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Abstract Background Iron-deficiency is associated with increased morbidity and mortality in non-communicable diseases. However, iron parameters are rarely assessed in dogs. Here, we aimed to assess and correlate iron parameters in dogs suffering from Canine Atopic Dermatitis (CAD) compared to non-atopic, healthy dogs. Results For this retrospective study, blood values and sera of 34 dogs with confirmed CAD were compared with 94 healthy non-atopic dogs. In our cohort, dogs with CAD had significantly lower mean corpuscular volume (MCV, ) mean corpuscular hemoglobin (MCH) but higher white blood cell counts due to increased levels of circulating neutrophils and monocytes. CAD patients also had elevated total protein and c-reactive protein (CRP), but lower albumin levels compared to our healthy control dogs, indicated low-grade inflammation in the CAD cohort. Spearman correlations associated negatively clinical symptom (CADESI-4/PVAS) with MCV; ceruloplasmin and hepcidin, but positively with serum iron. Only in the CAD-cohort, MCV, CRP and albumin-levels negatively affected serum iron-levels and were positively associated with ceruloplasmin. Linear regression analysis revealed that serum iron-levels in CAD subjects, were positively dependent on hematocrit (packed cell volume, PCV) and albumin, and negatively dependent with white blood cells and neutrophils numbers. In contrast, in the healthy cohort, hepcidin was the sole factor associated with serum iron. Conclusions A decreased iron status was associated with a higher symptom burden. Iron homeostasis differed markedly in healthy and atopic dermatitis dogs. CAD patients had depleted iron-stores and presented themselves with subclinical inflammation.

IntroductionCanine Parvovirus 2 (CPV-2) infection poses a significant global health risk to susceptible dogs. Hypocobalaminemia, defined as reduced serum cobalamin (CBL) concentrations, is a recognized complication in chronic enteropathies in adult dogs but remains poorly understood in the context of acute enteropathies, especially in young dogs. The aim of this study was to investigate the frequency and severity of hypocobalaminemia in young dogs with parvovirus enteritis and evaluation of CBL as a predictor of outcome.Materials and methodsThirty client-owned dogs diagnosed with parvovirus infection and thirty healthy controls were enrolled. Clinical, hematological, and biochemical tests, including CBL and serum methylmalonic acid (MMA) concentrations, were assessed.ResultsResults indicated a significantly higher prevalence of hypocobalaminemia in dogs with parvovirus enteritis compared to healthy controls, as well as a significant correlation with a disease severity score. Moreover, survivors demonstrated higher CBL concentrations than non-survivors, suggesting an eventual prognostic value of CBL status. However, parenteral CBL supplementation showed no significant effect on serum CBL or MMA concentrations, highlighting potential challenges in CBL uptake at the cellular level.DiscussionHypocobalaminemia in this population is caused by multiple factors such as reduced nutritional absorption, gastrointestinal losses, and increased metabolic demands. Further research is needed to develop tailored management strategies, evaluate the effectiveness of CBL supplementation, and understand the mechanisms behind hypocobalaminemia in parvovirus infection.

IntroductionBloodwork is a widely used diagnostic tool in veterinary medicine, as diagnosis and therapeutic interventions often rely on blood biomarkers. However, biomarkers available in veterinary medicine often lack sensitivity or specificity. Mass spectrometry-based proteomics technology has been extensively used in the analysis of biological fluids. It offers excellent potential for a more comprehensive characterization of the plasma proteome in veterinary medicine.MethodsIn this study, we aimed to identify and quantify plasma proteins in a cohort of healthy dogs and compare two techniques for depleting high-abundance plasma proteins to enable the detection of lower-abundance proteins via label-free quantification liquid chromatography-mass spectrometry. We utilized surplus lithium-heparin plasma from 30 healthy dogs, subdivided into five groups of pooled plasma from 6 randomly selected individuals each. Firstly, we used a commercial kit to deplete high-abundance plasma proteins. Secondly, we employed an in-house method to remove albumin using Blue-Sepharose.Results and discussionAmong all the samples, some of the most abundant proteins identified were apolipoprotein A and B, albumin, alpha-2-macroglobulin, fibrinogen beta chain, fibronectin, complement C3, serotransferrin, and coagulation factor V. However, neither of the depletion techniques achieved significant depletion of highly abundant proteins. Despite this limitation, we could detect and quantify many clinically relevant proteins. Determining the healthy canine proteome is a crucial first step in establishing a reference proteome for canine plasma. After enrichment, this reference proteome can later be utilized to identify protein markers associated with different diseases, thereby contributing to the diagnosis and prognosis of various pathologies.

Abstract Bear bile-farming is common in East and Southeast Asia and this farming practice often results in irreversible health outcomes for the animals. We studied long-term effects of chronic bacterial and sterile hepatobiliary inflammation in 42 Asiatic black bears (Ursus thibetanus) rescued from Vietnamese bile farms. The bears were examined under anesthesia at least twice as part of essential medical interventions. All bears were diagnosed with chronic low-grade sterile or bacterial hepatobiliary inflammation along with pathologies from other systems. Our main finding was that the chronic low-grade inflammatory environment associated with bile extraction in conjunction with the suboptimal living conditions on the farms promoted and accelerated the development of age-related pathologies such as chronic kidney disease, obese sarcopenia, cardiovascular remodeling, and degenerative joint disease. Through a biomimetic approach, we identified similarities with inflammation related to premature aging in humans and found significant deviations from the healthy ursid phenotype. The pathological parallels with inflammageing and immuno-senescence induced conditions in humans suggest that bile-farmed bears may serve as animal models to investigate pathophysiology and deleterious effects of lifestyle-related diseases.

Abstract The role of the gut microbiome in developing Inflammatory Bowel Disease (IBD) in humans and dogs has received attention in recent years. Evidence suggests that IBD is associated with alterations in gut microbial composition, but further research is needed in veterinary medicine. The impact of IBD treatment on the gut microbiome needs to be better understood, especially in a breed-specific form of IBD in Yorkshire Terriers known as Yorkshire Terrier Enteropathy (YTE). This study aimed to investigate the difference in gut microbiome composition between YTE dogs during disease and remission and healthy Yorkshire Terriers. Our results showed a significant increase in specific taxa such as Clostridium sensu stricto 1, Escherichia-Shigella, and Streptococcus, and a decrease in Bacteroides, Prevotella, Alloprevotella, and Phascolarctobacterium in YTE dogs compared to healthy controls. No significant difference was found between the microbiome of dogs in remission and those with active disease, suggesting that the gut microbiome is affected beyond clinical recovery.

Chronic diarrhea is a hallmark sign of canine chronic inflammatory enteropathy (CIE), leading to fluid and electrolyte losses. Electrolyte homeostasis is regulated by the renin-angiotensin-aldosterone-system (RAAS), which might be involved in (counter-)regulating electrolyte losses in canine CIE. Whether and which electrolyte transporters are affected or if RAAS is activated in canine CIE is unknown. Thus, intestinal electrolyte transporters and components of the RAAS were investigated in dogs with CIE. Serum RAAS fingerprint analysis by mass spectrometry was performed in 5 CIE dogs and 5 healthy controls, and mRNA levels of intestinal electrolyte transporters and local RAAS pathway components were quantified by RT-qPCR in tissue biopsies from the ileum (7 CIE, 10 controls) and colon (6 CIE, 12 controls). Concentrations of RAAS components and mRNA expression of electrolyte transporters were compared between both groups of dogs and were tested for associations among each other. In dogs with CIE, associations with clinical variables were also tested. Components of traditional and alternative RAAS pathways were higher in dogs with CIE than in healthy controls, with statistical significance for Ang I, Ang II, and Ang 1–7 (all p

Abstract Dysbiosis and perturbations of fecal metabolic profiles have been reported in dogs with inflammatory bowel disease. Currently the incidence of dysbiosis and the fecal metabolomic profile in Yorkshire Terriers with chronic enteropathy (YTE) and the effects of treatment are unknown. This prospective observational study analyzed the dysbiosis index (DI) and fecal bile acid, sterol and fatty acid profiles in 14 Yorkshire Terriers with active YTE, 11 dogs in clinical remission, and 26 healthy Yorkshire Terriers. YTE was associated with dysbiosis and a significant increase in fatty acids (docosanoate, p = 0.002; gondoate, p = 0.026; erucate, p

Chronic idiopathic intestinal inflammation is an increasing worldwide problem that affects companion animals, especially dogs, and human patients. Although these disease entities have been intensely investigated recently, many questions remain, and alternative therapeutic options are needed. Diarrhea caused by dysregulation of intestinal electrolyte transport and subsequent fluid and electrolyte losses often leads to secondary consequences for the patient. Currently, it is not exactly clear which mechanisms are involved in the dysregulation of intestinal fluid absorption, but differences in intestinal electrolyte shifts between human and canine patients suggest species-specific regulatory or counterregulatory mechanisms. Several intestinal electrolyte transporters are differentially expressed in human patients with inflammatory bowel disease (IBD), whereas there are virtually no studies on electrolyte transporters and their endocrine regulation in canine chronic inflammatory enteropathy. An important mechanism involved in regulating fluid and electrolyte homeostasis is the renin-angiotensin-aldosterone-system (RAAS), which may affect intestinal Na+ transport. While RAAS has previously been considered a systemic regulator of blood pressure, additional complex roles of RAAS in inflammatory processes have been unraveled. These alternative RAAS pathways may pose attractive therapeutic targets to address diarrhea and, thus, electrolyte shifts in human IBD and canine chronic inflammatory enteropathy. This article comparatively summarizes the current knowledge about electrolyte transport in human IBD and canine chronic inflammatory enteropathy and the role of RAAS and offers perspectives for novel therapeutic avenues.

Abstract Background Dogs with hypoadrenocorticism (HA) frequently show signs of gastrointestinal disease (SGD). The prevalence of dogs presented for chronic SGD with HA is unknown. Objectives The aims of this study were to determine the prevalence of HA in dogs with chronic SGD and to identify clinical and laboratory variables for HA in this population. Animals One hundred fifty‐one dogs with chronic SGD. Methods In this multicentered prevalence study a standardized workup was performed in prospectively enrolled dogs with SGD > 3 weeks duration. Basal serum cortisol concentration was measured in every dog with ACTH stimulation test (ACTHST) if basal serum cortisol concentration was

Abstract Background T cells play a key role in the pathogenesis of chronic inflammatory enteropathy (CIE) in dogs. Cluster of differentiation 3 (CD3) antigen serves as a marker for T cells. In human medicine, Ki‐67 is an indicator for cell growth but there are only a few studies in dogs with CIE. Objective To investigate Ki‐67 in relation to T cells as a marker for CIE in dogs. Animals Eleven dogs with CIE and 6 healthy beagle controls (CO). Methods Retrospective case‐control study. Dogs were clinically assessed by the Canine Chronic Enteropathy Clinical Activity Index (CCECAI). Duodenal mucosal biopsy samples were endoscopically obtained for histopathologic examination by means of the World Small Animal Veterinary Association score. Double‐labeled immunofluorescence was used to investigate colocalization of Ki‐67 and CD3 in epithelium and lamina propria (LP) of villi and crypts. Results Dogs with CIE had significantly higher clinical score (median, 5.0; interquartile range [IQR], 3‐7) compared to CO (all 0; P

Across Southeast Asia and China, more than 17000 Asian bears are kept under suboptimal conditions and farmed for their bile to meet the consumer demand for traditional medicine products. Years of unsterile and repetitive bile extraction contribute to the development of chronic sterile or bacterial cholecystitis, a pathology commonly diagnosed in formerly bile-farmed bears. In both human and veterinary medicine, the diagnostic value of the macroscopic bile examination for assessing gallbladder disease is unclear. The objective of this study is to identify the role of gallbladder bile color, viscosity, and turbidity, while comparing them with established markers of cholecystitis. Moreover, it aims to define the optimal duration of oral antibiotic treatment for chronic bacterial cholecystitis in bears associated with bile farming. Thirty-nine adult, formerly bile-farmed Asiatic black bears (Ursus thibetanus) were examined under anesthesia and underwent percutaneous ultrasound guided cholecystocentesis. A total of 59 bile samples were collected with 20 animals sampled twice to evaluate the therapeutic success. All bile aspirates were assessed macroscopically and microscopically followed by submission for bacterial culture and antimicrobial sensitivity. In the majority of bears, samples with cytological evidence of bactibilia lacked inflammatory cells and did not always correlate with positive bacterial cultures. The most common bacterial isolates were Enterococcus spp, Streptococcus spp and Escherichia coli. Based on our findings, the optimal duration of antibiotic treatment for chronic bacterial cholecystitis is 30 days. Moreover, unlike Gamma-glutamyl Transferase (GGT) and gallbladder wall thickness, the organoleptic properties of bile were found to be reliable markers of chronic gallbladder inflammation with color and turbidity indicating cholestasis. The current study highlights the importance of cholecystocentesis for the management of gallbladder disease and provides initial results on the possible diagnostic value of macroscopic bile examination.

BackgroundChronic kidney disease (CKD) is accompanied by increases in circulating fibroblast growth factor 23 (FGF23) and aldosterone levels. Here, we tested the hypothesis that aldosterone may be one of the driving forces behind increased FGF23 secretion in CKD.MethodsUsing data from a prospective study in humans, a retrospective study in dogs and cats, and an experimental study in 5/6-nephrectomized mice, we analyzed the relationship between circulating FGF23 and serum aldosterone levels in CKD across four species. To assess the effects of acute inhibition of aldosterone signaling on circulating FGF23, we acutely treated mice with established CKD with the mineralocorticoid receptor blocker canrenone (50 mg/kg iv/sc), and measured intact FGF23 before and 24 h as well as 72 h after start of administration of the drug.ResultsWe found a tight positive association between circulating intact FGF23 and serum aldosterone in human, canine, and feline CKD patients, as well as in experimental murine CKD (humans: rS = 0.57, p = 0.0368; dogs: rS = 0.66, p = 0.0019; cats: rS = 0.75, p = 0.0003; mice: rS = 0.49, p = 0.0004). Injection of canrenone in mice with established CKD did not lead to changes in FGF23 levels within 24 h, but reduced FGF23 in all mice at 72 h.ConclusionAldosterone may drive enhanced FGF23 secretion in CKD, possibly explaining the tight positive association between circulating intact FGF23 and aldosterone in human, canine, and feline CKD patients as well as in experimental CKD models.

Perturbations of metabolite profiles in human and canine enteropathies have been reported before. However, data in dogs are scarce and inconsistent. Currently, the metabolite profile in Yorkshire Terrier enteropathy (YTE) and the impact of treatment is unknown. The objective of this study was to investigate the plasma metabolome of 13 Yorkshire Terriers with YTE and compare it to 20 healthy Yorkshire Terriers. Furthermore, we studied the impact of treatment on the metabolome. In this prospective observational study, plasma metabolite profiles were analyzed by flow injection analysis-tandem mass spectrometry (FIA-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a targeted metabolomics kit. Metabolite analysis revealed that YTE is accompanied by changes in lipid and bile acid metabolism. YTE was associated with a significant decrease of long-chain fatty acids (octadecenoic acid, eicosadienoic acid, eicosatrienoic acid) and lower levels of long-chain acylcarnitines (tetradecanoylcarnitine, hexadecanoylcarnitine, hexadecenoylcarnitine, octadecenoylcarnitine) compared with healthy controls. Furthermore, taurodeoxycholic acid, a secondary bile acid, was decreased in plasma from YTE patients. These changes might be breed-specific and might be involved in the pathogenesis of YTE. Interestingly, changes in metabolite levels were not recovered after treatment and differed considerably from healthy controls.

Functional intestinal disorders constitute major, potentially lethal health problems in humans. Consequently, research focuses on elucidating the underlying pathobiological mechanisms and establishing therapeutic strategies. In this context, intestinal organoids have emerged as a potent in vitro model as they faithfully recapitulate the structure and function of the intestinal segment they represent. Interestingly, human-like intestinal diseases also affect dogs, making canine intestinal organoids a promising tool for canine and comparative research. Therefore, we generated organoids from canine duodenum, jejunum and colon, and focused on simultaneous long-term expansion and cell differentiation to maximize applicability. Following their establishment, canine intestinal organoids were grown under various culture conditions and then analyzed with respect to cell viability/apoptosis and multi-lineage differentiation by transcription profiling, proliferation assay, cell staining, and transmission electron microscopy. Standard expansion medium supported long-term expansion of organoids irrespective of their origin, but inhibited cell differentiation. Conversely, transfer of organoids to differentiation medium promoted goblet cell and enteroendocrine cell development, but simultaneously induced apoptosis. Unimpeded stem cell renewal and concurrent differentiation was achieved by culturing organoids in the presence of tyrosine kinase ligands. Our findings unambiguously highlight the characteristic cellular diversity of canine duodenum, jejunum and colon as fundamental prerequisite for accurate in vitro modelling.

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from different species (human, mouse, cat, dog), organs (intestine, kidney, brain, liver), and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, specifically covering the current and future uses of this exciting new insight model to the field of veterinary medicine.

Abstract Epithelial damage due to gastrointestinal disorders frequently causes severe disease in horses. To study the underlying pathophysiological processes, we aimed to establish equine jejunum and colon enteroids (eqJE, eqCE) mimicking the in vivo epithelium. Therefore, enteroids were cultivated in four different media for differentiation and subsequently characterized histomorphologically, on mRNA and on protein level in comparison to the native epithelium of the same donor horses to identify ideal culture conditions for an in vitro model system. With increasing enterocyte differentiation, the enteroids showed a reduced growth rate as well as a predominantly spherical morphology and less budding compared to enteroids in proliferation medium. Combined or individual withdrawal of stem cell niche pathway components resulted in lower mRNA expression levels of stem cell markers and concomitant differentiation of enterocytes, goblet cells and enteroendocrine cells. For eqCE, withdrawal of Wnt alone was sufficient for the generation of differentiated enterocytes with a close resemblance to the in vivo epithelium. Combined removal of Wnt, R-spondin and Noggin and the addition of DAPT stimulated differentiation of eqJE at a similar level as the in vivo epithelium, particularly with regard to enterocytes. In summary, we successfully defined a medium composition that promotes the formation of eqJE and eqCE consisting of multiple cell types and resembling the in vivo epithelium. Our findings emphasize the importance of adapting culture conditions to the respective species and the intestinal segment. This in vitro model will be used to investigate the pathological mechanisms underlying equine gastrointestinal disorders in future studies.

We evaluated the redox status, precisely glutathione levels, which have a major impact in cellular detoxification and antioxidant defence in IBD-derived and healthy intestinal organoids. Therefore, we wanted to explore the differences in terms of their redox balance and mitochondrial fitness. To this end, we introduced a Grx1-roGFP2 construct into the organoids by lentiviral transduction before performing a stress assay by treating the organoids with hydrogen peroxide and examined the GSH/GSSG ratio using confocal imaging. Using ratio imaging, we could detect statistically significant differences between healthy and IBD-derived samples. To gain more insight, we also performed a GSH/GSSG assay, which directly measured glutathione levels. This analysis revealed that both organoid lines had higher levels of oxidized glutathione due to the stress treatment demonstrated by a lower GSH/GSSG ratio compared to the untreated control. Nevertheless, the results showed no significant difference between healthy and IBD-derived organoids. We further challenged organoids with hydrogen peroxide after incubation with MitoTracker® to see if mitochondrial fitness might be different in IBD-derived organoids. However, these results were also very comparable. In summary, our preliminary findings indicate that both organoid lines demonstrate a well-functioning system in terms of analysis but show no clear difference between healthy and IBD-derived samples.

Abstract In contrast to humans and dogs, the skin microbiota of wolves is yet to be described. Here, we investigated the skin microbiota of dogs and wolves kept in outdoor packs at the Wolf Science Center (WSC) via 16S rRNA gene amplicon sequencing. Skin swab samples were also collected from human care takers and their pet dogs. When comparing the three canine groups, representing different degrees of human contact to the care takers and each other, the pet dogs showed the highest level of diversity. Additionally, while human skin was dominated by a few abundant phylotypes, the skin microbiota of the care takers who had particularly close contact with the WSC animals was more similar to the microbiota of dogs and wolves compared to the humans who had less contact with these animals. Our results suggest that domestication may have an impact on the diversity of the skin microbiota, and that the canine skin microbiota can be shared with humans, depending on the level of interaction.

Abstract Background In inflammatory bowel disease (IBD) in humans, phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is upregulated in mucosal epithelial cells and correlates with clinical severity. Hypothesis/Objective To investigate the expression pattern of pSTAT3 in the mucosa of dogs with chronic inflammatory enteropathy (CIE) and explore correlations between its expression and clinical and histopathological severity scoring. Animals Twenty‐eight canine CIE patients grouped into food‐responsive enteropathy (FRE; 9), steroid‐responsive enteropathy (SRE; 10), and protein‐losing enteropathy (PLE; 9). Ten healthy beagle dogs served as controls (CO). Methods Retrospective case control study. Immunohistochemistry was used to detect pSTAT3 in canine duodenal mucosa samples. Results Compared to CO, SRE (P

BackgroundInflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are common chronic enteropathies in dogs, of which the exact pathogenesis has not been fully understood. In people dyslipidemia has been reported in patients with IBD, and potential therapeutic benefits of polyunsaturated fatty acids (PUFA) in the treatment of IBD have been investigated. Studies on the phospholipid profile in dogs with IBD and FRD are still lacking.AimTo investigate the systemic phospholipid profile of dogs with IBD or FRD and to evaluate possible differences in phospholipids before and after treatment.MethodsThe phospholipids in whole blood and EDTA plasma of 32 dogs diagnosed with either IBD (n = 16) or FRD (n = 16) were analyzed by hydrophilic interaction liquid chromatography (HILIC) prior to and after initiation of treatment, which included an elimination diet enriched with PUFAs.ResultsA clear separation of the phospholipids between whole blood and plasma was demonstrated on principal component analysis plots. In addition to the type of specimen, treatment and disease severity were the most significant factors determining the variance of the phospholipid profile. An increase in lysolipids was observed after treatment. The phosphatidylcholine (PC) species changed from PC 38:4 before treatment to mainly lysophosphatidylcholine 18:0 after treatment. Furthermore, several differences in the abundance of individual phospholipids were identified between dogs with IBD and dogs with FRD and between treatment statuses using random forest analysis.ConclusionSignificant variances were identified in the phospholipid profiles of dogs with IBD and FRD. These were particularly determined by type of specimen used, disease severity and treatment status. After treatment, a shift of phospholipid species towards lysophosphatidylcholine 18:0 was observed. Future studies should further investigate the role of lipids in the pathophysiology of IBD and FRD as well as their potential therapeutic benefits.

Scientific information on spontaneous type I diabetes mellitus (DM) and treatment modalities in guinea pigs is scarce. As most diabetic guinea pigs are overweight and respond to dietary changes, a disorder resembling type II-DM in humans seems to be most prevalent in this species. In the present report, a nine-month-old female intact guinea pig (GP1) was presented because of a cataract and polyphagia. The physical examinations in GP1 and its littermate, GP2, were unremarkable. Laboratory tests revealed hyperglycemia, hyperlipidemia, elevated fructosamine concentrations, and glucosuria in GP1 and GP2. Not responding to dietary changes, an insulin-dependent diabetes mellitus was suspected in both animals. Treatment with 0.5 IU of glargine insulin (Lantus®) per guinea pig subcutaneously (s.c.) once daily was initiated in both animals. Monitoring included repeated clinical evaluations and the measurement of plasma glucose and fructosamine concentrations. Capillary glucose concentration was measured using a glucometer, and glucosuria was monitored by dipstick. Blood glucose concentrations decreased quickly in both GPs, and glucosuria resolved. Including several dose adjustments, DM remained controlled for over 1.5 years. Bilateral cataracts and lens-induced uveitis in GP1 were medically managed with only slight progression. This is the first report of guinea pigs with insulin-dependent diabetes mellitus that were successfully treated with long-acting basal insulin glargine.

Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS) and intrahepatic portosystemic shunts (IHPSS) was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS P

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. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver's first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible.