The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth rinse, gingival crevicular fluid (GCF), and peri-implantitis fluid (PISF)) is demanding. Several hosts and microbial factors may influence their expression, release, and levels. The type of saliva/oral fluids utilized for the diagnostics affects the analysis. High sensitivity and specificities together with sophisticated methods and techniques are essential for valuable outcome. We describe here recently developed practical, convenient, inexpensive, noninvasive, and quantitative mouth rinse and PISF/GCF/chair-side/point-of-care (PoC) lateral-flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyser) to detect, predict, and monitor successfully the course, treatment, and prevention of periodontitis and peri-implantitis, respectively. The tests have been independently and successfully validated to differentiate periodontal and peri-implant health and disease in Finland, Germany, Netherland, Sweden, Turkey, Nigeria, Malawi, and USA. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires additional studies utilizing these noninvasive screening, diagnostic, and preventive aMMP-8 PoC/chair-side technologies.

C ardiovascular disease is a leading mortality cause, which, despite a recent decline, still contributes to 4 million deaths per year, that is, almost half of all deaths in Europe, whereof ≈30% occurred at <65 years of age. 1It contributes to 22% of all disability-adjusted life-years lost in the European Union and a hospital discharge rate of 2400/100 000 inhabitants.2 Although traditional risk factors are behind a substantial proportion of cardiovascular disease, other factors are important.3 Chronic inflammation accelerates the progress of atherosclerosis, and inflammatory activation increases the risk for plaque rupture leading to acute coronary syndromes. 4,5 Editorial see p 549 Clinical Perspective on p 583Periodontal diseases are inflammatory conditions ranging from gingivitis to severe periodontitis, the latter with a prevalence of 9% in the western European population. 6 The prevalence is age dependent as exemplified by a survey from the United States where it increased from 11% in the age group 50 to 65 years to 20% among those >75 years. 7 The disease, which is diagnosed by clinical and radiographic examination, 8 is a chronic tissuedestructive inflammatory state, predominantly induced by Gramnegative bacteria colonizing the gingival crevice. Background-The relationship between periodontitis (PD) and cardiovascular disease is debated. PD is common in patients with cardiovascular disease. It has been postulated that PD could be causally related to the risk for cardiovascular disease, a hypothesis tested in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study. Methods and Results-Eight hundred five patients (<75 years of age) with a first myocardial infarction (MI) and 805 age-(mean 62±8), sex-(male 81%), and area-matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (≥80% remaining bone) or as mild-moderate (from 79% to 66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (≈100 variables). Statistical comparisons included the Student pairwise t test and the McNemar test in 2×2 contingency tables. Contingency tables exceeding 2×2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds ratios (95% confidence intervals) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; P<0.001). There was an increased risk for MI among those with PD (odds ratio, 1.49; 95% confidence interval, 1.21-1.83), which remained significant (odds ratio, 1.28; 95% confidence interval, 1.03-1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes mellitus, years of education, and marital status). Conclusions-In this large case-control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confoundin...

Background and ObjectiveAnalysis of inflammatory biomarkers in saliva could offer an attractive opportunity for the diagnosis of different systemic conditions specifically in epidemiological surveys. The aim of this study was to investigate if certain salivary biomarkers could be used for detection of common systemic diseases.Materials and MethodsA randomly selected sample of 1000 adults living in Skåne, a county in the southern part of Sweden, was invited to participate in a clinical study of oral health. 451 individuals were enrolled in this investigation, 51% women. All participants were asked to fill out a questionnaire, history was taken, a clinical examination was made and stimulated saliva samples were collected. Salivary concentrations of IL-1β, -6, -8, TNF-α, lysozyme, MMP-8 and TIMP-1 were determined using ELISA, IFMA or Luminex assays.ResultsSalivary IL-8 concentration was found to be twice as high in subjects who had experience of tumour diseases. In addition, IL-8 levels were also elevated in patients with bowel disease. MMP-8 levels were elevated in saliva from patients after cardiac surgery or suffering from diabetes, and muscle and joint diseases. The levels of IL-1β, IL-8 and MMP-8, as well as the MMP-8/TIMP-1 ratio were higher in subjects with muscle and joint diseases.ConclusionBiomarkers in saliva have the potential to be used for screening purposes in epidemiological studies. The relatively unspecific inflammatory markers used in this study can not be used for diagnosis of specific diseases but can be seen as markers for increased systemic inflammation.

This communication article addresses currently available rapid non-invasive methods to screen and detect periodontitis and dental peri-implantitis. In this regard, oral fluid biomarkers have been researched extensively but self-reported oral health (SROH)-questionnaires have also been developed. Both alternatives may offer a quick and easy way to screen and detect diseased patients. Active matrix metalloproteinase (aMMP-8) is one of the most validated biomarkers for screening and detecting periodontal breakdown related to periodontitis and peri-implantitis and monitoring their treatment effects revealing successful, less- and non-successful treatment results. Currently available aMMP-8 lateral-flow technologies allow this kind of analysis, as demonstrated here, to be conducted quantitatively online and real-time as point-of-care/chairside testing in dental and even medical care settings. In this study, an aMMP-8 peri-implant sulcular fluid point-of-care-test diagnosed peri-implantitis and healthy implants far more accurately than bleeding-on-probing or the other biomarkers, such as polymorphonuclear (PMN)/neutrophil elastase, myeloperoxidase and MMP-9. Although, SROH-questionnaires allow screening in similar settings but they lack the information about the current disease activity of periodontitis and peri-implantitis, which is of essential value in periodontal diagnostics and treatment monitoring. Thus, both methods can be considered as adjunct methods for periodontitis and peri-implant diagnostics, but the value of oral fluid biomarkers analysis does not seem to be substitutable.

Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic technologies, and is among the main goals of oral fluid researchers. The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth-rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) is demanding. Several factors influence their expression and release; these factors include the intracellular location, the molecular size and the flow characteristics of the biological fluid. The type of saliva/oral fluid utilized for the diagnostics affects the analysis. High sensitivity together with sophisticated methods and techniques are essential to get a useful outcome. We describe here a recently developed mouth-rinse that is practical, convenient and inexpensive, as well as PISF chair-side/point of care (PoC) lateral-flow active matrix metalloproteinase (aMMP-8) immunoassays to detect, predict and monitor the course and treatment of periodontitis and peri-implantitis.

Background: Peptidoglycan recognition protein 1 (PGLYRP1) is an antimicrobial and proinflammatory innate immunity protein activated during infections. We aimed to investigate whether PGYLRP1 and associated molecules of the immune response in saliva is a cumulative outcome result of both MI and periodontal inflammation. Methods and Results:Two hundred patients with MI and another 200 matched non-MI controls were included. A full-mouthexamination was conducted to assess periodontal inflammation and collection of stimulated saliva was performed 6 to 10 weeks after the first MI. PGLYRP1, triggering receptor expressed on myeloid cells 1 (TREM-1), interleukin-1 beta (IL-1β) were analyzed by ELISA.Matrix metalloproteinase (MMP)-8 levels were determined by IFMA. Compared to controls, MI patients showed higher salivary PGLYRP1, but not TREM-1 levels.The difference in PGLYRP1 levels remained after adjustment for covariates. In MI patients, the PGLYRP1 levels positively correlated with BOP and PPD 4 to 5 mm. Among non-MI subjects, the levels of PGLYRP1 correlated positively and significantly with BOP and total PPD. Salivary PGLYRP1 concentrations also showed strong positive correlations with levels of TREM-1, IL-1β and MMP-8. In multivariate linear regression analysis, in MI patients, BOP and former smokingstatus displayed an association with salivary PGLYRP1 concentration. Conclusion:MI patients showed higher salivary PGLYRP1 levels than healthy controls, also after adjusting for smoking, sex, age and periodontal health status. Salivary levels of PGLYRP1 may reflect the overall inflammatory burdenThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.