cohorts: dogs with a final diagnosis of cPSS (n=23) with and without clinical signs of HE, and healthy dogs (n=15). Results Melatonin concentrations were not significantly different (P=0.81) between healthy controls (median 27.2 pg/mL, range 19.8–161.5 pg/mL) and dogs with cPSS (median 25.7 pg/mL, range 18.5–244.9 pg/mL). Serum melatonin did not differ between cPSS patients with and without clinical signs of HE (P>0.99). No correlation was found between serum melatonin and blood ammonia (Spearman rank correlation coefficient, rs=−0.41, P=0.08). Conclusion Serum melatonin is not increased in canine cPSS with and without HE. We found no evidence that altered melatonin metabolism plays a role in the pathogenesis of cPSS-associated HE.

Background: Chronic Enteropathies (CE) are a common cause of morbidity in dogs. Chronic enteropathies are diagnosed in dogs with chronic gastrointestinal clinical signs (>3 weeks), inflammatory changes on intestinal biopsies and where no other underlying cause is determined based on a thorough, standardised diagnostic workup. Based on response to therapy, CE are sub-classified into food-responsive, antibiotic-responsive or steroid-responsive enteropathies. A significant proportion of dogs with a CE are food-responsive; however, there are limited peer-reviewed publications describing the clinical efficacy of the commercially available diets used to treat CE. Methods: In this study, we evaluated the response of 15 dogs with a CE to a commercially available dietetic food (Hill’s TM Prescription Diet TM i/d TM Sensitive Canine Dry). The dogs underwent a standard diagnostic evaluation, and did not receive concurrent anthelmintic, antibiotic, glucocorticoid or gastroprotectant therapies. The clinical efficacy of the dietary treatment was assessed by comparing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) before and a median of 13 days after dietary therapy. Results: We found that the CIBDAI significantly decreased following the introduction of the dietetic food (median CIBDAI score pre treatment 9, post treatment 2 (p

Hepatic encephalopathy is a frequent and debilitating complication of liver disorders. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. Healthy, privately owned dogs (n = 18) completed a prospective cohort study. Faecal samples were collected weekly, while the subjects were either on their usual diet (week 1), or a standardised diet (weeks 2–9), with added oral lactulose in weeks 6–7. DNA extraction and 16S rRNA gene sequencing were undertaken. Faecal samples from week 7 had a significantly lower microbiota richness/diversity, based on observed operational taxonomic units, Shannon/Chao1 indexes and Pielou’s Evenness. Beta diversity based on UniFrac distances was significantly different in week 7 compared to weeks 1, 5 and 9. At the phylum level, week 7 was associated with a significant increase of Firmicutes and Actinobacteria, and a decrease of Bacteroidetes and Fusobacteria, when compared to weeks 5 and 9. In summary, we have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy.

An 11-month-old female entire West Highland White Terrier presented for chronic diarrhea with acute deterioration in demeanor and progression to systemic inflammatory response syndrome. Transcutaneous abdominal ultrasonography identified colonic ulceration and secondary mucosal gas. Suspected hepatic portal vein gas and hepatic parenchyma gas were also visualized. The patient was stabilized and managed for ulcerative colitis. Based on endoscopic biopsies, the dog was diagnosed with severe, chronic, pyogranulomatous colitis. On repeat ultrasonographic evaluation the portal vein and hepatic gas had resolved but the patient deteriorated and was ultimately euthanized due to sepsis.

Craig Breheny and Adam Gow of the Royal (Dick) School of Veterinary Studies, University of Edinburgh, take a closer look at this unusual condition.

Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Interleukin (IL)-34 is a monocyte/macrophage growth factor, produced mainly by keratinocytes, that has been implicated in several human inflammatory conditions including human AD.Canine serum IL-34 concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores.Forty seven client-owned dogs diagnosed with AD and 25 healthy, unaffected control dogs.A commercially available IL-34 ELISA was optimized for the measurement of IL-34 in canine serum samples. Information regarding treatment, clinical lesion scores [Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04)] and pruritus Visual Analog Score (pVAS) were recorded for each dog at the time of serum collection.Dogs with AD had significantly increased serum IL-34 concentrations compared to controls. There was a significant positive correlation between IL-34 concentrations and CADESI-04 and pVAS scores. Concentrations of IL-34 remained increased in dogs with AD receiving steroids or the JAK1 inhibitor, oclacitinib, compared to unaffected control dogs.Serum IL-34 concentrations are increased in dogs with AD and are correlated with clinical severity and pruritus. IL-34 may be a suitable candidate therapeutic target for canine AD.La dermatite atopique (AD) est une dermatose inflammatoire fréquente chez le chien. L’interleukine (IL)-34 est un facteur de croissance des monocytes/macrophages principalement produit par les kératinocytes, et est impliqué dans plusieurs maladies inflammatoires de l’homme dont la dermatite atopique. HYPOTHÈSES: Les concentrations sériques d’IL-34 canin sont augmentées chez le chien atopique et corrèlent avec les scores de lésions cliniques et de prurit.Quarante sept chiens de propriétaires avec diagnostic d’AD et 25 chiens sains contrôles. MATÉRIELS ET MÉTHODES: Un test ELISA IL-34 disponible dans le commerce a été optimisé pour la mesure d’IL-34 des échantillons de serum de chien. Les données concernant le traitement, les scores clinique [Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04)] et de prurit pVAS (pruritus Visual Analog Score) ont été enregistrés pour chaque chien au moment du prélèvement de serum. RÉSULTATS: Les chiens avec AD avaient des concentrations sériques d’IL-34 significativement plus élevées comparé aux contrôles. Il y avait une corrélation positive significative entre les concentrations d’IL-34 et les scores de CADESI-04 et pVAS. Les concentrations d’IL-34 restaient élevées chez les chiens atopiques recevant des corticoïdes ou l’inhibiteur de JAK1, l’oclacitinib, comparé aux chiens non atteints.Les concentrations sériques d’IL-34 sont augmentées chez les chiens atopiques et sont corrélés avec la sévérité du prurit et la clinique. L’IL-34 pourrait être une cible thérapeutique adaptée pour l’AD canine.INTRODUCCIÓN: la dermatitis atópica (AD) es una enfermedad cutánea inflamatoria común en los perros. La interlequina (IL)-34 es un factor de crecimiento de monocitos/macrófagos, producido principalmente por queratinocitos, que se ha implicado en varias afecciones inflamatorias humanas, incluida la AD humana. HIPÓTESIS: las concentraciones de IL-34 en suero canino están aumentadas en perros con AD y se correlacionan con las lesiones clínicas y los valores de prurito. ANIMALES: cuarenta y siete perros propiedad de clientes diagnosticados con AD y 25 perros de control sanos y no afectados. MÉTODOS Y MATERIALES: se optimizó un ELISA IL-34 disponible comercialmente para la medición de IL-34 en muestras de suero canino. La información sobre el tratamiento, los valores de lesiones clínicas (Índice de extensión y severidad de la dermatitis atópica canina, 4ta reevaluación (CADESI-04)) y el valor visual análogo del prurito (pVAS) se registraron para cada perro en el momento de la recolección de suero. RESULTADOS: los perros con AD presentaron un incremento significativo en las concentraciones séricas de IL-34 en comparación con los controles. Hubo una correlación positiva significativa entre las concentraciones de IL-34 y los valores de CADESI-04 y pVAS. Las concentraciones de IL-34 permanecieron aumentadas en perros con AD que recibieron esteroides o el inhibidor de JAK1, oclacitinib, en comparación con los perros de control no afectados. CONCLUSIONES E IMPORTANCIA CLÍNICA: las concentraciones séricas de IL-34 aumentan en perros con AD y se correlacionan con la gravedad clínica y el prurito. IL-34 puede ser un candidato adecuado a objetivo terapéutico para la AD canina.Die atopische Dermatitis (AD) ist eine häufige entzündliche Hauterkrankung bei Hunden. Interleukin (IL)-34 ist ein Monozyten/Makrophagen Wachstumsfaktor, der hauptsächlich von Keratinozyten produziert wird und bei mehreren entzündlichen Erkrankungen des Menschen wie auch der humanen AD eine Rolle spielt.Die caninen IL-34 Serumkonzentrationen sind bei Hunden mit AD erhöht und korrelieren mit klinischen Veränderungen und den Pruritus Werten.Siebenundvierzig Hunde in Privatbesitz, die mit AD diagnostiziert worden waren sowie 25 gesunde, nicht betroffene Kontrollhunde nahmen an der Studie teil.Ein kommerziell erhältlicher IL-34 ELISA wurde für die IL-34 Messung in caninen Serumproben optimiert. Es wurden die Informationen in Bezug auf die Behandlung, die klinischen Veränderungswerte [Canine Atopic Dermatitis Extent and Severity Index, 4te Ausgabe (CADESI-04)] und die Pruritus Visual Analog Score (pVAS) für jeden Hund zum Zeitpunkt der Serumgewinnung festgehalten.Hunde mit AD zeigten im Vergleich zu den Kontrollen signifikant erhöhte IL-34 Konzentrationen. Es bestand eine signifikant positive Korrelation zwischen den IL-34 Konzentrationen und dem CADESI-04 und den pVAS Werten. Die Konzentrationen von IL-34 blieben bei Hunden mit AD während der Verabreichung von Steroiden oder dem JAK1 Inhibitor, Oclacitinib, im Vergleich zu nicht betroffenen Kontrollhunden erhöht.Die Serum IL-34 Konzentrationen sind bei Hunden mit AD erhöht und mit dem klinischen Schweregrad und dem Juckreiz korreliert. IL-34 könnte ein passender Kandidat als therapeutisches Ziel für die AD des Hundes sein.背景: 异位性皮炎 (AD) 是犬常见的炎性皮肤病。白细胞介素 (IL)-34是一种单核/巨噬细胞生长因子，主要由角质细胞产生，角质细胞也参与包括人AD在内的多种人类炎症。 假设: AD患犬的血清IL-34浓度升高，并且与临床病变和瘙痒评分相关。 动物: 诊断为AD的47只私家犬和25只健康、无症状的对照犬。 方法和材料: 对测定犬血清IL-34的市售IL-34ELISA进行优化。采集血清时，记录每只犬的治疗信息、临床病变评分 [犬异位性皮炎程度和严重性指数，第4版 (CADESI-04)] 和瘙痒评分 (pVAS)。 结果: 与对照组相比， AD患犬的血清IL-34浓度显著升高。IL-34浓度与CADESI-04、pVAS评分呈显著正相关。与无症状对照犬相比，接受类固醇或JAK1抑制剂-奥拉替尼的AD患犬，其IL-34浓度保持升高。 结论和临床重要性: AD患犬血清IL-34浓度升高，并且与临床严重性和瘙痒相关。IL-34可能是犬AD治疗的合适备选靶点。.背景: アトピー性皮膚炎（AD）は、犬の一般的な炎症性皮膚疾患である。インターロイキン（IL）-34は、主にケラチノサイトによって産生される単球/マクロファージ増殖因子であり、人ADを含むいくつかの人の炎症疾患に関与しているとされている。 仮説: イヌの血清IL-34濃度は、AD犬で増加し、臨床病変および掻痒スコアと相関する。 被験動物: ADと診断されたクライアント所有犬47頭および健常で弛緩していない対照犬25頭。 材料と方法: 商業的に利用可能なIL-34 ELISAが、犬血清サンプル中のIL-34の測定用に最適化された。治療に関する情報、臨床病変スコア[犬のアトピー性皮膚炎の程度と重症度指数（CADESI-04）]および掻痒性視覚アナログスコア（pVAS）は、血清採取時に各犬について記録された。 結果: AD犬は、対照群と比較して血清IL-34濃度が大幅に増加した。 IL-34濃度とCADESI-04およびpVASスコアの間に有意な正の相関があった。 IL-34の濃度は、罹患していない対照犬と比較して、ステロイドまたはJAK1阻害剤であるオクラシチニブを投与されているAD犬で増加したままであった。 結論と臨床的重要性: AD犬では血清IL-34濃度が増加し、臨床的重症度と掻痒と相関している。 IL-34は犬ADの適切な候補治療標的であり得る。.A dermatite atópica (DA) é uma dermatopatia inflamatória comum de cães. A interleucina (IL) -34 é um fator de crescimento de monócitos / macrófagos, produzido principalmente por queratinócitos, que tem sido implicado em várias condições inflamatórias humanas, incluindo a DA. HIPÓTESE: As concentrações séricas de IL-34 canina aumentam em cães com DA e se correlacionam com os escores clínicos de lesões e prurido.Quarenta e sete cães diagnosticados com DA pertencentes a clientes e 25 cães saudáveis ​​e não afetados. MÉTODOS E MATERIAIS: Um kit de ELISA para IL-34 disponível comercialmente foi otimizado para a mensuração de IL-34 em amostras de soro canino. Informações sobre o tratamento, escores de lesões [Índice de severidade e extensão da dermatite atópica canina, 4ª iteração (CADESI-04)] e a escala analógica visual de prurido (pVAS) foram registrados para cada cão no momento da coleta de soro.Cães com DA apresentaram aumento significativo das concentrações séricas de IL-34 em comparação aos controles. Houve uma correlação positiva significativa entre as concentrações de IL-34 e os escores CADESI-04 e pVAS. As concentrações de IL-34 permaneceram aumentadas em cães com DA recebendo esteroides ou o inibidor de JAK1, oclacitinib, em comparação com cães controle não afetados. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: As concentrações séricas de IL-34 estão aumentadas em cães com DA e estão correlacionadas com a gravidade clínica e o prurido. A IL-34 pode ser uma candidata adequada a alvo terapêutico para a DA canina.

Background – Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Macrophage migration inhibitory factor (MIF) initiates pro-inflammatory cytokine release in human AD and serum concentrations are correlated with disease severity.Hypothesis – Canine serum MIF concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores.Animals – Client owned dogs (n = 49) diagnosed with AD and 17 healthy, unaffected control dogs were usedfor the study.Methods and materials – A commercially available MIF ELISA was optimized for the dog and serum from clini-cal cases used. Information regarding treatment, Canine Atopic Dermatitis Extent and Severity Index, (CADESI-4) and pruritus Visual Analog Scale (pVAS) were recorded for each dog at the time of serum collection.Results – Dogs with AD which had not received steroid therapy and those treated with oclacitinib had significantly elevated serum MIF concentrations compared to controls. Concentrations of MIF were not significantly different in AD dogs receiving steroids compared to controls. There was no significant correlation between MIF concentrations and clinical scores (CADESI-4 or pVAS).Conclusions and clinical importance – Serum MIF concentrations are increased in dogs with AD and MIF might be a target for therapy.

Hyperammonaemia is a common complication of liver disease in dogs. High concentrations of ammonia can be detrimental to dogs with liver disease for several reasons, notably by causing hepatic encephalopathy (HE) which describes the wide range of neurological abnormalities ranging from altered behaviour to seizures that are well recognised complications in dogs with hepatic disorders. In human patients with liver disease, hyperammonaemia has also been linked to the development of other systemic complications such as dysregulation of the innate immune system. In contrast, the effects of hyperammonaemia on the canine innate immune system is currently unknown. The aim of this study was to investigate the effects of ammonia on the oxidative burst activity of canine polymorphonuclear cells in vitro. Blood obtained from healthy dogs (n = 8) was incubated with escalating concentrations of ammonia ranging from 0 to 250 μM, and the percentage of cells experiencing an oxidative burst was evaluated using a commercial kit (Phagoburst™) and flow cytometry. The spontaneous oxidative burst was evaluated without stimulation and also following stimulation with E coli. The pH of the blood was also measured at the differing ammonia concentrations. There was an increase in the percentage of cells experiencing a spontaneous oxidative burst from ammonia concentrations of 125 μM (p =

Hypermanganesemia is commonly recognized in human patients with hepatic insufficiency and portosystemic shunting. Since manganese is neurotoxic, increases in brain manganese concentrations have been implicated in the development of hepatic encephalopathy although a direct causative role has yet to be demonstrated. Evaluate manganese concentrations in dogs with a naturally occurring congenital shunt before and after attenuation as well as longitudinally following the changes in hepatic encephalopathy grade. Our study demonstrated that attenuation of the shunt resolved encephalopathy, significantly reduced postprandial bile acids, yet a hypermanganasemic state persisted. This study demonstrates that resolution of hepatic encephalopathy can occur without the correction of hypermanganesemia, indicating that increased manganese concentrations alone do not play a causative role in encephalopathy. Our study further demonstrates the value of the canine congenital portosystemic shunt as a naturally occurring spontaneous model of human hepatic encephalopathy.

Lethargy is a frequent and important clinical feature of anaemia; however, it does not absolutely correlate with the severity of anaemia. Manganese is efficiently absorbed through the gastrointestinal tract via divalent metal transporter 1 (DMT1), which is also responsible for iron transport. DMT1 is upregulated in iron deficiency (ID). Increased manganese concentrations are reported in ID anaemia (IDA) in various species. Manganese is neurotoxic and therefore may contribute to lethargy observed in some anaemic patients. In addition, anaemia and ID are common in human inflammatory bowel disease. Little is known about how anaemia influences manganese metabolism in veterinary patients and how common is anaemia in dogs with chronic enteropathy (CE). If elevated manganese concentrations are found, then potentially neurotoxicity may be contributing to morbidity in these cases. The objectives of this study were to investigate the hypothesis that whole blood manganese concentrations would be increased in dogs with anaemia, particularly in dogs with confirmed IDA, and that anaemia would be common in canine CE. Medical records from 2012-2016 were reviewed for dogs with CE that were anaemic, as well as dogs with confirmed IDA, where a sample suitable for manganese analysis was held in an archive. Manganese concentration was measured in whole blood from: 11 anaemic dogs with CE, 6 dogs with IDA, 9 non-anaemic ill controls, and 12 healthy controls. Mann-Whitney U and Kruskal-Wallis tests with post-test Dunn’s multiple comparisons tests were performed, with P

Background: Liver disease is a common cause of morbidity and mortality in dogs. Currently it is challenging to prognosticate in these cases. The aim of this study was to evaluate the utility of the haematological variables in prognosticating dogs with chronic hepatitis. Methods: Dogs with chronic hepatitis confirmed on histopathology had presenting haematological values retrospectively obtained and evaluated against survival time. Eighty two dogs met the inclusion criteria and their data analysed. Results: Neutrophilic patients, with a count greater than 12 x 109/l, controlled for sex and age, had a shorter survival time (p = < 0.01). In dogs, neutrophilia at presentation predicted a poor outcome, whereas the other haematological parameters were not prognostically informative. When the dogs were split into even quarters on the basis of their neutrophil count, those within the higher quartiles had poorer survival times. Neutrophilia was associated with a poorer survival time in comparison to those patients with a lower count. Conclusion: The relationship between neutrophils, inflammation and clinical outcome is deserving of future study in dogs with chronic hepatitis.

Objectives Increased whole blood manganese concentrations have been reported in humans with primary liver disease. Due to the neurotoxic effects of manganese, altered manganese homeostasis has been linked to the development of hepatic encephalopathy. Whole blood manganese concentrations are increased in cases of canine congenital portosystemic shunts, but it remains unclear whether dogs with primary hepatopathies also have altered manganese homeostasis. Methods Whole blood manganese concentrations were measured by graphite furnace atomic absorption spectrometry in 21 dogs with primary hepatitis, 65 dogs with a congenital portosystemic shunt, 31 dogs with non-hepatic illnesses and 18 healthy dogs. Results The whole blood manganese concentrations were significantly different between dogs with primary hepatitis, dogs with non-hepatic illnesses and healthy dogs (P=0·002). Dogs with primary hepatitis had significantly increased whole blood manganese concentrations compared with healthy dogs (P

A 2-year-old female Yorkshire Terrier dog presented with neurological deficits. Magnetic resonance imaging revealed an 8 mm in diameter mass centered left of midline arising from the quadrigeminal cistern, with a fatty or proteinaceous content. A further fat signal intensity focus was present in the tip of the temporal horn of the right lateral ventricle, in keeping with a “floating” fat embolus within the cerebrospinal fluid. A ruptured dermoid cyst was diagnosed. Within the frontal lobe on both sides were ill-defined and extensive high T2 signal areas, with mass effect within the white matter, and asymmetrical contrast enhancement following intravenous injection of gadolinium. Postmortem gross and histological examination confirmed the mass in the quadrigeminal cistern to be a dermoid cyst. In addition, severe multifocal necrotizing granulomatous leukoencephalomyelitis was found in the corona radiata and spinal cord. The relationship between these 2 pathologies is discussed.

OBJECTIVES: To compare serum vitamin D metabolites and plasma parathyroid hormone concentrations in dogs with inflammatory bowel disease and normal albumin concentration, dogs with inflammatory bowel disease and hypoalbuminaemia, healthy dogs and hospitalised ill dogs with non-gastrointestinal illness. METHODS: Serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D concentrations were measured in 36 healthy dogs, 49 hospitalised ill dogs with non-gastrointestinal illnesses, 21 dogs with inflammatory bowel disease and normoalbuminaemia and 12 dogs with inflammatory bowel disease and hypoalbuminaemia. Plasma parathyroid hormone and ionised calcium concentrations were measured in a subset of these dogs. RESULTS: Concentrations of serum 25 hydroxyvitamin D were lower in hypoalbuminaemic dogs with inflammatory bowel disease than in the healthy dogs (P

The concentrations of C-reactive protein (CRP), serum amyloid A, haptoglobin (Hp) and alpha(1)-acid glycoprotein were measured in dogs with clinical signs of nasal disease and compared with those of healthy dogs in order to determine the expression of these proteins in cases of canine nasal disease A significant difference (P

Background: Manganese (Mn) is an essential mineral that is a cofactor for many enzymes required in the synthesis of proteins, carbohydrates, and lipids. Because hepatic clearance is essential in Mn homeostasis, conditions in humans resulting in hepatic insufficiency including cirrhosis and both acquired and congenital portosystemic shunting have been reported to result in increased blood Mn concentrations and increased Mn content in the central nervous system. Because Mn toxicity causes neurologic disturbances, increased Mn concentrations have been implicated in the pathogenesis of hepatic encephalopathy. Hypotheses: Dogs with congenital portosystemic shunts (cPSS) have significantly higher whole blood Mn concentrations than do healthy dogs or those with nonhepatic illnesses. Animals: Eighteen dogs with cPSS, 26 dogs with nonhepatic illnesses, and 14 healthy dogs. Methods: Whole blood Mn was measured by graphite furnace atomic absorption spectrometry. The diagnosis of cPSS was made by ultrasonography or during celiotomy either by visual inspection of a shunting vessel or portovenography. Results: Dogs with a cPSS had significantly higher whole blood Mn concentrations than did healthy dogs and dogs with nonhepatic illnesses. Whole blood Mn concentrations were not significantly different between healthy dogs and dogs with nonhepatic illnesses. Conclusion and Clinical Importance: Dogs with a cPSS have significantly increased whole blood Mn concentrations. Additional studies are warranted to investigate the role of Mn in cPSS-associated hepatic encephalopathy.

the differential diagnosis in all cases of polydipsia/ polyuria, it should be remembered that primary diabetes insipidus is extremely uncommon. As a result, initial diagnostic efforts should be directed towards actively disproving a more common cause of PUPD or secondary diabetes insipidus (Table 1). Some causes may be suspected from the history, clinical signs or initial laboratory database (Fig. 1) whilst others may require more specific testing or may be difficult to rule out completely (e.g. hyperadrenocorticism). The history should be thoroughly reviewed for medications that may cause polyuria/polydipsia. Owners should be asked to measure and record unrestricted water intake over a few 24 hour periods to confirm true polydipsia (defined as >100 ml/kg/day).

OBJECTIVES The measurement of serum cardiac troponin I concentrations in dogs with a range of non-primary cardiac illnesses suggests that cardiac myocyte damage is commonplace. Dogs with primary immune-mediated haemolytic anaemia have increased serum cardiac troponin I concentrations at the time of diagnosis. However, it is unclear whether biochemical evidence of cardiac myocyte damage improves following successful treatment of anaemia. METHODS A haematology profile was performed and serum cardiac troponin I concentrations were measured in 19 dogs with primary immune-mediated haemolytic anaemia before and after treatment. RESULTS The haematocrit increased significantly (P = 0 · 0001) following treatment of primary IMHA (median pre: 0 · 13 L/L, median post: 0 · 33 L/L). The serum cardiac troponin I concentrations decreased significantly (P < 0 · 05) after treatment (median pre: 0 · 26 ng/mL, median post: 0 · 16 ng/mL). CLINICAL SIGNIFICANCE Serum cardiac troponin I concentration decreases following successful treatment of primary immune-mediated haemolytic anaemia. The clinical and prognostic significance of serum cardiac troponin I concentrations before and after treatment in dogs with primary immune-mediated haemolytic anaemia merits further investigation.

Dogs with spontaneous disorders of glucocorticoid production often have marked disturbances in calcium homeostasis. For example, hypercalcaemia is frequently observed in dogs with hypoadrenocorticism and secondary hyperparathyroidism is a common feature of canine hyperadrenocorticism. The mechanism(s) by which glucocorticoids modulate calcium homeostasis in dogs remains ill-defined. The hypothesis of this study is that a marked increase in serum cortisol concentrations would lead to an immediate negative calcium balance state which would drive a compensatory increase in parathyroid hormone (PTH) concentrations. This hypothesis was investigated by measuring serum cortisol and plasma PTH concentration in 19 dogs before and after administration of adrenocorticotrophic (ACTH) hormone. Post ACTH administration, there was a significant increase in serum cortisol, but not PTH, concentrations. The results of this study do not support the hypothesis that an increase in endogenous glucocorticoids influences calcium balance sufficiently to cause an immediate, compensatory increase in parathyroid hormone concentration.

Congenital portosystemic shunts (cPSS) are a well-recognised vascular anomaly in dogs. Recent studies have shown an association between inflammation and hepatic encephalopathy (HE), which is a common clinical syndrome in dogs with a cPSS. Pro-inflammatory cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α are frequently increased in the plasma of human patients with liver disease and have been implicated in the development of HE. In the current study, plasma concentrations of IL-2, IL-6, IL-8 and TNF-α were measured using a multiplex electrochemiluminescence immunoassay in 36 dogs with a cPSS and compared to 25 healthy dogs. There were no significant differences in plasma IL-2, IL-8 and TNF-α concentrations between the two groups; however, plasma concentrations of IL-6 were significantly higher in dogs with a cPSS compared to healthy dogs (P=0.02).

Objectives Xanthine urolithiasis and asymptomatic xanthinuria have been diagnosed in Cavalier King Charles spaniel dogs suggesting that primary xanthinuria may be a breed-related disorder, although its prevalence remains unclear. The hypothesis of this study was that asymptomatic xanthinuria is common in Cavalier King Charles spaniel dogs. Methods Free catch urine samples were collected from 35 client-owned Cavalier King Charles spaniel dogs and from 24 dogs of other breeds. The purine metabolites were measured by high-performance liquid chromatography. The urine ratios of xanthine/creatinine and hypoxanthine/creatinine were calculated and compared between the two groups of dogs. Results The urine concentrations of purine metabolites were not significantly different between the two groups and were very low in both. The urine concentrations of xanthine in all 35 Cavalier King Charles spaniel were markedly lower than in the previously reported case of xanthine urolithiasis in a UK Cavalier King Charles spaniel dog. Clinical Significance Asymptomatic xanthinuria was not detected in this UK Cavalier King Charles spaniel population. This data may be used as a reference for urinary purine metabolite concentrations in the dog.

Hepatic encephalopathy (HE) is a cause of significant morbidity and mortality in patients with liver disorders and a wide range of rodent models of HE have been described to facilitate studies into the pathogenesis and treatment of HE. However, it is widely acknowledged that no individual model perfectly mimics human HE and there is a particular need for spontaneous, larger animal models. One common congenital abnormality in dogs is the portosystemic shunt (cPSS) which causes clinical signs that are similar to human HE such as ataxia, disorientation, lethargy and occasionally coma. As inflammation has recently been shown to be associated with HE in humans, we hypothesised that inflammation would similarly be associated with HE in dogs with cPSS. To examine this hypothesis we measured C-reactive protein (CRP) in 30 healthy dogs, 19 dogs with a cPSS and no HE and 27 dogs with a cPSS and overt HE. There was a significant difference in CRP concentration between healthy dogs and dogs with HE (p < 0.001) and between dogs with HE and without HE (p < 0.05). The novel finding that there is an association between inflammation and canine HE strengthens the concept that HE in dogs with cPSS shares a similar pathogenesis to humans with HE. Consequently, dogs with a cPSS may be a good spontaneous model of human HE in which to further examine the role of inflammation and development of HE.

Dogs with liver disease have been shown to have increased serum C-reactive protein (CRP) concentrations. However, it is unclear whether dogs with liver disease also have increased serum haptoglobin concentrations. The aim of the study was to measure serum haptoglobin concentrations in healthy dogs, hospitalised dogs and dogs with liver diseases. Haptoglobin concentrations were measured in 30 healthy dogs, 47 hospitalised dogs with non-hepatic illness, 46 dogs with congenital portosystemic shunt (cPSS) and 11 dogs with primary hepatopathy. Haptoglobin concentrations were not significantly different between cPSS dogs with and without hepatic encephalopathy (HE), thus all cPSS dogs were considered as one group. Haptoglobin concentrations were significantly different between the remaining groups (P

XANTHINE urolithiasis is uncommon in dogs, with case series giving a prevalence of between 0.07 and 0.46 per cent (Houston and Moore 2009, Osborne and others 2009, Low and others 2010). The most common cause of canine xanthinuria is iatrogenic when allopurinol is administered, inhibiting xanthine dehydrogenase (XDH) (Bartges and Kirk 2008). In human beings, primary xanthinuria may be caused by enzyme deficiency or a cofactor abnormality. XDH deficiency may be isolated (type I), due to a missense mutation in the encoding gene for XDH, or in association with aldehyde oxidase deficiency, due to a missense mutation of the MCSU gene. Both are inherited in an autosomal recessive manner (Levartovsky and others 2000, Ichida and others 2001). Human beings with these defects may be asymptomatic with incidental hypouricaemia (Holmes and others 1974). Clinical signs, when they occur, are related to muscle deposition of xanthine causing myopathy, or renal dysfunction due to renal deposition (Nyhan 2005). A final cause of primary xanthinuria is an abnormality of the molybdenum cofactor required by xanthine oxidase, aldehyde oxidase and sulphite oxidase. Sulphite oxidase deficiency results in dramatic clinical signs of neonatal seizures and ophthalmic abnormalities (Wadman and others 1983). Xanthine uroliths appear uncommon in cats, with a prevalence of 0.1 per cent reported in uroliths submitted to the Minnesota Urolith Center, USA (Osborne and others 2004). There are case reports of xanthinuria in two domestic shorthair cats and one Himalayan cat (White and others 1997, Tsuchida and others 2007, Schweighauser and others 2009). Single nucleotide polymorphism analysis of the XDH gene in a xanthinuric Himalayan cat suggested that it had …