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      Efficacy of leflunomide for treatment of refractory inflammatory colorectal polyps in 15 Miniature Dachshunds

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          Abstract

          Inflammatory colorectal polyp (ICRP), common in miniature dachshunds, presents with hematochezia, tenesmus and mucoid feces. Although an 80% response rate has been reported when treated with prednisolone and cyclosporine, effective treatment is needed for the remaining 20% of ICRP dogs. Leflunomide is an immunosuppressive drug reported as effective in several immune-mediated diseases. In the present study, we retrospectively evaluated the efficacy and adverse effects of leflunomide in 15 ICRP dogs that were refractory to treatment with prednisolone and cyclosporine. Treatment efficacy was assessed by endoscopy, clinical symptoms and rectal palpation. Adverse effects were determined by clinical symptoms and blood testing during follow-up. The leflunomide treatment response rate was 93.3%. The median dosage of leflunomide and the median response time were 3 mg/kg (range: 1.7–4.0 mg/kg) and 35 days (range: 20–119 days), respectively. Adverse effects observed included lethargy (3 dogs), anorexia (1 dog), respiratory symptoms (1 dog), leukocytopenia (2 dogs), thrombocytopenia (1 dog), anemia (1 dog) and liver enzyme elevation (8 dogs). Most of the adverse effects improved with symptomatic treatment and leflunomide discontinuation or dosage reduction. In conclusion, leflunomide treatment is effective in ICRP dogs refractory to treatment with prednisolone and cyclosporine. Because several adverse effects were observed, close monitoring is needed during leflunomide treatment follow-up.

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          Increased expression of interleukin 17 in inflammatory bowel disease.

          Interleukin (IL) 17 is a cytokine which exerts strong proinflammatory activities. In this study we evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of patients with inflammatory bowel disease (IBD). Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n=20), Crohn's disease (CD) (n=20), infectious colitis (n=5), ischaemic colitis (n=8), and normal colorectal tissues (n=15). IL-17 expression was evaluated by a standard immunohistochemical procedure. Serum IL-17 levels were determined by ELISA. IL-17 mRNA expression was analysed by reverse transcriptase-polymerase chain reaction. IL-17 expression was not detected in samples from normal colonic mucosa, infectious colitis, or ischaemic colitis. In the inflamed mucosa of active UC and CD patients, IL-17 expression was clearly detectable in CD3(+) T cells or CD68(+) monocytes/macrophages. The average number of IL-17(+) cells was significantly increased in active UC and CD patients compared with inactive patients. IL-17 mRNA expression was not detected in normal mucosa but was detectable in the mucosa from active UC and CD patients. IL-17 was not detected in the sera from normal individuals, infectious colitis, or ischaemic colitis patients but IL-17 levels were significantly elevated in IBD patients. IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.
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            A retrospective study of inflammatory colorectal polyps in miniature dachshunds.

            Medical records of dogs with colorectal polyps were retrospectively reviewed, and clinical presentation of inflammatory colorectal polyps in miniature dachshunds was evaluated. Of 33 dogs found to have colorectal polyps, miniature dachshunds were markedly over-represented with 16 dogs (48%), of which 12 (75%) were found to have inflammatory polyps. Multiple polyps localized between the rectum and the descending colon was the most common finding in miniature dachshunds with inflammatory polyps. Twenty dogs (80%) out of 25 miniature dachshunds with inflammatory colorectal polyps responded to immunosuppressive therapy using prednisolone and cyclosporine. The results of this study indicate that miniature dachshunds are predisposed to develop inflammatory colorectal multiple polyps, for which immunosuppressive therapy may be a treatment option.
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              Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate combination in a rat model of rheumatoid arthritis

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                Author and article information

                Journal
                J Vet Med Sci
                J. Vet. Med. Sci
                JVMS
                The Journal of Veterinary Medical Science
                The Japanese Society of Veterinary Science
                0916-7250
                1347-7439
                10 October 2015
                February 2016
                : 78
                : 2
                : 265-269
                Affiliations
                [1) ]Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1–1–1, Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan
                Author notes
                [* ]Correspondence to: Ohno, K., Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1–1–1, Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan. e-mail: aohno@ 123456mail.ecc.u-tokyo.ac.jp
                Article
                15-0129
                10.1292/jvms.15-0129
                4785116
                26460312
                ef116c3b-a1be-4b3b-9c21-13f1630a8a7d
                ©2016 The Japanese Society of Veterinary Science

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

                History
                : 09 March 2015
                : 28 September 2015
                Categories
                Internal Medicine
                Full Paper

                canine,gastroenterology,ibd,small animal medicine
                canine, gastroenterology, ibd, small animal medicine

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