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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.

Aim: To relate cardiac biomarkers, such as cystatin C and growth differentiation factor-15 (GDF-15) in saliva to myocardial infarction (MI) and to periodontal status, and to investigate the relation between salivary and plasma cardiac biomarkers., Materials and Methods: Two hundred patients with MI admitted to coronary care units and 200 matched controls without MI were included. Dental examination and collection of blood and saliva samples was performed 6-10 weeks after the MI for patients and in close proximity thereafter for controls. Analysing methods: ARCHITECT i4000SR, Immulite 2000 XPi or ELISA., Results: The mean age was 62 ± 8 years and 84% were male. Total probing pocket depth, fibrinogen, white blood cell counts and HbA1c were higher in patients than controls. GDF-15 levels correlated with most of the included clinical variables in both study groups. No correlation was found between plasma and saliva levels of cystatin C or GDF-15., Conclusion: Salivary cystatin C and GDF-15 could not differentiate between MI patients and controls., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This study evaluates levels of matrix metalloproteinase (MMP)-8, MMP-9, and tissue inhibitor of MP-1 (TIMP-1) in biofluids of women with gestational diabetes mellitus (GDM) and systemically healthy counterparts with different statuses of periodontal health., Methods: Seventy-one women with GDM and gingivitis (Gg), 30 women with GDM and healthy periodontium (Gh), 28 systemically and periodontally healthy women (Hh), and 37 systemically healthy women with gingivitis (Hg) were evaluated. MMP-8, MMP-9, and TIMP-1 levels were determined in gingival crevicular fluid (GCF), saliva, and serum by immunofluorometric and enzyme-linked immunosorbent assays. Full-mouth clinical periodontal parameters were recorded., Results: GCF and serum MMP-8 concentrations, serum MMP-9 concentrations, and serum MMP-8/MMP-1 and MMP-9/MMP-1 molar ratios were significantly higher in Gg compared with Hg group (P <0.05). Serum MMP-8 levels and salivary TIMP-1 levels were higher in Gh compared with Hg group (P <0.05) whereas salivary MMP-8/TIMP-1 molar ratio was lower in Gh compared with Hg group (P <0.05). Elevated concentrations of GCF MMP-8 and MMP-9 were found in Gg compared with Gh group (P <0.05). Significant correlations were found between local levels of biomarkers and clinical periodontal parameters in only GDM group., Conclusion: GDM may modulate both local and circulating levels of MMP-8 especially when associated with gingivitis.

Background: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM., Methods: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae., Results: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12., Conclusions: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.

Periodontitis is a common infectious disease associated with increased risk for ischemic stroke though presently unclear mechanisms. In a case-control study, we investigated salivary levels of four periodontal pathogens, as well as systemic and local inflammatory markers. The population comprised 98 patients with acute ischemic stroke (mean ± SD, 68.2 ± 9.7 yrs; 45.9% women) and 100 healthy controls (69.1 ± 5.2 yrs; 47.0% women). Patients were more often edentulous and had fewer teeth than controls (13.8 ± 10.8 versus 16.6 ± 10.1). After adjusting for stroke risk factors and number of teeth, controls had higher saliva matrix metalloproteinase-8 (MMP-8), myeloperoxidase (MPO), IL-1β, Aggregatibacter actinomycetemcomitans, and serum LPS activity levels. Patients had higher serum MMP-8 and MPO, and they were more often qPCR-positive for A. actinomycetemcomitans (37.9% versus 19.0%) and for ≥3 periodontopathic species combined (50.0% versus 33.0%). We conclude that controls more often had evidence of current periodontal infection with higher periodontal pathogen amount, endotoxemia, local inflammation and tissue destruction. Stroke patients more often had evidence of end-stage periodontitis with edentulism and missing teeth. They were more often carriers of several periodontopathic pathogens in saliva, especially A. actinomycetemcomitans. Additionally, inflammatory burden may contribute to high systemic inflammation associated with elevated stroke susceptibility., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Neutrophil collagenase or collagenase-2 (matrix metalloproteinase [MMP]-8) belongs to the collagenase subgroup of the MMP superfamily of calcium- and zinc-dependent neutral proteinases. MMP-8 is catalytically the most competent proteinase to initiate type I collagen and extracellular matrix degradation associated with periodontal and peri-implant tissue destruction leading to tooth and dental implant loss. Regarding cardiovascular diseases, pathologically excessive MMP-8 has been implicated in atherosclerotic plaque destabilization and rupture probably through its proteolytic ability to thin the protecting collagenous fibrous cap lining coronary and other arteries. During the initiation and course of inflammatory responses in periodontitis, peri-implantitis and cardiovascular diseases, proinflammatory mediators including especially MMP-8 are up-regulated not only in affected tissues but also in the secreted, disease-affected, oral fluids (gingival crevicular fluid [GCF], peri-implant sulcular fluid [PISF], mouthrinse and saliva) as well as in serum and plasma. Regarding periodontitis, peri-implantitis and cardiovascular diseases, the oral fluid and serum MMP-8 analysis has proven to be a sensitive and an objective biomarker as an indicator of health, pathologic processes and pharmacologic response to therapeutic intervention including doxycycline medication as an MMP inhibitor. Oral fluids, i.e., GCF, PISF, mouthrinse and saliva are easily and non-invasively collected for the site- and patient-specific diagnostic analysis in periodontitis and peri-implantitis, whereas serum and/or plasma sample collection is required for diagnosis and monitoring of cardiovascular diseases. Research in periodontology and cardiology has identified a need for the development of innovative point-of-care diagnostic tests for MMP-8. We summarize and review the recent studies on these topics., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: In culture studies matrix metalloproteinase (MMP)-8 thins the protecting fibrous cap of the atherosclerotic plaque thereby increasing its vulnerability. Results on the association of serum MMP-8 concentrations and cardiovascular diseases (CVD) are, however, scarce and contradictory., Methods and Results: We analyzed the association between CVD or subclinical atherosclerosis and serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations of 1018 men with the follow-up time of 10 years. MMP-8 concentrations or MMP-8/TIMP-1 ratios were higher in men with prevalent CVD or subclinical atherosclerosis at baseline than those without. In men free of CVD at baseline, MMP-8 concentrations associated with acute myocardial infarction, death from coronary heart disease (CHD), CVD, or from any cause with relative risks (RR) (95% CI) of 1.138 (1.009 to 1.284), 1.188 (1.034 to 1.365), 1.171 (1.026 to 1.338), and 1.136 (1.018 to 1.269), respectively, and MMP-8/TIMP-1 ratio with CHD death with an RR of 1.206 (1.028 to 1.414) per standard deviation (SD) increase. In men with no prevalent CVD but with subclinical atherosclerosis at baseline, elevated serum MMP-8 concentration predicted CVD death with an RR of 3.03 (1.09 to 8.44). TIMP-1 concentrations alone had no predictive value., Conclusions: The results indicate that serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome.

Background: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV—Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. Methods: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. Results: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. Conclusion: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy. [ABSTRACT FROM AUTHOR]

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Objective: The aim of this study was to investigate the utility of the active matrix metalloproteinase (aMMP‐8)‐point‐of‐care (PoC) test as a quantitative real‐time chair‐side diagnostic tool for peri‐implant diagnosis, as well as assess the potentially developing and ongoing risk relative to the traditional clinical methods. Background: Current peri‐implant and periodontal disease diagnoses rely on clinical and radiological examinations. This case‐control study investigated the applicability of aMMP‐8‐PoC immunotest for quantitative real‐time diagnosis and monitoring of dental implants in health and disease. Methods: Sixty‐eight patients visiting a specialist clinic for maintenance following dental implant placement underwent assessment of their peri‐implant health. aMMP‐8‐PoC peri‐implant sulcular fluid (PISF) lateral‐flow immunotests were performed using ImplantSafe® technology quantitated by ORALyzer®. In addition, the PISF samples were analyzed for total MMP‐8, calprotectin, and interleukin (IL)‐6 by enzyme‐linked immunosorbent assays (ELISA), aMMP‐8 by western immunoblot, and MMP‐2 and MMP‐9 by gelatin zymography. Results: The aMMP‐8‐PoC test promptly recorded and reflected peri‐implant disease, differentiating it clearly from health. X‐ray findings (bone loss > 2 mm), peri‐implant pocket depth ≥ 3 mm, and bleeding on probing were significantly more prevalent among implants positive for the aMMP‐8‐PoC test. aMMP‐8/ORALyzer analysis was more precise in recording disease than total MMP‐8, calprotectin, IL‐6, MMP‐2, and MMP‐9. Conclusions: The aMMP‐8‐PoC test can be conveniently implemented to alert for and detect active collagenolysis affecting peri‐implant tissues, both in the early and advanced stages of the disease. Active and fragmented MMP‐8 exhibits a strong and significant association with peri‐implantitis as compared to total MMP‐8 and other biomarkers and can be utilized as the POC/chairside biomarker of choice in the new classification of peri‐implantitis. [ABSTRACT FROM AUTHOR]

Background: This cross-sectional study aims to investigate if a point-of-care (PoC) test of active matrix metalloproteinase-8 (aMMP-8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva.Methods: Forty-seven adolescents, aged 15 to 17 years, were tested with aMMP-8 PoC test, which was followed by a full-mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM-1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP-8 was used as the reference method.Results: Fourteen saliva samples out of a total of 47 showed positivity for aMMP-8 PoC test. Both the TREM-1 and the aMMP-8 (IFMA) levels were significantly elevated among the aMMP-8 PoC test positives compared with the PoC test negatives (P < 0.05). Moreover, aMMP-8 levels assessed by IFMA showed a strong positive correlation with TREM-1 levels in saliva (r = 0.777, P < 0.001). The number of sites with a probing depth of ≥4 mm was significantly lower among the adolescents that had a negative aMMP-8 PoC test result, and TREM-1 levels < 75 pg/mL (P < 0.05). In contrast, adolescents with a positive aMMP-8 PoC test result (i.e., elevated aMMP-8 levels) together with elevated TREM-1 levels had a significantly higher number of periodontal pockets with ≥4 mm (P < 0.001).Conclusion: The present study validated usability of aMMP-8 PoC test for predicting "proinflammatory" salivary profile and periodontal health status in adolescents. [ABSTRACT FROM AUTHOR]

Background: Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow‐up. We investigated whether serum matrix metalloproteinase 8 (MMP‐8) and tissue inhibitor of metalloproteinase 1 (TIMP‐1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. Methods: We analyzed serum MMP‐8 (S‐MMP‐8) and serum TIMP‐1 (s‐TIMP‐1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow‐up. Results: Elevated S‐MMP‐8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S‐MMP‐8 in patients with LSCC was significantly higher (P < .001). Increased S‐TIMP‐1 level in LSCC was associated with poor overall survival (P = .02) and recurrence‐free survival (P = .05). Conclusion: In RRP, high S‐MMP‐8 may predict malignant transformation. In LSCC, elevated S‐TIMP‐1 is connected to poor survival. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs), endopeptidases with diverse biochemical functions, can promote cancer cell invasion and metastasis by degrading the extracellular matrix. A high matrix metalloproteinase-14 (MMP-14) expression in gastric cancer tissue has been associated with metastasis and poor prognosis. To further understand this association, we investigated serum MMP-14 as a biomarker in gastric cancer patients. The patient cohort consisted of 240 gastric adenocarcinoma patients who underwent surgery at Helsinki University Hospital, Finland, between 2000 and 2009. We determined the soluble MMP-14 serum levels using an enzyme-linked immunosorbent assay. We then calculated the associations between serum levels and clinicopathologic variables using the Mann-Whitney U-test or the Kruskal-Wallis test. We constructed survival curves using the Kaplan-Meier method and calculating the hazard ratios using the Cox proportional hazard model. We revealed a positive association between a high serum MMP-14 level and stages III–IV (p = 0.029), and between a high serum MMP-14 and distant metastasis (p = 0.022). Patients with a low serum MMP-14 had a 5-year disease-specific survival of 49.2% (95% confidence interval [CI] 45.5–52.9), whereas patients with a high serum MMP-14 had a 5-year survival of 22.1% (95% CI 15.2–29.0; p = 0.001). High serum MMP-14 was a statistically significant prognostic factor among patients with an intestinal type of cancer (hazard ratio [HR] 3.54; 95% CI 1.51–8.33; p = 0.004), but not among patients with a diffuse type. The serum MMP-14 level remained an independent prognostic factor in our multivariate survival analysis (HR 1.55; 95% CI 1.02–2.35; p = 0.040). This study indicates for the first time that high serum soluble MMP-14 levels in gastric cancer serves as a marker for a poor prognosis, possibly indicating the presence of distant metastases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of anti‐rheumatic medications on salivary matrix metalloproteinase (MMP)‐8 levels and MMP‐8/TIMP (tissue inhibitor of MMPs)‐1 ratio in patients with rheumatoid arthritis (RA) and periodontal findings during a 1‐year follow‐up. Materials and Methods: Salivary MMP‐8 was measured by an immunofluorometric assay and TIMP‐1 by an enzyme‐linked immunosorbent assay of 53 patients with early untreated RA (ERA), naïve to synthetic disease modifying anti‐rheumatic drugs (DMARDs), of 28 patients with chronic RA (CRA), candidates for biologic DMARDs and of 43 age‐ and sex‐matched controls. Periodontal health was evaluated by bleeding on probing (BOP), pocket depth (PD), and periodontal inflammatory burden index (PIBI). Examinations were conducted twice for RA patients and once for controls. Results: Salivary MMP‐8 level and MMP‐8/TIMP‐1 ratio associated positively with PIBI in patients with chronic RA (MMP‐8: p < 0.001 at baseline, p = 0.002 after follow‐up; MMP‐8/TIMP‐1 ratio p < 0.001, p = 0.003, respectively) and in controls (MMP‐8: p = 0.010, MMP‐8/TIMP‐1 ratio: p = 0.010). Salivary MMP‐8 levels were highest at the early stage of RA. The used DMARDs, synthetic or biologic, did not affect salivary MMP‐8 concentrations. Conclusions: The use of synthetic or biologic DMARDs did not affect salivary MMP‐8 levels in RA patients regardless the duration of RA. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Matrix metalloproteinase (MMP)‐8, MMP‐9, tissue inhibitor of matrix metalloproteinase (TIMP)‐1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS). Materials and methods: The population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non‐periodontitis, and ACS versus non‐ACS patients were compared. Results: Saliva MMP‐8, MMP‐9 and MPO provided significant area‐under‐curve (AUC) values for periodontitis, 0.69 (<0.001), 0.66 (<0.001) and 0.68 (<0.001), respectively. Serum MMP‐8, MMP‐9 and MPO levels distinguished ACS from non‐ACS patients with AUCs of 0.73 (<0.001), 0.58 (0.03) and 0.68 (<0.001), respectively. Periodontitis confounded the use of serum MMP‐9 in diagnostics of ACS. Cardiac status complicated the use of saliva TIMP‐1 in periodontal diagnostics. Saliva biomarkers could not be used in ACS diagnosis, and serum biomarkers were not useful in diagnosis of periodontitis. Conclusions: MMP‐8, MMP‐9, TIMP‐1and MPO are valuable biomarkers for both ACS and periodontitis, but the selection of sample material is crucial; serum is suitable for ACS and saliva for periodontal diagnostic aid. [ABSTRACT FROM AUTHOR]

Background: Triggering receptor expressed on myeloid cells (TREM-1) is a cell-surface receptor involved in amplification of inflammatory response to bacterial infections, along with its ligand peptidoglycan recognition protein 1 (PGLYRP1). TREM-1 is shed by matrix metalloproteinases (MMPs) to its soluble (s) form. The aim of the study is to investigate association of sTREM-1 and PGLYRP1 with oral inflammatory burden among patients with chronic kidney disease (CKD) at predialysis and posttransplantation stages.Methods: One hundred forty-four patients with CKD were examined at predialysis, and oral infection foci were treated prior to kidney transplantation. Fifty-three patients were available for follow-up after transplantation. Oral inflammatory burden was assessed by the Periodontal Inflammatory Burden Index (PIBI) and Total Dental Index. sTREM-1, PGLYRP1, and interleukin (IL)-1β were measured in saliva by enzyme-linked immunosorbent assay, and MMP-8 was measured by immunofluorometric assay.Results: In the predialysis stage, sTREM-1 and PGLYRP1 were positively associated with IL-1β, MMP-8, and PIBI. More specifically, patients with deeper probing depth (PD) (at least two sites with ≥6 mm) had higher concentrations of salivary sTREM-1 and PGLYRP1 compared with those with shallower PD. Higher concentrations of PGLYRP1 and IL-1β were associated with a higher number of teeth (> 25). On follow-up, higher PGLYRP1 and sTREM-1 were associated with one or more sites with ≥4 mm PD.Conclusions: sTREM-1 and PGLYRP1 are elevated in patients with CKD with poor oral health and positively correlate with number of active periodontal pockets after oral infection therapy. Moreover, they positively correlate with MMP-8 and IL-1β. Hence, the salivary sTREM-1/PGLYRP1 axis could be useful as a diagnostic marker for oral infection within patients with CKD. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid ( GCF) from patients with chronic periodontitis ( CP) and asymptomatic apical periodontitis ( AAP). Materials and Methods Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained ( N = 106). Matrix metalloproteinases ( MMPs) -2 and -9 were determined by zymography; levels of MMP-8 by ELISA and IFMA and MPO by ELISA. IL-1, IL-6, TNF α, DKK-1, Osteonectin, Periostin, TRAP-5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed-effects models. Results The MMP-9 and MMP-8 were higher in CP, followed by AAP, versus healthy individuals ( p < 0.05). Pro MMP-2, MPO, IL-1, IL-6, PTN, TRAP-5 and OPG were significantly higher in CP when compared with AAP and healthy patients ( p < 0.05). The highest diagnostic accuracies were observed for Pro MMP-2, Pro MMP-9, MMP-8 and TRAP-5 ( AUC > 0.97) in CP, and for the active form of MMP-9 and MMP-8 ( AUC > 0.90) in AAP. Conclusion Gingival crevicular fluid composition is modified by CP and AAP. MMP-9 and MMP-8 show diagnostic potential for CP and AAP, whereas MMP-2 and TRAP-5 are useful only for CP. [ABSTRACT FROM AUTHOR]

Aim To identify the diagnostic accuracy of gingival crevicular fluid ( GCF) candidate biomarkers to discriminate periodontitis from the inflamed and healthy sites, and to compare the performance of two independent matrix metalloproteinase ( MMP)-8 immunoassays. Materials and Methods Cross sectional study. GCF ( N = 58 sites) was collected from healthy, gingivitis and chronic periodontitis volunteers and analysed for levels of azurocidin, chemokine ligand 5, MPO, TIMP-1 MMP-13 and MMP-14 by ELISA or activity assays. MMP-8 was assayed by immunofluorometric assay ( IFMA) and ELISA. Statistical analysis was performed using linear mixed-effects models and Bayesian statistics in R and Stata V11. Results MMP-8, MPO, azurocidin and total MMP-13 and MMP-14 were higher in periodontitis compared to gingivitis and healthy sites ( p < 0.05). A very high correlation between MPO and MMP-8 was evident in the periodontitis group ( r = 0.95, p < 0.0001). MPO, azurocidin and total levels of MMP-8, MMP-13 and MMP-14 showed high diagnostic accuracy (≥0.90), but only MMP-8 and MPO were significantly higher in the periodontitis versus gingivitis sites. MMP-8 determined by IFMA correlated more strongly with periodontal status and showed higher diagnostic accuracy than ELISA. Conclusions MPO and collagenolytic MMPs are highly discriminatory biomarkers for site-specific diagnosis of periodontitis. The comparison of two quantitative MMP-8 methods demonstrated IFMA to be more accurate than ELISA. [ABSTRACT FROM AUTHOR]

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8/TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1-3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277-4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600-7.831; P = 0.002) and 2.87 (1.171-7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8/TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295-8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to compare salivary and serum biomarker levels and degrees of matrix metalloproteinase (MMP) activation between patients with acute myocardial infarction (AMI) and systemically healthy patients (non-AMI) with similar periodontal conditions. Methods: A total of 92 patients (47 AMI and 28 non-AMI patients with gingivitis or periodontitis; and 17 systemically and periodontally healthy patients as a control group) were recruited. Clinical periodontal measurements were recorded; stimulated whole saliva and serum samples were collected. AMI patients were clinically examined within 3 to 4 days after admission to the coronary care unit. Saliva samples were analyzed for levels of MMP-8, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. Serums were tested for MMP-8, MMP-9, TIMP-1, and TIMP-2 levels by immunofluorometric assay and enzyme-linked immunosorbent assay. Molecular forms and degree of activation of salivary MMP-8, MMP-9, and MMP-13 were analyzed by computer-scanned immunoblots. Results: Total salivary MMP-8 assessed by immunofluorometric assay method and immunoblot densitometric units was higher in non-AMI than in AMI patients' saliva but a significantly higher percentage of AMI patients was activated polymorphonuclear leukocyte type (PMN) MMP-8 (P<0.001) regardless of periodontal diagnosis. Serum MMP-8, MMP-9, and TIMP-1 levels were significantly higher in AMI (for all markers and all comparisons, P <0.05). Characteristic for AMI was dominance of active PMN MMP-8 in saliva. Conclusions: Enhanced MMP-8 activation in the saliva of AMI patients is evidently, in part, of systemic origin. Consequently, AMI is reflected in serum but also in saliva. [ABSTRACT FROM AUTHOR]

Background: The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland. Methods: The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors. Results: Median MMP-8 values of male smokers were 112.03 µg/l compared to 176.89 µg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 µg/l versus 177.92 µg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10-3 ΔOD405/h versus 11.0 x 10-3 ΔOD405/h in nonsmokers (P = 0.02), and in female smokers 9.16 x 10-3 ΔOD405/h versus 10.88 x 10-3 ΔOD405/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls. Conclusions: Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values. [ABSTRACT FROM AUTHOR]

Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time diagnosis and assessment of periodontitis severity at the site level. Gingival crevicular fluid (GCF) was sampled from 30 healthy, 42 mild, and 59 severe periodontitis sites from thirty-one volunteers. MMP-8 concentrations were determined by time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the STATA package. Both active and total MMP-8-based methods discriminated among sites according to periodontal diagnosis and severity, with a positive correlation between the two tests (p < 0.001). (a) MMP-8 models showed the best performance in receiver operating characteristic (ROC) curves to discriminate between healthy and periodontitis sites (area under the curve [AUC] = 0.89), while (t) MMP-8 demonstrated a high diagnostic precision in the detection of mild from severe periodontitis sites (AUC ≥ 0.80). The use of (a) MMP-8 and (t) MMP-8 could represent a useful adjunctive tool for periodontitis diagnosis and severity. These results support the applicability of new point-of-care methods in the monitoring of high-risk periodontal patients. [ABSTRACT FROM AUTHOR]

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients. [ABSTRACT FROM AUTHOR]

Biomarkers represent promising aids in periodontitis, host-mediate diseases of the tooth-supporting tissues. We assessed the diagnostic potential of matrix metalloproteinase-8 (MMP-8), tartrate-resistant acid phosphatase-5 (TRAP-5), and osteoprotegerin (OPG) to discriminate between healthy patients', mild and severe periodontitis sites. Thirty-one otherwise healthy volunteers with and without periodontal disease were enrolled at the Faculty of Dentistry, University of Chile. Periodontal parameters were examined and gingival crevicular fluid was sampled from mild periodontitis sites (M; n = 42), severe periodontitis sites (S; n = 59), and healthy volunteer sites (H; n = 30). TRAP-5 and OPG were determined by commercial multiplex assay and MMP-8 by the immunofluorometric (IFMA) method. STATA software was used. All biomarkers showed a good discrimination performance. MMP-8 had the overall best performance in regression models and Receiver Operating Characteristic (ROC) curves, with high discrimination of healthy from periodontitis sites (area under the curve (AUC) = 0.901). OPG showed a very high diagnostic precision (AUC ≥ 0.95) to identify severe periodontitis sites (S versus H + M), while TRAP-5 identified both healthy and severe sites. As conclusions, MMP-8, TRAP-5, and OPG present a high precision potential in the identification of periodontal disease destruction, with MMP-8 as the most accurate diagnostic biomarker. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and -9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with mild therapeutic hypothermia treatment on the serum concentration of these enzymes. Methods: MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated from cardiac arrest. The samples were taken at 24 and 48h from restoration of spontaneous circulation (ROSC). The biomarker levels were compared between patients (N =51) and healthy controls (N =10) and between patients who did (N =30) and patients who did not (N =21) receive mild therapeutic hypothermia. Results: MMP-7 (median 0.47ng/ml), MMP-8 (median 31.16ng/ml) and MMP-9 (median 253.00ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50ng/ml) in cardiac arrest patients as compared with healthy controls at 24h from ROSC. Hypothermia treatment associated with attenuated elevation of MMP-9 (p =0.001) but not MMP-8 (p =0.02) or MMP-7 (p =0.69). Concentrations of MMPs -7, -8 and -9 correlated with the leukocyte count but not with C-reactive protein (CRP) or neurone-specific enolase (NSE) levels. Conclusion: We demonstrated that the systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest patients in the 48h post-resuscitation period relative to the healthy controls. Patients who received therapeutic hypothermia had lower MMP-9 levels compared to non-hypothermia treated patients, which generates hypothesis about attenuation of inflammatory response by hypothermia treatment. [Copyright &y& Elsevier]

• GCF aMMP-8 chairside test sensitivity was 83.9 % and 79.2 % for specificity. • Stage IV periodontitis group had higher GCF aMMP-8 levels than the other groups. • Salivary aMMP-8 levels of P-Stage IV, III and gingivitis groups were higher than healthy group. • Low aMMP-8 levels but not total/latent MMP-8 clearly indicates periodontal health. • aMMP-8 is useful diagnostic biomarker for early detection in the new periodontitis classification. There is a need for a reliable complementary diagnostic tool that ideally helps to screen, differentiate sites, activities of and predict future periodontal tissue destruction. The purpose of this cross-sectional study was to investigate the screening and prevention potential of the chair-side/point-of-care (PoC) diagnostic test of salivary active matrix metalloproteinase-8 (aMMP-8) levels at different stages of periodontal disease and periodontal health. 80 individuals were included in this study; 18 with periodontitis stage 3 (P-Stage III), 19 with periodontitis stage-4 (P-Stage IV), 21 with gingivitis, and 22 with clinically healthy periodontium (H). The aMMP-8 levels in GCF and saliva were analyzed by chairside point-of-care aMMP-8 lateral flow immunotest and also by a time-resolved immunofluorescence assay (IFMA). The sensitivity of the chair-side/PoC test was 83.9 % while specificity was 79.2 %. The aMMP-8 IFMA levels in GCF were significantly higher in P-Stage IV group than P-Stage III, gingivitis and healthy groups (p = 0.01, p = 0.001, p = 0.00, respectively). Moreover, P-Stage III and gingivitis groups had significantly higher aMMP-8 IFMA levels than the healthy group (p < 0.05). The aMMP-8 chair-side test showed promising results in its ability to recognize and predict the inflammatory status even at the very initial/early stages. aMMP-8 chair-side test could be a valuable adjunctive diagnostic and preventive tool to conventional clinical methods in detecting periodontal disease. [ABSTRACT FROM AUTHOR]

This study investigated the diagnostic utility of mouthrinse and saliva in aMMP-8 measurements to analyze patients' risk for active periodontal tissue destruction and progression of periodontal disease among 47 adolescents. Results show that measurements from mouthrinse produce better discrimination and should be used instead of saliva measurements. [ABSTRACT FROM AUTHOR]