Myeloperoxidase as a measure of polymorphonuclear leukocyte response in inflammatory status around immediately and delayed loaded dental implants: a randomized controlled clinical trial

Background: As well as gingival crevicular fluid (GCF), peri‐implant sulcus fluid (PISF) may have a potential diagnostic value for the early identification of metabolic and destructive processes. Purpose: The aim of this study was to analyze the potential impact of inflammation and loading on PISF myeloperoxidase (MPO) levels, in comparison with GCF. Materials and Methods: A total of 220 sites, dental implant (immediately [IL] or delayed loaded [DL]), and natural tooth, either healthy/noninflamed or gingivitis/inflamed, were classified. Clinical parameters were recorded, and GCF/PISF samples were obtained. GCF/PISF MPO levels were spectrophotometrically determined. Results: Clinical parameters demonstrated increases with the presence of gingival/peri‐implant inflammation. Total MPO levels were higher at inflamed tooth and implant sites compared to noninflamed/healthy sites (p < .05). Although they did not reach a significance level, inflamed IL sites had higher total MPO levels than inflamed DL sites (p = .401). Gingival index and total MPO levels exhibited significant correlations (p < .05). Conclusion: Using implants and natural teeth in the same study design, the findings of the present study support the close relationship between MPO production and inflammation, and may speculate a potential for loading of dental implants, contributing to the MPO content of PISF.     

Analysis of cathepsin-K activity at tooth and dental implant sites and the potential of this enzyme in reflecting alveolar bone loss

Background: Cathepsin‐K is an enzyme involved in bone metabolism which may make this feature important for both natural teeth and dental implants. The aims of the present study are to comparatively analyze the gingival crevicular fluid (GCF)/peri‐implant sulcus fluid (PISF) cathepsin‐K levels of natural teeth and dental implants, and to assess the potential relationship between this biochemical parameter and alveolar bone loss around natural teeth and dental implants. Methods: Probing depth, bleeding on probing, gingival index, and plaque index clinical parameters were assessed, and GCF/PISF samples were obtained from natural teeth/dental implants presenting with either clinical health, gingivitis/peri‐implant mucositis, or chronic periodontitis/peri‐implantitis. Cathepsin‐K activity levels of 42 GCF samples and 54 PISF samples were determined, and marginal bone loss (MBL) measures were calculated from digitalized standardized intraoral periapical radiographs obtained from natural teeth and dental implants by using cemento‐enamel junction and the actual distance between two consecutive threads of the dental implant as reference points for natural teeth and dental implants, respectively. Results: Comparing the natural teeth group with dental implant group with regard to MBL measure, cathepsin‐K activity, and GCF/PISF volume revealed no significant differences. In both natural teeth and dental implant groups, despite higher MBL measures, cathepsin‐K activity, and GCF/PISF volumes with the presence of inflammation, it was the presence of alveolar bone loss that lead to significantly higher values for these parameters. Conclusion: We suggest cathepsin‐K as a biochemical parameter for monitoring periodontal/peri‐implant alveolar bone loss.     

Clinical and radiographic peri‐implant parameters and proinflammatory cytokine levels among cigarette smokers,smokeless tobacco users,and nontobacco users

Background

It is postulated that clinical and radiographic peri‐implant parameters are worse and levels of interleukin (IL)‐1β and matrix metalloproteinase (MMP)‐9 in the peri‐implant sulcular fluid (PISF) are higher in cigarette‐smokers (CS) and smokeless‐tobacco users (STU) compared with nontobacco user (NTU).

Purpose

The present study aimed to compare clinical and radiographic peri‐implant inflammatory parameters and levels of IL‐1β and MMP‐9 levels among CS, STU, and NTU.

Materials and Methods

Forty‐five CS (Group‐1), 42 STU (Group‐2), and 44 NTU (Group‐3) were included. Demographic data was collected using a structured baseline questionnaire. Peri‐implant plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded and crestal bone loss (CBL) were assessed using standardized digital radiographs. PISF volume and levels of IL‐1β and MMP‐9 in PISF were quantified using enzyme‐linked immunosorbent assay. Clinical peri‐implant parameters and PISF IL‐1β and MMP‐9 concentrations were analyzed with Kruskal‐Wallis test. Bonferroni post hoc adjustment test was used for multiple comparisons. P‐value was set at .05.

Results

Peri‐implant PI and PD were significantly worse in group‐1 and group‐2 patients as compared to group‐3 individuals (P < .05). Peri‐implant CBL was also significantly higher in group‐1 and group‐2 compared with group‐3 (P < .05). Peri‐implant BOP was significantly higher in group‐2 and group‐3 as compared to group‐1 individuals (P < .05). The PISF volume (P < .05) collected and levels of IL‐1β and MMP‐9 were statistically significantly elevated among individuals in group‐1 and group‐2 compared with group‐3 (P < .01). There was no significant difference in PI, PD, CBL, and PISF levels of IL‐1β and MMP‐9 among participants in groups 1 and 2.

Conclusion

Clinical and radiographic peri‐implant parameters were compromised among CS and STU as compared to NTU. Increased expression of local proinflammatory cytokines may explain greater susceptibility of CS and STU to peri‐implant breakdown.     

Longitudinal Comparison of Cytokines in Peri‐Implant Fluid and Gingival Crevicular Fluid in Healthy Mouths

Background: Peri‐implant and gingival tissues provide important sealing and protective functions around implants and teeth, but comparisons of the immunologic responses of these tissues after implant placement have not been conducted. Cytokine levels were measured in peri‐implant crevicular fluid (PICF) and gingival crevicular fluid (GCF) as surrogate measures of immune function at subcrestally placed dental implants and healthy periodontal sites during a 1‐year monitoring period. Methods: A total of 27 dental implants were placed subcrestally in 21 periodontally healthy patients (mean age: 49.0 ± 13.4 years). Repeated clinical and cytokine measurements were obtained over 12 months. GCF and PICF samples were collected and analyzed by cytokine microarray. Data were examined by non‐parametric analysis of variance. Results: Plaque and bleeding indices were similar among all patients (P >0.05) at baseline. During 1 year of monitoring, the mean volumes of PICF and GCF were similar (P >0.05). The levels of interleukin (IL)‐4, ‐6, ‐10, and ‐12p70, tumor necrosis factor‐α, and interferon‐γ in GCF and PICF were not significantly different and did not vary over time (P >0.05). The levels of IL‐1α were higher in GCF than PICF at 1, 2, 6, and 12 months, as were the levels of IL‐8 at 1, 2, 4, 6, and 12 months (P <0.001). Transforming growth factor‐β1 in PICF and GCF exhibited time‐dependent increases, and vascular endothelial growth factor was reduced at 1 year without differences between PICF and GCF (P >0.05). Conclusion: Within the limitations of this study design, it can be concluded that after subcrestal implant placement, the immune response of peri‐implant and periodontal tissues, as assessed by cytokine levels in PICF and GCF, is similar.     

Evaluation of gingival crevicular fluid and peri‐implant sulcus fluid levels of periostin: A preliminary report

1 Background

Periostin is a protein present in alveolar bone and periodontal ligament whose function is related to response to external forces. The aims of this study are to detect levels of periostin in peri‐implant sulcular fluid (PISF) and gingival crevicular fluid (GCF) and to evaluate the relationship between periostin, pyridinoline cross‐linked carboxyterminal telopeptide of Type I collagen (ICTP), and C‐terminal cross‐linked telopeptide of Type I collagen (CTX) levels and clinical inflammatory symptoms and duration of functional loading.

2 Methods

The study population comprised nine women and four men with mean age 43.23 ± 12.48. Twenty “bone‐level designed” dental implants (DIs) placed in molar or premolar sites, without any signs of peri‐implant bone loss and with a restoration in function for at least 12 months, were included in the study with 20 contralateral natural teeth (NT) as controls. Clinical parameters and restoration dates of the implants were recorded. PISF, GCF, ICTP, CTX, and periostin levels were evaluated using enzyme‐linked immunosorbent assay.

3 Results

ICTP, CTX, and periostin levels were similar between DI and NT groups. There were no statistically significant differences between PISF and GCF values. When implants were grouped as healthy (gingival index [GI] = 0) and inflamed (GI ≥0), ICTP levels and PISF volume were lower in healthy implants compared with the inflamed group. Both periostin and CTX levels were negatively correlated with functioning time, suggesting less bone remodeling around DIs at later stages of functioning.

4 Conclusion

Findings of this study suggest collagen breakdown products may be used as markers to evaluate peri‐implant metabolism.     

TNF-alpha TGF-beta2 and IL-1beta levels in gingival and peri-implant crevicular fluid before and after de novo plaque accumulation

Aims: The aim of this split‐mouth study was to investigate levels of tumour necrosis factor alpha (TNF‐α), transforming growth factor beta (TGF‐β2) and interleukin‐1 beta (IL‐1β) in gingival crevicular fluid (GCF) and peri‐implant crevicular fluid (PICF) after a 21‐day‐period of de novo plaque accumulation in the same patient. Material and Methods: In 25 patients, samples of GCF and PICF were collected in the sulcus of the tooth and of the implant after professional hygiene. After the no‐hygiene phase (21 days), second samples of GCF and PICF were taken. Third samples were collected after 69 days of re‐establishment oral hygiene techniques. The crevicular fluids were used to determine the volume and the levels of TNF‐α, TGF‐β2 and IL‐1β. Results: The volume of the crevicular fluids increased significantly after 21 days of plaque accumulation around teeth and implants and decreased significantly by 69 days. TNF‐α and TGF‐β2 did not change significantly among the three different samples. A significant increase of IL‐1β was observed after plaque accumulation around the teeth GCF, whereas in the PICF the increase was not statistically significant. Conclusions: These data suggest that increased volumes of GCF and PICF could be useful markers of early inflammation in gingival and peri‐implant tissues. In the presence of de novo plaque, implants showed lower, and nearly significant, levels of IL‐1β compared with teeth.     

In vivo expression of proteases and protease inhibitor,a serpin,by periodontal pathogens at teeth and implants

Porphyromonas gingivalis and Tannerella forsythia secrete proteases, gingipains and KLIKK‐proteases. In addition, T. forsythia produces a serpin (miropin) with broad inhibitory spectrum. The aim of this pilot study was to determine the level of expression of miropin and individual proteases in vivo in periodontal and peri‐implant health and disease conditions. Biofilm and gingival crevicular fluid (GCF)/ peri‐implant sulcular fluid (PISF) samples were taken from healthy tooth and implant sites (n = 10), gingivitis and mucositis sites (n = 12), and periodontitis and peri‐implantitis sites (n = 10). Concentration of interleukin‐8 (IL‐8), IL‐1β and IL‐10 in GCF was determined by enzyme‐linked immunosorbent assay. Loads of P. gingivalis and T. forsythia and the presence of proteases and miropin genes were assessed in biofilm by quantitative PCR, whereas gene expression was estimated by quantitative RT‐PCR. The presence of P. gingivalis and T. forsythia, as well as the level of IL‐8 and IL‐1β, were associated with disease severity in the periodontal and peri‐implant tissues. In biofilm samples harboring T. forsythia, genes encoding proteases were found to be present at 72.4% for karilysin and 100% for other KLIKK‐protease genes and miropin. At the same time, detectable mRNA expression of individual genes ranged from 20.7% to 58.6% of samples (for forsylisin and miropsin‐1, respectively). In comparison with the T. forsythia proteases, miropin and the gingipains were highly expressed. The level of expression of gingipains was associated with those of miropin and certain T. forsythia proteases around teeth but not implants. Cumulatively, KLIKK‐proteases and especially miropin, might play a role in pathogenesis of both periodontal and peri‐implant diseases.     

Short‐Term Effects of Non‐Surgical Periodontal Treatment on the Gingival Crevicular Fluid Cytokine Profiles in Sites With Induced Periodontal Defects: A Study on Dogs With and Without Streptozotocin‐Induced Diabetes

Background: The aim of this study is to assess the short‐term effects of non‐surgical periodontal therapy (NSPT) on the gingival crevicular fluid (GCF) cytokine profile in sites with standardized periodontal bony defects in beagle dogs with and without diabetes. Methods: Four beagle dogs with streptozotocin (STZ)‐induced diabetes and four healthy dogs were included. Fasting blood glucose levels were measured using a glucometer. In all animals, a 3‐walled bony defect was created on the mesial surface of the second premolar and first molar in all quadrants. After 12 weeks, all animals underwent weekly NSPT for 3 weeks. Baseline and post‐NSPT GCF samples were collected, and levels of interleukin (IL)‐1, IL‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α were measured using enzyme‐linked immunosorbent assay. Statistical analyses were performed using a software program, and P values <0.05 were considered statistically significant. Results: Mean fasting blood glucose levels were significantly higher in dogs with induced diabetes than those without diabetes (P <0.01). At baseline, mean IL‐6 (P <0.01) and IL‐8 (P <0.05) levels were higher in dogs with diabetes than those without diabetes. A significant reduction in levels of IL‐1, IL‐1β, IL‐6, IL‐8, and TNF‐α was noted in dogs without diabetes 1 week after NSPT. However, this significant reduction (P <0.05) only appeared 2 weeks after NSPT in dogs with diabetes. Conclusions: NSPT reduces GCF levels of proinflammatory cytokines in dogs with and without STZ‐induced diabetes; however, chronic hyperglycemia seems to retard the effect of NSPT on GCF cytokine concentration.     

Is There an Interaction Between Polycystic Ovary Syndrome and Gingival Inflammation?

Background: The aim of this study is to evaluate the gingival crevicular fluid (GCF), saliva, and serum concentrations of tumor necrosis factor‐α (TNF‐α), TNF‐α receptor‐1 (TNF‐αR1), TNF‐αR2, and interleukin‐6 (IL‐6) in non‐obese females with polycystic ovary syndrome (PCOS) and either clinically healthy periodontium or gingivitis. Methods: Thirty‐one females with PCOS and healthy periodontium, 30 females with PCOS and gingivitis, and 12 systemically and periodontally healthy females were included in the study. GCF, saliva, and serum samples were collected, and clinical periodontal measurements, body mass index, and Ferriman‐Gallwey score (FGS) were recorded. Sex hormones, cortisol, and insulin levels were measured. TNF‐α, TNF‐αR1, TNF‐αR2, and IL‐6 were determined by enzyme‐linked immunosorbent assay. Kruskal‐Wallis followed by Bonferroni‐corrected post hoc Mann‐Whitney U tests were used to analyze the data. Results: The PCOS + gingivitis group revealed significantly higher GCF, saliva, and serum IL‐6 concentrations than the PCOS + healthy group (P <0.0001). The two PCOS groups exhibited significantly higher saliva TNF‐α concentrations than the control group (P = 0.024 and P = 0.013, respectively). The FGS index was significantly higher in the PCOS + gingivitis group than the PCOS + healthy group (P = 0.030). The PCOS + gingivitis group revealed significantly higher insulin concentration than the PCOS + healthy and control groups (P = 0.014 and P <0.0001, respectively). Serum TNF‐α, TNF‐αRs, and serum, GCF, and salivary IL‐6 levels correlated with the clinical periodontal measurements. Conclusions: PCOS and gingival inflammation appear to act synergistically on the proinflammatory cytokines IL‐6 and TNF‐α. Thus, PCOS may have an impact on gingival inflammation or vice versa. Additional studies are warranted to clarify the possible relationship between PCOS and periodontal disease.     

Does Obstructive Sleep Apnea Increase the Risk for Periodontal Disease? A Case‐Control Study

Background: A possible association between periodontitis and obstructive sleep apnea (OSA) has been suggested. The aim of this study is to compare periodontitis prevalence between controls and patients with OSA by assessing clinical periodontal parameters and gingival crevicular fluid (GCF) levels of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, and high‐sensitive C‐reactive protein (hs‐CRP); serum hs‐CRP was also sampled. Methods: A case‐control study was performed that included 163 individuals: 83 individuals (18 females and 65 males) with OSA and 80 non‐OSA individuals (23 females and 57 males) as controls. The test group was classified according to OSA severity. Clinical periodontal measurements were recorded, and GCF samples were collected. GCF hs‐CRP, IL‐lβ, and TNF‐α levels were analyzed using an enzyme‐linked immunosorbent assay method. Serum hs‐CRP was measured by latex‐enhanced immunoturbidimetric assay. Results: Prevalence of periodontitis in the OSA group (96.4%) was significantly higher than in the control group (75% [P <0.001]). Severe periodontitis prevalence was higher in the OSA group than control group. All periodontal clinical parameters and GCF IL‐lβ concentrations were significantly higher in patients with OSA than in controls (P = 0.001). No significant differences were found between the mild OSA and moderate‐to‐severe OSA groups. Additionally, there was no significant difference in GCF TNF‐α and hs‐CRP levels between the groups (P >0.05). Serum hs‐CRP levels were significantly higher in patients with OSA. A significant correlation was found between GCF IL‐1β and all clinical parameters. Conclusions: Results demonstrated higher prevalence of periodontitis and higher levels of GCF IL‐1β and serum hs‐CRP in patients with OSA. However, there is still a need for randomized clinical trials testing oral care interventions.     

Biomarkers and Bacteria Around Implants and Natural Teeth in the Same Individuals

Background: This cross‐sectional study assesses cytokine levels in peri‐implant crevicular fluid (PICF)/gingival crevicular fluid (GCF) and a selection of subgingival/submucosal plaque bacteria from clinically healthy or diseased sites in the same individuals. Methods: Samples from 97 implants/teeth (58 implants [19 healthy, 20 mucositis, 19 peri‐implantitis] and 39 natural teeth [19 healthy, 12 gingivitis, eight periodontitis] in 15 systemically healthy patients were investigated by immunoassay and real‐time polymerase chain reaction. Samples were obtained first, with probing depth, clinical attachment level, bleeding on probing, plaque index scores, and keratinized tissue width then recorded. Data were analyzed by Wilcoxon, Mann–Whitney U, and permutation tests on dependent, independent, and mixed dependent and independent samples and Spearman correlation. Results: Interleukin (IL)‐1β levels were significantly higher in PICF samples of healthy implants than in GCF samples of healthy teeth (P = 0.003), and soluble receptor activator of nuclear factor‐κB ligand (sRANKL) concentrations were significantly higher in the gingivitis than the mucositis group (P = 0.004). Biomarker levels were similar in peri‐implantitis and periodontitis groups (P >0.05). Actinomyces naeslundi and Streptococcus oralis levels were significantly higher in the healthy implant group than in healthy teeth (P <0.05). Prevotella intermedia and Treponema denticola (Td) levels were lower in the mucositis group than the gingivitis group (P <0.05). Prevotella oralis and S. oralis levels were significantly higher in the periodontitis group (P <0.05), and Td levels were significantly higher in the peri‐implantitis group (P <0.05). Conclusion: There were many similarities but, crucially, some differences in biomarker levels (IL‐1β and sRANKL) and bacterial species between peri‐implant and periodontal sites in the same individuals, suggesting similar pathogenic mechanisms.     

The evaluation of peri‐implant sulcus fluid osteocalcin,osteopontin, and osteonectin levels in peri‐implant diseases

1 Background

Peri‐implant mucositis is an inflammation of the soft tissues surrounding an implant. Peri‐implantitis refers to a process characterized by peri‐implant bone loss along with an inflammation of the soft tissues. Osteocalcin, osteopontin, and osteonectin proteins are related to bone remodeling. The aim of the present study was to investigate peri‐implant sulcus fluid (PISF) osteocalcin, osteopontin, and osteonectin levels in peri‐implant mucositis and peri‐implantitis.

2 Methods

Fifty‐two implants with peri‐implantitis, 46 implants with peri‐implant mucositis, and 47 control implants were included in the study. Clinical parameters including probing depth, modified sulcus bleeding index and modified plaque index were recorded. PISF osteocalcin, osteopontin, and osteonectin levels were analyzed by ELISA kits.

3 Results

There were no significant differences in PISF osteocalcin, osteopontin, and osteonectin total amounts between healthy controls, peri‐implant mucositis and peri‐implantitis groups (P > 0.05). Probing depths were not correlated with PISF osteocalcin, osteopontin, and osteonectin levels in the study groups (P > 0.05).

4 Conclusions

Soft tissue inflammation around dental implants does not cause a change in osteocalcin, osteopontin, and osteonectin levels in PISF. Also, peri‐implantitis does not seem to give rise to an increase in PISF levels of osteocalcin, osteopontin, and osteonectin.     

Possible impact of inflammatory status on C‐telopeptide pyridinoline cross‐links of Type I collagen and osteocalcin levels around oral implants with peri‐implantitis: a controlled clinical trial

Summary Detection of progression level of peri‐implantitis may help in the prevention of oral implant failure. C‐telopeptide pyridinoline crosslinks of Type I collagen (ICTP) and osteocalcin (OC) are specific markers of bone turnover and bone degradation. Determination of the ICTP and OC levels in the peri‐implant sulcus fluid (PISF) may predict the metabolic and/or inflammatory changes in the peri‐implant bone. The aim of this clinical study was to evaluate ICTP and OC levels in the PISF for oral implants with and without peri‐implant bone destruction and correlate these levels with the traditional clinical peri‐implant parameters (probing depth, plaque index, gingival index and gingival bleeding time index) and radiographic bone level measurements. Fifteen patients with 30 peri‐implant sites with bone destruction (radiographic bone loss) and health were included. Clinical parameters were measured and PISF was collected from the sites. Peri‐implant sulcus fluid ICTP and OC levels were detected by radioimmunoassay technique from PISF samples. All clinical parameters demonstrated a significant increase in peri‐implantitis sites compared with healthy sites. The PISF volume of the peri‐implantitis sites was also significantly higher than of the healthy peri‐implant sites. Although not statistically significant, a trend of increase was demonstrated in ICTP PISF samples sampled from peri‐implantitis sites compared with healthy sites. A significant increase was noticed for OC PISF level in peri‐implantitis sites compared with healthy ones. As well as peri‐implant clinical measurements, volumetric changes at PISF may be counted as an important clinical parameter to distinguish the bone destruction sites from healthy sites around oral implants.     

Osmotic pressure of periimplant sulcular and gingival crevicular fluids: a split-mouth, randomized study of its measurement and clinical significance

Objectives: This study comparatively investigated periimplant sulcular fluid (PISF) and gingival crevicular fluid (GCF) by means of the osmotic pressure (OP) levels of PISF (PISFOP) and GCF (GCFOP). It was a preliminary research that aimed to quantify PISFOP and GCFOP as well as to evaluate their clinical significances around implants and teeth. Material and methods: Partially edentulous implant patients treated by the same clinicians and using the same implant system were randomized in a split‐mouth trial design. Fifty‐four implants and teeth from these patients were selected in the same mouth and jaw as matched pairs of samples, i.e. as symmetrical or corresponding implant and tooth. PISFOP/GCFOP measurement was performed by an osmometer following PISF/GCF sampling procedures. Clinical significance was evaluated by the correlations between PISFOP/GCFOP and some clinical examination parameters of periimplant/periodontal soft tissues. These parameters included Silness–Löe plaque index (PI), Löe–Silness gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD) and probing attachment level (PAL). Results: PISFOP was higher than GCFOP, and GI, BOP, PPD and PAL were higher in the implant group than in the tooth group (P<0.05). PISFOP positively correlated with the clinical parameters of implants (P<0.01 for PI, GI and BOP; P<0.05 for PPD and PAL), and GCFOP positively correlated with the clinical parameters of teeth (P<0.01 for PPD; P<0.05 for PI, GI, BOP and PAL). Conclusions: The results reveal that PISFOP and GCFOP may be measured by osmometer, and their levels may be related with the clinical conditions of periimplant/periodontal soft tissues. To cite this article:
Sakallιo?lu U, Lütfio?lu M, Sakallιo?lu EE, Sert S, Ceylan G. Osmotic pressure of periimplant sulcular and gingival crevicular fluids: a split‐mouth, randomized study of its measurement and clinical significance.
Clin. Oral Impl. Res. 22 , 2011; 706–710
doi: 10.1111/j.1600‐0501.2010.02044.x     

Effect of Non‐Surgical Periodontal Treatment on Gingival Crevicular Fluid and Serum Endocan,Vascular Endothelial Growth Factor‐A,and Tumor Necrosis Factor‐Alpha Levels

Background: Periodontitis is a chronic inflammatory disease that occurs due to the interaction between pathogenic microorganisms and host defenses. Endocan is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Aims of the study are to determine serum and gingival crevicular fluid (GCF) endocan levels in the pathogenesis of periodontal diseases, supported with vascular endothelial growth factor (VEGF‐A) and tumor necrosis factor (TNF)‐alpha levels. This study additionally aims to evaluate correlation between GCF endocan levels, VEGF‐A, and TNF‐α levels with periodontal probing depth (PD). Methods: The study consists of two groups: group 1 (n = 20), healthy individuals; group 2 (n = 20), individuals with generalized chronic periodontitis (CP). Clinical measurements were recorded; GCF and serum samples were obtained from each participant before and 6 weeks after therapy. Levels of biomarkers were measured by enzyme‐linked immunosorbent assay. Intergroup comparisons of biochemical and clinical parameters were analyzed by Kruskal–Wallis/Bonferroni‐adjusted Mann–Whitney U test using statistical software. Results: Serum and GCF endocan, VEGF‐A, and TNF‐α levels were significantly higher in patients with CP than in healthy individuals (P <0.001) and decreased after treatment (P <0.03). A significant correlation was observed between GCF TNF‐α and PD (4 mm ≤ PD ≤5 mm and PD ≥6 mm). A significant relationship was found among GCF endocan and TNF‐α, VEGF‐A, CAL, and GI for all groups (P <0.05). Conclusions: Endocan and TNF‐α levels, both in GCF and serum, increased from health to periodontitis and decreased with non‐surgical periodontal treatment. Within the limits of the study, endocan may be considered as a potential inflammatory marker for periodontal disease.     

Effect of Intensive Oral Hygiene Regimen During Pregnancy on Periodontal Health,Cytokine Levels,and Pregnancy Outcomes: A Pilot Study

Background: Data are limited on the potential effect of intensive oral hygiene regimens and periodontal therapy during pregnancy on periodontal health, gingival crevicular fluid (GCF) and serum cytokines, and pregnancy outcomes. Methods: A clinical trial was conducted on 120 community‐dwelling, 16‐ to 35‐year‐old pregnant women at 16 to 24 weeks of gestation. Each participant presented with clinical evidence of generalized, moderate‐to‐severe gingivitis. Oral hygiene products were provided, together with instructions for an intensive daily regimen of hygiene practices. Non‐surgical therapy was provided at baseline. Oral examinations were completed at baseline and again at 4 and 8 weeks. In addition, samples of blood and GCF were collected at baseline and week 8. Mean changes in clinical variables and GCF and serum cytokine levels (interleukin [IL]‐1β, IL‐6, tumor necrosis factor [TNF]‐α) between baseline and week 8 were calculated using paired t test. Pregnancy outcomes were recorded at parturition. Results: Results indicated a statistically significant reduction in all clinical variables (P <0.0001) and decreased levels of TNF‐α (P = 0.0076) and IL‐1β (P = 0.0098) in GCF during the study period. The rate of preterm births (<37 weeks of gestation) was 6.7% (P = 0.113) and low birth weight (<2,500 g) was 10.2% (P = 1.00). Conclusions: Among the population studied, intensive instructions and non‐surgical periodontal therapy provided during 8 weeks at early pregnancy resulted in decreased gingival inflammation and a generalized improvement in periodontal health. Large‐scale, randomized, controlled studies are needed to substantiate these findings.     

Can Peri‐Implant Crevicular Fluid Assist in the Diagnosis of Peri‐Implantitis? A Systematic Review and Meta‐Analysis

Background: A broader understanding of the immune inflammatory profile of peri‐implant diseases could be helpful in the development of host‐targeted preventive and therapeutic strategies. The aim of this study is to answer two clinical questions: 1) whether patients with peri‐implantitis (PP) present higher prevalence of any specific inflammatory cytokine in peri‐implant crevicular fluid (PICF) compared with healthy patients; and 2) whether local inflammation measured in PICF can be used as a predictor for incipient PP. Methods: A systematic review of the literature on the most common cytokines released in PICF in healthy and PP‐affected sites was conducted from 1996 up to and including October 2013 using predefined search strategies. Cross‐sectional and prospective longitudinal studies were considered. Meta‐analyses were done separately for healthy, mucositis (MU), and PP outcomes. Results: Interleukin (IL)‐1β was the most studied cytokine (n = 12), followed by tumor necrosis factor (TNF)‐α (n = 10). Other cytokines were also linked to PP, such as IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, and IL‐17. Statistical differences were revealed when IL‐1β release was compared between healthy implant sites and PP (P = 0.001) or MU sites (P = 0.002), respectively; when PP and MU were compared, no statistical differences could be detected (P = 0.80). For TNF‐α release, significant differences were found between healthy and PP implants (P = 0.02). Conclusions: PICF containing inflammatory mediators, such as IL‐1β and TNF‐α, can be used as additional criteria for a more robust diagnosis of peri‐implant infection. Additionally, once the inflammatory process is installed, no differences were found between peri‐implant MU and PP.     

Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment

Oral Diseases (2012) 18 , 299–306 Objective: The aim of this study was to evaluate the effects of periodontal treatment on serum and gingival crevicular fluid (GCF) proinflammatory cytokine levels in hyperlipidemic patients with periodontitis. Materials and Methods: Fifty‐two patients with hyperlipidemia and periodontitis and 28 systemically healthy controls with periodontitis (C) were included in the study. Hyperlipidemic groups were divided into two groups as suggested diet (HD) and prescribed statin (HS). The clinical periodontal parameters, fasting venous blood, and GCF samples were obtained, and serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL) 1‐beta, and IL‐6 levels were evaluated at baseline and at 3 months follow‐up (3MFU) after the completion of the non‐surgical periodontal treatment that included scaling and root planning. Results: Percentage of bleeding on probing was significantly higher in the HS group than both the HD and C groups. In the HD and HS groups, there were significant decreases in serum IL‐6 and GCF TNF‐α levels between the 3MFU and baseline. A significant decrease was also found in GCF IL‐6 at the end of the study period in the HS group. Conclusion: The combination of the periodontal therapy and antilipemic treatment may provide beneficial effects on the metabolic and inflammatory control of hyperlipidemia.     

Level of Interleukin‐35 in Gingival Crevicular Fluid,Saliva, and Plasma in Periodontal Disease and Health

Background: A novel member of the interleukin (IL)‐12 family, IL‐35 is an important inhibitory cytokine released by regulatory T cells. The aim of this study is to evaluate gingival crevicular fluid (GCF), saliva, and plasma levels of IL‐35 in periodontal disease and health. Methods: Samples of GCF, whole saliva, and plasma were obtained from systemically healthy, non‐smoking individuals with gingivitis (n = 20) or chronic periodontitis (CP) (n = 20) and periodontally healthy individuals (n = 20). Full‐mouth clinical periodontal measurements, including probing depth (PD), bleeding on probing, gingival index, and plaque index (PI), were also recorded. Enzyme‐linked immunosorbent assay was used to determine IL‐35 levels in the samples. Data were tested statistically by analysis of variance and Pearson rank correlation test. Results: All clinical parameters were significantly higher in the CP group than the healthy and gingivitis groups (P <0.001). The GCF total amount of IL‐35 was significantly higher in the CP group than the other groups (P = 0.04), whereas the GCF concentration of IL‐35 was significantly higher in the healthy group than the other groups (P = 0.002). There were significant differences among the study groups in terms of salivary IL‐35 level (P <0.001), with the highest level observed in the healthy group and the lowest in the CP group. There was no statistical difference between groups in plasma levels of IL‐35 (P >0.05). There was a positive correlation between GCF total amount of IL‐35 and PD (r = 0.338, P = 0.03) and PI (r = 0.374, P = 0.005) parameters. Conclusions: IL‐35 could have an important role in suppressing periodontal inflammation and maintaining periodontal health. Additional studies are required to evaluate its role in periodontal diseases.     

Proinflammatory and Anti‐Inflammatory Cytokines in Gingival Crevicular Fluid and Serum of Patients With Rheumatoid Arthritis and Patients With Chronic Periodontitis

Background: The aim of this study is to evaluate proinflammatory and anti‐inflammatory cytokine levels in gingival crevicular fluid (GCF) and serum of rheumatoid arthritis (RA) and chronic periodontitis (CP) patients to assess whether cytokine profiles distinguish patients with RA and patients with CP while using healthy patients as background controls. Methods: A total of 49 patients, 17 patients with RA (three males and 14 females; mean age: 47.82 ± 10.74 years), 16 patients with CP (10 males and six females; mean age: 44.00 ± 7.00 years), and 16 controls (eight males and eight females; mean age: 28.06 ± 6.18 years) were enrolled. Patients with RA were under the supervision of rheumatologists; 15 of the patients with RA were being treated with methotrexate–sulfasalazine combined therapy, and two of the patients were being treated with leflunomid therapy. Periodontal parameters (plaque index, gingival index, probing depth, and clinical attachment level) were recorded. Interleukin (IL)‐1β, IL‐4, IL‐10, and tumor necrosis factor‐α (TNF‐α) were determined in GCF and IL‐1β and IL‐10 in serum by enzyme‐linked immunosorbent assay. Results: There were significant differences found among RA, CP, and control groups for all periodontal parameters (P <0.05). The total amount and concentration of GCF IL‐1 β, IL‐4, IL‐10, and TNF‐α were similar in RA and CP patients (P >0.05). Although the total amount and concentration of serum IL‐10 was not significantly different among the groups (P >0.05), serum IL‐1β was significantly lower in the RA group compared to CP patients and controls and was higher in GCF of the RA group compared to the CP group. Conclusions: Although clinical periodontal disease parameters indicated more severe periodontal disease in CP compared to RA patients, immunologic evaluation did not reveal consistent results regarding proinflammatory and anti‐inflammatory cytokine levels. This might be a result of the use of non‐steroidal anti‐inflammatory drugs and rheumatoid agents by patients with RA.