ABSTRACT
A 14-year-old intact female diabetic dog presented with seizures and hyperglycemic hyperosmolar syndrome. Radiographs revealed gas-filled tubular structures in the right and left caudal abdomen, raising concerns of emphysematous pyometra or small intestinal ileus. Ultrasonography played a pivotal role in confirming emphysematous pyometra, a technique previously documented only once in veterinary practice. This report also presents the first documented case of emphysematous pyometra in a diabetic dog attributed to Klebsiella pneumoniae and complicated by emphysematous hepatitis.
Subject(s)
Dog Diseases , Klebsiella Infections , Klebsiella pneumoniae , Pyometra , Animals , Dogs , Klebsiella Infections/veterinary , Klebsiella Infections/diagnosis , Klebsiella Infections/complications , Female , Dog Diseases/diagnostic imaging , Dog Diseases/microbiology , Dog Diseases/diagnosis , Klebsiella pneumoniae/isolation & purification , Pyometra/veterinary , Pyometra/complications , Pyometra/diagnostic imaging , Emphysema/veterinary , Emphysema/diagnostic imaging , Ultrasonography/veterinary , Hepatitis, Animal/diagnosis , Hepatitis, Animal/microbiology , Hepatitis, Animal/diagnostic imaging , Hepatitis, Animal/complications , Diabetes Complications/veterinary , Anti-Bacterial Agents/therapeutic useABSTRACT
A geriatric female giant panda developed grave signs of illness and was diagnosed with suspected hepatobiliary tract obstruction or other severe hepatic disease such as advanced cholangiohepatitis. The giant panda was euthanized and post mortem computed tomography was performed prior to necropsy. Common bile duct obstruction at the major duodenal papilla by a mineral attenuating calculus causing dilatation of common bile and gallbladder with concurrent multiple areas of liver abscess were detected by postmortem computed tomography. These were confirmed with gross necropsy. This is the first case report of common bile duct obstruction by mineral calculus with concurrent severe cholangiohepatitis in a giant panda.
Subject(s)
Calculi , Cholestasis , Ursidae , Animals , Autopsy , Calculi/diagnostic imaging , Calculi/veterinary , Cholangitis/complications , Cholangitis/diagnostic imaging , Cholangitis/veterinary , Cholestasis/complications , Cholestasis/diagnostic imaging , Cholestasis/veterinary , Euthanasia, Animal , Female , Hepatitis, Animal/complications , Tomography, X-Ray Computed/veterinaryABSTRACT
BACKGROUND: Retinol-binding protein 4 (RBP4) is elevated and associated with inflammation in metabolic diseases. Disruption of the retinol cascade and O-GlcNAcylation of the RBP4 receptor (STRA6) are found in diabetic kidneys. OBJECTIVES: We investigated whether the disruption of the retinol cascade induces RBP4 overproduction and if O-linked GlcNAc modification targets RBPR2 and contributes to the disruption of retinol cascades in diabetic livers. METHODS: Western blot or immunohistochemistry for RBPR2, CRBP1, LRAT, RALDH, RARα, RARγ, RXRα, RBP4, GFAT, OGT, OGA and inflammatory markers, as well as ELISA for RBP4, were performed in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. Immunoprecipitation and dual fluorescence staining were used to explore O-GlcNAc-modified RBPR2 and RBP4 binding activity on RBPR2. Transfection of the CRBP1 gene was done to verify whether a disrupted retinol cascade induces RBP4 overproduction. OGT silencing was done to investigate the association of O-GlcNAcylation with the disruption of retinol cascade. RESULTS: Disruption of retinol cascade, RBP4 overproduction, O-GlcNAcylation of RBPR2, decreased RBP4 binding activity on RBPR2 and inflammation were found in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. CRBP1 gene transfection reversed the suppression of the cellular retinol cascade and simultaneously attenuated the RBP4 overproduction and inflammation in high glucose-treated hepatocytes. The silencing of OGT reversed the disruption of the cellular retinol cascade, RBP4 overproduction and inflammation induced by high glucose in hepatocytes. CONCLUSIONS: This study indicates that the disruption of cellular retinol cascade is strongly associated with RBP4 overproduction and inflammation in diabetic livers. RBPR2 is one target for high glucose-mediated O-linked GlcNAc modification, which causes liver retinol dyshomeostasis.
Subject(s)
Diabetes Mellitus/metabolism , Homeostasis , Retinol-Binding Proteins, Plasma/metabolism , Vitamin A/metabolism , Adipose Tissue/metabolism , Animals , Hepatitis, Animal/complications , Hyperglycemia/complications , Hyperlipidemias/complications , Liver/metabolism , Mice , Mice, Inbred C57BL , Retinol-Binding Proteins, Cellular/genetics , Retinol-Binding Proteins, Plasma/genetics , Signal TransductionABSTRACT
A 9 mo old female intact golden retriever presented for evaluation of chronic lethargy and decreased appetite. The serum biochemistry profile revealed increased liver enzymes consistent with a mixed hepatocellular and cholestatic pattern. A multiphase computed tomography angiography was performed to evaluate for a portosystemic shunt. Numerous hyperattenuating nodules were identified throughout the liver on the noncontrast-enhanced series. Histologic evaluation of percutaneous needle biopsy samples of a liver nodule showed a rare form of hepatitis called lobular dissecting hepatitis. Lobular dissecting hepatitis should be considered as a differential in young dogs with precontrast hyperattenuating hepatic nodules on noncontrast-enhanced computed tomography.
Subject(s)
Dog Diseases/diagnostic imaging , Hepatitis, Animal/diagnostic imaging , Aging , Amoxicillin/therapeutic use , Animal Feed/analysis , Animals , Anti-Bacterial Agents/therapeutic use , Dietary Proteins/administration & dosage , Dog Diseases/etiology , Dog Diseases/pathology , Dog Diseases/therapy , Dogs , Female , Gastrointestinal Agents/therapeutic use , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/veterinary , Hepatitis, Animal/complications , Hepatitis, Animal/pathology , Hepatitis, Animal/therapy , Lactulose/therapeutic use , Liver/diagnostic imaging , Liver/pathology , Omeprazole/therapeutic use , Tomography, X-Ray Computed/veterinaryABSTRACT
BACKGROUND: Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. HYPOTHESIS/OBJECTIVES: To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. ANIMALS: Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled. Six dogs without hepatic disease also were evaluated as healthy controls. METHODS: Dogs with hepatic disorders were prospectively included. Contrast-enhanced ultrasonography of the HV was performed for 2 minutes. Washout ratio was defined as the attenuation rate from peak intensity to the intensity at the end of the CEUS study. RESULTS: Washout ratio in the hepatitis group (median, 18.0%; range, 2.0-37.0%) was significantly lower than that of the PHPV (median, 52.2%; range, 11.5-86.3%), cPSS (median, 60.0%; range, 28.6-77.4%), other hepatopathy (median, 70.5%; range, 26.6-88.4%), and normal (median, 78.0%; range, 60.7-91.7%) groups. The area under the receiver operating characteristic curve for hepatitis was 0.960, with a 95% confidence interval (CI) of 0.853-0.990. Washout ratio ≤37.1% resulted in a sensitivity of 100% (95% CI, 78.5-100%) and specificity of 85.2% (95% CI, 67.5-94.1%) for the prediction of hepatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Washout ratio can distinguish hepatitis from the other noninflammatory disorders with high accuracy. This result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis.
Subject(s)
Contrast Media/administration & dosage , Dog Diseases/physiopathology , Hepatic Veins/diagnostic imaging , Hepatitis, Animal/physiopathology , Inflammation/veterinary , Animals , Case-Control Studies , Dogs , Female , Hepatitis, Animal/complications , Hepatitis, Animal/diagnostic imaging , Inflammation/complications , Inflammation/diagnostic imaging , Inflammation/physiopathology , Male , Prospective Studies , Severity of Illness Index , Ultrasonography/veterinaryABSTRACT
AIM: Depression associating patients with chronic liver diseases is a major treatment goal. This study aimed to evaluate the potential hepatoprotective and antidepressant effects of celecoxib in a model of experimental autoimmune hepatitis (EAH) and depressive-like behavior in C57BL/6 mice. MAIN METHODS: EAH was induced by immunization with S-100 liver antigen emulsified in complete Freund's adjuvant (CFA). Mice were randomly allocated to 5 groups; control phosphate buffered saline group; control CFA group; EAH group, and 2 groups of EAH plus celecoxib (7.5 or 15mg/kg/d respectively). Mice were assessed behaviorally by novelty-suppressed test, tail suspension test, locomotor assessment and forced swimming tests. Serum liver enzymes and hepatic hydroxyproline content were biochemically analyzed. Histopathological analysis for liver and brain sections and immunohistochemical studies for hepatic and hippocampal tumor necrosis factor (TNF-α), nuclear factor Kappa-B (NF-κB) and caspase-3 were performed. KEY FINDINGS: EAH group exhibited significant depressive-like changes, increase in liver enzymes and hepatic hydroxyproline content. Signs of autoimmune hepatitis and structural changes in hippocampus were confirmed by histopathological studies. Immunohistochemical examination revealed overexpression of hepatic and hippocampal TNF-α, NF-κB and caspase-3 positive cells. Celecoxib (7.5mg/kg/d) significantly ameliorated hepatic biochemical changes, hepatic and hippocampal histopathological and immunohistochemical changes induced in EAH group. Celecoxib (15mg/kg/d) significantly ameliorated the behavioral changes, histopathological and immunohistochemical changes in hippocampus, with non-significant change in hepatic biochemical profile, histopathological and immunohistochemical changes induced in EAH group. SIGNIFICANCE: The celecoxib (7.5mg/kg/d) through its anti-inflammatory effect may represent a new therapeutic approach to treat autoimmune hepatitis associated with depressive symptoms.
Subject(s)
Celecoxib/pharmacology , Depression/complications , Depression/drug therapy , Hepatitis, Animal/complications , Liver/drug effects , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , Behavior, Animal/drug effects , Brain/pathology , Caspase 3/metabolism , Celecoxib/therapeutic use , Depression/psychology , Dose-Response Relationship, Drug , Hepatitis, Animal/immunology , Hepatitis, Animal/metabolism , Hepatitis, Animal/pathology , Hippocampus/metabolism , Hydroxyproline/metabolism , Liver/immunology , Liver/metabolism , Liver/pathology , Male , Mice , S100 Proteins/adverse effects , S100 Proteins/immunologyABSTRACT
UNLABELLED: The majority of hepatocellular carcinoma develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and ß-catenin (CAT), followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride. Also, the impact of DDC-induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT-CAT or AKT-NRAS(G12V) . Treatment with DDC and carbon tetrachloride significantly facilitated the adenoma-to-carcinoma conversion and accelerated the growth of AKT-CAT tumors. Furthermore, DDC treatment altered the morphology of AKT-CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT-CAT tumors revealed that cellular growth and proliferation were mainly affected by chronic inflammation and caused up-regulation of Cxcl16, Galectin-3, and Nedd9, among others. Integration with transcriptome profiles from human hepatocellular carcinomas further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRAS(G12V) tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT-NRAS(G12V) tumors. CONCLUSION: Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation. (Hepatology 2016;63:1888-1899).
Subject(s)
Hepatitis, Animal/complications , Liver Neoplasms, Experimental/etiology , Oncogenes , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Carbon Tetrachloride , Cell Line , Chemokine CXCL16 , Chemokine CXCL6/metabolism , Female , Galectin 3/metabolism , Hepatitis, Animal/chemically induced , Liver Neoplasms, Experimental/metabolism , Mice , Phenotype , Pyridines , Transcriptome , Tumor MicroenvironmentABSTRACT
Pancreatitis in cats is frequently accompanied by concurrent disease in other organ systems. Co-morbidities include hepatic lipidosis, inflammatory liver disease, bile duct obstruction, diabetes mellitus, inflammatory bowel disease, vitamin deficiency (B12/cobalamin, folate or K), intestinal lymphoma, nephritis, pulmonary thromboembolism and pleural and peritoneal effusions. "Triaditis" is the term used to describe concurrent inflammation of the pancreas, liver and small intestines. Triaditis has been reported in 50 to 56% of cats diagnosed with pancreatitis and 32 to 50% of those with cholangitis/inflammatory liver disease. A definitive diagnosis of triaditis is based on the histopathological evaluation of each organ. However, the specific conditions of each organ that constitute a diagnosis of triaditis remains to be defined. While the aetiopathogenesis of pancreatitis and its relationship to inflammation in other organ systems is unclear, preliminary studies point to a heterogeneous group of conditions with differential involvement of host inflammatory and immune responses and enteric bacteria. Comprehensive, prospective studies that simultaneously evaluate the presence of predefined clinical, clinicopathological and histopathological abnormalities, coupled with high-resolution evaluation of pancreaticobiliary morphology, immunological profiling and screening for bacterial colonisation are required to advance diagnosis and therapy.
Subject(s)
Cat Diseases/etiology , Enteritis/veterinary , Hepatitis, Animal/complications , Pancreatitis/veterinary , Animals , Cat Diseases/therapy , Cats , Enteritis/complications , Enteritis/etiology , Enteritis/therapy , Hepatitis, Animal/etiology , Hepatitis, Animal/therapy , Pancreatitis/etiology , Pancreatitis/therapyABSTRACT
BACKGROUND: Copper-associated hepatitis (CAH) has been well described in Labrador Retrievers. However, the association of CAH with proximal renal tubular dysfunction in this breed has not been characterized. OBJECTIVES: To report clinical features, hepatic and renal histopathologic findings, tissue copper concentrations, and outcome of Labradors with CAH and proximal renal tubular disease. ANIMALS: Nine Labrador Retrievers with renal glucosuria and biopsy-confirmed CAH. METHODS: Clinical, clinicopathologic, and light microscopic findings were retrospectively reviewed. Rhodanine staining or atomic emission spectroscopy was performed on all hepatic samples and available renal tissue (4 dogs) to assess copper concentrations. RESULTS: Eight dogs had a history of polyuria and polydipsia, and all dogs had increased serum bilirubin concentrations. Five dogs had hyperchloremic metabolic acidosis. Three dogs with acidemia had paradoxical alkalinuria. All renal specimens had increased copper concentrations. Renal tubular vacuolization, degeneration, and regeneration were observed on light microscopy. Four dogs died within 10 days of diagnosis. One dog survived 2 months; 4 dogs survived more than 1 year. In long-term survivors, including 2 that did not undergo immediate copper chelation, resolution of renal tubular dysfunction occurred within weeks to months. CONCLUSIONS AND CLINICAL IMPORTANCE: Labrador Retrievers with CAH can develop clinical and laboratory evidence of renal tubular dysfunction in association with increased renal copper concentrations. Given the rarity of renal tubular disorders, detection of renal glucosuria and increased ALT activity in a Labrador Retriever is suggestive of CAH. Although renal tubular dysfunction may indicate advanced disease, successful long-term outcome is possible with a variety of therapies.
Subject(s)
Copper/metabolism , Dog Diseases/etiology , Hepatitis, Animal/complications , Kidney Diseases/veterinary , Kidney Tubules/pathology , Animals , Dog Diseases/pathology , Dogs , Glycosuria/veterinary , Hepatitis, Animal/metabolism , Kidney Diseases/pathology , Proteinuria/veterinary , Retrospective StudiesABSTRACT
A 5-year-old female Chihuahua was presented for acute collapse. Laboratory examinations showed markedly elevated levels of hepatobiliary enzymes. Empiric antibiotic therapy for bacterial infection of the liver was ineffective. The clinical signs worsened with the development of hyponatremia with hypoosmolality and elevated urine sodium levels. The dog was suspected of having acute cholangiohepatitis associated with an immune-mediated disease. Subsequently, it was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) on the basis of the specific disease criteria. Further tests showed normal function of the adrenal and thyroid glands, and MRI and cerebrospinal fluid (CSF) analysis did not show any intracranial diseases. Immunosuppressive therapy and water restriction resolved the clinical signs and improved the SIADH in this dog. This case indicates that SIADH can occur concurrently with suspected immune-mediated liver disease in dogs.
Subject(s)
Dog Diseases/pathology , Hepatitis, Animal/complications , Inappropriate ADH Syndrome/veterinary , Liver Failure/veterinary , Animals , Cyclosporine/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/etiology , Dogs , Female , Hepatitis, Animal/immunology , Immunosuppressive Agents/therapeutic use , Inappropriate ADH Syndrome/complications , Liver Failure/complications , Liver Failure/drug therapy , Prednisolone/therapeutic useABSTRACT
This is the first report of Escherichia coli isolates producing CTX-M-15, the predominant type of extended-spectrum ß-lactamase (ESBL) associated with clinical disease in humans in the United Kingdom, in a United Kingdom pet dog. This report also describes the first isolation of CTX-M/Tem ESBL-positive E. coli from bile in dogs with hepatobiliary disease.
Subject(s)
Cholangitis/veterinary , Dog Diseases/microbiology , Escherichia coli Infections/veterinary , Escherichia coli/enzymology , Hepatitis, Animal/complications , beta-Lactamases/analysis , Animals , Anti-Bacterial Agents/pharmacology , Bile/microbiology , Cholangitis/complications , Cholangitis/microbiology , Dogs , Escherichia coli/isolation & purification , Escherichia coli Infections/complications , Escherichia coli Infections/microbiology , Female , Hepatitis, Animal/microbiology , Microbial Sensitivity Tests , United KingdomABSTRACT
Helicobacter marmotae has been identified in the inflamed livers of Eastern woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV), as well as from the livers of WHV-negative woodchucks. Because the majority of WHV-positive woodchucks with hepatic tumours were culture or PCR positive for this helicobacter, and WHV-negative woodchucks with H. marmotae had hepatitis, the bacterium may have a role in tumour promotion related to chronic inflammation. In this study, the type strain of H. marmotae was inoculated intraperitoneally into 48 male and female A/J mice, a strain noted to be susceptible to Helicobacter hepaticus-induced liver tumours. Sixteen mice served as mock-dosed controls. At 6, 12 and 18 months post-inoculation (p.i.), there were statistically significant (P<0.05) differences in mean inflammation scores for the caecum and proximal colon between experimentally infected and control mice. Differences in hepatic inflammation were significant (P<0.05) at 6 and 12 months p.i. between the two groups but not at the 18 month time point. Two infected male mice had livers with severe hepatitis, and the liver samples were culture positive for H. marmotae. Serum IgG levels in the mice dosed with H. marmotae were elevated for the duration of the study. These results demonstrate that the woodchuck helicobacter can successfully colonize mice and cause enterohepatic disease. In the future, a mouse-adapted strain of H. marmotae could be selected to maximize colonization and lesion development. Such a woodchuck helicobacter-infected mouse model could be used to dissect potential mechanisms of microbial co-carcinogenesis involved in tumour development in woodchucks with WHV and in humans with hepatitis B virus.
Subject(s)
Disease Models, Animal , Enteritis/veterinary , Helicobacter Infections/veterinary , Helicobacter/pathogenicity , Hepatitis, Animal/pathology , Animals , Antibodies, Bacterial/blood , Enteritis/complications , Enteritis/pathology , Female , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Hepatitis, Animal/complications , Immunoglobulin G/blood , Liver/pathology , Male , Marmota , Mice , Mice, Inbred A , Severity of Illness IndexABSTRACT
A case of acquired skin fragility syndrome associated with hepatic disease in a 9-year-old, spayed female, domestic shorthair cat is described. The cat was admitted to the veterinary hospital of the University of São Paulo (Brazil) with a 6-week history of vomiting, inappetence and weight loss. Remarkable signs were weakness, lethargy and profound jaundice that had been present for 10 days according to the owner. On completion of the physical examination, when the cat was gently manipulated for blood collection the thoracic limb and interscapular skin tore. Liver enzymes and bilirubin levels were all above the normal range. On histological examination of skin and liver, Masson's trichrome stain showed collagen fibre alteration and major hepatocyte abnormalities. Findings were consistent with feline skin fragility syndrome associated with cholangiohepatitis and hepatic lipidosis.
Subject(s)
Cat Diseases/diagnosis , Cholangitis/veterinary , Fatty Liver/veterinary , Hepatitis, Animal/diagnosis , Skin Diseases/veterinary , Animals , Cats , Cholangitis/complications , Cholangitis/diagnosis , Fatal Outcome , Fatty Liver/complications , Fatty Liver/diagnosis , Female , Hepatitis, Animal/complications , Skin Diseases/diagnosis , Skin Diseases/etiology , SyndromeABSTRACT
OBJECTIVE: To describe frequency, types, and clinical outcomes of extrapulmonary disorders (EPDs) in foals in which Rhodococcus equi infection was diagnosed, and to identify factors determined at the time of admission that differentiated foals that developed EPDs from foals with R equi infection identified only in the lungs. DESIGN: Retrospective case series. ANIMALS: 150 foals aged 3 weeks to 6 months with a diagnosis of R equi infection. PROCEDURES: Medical records were reviewed for information on date of admission, signalment, history, clinical signs, diagnostic testing, treatment, duration of hospitalization, invoice, and outcome. For each EPD identified, further information was collected on the identification, location, treatment, and outcome of the lesion. RESULTS: Of 150 foals with R equi infections, 111 (74%) had at least 1 of 39 EPDs. Survival was significantly higher among foals without EPDs (32/39 [82%]) than among foals with EPDs (48/111 [43%]), but many EPDs were only recognized after death. Risk factors significantly associated with EPDs included referral status, duration of clinical signs prior to admission, leukocytosis, and neutrophilia. Foals with EPDs also had a higher heart rate and BUN concentration than foals without. CONCLUSIONS AND CLINICAL RELEVANCE: Practitioners should recognize that extrapulmonary manifestations of R equi occur with high prevalence affecting diverse organ systems, that multiple systems are generally affected when EPDs occur, and that suspicion of R equi infection should prompt evaluation and monitoring of extrapulmonary sites. Improved recognition of the presence of these disorders will help practitioners to better advise their clients in the treatment and outcome of foals with R equi infections.
Subject(s)
Actinomycetales Infections/veterinary , Horse Diseases/microbiology , Rhodococcus equi , Abdominal Abscess/complications , Abdominal Abscess/microbiology , Abdominal Abscess/veterinary , Actinomycetales Infections/complications , Actinomycetales Infections/microbiology , Actinomycetales Infections/mortality , Animals , Central Nervous System Diseases/complications , Central Nervous System Diseases/microbiology , Central Nervous System Diseases/veterinary , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/veterinary , Hematologic Diseases/complications , Hematologic Diseases/microbiology , Hematologic Diseases/veterinary , Hepatitis, Animal/complications , Hepatitis, Animal/microbiology , Horses , Lymphadenitis/complications , Lymphadenitis/microbiology , Lymphadenitis/veterinary , Musculoskeletal Diseases/complications , Musculoskeletal Diseases/microbiology , Musculoskeletal Diseases/veterinary , Peritonitis/complications , Peritonitis/microbiology , Peritonitis/veterinary , Retrospective Studies , Uveitis/complications , Uveitis/microbiology , Uveitis/veterinaryABSTRACT
Chronic inflammation and increased visceral adipose tissue (VAT) are key elements of the metabolic syndrome. Both are considered to play a pathogenic role in the development of liver steatosis and insulin resistance. The aim of the present study was to investigate the hypothesis that an inflamed intestine, induced both by diet and chemical irritation, could induce persistent inflammation in VAT. Female C57BL/6JOlaHsd mice were used. In study I, groups of mice (n = 6 per group) were given an obesity-inducing cafeteria diet (diet-induced obesity) or regular chow only (control) for 14 weeks. In study II, colitis in mice (n = 8) was induced by 3% dextran sulfate sodium in tap water for 5 days followed by 21 days of tap water alone. Healthy control mice (n = 8) had tap water only. At the end of the studies, all mice were killed; and blood and tissues were sampled and processed for analysis. Body weight of diet-induced obese mice was greatly increased, with evidence of systemic inflammation, insulin resistance, and liver steatosis. Tissue inflammation indexed by proinflammatory cytokine expression was recorded in liver, mesenteric fat, and proximal colon/distal ileum, but not in subcutaneous or perigonadal fat. In dextran sulfate sodium-induced colitis mice, mesenteric fat was even more inflamed than the colon, whereas a much milder inflammation was seen in liver and subcutaneous fat. The studies showed both diet- and colitis-initiated inflammation in mesenteric fat. Fat depots contiguous with intestine and their capacity for exaggerated inflammatory responses to conditions of impaired gut barrier function may account for the particularly pathogenic role of VAT in obesity-induced metabolic disorders.
Subject(s)
Gastroenteritis/complications , Hepatitis, Animal/complications , Obesity/complications , Panniculitis, Peritoneal/complications , Animals , Body Weight/physiology , Cytokines/blood , Cytokines/metabolism , Diet, Atherogenic , Female , Gastroenteritis/blood , Gastroenteritis/pathology , Gastroenteritis/veterinary , Hepatitis, Animal/blood , Hepatitis, Animal/pathology , Intestinal Mucosa/metabolism , Intestines/pathology , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/etiology , Obesity/pathology , Obesity/veterinary , Organ Size , Panniculitis, Peritoneal/blood , Panniculitis, Peritoneal/pathology , Panniculitis, Peritoneal/veterinaryABSTRACT
An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was consistent with chronic active hepatitis. The mare was treated with intravenous fluids and antimicrobials, pentoxyfilline, branched-chain amino acids and dietary manipulation. Clinical improvement was observed initially; however, 3 weeks later, deterioration in the mare's condition necessitated euthanasia. Pathological lesions at necropsy were restricted to the liver and brain. The liver was diffusely firm with a prominent reticular pattern on the cut surface. A large choledocholith was present in the main bile duct of the left liver lobe. Histopathological examination of the liver revealed severe fibrosis, with hyperplastic bile ducts and mononuclear and neutrophilic inflammation. Pathological changes consistent with hepatic encephalopathy, (Alzheimer type II cells), were evident in the cerebrum of both the mare and the fetus.
Subject(s)
Hepatic Encephalopathy/veterinary , Horse Diseases/pathology , Pregnancy Complications/veterinary , Animals , Brain/pathology , Diagnosis, Differential , Fatal Outcome , Female , Hepatic Encephalopathy/complications , Hepatic Encephalopathy/pathology , Hepatitis, Animal/complications , Hepatitis, Animal/diagnosis , Hepatitis, Animal/pathology , Horse Diseases/diagnosis , Horses , Liver/pathology , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/pathologyABSTRACT
A new spectrophotometric method for quantitation of acetyl-CoA synthetase (ACAS) activity is developed. It has been applied for ACAS assay in the liver tissues of a woodchuck model of hepatitis virus-induced hepatocellular carcinoma (HCC). The assay is based on the established pyrophosphate (PPi) detection system. ACAS activity is indexed by the amount of PPi, the product of ACAS reaction system of activated form of acetate (acetyl-CoA) with ACAS catalysis. PPi is determined quantitatively as the amount of chromophore formed with molybdate reagent, 1-amino-2-naphthol-4-sulfonic acid in bisulfite and 2-mercaptoethanol. PPi reacts with molybdate reagent to produce phosphomolybdate and PPi-molybdate complexes. 2-mercaptoethanol is responsible for color formation which has the peak absorbance at 580 nm. This method was sensitive from 1 to 20 nmol of PPi in a 380-mul sample (1-cm cuvette). A ten-fold excess of Pi did not interfere with the determination of PPi. To study the major metabolic pathways of imaging tracer [1-(11)C]-acetate in tumors for detection of HCC by Positron Emission Tomography (PET), the activity of one of the key enzymes involved in acetate or [1-(11)C]-acetate metabolism, ACAS was assayed by this newly developed assay in the tissue samples of woodchuck HCCs. A significant increase of ACAS activity was observed in the liver tissues of woodchuck HCCs as compared with neighboring regions surrounding the tumors (P<0.05). The respective ACAS activities in the subcellular locations were also significantly higher in HCCs than in the surrounding tissues (P<0.05) (total soluble fraction: 876.61+/-34.64 vs. 361.62+/-49.97 mU/g tissue; cytoplasmic fraction: 1122.02+/-112.39 vs. 732.32+/-84.44 mU/g tissue; organelle content: 815.79+/-100.77 vs. 547.91+/-97.05 mU/ g tissue; sedimentable fragment: 251.92+/-51.56 vs. 90.94+/-18.98 mU/ g tissue). The finding suggests an increase in ACAS activity in the liver cancer of woodchuck models of HCC as compared to that in the normal woodchuck liver. The developed assay is rapid, simple and accurate and is suitable for the investigation of ACAS activity under physiologic and pathophysiologic conditions.
Subject(s)
Acetate-CoA Ligase/metabolism , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/enzymology , Hepatitis, Animal/complications , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/enzymology , Animals , Carbon Radioisotopes , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/virology , Colorimetry , Disease Models, Animal , Liver Neoplasms/etiology , Liver Neoplasms/virology , Marmota , Positron-Emission TomographyABSTRACT
BACKGROUND/AIMS: Adipose tissue produces a number of adipocytokines, including adiponectin, leptin, and tumor necrosis factor-alpha. Obesity, which is associated with low plasma adiponectin levels, is an independent risk factor for various liver diseases including nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the effects of adiponectin on the progression of NASH to cirrhosis and tumor formation using adiponectin-knockout (KO) mice. METHODS: Using a choline-deficient L-amino acid-defined (CDAA) diet-induced mouse NASH model, liver histology and oxidative stress markers were investigated in KO and wild-type (WT) mice. RESULTS: Hepatic steatosis was enhanced to a greater extent in KO mice, compared to WT mice after a 1-week CDAA diet. After 24 weeks, 6 out of 14 KO mice developed liver cirrhosis and hepatic tumors, whereas the 15 WT mice showed only simple steatosis. In KO mice, hepatic cytochrome P450 2E1 levels were upregulated, and markers of oxidative stress (thiobarbituric acid reactive substances, 8-hydroxydeoxyguanosine-positive cells) were significantly increased compared with WT mice. CONCLUSIONS: Our results indicate that lack of adiponectin enhances the progression of hepatic steatosis, fibrosis, and hepatic tumor formation in an animal model of NASH. Hypoadiponectinemia in obesity could be a risk factor for NASH-related hepatic tumor formation.
Subject(s)
Adiponectin/blood , Fatty Liver/complications , Hepatitis, Animal/complications , Liver Neoplasms/etiology , Adiponectin/genetics , Amino Acids/administration & dosage , Animals , Biomarkers/blood , Choline Deficiency , Cytochrome P-450 CYP2E1/analysis , Cytochrome P-450 CYP2E1/metabolism , Diet , Disease Models, Animal , Disease Progression , Fatty Liver/pathology , Hepatitis, Animal/pathology , Lipogenesis/genetics , Liver/enzymology , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Mice , Mice, KnockoutABSTRACT
The aim of the study was to determine the presence of swine hepatitis E virus (HEV) RNA and antibodies in postweaning multisystemic wasting syndrome-affected (n=114) and non-affected (n=46) pigs and the possible association with hepatitis lesions. Forty-four pigs were RT-PCR positive (28.2%); 25 of them were PMWS cases, while 19 were non-PMWS pigs. In both groups, HEV RT-PCR results were associated with hepatitis (OR=5.61 for PMWS-affected pigs and OR=5.17 for non-PMWS affected pigs; p=0.01). No interaction was detected in a logistic regression between PMWS occurrence and HEV infection for the development of hepatitis lesions. Seropositivity to HEV was more likely to occur in pigs with hepatitis (51.9%) compared to pigs without hepatitis (36.1%; p=0.03). Significant differences in optical densities were notices comparing the lesional stage of pigs (p=0.009). While pigs with slight or moderate hepatitis were seropositive, pigs with more severe lesions were seronegative to HEV. These results indicate that swine HEV infection can be a significant contributor to the development of moderate hepatitis in pigs regardless of the PMWS status.
Subject(s)
Hepatitis E virus/isolation & purification , Hepatitis, Animal/virology , Porcine Postweaning Multisystemic Wasting Syndrome/virology , Animals , Genotype , Hepatitis Antibodies/isolation & purification , Hepatitis E virus/genetics , Hepatitis, Animal/complications , Liver/pathology , Liver/virology , Phylogeny , Porcine Postweaning Multisystemic Wasting Syndrome/complications , RNA, Viral/isolation & purification , SwineABSTRACT
Essential mixed cryoglobulinemia in humans is strongly associated with chronic hepatitis C virus infection. It remains controversial whether liver injury in hepatitis C is primarily attributable to direct viral cytopathic effect or to an immune-mediated response. We characterized the role of cryoglobulinemia in the development of liver disease in thymic stromal lymphopoietin (TSLP) transgenic mice that produce mixed cryoglobulinemia and develop hepatitis. The role of immune complexes in this animal model was evaluated using techniques of light, immunofluorescence, and electron microscopy. To assess the role of Fc receptor engagement in mediation of the disease, TSLP transgenic mice were crossbred with mice deficient for immunoglobulin-binding receptor gamma IIb (FcgammaRIIb). Livers from the TSLP transgenic animals showed mild to moderate liver injury, minimal to mild fibrosis, and deposition of immunoglobulin around the portal tracts. TSLP transgenic mice deficient in inhibitory FcgammaRIIb had more severe hepatitis and accelerated mortality. TSLP-associated hepatitis bears strong similarity to hepatitis C virus-related hepatitis as it occurs in humans, making this a valuable model system of chronic hepatitis and fibrosis to study therapies aimed at manipulating immune responses. Periportal immune complex deposition may play an important role in the pathogenesis of hepatitis occurring in the setting of systemic cryoglobulinemia.