Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs.

Background: Hepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations.

Leukoencephalomyelopathy in cats linked to abnormal fatty acid composition of the white matter of the spinal cord and of irradiated dry cat food.

Four outbreaks of leukoencephalomyelopathy in colonies of SPF cats on a long-term diet of irradiated dry cat food were observed in the Netherlands between 1989 and 2001. As a primary defect in myelin formation was suspected to be the cause of the disease and myelin consists mainly of lipids and their fatty acids, we investigated the fatty acid composition of the white matter of the spinal cord of affected and control cats and of irradiated and non-irradiated food. The irradiated food had low levels of alpha-linolenic acid compared to linoleic acid as well as a high total omega-6:omega-3 ratio of 7:1 in the irradiated and of 2:1 in the non-irradiated food.

Cellular characteristics of keratin 19-positive canine hepatocellular tumours explain its aggressive behaviour.

The expression of the hepatic progenitor cell marker keratin 19 (K19) in canine hepatocellular carcinomas is linked with a poor prognosis. To better understand this aggressive behaviour, K19-positive hepatocellular carcinomas (n=5) and K19-negative hepatocellular adenomas (n=6) were immunohistochemically stained for proteins involved in malignant tumour development. The K19-positive carcinomas showed marked positivity for platelet-derived growth factor receptor alpha polypeptide (PDGFRα), laminin, integrin beta-1/CD29, B-cell-specific Moloney murine leukaemia virus Integration site 1, glypican-3 (GPC-3) and prominin-1/CD133, in contrast with K19-negative hepatocellular adenomas.

Sensitivity and Specificity of Plasma ALT, ALP, and Bile Acids for Hepatitis in Labrador Retrievers.

Background: Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA).

Objectives: To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH).

Animals: 191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology.

Gene expression patterns in the progression of canine copper-associated chronic hepatitis.

Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport.

Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers.

Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders.

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation.

Dietary management of labrador retrievers with subclinical hepatic copper accumulation.

Background: Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper-associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver.

Objective: To investigate the effect of a low-copper, high-zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations.

Enhanced Wnt/β-catenin and Notch signalling in the activated canine hepatic progenitor cell niche.

Background: The liver has a large regenerative capacity. Hepatocytes can replicate and regenerate a diseased liver. However, as is the case in severe liver diseases, this replication may become insufficient or exhausted and hepatic progenitor cells (HPCs) can be activated in an attempt to restore liver function.

Classification of primary hepatic tumours in the cat.

Hepatic tumours in dogs have recently been re-classified to follow a revised human classification system that takes account of identified hepatic progenitor cells. This study investigated the presence and relative frequency of morphological types of feline primary hepatic neoplasms and aimed to determine whether a similar new classification scheme could be applied in cats. Feline primary liver tumours (n = 61) were examined histologically and with a series of immunohistochemical markers.

Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs.

Background: COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease.

Methods: Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years.

The canine hepatic progenitor cell niche: molecular characterisation in health and disease.

Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH), in which HPCs are massively activated. Gene expression of HPC, hepatocyte and biliary markers was determined by quantitative reverse transcriptase PCR.

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever.

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which D-penicillamine is the most commonly used. D-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc.

Classification of primary hepatic tumours in the dog.

Many advances have been made in the characterisation of primary liver tumours in humans, in particular relating to the identification and role of hepatic progenitor cells, resulting in a new classification. The aim of the present study was to investigate the presence and relative frequency of morphological types of canine primary hepatic neoplasms and to determine whether a classification similar to the human scheme can be applied to these canine neoplasms. Canine primary liver tumours (n=106) were examined histologically and with the immunohistochemical markers keratin 19, HepPar-1, epithelial membrane antigen/mucin-1, CD10, neuron-specific enolase and chromogranin-A.

A retrospective study of oral prednisolone treatment in canine chronic hepatitis.

Background: Only one study reports prednisone to prolong survival in dogs with chronic hepatitis irrespective of the causative agent. The aim of this retrospective study was to investigate the effects of prednisolone treatment on survival, clinicopathological variables, and histological grade and stage of idiopathic chronic hepatitis in 36 dogs.

Animals And Methods: Medical records were reviewed of 36 prednisolone-treated dogs (median age: 8.

American Cocker Spaniel chronic hepatitis in Japan.

Background: American Cocker Spaniels are predisposed to chronic hepatitis.

Objective: To describe the clinical and histological features of chronic hepatitis in Japanese American Cocker Spaniels.

Animals: Thirteen cases examined from 2003 to 2009.

Urinary excretion of copper, zinc and iron with and without D-penicillamine administration in relation to hepatic copper concentration in dogs.

Hereditary copper-associated hepatitis in dogs resembles Wilson's disease, a copper storage disease in humans. Values for urinary copper excretion are well established in the diagnostic protocol of Wilson's disease, whereas in dogs these have not been evaluated. The objectives of this study were to characterize both basal and D-penicillamine induced urinary copper, zinc and iron excretion in dogs in relation to hepatic copper concentration.

D-penicillamine treatment of copper-associated hepatitis in Labrador retrievers.

d-penicillamine is effectively used in the lifelong treatment of copper toxicosis in Bedlington terriers and Wilson's disease in humans. A complex form of copper-associated hepatitis has recently been characterized in the Labrador retriever. The aims of this study were to evaluate the effectiveness of d-penicillamine treatment for copper-associated hepatitis in this breed, to study the effects on hepatic copper, iron and zinc concentrations, and to evaluate parameters to predict optimal duration of treatment.

[Gastro-intestinal lymphocytic and sclerosing leiomyositis (pseudoobstruction) in a dog].

The clinical, ultrasonographic and radiologic aspects and the pathology of gastro-intestinal lymphocytic and sclerosing leiomyositis (pseudoobstruction) are described in a 14 month old, male American Staffordshire terrier.

Association of dietary copper and zinc levels with hepatic copper and zinc concentration in Labrador Retrievers.

Background: Copper-associated hepatitis is an inherited disease in the Labrador Retriever. Apart from genetic factors, dietary intake of copper and zinc are suspected to play a role in the pathogenesis.

Objectives: To investigate whether dietary copper and zinc levels of commercially available dry diets are associated with hepatic copper and zinc concentrations in Labrador Retrievers.

COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model for chronic hepatitis and fibrosis.

New therapeutic concepts developed in rodent models should ideally be evaluated in large animal models prior to human clinical application. COMMD1-deficiency in dogs leads to hepatic copper accumulation and chronic hepatitis representing a Wilson's disease like phenotype. Detailed understanding of the pathogenesis and time course of this animal model is required to test its feasibility as a large animal model for chronic hepatitis.

Reversible pulmonary hypertension associated with lungworm infection in a young cat.

Two ten-week-old kittens presented with dyspnea. Two weeks later dyspnea had worsened and both kittens had developed a heart murmur. One kitten died and necropsy showed severe granulomatous pneumonia and moderate bronchi(oli)tis and peribronchi(oli)tis caused by Aelurostrongylus abstrusus.

Recombinant hepatocyte growth factor treatment in a canine model of congenital liver hypoplasia.

Background: Although the liver has a large regenerative capacity, in many hepatopathies, these repair mechanisms fail. The therapeutic potential of hepatocyte growth factor (HGF) has been proven in numerous toxin-induced liver failure models in rodents, but never in spontaneously occurring liver diseases in larger animal models.

Aim: The aim of this study was to induce liver growth in a hypoplastic liver by the administration of exogenous recombinant HGF.

A randomized, open-label, positively-controlled field trial of a hydrolyzed protein diet in dogs with chronic small bowel enteropathy.

Background: Hydrolyzed protein diets are commonly used to manage canine chronic enteropathies (CE), but their efficacy has not yet been critically evaluated.

Hypothesis: A hydrolyzed protein diet is superior to that of a highly digestible (control) diet in the management of CE in dogs.

Animals: Twenty-six dogs (18 test diet, 8 control diet) referred for investigation and management of naturally occurring chronic small intestinal disease.

Apoptosis in postweaning multisystemic wasting syndrome (PMWS) hepatitis in pigs naturally infected with porcine circovirus type 2 (PCV2).

The degree of apoptosis in the livers of pigs with hepatitis due to naturally-occurring postweaning multisystemic wasting syndrome (PMWS) was evaluated semi-quantitatively by immunohistochemical detection of the apoptotic marker cleaved caspase-3 (CCasp3). The amount and distribution of porcine circovirus type 2 (PCV2) virus in the liver was evaluated using in situ hybridisation. Livers with mild, stage I hepatitis exhibited similar degrees of apoptosis to controls; those with stage II lesions had variable apoptotic rates, ranging from mild to high, and in livers with more severe, stage III hepatitis, high levels of hepatocyte apoptosis was a feature.