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      Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

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          Abstract

          The increasing use of the common marmoset ( Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

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          C-reactive protein as a marker for inflammatory bowel disease.

          The production of CRP occurs almost exclusively in the liver by the hepatocytes as part of the acute phase response upon stimulation by IL-6, TNF-alphaand IL-1-betaoriginating at the site of inflammation. Its short half-life makes CRP a valuable marker to detect and follow up disease activity in Crohn's disease (CD). In contrast, ulcerative colitis has only a modest to absent CRP response despite active inflammation, and the reason for this is unknown. In CD, serum levels of CRP correlate well with disease activity and with other markers of inflammation as the CDAI, serum amyloid, IL-6 and faecal calprotectin. CRP is a valuable marker for predicting the outcome of certain diseases as coronary heart disease and haematological malignancies. An increased CRP (>45 mg/L) in patients with IBD predicts with a high certainty the need for colectomy and this by reflecting severe ongoing and uncontrollable inflammation in the gut. Finally, trials with anti-TNF and anti-adhesion molecules have shown that a high CRP predicts better response to these drugs. However, whether we need to include CRP as an inclusion criterion for future trials with biologicals is still a matter of debate. Copyright 2004 Lippincott Williams & Wilkins
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            In inflammatory bowel disease (IBD), experimental models have proven to be important tools for detecting potential therapeutic agents and for investigating the mechanisms of pathogenesis. This review is intended to cover recent advances in basic IBD model applications. The use of more than 20 animal models has allowed the detection of numerous protective pharmacological agents, including a number of immunomodulatory agents that have entered the therapeutic armamentarium. The models have been classified into five main categories based on the methods of induction: gene knockout (KO), transgenic, chemical, adoptive transfer, and spontaneous (each with subcategories).
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              Ionized calcium.

              Calcium is the most abundant mineral in the human body. While most of the body's calcium is sequestered in the skeleton, the free, hydrated cation in solution is a key physiologic mediator in a host of metabolic and regulatory processes. The free cation concentration in the extracellular fluid, historically referred to as "ionized calcium" in clinical medicine, is frequently assayed in patients with suspected or known derangements of calcium metabolism. There is controversy in the literature as to whether direct measurement of ionized calcium, measurement of total (free plus chelated or protein-bound) calcium, or adjustment of total calcium for albumin concentration is the best or most practical clinical measure of calcium, as the three methods differ in costs and clinical sensitivities. This manuscript will review calcium biochemistry and homeostasis, compare the utilities of different methods of assessing calcium homeostasis, and discuss appropriate utilization of ionized calcium testing. Copyright © 2011 Elsevier B.V. All rights reserved.
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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
                6 December 2013
                : 8
                : 12
                : e82747
                Affiliations
                [1 ]Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [2 ]Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [3 ]Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota, United States of America
                University of Toronto, Canada
                Author notes

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

                Conceived and designed the experiments: VKB GCS EKH KAMP. Performed the experiments: VKB NPS EKH KAMP. Analyzed the data: VKB GCS CSC EJO MCZ JLM EKH KAMP. Contributed reagents/materials/analysis tools: MCZ JLM RJA KAMP. Wrote the paper: VKB EKH KAMP.

                Article
                PONE-D-13-32362
                10.1371/journal.pone.0082747
                3855796
                baab8b98-364b-436f-b161-e2c4204581be
                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
                : 7 August 2013
                : 28 October 2013
                Page count
                Pages: 10
                Funding
                This work was funded by a grant to EKH, KAMP, GCS, MCZ, JLM, and RJA from the ACLAM Foundation ( http://www.aclam.org/foundation). VKB, GCS, and KAMP were additionally supported by NIH 5T32OD011089-37. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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