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      The immunohistochemical evaluation of selected markers in the left atrium of dogs with end-stage dilated cardiomyopathy and myxomatous mitral valve disease – a preliminary study

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          Abstract

          Background

          Dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are the most common diseases noted in dogs. Although their pathogenesis varies, both include a significant enlargement of the left atrium.

          The study was carried out on left atrial specimens obtained from 56 dogs, including those from 34 dogs with clinically diagnosed MMVD, 15 dogs with DCM and 7 dogs without heart disease (control group). Dogs in the MMVD and the DCM groups presented with left atrial enlargement and stage D heart failure. The specimens underwent immunohistochemical examination using desmin, vimentin, periostin and caspase-3 antibodies.

          Results

          There were alterations in the expression of the studied proteins in the study groups compared to the control group. The changes included: irregularity of desmin cross-striation and desmosomes, a higher amount of vimentin-positive cells, a change in the periostin expression pattern from cytoplasmic to extracellular, and a lower expression of caspase-3. The alterations were more pronounced in the DCM group than in the MMVD group.

          Conclusions

          During heart failure, the pattern of desmin, vimentin, periostin and caspase-3 expression alters in the left atrium, regardless of the cause. The changes are more pronounced in dogs with DCM than in dogs with MMVD and similar left atrial enlargement, suggesting that volume overload may not be the only cause of myocardial changes in DCM.

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          Most cited references27

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          [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue].

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            Biochemical pathways of caspase activation during apoptosis.

            Caspase activation plays a central role in the execution of apoptosis. The key components of the biochemical pathways of caspase activation have been recently elucidated. In this review, we focus on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway. In the cell surface death receptor pathway, activation of caspase-8 following its recruitment to the death-inducing signaling complex (DISC) is the critical event that transmits the death signal. This event is regulated at several different levels by various viral and mammalian proteins. Activated caspase-8 can activate downstream caspases by direct cleavage or indirectly by cleaving Bid and inducing cytochrome c release from the mitochondria. In the mitochondrial-initiated pathway, caspase activation is triggered by the formation of a multimeric Apaf-1/cytochrome c complex that is fully functional in recruiting and activating procaspase-9. Activated caspase-9 will then cleave and activate downstream caspases such as caspase-3, -6, and -7. This pathway is regulated at several steps, including the release of cytochrome c from the mitochondria, the binding and hydrolysis of dATP/ATP by Apaf-1, and the inhibition of caspase activation by the proteins that belong to the inhibitors of apoptosis (IAP).
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              Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

              There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.
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                Author and article information

                Contributors
                izabela.janus87@gmail.com
                malgorzata.kandefer@gmail.com
                rafal.ciaputa@gmail.com
                agnieszkann@poczta.onet.pl
                urszula.paslawska@up.wroc.pl
                massimiliano.tursi@unito.it
                marcin.nowak@up.wroc.pl
                Journal
                Ir Vet J
                Ir Vet J
                Irish Veterinary Journal
                BioMed Central (London )
                0368-0762
                2046-0481
                1 December 2016
                1 December 2016
                2016
                : 69
                : 18
                Affiliations
                [1 ]Division of Pathomorphology and Veterinary Forensics, Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wroclaw, 50375 Poland
                [2 ]Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Wroclaw University of Environmental and Life Sciences, Wroclaw, 50366 Poland
                [3 ]Department of Animal Sciences, University of Turin, Grugliasco, TO Italy
                Author information
                http://orcid.org/0000-0001-5166-856X
                Article
                77
                10.1186/s13620-016-0077-2
                5134068
                557ea858-0c75-404f-b36b-9469d21e49e9
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 January 2016
                : 15 November 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Veterinary medicine
                dilated cardiomyopathy,myxomatous mitral valve disease,dcm,mmvd,immuniohistochemistry,left atrium

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