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ABSTRACT: A retrospective study was performed to evaluate the effect of treatment with prednisolone or ursodeoxycholic acid (UDCA) on the survival times of 26 cats with lymphocytic cholangitis, and to determine prognostic factors. Most affected cats were males (76.9%, P=0.006) and a breed predisposition for the Norwegian Forest Cat was demonstrated (P=0.021). Clinical signs included weight loss, icterus, anorexia, vomiting, and listlessness. Blood analyses revealed elevated hepatic enzymes, bile acids and hypergammaglobulinaemia. Breed, sex, and therapeutic regimen were significantly associated with survival times. Prednisolone treatment resulted in a statistically longer survival time compared to UDCA.
The Veterinary Journal 07/2012; · 2.24 Impact Factor
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ABSTRACT: In this study, we have successfully used molecular methods based on the amplification of the 16S ribosomal RNA gene on feline bile samples to show that bile of cats with LC is not sterile. This is probably due to the fact that the inflammatory process in the biliary tree causes dilatations. As a result, bacteria can easily migrate from the intestines via the common bile duct. The diversity of species identified and the presence of Helicobacter spp. DNA in both patients and controls suggests that bacteriobilia is secondary to the disease and is not the cause of LC.
Veterinary Microbiology 11/2011; 156(1-2):217-21. · 3.33 Impact Factor
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ABSTRACT: A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated.
Veterinary Immunology and Immunopathology 08/2011; 144(3-4):346-54. · 2.08 Impact Factor
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ABSTRACT: Feline chronic gingivitis/stomatitis (FCGS) is a painful inflammatory disease in cats. Extraction of teeth, including all premolars and molars, has been shown to be the therapy of choice in cats not responding sufficiently to home care (e.g. tooth brushing) and/or medical treatment (corticosteroids and/or antibiotics). In this study, we hypothesize that a cat food with an omega-6 polyunsaturated fatty acid (ω6 PUFA) to ω3 PUFA ratio of 10:1 reduces inflammation of the FCGS and accelerates soft tissue wound healing of the gingiva after dental extractions, compared to a cat food with a ω6:ω3 PUFA ratio of 40:1. The cats were fed diets with chicken fat and fish oil as sources of fatty acids. In one diet, part of the fish oil was replaced by safflower oil, resulting in two diets with ω6:ω3 PUFA ratios of 10:1 and 40:1. This double-blinded study in two groups of seven cats revealed that dietary fatty acids influence the composition of plasma cholesteryl esters and plasma levels of inflammatory cytokines. The diet with the 10:1 ratio lowered PGD(2) , PGE(2) and LTB(4) plasma levels significantly, compared to the diet with the 40:1 ratio (p = 0.05, p = 0.04, and p = 0.02 respectively). However, feeding diets with dietary ω6:ω3 PUFA ratios of 10:1 and 40:1, given to cats with FCGS for 4 weeks after extraction of all premolars and molars, did not alter the degree of inflammation or wound healing.
J Anim Physiol a Anim Nutr 07/2011; 96(4):671-80. · 0.86 Impact Factor
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ABSTRACT: Inflammation of the bile ducts is common in cats. This review article reports on what is currently known about the various types of cholangitis (i.e., cholangitis caused by liver flukes, neutrophilic cholangitis, and lymphocytic cholangitis). Treatment is available for cholangitis caused by liver flukes and for neutrophilic cholangitis, and the prognosis is good. However, the cause of lymphocytic cholangitis is not known and there is currently no evidence-based therapy. Several causes are mentioned in the literature, but more research is needed in order to establish the cause of this disease and to develop an appropriate therapy.
Tijdschrift voor diergeneeskunde 05/2011; 136(5):332-8. · 0.19 Impact Factor
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ABSTRACT: Both vitamin D and inflammatory cytokines can stimulate osteoclast formation and activity. We studied the effect of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D), and interleukin-6 (IL-6), on the formation and activity of feline osteoclasts, using peripheral blood mononuclear cells (PBMCs) from cats with and without tooth resorption (TR(+) and TR(-)) as a source of osteoclast precursors. The formation of osteoclast-like cells (defined as multinucleated, tartrate-resistant acid phosphatase-positive cells) was assessed at 7 and 14 days. In the presence of M-CSF and RANKL, with and without IL-6, more osteoclasts were formed from TR(-) PBMCs than from TR(+) PBMCs on plastic. More osteoclasts were formed from TR(+) PBMCs on bone slices in the presence of M-CSF/RANKL with 1,25(OH)(2)D. This opposite effect may be due to a higher expression of the vitamin D receptor (VDR) in TR(+) osteoclasts and precursors on bone. Formation of resorption pits was analyzed and confirmed with scanning electron microscopy. In conclusion, we propose that TR(+) PBMCs when cultured on bone are sensitive to 1,25(OH)(2)D, whereas the differentiation of TR(-) PMBCs on bone seem more sensitive to IL-6, suggesting that osteoclast precursors from cats with and without tooth resorption respond differently to osteoclast stimulating factors.
Research in Veterinary Science 04/2011; 92(2):311-6. · 1.65 Impact Factor
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ABSTRACT: Chronic inflammatory liver disease regardless of aetiology leads to failing regeneration and fibrosis, ending in cirrhosis. Both in man and in animals this worldwide health problem has no definitive cure. Chronic liver injury causes hepatic stellate cells to proliferate and differentiate into matrix-producing cells. New therapeutic options will be developed upon detailed understanding of the molecular mechanisms driving liver fibrosis. This may lead to new anti-fibrotic therapies which need to be tested in suitable models before application in the veterinary and human clinic. On the other side, to restore the failing regenerative capacity of the diseased liver cells, adult progenitor cells are of interest, as an alternative to whole organ transplantation. In order to find the most suitable large animal model it is important to recognise that the typical histopathological reaction pattern of the liver can differ between mammalian species. It is therefore imperative that specialists in veterinary internal medicine and pathology, being familiar with the diseases and pathologies of the liver in different animal species, are teaming-up in finding the best models for veterinary and human liver diseases. Several large animal models have been mentioned, like pigs, sheep, and dogs. Based on the observations that man and dog share the same hepatopathies and have identical clinical, pathological and pathogenetic reaction patterns during the development of liver disease, the dog seems to be a properly suited species to test new therapeutic strategies for pets and their best friends.
The Veterinary quarterly. 03/2011; 31(1):49-60.
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ABSTRACT: Disparities in longitudinal growth within a species can be partly explained by endocrinological differences. We hypothesized that regulatory networks acting locally in the growth plate may also be important. We tested this hypothesis by evaluating the IGF/IGFBP expression, the vitamin D pathway, and the PTHrP-Indian hedgehog (IHH) feedback loop in rib growth plates from 10- and 21-wk-old small- (Miniature Poodles, MP) and large-breed dogs (Great Danes, GD) using immunohistochemistry and quantitative (q)PCR. The rib growth plates of GD were 1.7 times thicker compared with those of MP, with larger proliferative (in absolute terms) and larger hypertrophic (in absolute and relative terms) zones. IGF/IGFBP gene expression profiling of the growth plates revealed decreased gene expression of igfbp2, -4, and -6 and an unaltered expression of igf-I and igf-II and their respective receptors in GD vs. MP. Immunohistochemistry and qPCR findings showed that the vitamin D pathway was more active in GD than in MP. Staining for 1α- and 24-hydroxylase was more abundant and intense in GD and the gene expressions of 1α-hydroxylase and the vitamin D receptor-driven 24-hydroxylase were six- and eightfold higher in GD vs. MP, respectively. Consistent with the immunohistochemistry findings, the expression of mRNA for components of the parathyroid hormone-related peptide (PTHrP)-IHH loop was different in GD compared with MP, with there being a relative threefold downregulation of Pthrp and a tenfold upregulation of Ihh in GD vs MP. These differences suggest that the effects of IHH in the regulation of chondrocyte proliferation and hypertrophy, both independently of PTHrP, can become more dominant during rapid growth rates. In conclusion, our data suggest that, in addition to modest endocrine differences, more pronounced changes in the expression of locally acting regulatory networks, such as the IGF system, vitamin D pathway, and PTHrP-IHH feedback loop are important contributors to within-species disparities in growth rates.
AJP Endocrinology and Metabolism 12/2010; 299(6):E1044-52. · 4.75 Impact Factor
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ABSTRACT: The periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia are strongly associated with periodontal disease and are highly prevalent in humans with periodontitis. Porphyromonas and Tannerella spp. have also been isolated from the oral cavity of cats. The oral microflora in animals was compared with those in humans in earlier studies, but no studies are available on the comparison of the oral microflora from pets and their respective owners. The aim of this study was to determine the presence of these bacteria in the oral microflora of cats and their owners, since animal to human transmission, or vice versa, of oral pathogens could have public health implications. This study investigated the prevalence of Porphyromonas gulae, P. gingivalis, and T. forsythia in the oral microflora of cats and their owners, using culture and polymerase chain reaction (PCR). All Porphyromonas isolates from cats (n=64) were catalase positive, whereas the Porphyromonas isolates from owners (n=7) were catalase negative, suggesting that the isolates from cats were P. gulae whereas those from the owners were P. gingivalis. T. forsythia was recovered from both cats (n=63) and owners (n=31); the proportion of T. forsythia relative to the total CFU was higher in cats with periodontitis than in cats without periodontal disease. Genotyping of T. forsythia isolates (n=54) in six cat/owner couples showed that in one cat/owner couple the T. forsythia isolates (n=6) were identical. These T. forsythia isolates were all catalase positive, which led us to hypothesize that transmission from cats to owners had occurred and that cats may be a reservoir of T. forsythia.
Veterinary Microbiology 02/2010; 144(1-2):147-52. · 3.33 Impact Factor
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ABSTRACT: Pituitary-dependent hypercortisolism (PDH), which is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, is a common endocrinopathy in dogs. Dogs with non-enlarged pituitaries harboring a microadenoma have a better prognosis than those with enlarged pituitaries. The aim of this study was to investigate the expression of the proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) and the cell-cycle inhibitor p27kip1 in corticotroph adenomas in enlarged and non-enlarged pituitaries. The expression of Ki-67, PCNA, and p27kip1 was analyzed by immunohistochemical staining of 17 pituitary adenoma samples harvested during pituitary surgery in dogs with PDH. The labeling index was calculated by counting the number of immunopositive cells per 1,000 cells. The mean (+/- standard deviation) labeling index for Ki-67 was 8.4%+/-14.2% for the group with enlarged pituitaries, and 8.8%+/-5.5% for the group with non-enlarged pituitaries; that for PCNA was 35.5%+/-12.2% and 37.0%+/-15.5%; and that for p27kip1 was 29.3%+/-22.6% and 42.5%+/-27.9%, respectively. No significant differences in Ki-67, PCNA, and p27kip1 labeling indices were found between enlarged and non-enlarged pituitaries. However, a trend toward significance was observed when comparing the expression of p27kip1 in enlarged pituitaries versus normal pituitary tissue. It is concluded that Ki-67 and PCNA are not useful as proliferative markers for studying the pathobiology of pituitary corticotroph adenomas in dogs.
Domestic animal endocrinology 12/2009; 38(4):244-52. · 1.65 Impact Factor
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ABSTRACT: The liver progenitor cell compartment in the normal canine liver and in spontaneous canine acute (AH) and chronic hepatitis (CH) was morphologically characterised and compared to its human equivalents. Immunohistochemistry was performed for cytokeratin-7 (CK7), human hepatocyte marker (Hep Par 1), multidrug resistance-associated protein-2 (MRP2), and breast cancer resistance protein (BCRP) on paraffin and frozen sections from canine and human tissues. Normal liver showed similar morphology and immunohistochemical reaction of the progenitor cell compartment/canal of Hering in man and dog. In addition, a ductular reaction, comparable in terms of severity, location and immunohistochemical characteristics, was observed in canine and human AH and CH. CK7 was a good marker for canine progenitor cells, including intermediate cells, which were positively identified in cases of AH and CH. In both species, BCRP was expressed in both hepatocytes and bile ducts of the normal liver, and in ductular reaction in AH and CH. MRP2 detected bile canalicular membranes in man and dog. These findings underline the similarities between canine and human liver reaction patterns and may offer mutual advantage for comparative research in human and canine spontaneous liver diseases.
The Veterinary Journal 05/2009; 184(3):308-14. · 2.24 Impact Factor
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ABSTRACT: A deletion in the copper metabolism (Murr1) domain containing 1 (COMMD1) gene is associated with hepatic copper toxicosis in dogs, yet evidence of copper retention in COMMD1-depleted hepatic cells has not been shown. In a dog hepatic cell line, we analysed the copper metabolic functions after an 80% (mRNA and protein) COMMD1 reduction with COMMD1-targeting siRNAs. Exposure to 64Cu resulted in a significant increase in copper retention in COMMD1-depleted cells. COMMD1-depleted cells were almost three times more sensitive to high extracellular copper concentrations. Copper-mediated regulation of metallothionein gene expression was enhanced in COMMD1-depleted cells. Based on the increased copper accumulation and enhanced cellular copper responses upon COMMD1 reduction, we conclude that COMMD1 has a major regulatory function for intracellular copper levels in hepatic cells.
Animal Genetics 05/2007; 38(2):168-70. · 2.40 Impact Factor
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ABSTRACT: The causes of hepatitis in dogs are mostly unknown. Known causes of canine hepatitis are infectious (CAV-1), toxic (e.g. aflatoxin), and metabolic (copper accumulation). In order to understand the unknown causes, research in this field is necessary. Despite the marked progress in the knowledge on viral causes for human hepatitis, the involvement of infectious agents in the pathogenesis of hepatitis in the dog is still largely unknown. It is, like in human hepatitis, very likely that more than one causative infectious agent may cause hepatitis in the dog. This review presents the various forms of hepatitis in the dog, the known infectious and non-infectious causes of canine hepatitis, the infectious causes of hepatitis in man and other animals, and finally our recent infection and molecular studies to investigate possible infectious causes of canine hepatitis.
The Veterinary quarterly 10/2004; 26(3):107-14. · 1.47 Impact Factor
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ABSTRACT: Chronic hepatitis in Doberman pinschers is predominantly seen in female dogs, usually between 4 and 7 years of age and was first recognized in the early eighties. The histopathological characteristics of Doberman hepatitis are those of micronodular cirrhosis with histological features of fibrosis, piece meal necrosis and progressive lymphocyte and plasma cell infiltration of the portal triads. Currently there are two hypotheses on the pathogenesis although neither of them has been elucidated. The first hypothesis is that of a copper toxicosis. The second is that of autoimmunity. Similarities and differences with other breeds and studies on both hypotheses are reviewed, as well as results of recent research of our group. Based on recent findings chronic hepatitis in Doberman pinschers is most likely to be a form of copper toxicosis. Although there are several indications that suggest autoimmunity as well, this still remains unclear.
The Veterinary quarterly 10/2004; 26(3):98-106. · 1.47 Impact Factor
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ABSTRACT: The periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia are strongly associated with periodontal disease and are highly prevalent in humans with periodontitis.Porphyromonas and Tannerella spp. have also been isolated from the oral cavity of cats. The oral microflora in animals was compared with those in humans in earlier studies, but no studies are available on the comparison of the oral microflora from pets and their respective owners. The aim of this study was to determine the presence of these bacteria in the oral microflora of cats and their owners, since animal to human transmission, or vice versa, of oral pathogens could have public health implications.This study investigated the prevalence of Porphyromonas gulae, P. gingivalis, and T. forsythia in the oral microflora of cats and their owners, using culture and polymerase chain reaction (PCR). All Porphyromonas isolates from cats (n = 64) were catalase positive, whereas the Porphyromonas isolates from owners (n = 7) were catalase negative, suggesting that the isolates from cats were P. gulae whereas those from the owners were P. gingivalis. T. forsythia was recovered from both cats (n = 63) and owners (n = 31); the proportion of T. forsythia relative to the total CFU was higher in cats with periodontitis than in cats without periodontal disease. Genotyping of T. forsythia isolates (n = 54) in six cat/owner couples showed that in one cat/owner couple the T. forsythia isolates (n = 6) were identical. These T. forsythia isolates were all catalase positive, which led us to hypothesize that transmission from cats to owners had occurred and that cats may be a reservoir of T. forsythia.
Veterinary Microbiology.
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ABSTRACT: Background: To minimize the necessary number of biopsies for molecular and histological research we evaluated different sampling techniques, fixation methods, and storage procedures for canine liver tissue. For addressing the aim, three biopsy techniques (wedge biopsy, Menghini, Truecut), four storage methods for retrieval of RNA (snap freezing, RNAlater, Boonfix, RLT-buffer), two RNA isolation procedures (Trizol and RNAeasy), and three different fixation protocols for histological studies (10% buffered formalin, RNAlater, Boonfix) were compared. Histological evaluation was based on hematoxylin-eosin (HE) and reticulin (fibrogenesis) staining, and rubeanic acid and rhodanine stains for copper. Immunohistochemical evaluation was performed for cytokeratin-7 (K-7), multidrug resistance binding protein-2 (MRP-2) and Hepar-1. Results: RNA quality was best guaranteed by the combination of a Menghini biopsy with NaCl, followed by RNAlater preservation and RNAeasy mini kit extraction. These results were confirmed by quantitative RT-PCR testing. Reliable histological assessment for copper proved only possible in formalin fixed liver tissue. Short formalin fixation (1–4 hrs) improved immunohistochemical reactivity and preservation of good morphology in small liver biopsies. Conclusion: At least two biopsies (RNAlater and formalin) are needed. Since human and canine liver diseases are highly comparable, it is conceivable that the protocols described here can be easily translated into the human biomedical field.
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ABSTRACT: Background: When hepatocyte replication during liver disease is insufficient for regeneration, liver progenitor cells (LPCs) are activated. The cells and stroma in the immediate environment of LPCs, together termed the LPC niche, are thought to play an important role in this activation. Among these cells are the hepatic stellate cells (HSCs)/myofibroblasts (MFs). Aims/ Methods: We assessed the activation of HSC/MFs and LPCs in relation to the histological location and extent of liver disease in immunohistochemically (double) stained serial sections. Markers of HSC/MFs [a-smooth muscle actin, glial fibrillary acidic protein (GFAP), neurotrophin 3 and neural-cell adhesion molecule], markers of LPCs (keratin 7 and keratin 19) and a proliferation marker (Ki67) were used. A very relevant spontaneous model to evaluate LPC niche activation in a translational approach seems to be the dog. Therefore, both human and canine liver diseases with different degree of fibrosis and disease activity were included. Results: In human and canine liver disease, type and extent of LPC niche activation depended on type and severity of disease (Po0.05) and corresponded to the main location of disease. Activated HSCs surrounded the activated LPCs. In chronic hepatitis and nonalcoholic steatohepatitis lobular-type HSCs were activated, while during biliary disease portal/septal MFs were mainly activated. In canine liver, GFAP further presented as an early marker of HSC activation. Activation of the LPCs correlated with disease location and severity (Po0.01), and was inversely related to hepatocyte proliferation, as was previously shown in man. Conclusion: A shared involvement of HSC/MFs, LPCs and disease severity during hepatic disease processes is shown, which is highly similar in man and dog.
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