{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:13:01Z","timestamp":1767913981220,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T00:00:00Z","timestamp":1428883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2016,2]]},"abstract":"Background and Objective<\/jats:title>The multifunctional molecules adrenomedullin (AM<\/jats:styled-content>) and nitric oxide (NO<\/jats:styled-content>) are both involved in the host response to microbial challenge during periodontal disease. Whether they coexist in periodontal inflammation and if equally produced in the different forms of periodontal disease has not previously been investigated. The aims of this study were to describe the locations ofAM<\/jats:styled-content>andNO<\/jats:styled-content>in healthy and inflamed gingival tissues and to determine and compare their levels in the gingival crevicular fluid and saliva of patients with gingivitis, chronic periodontitis and aggressive periodontitis.<\/jats:p><\/jats:sec>Material and Methods<\/jats:title>AM<\/jats:styled-content>and inducible nitric oxide synthase (iNOS<\/jats:styled-content>) were immunolocalized in clinically healthy and inflamed gingival tissue sections. The cells expressingAM<\/jats:styled-content>and iNOS<\/jats:styled-content>were characterized using immunocytochemistry with different markers for macrophages [cluster differentiation (CD)<\/jats:styled-content>68 andCD<\/jats:styled-content>14)], dendritic cells (CD<\/jats:styled-content>83), neutrophils [neutrophil gelatinase\u2010associated lipocalin (nGAL<\/jats:styled-content>)] and natural killer cells (CD<\/jats:styled-content>56). In an initial study, the levels ofAM<\/jats:styled-content>andNO<\/jats:styled-content>were also measured in samples ofgingival crevicular fluid<\/jats:styled-content>and saliva obtained from patients with a diagnosis of gingivitis (n<\/jats:italic>\u00a0=\u00a09), chronic periodontitis (n<\/jats:italic>\u00a0=\u00a09) and aggressive periodontitis (n<\/jats:italic>\u00a0=\u00a09) using an ELISA and the nitrate\/nitrite (NO<\/jats:styled-content>metabolites)G<\/jats:styled-content>riess assay, respectively.<\/jats:p><\/jats:sec>Results<\/jats:title>Low levels ofAM\u2010<\/jats:styled-content>and iNOS\u2010<\/jats:styled-content>expressing cells were detected in healthy gingival tissues in comparison with three\u2010fold higher levels of these cells in inflamed tissues. These cells were localized mainly in the epithelial layer but were also present in deeper connective tissue.AM<\/jats:styled-content>and iNOS<\/jats:styled-content>were co\u2010localized in particular cells within inflamed tissues, namelyCD<\/jats:styled-content>68+<\/jats:sup>(52%) andCD<\/jats:styled-content>14+<\/jats:sup>(36%) macrophages, but also in nGAL<\/jats:styled-content>+<\/jats:sup>neutrophils (16%) andCD<\/jats:styled-content>83+<\/jats:sup>dendritic cells (14%). Interestingly,AM<\/jats:styled-content>andNO<\/jats:styled-content>levels in saliva were both found to be higher (p<\/jats:italic>\u00a0<\u00a00.01) in patients with aggressive periodontitis than in patients with chronic periodontitis or gingivitis. In contrast, ingingival crevicular fluid<\/jats:styled-content>, the levels ofNO<\/jats:styled-content>showed marked differences among patients with chronic periodontitis, aggressive periodontitis and gingivitis (p<\/jats:italic>\u00a0<\u00a00.01), and the levels ofAM<\/jats:styled-content>were higher (p<\/jats:italic>\u00a0<\u00a00.01) in both chronic and aggressive periodontitis compared with gingivitis alone.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The data presented demonstrate a functional linkage betweenAM<\/jats:styled-content>andNO<\/jats:styled-content>in periodontal disease, with salivary andgingival crevicular fluid<\/jats:styled-content>levels possibly associated with different forms and severities of periodontal disease. Exacerbated production of bothAM<\/jats:styled-content>andNO<\/jats:styled-content>in saliva suggests their potential use as salivary markers of aggressive periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12273","type":"journal-article","created":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T13:15:09Z","timestamp":1428930909000},"page":"16-25","source":"Crossref","is-referenced-by-count":42,"title":["Detection of adrenomedullin and nitric oxide in different forms of periodontal disease"],"prefix":"10.1111","volume":"51","author":[{"given":"Q. A.","family":"Hussain","sequence":"first","affiliation":[{"name":"Institute of Dentistry Barts and The London School of Medicine & Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. 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