Effect Of Elastomeric Separator On Microbial Count In Gingival Crevicular Fluid.

BACKGROUND: The separators are a preliminary step for band insertion, but there is a potential risk of bacteraemia during their placement, particularly in susceptible patients. The objective of the study is to determine the effect of separators on the bacterial count in gingival crevicular fluid (GCF) and to assess the efficacy of chlorhexidine mouth rinse and saline irrigation in the reduction of the bacterial count. METHODS: This randomized controlled trial was conducted on 51 participants who were divided into three equal g roups randomly (brushing only/control, saline irrigation, and 2% chlorhexidine mouthwash rinse). The inclusion criteria were age between 18-25 years, good oral hygiene, gingival and plaque index <1, no previous orthodontic treatment, and healthy individuals. The bacterial count was obtained from GCF samples after two hours, on the third day, and on the seventh day. Kruskal Wallis test was used to compare the bacterial count among the three groups, and post hoc analysis was done using Dunn's test. Friedman test was applied to see the difference at three-time points in each group. RESULTS: In both saline and chlorhexidine groups the mean bacterial count decreased significantly from baseline to 3rd day and 7th day after separator placement (p<0.001). For the third day, a significant difference was found in control versus saline and control versus chlorhexidine. No significant difference was found between saline and chlorhexidine on the third day. Similar results were found on the 7 thday. For controls, the bacterial count increased with time and for both saline and chlorhexidine groups the bacterial count decreased. The highest decrease in the bacterial count was found for the chlorhexidine group. CONCLUSIONS: After the placement of separators, there was an increase in the bacterial count in GCF. Notably, chlorhexidine was found to be more effective than saline irrigation in reducing the bacterial count.

Effects of Kangfuxinye on NF-κB and Inflammatory Cytokines in Gingival Crevicular Fluid of Patients with Orthodontic Gingivitis Caused by Orthodontic Treatment.

Explore the Kangfuxinye effection on the expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inflammatory cytokines (IC) in the gingival crevicular fluid of patients with orthodontic gingivitis caused by orthodontic treatment. 98 patients with orthodontic gingivitis in Qingdao Stomatological Hospital caused by orthodontic treatment were divided into two groups, namely, the control treatment group and the Kangfuxinye treatment group. In this study, the expressions of those proteins and IC in gingival crevicular fluid before and after treatment were analyzed at first, and the correlations of the NF-κB p65 expression with IC were explored. Then the differences in the expressions of those proteins and IC and the efficacy between the control treatment group and the Kangfuxinye treatment group were analyzed. Compared with those before treatment, the expressions of NF-κB-related proteins and IC interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF)] were significantly decreased after treatment (p<0.05). After treatment, the expression of NF-κB p65 was positively correlated with IL-1ß, TNF-α and VEGF, but negatively related to IL-4 and IL-10. In addition, compared with the control treatment, Kangfuxinye significantly reduced the expressions of those proteins and their messenger ribonucleic acids (mRNAs) (p<0.05), decreased the expressions of IL-1ß, TNF-α and VEGF (p<0.05) but improved the total effective rate of treatment. Kangfuxinye can reduce the NF-κB expressions and IC in the gingival crevicular fluid of patients with orthodontic gingivitis caused by orthodontic treatment and enhance the efficacy.

Increased expression of advanced glycation endproducts in the gingival crevicular fluid compromises periodontal status in cigarette-smokers and waterpipe users.

BACKGROUND: The aim was to assess the association between levels of advanced glycation endproducts (AGEs) in the gingival crevicular fluid (GCF) and periodontal parameters among cigarette-smokers and waterpipe-users. METHODS: Self-reported cigarette-smokers; waterpipe-users and never-smokers were included. Demographic data was recorded using a questionnaire. Periodontal parameters (plaque index [PI], gingival index [GI], clinical attachment loss [AL], probing depth [PD], and marginal bone loss [MBL]) were assessed in all groups. The GCF samples were collected using standard techniques and assessed for AGEs levels using enzyme-linked immunosorbent assay. Sample-size estimation was done and group-comparisons were done. Correlation between levels of GCF AGEs levels and periodontal parameters was assessed using a logistic regression model. Level of significance was set at P < 0.01. RESULTS: Eighty-two individuals (28 cigarette-smokers, 28 waterpipe-users and 26 never-smokers) were included. There was no difference in mean ages of all patients. Cigarette-smokers had a smoking history of 5.1 ± 0.2 pack years and waterpipe-users were using waterpipe for 4.4 ± 0.6 years. There was no statistically significant difference in PI, GI, clinical AL, PD and MBL in all groups. Levels of AGEs were significantly higher among cigarette-smokers (P < 0.001) and waterpipe-users (P < 0.001) than never-smokers. There was no significant correlation between levels of GCF AGEs levels and periodontal parameters in all groups. CONCLUSION: Clinical periodontal status of individuals with a short history of cigarette-smoking and waterpipe-usage may appear similar to never-smokers. On a molecular level, cigarette-smoking and waterpipe-users express raised levels of AGEs than never-smokers that sirens about the ongoing yet latent periodontal inflammatory process.

Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation.

BackgroundGingivitis and periodontitis are prevalent inflammatory diseases of the periodontal tissues. Current treatments are often ineffective or do not prevent disease recurrence. Uncontrolled complement activation and the resulting chronic gingival inflammation are hallmarks of periodontal diseases. We determined the efficacy and safety of a complement 3-targeted therapeutic, AMY-101, which was locally administered to adult patients with periodontal inflammation.MethodsThirty-two patients with gingival inflammation were enrolled in a randomized, placebo-controlled, double-blind, split-mouth phase IIa trial that followed a dose escalation study to select a safe and effective dose in an additional 8 patients. Half of the patient's mouth was randomly assigned to AMY-101 (0.1 mg/site) or placebo injections at sites of inflammation, administered on days 0, 7, and 14, and then evaluated for safety and efficacy outcomes on days 28, 60, and 90. The primary efficacy outcome was a change in gingival inflammation, measured by a modified gingival index (MGI), and secondary outcomes included changes in bleeding on probing (BOP), the amount of plaque, pocket depth, clinical attachment level, and gingival crevicular fluid levels of matrix metalloproteinases (MMPs) over 90 days.ResultsA once-weekly intragingival injection of AMY-101 for 3 weeks was safe and well tolerated in all participants and resulted in significant (P < 0.001) reductions in clinical indices measuring gingival inflammation (MGI and BOP). AMY-101 significantly (P < 0.05) reduced MMP-8 and MMP-9 levels, indicators of inflammatory tissue destruction. These therapeutic effects persisted for at least 3 months after treatment.ConclusionAMY-101 treatment resulted in a significant and sustainable reduction in gingival inflammation without adverse events and, we believe, merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions.Trial registrationClinicalTrials.gov identifier NCT03694444.FundingAmyndas Pharmaceuticals.

The neutrophil subset defined by CD177 expression is preferentially recruited to gingival crevicular fluid in periodontitis.

In recent years, the concept of distinct subpopulations of human neutrophils has attracted much attention. One bona fide subset marker, exclusively expressed by a proportion of circulating neutrophils in a given individual, and therefore dividing neutrophils in two distinct subpopulations, is the glycoprotein CD177. CD177 is expressed on the plasma and granule membranes of 0-100% of circulating neutrophils depending on the donor. Several in vitro studies have linked CD177 to neutrophil transmigration, yet very few have looked at the role of CD177 for tissue recruitment in vivo. We investigate whether the CD177+ and CD177- neutrophil subsets differ in their propensity to migrate to both aseptic- and microbe-triggered inflamed human tissues. Microbe-triggered neutrophil migration was evaluated in samples of gingival crevicular fluid (GCF) from patients with periodontitis, whereas neutrophil migration to aseptic inflammation was evaluated in synovial fluid from patients with inflammatory arthritis, as well as in exudate from experimental skin chambers applied on healthy donors. We found that the proportion of CD177+ neutrophils was significantly higher in GCF from patients with periodontitis, as compared to blood from the same individuals. Such accumulation of CD177+ neutrophils was not seen in the two models of aseptic inflammation. Moreover, the proportion of CD177+ neutrophils in circulation was significantly higher in the periodontitis patient group, as compared to healthy donors. Our data indicate that the CD177+ neutrophil subset is preferentially recruited to the gingival crevice of periodontitis patients, and may imply that this subtype is of particular importance for situations of microbe-driven inflammation.

Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.

COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans.

Anti-biofilm and anti-inflammatory effect of a herbal nanoparticle mouthwash: a randomized crossover trial.

Laboratory evidence has demonstrated the antimicrobial effect of Melaleuca alternifolia (MEL) against oral microorganisms. This randomized, double-blind, crossover clinical trial, compared the anti-biofilm and anti-inflammatory effects of MEL nanoparticles with 0.12% chlorhexidine gluconate (CHX) on biofilm-free (BF) and biofilm-covered (BC) surfaces. Before each experimental period, the participants refrained from all oral hygiene practices for 72 hours. The 60 participants were randomly assigned to professional prophylaxis in two quadrants (Q1-Q3 or Q2-Q4), and rinsed with MEL or CHX for four days. The Quigley & Hein plaque index (QHPI), gingival crevicular fluid (GCF) volume, and participants' perceptions were assessed. CHX showed significantly lower mean QHPI on BF (2.65 ± 0.34 vs. 3.34 ± 0.33, p < 0.05) and BC surfaces (2.84 ± 0.37 vs. 3.37 ± 0.33, p < 0.05). Intragroup comparisons indicated reductions in GCF in all the groups, with significant differences only for CHX on BF surfaces (p < 0.05). Intergroup comparisons revealed no significant differences (p > 0.05). Based on individual perceptions, CHX had better taste and biofilm control, but resulted in a greater change in taste. Nevertheless, MEL demonstrated anti-inflammatory effects similar to those of CHX. Further clinical trials testing different protocols, concentrations and follow-up periods are required to establish its clinical application.

Participación de la leptina en la enfermedad periodontal / Participation of leptin in periodontal disease

Las proteínas participan en el resguardo del estado fisiológico de los tejidos buco-dentales, contribuyendo en la protección y recuperación de los mismos. En el caso de la leptileptina, una citoquina tipo I reconocida por regular la ingesta de alimentos y el gasto energético, la evidencia actual señala además su rol en la inmunidad e inflamación, induciendo la producción de otras citoquinas y estimular la fagocitosis. Siendo la enfermedad periodontal la segunda patología bucodental más prevalente en el mundo, caracterizada por inflamación crónica, inducida por bacterias periodontopatógenas, es necesario conocer los elementos biológicos que participan en la patogenia de la misma. La siguiente revisión bibliográfica tiene como propósito discernir la participación de la leptina en la enfermedad periodontal. En el periodonto la leptina participa exhibiendo un comportamiento protector, donde la disminución de los niveles del péptido en encía, fluido crevicular gingival (FCG) y saliva, es inversamente proporcional al grado de severidad de la enfermedad periodontal; permitiendo considerar que la valoración de leptina en FCG puede ser empleada como herramienta de diagnóstico y pronóstico de las alteraciones periodontales

Proteins participate in the protection of the physiological state of the oral tissues, contributing in the protection and recovery of them. In the case of leptin, a type I cytokine, recognized for regulating food intake and energy expenditure, current evidence also points to its role in immunity and inflammation, inducing the production of other cytokines and stimulating phagocytosis. Being the periodontal disease the second most prevalent oral pathology in the world, characterized by chronic inflammation, induced by periodontopathogenic bacteria, it is necessary to know the biological elements that participate in the pathogenesis of it. The purpose of the following literature review is to discern the participation of leptin in periodontal disease. In the periodontium leptin participates exhibiting a protective behavior, where the decrease in the levels of the peptide in the gingiva, gingival crevicular fluid (FCG) and saliva, is inversely proportional to the degree of severity of the periodontal disease; allowing to consider that the evaluation of leptin in FCG can be used as a tool for diagnosis and prognosis of periodontal alterations

Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis.

Periodontitis is a prevalent chronic inflammatory disease associated with dysbiosis. Although complement inhibition has been successfully used to treat periodontitis in animal models, studies globally analyzing inflamed tissue proteins to glean insight into possible mechanisms of action are missing. Using quantitative shotgun proteomics, we aimed to investigate differences in composition of inflammatory gingival tissue exudate ("gingival crevicular fluid"; GCF), before and after local administration of an inhibitor of the central complement component, C3, in nonhuman primates. The C3 inhibitor, Cp40 (also known as AMY-101) was administered locally in the maxillary gingival tissue of cynomolgus monkeys with established periodontitis, either once a week (1×-treatment; n = 5 animals) or three times per week (3×-treatment; n = 10 animals), for 6 weeks followed by another 6 weeks of observation in the absence of treatment. 45 GCF samples were processed for FASP digestion and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Data were processed using the ProgenesisQI software. The statistical significance of differences between the groups was determined by RM-ANOVA, and a protein expression change was considered as a true regulation at >2-fold and p < 0.05. The human orthologues were subjected to Gene Ontology analyses using PANTHER. Data are available via ProteomeXchange with identifier PXD009502. 573 proteins with >2 peptides were longitudinally quantified. Both 3× and 1× administration of Cp40 resulted in significant down-regulation of dozens of proteins during the 6-week course of treatment as compared to baseline. Following drug withdrawal at 6 weeks, more than 50% of the down-regulated proteins showed increased levels at week 12. The top scored pathway was "complement activation, alternative pathway", and several proteins involved in this pathway were down-regulated at 6 weeks. We mapped the proteomic fingerprint changes in local tissue exudate of cynomolgus monkey periodontitis in response to C3 inhibition and identified the alternative pathway of complement activation and leukocyte degranulation as main targets, which are thus likely to play significant roles in periodontal disease pathogenesis. Label-free quantitative proteomics strategies utilizing GCF are powerful tools for the identification of treatment targets and providing insights into disease mechanisms.

Effect of systemic long-term, low-dose aspirin on periodontal status and soluble CD14 in gingival crevicular fluid: a case-control study.

AIM: In the present study, we evaluated the effect of systemic long-term, low-dose aspirin on the periodontal status and gingival crevicular fluid (GCF) concentrations of aspirin-triggered lipoxins (ATL) and soluble CD14 (sCD14). METHODS: The study group consisted of 45 patients who were on long-term, low-dose aspirin therapy, and the control group included patients not on aspirin therapy. Mean bleeding index, plaque index (PI), probing depth (PD), and clinical attachment loss (CAL) were recorded. GCF samples were analyzed for concentrations of ATL, and sCD14 using enzyme-linked immunosorbent assay method. RESULTS: The means of PI, PD, and CAL were higher for the control group compared to the study group. The mean concentration of ATL was significantly higher for the study group (49.13 ± 37.39 ng/mL). The mean concentration of sCD14 was higher in the control group (5.75 ± 3.91 µg/mL). There was a negative correlation in the study group between concentrations of ATL with PD (r = -0.54) and CAL (r = -0.123). There was a positive correlation between sCD14 and CAL (r = 0.047) in the study group. A negative correlation was also observed between concentrations of sCD14 and ATL (r = -0.134) in the study group. CONCLUSION: The results indicate better periodontal status among long-term aspirin users compared to non-aspirin users.

Effects of a cyclic NSAID regimen on levels of gingival crevicular fluid prostaglandin E2and Interleukin-1ß: A 6-month randomized controlled clinical trial.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for inflammation control and pain relief. However, while the adjunct use of NSAIDs is avoided for periodontal therapy because of related side effects, cyclic administration of NSAIDs may reduce or eliminate these effects. We evaluated the effect of a cyclic diclofenac potassium (DP) regimen on clinical parameters and levels of prostaglandin E2 (PGE2) and interleukin-1ß (IL-1ß) in the gingival crevicular fluid (GCF) of individuals with periodontitis. MATERIALS AND METHODS: The study protocol was approved by the Ethics Committee (2000/071). Forty-one individuals with chronic periodontitis (33 men, 8 women) were divided into two groups (test and control) after initial periodontal therapy. During this 6-month, randomized, double-blind, placebo-controlled study, test (n = 28) and control (n = 13) groups were administered a cyclic regimen of DP (50 mg, twice daily) or placebo. Clinical measurements and GCF sample collections were made at baseline, 2, 4, and 6 months. GCF levels of PGE2and IL-1ß were determined using enzyme immunoassay and enzyme-linked immunoassay kits, respectively. RESULTS: At baseline, no significant differences existed between groups for plaque indices, gingival indices, bleeding on probing, probing depth (PD), or attachment levels (P > 0.05). Compared with the control group, cyclic regimen in the test group suppressed increased levels of PGE2found in GCF at the end of the study (P < 0.05). Significant differences for PD and relative attachment gain were also noted in favor of the test group (P < 0.05). CONCLUSIONS: These results suggest that a cyclic regimen of DP may be efficacious in the management of chronic periodontitis in adults.

The anti-inflammatory effect of locally delivered nano-doxycycline gel in therapy of chronic periodontitis.

BACKGROUND AND OBJECTIVE: To date, various drugs as host modulating agents had been suggested as adjunctive treatment modality in the therapy of chronic periodontal disease. In this study, the anti-inflammatory effect of subgingivally delivered nanostructured doxycycline gel (nDOX) was evaluated and compared to conventional doxycycline gel (DOX) used as adjunct to scaling and root planning (SRP) in the treatment of moderate chronic periodontitis to reduce probing pocket depth. MATERIAL AND METHODS: Nanostructured doxycycline gel (nDOX) was prepared using spray-drying technique with chitosan (CH) as a matrix polymer, followed by dispersion in polyvinyl alcohol (PVA). The deepest periodontal pocket in 45 patients suffering from moderate chronic periodontitis was selected. The patients were divided into three groups following scaling and root planning (SRP); group I: SRP + nDOX, group II: SRP + DOX and group III: SRP + placeboCH. Plaque Index (PI), Gingival Index (GI), pocket depth (PD) and clinical attachment level(CAL), as well as ginigival crevicular fluid levels of (GCF) IL-6 and TNF-α were assessed at baseline, 1 and 3 months following local drug application. RESULTS: Group I showed significant reduction in probing depth and attachment gain compared with group II and III at one and three months period. The inflammatory mediators levels were significantly reduced in all treatment groups at one-month period. Except for group I, the reduced values were observed at three-month period. CONCLUSION: The results suggest that treatment with nDOX gel as an adjunct to SRP had anti-inflammatory effect by improving both clinical parameters and inflammatory markers up to three months period.

In vitro oral epithelium cytotoxicity and in vivo inflammatory inducing effects of anesthetic rice gel.

In vitro cytotoxicity of lidocaine hydrochloride (LH) and prilocaine hydrochloride (PH) to oral epithelial cells, isolated from tissue specimens of healthy volunteers, were evaluated. Cell vitality after treating with 1-20% anesthetic solutions for 5 and 30 min was investigated using F-actin and 4',6-diamidino-2-phenylindole staining technique and observed by fluorescence microscopy. Vitality rate of more than 90% was found in all anesthetic groups at both durations whereas no survived cell was found in a positive control group (sodium dodecyl sulfate). Lactate dehydrogenase (LDH) assay was performed to confirm the safety of both anesthetic solutions. Cell culture medium after treating with LH or PH for 5 and 30 min were collected and analyzed using commercial kits. The results showed no significant difference between the test groups and negative control group (untreated culture) with low LDH levels. In vivo inflammatory inducing effect of 5, 10, 20% LH or PH loaded rice gels was investigated in healthy volunteers. Tumor necrosis factor alpha (TNF-α) in gingival cervicular fluid was determined by ELISA technique. It was found that the expression of TNF-α was not different from the baseline. The expression of this inflammatory mediator caused by the commercial gel was higher than those of both anesthetic rice gels. It might be due to the effects of other excipients in the formulation of the commercial product. It is concluded that LH or PH possess no cytotoxicity to oral epithelium and the developed rice gel base and LH and PH rice gels do not induce inflammatory effect to oral tissues.

Efficacy assessment of local doxycycline treatment in periodontal patients using multivariate chemometric approach.

The aim of our study was application of chemometric algorithms for multivariate data analysis in efficacy assessment of the local periodontal treatment with doxycycline (DOX). Treatment efficacy was evaluated by monitoring inflammatory biomarkers in gingival crevicular fluid (GCF) samples and clinical indices before and after the local treatment as well as by determination of DOX concentration in GCF after the local treatment. The experimental values from these determinations were submitted to several chemometric algorithms: principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA). The data structure and the mutual relations of the selected variables were thoroughly investigated by PCA. The PLS-DA model identified variables responsible for discrimination of classes of data, before and after DOX treatment. The OPLS-DA model compared the efficacy of the two commonly used medications in periodontal treatment, chlorhexidine (CHX) and DOX, at the same time providing insight in their mechanism of action. The obtained results indicate that application of multivariate chemometric algorithms can be used as a valuable approach for assessment of treatment efficacy.

EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial.

The enamel matrix derivative (EMD) contains hundreds of peptides in different levels of proteolytic processing that may provide a range of biological effects of importance in wound healing. The aim of the present study was to compare the effect of EMD and its fractions on the cytokine profiles from human gingival fibroblasts in vitro and in gingival crevicular fluid (GCF) in a randomized controlled split-mouth clinical study (n = 12). Levels of cytokines in cell culture medium and in GCF were measured by Luminex over a 2-week period. In the clinical study, levels of pro-inflammatory cytokines and chemokines were increased, whereas the levels of transforming growth factor-α (TGF-α) and platelet-derived growth factor-BB (PDGF-BB) were reduced. The in vitro study showed that EMD and its high and low molecular weight fractions reduced the secretion of pro-inflammatory cytokines and chemokines compared to untreated cells. EMD had an effect on levels of cytokines related to fibroplasia, angiogenesis, inflammation and chemotaxis both in vitro and in vivo, however, the anti-inflammatory effect induced by EMD observed in the in vitro study could not be confirmed clinically.

Statin intake is associated with MMP-1 level in gingival crevicular fluid of patients with periodontitis.

BACKGROUND: This study was conducted to assess whether statin intake is associated with clinical parameters of periodontitis and matrix metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) of non-diabetic and diabetic patients. METHODS: We first determined the effect of simvastatin on MMP expression in mononuclear cells. We then recruited 117 non-diabetic and diabetic patients, who all had periodontitis and took or did not take statin, and measured periodontal probing depth (PPD) and clinical attachment level (CAL), and collected gingival crevicular fluid (GCF) to quantify MMPs. RESULTS: The in vitro studies showed that simvastatin potently inhibited the expression of MMP-1, MMP-8, and MMP-9 upregulated by lipopolysaccharide (LPS) and high glucose in mononuclear cells. The patient study showed that, after adjusting for age and smoking status, PPD in diabetic patients on statin was significantly less than that in diabetic patients not on statin. MMP-1 level in GCF of non-diabetic and diabetic patients on statin was lower than that of non-diabetic and diabetic patients not on statin, respectively. No difference was found for MMP-8 and -9 levels in GCF. CONCLUSION: Statin intake is associated with reduced PPD in diabetic patients and MMP-1 level in GCF in either non-diabetic or diabetic patients.

Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial.

BACKGROUND AND OBJECTIVE: The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites. MATERIAL AND METHODS: This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1ß, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid. RESULTS: The levels of IL-1ß, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1ß increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1ß decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1ß, IL-6 and TNF-α were closely correlated with each other. CONCLUSION: This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

The effect of initial periodontal treatment on plasma, gingival crevicular fluid and salivary levels of 8-hydroxy-deoxyguanosine in obesity.

OBJECTIVE: Recent studies have shown adverse effects on the periodontium from the increased production of reactive oxygen species (ROS) in obesity. The purpose of this study was to investigate the effects of obesity on 8-hydroxy-deoxyguanosine (8-OHdG) levels in the bodily fluids of patients with and without periodontal disease and to evaluate changes after initial periodontal treatment. DESIGN: Forty-five obese individuals and 45 normal-weight individuals were included in this study. Obese and normal-weight groups were classified into three sub-groups: chronic periodontitis (CP), gingivitis (G) and periodontally healthy controls (CTRL). Gingival crevicular fluid (GCF), plasma, saliva samples and clinical measurements were obtained at baseline and a month after initial periodontal treatment. Levels of 8-OHdG were analysed by ELISA. RESULTS: While plasma 8-OHdG levels were significantly higher at baseline in the obese patients with periodontal disease than in the normal-weight individuals (P<0.05), no significant differences in GCF and saliva 8-OHdG levels were found (P ˃ 0.05). GCF and salivary 8-OHdG levels in obese patients with G and CP were significantly higher than in CTRL groups at baseline (P<0.05). After treatment, 8-OHdG levels were decreased in all groups with periodontal disease (P<0.01). Statistically significant positive correlations were observed between GCF 8-OHdG levels and GI in all the groups (P<0.001). CONCLUSIONS: The significant increase of plasma 8-OHdG levels in obese patients did not correlate with saliva and GCF 8-OHdG levels when compared to normal-weight individuals. Periodontal treatment had a positive effect on the periodontal parameters and 8-OHdG levels of both obese and normal-weight individuals.

Effects of curcumin on crevicular levels of IL-1ß and CCL28 in experimental gingivitis.

BACKGROUND: Curcumin has anti-inflammatory properties. The aim of this study was to compare interleukin-1ß (IL-1ß) and chemokine (C-C motif) ligand 28 (CCL28) levels following a topical application of curcumin (CRM), chlorhexidine (CHX) and chlorhexidine-metronidazole (CHX-MTZ) in an experimental gingivitis human model. METHODS: Sixty systemically healthy selected subjects were randomly assigned to one of three topical antigingivitis gels. Each gel was applied twice daily for 10 minutes as the sole method of oral hygiene for 29 days on the test quadrant only. Modified gingival index (MGI), plaque index (PI), bleeding on probing (BOP) and probing depth (PD) were assessed at baseline, 29 days and 60 days. Estimation of IL-1ß and CCL28 levels in gingival crevicular fluid was done at baseline and at 29 days. RESULTS: The increase of IL-1ß in the CRM (14.52 ± 16.6 pg/ml) and CHX-MTZ (31.63 ± 15.96) groups was significantly less than that of the CHX group (70.55 ± 38.81). Similar results were also observed for CCL28 (CRM: 8.12 ± 8.78 pg/ml; CHX-MTZ: 12.81 ± 18.68; CHX: 41.15 ± 22.82). All groups had a significant increase in MGI, PI and BOP at 29 days. CONCLUSIONS: The anti-inflammatory potential of topical curcumin was similar to CHX-MTZ but superior to CHX in affecting IL-1ß and CCL28 levels.

Biofilm Lysine Decarboxylase, a New Therapeutic Target for Periodontal Inflammation.

BACKGROUND: Lysine, a nutritionally essential amino acid, enters the oral cavity in gingival crevicular fluid (GCF). During oral hygiene restriction (OHR), lysine decarboxylase (LDC) in dento-gingival biofilms converts lysine to cadaverine. Lysine depletion impairs the dental epithelial barrier to bacterial proinflammatory products. Antibodies to LDC from Eikenella corrodens (Ecor-LDC) inhibit LDC activity and retard gingival inflammation in beagle dogs. Whether E. corrodens is the major source of LDC in dental biofilms and whether the lysine analog tranexamic acid (TA) inhibits LDC activity, biofilm accumulation, and GCF exudation in a human gingivitis model were examined. METHODS: Antibodies raised in goats to LDC-rich extracts from E. corrodens cell surfaces were used to inhibit Ecor-LDC and detect it in biofilm extracts using Western blots. Ecor-LDC activity was measured at pH 4.0 to 11.0 and its TA dissociation constant (Ki) at pH 7.0. Young adults used a 5% or 10% TA mouthwash three times daily during OHR for 1 week. RESULTS: Ecor-LDC antibodies and TA inhibited biofilm LDC. Ki of TA for Ecor-LDC was 940 µM. TA reduced plaque index (PI) by downshifting the PI correlation with biofilm lysine content after OHR without TA. GCF was correspondingly suppressed. However, greater TA retention in saliva partially relieved GCF suppression but not biofilm lysine depletion. CONCLUSIONS: TA slightly inhibits LDC but strongly reduces biofilm by inhibiting bacterial lysine uptake. Unfortunately, TA may impair dental epithelial attachments by also inhibiting lysine transporter uptake. Ecor-LDC inhibitors other than lysine analogs may maintain sufficient lysine levels and attachment integrity to prevent periodontal inflammation.