Veli Özgen Öztürk

Gingival crevicular fluid calprotectin, osteocalcin and cross-linked N-terminal telopeptid levels in health and different periodontal diseases

Aim: The aim of the present study was to investigate gingival crevicular fluid (GCF) calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx) levels in health along with different periodontal diseases. Material and methods: Twenty chronic periodontitis (CP), 20 generalized aggressive periodontitis (G-AgP), 20 gingivitis and 20 healthy subjects were included. Probing depth, clinical attachment level, plaque index and papillary bleeding index was recorded. GCF calprotectin, osteocalcin and NTx levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: CP, G-AgP and gingivitis groups had higher GCF calprotectin total amount compared to healthy subjects (p < 0.008). CP and G-AgP groups had similar, but higher levels compared to gingivitis groups (p < 0.008). CP and G-AgP groups had lower GCF osteocalcin total amount compared to gingivitis and healthy groups (p < 0.008). CP group had higher GCF NTx but lower osteocalcin total amount and osteocalcin/NTx ratio than the G-AgP group (p < 0.008) Conclusions: Our results suggest that elevated GCF calprotectin levels play a role as a reliable inflammatory marker in the pathogenesis of periodontal disease. Fluctuating GCF levels of osteocalcin and NTx might point out to the abnormal bone turnover in periodontitis. Our data document for the first time the role of NTx in the pathogenesis of different periodontal diseases.

Gingival crevicular fluid interleukin-36β (-1F8), interleukin-36γ (-1F9) and interleukin-33 (-1F11) levels in different periodontal disease

BACKGROUND Periodontal inflammation is driven by the coordinated action of a number of factors, including the IL-1 family. Our study aimed to examine the levels of interleukin (IL)-36β, IL-36γ and IL-33 levels in gingival crevicular fluid (GCF) from patients with different periodontal diseases. MATERIALS AND METHODS A total of 80 subjects, 20 patients with generalized aggressive periodontitis (G-AgP), 20 patients with chronic periodontitis (CP), 20 with gingivitis and 20 periodontally healthy subjects were included. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, papillary bleeding index and plaque index. GCF cytokine levels were analysed by ELISA. RESULTS CP, gingivitis and healthy groups had similar GCF IL-36β total amount (p>0.008). G-AgP group had elevated IL-36β total amount compared to CP group (p<0.008). G-AgP group had similar GCF IL-36β total amount to gingivitis and healthy groups (p>0.008). GCF IL-36γ and IL-33 total amounts of the study groups were similar (p>0.05). CONCLUSIONS The present study demonstrated for the first time the presence of IL-36β, IL-36γ and IL-33 GCF levels with different periodontal diseases. High levels of IL-36-β in the AgP group in comparison to CP group might suggest that periodontitis in the aggressive form could be related to the increase in GCF IL-36β.

Gingival Crevicular Fluid Osteocalcin, N-Terminal Telopeptides, and Calprotectin Levels in Cyclosporin A-Induced Gingival Overgrowth

BACKGROUND The aim of this cross-sectional study is to investigate gingival crevicular fluid (GCF) osteocalcin, cross-linked N-terminal telopeptide (NTx), and calprotectin levels in cyclosporin A (CsA)-induced gingival overgrowth (GO). METHODS Forty medicated patients with CsA including 20 with GO (CsA GO+), 10 without GO (CsA GO-), 10 with GO and chronic periodontitis (CsA CP) and 60 patients with CP alone, 20 patients with gingivitis, and 20 healthy patients were enrolled. Probing depth, clinical attachment level, plaque index, and papillary bleeding index were recorded. GCF calprotectin, osteocalcin, and NTx levels were analyzed by enzyme-linked immunosorbent assay. Parametric tests were used for statistical analysis. RESULTS The CsA GO+ and CP groups had significantly lower GCF osteocalcin levels and osteocalcin/NTx ratio than the healthy group, whereas GCF osteocalcin levels and osteocalcin/NTx ratio in the gingivitis group were higher than the CsA GO+, CsA GO-, CsA CP, and CP groups (P <0.05). The CP group had elevated GCF calprotectin levels compared to the other study groups (P <0.05). The CsA GO+ and CsA GO- groups also had higher GCF calprotectin levels compared to the CsA CP, gingivitis, and healthy groups (P <0.05). CONCLUSIONS Increased GCF calprotectin and decreased GCF osteocalcin levels in the CsA GO+ and CsA GO- groups might suggest that CsA plays a role on the levels of these markers. The similarity of GCF osteocalcin, NTx, and calprotectin levels in the CsA GO+ and CsA GO- groups might suggest that these molecules are not involved in the pathogenesis of GO.

Spectrophotometric and computerized evaluation of tooth bleaching employing 10 different home-bleaching procedures: In-vitro study

Objective: The aim of this in-vitro study was to evaluate the efficacy of bleaching products, determine the applicability and validation of the measurement methods. Materials and Methods: Freshly extracted 110 human incisor teeth were stained with whole blood and hemolysate solution prior to the application of 10 different home-bleaching products. Spectrophotometric measurements of the tooth shades were performed for each specimen before and after bleaching at the 1 st , 3 rd , 7 th , and 14 days. Differences in lightness (Δl ), chroma (Δc ), hue (Δh ) values and shade changes were measured to evaluate process. Computerized digital imaging analyses to determine the color changes were performed with  Photoshop CS4 software (Adobe, San Jose, CA, USA). Statistical analyses were performed with analysis of variance, Scheffe and Tukey tests. Results: In all of the test groups regardless of the material used, a significant increase in lightness and hue, and decrease of chroma were observed, as compared to the control group. After recommended bleaching applications, Δl and Δh values respectively increased in group Zaris White and Brite (ZWB) and group Pola Night and Δc values showed significant decrease in groups ZWB and Rembrandt REM3 (P < 0.05). At the end of the procedure both spectrophotometric and digital imaging analysis showed ZWB was the most effective product among the others while Yotuel and Happy Smile were the least (P < 0.05). Conclusions: Home-bleaching systems showed slower but almost permanent bleaching effect likewise office-based methods. Both software and spectrophotometric analyses have advantages such as evaluating the results objectively and numerically, also treatment outcomes could be preserved.

Salivary and Serum Markers Related to Innate Immunity in Generalized Aggressive Periodontitis

BACKGROUND Host inflammatory and immune responses play an important role in aggressive periodontitis (AgP). Thus, this study aims to evaluate levels of the innate immunity-related markers calprotectin, colony-stimulating factor (CSF)-1, macrophage migration inhibitory factor (MIF), monokine induced by interferon-γ (MIG), and matrix metalloproteinase (MMP)-8 in serum and saliva from patients with generalized AgP and those with gingivitis or a healthy periodontium. METHODS This study enrolled 40 individuals (17 males and 23 females; mean age 33.30 ± 9.31 years), 15 with generalized AgP, 15 with gingivitis, and 10 who were periodontally healthy. Full-mouth periodontal examinations were performed, and serum and saliva were collected. Levels of calprotectin, CSF-1, MIF, MIG, and MMP-8 were measured using enzyme-linked immunosorbent assays. RESULTS In serum, mean levels of calprotectin were 2.06-fold higher in patients with AgP than in healthy patients (P = 0.01). Serum levels of MMP-8 were significantly elevated in patients with AgP compared with both healthy patients and those with gingivitis, by 2.60-fold and 2.77-fold, respectively (P = 0.03 and P = 0.009, respectively). In saliva, levels of MMP-8 were 5.66-fold higher in patients with AgP than in healthy patients (P = 0.02). CSF-1, MIF, and MIG levels in both serum and saliva did not differ significantly among the groups. CONCLUSIONS Serum levels of calprotectin and MMP-8 are elevated in patients with AgP. MMP-8 levels are also increased in saliva from patients with AgP. These results support involvement of innate immune response in the pathogenesis of AgP.

Targeted proteomics guided by label-free quantitative proteome analysis in saliva reveal transition signatures from health to periodontal disease

Periodontal diseases are among the most prevalent worldwide, but largely silent, chronic diseases. They affect the tooth-supporting tissues with multiple ramifications on life quality. Their early diagnosis is still challenging, due to lack of appropriate molecular diagnostic methods. Saliva offers a non-invasively collectable reservoir of clinically relevant biomarkers, which, if utilized efficiently, could facilitate early diagnosis and monitoring of ongoing disease. Despite several novel protein markers being recently enlisted by discovery proteomics, their routine diagnostic application is hampered by the lack of validation platforms that allow for rapid, accurate and simultaneous quantification of multiple proteins in large cohorts. Here we carried out a pipeline of two proteomic platforms; firstly, we applied open ended label-free quantitative (LFQ) proteomics for discovery in saliva (n = 67, including individuals with health, gingivitis, and periodontitis), followed by selected-reaction monitoring (SRM)-targeted proteomics for validation in an independent cohort (n = 82). The LFQ platform led to the discovery of 119 proteins with at least 2-fold significant difference between health and disease. The 65 proteins chosen for the subsequent SRM platform included 50 functionally related proteins derived from the significantly enriched processes of the LFQ data, 11 from literature-mining, and four house-keeping ones. Among those, 60 were reproducibly quantifiable proteins (92% success rate), represented by a total of 143 peptides. Machine-learning modeling led to a narrowed-down panel of five proteins of high predictive value for periodontal diseases with maximum area under the receiver operating curve >0.97 (higher in disease: Matrix metalloproteinase-9, Ras-related protein-1, Actin-related protein 2/3 complex subunit 5; lower in disease: Clusterin, Deleted in Malignant Brain Tumors 1). This panel enriches the pool of credible clinical biomarker candidates for diagnostic assay development. Yet, the quantum leap brought into the field of periodontal diagnostics by this study is the application of the biomarker discovery-through-verification pipeline, which can be used for validation in further cohorts.

Gingival crevicular fluid and plasma oxidative stress markers and TGM-2 levels in chronic periodontitis

OBJECTIVE This study was aimed to evaluate the gingival crevicular fluid (GCF) and plasma transglutaminase-2 (TGM-2), total antioxidant capacity (TAC), total oxidant status (TOS), ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) in patients with chronic periodontal disease. MATERIALS AND METHODS Twenty patients with chronic periodontitis (CP), 20 patients with gingivitis and 20 healthy subjects were enrolled in the study. Clinical periodontal parameters including probing depth, clinical attachment level, plaque index and papillary bleeding index were recorded. GCF and plasma levels of TGM-2, TAC, TOS, TBARS and FRAP were analyzed. RESULTS GCF TGM-2 was significantly lower in CP group than in gingivitis patients (P=0.006). GCF FRAP in CP and gingivitis groups was significantly lower than in healthy subjects (P<0.001). Plasma FRAP level was lower in gingivitis group when compared to healthy subjects (P=0.003). There was no significant difference in GCF and plasma TAC, TOS, TBARS and plasma TGM-2 levels among the study groups (P>0.05). GCF TGM-2 level was positively correlated with GCF TAC and negatively correlated with CAL. CONCLUSIONS Decreased FRAP in GCF and plasma indicating lower antioxidant status of CP patients might suggest the role of oxidative stress in periodontitis. GCF TGM-2 data might suggest that TGM2 is associated with stabilization of the extracellular matrix and wound healing in periodontium rather than gingival inflammation.

Treatment of lateral open bite with vertical dentoalveolar distraction osteogenesis.

The aim of this article is to describe the surgical, orthodontic, and periodontal treatment of an adult patient with a lateral open bite, anterior crowding, and gingival recession on the mandibular right lateral incisor. The lateral open bite, which resisted conventional mechanics, was successfully corrected by the combination of dento-osseous osteotomies and vertical alveolar distraction using orthodontic multibracket appliances in conjunction with nickel-titanium archwires and intermaxillary elastics. After the orthodontic treatment, the denuded root surface of the mandibular right lateral incisor was closed using a coronally advanced flap technique with platelet-rich fibrin. The results at the 2-year posttreatment follow-up were satisfactory from both the occlusal and the periodontal standpoints.

Effect of orthodontic force magnitude on cytokine networks in gingival crevicular fluid: a longitudinal randomized split-mouth study

OBJECTIVE To compare effect of two different orthodontic forces on maxillary canine distalization via evaluation of 30 analytes including cytokines, growth factors, and chemokines in gingival crevicular fluid (GCF) obtained from tension and compression sites. DESIGN Longitudinal, split-mouth, randomized controlled trial. METHODS The upper right and left canines were randomly distalized by a continuous force of either 75 or 150 g, in 15 individuals with Class II division 1 malocclusion. GCF samples were obtained from the tension and the pressure sides of each canine at appliance placement (baseline) and after force application at 24 hours and 28 days without reactivation of the coil spring. The protein content of GCF was analysed by a multiplexed immunoassay. The effects of force, side, and time on the analyte levels were assessed by the Brunner-Langer method. OUTCOME The changes of GCF analyte levels from baseline to 24 hours and 28 days. RANDOMIZATION Coin flipping was used for allocation of two forces. BLINDING The participants and periodontist who performed clinical measurements and GCF sampling were blinded to group assignment and interventions (double-blinded trial). RESULTS All patients completed the study. No harm was observed. When compared to baseline, both forces caused significant up-regulation of tumour necrosis factor-α and interleukin (IL)-1RA in the tension and the pressure sides at 28 days (P < 0.05), but not at 24 hours. Although GCF volume was similar between the two force groups over time (P > 0.05), IL-8 and MCP-1 levels in GCF were significantly lower at the pressure sites receiving higher force (150 g) at 24 hours (P < 0.05). LIMITATIONS Although sample size (15 patients, 30 teeth) was adequate according to the initial power calculation, borderline significances may indicate lack of power or large variability among the samples. CONCLUSIONS Although a higher force of 150 g did not result in increased cumulative canine movement or GCF production, selective host mediators were differentially regulated by the magnitude and duration of the force. REGISTRATION AND TRIAL PROTOCOL The trial was registered retrospectively in the U.S. National Institutes of Health Clinical Trials Registry. Full details of trial protocol NCT03555747 are available on request.

Interleukin-6 Family of Cytokines in Crevicular Fluid of Renal Transplant Recipients With and Without Cyclosporine A–Induced Gingival Overgrowth

BACKGROUND Interleukin (IL)-6 family of cytokines, including IL-6, oncostatin M (OSM), leukemia inhibitory factor (LIF), and IL-11, have fibrogenic features. The current study determines gingival crevicular fluid (GCF) levels of fibrosis-related IL-6-type cytokines in cyclosporine A (CsA)-induced gingival overgrowth (GO). METHODS Eighty non-smokers were included (40 CsA-medicated renal transplant patients with GO [GO+; n = 20] or without GO [GO-; n = 20], 20 individuals with gingivitis, and 20 healthy participants). Probing depth and plaque, papilla bleeding, and hyperplastic index scores were recorded. GCF samples were obtained from the mesio-buccal aspects of two teeth. GCF IL-6, IL-1β, OSM, LIF, and IL-11 levels were analyzed by enzyme-linked immunosorbent assay. RESULTS The GO+ and GO- groups had higher IL-6 total amounts than the healthy group (P <0.008). IL-1β total amounts in the GO+ group were significantly higher than in both the healthy and GO- groups (P <0.008). OSM total amount was elevated in the GO+ and GO- groups compared with both the gingivitis and healthy groups (P <0.008). All groups had similar LIF and IL-11 total amounts (P >0.008). Moderate positive correlations were detected among IL-6, IL-1β, OSM, and IL-11 total amount in GCF and clinical parameters (P <0.05). CONCLUSIONS IL-6 and OSM increases in GCF as a result of CsA usage or an immunosuppressed state irrespective of the severity of inflammation and the presence of GO. The IL-6 family of cytokines might not be directly involved in biologic mechanisms associated with CsA-induced GO. Lack of an association between assessed IL-6 cytokines and CsA-induced GO might indicate distinct effects of these cytokines on fibrotic changes of different tissues.