Obesity and cathepsin S in periodontal health and disease: A prospective clinical observational study.

The purpose of this study was to investigate the effects of obesity on reduced and oxidized glutathione (GSH and GSSG) levels in the gingival crevicular fluid, plasma and saliva of patients with chronic periodontitis and to evaluate the changes after nonsurgical periodontal therapy. The study included 60 patients: 30 patients with chronic periodontitis (15 obese patients and 15 normal weight patients) and 30 healthy control subjects (15 obese patients and 15 normal weight patients). Gingival crevicular fluid, plasma and saliva samples were collected, and clinical periodontal measurements were recorded at baseline and at the first month after periodontal therapy from patients with chronic periodontitis. GSH and GSSG levels were analyzed with spectrophotometry. The GSH levels in the plasma, saliva and gingival crevicular fluid in obese individuals with chronic periodontitis were lower than in normal weight individuals at baseline (p < 0.01). There was a significant difference in the GSH/GSSG ratio in plasma and gingival crevicular fluid between the obese and normal weight groups at baseline (p < 0.01). The GSH levels in plasma, gingival crevicular fluid and saliva were significantly increased in both chronic periodontitis groups after nonsurgical periodontal therapy (p < 0.01). A significant positive correlation was found between GSH levels in saliva, plasma and gingival crevicular fluid in all groups (p < 0.001). The study revealed that obesity in patients with chronic periodontitis is associated with decreased GSH levels and the GSH/GSSG ratio. Moreover, nonsurgical periodontal therapy may be helpful for improvement in glutathione values in obese and normal weight individuals with chronic periodontitis.

PurposeThe present study was conducted to evaluate the impact of scaling and root planing (SRP) on the C-reactive protein (CRP) levels of gingival crevicular fluid (GCF) and serum in chronic periodontitis patients with type 2 diabetes mellitus (T2DM-CP) or without type 2 diabetes mellitus (NDM-CP).MethodsForty-eight human participants were divided into two groups: an experimental (T2DM-CP) group (group I, n=24) comprising chronic periodontitis patients with random blood sugar ≥200 mg/dL and type 2 diabetes mellitus, and control (NDM-CP) group (group II, n=24) of those with chronic periodontitis and random blood sugar <200 without T2DM for the study. All subjects underwent nonsurgical periodontal therapy (NSPT) including complete SRP and subgingival debridement. Periodontal health parameters, plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), GCF volume (GCF vol), GCF-CRP, random blood glucose (RBS), glycated hemoglobin, and systemic inflammatory markers, serum CRP, total leukocyte count (TLC), neutrophil count (Neutr) and lymphocyte count (Lymph), were evaluated at baseline, 1 month, and 3 months after SRP.ResultsNSPT resulted in statistically significant improvement in periodontal health parameters (PI, GI, PPD, CAL, GCF vol), CRP levels in serum as well as GCF of both groups I and II. The mean improvement in periodontal health parameters (PI, GI, PPD, CAL, GCF vol), CRP levels in serum and GCF was greater in group I than group II after NSPT. There was nonsignificant increase in GCF-CRP, TLC, Lymph, and RBS, and a significant increase in Neutr and Serum CRP in group II at 1 month. The Serum CRP level of 20 out of 24 group II patients had also increased at 1 month.ConclusionsThe CRP levels in both GCF and serum were higher in T2DM-CP patients than in NDM-CP patients. Although there was a significant improvement in both the groups, greater improvement was observed in both GCF and serum samples of T2DM-CP patients.Graphical

MMP-8 is a prominent collagenase in periodontal disease. This cross-sectional study examined whether MMP-8 levels in saliva and gingival crevicular fluid (GCF) are associated with periodontitis in a Swiss population. A total of 258 subjects (107m, 151 f, mean age: 43.5yr; range: 21-58yr) acquired from the Swiss bone marrow donor registry participated in the study. Saliva and GCF samples were collected from subjects followed by a thorough dental and periodontal examination. MMP-8 levels were determined with immunofluorometric assay. Associations of MMP-8 levels with periodontal diagnosis, probing pocket depth (PPD) and bleeding on probing were statistically analysed with Pearson chi-square test, Spearman's rho and logistic regression analysis. MMP-8 in GCF correlated with MMP-8 in saliva (p<.001). Periodontitis was more common (p<.001) among subjects with high levels of MMP-8 in saliva and/or GCF compared with subjects with low levels of MMP-8. Higher MMP-8 levels in GCF and saliva were associated with any periodontal diagnosis (mild, moderate or severe), greater PPD, and bleeding on probing (p<.05). When age, gender, smoking, body mass index, number of medications and decayed, missing and filled teeth were adjusted for, all observed associations remained statistically significant. The area under curve of receiver-operating characteristic was 0.67 for saliva and 0.71 for GCF. Elevated MMP-8 levels both in saliva and GCF are associated with periodontitis in a normal adult population.

The aim of this study was to measure melatonin levels in the gingival crevicular fluid and saliva of subjects with healthy periodontal tissues, plaque-induced gingival inflammation, chronic periodontitis and aggressive periodontitis. A total of 70 subjects were examined and assigned to four groups: healthy periodontium (10 subjects); plaque-induced gingival inflammation (20 subjects); chronic periodontitis (20 subjects); and aggressive periodontitis (20 subjects). Gingival crevicular fluid and saliva samples were collected from each subject and analyzed using ELISAs. The melatonin levels in both gingival crevicular fluid and saliva were lower in patients with chronic periodontitis (10.4 and 12.8 pg/mL, respectively) and aggressive periodontitis (8.4 and 8.8 pg/mL, respectively) than in patients with gingivitis (13.9 and 17.6 pg/mL, respectively) and in healthy subjects (16.6 and 22.9 pg/mL, respectively). The mean melatonin levels in both gingival crevicular fluid and saliva were statistically significantly higher in healthy patients compared with patients with chronic periodontitis and aggressive periodontitis; however, there was no significant difference in the plaque-induced gingival inflammation between the study groups. The melatonin levels in gingival crevicular fluid and saliva are decreased in diseased periodontal tissues, especially periodontitis. The melatonin level was lowest in the aggressive periodontitis group.

The incidence and progression of the periodontal disease depend on periodontal microflora and the multifaceted response of the host, and these interactions are mediated by cytokines and chemokines. Interleukin-18 (IL-18) is a proinflammatory cytokine of the IL-1 superfamily. The aim of the present study was the assessment of the periodontal therapy in IL-18 level in periodontal disease and health. Based on clinical attachment loss (CAL), probing pocket depth (PPD), gingival index (GI), and plaque index (PI) patients were divided into three groups: Group I with healthy patients, group II with chronic periodontitis, and group III with posttreatment patients having periodontitis. Mean PI, PPD, CAL, and gingival crevicular fluid (GCF) volume were significantly higher in groups II and III compared with group I. However, there were no significant differences between GI in groups I, II, and III. The total amount of IL-18 in GCF was significantly higher in group II when compared with groups I and III (p < 0.05). The present study confirmed that the IL-18 level in GCF was lower in healthy patients, higher in periodontally involved patients, and reduced at baseline, 3 and 6 weeks after nonsurgical periodontal therapy. The IL-18 might be hypothetically beneficial in distinguishing health from disease and monitoring periodontal disease activity.

Aim: Drug-induced gingival overgrowth has a multifactorial nature and the pathogenesis is still uncertain. It has been suggested that Nitric Oxide (NO) might play a role in the pathogenesis of drug-induced gingival overgrowth due to the contribution of NO to immune response and matrix degradation. NO levels in biological fluids have been used as a diagnostic biomarker in many diseases. The aim of this study is to determine whether NO levels in plasma, saliva, and gingival crevicular fluid (GCF) can serve as a potential biomarker for the evaluation of drug-induced gingival overgrowth risk.Materials and Methods: A total of 104 patients, receiving cyclosporine A (n = 35), phenytoin (n = 25), nifedipine (n = 26), or diltiazem (n = 18) participated in the study. The amount of gingival overgrowth was evaluated with two indices and was given as percentage. Periodontal clinical parameters including plaque index (PI), gingival index (GI), gingival bleeding time index (GBTI), and probing depth (PD) were also assessed. Saliva, GCF, and plasma samples were obtained from each participants. Nitrite and nitrate levels in saliva, GCF, and plasma were analyzed by Griess reagent.Results: Salivary nitrite and nitrate levels in responders were significantly higher than those in non-responders in only phenytoin group (p < 0.05). Nitrite and nitrate levels of gingival crevicular fluid and plasma did not significantly differ between responders and non-responders in all study groups (p > 0.05). Salivary nitrite levels exhibited a significant correlation with PD, GBTI, severity of gingival overgrowth (%GO), and GCF volume (p < 0.05). Additionally, a strong positive correlation was detected between saliva and plasma nitrate levels (p < 0.005). However, both nitrite and nitrate levels in GCF and plasma demonstrated no significant correlation with clinical parameters, GO severity, and GCF volume (p > 0.05).Conclusion: Salivary nitrite and nitrate levels could be used as periodontal disease biomarkers in phenytoin induced gingival overgrowth, and that saliva seems to have a better diagnostic potential than GCF and plasma for the evaluation of drug-induced gingival overgrowth risk. However, when all drug groups were considered, saliva nitrite and nitrate levels could not be used as a biomarker for drug-induced gingival overgrowth.

Background:Reactive oxygen metabolites (ROMs) produced in periodontitis could contribute to excessive tissue damage. Thus, treatment of chronic periodontitis may decrease the ROM levels. The aim of this study is to evaluate the ROM levels in plasma, saliva, and gingival crevicular fluid (GCF) in generalized chronic periodontitis (GCP) patients before and after nonsurgical periodontal treatment.Materials and Methods:Two groups were included in this study. Group I consisted of 30 healthy controls (C) and Group II consisted of 30 subjects with GCP. Plaque index (PI), papillary bleeding index, Probing Depth (PD), and clinical attachment level were recorded. GCF, saliva, and plasma samples were collected from both groups. ROM levels were assessed. A baseline comparison was made between the two groups. Nonsurgical periodontal treatment was carried out for Group II subjects. Two months posttreatment, the clinical parameters and ROM levels in GCF, saliva, and plasma were reassessed in Group II, and the data were compared with their baseline values. Statistical analysis was done using SPSS 20 software and results were derived.Results:Two months posttreatment, Group II exhibited significant reduction in ROM levels in plasma, saliva, and GCF with significant decrease in PI, bleeding on probing, probing depth, and attachment loss.Conclusion:Thus, significant oxidative stress may occur in chronic periodontitis and nonsurgical periodontal therapy may be regarded as an effective treatment modality to treat the diseased periodontium, thereby preventing possible systemic diseases in future.

The level of Substance-P in gingival crevicular fluid has been found to correlate with clinical measures of periodontal disease. The present study was designed to assess the relationship between clinical parameters and levels of Substance-P in the gingival crevicular fluid from inflamed gingiva, periodontitis sites and after treatment of periodontitis sites, and to correlate them to the Substance-P levels of plasma. Thirty, age- and gender-matched subjects were divided into three groups (healthy, gingivitis and chronic periodontitis) based on modified gingival index scores and clinical attachment loss. A fourth group consisted of 10 subjects from the periodontitis group, 6-8 wk after initial therapy. Plasma and gingival crevicular fluid samples were collected and quantified for Substance-P using an enzyme immunoassay. The mean concentration of Substance-P, both in gingival crevicular fluid and plasma, was observed to be highest in the periodontitis group (45.13 pg/mL in gingival crevicular fluid and 67.8 pg/mL in plasma) and lowest in the healthy group (6.07 pg/mL in gingival crevicular fluid and below the detection level in plasma). The mean Substance-P concentration in the gingivitis group (11.42 pg/mL in gingival crevicular fluid and 38.8 pg/mL in plasma) and in the after-treatment group (7.58 pg/mL in gingival crevicular fluid and 39.7 pg/mL in plasma) lay between the highest and lowest values. In all groups the gingival crevicular fluid levels showed a statistically significant positive correlation with that of plasma and clinical attachment loss. Substance-P levels were highest in the gingival crevicular fluid from sites with periodontal destruction; however, periodontal treatment resulted in the reduction of Substance-P levels. Gingival crevicular fluid and plasma Substance-P levels showed a positive correlation in all of the groups.

The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of 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.

The aim of this study is to determine the levels of MFG-E8 and interleukin (IL)-1β in saliva and gingival crevicular fluid (GCF) associated with periodontal health and disease. Whole saliva and GCF samples were obtained from systemically healthy participants who were either periodontally healthy (n = 24) or suffered from gingivitis (n = 25) or chronic periodontitis (n = 25). Full-mouth clinical periodontal measurements, including bleeding on probing, probing depth, gingival index, plaque index, and clinical attachment level were also recorded. Enzyme-linked immunosorbent assay was used to estimate MFG-E8 and IL-1β levels in the samples. Analysis of variance, Kruskal-Wallis tests, and Pearson correlation tests were used to analyse the data statistically. The total level of MFG-E8 in GCF was significantly higher in the healthy group than in the other two groups (P = 0.01). Salivary MFG-E8 levels did not differ significantly among the groups. There were negative correlations between the level of MFG-E8 in GCF and probing depth (P = 0.03), bleeding on probing (P = 0.001), plaque index (P = 0.003), and gingival index (P = 0.003). The total level of IL-1β in GCF was significantly lower in the healthy group than in the groups with gingivitis and chronic periodontitis (P < 0.001). Salivary IL-1β levels showed significant differences across all three groups (P < 0.001). The level of MFG-E8 in GCF was higher in the healthy group than in the periodontal disease groups. Furthermore, there was no difference between gingivitis and periodontitis groups. The relationship between MFG-E8 and periodontal status should be further investigated.

Background: Periodontal disease is an inflammation caused by host parasite interaction leading to the destruction of tooth supporting structures. During inflammation there is an elevated levels of biochemical signalling molecules. A disintegrin and metalloproteinase 8 (ADAM8) molecule has been implicated in various physiologic functions and pathologies. The expression of ADAM8 is upregulated in inflammatory conditions, and with upregulated expression they play a pivotal role in inflammation, immunity and osteoclastogenesis. Objective: To evaluate ADAM8 levels in gingival crevicular fluid (GCF) collected from healthy individuals and individuals with periodontal disease at baseline and in the periodontal disease group after nonsurgical periodontal therapy. Methods: In total, 48 subjects aged 20–65 years were divided into separate groups: a periodontally healthy group (group 1: males, n = 7, females, n = 9), a chronic gingivitis group (group 2: males, n = 6, females, n = 10), and a chronic periodontitis group (group 3: males, n = 8, females, n = 8). GCF samples were collected from all the groups at baseline and 3 months after nonsurgical periodontal therapy in the chronic gingivitis (group 4) and chronic periodontitis (group 5) cases. Statistical analysis was performed using Shapiro-wilk normality test, One way ANOVA test, Kruskal-Wallis test followed by Mann-Whitney U test, Spearman’s rank correlation test and multiple linear regression analysis was done. The level of significance was determined at P < 0.05. Results: ADAM8 levels in the gingival crevicular fluid was significantly higher in group 3 (26,416.25 ± 7,817.59) than groups 1 and 2 at baseline at P < 0.001. After non-surgical periodontal therapy, ADAM8 levels in the gingival crevicular fluid was significantly reduced for group 2 (13,186.88 ± 3,247.62) and group 3 (18,375.63 ± 3,339.07) at P < 0.001. Conclusion: ADAM8 levels were increased in chronic gingivitis (group 2) and chronic periodontitis group (group 3) and reduced after non-surgical periodontal therapy in groups 2 and 3.

The aim of this study was to determine the levels of resolvin D1 (RVD1) in the gingival crevicular fluid (GCF) and saliva in the patients with periodontitis and healthy subjects, and also to evaluate the effects of non-surgical periodontal treatments (NSPTs) on RVD1 levels. Fifteen patients with Stage III Grade B periodontitis (P) and 11 periodontally healthy individuals (H) were included in this study. Clinical periodontal measurements, GCF, and saliva samples were collected from each individual at baseline and 6weeks after NSPTs in periodontitis group. GCF and saliva levels of RVD1 were analyzed by enzyme-linked immunosorbent assay. GCF total and concentration levels of RVD1 were significantly lower in the periodontitis group than in the healthy group and significantly increased after NSPTs in periodontitis (p < 0.001). There was no statistically significant difference in saliva RVD1 levels between healthy and periodontitis group and also before and after NSPTs in periodontitis (p > 0.05). Significant negative correlations were found between all periodontal clinical parameters and GCF volume with both GCF total amount and concentrations of RVD1 (p < 0.01). There was a positive correlation between GCF total amount and concentrations of RVD1 (r = 0.762, p < 0.01). GCF levels of RVD1 might be promising biomarkers for monitoring the susceptibility to periodontitis and predicting periodontal status. RVD1 may be valuable biomarker to observe the healing process after periodontal treatment as increased GCF levels might project clinical improvements post-treatment. Accordingly, observing GCF RVD1 levels might be helpful to determine individuals require further periodontal treatment.

Background:Considering the role of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the pathogenesis of periodontitis, the present study is to estimate the levels of MMP-3 and TIMP-1 in gingival crevicular fluid (GCF) in periodontal health, disease and to evaluate the effect of periodontal therapy on MMP-3 and TIMP-1 concentrations in GCF.Materials and Methods:A periodontal examination and collection of GCF by extra-crevicular method was performed in 30 subjects selected randomly and categorized into 3 groups. Group I consists of 10 subjects Group II consists of 20 patients and Group III consists of 20 patients of Group II. Non surgical periodontal therapy was performed, and GCF was collected after 8 weeks from the same site of 20 chronic periodontitis patients who are considered as Group III. MMP- 3 and TIMP-1 levels were estimated in GCF-samples by using enzyme-linked immunosorbent assay. The findings were analyzed using the software and descriptive statistical methods such as Mann- Whitney U-test and Kruskal-Wallis test. P value < 0.001 was considered significant.Results:MMP-3 and TIMP-1 was detected in all samples. Highest mean MMP-3 concentrations in GCF were obtained for Group II (7.490 ng/ml) while the lowest concentrations were seen in Group I (0.344 ng/ml) and Group III (2.129 ng/ml). This suggests that MMP-3 levels in GCF increases proportionally with the progression of periodontal disease and decreases after treatment. Lowest mean TIMP-1 concentrations in GCF were obtained for Group-II (1.592 ng/ml), while the highest concentrations were seen in Group-I (8.78 ng/ml) and Group-III (6.40 ng/ml). This suggests that TIMP-1 levels in GCF decreases proportionally with progression of periodontal disease and increases after treatment.Conclusion:There is a substantial increase in the concentrations of MMP-3 and decrease in TIMP-1 as periodontal disease progress. Since MMP-3 and TIMP-1 levels in GCF are positively correlated with gingival index, probing pocket depth, and clinical attachment loss, MMP-3, and TIMP-1 may be considered as a Novel Biomarkers in periodontal disease. However, controlled, longitudinal studies are needed to confirm this possibility.

The aim of this study was to determine how estrogen status may possibly influence gingival crevicular fluid (GCF) alkaline phosphatase (ALP) levels in estrogen-deficient (ED) and -sufficient (ES) postmenopausal women at baseline (BL) and 1 year after periodontal phase I treatment (AT). Thirty-six postmenopausal women on estrogen supplements (mean serum estradiol levels >30 pg/ml; estrogen sufficient) and 37 postmenopausal women not on estrogen supplements (mean serum estradiol levels <30 pg/ml; ED) were divided into two subgroups as chronic periodontitis and clinically healthy controls after clinical and radiographic examination. The ES group consisted of 19 control (ES/C) and 17 chronic periodontitis (ES/P) patients, and the ED group consisted of 20 control (ED/C) and 17 chronic periodontitis (ED/P) patients. Plaque (PI) and gingival (GI) indices, bleeding on probing (BOP), probing depths (PD), clinical attachment loss (CAL) scores, and GCF samples were recorded at BL and AT. The levels of ALP in the GCF were measured photometrically. The paired samples Student t and Wilcoxon tests were used to compare the ALP levels and clinical parameters between BL and AT. The correlation among the ALP and clinical parameters was analyzed using the Pearson correlation. The mean of all clinical parameters (PI, GI, BOP, PD, and CAL) was significantly (P <0.05) higher in periodontitis groups (ES/P and ED/P) than controls (ES/C and ED/C). Periodontitis groups (ES/P and ED/P) demonstrated significantly increased GCF volumes and GCF ALP levels (P <0.05) compared to controls (ES/C and ED/C). There were no significant differences in the concentrations of ALP between periodontitis and control groups (P >0.05). The BL GCF ALP total levels of the ED/P group were significantly higher than the ES/P group (P <0.05). The BL and AT serum ALP levels of the ED/P group were not significantly but were numerically higher than the ES/P group. One year after periodontal treatment, the GCF volume, GCF ALP total, and concentrations decreased significantly in both periodontitis groups (P <0.05). However, the GCF ALP levels were still numerically higher in the ED/P group. A positive statistical correlation was found between total ALP levels and PD (r = 0.621; P <0.05). These data suggest that the presence of ALP in GCF is not simply a reflection of the local inflammation state and that a patient's estrogen status may possibly influence local ALP levels in GCF.