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BACKGROUND: It is unclear whether a low total 25(OH)D concentration is a cause or consequence of illnesses. To address this knowledge gap, studies measuring free and total 25(OH)D during the evolution and resolution of an inflammatory process are required.OBJECTIVES: Serum total and free 25(OH)D concentrations would transiently decline after cruciate surgery in dogs.ANIMALS: Seventeen client-owned dogs with a spontaneous cranial cruciate ligament rupture (CCLR).METHODS: A longitudinal cohort study involving the measurement of serum concentrations of total and free 25(OH)D, total calcium, creatinine, albumin, phosphate, C-reactive protein and plasma ionized calcium, at 1 day before and a median time of 1 and 60 days after surgical treatment of CCLR.RESULTS: Median serum concentrations of total 25(OH)D before surgery (80.3 nmoL/L [range, 43.5-137.3]) significantly declined immediately after surgery; (64.8 nmoL/L [range, 36.3-116.5] 1 day after surgery, P CONCLUSION AND CLINICAL IMPORTANCE: This study reveals the difficulties of assessing vitamin D status in dogs following elective surgery.

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: 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.

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in-clinic laboratory tests. No independent, evidence-based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe.

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 =

Urine dipstick results may vary between operators/methods. The magnitude of variation across the veterinary field is currently unknown. The aim of this study was to compare the precision of urine dipstick results between standard direct visual and automated reading methods, when performed by several operators. Urine samples were pooled and divided into three aliquots: one plain, one with glucose, and one with serum. Final year students, veterinary surgeons and veterinary nurses, blinded to each sample, were then asked to perform dipstick analysis with direct visualization and an automated analyser, and their technique was observed. A subsequent session was undertaken with samples which had pH titrated to achieve an acidic, neutral or alkaline value. Sixty-four veterinary students, 20 veterinary surgeons and seven veterinary nurses, performed the first (n=61) or second (n=30) part of the study. Precision was greater using the automated reader. The most common observed technique errors were; lack of sample mixing, for both visual and automated methods, and not timing readings as per manufacturer instructions, when performing visual analysis. This study suggests that in an environment with multiple operators, as is the case in veterinary teaching or large private hospitals, automated urine dipstick reading improves precision of results.

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

Summary In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2. An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine., Highlights • A population-based genetics study of dogs that required diagnostic imaging • Resolution of a QTL associated with face length reduction (brachycephaly) • Association of brachycephaly with a retrotransposon that disrupts SMOC2 splicing • The SMOC2 locus explains up to 36% of face length variation in dogs, Uncovering the molecular basis of dogs’ vastly diverse skull shapes requires individualized approaches to morphometrics and genotyping. Using data from veterinary referral patients, Marchant et al. shed light on a large effect locus that is responsible for face length reduction (brachycephaly).

This article reviews hepatic encephalopathy (HE) in companion animals. Clinical signs and categories of hepatic disease likely to cause HE are discussed. Ammonia has a key role in pathogenesis and current concepts in body ammonia metabolism are reviewed. Inflammation and manganese accumulation are also thought to be important in pathogenesis. Treatment of HE in acute and chronic cases is discussed along with the rationale for current treatment recommendations. Potential avenues for new treatments and human treatments, which may be transferable to companion animals, are reviewed.

Low-density lipoprotein (LDL) uptake is one of a number of tests used to demonstrate hepatocyte-like function after stem cell differentiation. Use of two compounds; LDL and acetylated LDL has been described despite each having different mechanisms of uptake. Three primary hepatocyte cultures and three sets of mesenchymal stromal cell (MSCs) cultures, derived from both adipose tissue and bone marrow, were harvested from dogs. Those cells were compared to commercially available human and mouse bone marrow derived MSCs. LDL receptor expression was demonstrated by gene expression and immunofluorescence in all primary hepatocyte cultures, undifferentiated canine bone marrow mesenchymal stromal cells (MSCs) and canine adipose MSCs. Undifferentiated human and mouse bone marrow MSCs also expressed the LDL receptor. In vitro, canine hepatocytes took up labelled LDL but not acetylated LDL. All undifferentiated MSCs took up LDL but not acetylated LDL. In conclusion, LDL and not acetylated LDL is a test of canine hepatocyte-like phenotype but this is not tissue or species specific and therefore is not informative assay when testing proof of MSC to hepatocyte differentiation.

Highlights ► Full-length feline CSF-1R has been cloned and expressed in a stable cell line. ► The biological activity of human, mouse and porcine CSF-1 has been evaluated. ► Human and mouse IL-34 are also biologically active on the feline CSF-1R. ► The potential therapeutic applications of CSF-1 is discussed., Colony stimulating factor (CSF-1) and its receptor, CSF-1R, have been previously well studied in humans and rodents to dissect the role they play in development of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, IL-34 has been described in several species. In this study, we have cloned and expressed the feline CSF-1R and examined the responsiveness to CSF-1 and IL-34 from a range of species. The results indicate that pig and human CSF-1 and human IL-34 are equally effective in cats, where both mouse CSF-1 and IL-34 are significantly less active. Recombinant human CSF-1 can be used to generate populations of feline bone marrow and monocyte derived macrophages that can be used to further dissect macrophage-specific gene expression in this species, and to compare it to data derived from mouse, human and pig. These results set the scene for therapeutic use of CSF-1 and IL-34 in cats.