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      The influence of apical periodontitis on the concentration of inflammatory mediators in peripheral blood plasma and the metagenomic profiling of endodontic infections: Study design and protocol

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          Abstract

          Increased systemic inflammation has been identified in presence of oral disease, specifically endodontic disease. It is important to investigate whether treatment of the oral disease ameliorates systemic inflammation. Furthermore, there is no information about the extent to which different microorganisms may trigger inflammatory response.

          Objectives

          Primarily (i) to compare the plasma concentrations of inflammatory mediators of apical periodontitis (AP) subjects to controls, (ii) to evaluate whether elimination of the endodontic infection reduces systemic inflammation (iii) to investigate the microbiome of root canal infections. Secondarily i) to correlate the inflammatory mediator data with the microbiome data to investigate whether the type of infection influences the type and severity of the inflammatory condition ii) to examine patterns in the inflammatory mediator data before and after tooth extraction in order to establish a biomarker signature of AP/oral disease.

          This is a multi-centre prospective case-control intervention study. The cohort will consist of 30 healthy human volunteers with one or two teeth with a root-tip inflammation and 30 matched healthy controls. Peripheral blood will be drawn at 6 time points, 3 before and 3 after the extraction of the tooth with apical periodontitis. The teeth will be pulverized, DNA extraction and sequencing will be performed.

          This study aims to compare the concentration of inflammatory blood plasma proteins in between AP-subjects and controls at different time points before and after the tooth extraction in a systematic and complete way. Additionally the composition of the root canal microbiome in association with the inflammatory response of the host will be assessed.

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          Most cited references34

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          Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors

          Gingipains from Porphyromonas gingivalis drive Alzheimer’s pathology and can be blocked with small-molecule inhibitors.
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            A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

            To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.
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              Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings.

              This study evaluated the prevalence of bacterial biofilms in untreated and treated root canals of teeth evincing apical periodontitis. The associations of biofilms with clinical conditions, radiographic size, and the histopathologic type of apical periodontitis were also investigated. The material comprised biopsy specimens from 106 (64 untreated and 42 treated) roots of teeth with apical periodontitis. Specimens were obtained by apical surgery or extraction and were processed for histopathologic and histobacteriologic techniques. Bacteria were found in all but one specimen. Overall, intraradicular biofilm arrangements were observed in the apical segment of 77% of the root canals (untreated canals: 80%; treated canals: 74%). Biofilms were also seen covering the walls of ramifications and isthmuses. Bacterial biofilms were visualized in 62% and 82% of the root canals of teeth with small and large radiographic lesions, respectively. All canals with very large lesions harbored intraradicular biofilms. Biofilms were significantly associated with epithelialized lesions (cysts and epithelialized granulomas or abscesses) (p 0.05). Extraradicular biofilms were observed in only 6% of the cases. The overall findings are consistent with acceptable criteria to include apical periodontitis in the set of biofilm-induced diseases. Biofilm morphologic structure varied from case to case and no unique pattern for endodontic infections was identified. Biofilms are more likely to be present in association with longstanding pathologic processes, including large lesions and cysts. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Contemp Clin Trials Commun
                Contemp Clin Trials Commun
                Contemporary Clinical Trials Communications
                Elsevier
                2451-8654
                05 December 2020
                March 2021
                05 December 2020
                : 21
                : 100686
                Affiliations
                [a ]Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
                [b ]Tandheelkundig Centrum Molenvliet, Alphen aan den Rijn, the Netherlands
                [c ]Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, Glasgow, UK
                [d ]Department of Endodontics, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
                Author notes
                []Corresponding author. Academic Centre for Dentistry Amsterdam (ACTA), Department Of Preventive Dentistry, Gustav Mahlerlaan 3004, 1081, LA, Amsterdam, the Netherlands. a.c.georgiou@ 123456acta.nl
                Article
                S2451-8654(20)30170-8 100686
                10.1016/j.conctc.2020.100686
                7810621
                33490705
                86d8a80c-54d9-4afc-9cb3-ce0ad23390ed
                © 2020 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 June 2020
                : 10 November 2020
                : 1 December 2020
                Categories
                Article

                chronic apical periodontitis,inflammatory mediators,endodontic infection,systemic health

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