Candidate circulating microRNA biomarkers in dogs with chronic pancreatitis.

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis. HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers. ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17). METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, mouse, and human genomes. Differentially expressed microRNAs were identified and the potential mechanistic relevance explored using Qiagen Ingenuity Pathway Analysis (IPA). RESULTS: Reads mapping to 196 mature microRNA sequences were detected. Eight circulating microRNAs were significantly differentially expressed in dogs with pancreatitis (≥2-fold change and false discovery rate <0.05). Four of these mapped to the canine genome (cfa-miR-221, cfa-miR-222, cfa-miR-23a, and cfa-miR-205). Three mapped to the murine genome (mmu-miR-484, mmu-miR-6240, mmu-miR-101a-3p) and 1 to the human genome (hsa-miR-1290). Expression in dogs with pancreatitis was higher for 7 microRNAs and lower for mmu-miR-101a-3p. Qiagen IPA demonstrated a number of the differently expressed microRNAs are involved in a common pancreatic inflammatory pathway. CONCLUSIONS: The significantly differentially expressed microRNAs represent promising candidates for further validation as diagnostic biomarkers for canine pancreatitis.

Serum metabolomic profiles in dogs with chronic enteropathy.

BACKGROUND: Metabolic profiles differ between healthy humans and those with inflammatory bowel disease. Few studies have examined metabolic profiles in dogs with chronic enteropathy (CE). HYPOTHESIS: Serum metabolic profiles of dogs with CE are significantly different from those of healthy dogs. ANIMALS: Fifty-five dogs with CE and 204 healthy controls. METHODS: A cross-sectional study. The serum concentrations of 99 metabolites measured using a canine-specific proton nuclear magnetic resonance spectroscopy platform were studied. A 2-sample unpaired t-test was used to compare the 2 study samples. The threshold for significance was set at P < .05 with a Bonferroni correction for each metabolite group. RESULTS: Nineteen metabolites and 18 indices of lipoprotein composition were significantly different between the CE and healthy dogs. Four metabolites were significantly higher in dogs with CE, including phenylalanine (mean and SD) (healthy: 0.0417 mmol/L; [SD] 0.0100; CE: 0.0480 mmol/L; SD: 0.0125; P value: <.001) and lactate (healthy: 1.8751 mmol/L; SD: 0.7808; CE: 2.4827 mmol/L; SD CE: 1.4166; P value: .003). Fifteen metabolites were significantly lower in dogs with CE, including total fatty acids, and glycine (healthy: 0.2273 mmol/L; SD: 0.0794; CE: 0.1828 mmol/L; SD CE: 0.0517; P value: <.001). CONCLUSIONS AND CLINICAL IMPORTANCE: The metabolic profile of dogs with CE is significantly different from that of healthy dogs, this opens novel research avenues to develop better diagnostic and prognostic approaches as well as therapeutic trials.

Investigation of a relationship between serum concentrations of microRNA-122 and alanine aminotransferase activity in hospitalised cats.

OBJECTIVES: Current blood tests to diagnose feline liver diseases are suboptimal. Serum concentrations of microRNA (miR)-122 have been shown in humans, dogs and rodents to be a sensitive and specific biomarker for liver injury. To explore the potential diagnostic utility of measuring serum concentrations of miR-122 in cats, miR-122 was measured in a cohort of ill, hospitalised cats with known serum alanine aminotransferase (ALT) activity. METHODS: In this retrospective study, cats were grouped into those with an ALT activity within the reference interval (0-83 U/l; n = 38) and those with an abnormal ALT activity (>84 U/l; n = 25). Serum concentrations of miR-122 were measured by real-time quantitative PCR and the relationship between miR-122 and ALT was examined. RESULTS: miR-122 was significantly higher in the group with high ALT activity than the ALT group, within normal reference limits (P <0.0004). There was also a moderately positive correlation between serum ALT activity and miR-122 concentrations (P <0.001; r = 0.52). CONCLUSIONS AND RELEVANCE: Concentrations of miR-122 were reliably quantified in feline serum and were higher in a cohort of cats with increased ALT activity than in cats with normal ALT activity. This work highlights the potential diagnostic utility of miR-122 as a biomarker of liver damage in cats and encourages further investigation to determine the sensitivity and specificity of miR-122 as a biomarker of hepatocellular injury in this species.

Evaluation of resting cortisol concentration testing in dogs with chronic gastrointestinal signs.

BACKGROUND: Resting cortisol concentrations are routinely measured in dogs with chronic gastrointestinal signs to rule out hypoadrenocorticism based on a concentration >2 µg/dL (>55 nmol/L). HYPOTHESIS/OBJECTIVES: To assess the cross-sectional prevalence of hypoadrenocorticism in a group of dogs with chronic gastrointestinal signs presented to a referral internal medicine service. ANIMALS: Two-hundred and eighty-two client-owned dogs with chronic gastrointestinal signs and with resting cortisol concentration testing performed. METHODS: Retrospective review of medical records (final diagnosis, resting cortisol concentration, and adenocorticotropic hormone [ACTH] stimulation test results) of a referral population of dogs between May 2013 and September 2017. RESULTS: Resting cortisol concentration was <2 µg/dL (<55 nmol/L) in 79 patients (28%). Repeated resting cortisol concentration measurements were performed in 28 dogs, and in 8, resting cortisol concentrations remained <2 µg/dL (<55 nmol/L). Post-ACTH cortisol concentration was <2 µg/dL (<55 nmol/L) in 1 dog, consistent with a diagnosis of hypoadrenocorticism and giving a prevalence estimate of hypoadrenocorticism in this population of dogs of 0.3% (95% confidence interval [95CI], 0.03-1.5%). In 19 dogs with an initial resting cortisol concentration <2 µg/dL (<55 nmol/L), hypoadrenocorticism was excluded based on a repeat resting cortisol concentration >2 µg/dL (>55 nmol/L). Overall, the most common diagnosis was chronic primary inflammatory enteropathy (176/282, 62.4%), followed by extragastrointestinal neoplasia (17/282, 6%), protein-losing enteropathy, pancreatitis and megaesophagus (10/282, 3.5% each). CONCLUSIONS AND CLINICAL IMPORTANCE: Although dogs with hypoadrenocorticism can present with chronic gastrointestinal signs, it was the final diagnosis in only 1 of 282 dogs presenting to a referral internal medicine service for signs of chronic enteropathy. Repeated resting cortisol concentration may be considered as a test to try and exclude hypoadrenocorticism.

Seasonal variation in serum metabolites of northern European dogs.

BACKGROUND: Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs. HYPOTHESIS: There is seasonal variation in the serum metabolite profiles of healthy dogs. ANIMALS: Eighteen healthy, client-owned dogs. METHODS: A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12-month period. Metabolic profiling was conducted using a canine-specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite. RESULTS: We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6-13 mg/dL [0.14-0.33 mmol/L], P < .008), with a peak concentration of 264 mg/dL (6.83 mmol/L) in June and trough concentration of 236 mg/dL (6.12 mmol/L) in December. In contrast, there was a significantly lower concentration of lactate (mean 20 mg/dL [2.27 mmol/L] with a seasonal component amplitude of 4 mg/dL [0.42 mmol/L]; 95% CI 2-6 mg/dL [0.22-0.62 mmol/L], P < .001) during the summer months compared to the winter months, with a peak concentration of 26 mg/dL (2.9 mmol/L) in February and trough concentration of 14 mg/dL (1.57 mmol/L) in July. CONCLUSIONS AND CLINICAL IMPORTANCE: We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.

Retrospective evaluation of red blood cell distribution width as a prognostic factor in critically ill dogs (December 2016 to April 2017): 127 cas.

OBJECTIVE: To evaluate the association between RBC distribution width (RDW) and in-hospital mortality, length of hospitalization, and leukocyte count in critically ill dogs. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: One hundred and twenty-seven dogs admitted to the ICU from December 2016 to April 2017. Patients were included if they had a CBC performed within the first 24 h of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall in-hospital mortality rate was 29% (37/127), and median length of hospital stay was 3 days (interquartile range [IQR], 5). The median RDW value was 13.8% (IQR, 1.6%; reference interval, 11.9%-14.5 %). The canine Acute Patient Physiologic and Laboratory Evaluation (APPLE) fast score was calculated in 81 of 127 (64%) patients; the median score was 24/50 (IQR, 9). There was no significant correlation between RDW and APPLE fast score (P = 0.163). Subgroup analysis was performed according to the following diagnostic categories: abdominal (36%; 46/127), hematological (13%; 16/127), respiratory (13%; 16/127), neurological (12%; 15/127), cardiovascular (11%; 14/127), integument (3%; 4/127), trauma (3%; 4/127), musculoskeletal (2%; 3/127), and others (7%; 9/127). Increased RDW was not associated with in-hospital mortality overall (P = 0.381) or in any individual subgroup analysis. No association was found between length of hospitalization and RDW values in either survivors (P = 0.548) or nonsurvivors (P = 0.083). The correlation between RDW and leukocyte count was nonsignificant (P = 0.12). CONCLUSIONS: In this study, admission RDW was not associated with in-hospital mortality or length of hospitalization in critically ill dogs. The correlation between RDW and leukocyte count was nonsignificant.

Investigation of hypomagnesaemia prevalence and underlying aetiology in a hospitalised cohort of dogs with ionised hypocalcaemia.

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.

Relationship between vitamin D status and clinical outcomes in dogs with a cranial cruciate ligament rupture.

Cranial cruciate ligament rupture (CCLR) is one of the most common orthopaedic disorders diagnosed in dogs yet the factors which influence postoperative clinical outcomes are poorly understood. Low vitamin D status has been linked to poorer clinical outcomes in human patients undergoing elective orthopaedic surgery. The aim of this study was to examine the relationship between pre-operative vitamin D status, as defined by serum 25 hydroxyvitamin D (25(OH)D) concentrations, and initial disease severity and clinical outcomes in dogs undergoing surgical treatment for a CCLR. Serum 25(OH)D concentrations were measured in 44 dogs with a CCLR on the day before surgery. C-reactive protein concentrations were measured at a median time of 1 day post-surgery and the patient's clinical and radiographic response to CCLR surgical treatment was assessed at a median timepoint of 60 days post-surgery. Serum 25(OH)D concentrations in dogs with a CCLR was not significantly different to a population of healthy dogs (median 74.1 nmol/L and 88.40 nmol/L, respectively). There was no significant correlation between pre-operative serum 25(OH)D concentrations and length of pre-diagnosis clinical signs, pre-operative lameness scores or day 1 post-operative CRP concentrations. Thirty nine of the 44 dogs were re-examined at a median 60 days post-surgery. There was no relationship between the day 60 lameness scores and pre-operative serum 25(OH)D concentrations. In summary, we discovered that the vitamin D status of dogs with a CCLR was not significantly lower than healthy dogs and pre-operative serum 25(OH)D concentrations were not correlated to either pre-surgical disease severity or post-operative clinical outcomes.

Effects of surgery on free and total 25 hydroxyvitamin D concentrations in dogs.

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 < .005) before increasing to become nonsignificantly different from concentrations before surgery at day 60 after surgery (median 78.0 nmoL/L [range, 24.2-115.8], P = .14). In contrast, median free 25(OH)D concentrations before surgery (7.6 pg/mL [range, 3.8-12.2]) significantly increased immediately after surgery (9.2 pg/mL [range, 5.2-15.7], P < .05) before declining to become nonsignificantly different from before surgery concentrations at day 60 after surgery (median 6.2 pg/mL [range, 4.0-15.8], P = .37). CONCLUSION AND CLINICAL IMPORTANCE: This study reveals the difficulties of assessing vitamin D status in dogs following elective surgery.

Measurement of serum Interleukin 34 (IL-34) and correlation with severity and pruritus scores in client-owned dogs with atopic dermatitis.

BACKGROUND: 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. HYPOTHESIS: Canine serum IL-34 concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores. ANIMALS: Forty seven client-owned dogs diagnosed with AD and 25 healthy, unaffected control dogs. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL IMPORTANCE: 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.

The use of smartphone-obtained images to extrapolate canine packed cell volume.

OBJECTIVE: To determine whether a smartphone-obtained image can be used to extrapolate the PCV of canine blood samples. DESIGN: Prospective study of surplus blood obtained from clinical cases. SETTING: University teaching hospital. INTERVENTIONS: Blood samples were placed on filter paper, and images were obtained with a smartphone in different environments. These results were then compared to the PCV measurements on the same samples following the World Health Organization guidelines. MEASUREMENTS: Sixty-nine samples were assessed and identified that smartphone images, obtained in a controlled environment, were able to predict the PCV of the samples. This prediction was most accurate when assessing samples of a normal erythroid mass or polycythemic samples. CONCLUSIONS: The results of this study suggest that smartphone-obtained images do have a utility in predicting canine PCV. If this can be incorporated into a smartphone application, there would be scope to use this in low resource settings.

Vitamin D status is seasonally stable in northern European dogs.

BACKGROUND: Numerous studies in veterinary species have recently linked vitamin D status with nonskeletal 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 ultraviolet (UV) exposure, therefore, is unlikely to be replicated in these animals. OBJECTIVES: The objective of this study was to investigate the natural variation in 25-hydroxyvitamin-D concentrations in dogs subject to seasonal UV exposure. METHODS: This longitudinal study followed 18 healthy dogs fed a standardized diet over 1 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. RESULTS: Although 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 with exposure to UV radiation. Nonetheless, variation in 25-hydroxyvitamin-D concentrations between individual dogs was detected. CONCLUSIONS: Given 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 investigation.

Evaluation of the effect of urine dip vs urine drip on multi-test strip results.

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.

Standard operating procedure reduces interoperator variation and improves accuracy when measuring packed cell volume.

OBJECTIVE: To evaluate whether a standard operating procedure (SOP) for canine packed cell volume (PCV) measurement reduces operator-dependent variation and improves accuracy within a veterinary teaching hospital environment. MATERIALS AND METHODS: Clinical staff and final-year undergraduate veterinary students were recruited to perform PCV measurements in blinded duplicate samples. Participants were randomly allocated to perform this with or without an SOP. Participants' results were compared against a reference, generated by the authors following the World Health Organization guidelines. RESULTS: The study population comprised 18 clinical staff and 39 students. Three clinical staff and seven students displayed errors consistent with inaccurate reading, only one of whom had access to the SOP. Five students and two clinical staff had errors attributable to incorrect preparation, with only one having access to the SOP. Interoperator variation was significantly less using the SOP. Using the SOP, 95 per cent of the results were within 0.0125 l/l of the reference value, in comparison with within 0.09 l/l without SOP. Interoperator variation was significantly less in the SOP group (P=0.0025). CLINICAL SIGNIFICANCE: Using the SOP resulted in less variation and more accurate results. This confirms that PCV measurement with an SOP can truly be a 'waived' test.

Measurement of serum macrophage migration inhibitory factor (MIF) and correlation with severity and pruritus scores in client owned dogs with atopic dermatitis.

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 used for the study. METHODS AND MATERIALS: A commercially available MIF ELISA was optimized for the dog and serum from clinical 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.

The effect of ammonia on canine polymorphonuclear cells.

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 = <0.05) and above (p = <0.01), with a 4.9 fold increase at 200 µM (p = < 0.001). In those cells stimulated with E coli, incubation with increasing ammonia concentrations did not result in a significant difference in oxidative burst from baseline (p = 0.953). There was no statistically significant difference between the pH of the blood at the various ammonia concentrations (p = 0.2) suggesting that the difference in spontaneous oxidative burst was due to the ammonia rather than simply a change in pH conditions. In summary, the spontaneous oxidative burst of neutrophils was significantly increased from baseline. This supports a potential role of ammonia in contributing to innate immune system dysfunction in dogs with liver disease, and may present a future therapeutic target.

Hepatic Encephalopathy.

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.

IMAGING DIAGNOSIS-A CASE OF SPONTANEOUS HEPATIC PORTAL VEIN GAS IN AN 11-MONTH-OLD WEST HIGHLAND WHITE TERRIER.

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.

Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis.

Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE) and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low) was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high) (p<0.001). A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study.

Low-Density Lipoprotein Uptake Demonstrates a Hepatocyte Phenotype in the Dog, but Is Nonspecific.

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 (AcLDL), has been described despite each having different mechanisms of uptake. Three primary hepatocyte cultures and three sets of mesenchymal stromal cell (MSC) 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 MSCs and canine adipose MSCs. Undifferentiated human and mouse bone marrow MSCs also expressed the LDL receptor. In vitro, canine hepatocytes took up labeled LDL, but not AcLDL. All undifferentiated MSCs took up LDL, but not AcLDL. In conclusion, LDL and not AcLDL 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.