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      Narrative review of therapies for chronic enteropathies in dogs and cats

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          Abstract

          Background

          The optimal medical treatment for chronic enteropathy (CE) in dogs and cats is controversial. Sequential treatment using diet, antimicrobials, and immunosuppressive drugs is the most common strategy used by clinicians.

          Objectives

          To review the evidence for the effectiveness of dietary, drug, and alternative health interventions for inducing clinical remission in dogs and cats with CE.

          Animals

          Retrospective study of dogs and cats with a diagnosis of chronic enteropathy.

          Methods

          MEDLINE and Centre for Agriculture and Bioscience International (CABI) databases (1950 to March 2017) were searched for randomized controlled trials (RCTs), observational studies, and case series. The primary outcome was induction of clinical remission. All studies were evaluated using the quality of evidence grading guidelines (I‐IV), which assign a score defining the strength and quality of the evidence.

          Results

          Twenty‐two studies (11 RCTs in dogs and 2 in cats and 9 cohort studies or case series) met the inclusion criteria for inducing remission of gastrointestinal (GI) signs. Of the 13 RCTs achieving grade I scores, 10 studies (totaling 218 dogs and 65 cats) compared single treatment: diet (n = 3), immunosuppressives (n = 3), antimicrobials (n = 2), anti‐inflammatory drugs (n = 1), and probiotics (n = 1). Three case series (grade III) reported clinical remission using an elimination diet fed to 55 cats and use of enrofloxacin to induce remission in dogs with granulomatous colitis (2 studies totaling 16 dogs).

          Conclusions and Clinical Importance

          The current evidence for treatment of CE is much greater in dogs than in cats. There is sufficient strong evidence to recommend the use of therapeutic GI diets, glucocorticoids, enrofloxacin, or some combination of these in dogs with CE. Therapeutic GI diets and glucocorticoids are most useful in cats with CE.

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          Most cited references60

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          Isolation and in vitro expansion of human colonic stem cells.

          Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic cells with the longest telomeres and elevated expression of intestinal stem cell (ISC) marker genes. Moreover, using culturing conditions that recreate the ISC niche, a substantial proportion of EPHB2-high cells can be expanded in vitro as an undifferentiated and multipotent population.
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            Chronic enteropathies in dogs: evaluation of risk factors for negative outcome.

            Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be applied to predict outcome of disease. Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group) followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroid-treatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that were treated with immunosuppressive doses of steroids. Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves. Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (<200 ng/L) and hypoalbuminemia (<20 g/L) as risk factors for negative outcome. Based on the factors identified by logistic regression and ROC curve analysis, a new clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.
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              Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis.

              Changes in epithelial tight junction protein expression and apoptosis increase epithelial permeability in inflammatory bowel diseases. The effect of the probiotic mixture VSL#3 on the epithelial barrier was studied in dextran sodium sulfate (DSS)-induced colitis in mice. Acute colitis was induced in BALB/c mice (3.5% DSS for 7 days). Mice were treated with either 15 mg VSL#3 or placebo via gastric tube once daily during induction of colitis. Inflammation was assessed by clinical and histological scores. Colonic permeability to Evans blue was measured in vivo. Tight junction protein expression and epithelial apoptotic ratio were studied by immunofluorescence and Western blot. VSL#3 treatment reduced inflammation (histological colitis scores: healthy control 0.94 +/- 0.28, DSS + placebo 14.64 +/- 2.55, DSS + VSL#3 8.43 +/- 1.82; P = 0.011). A pronounced increase in epithelial permeability in acute colitis was completely prevented by VSL#3 therapy [healthy control 0.4 +/- 0.07 (extinction/g), DSS + placebo 5.75 +/- 1.67, DSS + VSL#3 0.26 +/- 0.08; P = 0.003]. In acute colitis, decreased expression and redistribution of the tight junction proteins occludin, zonula occludens-1, and claudin-1, -3, -4, and -5 were observed, whereas VSL#3 therapy prevented these changes. VSL#3 completely prevented the increase of epithelial apoptotic ratio in acute colitis [healthy control 1.58 +/- 0.01 (apoptotic cells/1,000 epithelial cells), DSS + placebo 13.33 +/- 1.29, DSS + VSL#3 1.72 +/- 0.1; P = 0.012]. Probiotic therapy protects the epithelial barrier in acute colitis by preventing 1) decreased tight junction protein expression and 2) increased apoptotic ratio.
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                Author and article information

                Contributors
                ajergens@iastate.edu
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                0891-6640
                1939-1676
                06 December 2018
                Jan-Feb 2019
                : 33
                : 1 ( doiID: 10.1111/jvim.2019.33.issue-1 )
                : 11-22
                Affiliations
                [ 1 ] Department of Veterinary Clinical Sciences College of Veterinary Medicine, Iowa State University Ames Iowa
                [ 2 ] Department of Veterinary Diagnostic and Production Animal Medicine College of Veterinary Medicine, Iowa State University Ames Iowa
                Author notes
                [*] [* ] Correspondence

                Albert E. Jergens, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

                Email: ajergens@ 123456iastate.edu

                Author information
                https://orcid.org/0000-0001-7878-2370
                https://orcid.org/0000-0003-2375-8685
                Article
                JVIM15345
                10.1111/jvim.15345
                6335544
                30523666
                e7569052-710f-45c7-8cc8-a7cc698b5cb3
                © 2018 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 http://creativecommons.org/licenses/by-nc/4.0/ 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
                : 23 December 2017
                : 05 October 2018
                Page count
                Figures: 2, Tables: 6, Pages: 12, Words: 10191
                Categories
                Review
                Small Animal
                Review
                Gastroenterology
                Custom metadata
                2.0
                jvim15345
                January/February 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.4 mode:remove_FC converted:17.01.2019

                Veterinary medicine
                antibiotics,cyclosporine,diet,drug treatment,immunosuppressives,inflammatory bowel disease,prednisone,quality of evidence guidelines,randomized controlled trial

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