Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

OBJECTIVES: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. MATERIALS AND METHODS: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. CONCLUSIONS: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. CLINICAL RELEVANCE: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

The impact of electronic cigarettes on peri-implant health: A systematic review and meta-analysis.

OBJECTIVES: Recent literature suggests that the use of electronic cigarette (e-cigarette) is a substantial contributing factor to the unsuccessful outcomes of dental implant procedures. Our aim was to systematically review the effect of e-cigarette use on clinical (PI, PD, BOP), radiographic (bone loss), and immunologic (IL-1ß) peri­implant parameters. DATA: Main search terms used in combination: electronic cigarette, peri­implantitis, vaping. SOURCES: An electronic search was undertaken for MEDLINE, EMBASE, COCHRANE, and SCOPUS databases between 2017 and 2023. STUDY SELECTION: The study protocol was developed according to PRISMA guidelines, and the focus question was formulated according to the PICO strategy. No restriction was accepted regarding language or year to avoid selection bias; the initial database search yielded 49 publications. Following the selection process, only seven studies met the inclusion criteria. Seven studies were statistically analyzed via MedCalc program. A pooled effect was deemed statistically significant if the p-value was less than 0.05. CONCLUSION: Electronic cigarettes cause an increase in probing depth, bone loss, and the level of IL-1ß, one of the bone destruction mediators in the tissues around the implant, and a decrease in bleeding on probing. CLINICAL SIGNIFICANCE: E-cigarette is a potential risk factor for the healing process and the results of implant treatment, similar to cigarettes. Performing clinical research to evaluate the e-cigarette effect on peri­implantitis in an age and gender-match population is needed.

The effect of smoking on clinical and biochemical early healing outcomes of coronally advanced flap with connective tissue graft: Prospective cohort study.

BACKGROUND: This study aimed to determine the effects of smoking on early (≤3 months) clinical outcomes and relevant molecular biomarkers following root coverage surgery. METHODS: Eighteen smokers and 18 nonsmokers, status biochemically verified, with RT1 gingival recession defects were recruited and completed study procedures. All patients received coronally advanced flap plus connective tissue graft. Baseline and 3 month recession depth (RD), recession width (RW), keratinized tissue width (KTW), clinical attachment level (CAL), and gingival phenotype (GP) were recorded. Root coverage (RC) percentage and complete root coverage (CRC) were calculated. Recipient (gingival crevicular fluid) and donor (wound fluid) site VEGF-A, HIF-1α, 8-OHdG, and ANG levels were determined. RESULTS: There were no significant intergroup differences for any baseline or postoperative clinical parameters (P > 0.05), except for whole mouth gingival index (increased in nonsmokers at 3 months; P < 0.05). Compared to baseline, RD, RW, CAL, KTW, and GP significantly improved postoperatively, without significant intergroup differences. There were no significant intergroup differences for RC (smokers = 83%, nonsmokers = 91%, P = 0.069), CRC (smokers = 50%, nonsmokers = 72%, P = 0.177), and CAL gain (P = 0.193). The four biomarker levels significantly increased postoperatively (day 7; P ≤ 0.042) in both groups and returned to baseline (day 28) without significant intergroup differences (P > 0.05). Similarly, donor site parameters were not different between groups. Strong correlations, consistent over time, were found between biomarkers implicated in angiogenesis (VEGF-A, HIF-1α, and ANG). CONCLUSIONS: The early (3 month) clinical and molecular changes after root coverage surgery utilizing a coronally advanced flap plus connective tissue graft are similar between smokers and nonsmokers.

Wnt signaling in periodontitis.

OBJECTIVE: This study aimed to evaluate the Wnt/ß-catenin signaling pathway activity in gingival samples obtained from patients with periodontitis. MATERIALS AND METHODS: Fifteen patients with stage III grade B (SIIIGB) and eleven with stage III grade C (SIIIGC) periodontitis were included and compared to 15 control subjects. ß-Catenin, Wnt 3a, Wnt 5a, and Wnt 10b expressions were evaluated by Q-PCR. Topographic localization of tissue ß-catenin, Wnt 5a, and Wnt 10b was measured by immunohistochemical analysis. TNF-α was used to assess the inflammatory state of the tissues, while Runx2 was used as a mediator of active destruction. RESULTS: Wnt 3a, Wnt 5a, and Wnt 10b were significantly higher in gingival tissues in both grades of stage 3 periodontitis compared to the control group (p < 0.05). ß-Catenin showed intranuclear staining in connective tissue in periodontitis, while it was confined to intracytoplasmic staining in epithelial tissue and the cell walls in the control group. Wnt5a protein expression was elevated in periodontitis, with the most intense staining observed in the connective tissue of SIIIGC samples. Wnt10b showed the highest density in the connective tissue of patients with periodontitis. CONCLUSIONS: Our findings suggested that periodontal inflammation disrupts the Wnt/ß-catenin signaling pathway. CLINICAL RELEVANCE: Periodontitis disrupts Wnt signaling in periodontal tissues in parallel with tissue inflammation and changes in morphology. This change in Wnt-related signaling pathways that regulate tissue homeostasis in the immunoinflammatory response may shed light on host-induced tissue destruction in the pathogenesis of the periodontal disease.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Does smoking influence tryptophan metabolism in periodontal inflammation? A cross-sectional study.

OBJECTIVES: The aim of this study was to identify the effects of smoking and periodontal inflammation on tryptophan-kynurenine metabolism as well as the correlation between these findings and clinical periodontal parameters. BACKGROUND: It has been shown that the tryptophan amino acid's primary catabolic pathway, the kynurenine pathway (KP), may serve as a key biomarker for periodontal disease. Although there are studies investigating the effect of smoking on KYN-TRP metabolism, the effect of smoking on periodontal disease through KP has not been revealed so far. METHODS: The salivary and serum samples were gathered from 24 nonsmoker (NS-P) stage III, grade B generalized periodontitis and 22 smoker (S-P) stage III, grade C generalized periodontitis patients, in addition to 24 nonsmoker (NS-C) and 24 smoker (S-C) periodontally healthy control individuals. Saliva and serum IL-6, kynurenine (KYN), and tryptophan (TRP) values, and KYN/TRP ratio were analyzed by liquid chromatography-mass spectrometry. Clinical periodontal measurements were recorded. RESULTS: Salivary TRP values were significantly higher in both periodontitis groups than control groups (p < .05). Salivary KYN values were highest in NS-P group (p < .05). Salivary KYN values did not differ significantly between periodontitis groups (p = .84). Salivary KYN/TRP ratio was significantly lower in NS-P group compared to other groups (p < .001). Serum TRP value is higher in S-P group than other groups; however, significant difference was found in S-C group (p < .05). Serum KYN values were significantly lower in smokers than nonsmokers. Serum KYN/TRP ratio is higher in NS-P group. NS-P group has the highest salivary IL-6 levels, NS-C group has the lowest values (p < .05). CONCLUSIONS: Our results point out that smoking exacerbates inflammation in the periodontium and increases TRP destruction and decreases IDO activity by suppressing KP in serum. As a result, kynurenine and its metabolites may be significant biomarkers in the link between smoking and periodontal disease.

Asymmetric and symmetric dimethylarginine gingival crevicular fluid levels in periodontitis.

OBJECTIVE: This study aimed to evaluate the level of ADMA (asymmetric dimethylarginine), SDMA (symmetric dimethylarginine), and IL-1ß (Interleukin-1ß) in gingival crevicular fluid (GCF) from periodontitis patients and control subjects. BACKGROUND: ADMA and SDMA are potentially hazardous non-proteinogenic amino acids that limit nitric oxide (NO) synthesis and have many functions in various human disorders. ADMA causes a structural change in nitric oxide synthase, while SDMA blocks arginine cell uptake. Increased plasma ADMA has been widely recognized as a "trigger" initiating impaired NO bioavailability and vascular dysfunction, which ultimately leads to oxidative stress. METHODS: Twenty-five patients with periodontitis (P) (Stage III, Grade C, n = 25) and 20 control (C) subjects were included in the study. The IL-1ß level of GCF was measured by enzyme immunoassay (ELISA) and ADMA and SDMA by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Periodontitis patients had higher clinical parameters than controls (p < .001). Levels of IL-1ß, ADMA and SDMA GCF were statistically significantly higher in group P than in group C (respectively; p = .003, p < .0001, p < .0001). There was no difference in the ADMA/SDMA ratio (p = .312) between the groups. There were significant positive correlations between clinical periodontal parameters and IL-1ß, ADMA, and SDMA levels (p < .05). ADMA and SDMA levels were significantly correlated with IL-1ß (p < .05). CONCLUSIONS: These findings suggest that ADMA and SDMA may be involved in the pathogenesis of the periodontal disease.

Do arginine metabolites have a role in periodontitis due to smoking? A new perspective.

OBJECTIVES: Cigarette consumption is common around the world and besides its negative effects on health, and its effects on periodontitis draw attention. Arginine metabolites are involved in the pathogenesis of several systemic inflammatory diseases' including cardiovascular diseases. Our aim was to determine periodontitis and healthy individuals' arginine metabolites and IL-6 levels in saliva and serum and to evaluate those according to smoking status. MATERIALS AND METHODS: The study consisted of four groups: healthy individuals (control [C]; n = 20), smokers with healthy periodontium (S-C; n = 20), nonsmokers with Stage-III Grade-B generalized periodontitis (P; n = 20) and smokers with Stage-III Grade-C generalized periodontitis (S-P; n = 18). Periodontal parameters were measured. Analysis of methylated arginine metabolites was performed by LC-MS/MS, and IL-6 levels were determined by ELISA kits. RESULTS: In nonsmokers, salivary concentrations of asymmetric dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were higher in the periodontitis than control (p < 0.001, p = 0.010). Smokers with periodontitis exhibited higher ADMA (p = 0.033, p < 0.001) and arginine (p = 0.030, p = 0.001) saliva concentrations than smoking and nonsmoking controls. CONCLUSIONS: Our results demonstrated that salivary concentrations of ADMA and SDMA were associated with periodontitis. Smoking increased ADMA, SDMA and NG -monomethyl L-arginine (L-NMMA) levels in serum only in periodontitis patients.

Influence of periodontal inflammation on tryptophan-kynurenine metabolism: a cross-sectional study.

OBJECTIVES: Kynurenine pathway (KP) is the primary way of degrading tryptophan (TRP) and generates several bioactive metabolites (such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3OHKYN)) to regulate biological processes that include host-microbiome signaling and immune cell response. This study is aimed to determine the relationship between periodontal inflammation and tryptophan-kynurenine metabolism and identify their association with periodontal clinical parameters. MATERIALS AND METHODS: Saliva and serum samples were collected from 20 stage III, grade B generalized periodontitis patients, and 20 periodontally healthy control individuals. Samples were analyzed for IL-6, KYN, TRP, KYN/TRP ratio, KYNA, 3OHKYN, picolinic acid (PA), and quinolinic acid (QA) by liquid chromatography-mass spectrometry. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) were recorded. RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). Salivary IL-6, TRP, KYN, KYNA, PA, and QA levels were significantly higher and KYN/TRP ratio was significantly lower in periodontitis group than control group (p < 0.05). Serum KYN, KYN/TRP ratio and PA levels were significantly higher in periodontitis group than control group (p < 0.05). PPD, BOP, PI, and CAL had significantly positive correlations with salivary IL-6, TRP, PA, QA, and serum KYN and significantly negative correlations with salivary KYN/TRP ratio. CONCLUSIONS: Our results suggest that periodontal inflammation plays a role in local and systemic tryptophan-kynurenine metabolism. CLINICAL RELEVANCE: Due to their effects on the immune and inflammatory systems, kynurenines may be potential agents for diagnosis and treatment of periodontal diseases.

Astaxanthin Enhances Gingival Wound Healing following High Glucose-Induced Oxidative Stress.

Fibroblasts of the gingiva play a key role in oral wound healing in diabetes. In this study, effects of astaxanthin (ASTX), a xanthophyll carotenoid, were tested on gingival fibroblasts in a wound healing assay in vitro. The aim of this study was to determine whether ASTX can recover delayed wound healing or not when oxidative stress is elevated by high glucose exposure. For this purpose, human gingival fibroblasts were incubated with or without ASTX following exposure to systemic doses of low glucose (LG) and high glucose (HG) in culture media (5- and 25-, 50 mM D-glucose in DMEM Ham's F12) following 24 hours of incubation. Levels of ROS (Reactive oxygen species) were determined for each experimental group by confocal microscopy. Cell proliferation and viability were assessed by an automated cell counter with trypan blue assay. Wound healing assay was designed in 60 mm petri dishes. Cells were exposed to 5-, 25-, and 50 mM glucose for 24 hours, and a straight line free of cells was created upon full confluency. 100 µM ASTX was added to the recovery group, simultaneously. Cells were monitored with JuLIⓇ-Br Cell History Recorder. ROS levels were significantly increased with increasing glucose levels, while cell proliferation and viability demonstrated a negative correlation with increasing oxidative stress. ROS levels significantly decreased in the 100 µM ASTX-treated group compared to the gingival fibroblasts treated with 50 mM HG medium-only, as well as growth rate and viability. Wound healing was delayed in a dose-dependent manner following high glucose exposure, while ASTX treatment recovered wounded area by 1.16-fold in the 50 mM HG group. Our results demonstrated that ASTX enhances gingival wound healing through its antioxidative properties following high glucose induced oxidative stress. Therefore, ASTX can be suggested as a promising candidate to maintain oral health in chronic wounds of the oral tissues related to diabetes.

Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients.

OBJECTIVES: Methylated arginine metabolites and nitric oxide synthase (NOS) play a critical role in regulating endothelial function. The aim of this study was to determine levels of NOS, and methylated arginine metabolites (ADMA, SDMA, homoarginine, arginine, and L-NMMA) and IL-6 in serum and saliva in patients with advanced periodontal diseases and identify their association with clinical parameters. MATERIALS AND METHODS: The study consisted of two groups: healthy individuals (control: n = 24), and generalized Stage III Grade B periodontitis (P: n = 21). Clinical periodontal parameters (probing pocket depth, bleeding on probing, clinical attachment level) were recorded. IL 6 and NOS levels in saliva and serum were analyzed by enzyme-linked immunosorbent assay (ELISA). ADMA, SDMA, homoArg, arginine, and L-NMMA in saliva and serum were analyzed by liquid chromatography-mass spectrometry (LC MS/MS). RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). In periodontitis group, NOS, ADMA, and arginine levels in saliva were statistically significantly higher than control group (p < 0.05). Serum levels of SDMA were statistically significantly lower, and IL-6 was statistically significantly higher in P group than C group (p < 0.05). ADMA, NOS, and arginine levels were significantly positive correlated with all clinical periodontal parameters (p < 0.05). CONCLUSIONS: These findings suggest that there is a relationship between severity of periodontal disease and endothelial dysfunction by means of ADMA. Salivary ADMA may be related with periodontal inflammation. CLINICAL RELEVANCE: ADMA levels in periodontal inflammation are associated with endothelial dysfunction. According to the results of our study, periodontal inflammation is effective on both local and systemic methylated arginine metabolites and nitric oxide synthase levels. This may shed light on the relationship between periodontal disease and systemic status.

Free amino acid composition of saliva in patients with healthy periodontium and periodontitis.

OBJECTIVES: To identify and compare the free amino acids in the saliva of periodontitis patients and healthy individuals and to assess their levels in different periodontal disease types. MATERIALS AND METHODS: There were three groups: healthy individuals (control (C); n = 20), Stage III Grade B generalized periodontitis (GP-B; n = 20), and Stage III Grade C generalized periodontitis (GP-C; n = 20). Clinical periodontal parameters were measured. Amino acid analysis of the saliva was accomplished by liquid chromatography-mass spectrometry (LC MS/MS), taking the mean concentration. RESULTS: Citrulline and carnosine concentrations were significantly higher in patients with periodontitis than in the control group (p < 0.017). Methionine, glutamic acid, and arginine showed significantly higher concentrations in GP-C, whereas proline and tryptophan showed higher concentrations in the GP-B group (p < 0.017). There was a significant correlation between methionine, citrulline, arginine, and carnosine and clinical periodontal parameters. CONCLUSIONS: Our results demonstrate that periodontal status and disease type can result in variations in salivary amino acid (AA) content in correlation with clinical inflammatory signs. The significant correlation of methionine, citrulline, carnosine, and arginine with clinical parameters, regardless of systemic status, suggests that the levels of different salivary free AAs play roles in periodontitis. CLINICAL RELEVANCE: Salivary free AAs may be suggested as a potential diagnostic compound in patients with periodontitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04642716.

Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1).

OBJECTIVE: The aim of this study was to determine differences in GCF and serum levels of fractalkine/CX3CL1 and its receptor/ CX3CR1 between the patients with stage III/grade B periodontitis and periodontally healthy subjects. BACKGROUND: Fractalkine (CX3CL1), the only member of CX3C chemokine family, is involved in the pathogenesis of several systemic inflammatory diseases' disorders including rheumatoid arthritis, cardiovascular diseases, tonsillitis, and diabetes mellitus. It has critical functions in inflammatory cell migration, adhesion, and proliferation. METHODS: 20 stage III/grade B periodontitis (P) and 20 healthy individuals (control; C) were included in this clinical study (all never smokers and systemically healthy). Clinical periodontal parameters were measured. Serum and GCF levels of CX3CL1, CX3CR1, and IL-1ß were quantified by enzyme-linked immunosorbent assay and reported as total amounts and concentration. RESULTS: The GCF concentrations and also total amount of CX3CL1, CX3CR1, and IL-1ß were statistically significantly higher in the patients with periodontitis compared with control group (P < 0.05). CX3CL1, CX3CR1, and IL-1ß levels in the GCF were significantly and positively correlated with all the clinical periodontal parameters (PI, PPD, BOP, and CAL; P < 0.01, P < 0.05). There was a significant correlation between IL-1ß, CX3CL1, and CX3CR1 concentrations in the GCF (respectively; r = 0.838 and r = 0.874, P < 0.01). CONCLUSION: Fractalkine and its receptor may play role in mechanisms through the regulation of inflammation or on the pathogenesis of periodontal disease.

Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross-sectional study.

BACKGROUND: Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS: Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS: Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P < 0.001). Salivary MDA levels were significantly higher in all disease groups compared to H-H group (P ≤ 0.004). Serum AGE levels were significantly higher in diabetic groups than systemically healthy groups (P < 0.001) and in H-P compared to H-H (P < 0.001). Bleeding on probing (BOP) and clinical attachment level (CAL) strongly correlated with salivary 8-OHdG and serum hsCRP (P < 0.001). In systemically healthy patients, salivary 8-OHdG was the most accurate marker to differentiate periodontitis from controls (AUC = 0.84). In diabetics salivary 4-HNE and RAGE were the most accurate (AUC = 0.85 for both). CONCLUSION: Salivary 8-OHdG alone or in combination with 4-HNE, AGE and RAGE for diabetics, and salivary 8-OHdG alone or in combination with MDA and hsCRP for systemically healthy persons, could potentially serve as non-invasive screening marker(s) of periodontitis.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis.

Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

A disintegrin-like and metalloproteinase with thrombospondin-1 (ADAMTS-1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor-A, hypoxia-inducible factor-1α, and clinical parameters in patients with advanced periodontitis.

BACKGROUND: ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin) are a family of proteinases that are structurally similar to the family of matrix metalloproteinases with critical roles in damage and repair of the extracellular matrix. Their functions are closely related to inflammation, hypoxia, and vascularization. Our aim was to determine levels of ADAMTS-1 in gingival crevicular fluid (GCF) in patients with advanced periodontal diseases and identify their association with hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF-A), and clinical parameters of periodontitis. METHODS: The study consisted of three groups: healthy individuals (control; n = 20), generalized chronic periodontitis (CP; n = 21), and generalized aggressive periodontitis (GAgP; n = 20). Clinical parameters were measured. Levels of ADAMTS-1, VEGF-A, and HIF-1α in GCF and serum were quantified by enzyme-linked immunosorbent assay (ELISA) and reported as total amounts and concentration. RESULTS: ADAMTS-1 total amount in GCF were significantly higher in patients with CP and GAgP compared with healthy individuals (P < 0.05). HIF-1α total amount in GCF were also higher in periodontitis groups compared with the control group (P < 0.05). GCF total VEGF-A content was significantly higher in the GAgP group compared with the CP and the controls (respectively; P = 0.023, P = 0.003). There was a significant correlation between ADAMTS-1, VEGF-A, and HIF-1α levels in the GCF and clinical periodontal parameters (probing depth [PD], bleeding on probing [BOP], and clinical attachment loss (CAL); P < 0.05). CONCLUSION: ADAMTS-1 may play a role in advanced periodontal disease pathogenesis in correlation with tissue hypoxia and vascularization.

Evaluation of 0.2% delmopinol mouth rinse for prevention of peri-implant mucositis and peri-implantitis: A randomized controlled canine study.

OBJECTIVES: To evaluate the effectiveness of 0.2% delmopinol mouth rinse in maintenance of peri-implant tissue health and prevention or inhibition of peri-implant mucositis and peri-implantitis. MATERIALS AND METHODS: Four weeks following tooth extraction, eight titanium dental implants, were placed in six dogs' mandibles. Three dogs were assigned to the test or placebo mouth rinse. Eight weeks following implant installation (T2) ligature was placed to induce peri-implant disease. Clinical and radiographic assessment was performed during the study period as well as micro-CT analysis and histologic assessment to evaluate Bone-Implant Contact at the end of the follow-up (T4). RESULTS: Plaque at implant sites before ligature placement (T2) was lower for the test group (0.7 ± 1.0 vs 1.5 ± 1.3, P < .05). The ratio of affected implant (PD ≧4 mm) at T2 and T4 in the test group was significantly smaller than that of the placebo group (T2, 17% vs 47%, P < .01; T4, 67% vs 83%, P < .05). The test agent also seemed to be effective in partially preventing bone loss induced by ligature placement according to the Computed Tomography and histologic analysis (test, 1.1 ± 0.8 mm; placebo, 1.5 ± 0.9 mm). CONCLUSIONS: Within the limits of this animal model study, the results of the study indicate that the 0.2% delmopinol rinse might play a role in prevention of peri-implant disease development.

A Novel Systemic Indicator of Periodontal Tissue Damage: Ischemia Modified Albumin.

BACKGROUND: Ischemia-modified albumin (IMA) is a systemic indicator of inflammatory diseases and is suggested as an oxidative stress marker. OBJECTIVE: To determine the IMA and high-sensitivity C-reactive protein (hsCRP) serum levels for patients with chronic periodontitis (CP) and to evaluate the impact of non-surgical periodontal therapy on serum IMA and hsCRP levels. METHODS: Twenty one systemically healthy patients with CP and 15 systemically and periodontally healthy controls (C) were enrolled in the study. Periodontal pocket depth (PPD), bleeding on probing (BOP) and attachment loss (AL) were recorded at the time of diagnosis and 6 weeks after the nonsurgical periodontal therapy. Blood samples were obtained before and after treatment from all groups, and serum IMA and hsCRP levels were evaluated by ELISA method. RESULTS: All of the clinical findings were found to be elevated in the CP group in comparison to C group (p<0.05). Levels of IMA and hsCRP were higher in the CP group (p<0.05) and decreased after non-surgical periodontal therapy (p<0.05). Positive correlations were determined between PPD, BOP and hsCRP (p<0.05) as well as between PPD, AL, BOP and IMA levels (p<0.01) before treatment. A significant positive correlation was also observed between hsCRP and IMA (p<0.01) before and after treatment. CONCLUSION: IMA is a marker indicating systemic inflammation during periodontal disease, and is significantly reduced as a result of non-surgical periodontal therapy. Therefore, IMA might be suggested as a useful indicator of periodontal disease.

Molecular basis for immunohistochemical and inflammatory changes during progression of gingivitis to periodontitis.

Two common diseases - gingivitis and periodontitis - affect the periodontium. Symptoms of disease entities are used for distinguishing various forms of gingivitis and periodontitis. Gingivitis follows a linear and progressive course when a healthy individual stops oral care, as shown by the experimental gingivitis model. It is not known if and when gingivitis transforms into periodontitis. A very limited number of studies present direct evidence regarding the histological changes over time and how they correlate to the clinical transition from gingivitis to periodontitis. This review focuses on the pathological changes that occur during the progression of gingivitis into periodontitis through discussing the molecular, cellular and immunohistochemical aspects of the inflammatory process. Molecular pathways regulating periodontal inflammation also determine the outcomes of disease and healing. Treatment of inflammatory diseases, particularly periodontitis in which extensive tissue damage could result from the inflammatory process, needs to target full restoration of the lost tissues. This can only be accomplished by a thorough understanding of the activation and resolution of periodontal disease and of the molecular events that occur during these phases.