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      Histochemical and Immunohistochemical Characterizations of Hepatic Trematodiasis in Odontocetes

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          Abstract

          Hepatic trematodiasis is a common condition in a number of free-ranging cetacean species, which occasionally result in severe hepatic and/or pancreatic lesions. However, even the basic pathological information of this disease is unknown for the majority of affected species. The current study describes and compares the histomorphology and immune reaction induced by hepatic trematodes of the family Brachycladiidae in the liver of the harbor porpoise ( Phocoena phocoena, n = 8), Dall's porpoise ( Phocoenoides dalli, n = 8), and Hubbs' beaked whale ( Mesoplodon carlhubbsi, n = 2). Immunohistochemistry for eight antibodies (CK19, CD3, Foxp3, CD20, Iba1, CD68, CD163, and CD204) was conducted to analyze the pathology of these parasitic infections. In all three odontocete species, the changes observed in the trematode-affected biliary epithelium were comparable with marked hyperplasia and goblet cell metaplasia, as well as lymphoplasmacytic and eosinophilic inflammation. Additionally, regions of the Glisson's sheath were diffusely and severely fibrotic in all examined species, regardless of the physical presence of trematodes. Differences among the three species included the presence of characteristic lymphoid follicles formed in the fibrotic bile duct walls of only the two porpoise species. In the Hubbs' beaked whale, the degree of lymphoplasmacytic cholangitis was more severe, and ductular reaction was generally more prominent. In terms of the overall macrophage population among the three species, CD163- and CD204-positive cells (M2 macrophages) outnumbered Iba1- and CD68-positive cells (M1 macrophages), indicating a chronic infection stage in all analyzed individuals. Species-specific differences among the infiltrating macrophages included numbers of CD68-positive cells being significantly more abundant in the harbor porpoises, whereas CD163-positive cells were significantly more numerous in the Dall's porpoises. The numbers of CD204-positive macrophages were higher in the Hubbs' beaked whales compared to those in the porpoises. Trematode species of the harbor and Dall's porpoises were Campula oblonga, while they were Oschmarinella macrorchis in the Hubbs' beaked whales. This study concludes that interspecies differences in the tissue reactions to hepatic trematode infections are present among odontocete species and that the immune reaction varies depending on the species. This information aids in furthering our understanding of the pathogenesis of hepatic trematodiasis in cetaceans.

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          Most cited references51

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          Liver fibrosis.

          Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
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            Liver fibrosis – from bench to bedside

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              Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat.

              Hepatic morphological abnormalities were examined in rats whose bile ducts had been either cannulated and then obstructed or irreversibly ligated for 5, 10, 15 and 28 days or longer. Throughout the experiment most of the morphological changes observed in the cannulated group were comparable to those in the ligated group. Portal inflammation and marginal bile duct proliferation were noted with the same frequency in both groups. Biliary obstruction for 15 days or more led to cirrhosis. After 28 days obstruction, five out of six cannulated rats and four out of six ligated animals respectively developed cirrhosis. The development of cirrhosis was progressive and associated with ascites. It is concluded that in the rat the morphological sequelae of long term cholestasis induced by either cannulation and obstruction or ligation of bile ducts are similar and are accompanied by cirrhosis. The advantages of this experimental model for the study of human cirrhosis are discussed.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                30 June 2020
                2020
                : 7
                : 336
                Affiliations
                [1] 1Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine , Obihiro, Japan
                [2] 2United Graduate School of Veterinary Sciences, Gifu University , Gifu, Japan
                Author notes

                Edited by: Stephen Raverty, Animal Health Centre, British Columbia Ministry of Agriculture, Canada

                Reviewed by: Francisco José Pallarés, University of Murcia, Spain; Ettore Napoli, University of Messina, Italy; Takeshi Izawa, Osaka Prefecture University, Japan

                *Correspondence: Shotaro Nakagun snakagun@ 123456gmail.com

                This article was submitted to Veterinary Experimental and Diagnostic Pathology, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2020.00336
                7344244
                32714946
                8a8d3792-329e-4a43-b9e4-7530c40b81b3
                Copyright © 2020 Nakagun and Kobayashi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 March 2020
                : 14 May 2020
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 54, Pages: 13, Words: 8089
                Funding
                Funded by: Japan Society for the Promotion of Science 10.13039/501100001691
                Categories
                Veterinary Science
                Original Research

                cetacean,liver,fluke,pathology,parasite,macrophage,campula oblonga,oschmarinella macrorchis

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