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Öğe A comparative analysis of treatment-related changes in the diagnostic biomarker active metalloproteinase-8 levels in patients with periodontitis(2023) Keskin, Mutlu; Rintamarttunen, Juulia; Gülçiçek, Emre; Räisänen, Ismo T.; Gupta, Shipra; Tervahartiala, Taina; Pätilä, Tommi; Sorsa, TimoBackground: 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.Öğe Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: A pilot study(Taylor & Francis Ltd, 2020) Keskin, Mutlu; Lahteenmaki, Hanna; Rathnayake, Nilminie; Raisanen, Ismo T.; Tervahartiala, Taina; Parnanen, Pirjo; Sorsa, TimoBackground: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. Research design and methods: Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe (R)/ORALyzer (R)) for aMMP-8 and ELISA for IL-6. Results: HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. Conclusions: Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.Öğe aMMP-8 oral Fluid PoC test in relation to oral and systemic diseases(2022) Sorsa, Timo; Nwhator, Solomon Olusegun; Sakellari, Dimitra; Grigoriadis, Andreas; Umeizudike, Kehinde Adesola; Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Parnanen, Pirjo; Gupta, Shipra; Mohindra, Ritin; Bostancı, Nagihan; Buduneli, Nurcan; Raisanen, Ismo TapaniThe manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75-85% and specificity in the range of 80-90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.Öğe Author Response: Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study(2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, Timo...Öğe Induction of collagenolytic MMP-8 and -9 tissue destruction cascade in mouth by head and neck cancer radiotherapy: a cohort study(2023) Brandt, Ella; Keskin, Mutlu; Raisanen, Ismo; Tervahartiala, Taina; Makitie, Antti; Harmankaya, İlknur; Karaçetin, Didem; Hagström, Jaana; Rautava, Jaana; Sorsa, TimoThe effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (n = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe®/ORALyzer® (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment.Öğe Oral cavity beta-defensin levels are regulated differently during radiotherapy in head and neck cancer patients(MDPI, 2023) Keskin, Mutlu; Suomi, Emma; Harmankaya, İlknur; Karaçetin, Didem; Sorsa, Timo; Gürsoy, Ulvi KahramanBackground: Human beta-defensins (hBDs) are small cationic peptides of the epithelium with broad antimicrobial and immune response-regulatory activities. hBDs are also related to oncogenesis, and their secretion profiles are affected by radiotherapy treatment. The present study aimed to investigate the oral cavity hBD 1-3 levels in head and neck cancer patients and its relation to radiotherapy treatment. Methods: Sixteen head and neck cancer patients (all with a history of smoking) were included in this study. Periodontal parameters were measured before radiotherapy, and medical information was collected from registries. Oral rinses of the patients were collected before radiotherapy; on the 1st, 3rd, and 6th weeks of radiotherapy; and the 1st month following the end of radiotherapy. hBD 1–3 levels were measured using ELISA. Results: Oral hBD-1 levels increased during radiotherapy at week 6 (p = 0.019). hBD-1 levels returned to pretreatment levels after the end of radiotherapy. No significant change was detected for hBD-2 or hBD-3 levels during or after radiotherapy. Conclusions: The constant expression of hBD-1, which is distinct from the infection and inflammation-dependent expression profiles of hBD-2 and hBD-3, may explain why this peptide is the only one affected by radiotherapy.Öğe Oral cavity calprotectin and lactoferrin levels in relation to radiotherapy(2022) Keskin, Mutlu; Kompuinen, Jenna; Harmankaya, İlknur; Karaçetin, Didem; Nissilä, Verneri; Gürsoy, Mervi; Sorsa, Timo; Gürsoy, Ulvi KahramanBackground: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.Öğe Periodontal disease - a late complication of head and neck cancer radiotherapy(2024) Brandt, Ella; Keskin, Mutlu; Raisanen, Ismo T.; Makitie, Antti; Patila, Tommi; Sorsa, Timo; Gupta, Shipra...Öğe Radiotherapy increases aMMP-8-levels and neutrophil/lymphocyte ratio rapidly in head and neck cancer patients: a pilot study(2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, TimoRadiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.
