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      Hepatic and Plasma Endothelin‐1 in Dogs with Chronic Hepatitis

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          Abstract

          Background

          Endothelin (ET)‐1 is a 21‐amino‐acid peptide with potent vasoactive properties, which increases intrahepatic resistance in patients with chronic hepatitis (CH) or cirrhosis. ET‐1 concentrations have not been investigated in dogs with CH.

          Hypothesis/Objectives

          This study compared hepatic and plasma ET‐1 levels in healthy dogs and in dogs with CH, and examined the relationship between the plasma ET‐1 level and portal vein pressure in dogs with CH.

          Animals

          Fourteen healthy dogs and twenty dogs with CH were used in this study.

          Methods

          Prospective case‐control study. Hepatic ET‐1 mRNA expression was determined by real‐time reverse transcription polymerase chain reaction, and hepatic and plasma ET‐1 levels were assessed using ELISA. Splenic pulp pressure (SPP), as an indicator of portal vein pressure, was measured laparoscopically.

          Results

          Hepatic ET‐1 mRNA levels were 3.7 times higher in dogs with CH than in healthy dogs ( P = .008). The median hepatic and plasma ET‐1 protein levels were significantly higher in dogs with CH than in healthy dogs (13.20 pg/mg wet liver vs. 3.42 pg/mg wet liver, P = .004, and 0.99 pg/mL vs. 0.71 pg/mL, P = .013, respectively). Moreover, there was a weak but significant correlation between plasma ET‐1 level and SPP in dogs with CH ( P = .036; r s = 0.53).

          Conclusions and clinical importance

          The results indicate that ET‐1 might play an important role in the pathogenesis of portal hypertension caused by CH.

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          Most cited references34

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          Development and evaluation of canine reference genes for accurate quantification of gene expression.

          In determining relative gene expression by quantitative measurements of mRNA levels using real-time quantitative PCR, internal standards such as reference genes are essential. Large-scale studies evaluating (candidate) reference genes for veterinary research have not been conducted as thoroughly as for human research, although they are equally important. Our goal was to design and evaluate a genome-wide panel of reference genes from different functional classes. First, primers were optimized using mRNA from canine cell lines and from 30 tissues of one dog as template and SYBR green as fluorescent probe. Second, the expression variation and stability of a gene within one specific tissue were determined. Prostate, kidney, mammary gland, left ventricle, and liver tissues from five to nine dogs of different breeds, sexes, ages, body weights, and disease status were used. Averaging relative stabilities over these tissues revealed the usefulness of individual genes as reference genes. Furthermore, according to expression variation of a reference gene within a specific tissue, usually two to four reference genes are sufficient. Taken together, ribosomal protein S19 (RPS19), ribosomal protein S5 (RPS5), beta-2-microglobulin (B2M), and hypoxanthine phosphoribosyltransferase (HPRT) are advocated. However, the optimal set of reference genes depends on the tissue and should be selected and evaluated for each series of experiments.
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            Clearance of circulating endothelin-1 by ETB receptors in rats.

            Exogenous endothelin (ET) is rapidly cleared from the circulation. We investigated which ET receptor subtypes (ETA and ETB) participate in ET-1 clearance. Following an intravenous (i.v.) bolus dose of [125I]ET-1 in anesthetized rats, radioactivity was rapidly cleared from the circulation and trapped by the lungs, kidneys and liver. Tissue distribution of the radioactivity was significantly inhibited in the lungs and kidneys, but not in the liver by infusion of the ETB antagonist BQ-788 (0.1 mg/kg/min i.v.), and the ET-1 clearance rate was reduced, while the ETA antagonist BQ-123 had no such effect. Furthermore, in isolated perfused rat lungs, about 80% of bolus-injected [125I]ET-1 was retained by the lungs after one passage. The retention of ET-1 was significantly inhibited by infusion of 1 microM BQ-788, but not BQ-123. These results suggest that ETB receptors play an important role in the clearance of ET-1.
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              Primary hepatitis in dogs: a retrospective review (2002-2006).

              Little is known about etiology, disease progression, treatment outcome, survival time, and factors affecting prognosis in dogs with primary hepatitis (PH). To review retrospectively different forms of hepatitis in a referral population, by the World Small Animal Veterinary Association Standardization criteria. One-hundred and one dogs examined for histologically confirmed PH between 2002 and 2006. Dogs with nonspecific reactive hepatitis were excluded. Retrospective study. Medical records were reviewed for prevalence, signalment, clinical and clinicopathologic manifestation, outcome, survival time, and prognostic factors for shortened survival. PH occurred in 0.5% of dogs in this referral population. Acute (AH) and chronic hepatitis (CH) were diagnosed in 21 and 67 dogs, respectively. Progression from AH to CH occurred in 5/12 of the repeatedly sampled dogs. CH was idiopathic in 43 (64%) dogs, and was associated with copper accumulation in 24 (36%) dogs. Median survival time was longer in dogs with AH than in dogs with CH (either idiopathic or copper associated), and dogs with lobular dissecting hepatitis had the shortest survival time. Prognostic factors predicting shortened survival were associated with decompensated liver function and cirrhosis at initial examination. The majority of PH in dogs is CH. Previous studies appear to have underestimated the etiologic role of copper in both AH and CH. Prognosis is reduced in dogs with hepatic cirrhosis or cirrhosis-related clinical findings. Further research into etiology and treatment effectiveness in all PH forms is needed.
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                Author and article information

                Contributors
                sakai.manabu@nihon-u.ac.jp
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0891-6640
                1939-1676
                14 March 2017
                May-Jun 2017
                : 31
                : 3 ( doiID: 10.1111/jvim.2017.31.issue-3 )
                : 764-769
                Affiliations
                [ 1 ] Department of Veterinary Medicine College of Bioresource SciencesNihon University Fujisawa KanagawaJapan
                Author notes
                [*] [* ]Corresponding author: M. Sakai, Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252‐0880, Japan; e‐mail: sakai.manabu@ 123456nihon-u.ac.jp
                Author information
                http://orcid.org/0000-0002-6446-1629
                Article
                JVIM14687
                10.1111/jvim.14687
                5435058
                28295621
                7a3ccb41-5d2e-4692-bf7e-ac10cd05d49c
                Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 August 2016
                : 11 January 2017
                : 09 February 2017
                Page count
                Figures: 4, Tables: 1, Pages: 6, Words: 4840
                Funding
                Funded by: Japanese Society for the Promotion of Science (JSPS)
                Funded by: Grant‐in‐Aid for Young Scientists B
                Award ID: 20780228
                Funded by: Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan
                Categories
                Standard Article
                SMALL ANIMAL
                Standard Articles
                Hepatology
                Custom metadata
                2.0
                jvim14687
                May/June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:17.05.2017

                Veterinary medicine
                canine,chronic liver disease,portal hypertension,vasoactive peptide
                Veterinary medicine
                canine, chronic liver disease, portal hypertension, vasoactive peptide

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