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      Development of Autoimmune Hair Loss Disease Alopecia Areata Is Associated with Cardiac Dysfunction in C3H/HeJ Mice

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          Abstract

          Alopecia areata (AA) is a chronic autoimmune hair loss disease that affects several million men, women and children worldwide. Previous studies have suggested a link between autoimmunity, stress hormones, and increased cardiovascular disease risk. In the current study, histology, immunohistology, quantitative PCR (qPCR) and ELISAs were used to assess heart health in the C3H/HeJ mouse model for AA and heart tissue response to adrenocorticotropic hormone (ACTH) exposure. Mice with AA exhibited both atrial and ventricular hypertrophy, and increased collagen deposition compared to normal-haired littermates. QPCR revealed significant increases in Il18 (4.6-fold), IL18 receptor-1 ( Il18r1; 2.8-fold) and IL18 binding protein ( Il18bp; 5.2-fold) in AA hearts. Time course studies revealed a trend towards decreased Il18 in acute AA compared to controls while Il18r1, Il18bp and Casp1 showed similar trends to those of chronic AA affected mice. Immunohistochemistry showed localization of IL18 in chronic AA mouse atria. ELISA indicated cardiac troponin-I (cTnI) was elevated in the serum and significantly increased in AA heart tissue. Cultures of heart atria revealed differential gene expression between AA and control mice in response to ACTH. ACTH treatment induced significant increase in cTnI release into the culture medium in a dose-dependent manner for both AA and control mice. In conclusion, murine AA is associated with structural, biochemical, and gene expression changes consistent with cardiac hypertrophy in response to ACTH exposure.

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          Left ventricular hypertrophy: pathogenesis, detection, and prognosis.

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            Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up.

            Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules related to the selective loss of melanocytes. The prevalence of the disease is around 1% in the United States and in Europe, but ranges from less than 0.1% to greater than 8% worldwide. A recorded predominance of women may reflect their greater willingness to express concern about cosmetically relevant issues. Half of all patients develop the disease before 20 years of age. Onset at an advanced age occurs but is unusual, and should raise concerns about associated diseases, such as thyroid dysfunction, rheumatoid arthritis, diabetes mellitus, and alopecia areata. Generalized vitiligo is the most common clinical presentation and often involves the face and acral regions. The course of the disease is unpredictable and the response to treatment varies. Depigmentation may be the source of severe psychological distress, diminished quality of life, and increased risk of psychiatric morbidity. Part I of this two-part series describes the clinical presentation, histopathologic findings, and various hypotheses for the pathogenesis of vitiligo based on past and current research. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
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              Cardiac troponin I. A marker with high specificity for cardiac injury.

              Levels of MBCK can be increased in patients with skeletal muscle injury or renal failure in the absence of myocardial injury, causing diagnostic confusion. This study was designed to determine whether measurement of cardiac troponin I (cTnI), a myocardial regulatory protein with comparable sensitivity to MBCK, has sufficient specificity to clarify the etiology of MBCK elevations in patients with acute or chronic skeletal muscle disease or renal failure. Of the patients (n = 215) studied, 37 had acute skeletal muscle injury, 10 had chronic muscle disease, nine were marathon runners, and 159 were chronic dialysis patients. Patients were evaluated clinically, by ECG, and by two-dimensional echocardiography. Total creatine kinase (normal, < 170 IU/L) was determined spectrophotometrically, and cTnI (normal, < 3.1 ng/mL) and MBCK (normal, < 6.7 ng/mL) were determined with specific monoclonal antibodies. Values above the upper reference limit were considered "elevated." Elevations of total creatine kinase were common, and elevations of MBCK occurred in 59% of patients with acute muscle injury, 78% of patients with chronic muscle disease and marathon runners, and 3.8% of patients with chronic renal failure. Some of the patients were critically ill; five patients were found to have had myocardial infarctions and one had a myocardial contusion. cTnI was elevated only in these patients. Elevations of cTnI are highly specific for myocardial injury. Use of cTnI should facilitate distinguishing whether elevations of MBCK are due to myocardial or skeletal muscle injury.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                26 April 2013
                : 8
                : 4
                : e62935
                Affiliations
                [1 ]Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
                [2 ]University of British Columbia, Vancouver, BC, Canada
                [3 ]Department of Pathology and Laboratory Medicine, James Hogg Research Centre, Institute for Heart and Lung Health, University of British Columbia, Vancouver, BC, Canada
                [4 ]Department of Dermatology and Skin Science, Vancouver General Hospital, Vancouver, BC, Canada
                Baylor College of Medicine, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: EW JS DJG KJM. Performed the experiments: EW KC MY NA. Analyzed the data: EW KC MY. Contributed reagents/materials/analysis tools: MY. Wrote the paper: EW KJM.

                Article
                PONE-D-12-32754
                10.1371/journal.pone.0062935
                3637254
                23658656
                ee16ac02-3f20-4760-802b-0f885962c8c5
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 October 2012
                : 26 March 2013
                Page count
                Pages: 12
                Funding
                This work was supported by grants from the Canadian Dermatology Foundation (CDF) and the Canadian Institutes of Health Research (CIHR; MOP-82927). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Histology
                Immunology
                Immunologic Techniques
                Immunoassays
                Immunohistochemical Analysis
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Cardiovascular
                Clinical Immunology
                Autoimmune Diseases
                Dermatology
                Hair and Nail Diseases

                Uncategorized
                Uncategorized

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