Increased of IL-18 levels are associated with periodontitis: a systematic review and meta-analysis.

BACKGROUND: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1ß, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. METHODS: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/BS9GM . A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. RESULTS: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). CONCLUSION: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis.

Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker of stage III-IV, grade C periodontitis through the impact of post-radiotherapy on head and neck cancer patients.

BACKGROUND: The urokinase-type plasminogen activator receptor (uPAR) plays an essential function in leukocytes and endothelial homeostasis and, therefore, in the development of chronic periodontitis. METHODS: The study enrolled 150 participants, 50 chronic periodontitis with head and neck cancer post radiotherapy (CP + HNC post-RT) patients, 50 chronic periodontitis (CP) without HNC patients, and 50 healthy controls. Clinical Attachment Loss (CAL), Probing Pocket Depth (PPD), Plaque Index (PI), and Gingival Bleeding Index (GBI) were recorded. An enzyme-linked immunosorbent assay (ELISA) was constructed to quantify serum (suPAR) levels. RESULTS: Stage and grade of periodontitis were stage III-IV, grade C in patients (CP + HNC post-RT), stage I-III, grade A/B in patients (CP without HNC), and absent in (healthy). Chronic periodontitis with HNC post-RT patients presented a significantly higher proportion of suPAR levels (506.7 pg/ml) compared to chronic periodontitis without HNC and healthy controls (423.08 pg/ml and 255.9 pg/ml), respectively. A significant positive correlation was found between serum suPAR levels and CAL, PPD, PI, and GBI in the periodontal disease groups. ROC results of suPAR (AUC = 0.976 for CP + HNC post-RT, AUC = 0.872 for CP without HNC). Hyposalivation appeared in patients (CP + HNC post-RT; 0.15 [0.11-0.23] ml/min, P = 0.001) and (CP without HNC; 0.30 [0.25-0.41] ml/min, P = 0.001), compared to healthy controls; 0.35 [0.28-0.54] ml/min, P = 0.001). CONCLUSION: The study showed a significant elevation in serum suPAR levels in CP + HNC post-RT patients compared to the CP without HNC and control groups. CLINICAL TRIAL REGISTRATION: The study was registered retrospectively; clinicaltrials.gov identifier: NCT06529588. Date of registration: July 31, 2024 https://clinicaltrials.gov/study/NCT06529588 .

Association of vitamin D in patients with periodontitis: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Vitamin D has been considered to possess anti-inflammatory and antimicrobial activity, which may be a link for the known interaction of periodontitis (CP) and coronary heart disease (CHD). This study investigated the association between serum vitamin D levels and periodontitis in patients with CP and with CHD. Furthermore, the objective was to determine whether periodontitis and CHD had an impact on serum vitamin D levels. MATERIAL AND METHODS: Using a cross-sectional design, a total of 46 patients with CP, 45 patients with CHD, 45 patients with both CP and CHD, and 43 healthy patients were enrolled in the present study. RESULTS: Patients in the CP (17.4 ± 5.2 ng/mL) and in the CP + CHD (16.5 ± 5.6 ng/mL) group presented a significantly lower mean serum level of 25(OH)vitamin D compared to patients in the CHD (24.6 ± 3.7 ng/mL) and healthy control groups (29.9 ± 5.4 ng/mL) (P < .001). 25(OH)vitamin D levels were positively correlated with the number of teeth and negatively with C-reactive protein (CRP) and all periodontal parameters (P < .001). In all patients, there was a proportional increase of 25(OH)vitamin D levels with a progressive increase in number of teeth (P-trend <.001) while there were a proportional decrease in 25(OH)vitamin D levels with a progressive increase in clinical attachment level (CAL, P-trend = .001), probing depth (PD, P-trend = .006), and bleeding sites (BOP, P-trend <.001) levels. CONCLUSION: Patients with CP and CP + CHD presented significantly lower serum levels of vitamin D compared to CHD and healthy controls. Moreover, the presence of CP negatively influenced serum vitamin D levels.

Is sialic acid a promising marker for periodontal diseases?

OBJECTIVE: Periodontal diseases are inflammatory chronic infections. Sialic acid (SA) is an acute phase reactant by itself. The aim of this study is to investigate the relationship between salivary and serum SA levels and clinical parameters in different forms of periodontal diseases. SUBJECT AND METHODS: Systemically healthy subjects were included in the study; patients with chronic gingivitis (CG) (n = 10), chronic periodontitis (CP) (n = 10), and aggressive periodontitis (AgP) (n = 10), and ten volunteers with healthy periodontium as the control group. Total SA levels were determined by Warren's thiobarbituric acid method in whole saliva, parotis saliva, and serum samples of subjects before and 3 months after nonsurgical periodontal treatment. Full mouth clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were also recorded. RESULTS: Before treatment, in both periodontitis groups salivary and serum SA levels were higher than those of controls (P = 0.001). Both salivary and serum SA levels decreased significantly in the patient groups after treatment (P < 0.001). Multiple comparisons of baseline clinical parameters in all groups revealed significant differences (P = 0.001) and these parameters decreased significantly on the 90th day (P < 0.01). There were positive correlations between SA levels and periodontal indices of the CG, CP, and AgP groups (P < 0.05). CONCLUSION: Our results suggest that SA level in both saliva and serum may be a potentially useful marker to determine inflammatory changes and investigate different forms of periodontal diseases.

Effects of exercise on periodontal parameters in obese women.

BACKGROUND: Several studies have demonstrated an association between obesity, periodontitis, and exercise. AIMS: This study aimed to investigate the effects of regular exercise on obese women with periodontal disease, using serum, saliva, and gingival crevicular fluid (GCF) samples. A before-after study design was adopted to evaluate the effects of 12 weeks of regular exercise on obese women grouped according to periodontal status, without a control group (no exercise). The study sample comprised of 15 patients without periodontitis (NP group) and 10 patients with chronic periodontitis (CP group), from whom periodontal parameters were measured and serum, saliva, and GCF samples were collected. Body mass index (BMI), anthropometric measurements, somatotype-motoric tests, and maximal oxygen consumption (VO2max) were recorded at baseline and after exercise. SUBJECTS AND METHODS: Med Calc was used for statistical analysis. RESULTS: After exercise, a significant decrease in BMI and a significant increase in VO2max were observed in both groups. A significant decrease in probing depth and clinical attachment loss, serum leptin, GCF tumor necrosis factor-α(TNF-α) and leptin, and a significant increase in GCF resistin were observed in the CP group. A significant decrease in serum TNF-α and leptin levels and a significant increase in serum resistin and GCF TNF-α, leptin, resistin, and adiponectin levels were observed in the NP group. Significant correlations between bleeding on probing and levels of interleukin-1ß and leptin in GCF were observed in the CP group. CONCLUSIONS: This study showed that regular exercise exerts different impacts with respect to clinical and biochemical aspects of periodontal and systemic conditions in obese women.

Relationship between serum 25-hydroxyvitamin D3 levels and severity of chronic periodontitis in type 2 diabetic patients: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Serum 25-hydroxyvitamin D3 (25(OH)D3 ), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms. MATERIAL AND METHODS: A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3 , interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue. RESULTS: Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = -0.623), serum IL-1ß (r = -0.392), serum TNF-α (r = -0.218), PD (r = -0.269), and CAL (r = -0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p-STAT5 protein levels were increased in this group. CONCLUSIONS: Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL-1ß levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis.

BACKGROUND AND OBJECTIVE: Little is known about the correspondence of cytokines detected among the different biological matrices used in periodontal research and whether locally-detected cytokine mRNA can also be identified at the translated protein level. The aims of this study were to compare: (a) the detection of classic cytokines at protein level in corresponding samples of serum, gingival tissue and gingival crevicular fluid (GCF) in subjects with periodontitis and (b) the detection of cytokines at protein level in GCF and tissue with their detection at mRNA level in tissue. MATERIAL AND METHODS: Protein concentrations of IL-1ß, IL-6 and TNF-α were measured in corresponding samples of GCF, gingival tissue and serum from 125 subjects with chronic periodontitis by multiplex immunoassay. The mRNA levels of these cytokines were evaluated in the same gingival tissue by qPCR. RESULTS: The mean protein concentrations of IL-1ß and TNF-α were higher in tissue and GCF than in serum (P < 0.05). The mean protein concentration of IL-6 was higher in tissue, followed by serum and GCF, respectively (P < 0.05). Using serum as the gold standard, detection of IL-1ß in GCF and IL-6 in tissue had the highest sensitivity (100%), while detection of IL-6 in the GCF had the lowest sensitivity (77.9%). Using tissue as the gold standard, the detection sensitivities of IL-1ß, IL-6 and TNF-α were 93.6%, 78.4% and 94.2%, respectively, in GCF. Using mRNA as the gold standard, the detection of IL-1ß and IL-6 at the protein level in tissue (100.0%) had the highest sensitivity, while the detection of IL-6 in GCF (77.9%) had the lowest sensitivity. CONCLUSION: Tissue and GCF exhibited overall higher protein concentrations of cytokines than serum. GCF presented good reliability for identifying the target cytokines at protein level, when compared with detecting tissue cytokines at protein level. GCF and tissue presented high sensitivities for detecting cytokines at the protein level, when compared with detecting tissue cytokines at the mRNA level. The sensitivity for the identification of cytokines in the GCF depended on the target cytokine, where IL-6 was the least likely cytokine to be detected in this matrix.

Relationship between periodontal outcomes and serum biomarkers changes after non-surgical periodontal therapy.

The systemic effect of chronic periodontitis (CP) has been suggested by several studies as an etiologic factor and modulator of diseases based on the changes in the inflammatory marker levels. This study aimed to investigate the relationship between the changes in clinical periodontal outcomes and serum biomarkers (CRP, IL-6, albumin and percentage of leukocytes) after non-surgical periodontal therapy in systemically healthy adults. An interventional study was conducted with a sample of 29 individuals without CP (control group) and 33 with CP (CP group). Periodontal clinical variables were recorded, and the serum levels of inflammatory markers were measured. Statistical analysis included the chi-square and Student's t-tests and Pearson's correlation analysis. After 90 days of non-surgical periodontal treatment, a reduction of periodontal parameters and IL-6 in both groups could be observed (P < 0.001). The correlation analysis revealed a directly proportional correlation between changes in the probing depth (r = 0.349, P = 0.049) and clinical attachment level (r = 0.374, P = 0.034) with CRP in the CP group. The findings suggest a reduction of IL-6 serum concentration and periodontal clinical measures 90 days after periodontal therapy in both groups.

The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and/or smoking habit.

OBJECTIVE: This study assessed the impact of chronic periodontitis (CP) and CP associated with type 2 diabetes mellitus (DM) and/or smoking on the serum ratios of pro- to anti-inflammatory cytokines. MATERIALS AND METHODS: Subjects were assigned into one of the following groups: control (n = 25, non-diabetic non-smokers with no history of periodontitis), CP (n = 26, non-diabetic non-smokers with CP), DMCP (n = 30, non-smokers with DM and CP), SCP (n = 27, non-diabetic smokers with CP), and SDMCP (n = 22, smokers with type 2 DM and CP). Serum levels of 18 cytokines were measured using multiplex immunoassays. RESULTS: Six ratios of pro-inflammatory to anti-inflammatory cytokines were significantly higher in the CP group than in the control group (p < 0.05). Eleven, seventeen and nine ratios of pro-inflammatory to anti-inflammatory cytokines were significantly higher in the DMCP, SCP and SDMCP groups than in the control group, respectively (p < 0.05). The SCP group presented higher serum ratios of tumor necrosis factor (TNF)-α/interleukin (IL)-4, TNF-α/IL-5, IL-17/IL-13 and IL-6/IL-13 (p < 0.05) than the CP group. Cluster analysis revealed a relevant cluster composed of ten cytokines (IL-17, IL-23, interferon-γ, IL-12, IL-1ß, IL-2, IL-21, IL-6, IL-4 and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in the serum of subjects from the DMCP group. CONCLUSIONS: The ratios of pro- to anti-inflammatory cytokines shift to favor a pro-inflammatory status in the serum of patients with CP and even more when CP is associated with one or both risk factors. CLINICAL RELEVANCE: CP and CP associated with hyperglycemia and/or smoking might contribute to a systemic inflammatory burden and increased risk of systemic complications.

Evaluation and comparison of serum vitamin D and calcium levels in periodontally healthy, chronic gingivitis and chronic periodontitis in patients with and without diabetes mellitus - a cross-sectional study.

Objective: Limited data are available with respect to the relation of vitamin D and calcium with periodontal infections and type-2 diabetes mellitus (T2DM). The aim of this cross-sectional study was to evaluate the levels of vitamin D and calcium in serum of periodontally healthy, chronic gingivitis and chronic periodontitis patients with and without T2DM. Material and methods: The study evaluated 100 patients equally divided into five groups (Group I to Group V) according to the inclusion criteria. Clinical parameters and serum 25-hydroxyvitamin D level were assessed. Other laboratory investigations comprised of random blood sugar, glycated haemoglobin and serum calcium. Results: The probing pocket depth and clinical attachment loss were found to be greater in chronic periodontitis and chronic periodontitis with diabetes mellitus, while the vitamin D and calcium levels were found to be least in these groups. When vitamin D and calcium levels were compared between periodontal disease with diabetes to that of non-diabetics, statistically significant difference were found between the two with p-value of .001 indicating decrease in levels of vitamin D and calcium with increase in RBS and HbA1c values. Conclusion: Vitamin D and calcium levels are inversely correlated with random blood sugar and glycated haemoglobin and also probing pocket depth and clinical attachment loss, thus contributing towards increase in periodontal disease severity.

The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two common chronic diseases with bidirectional relationship. Oxidative stress plays a key role in the pathogenesis of these two diseases. The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis (CP). MATERIALS AND METHODS: In this double-blind clinical trial study, 50 type 2 DM patients with CP were randomly allocated to the intervention and control groups. The intervention and control groups received either 6 mg melatonin or placebo (2 tablets) once a day. Serum levels of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), hs-C-reactive protein (hs-CRP), clinical attachment loss (CAL), pocket depth (PD), bleeding on probing (BOP) and plaque index were evaluated in all subjects pre- and post-intervention. RESULTS: Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention. The mean changes of melatonin were significantly higher in intervention group compared with control group. IL-6 and hs-CRP levels were significantly (p = 0.008 and p = 0.017, respectively) reduced in the intervention group. The mean changes of IL-6 were significantly lower in the intervention group compared with the control group (p = 0.04). In the intervention group, PD and CAL were significantly decreased after intervention (p < 0.001). There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention (p < 0.001). CONCLUSIONS: Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP.

Folate-receptor 1 level in periodontal disease: a pilot study.

BACKGROUND: The purpose of this study was to investigate gingival crevicular fluid (GCF) and serum folate-receptor 1 (FOLR1) levels in subjects with different periodontal status. METHODS: The study consists of three groups: Healthy group (n = 15), gingivitis group (n = 15) and chronic periodontitis group (n = 15). Clinical periodontal parameters including probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI) and bleeding on probing (BOP) were assessed. GCF and serum samples were collected from each patient and were analyzed FOLR1 levels by enzyme-linked immunosorbent assay. RESULTS: The values of FOLR1 in GCF were higher in gingivitis and periodontitis groups than among patient in control group (p < 0.016). Serum FOLR1 levels showed no significant difference between the groups. A significant correlation was observed between FOLR1 levels of GCF and BOP (p < 0.05). CONCLUSIONS: Our preliminary data suggest that FOLR1 is not useful in monitoring the periodontal disease. Further studies are necessary to clarify the role, regulation and function of folate and it's receptors in the pathogenesis of periodontal disease.

Effect of non-surgical periodontal therapy on glycemic control of type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice. METHODS: We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias. RESULTS: Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI - 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11). CONCLUSION: The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.

Elevated serum rheumatoid factor, anti-citrullinated protein antibodies and active rheumatoid arthritis disease are not associated with chronic periodontitis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of the joints with the involvement of other systems. Previous studies have demonstrated its association with chronic periodontitis (CP), a chronic inflammatory disease of tooth-supporting tissues. Positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) in RA patients have been found to be associated with CP. The aim of this study is to determine the prevalence of CP in RA patients, and to investigate the association of ACPA, RF status and RA disease activity with CP and non-CP RA patients. MATERIALS AND METHODS: A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed. RESULTS: Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients. CONCLUSION: In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.

[Soluble forms of adhesive molecules in blood serum as a marker of endothelial dysfunction in chronic generalized parodontitis.]

An important factor in the pathogenesis of chronic inflammation in periodontitis is endothelial dysfunction (ED). Adhesion molecules are markers of impaired barrier function, adhesive properties and vascular permeability. The study of the concentration of soluble adhesion molecules is very promising in the diagnosis of ED. The purpose of this research was to study changes in the concentration of soluble forms of adhesive molecules of the selectin family and the immunoglobulin superfamily when used as markers of systemic manifestations of ED in the dynamics of the treatment of chronic generalized periodontitis (CP) using surgical and therapeutic schemes. 60 patients with CP (33 women and 27 men) and 20 clinically healthy volunteers (10 men and 10 women) were examined. The state of the endothelium was assessed by the content in the serum of soluble forms of adhesive molecules - sP- and sE-selectins, intercellular adhesive molecules of type 1 (sICAM-1), vascular molecules of cell adhesion of type 1 (VCAM-1) by ELISA. The short-term results of non-surgical treatment of CP are more effective in correction of vascular wall adhesive properties disorders compared with surgical treatment. Conservative treatment of chronic hepatitis C effectively adjusted the blood content of adherent endothelium molecules in women than in men. The long-term results of applying this scheme were characterized by partial preservation of a positive effect on the adhesive properties of the endothelium, however, long-term results were inferior to short-term ones. Surgical treatment of CP in women in the early postoperative period was accompanied by reactive impairment of the adhesive properties of the endothelium. The long-term results of this treatment regimen testified to its greater effectiveness. In women, the effectiveness of treatment of CP in restoring the adhesive properties of the endothelium was higher than in men. The results obtained allow us to conclude that the systemic manifestations of ED in CP were characterized by an increase in the concentration in the blood of soluble forms of adhesion molecules. The dynamics of the concentration of adhesive molecules during the treatment of СР testified to the dependence of the sex of patients on the effectiveness of the influence of therapeutic and surgical treatment regimens on the systemic manifestations of ED.

Serum vitamin D levels and chronic periodontitis in adult, Caucasian population-a systematic review.

The aim of this systematic review was to explore the relationship between serum vitamin D levels and periodontal disease. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The focused PICO question was: Are serum vitamin D levels (I) associated with gingivitis or periodontitis (C) in healthy humans (P)? PubMed (Medline), Embase, Science Direct, the Cochrane library, and grey literature were searched up to 31 July 2017. Two reviewers independently selected studies and extracted data. Quality, risk of bias, and heterogeneity of the studies were assessed using the Newcastle-Ottawa Scale. In total, 365 studies were identified and 24 were analyzed. Seven studies fulfilled the inclusion criteria. Four case-control studies showed an influence of vitamin D and its metabolites on periodontal health status/disease. One interventional study suggested the proposed anti-inflammatory role of vitamin D. Two cross-sectional studies failed to show a relationship between vitamin D and periodontal condition. The literature on the effect of serum vitamin D levels on periodontal status remains scarce and controversial. Some data, however, support a "perio-protective" role for vitamin D. There is a need for well-designed randomized clinical trials to explore the possible anti-inflammatory effect of vitamin D on periodontal health.

Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey.

BACKGROUND AND OBJECTIVES: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. MATERIAL AND METHODS: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). RESULTS: The concentrations of PCSK9 and hs-CRP were increased (P = .001 and .042, respectively), and the concentration of TBIL was decreased (P = .046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P = .038, .007, .002, and .049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized ß = .243, P = .040; standardized ß = -.443, P = .0002; respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. CONCLUSION: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

Levels of serum retinol-binding protein 4 before and after non-surgical periodontal treatment in lean and obese subjects: An interventional study.

AIM: We aimed to evaluate serum RBP4 levels before and after periodontal therapy in lean and obese subjects with chronic periodontitis (CP) in order to determine its possible association with periodontitis. MATERIALS AND METHODS: This is an interventional study for which a total of 112 lean and 119 obese subjects were recruited. Patients with CP were evaluated before and after three months of non-surgical periodontal treatment. Periodontal, anthropometric, biochemical parameters and serum levels of TNF-α, IL-6, hs-CRP and RBP4 were assessed. RESULTS: Serum RBP4 levels were associated with an increased probability of periodontitis (OR = 1.60; 95% CI: 1.02-2.50), showing patients with CP to have higher RBP4 levels than those without CP in both lean and obese populations (3.35 vs 3.06 and 3.74 vs 3.21, respectively). Following periodontal treatment, RBP4 and TNF-α decreased, and all periodontal parameters improved to the same extent in both groups, except for number of teeth with probing depth (PD) ≥4 mm, which improved to a less extent in obese than in lean subjects. In the multivariable regression model, the number of teeth with PD ≥4 mm was independently associated with RBP4 (ß = 0.192). CONCLUSION: RBP4 was associated with chronic periodontitis before and after non-surgical periodontal treatment.

Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: A randomized controlled trial.

BACKGROUND: Periodontitis and diabetes are highly prevalent conditions whose association has long been recognized. OBJECTIVE: To evaluate the effect of non-surgical periodontal treatment on serum HbA1c (haemoglobin A1c or glycated haemoglobin) levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 6-month, single-masked, randomized clinical trial based on 90 patients (HbA1c: 7.7% (61 mmol/mol) ± 1.13%) who were randomly assigned to either the treatment group (oral hygiene instructions + scaling and root planing using ultrasound and Gracey curettes) or the control group (oral hygiene instructions + supragingival removal of plaque and calculus using ultrasound). Pocket depth, gingival index, and plaque index were assessed at baseline and after 3 and 6 months together with determinations of fasting plasma glucose, HbA1c, and bacterial counts. RESULTS: Treatment significantly improved the periodontal and metabolic parameters (p < .05), whereas in the control group no improvement was observed. These results were consistent with the bacteriological results in most but not all cases. CONCLUSION: Non-surgical periodontal treatment resulted in a better glycaemic status of type 2 diabetes patients and demonstrated the importance of oral health in their general health.