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Aim: Periodontal disease (PD) screening models based on a self-reported questionnaire were previously established and externally validated. The aim of the present study is to explore whether the screening models could be modified to improve prediction performance; this methodology is called 'updating'., Methods: Updating the models for 'total' and 'severe' PD was performed using two datasets. One dataset from a previous study (n = 155) was used to explore the updating, and a second (n = 187, built for the current study) was used to validate whether updating improved performance. Updating was based on different statistical approaches, including model recalibration and revision. Discrimination and calibration were assessed after updating., Results: For 'total' PD, the update based on model revision improved its performance. However, still low AUCs were found: 0.64 (0.56-0.73) and 0.61 (0.53-0.69) with corresponding O:E ratios 1.00 (0.80-1.23) and 0.92 (0.75-1.13) in the update and validation cohorts, respectively. For 'severe' PD, performance of the original model without update performed still the best; AUCs were 0.72 (0.61-0.83) and 0.75 (0.66-0.84) in the update and validation cohorts, respectively, with corresponding O:E ratios 0.60 (0.38-0.84) and 0.62 (0.42-0.87)., Conclusions: The updating methodology did not further improve the performance of the original 'severe' PD screening model; it performed satisfactorily in the medical care setting. Despite updating attempts, the screening model for 'total' PD remained sub-optimal. Screening for 'severe' PD can now be implemented in the medical care setting., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

What is the prevalence of temporomandibular dysfunction in patients with early rheumatoid arthritis and individuals at risk of rheumatoid arthritis? 3 groups (of 50 participants each) were examined for a possible TMD diagnosis: 1. patients with early rheumatoid arthritis, 2. at-risk individuals, and 3. healthy controls. A possible association with bruxism, determined on the basis of self-reporting and clinical features, was also examined. At-risk patients had a higher prevalence of TMD pain diagnoses compared to healthy controls (p = 0.046). Within the early rheumatoid arthritis group, seronegative patients had a higher prevalence of TMD pain diagnoses than seropositive patients (p = 0.048). No further differences in the prevalence of TMD diagnoses were found between the groups. Participants with a TMD pain diagnosis were more often diagnosed with probable sleep bruxism than those without a TMD pain diagnosis. The prevalence of TMD pain is increased in individuals at risk of rheumatoid arthritis and seronegative early rheumatoid arthritis patients, and is associated with signs of bruxism.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

Background: Periodontitis is a chronic multifactorial inflammatory disease of the supportive tissues of the teeth. In more recent years, remarkable epidemiological and pathophysiological associations between periodontitis and cardiovascular disease (CVD) have been presented. Whether or not treatment of periodontitis is valuable for primary or secondary prevention of cardiovascular disease, has not yet been fully established. In this practice-based pilot study we focused on primary prevention of cardiovascular disease, by investigating the effect of periodontal treatment on the earliest detectable stage of CVD; endothelial dysfunction., Methods: Otherwise healthy periodontitis and non-periodontitis participants 45-70 years of age were included in the study. One year after completing periodontal (non-surgical and surgical) treatment of the periodontitis patients and 1 year after inclusion of the controls, all baseline measurements were repeated. Full-mouth examinations were performed by a periodontist to determine their Periodontal Inflamed Surface Area (PISA) score and other dental parameters. To assess the cardiovascular conditions, endothelial function through the reactive hyperemia index (RHI) assessed by the EndoPAT™, and several physical and biochemical parameters were measured., Results: 21 patients with diagnosed, untreated periodontitis and 21 participants without periodontitis were included in this follow-up study. After periodontal therapy in the periodontitis patients, the PISA reduced significantly. The RHI did not show a significant improvement after treatment of the periodontitis patients (-0.1 ± 0.8, p = 0.524). Similarly, other secondary cardiovascular outcome measurements, hsCRP, total cholesterol, HDL cholesterol, triglycerides, HbA1c, and systolic blood pressure did not improve significantly after periodontal treatment. Controls did not show any significant changes in the RHI, in other CVD parameters and in the PISA after 1-year follow-up., Conclusion: In this practice-based pilot study, periodontal treatment did not improve the endothelial function in otherwise healthy adults with periodontitis. Future studies are needed to be of larger size and could focus on periodontitis patients with co-morbidities to investigate whether periodontal treatment has secondary preventive effect on endothelial function and other CVD parameters., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ISRCTN55656827]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Donders, Veth, Edens, van ’t Hof, de Lange and Loos.)

Objectives: Medical professionals should advise their patients to visit a dentist if necessary. Due to the lack of time and knowledge, screening for periodontitis is often not done. To alleviate this problem, a screening model for total (own teeth/gum health, gum treatment, loose teeth, mouthwash use, and age)/severe periodontitis (gum treatment, loose teeth, tooth appearance, mouthwash use, age, and sex) in a medical care setting was developed in the Academic Center of Dentistry Amsterdam (ACTA) [1]. The purpose of the present study was to externally validate this tool in an outpatient medical setting., Materials and Methods: Patients were requited in an outpatient medical setting as the validation cohort. The self-reported oral health questionnaire was conducted, demographic data were collected, and periodontal examination was performed. Algorithm discrimination was expressed as the area under the receiver operating characteristic curve (AUROCC). Sensitivity, specificity, and positive and negative predictive values were calculated. Calibration plots were made., Results: For predicting total periodontitis, the AUROCC was 0.59 with a sensitivity of 49% and specificity of 68%. The PPV was 57% and the NPV scored 55%. For predicting severe periodontitis, the AUROCC was 0.73 with a sensitivity of 71% and specificity of 63%. The PPV was 39% and the NPV 87%., Conclusions: The performance of the algorithm for severe periodontitis is found to be sufficient in the current medical study population. Further external validation of periodontitis algorithms in non-dental school populations is recommended., Clinical Relevance: Because general physicians are obligated to screen patients for periodontitis, it is our general goal that they can use a prediction model in medical settings without an oral examination., (© 2021. The Author(s).)

Background: Periodontitis is a chronic multifactorial inflammatory disease of the supportive tissues of the teeth. Pathophysiological evidence suggests a possible common inflammatory background between periodontitis and cardiovascular diseases (CVD). Pathological and epidemiological associations between these two diseases have been presented, but are still debated. This study aimed to investigate the association between the inflammatory burden of periodontitis and the presence and extent of coronary calcification. Secondary aims were to study other cardiovascular parameters and cardiovascular risk predictors in relation to periodontitis and dental health., Methods: Healthy periodontitis or non-periodontitis patients 45-70 years of age were included in a prospective cross-sectional study. Full-mouth examinations were performed by a periodontist to determine their Periodontal Inflamed Surface Area (PISA) score and other dental parameters. To assess the cardiovascular conditions, Coronary Artery Calcium (CAC) scores, endothelial function assessments by the EndoPAT ™, and several physical and biochemical examinations were performed., Results: Seventy-one patients were included. Elevated CAC scores and endothelial dysfunction were not significantly related to PISA or dental health. PISA was significantly related to the Framingham and Reynolds CVD risk predictors, but were no longer significant after correction for confounders. The same applied to the significant relations between tooth loss, dental plaque and bleeding scores and the CVD risk predictors., Conclusions: Periodontitis is associated with increased CVD risk, but is not an independent risk factor. This link is still important to make to bridge the gap between dentistry and general medicine and to identify patients at risk for CVD in an earlier stage., (© 2021 The Authors.)

Aim: This study explores the association between Coronary Artery Calcium (CAC) scores and dental pathology such as missing teeth, the (peri-apical) health status and restoration grade of the teeth, and the grade of alveolar bone loss seen on a dental panoramic radiograph (Orthopantomograph-OPG)., Materials and Methods: In this retrospective cross-sectional study, data was collected from three hospitals spread in the Netherlands. Patients were included when a CAC score and an OPG were available, both recorded within a maximum period of 365 days from 2009-2017. The CAC score was measured on a CT scan, using the Agatston method. To assess dental pathology, the number of missing teeth, the number of dental implants, alveolar bone loss, caries, endodontic treatments, peri-apical radiolucencies, bone loss at implants, impacted teeth and dental cysts, were determined on the OPG. All observers were calibrated. The electronic health records provided information about: gender, age, smoking, Diabetes Mellitus, hypercholesterolemia, hypertension and Body Mass Index (BMI)., Results: 212 patients were included. We found a statistically significant association between the number of missing teeth and the CAC score. When modeling age, sex, and other well-known risk factors for cardiovascular disease, the significant correlation was no longer present after multivariate correction. Furthermore, the results showed a trend for more teeth with peri-apical lesions and a higher percentage of mean alveolar bone loss in the group with the highest CAC scores., Conclusion: This study showed that being edentulous or missing teeth is correlated to higher CAC scores however failed to be an independent predictor of atherosclerotic cardiovascular diseases. The number of (missing) teeth is an easily accessible marker and could be used as a marker for atherosclerotic cardiovascular disease (ACVD) risk by almost any healthcare worker. The current study needs to be considered as an explorative pilot study and could contribute to the design of further (prospective) studies on the relationship between dental pathology and coronary artery calcification by adding clinical information and extra cardiovascular biomarkers., Competing Interests: The authors have declared that no competing interests exist.

Ideal restoration material for caries would allow attachment of gingival epithelia. The attachment of epithelial cells to specimens of the 4 most commercially used well- or partially-cured resin composites, with and without TEGDMA, was assessed. Effects of resin composite on the Ca9-22 gingival epithelial cell-line were assessed by measuring the cytotoxicity, viability and gene expression for attachment, apoptosis, ROS-production, pro-inflammatory cytokines, and matrix metalloproteinases. As controls, cells on tissue culture plastic or bovine tooth enamel specimens were used. Significantly less cell attachment was measured on freshly made resin-composite specimens. Concomitantly, significantly higher cytotoxicity was measured in the presence of freshly made resin-composite specimens. However, after 8 d of leakage, the cell attachment to and cytotoxicity of the resin composite was comparable to bovine tooth enamel. Significantly higher expressions of IL6, MMP2, BCL6 and ITGA4 were measured in cells attached to resin-composite surfaces than controls. There were no significant differences between the results using different conditions of resin composite, with or without TEGDMA and well or partially cured. Less cell attachment and presence of more inflammatory markers were observed on all freshly-made resin-composite surfaces. However, after a leakage period attachment of cells to the resin composite improved to the level of natural tooth materials such as enamel. This indicated that the negative effects of resin composites on epithelial cells might be transient.

Gingivitis and periodontitis can worsen with reduced immune fitness. Various causes can reduce immune fitness in a host, as a result of which the balance between the host and the microbiome is disturbed. Among others, lifestyle factors, such as stress and smoking, can have a negative influence on immune fitness. An association has been demonstrated between stress and periodontitis and also acute necrotising ulcerative gingivitis or periodontitis. There are indications that neurons are able to secrete pro-inflammatory cytokines and chemokines that worsen chronic inflammatory reactions in the periodontium and compromise immune fitness. In vitro studies show high cortisol levels may contribute to the increased growth of P. gingivalis. Stress as a risk factor for periodontitis and the role of stress as a negative influence on the results of periodontal treatment are difficult to estimate clinically. Nevertheless, attention to and awareness of stress as an aspect of the comprehensive set of risk factors for periodontitis can diminish its negative impact on immune fitness.

Objectives/aims: Rheumatoid arthritis (RA) is an autoimmune disease affecting the joints, including the temporomandibular joint (TMJ). Early diagnosis and treatment can alleviate symptoms and prevent progression. Predictors for disease outcome in individuals at risk for RA are therefore valuable. While limited information is available on the prevalence of TMJ involvement in early RA, previous studies suggest that RA, periodontitis and the oral microbiome are interrelated. Predictive factors for RA development may thus be present in the oral cavity. Our two aims are: (1) to assess the prevalence of TMJ involvement in early RA, and (2) to investigate the predictive value of oral factors in RA development., Materials and Methods: We will include 150 individuals in this multi-center, prospective cohort study: 50 patients with early RA, 50 at-risk individuals, and 50 healthy controls. At baseline, the TMJ, periodontal health, and the oral microbiome will be examined. The general health will be followed over time, on four occasions up to 3 years., Discussion: Our results will provide insight into the prevalence and clinical characterization of TMJ involvement in early RA. For at-risk individuals, oral factors can be studied as possible predictors for the development of RA., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts ( n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk ( P < 5 × 10 -5 ). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST , indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 ( P = 5 × 10 -07 ), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 ( P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.

Objectives: What is the family history of periodontal disease and the prevalence of smoking status among patients with professionally diagnosed periodontitis? Are these factors related to extent and severity of periodontitis?, Methods: Over a 10-year period, referred patients from a clinic for periodontology in the Netherlands were examined in a cross-sectional study. Patients received at the intake appointment a full-mouth periodontal examination. Data regarding family history of periodontitis and smoking status were recorded., Results: A total of 5375 adult periodontitis patients were included in this study sample with a mean age of 50 years. The prevalence of smoking was 34% and 37% of the subjects had at least one parent or sibling with periodontitis. The chance to have severe periodontitis was higher if the patient was male, smoker or had a brother with periodontitis. Being male, smoker and having a parent with periodontitis were significantly associated with a larger extent of periodontitis., Conclusions: Within the investigated population familial aggregation, smoking status, age and gender are factors that were related to extent and severity of adult periodontitis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the past, epidemiological studies focused on cavitated stages of caries. The arrival of the International Caries Detection and Assessment System (ICDAS) in 2004 allowed for clinical measurements of the initial stages of enamel caries. However, since the introduction, most studies applying the ICDAS still have studied the diseased population. The objective of this cross-sectional observational study was to describe early enamel caries in a large healthy young adult population and determine the relationship with diet and oral hygiene measures. The study population consisted of 268 healthy participants without frank cavitation. The examinations were done visually and radiographically using ICDAS on all tooth surfaces. In total, 8.6% of the surfaces (occlusal > approximal > smooth) had caries, of which 92.0% were confined to enamel (28.5% ICDAS score 1, 54.0% score 2, 8.6% score 3). Thirteen percent of the occlusal and 63% of the approximal caries were found with radiography. Thus, radiography is quintessential for the diagnosis of approximal enamel lesions. We found a positive correlation between enamel caries (ICDAS 1 to 3) and the consumption of mono- and disaccharides and carbohydrates ( r = 0.226 and r = 0.188, respectively, both P < 0.01), as well as a negative correlation with alcohol consumption ( r = -0.202, P < 0.01). There was also a positive correlation between enamel caries and the energy intake from mono- and disaccharides (sugar kJ, r = 0.206, P < 0.01), which was independent of body mass index. Only 11 participants consumed less than 10% of total energy as sugar kJ, which is the recommended percentage of kJ from free sugar by the World Health Organization. No clear correlation was found with oral hygiene. In conclusion, in this healthy young adult population, caries was found in 97.8% of the subjects, mostly initial enamel caries (ICDAS 1 to 2) in the occlusal surface of molars, and was related with dietary factors.

Aim: To report on our implementation process within the existing local curriculum of all periodontal competences and assessments as proposed in the 2010 European consensus meeting., Material and Method: In 2011, a workshop for all teaching staff at the Department of Periodontology, ACTA, an education and assessment blueprint, was developed to test for missing education and assessment of European competences, divided into seven domains. This was repeated in 2013. An oral evaluation of the staff followed both meetings., Results: It appeared that eight of 58 (14%) European competences were not taught, and 21 (35%) competences were not assessed. After evaluation of the results on the actual curriculum and the assessment programme, shared decisions were made about how to teach and assess the missing competences within the local periodontal educational programme. The second workshop in 2013 revealed still 8 (14%) competences were not taught and 8 (14%) competences were not assessed. Staff appreciated the used method of validation; it gave insight and an overview of the curriculum. The existence of the European consensus report for undergraduate periodontal education, based on seven domains, has been instrumental and essential., Conclusion: The development of a blueprint from the education programme and concomitant assessment methods in periodontology by participating teaching staff gives a validation and appreciation of the curriculum and will improve the quality of education and assessment. It is advised that for quality control of the curriculum, dental schools could do this exercise for all their specialties if European consensus reports exist., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy with or without antibiotics. Antibiotics resulted in a greater influence on the microbiome 3 months after therapy, but this difference disappeared at 6 months. Greater microbial diversity, specific taxa and certain microbial co-occurrences at baseline and not the use of antibiotics predicted better clinical treatment outcomes. Our results demonstrate the predictive value of specific subgingival bacterial profiles for the decision to prescribe antibiotics in the treatment of periodontitis, but they also indicate the need for alternative therapies based on ecological approaches.

Increased arterial stiffness (AS) is an important indicator for atherosclerotic cardiovascular disease (ACVD). Epidemiologically, periodontitis and ACVD are associated. Therefore, we aimed to investigate AS in periodontitis patients and controls. In addition, we explored the effect of periodontal therapy on AS in a sub-group of cases. Pulse-wave velocity (PWV), a non-invasive chair-side function test for AS, was measured in periodontitis patients (n=57; mean age 46.6 years) and compared with a reference group (n=48; mean age 45.5 years). In addition, 45 cases (mean age 46.9 years) were 6 months followed after periodontal treatment, to explore a possible effect on arterial function. Periodontitis patients showed a significantly increased PWV compared with the reference group (8.01±0.20 vs. 7.36±0.22 m s(-1) respectively; P=0.029) and this remained significant after adjustments for ACVD risk factors (P=0.019). After periodontal therapy, no significant reduction in PWV was seen (8.00±1.8 to 7.82±1.6 m s(-1); P=0.13), but systolic blood pressure (SBP) was significantly reduced (119.8±14.6 to 116.9±15.1 mm Hg; P=0.040). It can be concluded that periodontitis is associated with increased AS. This confirms with a new parameter the association of periodontitis with ACVD. Although periodontal treatment did not lower AS significantly, a modest reduction of SBP after 6 months was observed.

The evidence for an association between systemic diseases and periodontitis is strongest with diabetes mellitus type 2 and cardiovascular disease. There is a moderate association of periodontitis with adverse pregnancy outcomes and rheumatoid arthritis. Periodontal treatment has, on average, a positive effect on reducing systemic infection and improving the condition of the vascular system. For diabetes patients, periodontal treatment can also have a positive effect on metabolic regulation. There is insufficient evidence that periodontal treatment prevents adverse pregnancy outcomes and rheumatoid arthritis.

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial 'hypothesis-dependent' candidate-gene polymorphism studies did not report valid genetic risk loci. Following a large-scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of 'hypothesis-free' genome-wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published - one reported genome-wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well-designed genetic study with large and sufficiently powered case-control samples of severe phenotypes, are also discussed., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the May edition of The Nederlands Tijdschrift voor Tandheelkunde the editorial commentary was devoted to the question to what extent the treatment of periodontitis in patients with diabetes mellitus is worthwhile. B.G. Loos, W.J. Teeuw, V. Gerdes and F. Abbas offer a response to this commentary and argue that the treatment of periodontitis in patients with diabetes mellitus is always worthwhile.

Interrelationships between periodontal infection and systemic conditions such as cardiovascular disease, adverse pregnancy outcomes, and head-and-neck cancer have become increasingly appreciated in recent years. Periodontitis is associated with cardiovascular disease (CVD) and, experimentally, with measures of atherosclerosis and endothelial dysfunction. Periodontal therapy may reduce atherosclerotic changes and improve endothelial function. Preliminary findings suggest a role for the genetic locus ANRIL in the pathobiology of both CVD and periodontitis. Periodontal pathogens induce anticardiolipin in periodontitis patients by molecular mimicry of the serum protein β-2 glycoprotein I. These antibodies have biological and pathological activities consistent with those reported for other infection-induced antiphospholipid antibodies. Anticardiolipin may explain some of the observed associations between periodontitis and systemic conditions such as CVD and adverse pregnancy outcomes. The oral commensal Fusobacterium nucleatum (Fn) becomes pathogenic on migration to extra-oral sites. Fn infection of the fetal-placental unit has been linked to pregnancy complications, including preterm birth, stillbirth, and early-onset neonatal sepsis. Reagents aimed at inhibiting or resolving inflammatory responses may be used to treat or prevent pregnancy complications due to bacterial infection. Chronic periodontitis may be independently associated with head-and-neck squamous cell carcinoma (HNSCC) through direct toxic effects of bacteria and their products, and/or through indirect effects of inflammation. Additionally, chronic periodontitis may facilitate the acquisition and persistence of oral HPV infection, a recently emerged risk factor for HNSCC.

Background: This study aims to expand on a previously presented cellular automata model and further explore the non-linear dynamics of periodontitis. Additionally the authors investigated whether their mathematical model could predict the two known types of periodontitis, aggressive (AgP) and chronic periodontitis (CP)., Methods: The time evolution of periodontitis was modeled by an iterative function, based on the hypothesis that the host immune response level determines the rate of periodontitis progression. The chaotic properties of this function were investigated by direct iteration, and the model was validated by immunologic and clinical parameters derived from two clinical study populations., Results: Periodontitis can be described as chaos with the level of the host immune response determining its progression rate; the dynamics of the proposed model suggest that by increasing the host immune response level, periodontitis progression rate decreases. Renormalization transformations show the presence of two overlapping zones of disease activity corresponding to AgP and CP. By k-means cluster analysis, immunologic parameters corroborated the findings of the renormalization transformations. Periodontitis progression rates are modeled to scale with a power law of 1.3, and the mean exponential speed of the system is found to be 1.85 (metric entropy); clinical datasets confirmed the mathematical estimates., Conclusions: This study introduces a mathematical model that identifies periodontitis as a non-linear chaotic process. It offers a quantitative assessment of the disease progression rate and identifies two zones of disease activity that correspond to the existing classification of periodontitis in the AgP and CP types.

Background and Objective: To assess inflammatory reactions of fibroblasts in the pathophysiology of peri-implantitis, we compared the pro-inflammatory and matrix-degrading responses of gingival and granulation tissue fibroblasts from periodontally healthy controls, peri-implantitis, and periodontitis lesions to an in vitro challenge with Porphyromonas gingivalis., Methods: Fibroblasts from periodontally healthy, peri-implantitis and periodontitis donors were challenged with viable P. gingivalis. The inflammatory reactions of fibroblasts were analyzed before and after 6 h P. gingivalis challenge, and 2.5 and 18 h after removal of the challenge. Gene expression and induction of pro-inflammatory mediators, and matrix metalloproteinases (MMPs) were assessed by real-time polymerase chain reaction. Protein expression was measured by enzyme-linked immunosorbent assay., Results: Non-challenged fibroblasts from peri-implantitis and periodontitis lesions expressed higher levels of interleukin (IL)-1β, IL-8, and monocyte chemotactic protein (MCP)-1 than fibroblasts from periodontally healthy individuals. The P. gingivalis challenge induced expression of IL-1β, IL-8, IL-6, MCP-1, and MMP-1 in periodontitis and peri-implantitis fibroblasts, but not in fibroblasts from periodontally healthy individuals. MMP-8 expression was higher in non-challenged peri-implantitis fibroblasts than in fibroblasts from periodontally healthy individuals. However, the P. gingivalis challenge downregulated MMP-8 gene expression in peri-implantitis fibroblasts. After removal of the P. gingivalis challenge, peri-implantitis fibroblasts sustained higher induction of IL-1β, MCP-1, and MMP-1 compared to periodontitis fibroblasts., Conclusions: Fibroblasts from peri-implantitis and periodontitis lesions gave a more pronounced inflammatory response to the P. gingivalis challenge than fibroblasts from healthy donors. They may therefore be involved in the development of inflammation in peri-implantitis and periodontitis. Moreover, the sustained upregulation of inflammatory mediators and MMP-1 in peri-implantitis fibroblasts may play a role in the pathogenesis of peri-implantitis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The present study aims to extend recent findings of a non-linear model of the progression of periodontitis supporting the notion that aggressive periodontitis (AgP) and chronic periodontitis (CP) are distinct clinical entities. This approach is based on the implementation of recursive partitioning analysis (RPA) to evaluate a series of immunologic parameters acting as predictors of AgP and CP., Methods: RPA was applied to three population samples, that were retrieved from previous studies, using 17 immunologic parameters. The mean values of the parameters in control subjects were used as the cut-off points. Leave-one-out cross-validation (LOOCV) prediction errors were estimated in the proposed models, as well as the Kullback-Leibler divergence (DKL) of the distribution of positive results in AgP compared to CP and negative results in CP compared to AgP., Results: Seven classification trees were derived showing that the relationship of interleukin (IL)-4, IL-1, IL-2 has the highest potential to rule out or rule in AgP. On the other hand, immunoglobulin (Ig)A, IgM used to rule out AgP and cluster of differentiation 4 (CD4)/CD8, CD20 used to rule in AgP showed the least LOOCV cost. Penalizing DKL with LOOCV cost promotes the IL-4, IL-1, IL-2 model for ruling out AgP, whereas the single CD4/CD8 ratio with a lowered discrimination cut-off point was used to rule in AgP., Conclusions: Although a test is unlikely to have both high sensitivity and high specificity, the use of immunologic parameters in the right model can efficiently complement a clinical examination for ruling out or ruling in AgP.

Chronic inflammatory diseases like periodontitis have a complex pathogenesis and a multifactorial etiology, involving complex interactions between multiple genetic loci and infectious agents. We aimed to investigate the influence of genetic polymorphisms and bacteria on chronic periodontitis risk. We determined the prevalence of 12 single-nucleotide polymorphisms (SNPs) in immune response candidate genes and 7 bacterial species of potential relevance to periodontitis etiology, in chronic periodontitis patients and non-periodontitis control individuals (N = 385). Using decision tree analysis, we identified the presence of bacterial species Tannerella forsythia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and SNPs TNF -857 and IL-1A -889 as discriminators between periodontitis and non-periodontitis. The model reached an accuracy of 80%, sensitivity of 85%, specificity of 73%, and AUC of 73%. This pilot study shows that, on the basis of 3 periodontal pathogens and SNPs, patterns may be recognized to identify patients at risk for periodontitis. Modern bioinformatics tools are valuable in modeling the multifactorial and complex nature of periodontitis.

Background and Objective: The aim of the study was to compare the detection of Porphyromonas gingivalis using a fluorescence resonance energy transfer (FRET) technology with commonly used diagnostic methods in salivary and subgingival plaque samples from subjects with dental implants. P. gingivalis was considered as a marker for a pathogenic microbiota., Material and Methods: Ninety-seven adult subjects were recruited, including periodontally healthy controls with no dental implants, implant controls with no peri-implant disease and patients with peri-implant disease. Saliva and subgingival/submucosal plaque samples were collected from all subjects and were analyzed using culture, real-time PCR and FRET technology employing P. gingivalis-specific substrates., Results: It was found that the P. gingivalis-specific substrates were highly suitable for detecting the presence of P. gingivalis in saliva and in subgingival plaque samples, showing comparable specificity to culture and real-time PCR., Conclusion: We applied the FRET technology to detect P. gingivalis in implant patients with or without an implant condition and in controls without implants. The technique seems suitable for detection of P. gingivalis in both plaque and saliva samples. However, with all three techniques, P. gingivalis was not very specific for peri-implantitis cases. Future work includes fine-tuning the FRET technology and also includes the development of a chair-side application., (© 2012 John Wiley & Sons A/S.)

In order to gain insight into the degree to which periodontal disease is related to quality of life, research was carried out among 85 patients with moderate or severe periodontal disease in which they were asked to complete the Oral Health Impact Profile-NL49. Their scores on this questionnaire were compared with the scores of 85 control subjects of comparable age and gender. The patients with periodontal disease demonstrated significantly worse scores compared to the control group and patients with severe periodontal disease had scores which were statistically significantly worse than patients with moderate periodontal disease. The results of this study suggest a causal negative association of periodontal disease with quality of life.

COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were associated with periodontitis in populations of European ethnicity, we genotyped the single-nucleotide polymorphisms (SNPs) rs689466 and rs6681231, the latter a haplotype tagging SNP (htSNP) for rs20417 (r2>0.95), in our large-analysis population of individuals with aggressive (n = 532) and chronic periodontitis (n = 1052), and 2873 healthy control individuals. The rare G allele of htSNP rs6681231 was associated with aggressive periodontitis prior to and after adjustment for the covariates smoking, diabetes, and gender, with an odds ratio of 1.57 (95% confidence interval 1.18-2.08; p = 0.002). The validation of the association of rs20417 by the htSNP rs6681231 provides evidence for a general genetic risk of COX-2 variants in the pathogenesis of periodontitis.

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

Smoking is a strong risk factor for periodontitis. Treated patients who smoke show increased risk for further periodontal breakdown, despite receiving maintenance care. Previous work indicated that such patients have a monocytic cytokine response favoring Th2 activity. The purpose of this study was to investigate the T lymphocytic cytokine production representing Th1 and Th2 subpopulations in smokers and non-smokers. Venous blood was collected from 30 treated periodontitis patients (12 smokers) and 24 healthy subjects (12 smokers). Whole blood cell cultures were stimulated and interferon (IFN)-gamma and interleukin (IL)-13 were measured in the culture supernatants, representing types 1 and 2 Th subpopulations, respectively. Unadjusted data showed that smokers had more lymphocytes, and higher levels of IFN-gamma and IL-13, irrespective of being periodontal patient. However in a multivariate analysis, increased IFN-gamma production was not significantly explained by smoking, while higher IL-13 was strongly explained by smoking (21%, p<0.001). We suggest that the increased Th activity and specifically an elevated Th2 profile in smokers may constitute a risk for smoking patients which may induce conversion of periodontal stability into progressive disease. This phenomenon may be equally important in other conditions, where connective tissue and bone loss are hallmarks of disease pathophysiology.

Background: NOD proteins are part of innate immunity mechanisms. They play a role in epithelial barrier functions and inflammatory responses to bacteria. Single nucleotide polymorphisms (SNPs) in the NOD1 gene have proven to be associated with inflammatory bowel disease (IBD) and asthma., Objective: To investigate SNPs in the NOD1 gene in relation to aggressive periodontitis (AgP), a multifactorial, inflammatory disease of the supporting tissues of the teeth., Materials and Methods: Five SNPs in the NOD1 gene (4 intronic and 1 exonic) were tested for association in a total of 415 AgP patients and 874 controls both of Northern European ancestry., Results: The frequencies of the rare SNP alleles ranged between 21% and 26% among cases, and 20-27% among controls, and were not statistically different between cases and controls. Two SNPs were in strong linkage disequilibrium (r(2) = 0.97 in cases and 0.94 in controls). The overall haplotype distributions did not differ between cases and controls. We observed 8 haplotypes with a frequency of >or=1% among cases and/or controls, but none of these haplotype frequencies differed significantly among cases and controls. Logistic regression analyses with adjustment for gender and smoking status did not reveal significant associations with AgP for any of the 5 SNPs. This study had a power of >or=95% to detect associations with variants carrying relative risks of >or=1.5 for heterozygote carriers and >or=2.25 for homozygote carriers., Conclusions: Although SNPs in the NOD1 gene have been strongly associated with cases of IBD, the current study failed to show an association of NOD1 SNPs with AgP.

We previously demonstrated a role for alpha11beta1 integrin in periodontal ligament (PDL)-driven tooth eruption in the mouse. To explore a possible role for alpha11beta1 in the human periodontium, we have characterized the expression and function of alpha11 in human PDL tissue, in human PDL fibroblasts (hPDLF), and in human gingival fibroblasts (hGF). alpha11 expression was detected in PDL tissue, in hPDLF, and in hGF cells. Platelet-derived growth factor-BB and insulin-like growth factor II stimulated contraction of collagen lattices by both types of fibroblasts. alpha2 integrin blocking antibodies and the use of alpha11 siRNA demonstrated a role for both alpha2beta1 and alpha11beta1 in collagen lattice remodeling. Analysis of the proximal ITGA11 promoter from persons with chronic periodontal disease failed to reveal any polymorphism. Analysis of our data shows that alpha11beta1 is a major collagen receptor on cultured human PDL cells and implies that it is also functionally important in the PDL in vivo.

Background and Objective: Smoking is associated with increased severity of periodontitis. The underlying mechanisms of this phenomenon are not well understood. The purpose of the present study was to compare the monocyte-derived T cell directing (Th1/Th2) response and pro-inflammatory cytokine production in ex vivo whole blood cell cultures (WBCC) of smoking and non-smoking chronic periodontitis patients., Material and Methods: Venous blood was collected from 29 periodontitis patients (18 non-smokers and 11 smokers) receiving supportive periodontal treatment, and diluted 10-fold for WBCC. The WBCC were stimulated for 18 h with Neisseria meningitidis lipo-oligosaccharide (LOS) or Porphyromonas gingivalis sonic extract (Pg-SE). The production of the T cell directing cytokines interleukin (IL)-12 p40 and IL-10, as well as the pro-inflammatory cytokines IL-1beta, IL-6 and IL-8, was measured in the culture supernatants., Results: After LOS stimulation of WBCC, smokers showed a lower IL-12 p40/IL-10 ratio than non-smokers (P < 0.05). Interleukin-1beta production was significantly lower in smokers compared with non-smokers after stimulation with either LOS or Pg-SE (P < 0.05). Interleukin-6 and IL-8 production was similar in WBCC from both smokers and non-smokers, for both LOS and Pg-SE., Conclusion: A more pronounced Th2 response in smoking periodontitis patients may be related to increased severity of the disease.

Background and Objective: Radiographs are an essential adjunct to the clinical examination for periodontal diagnoses. Over the past few years, digital radiographs have become available for use in clinical practice. Therefore, the present study investigated whether measuring alveolar bone loss, using digital radiographs with a newly constructed dental image analyzer tool was comparable to the conventional method, using intra-oral radiographs on film, a light box and a Schei ruler., Material and Methods: Alveolar bone loss of the mesial and distal sites of 60 randomly selected teeth from 12 patients with periodontitis was measured using the conventional method, and then using the dental image analyzer tool, by five dentists. The conventional method scored bone loss in categories of 10% increments relative to the total root length, whereas the software dental image analyzer tool calculated bone loss in 0.1% increments relative to the total root length after crucial landmarks were identified., Results: Both methods showed a high interobserver reliability for bone loss measurements in nonmolar and molar sites (intraclass correlation coefficient > or = 0.88). Also, a high reliability between both methods was demonstrated (intraclass correlation coefficient nonmolar sites, 0.98; intraclass correlation coefficient molar sites, 0.95). In addition, the new dental image analyzer tool showed a high sensitivity (1.00) and a high specificity (0.91) in selecting teeth with > or = 50% or < 50% alveolar bone loss in comparison with the conventional method., Conclusion: This study provides evidence that, if digital radiographs are available, the dental image analyzer tool can reliably replace the conventional method for measuring alveolar bone loss in periodontitis patients.

Background: Periodontitis is associated with an increased risk for cardiovascular diseases (CVD), but the underlying mechanisms are poorly understood. Recently, we showed that platelets from periodontitis patients are more activated than those from controls., Objective: Given the regularly occurring bacteremic episodes in periodontitis patients, we hypothesized that platelets and/or leukocytes from periodontitis patients are more sensitive to stimulation by oral bacteria, in particular the known periodontal pathogens, than platelets from control subjects., Methods: Three-color flow cytometry analysis was performed to quantify activation of platelets (P-selectin, PAC-1, CD63) and leukocytes (CD11b) in whole blood from patients with periodontitis (n = 19) and controls (n = 18), with and without stimulation by oral bacteria. Phagocytosis was assessed by using green-fluorescent protein (GFP)-expressing Aggregatibacter actinomycetemcomitans (Aa)., Results: Neutrophils and monocytes were activated by all species of oral bacteria tested, but no differences were observed between patients and controls. In response to several species of oral bacteria, platelets from periodontitis patients showed, compared with controls, increased exposure of P-selectin (P = 0.027) and increased formation of platelet-monocyte complexes (P = 0.040). Platelet-leukocyte complexes bound and/or phagocytosed more GFP-Aa than platelet-free leukocytes (for neutrophils and monocytes, in both patients and controls, P < 0.001)., Conclusions: In periodontitis, increased platelet response to oral bacteria is paralleled by increased formation of platelet-leukocyte complexes with elevated capacity for bacterial clearance. We speculate that activated platelets and leukocytes might contribute to increased atherothrombotic activity.

Variance in expression of receptors for immunoglobulin G (FcgammaRs), complement (CR3) and lipopolysaccharide (mCD14) on polymorphonuclear neutrophils (PMNs) and monocytes might affect susceptibility for infection with certain pathogens in periodontitis, a chronic infectious disease of tooth-supportive tissues. Levels of FcgammaRI, IIa, III, CR3 and mCD14 on PMNs and monocytes were measured in 19 periodontitis patients and 18 healthy controls. Subgingival infection with Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) was determined. Activation of PMNs and monocytes in response to stimulation with Aa and Pg was assessed by means of change in mCD14 expression. Periodontitis is associated with an enrichment of the FcgammaRIII(+) monocytes (P = 0.015) with concomitant low mCD14 (P = 0.001). Unadjusted data showed that the subjects culture-positive for Aa (Aa(+)) had significantly lower expression of monocytic FcgammaRI (P = 0.005) and FcgammaRIIa (P = 0.015) than Pg(+) subjects. The FcgammaRI was still lower on monocytes from Aa(+) subjects after adjusting for the background factors (P = 0.037). PMNs from Aa(+) subjects responded in a hyper-reactive manner, in particular when stimulated with Aa (P = 0.011). Lower FcgammaRs expression by monocytes is related to a higher susceptibility of a subject to become infected with Aa. The higher proportion of FcgammaRIII(+) monocytes may be involved in the chronicity of this condition. Hyper-reactive PMNs in Aa(+) subjects may contribute to accelerated breakdown of tooth-supportive tissues.

Periodontitis is a complex, multifactorial disease and the susceptibility is genetically determined. In the last decade a multitude of research projects on genotyping of patients and controls in search of putative genetic risk factors has been performed. The disease (phenotype) however is also dependent on the presence of environmental and lifestyle factors, and their interaction with the various genes. Many candidate genes have been proposed and studied in relation to periodontitis. Most of the studied candidate genes code for proteins that play a role in the innate immune system. Some variants of candidate genes (gene polymorphisms) in the IL1 gene cluster and the FcgammaR genes are possibly associated with periodontitis. However till today there is no strong evidence for target genes and gene polymorphisms that play a key role in the susceptibility to and severity of periodontitis. Therefore genetic testing for periodontitis is currently not indicated.

Background: Receptors for the Fc part of IgG (FcgammaRIIa) on polymorphonuclear leukocytes (PMN) mediate phagocytosis and cell activation. Previous results show that one of the genetic variants of the FcgammaRIIa, the 131 H/H, is associated with more periodontal breakdown than the R/R. This may be due to hyper-reactivity of the H/H-PMNs upon interaction with bacteria., Aim: To study whether the FcgammaRIIa genotype modifies the PMN reactivity in periodontitis patients., Material and Methods: A cohort of 98 periodontitis patients was genotyped. From these, 10 H/H and 10 R/R consented to participate. PMNs were incubated with immune serum-opsonized Actinobacillus actinomycetemcomitans (A.a.). Phagocytosis, degranulation (CD63 and CD66b expression), respiratory burst and elastase release were assessed., Results: Patients of the H/H genotype showed more bone loss than those with the H/R or R/R genotype (p=0.038). H/H-PMNs phagocytosed more opsonized A.a. than did R/R-PMNs (p=0.019). The H/H-PMNs also expressed more CD63 and CD66b than did the R/R-PMNs (p=0.004 and 0.002, respectively) and released more elastase (p=0.001)., Conclusions: The genotyping results confirm previous reports that more periodontal destruction occurs in the H/H genotype than in the H/R or R/R genotype. The functional studies indicate a hyper-reactivity of the H/H-PMN in response to bacteria, which may be one of several pathways leading to more periodontal breakdown.

Objectives: Periodontitis is a chronic infectious disease and has been associated with cardiovascular diseases (CVD). We investigated whether plasma levels of markers of a prothrombotic state were elevated in patients with periodontitis in comparison with healthy controls., Materials and Methods: Untreated patients with moderate (n=53) and severe periodontitis (n=38) and healthy controls (n=39) were recruited. Levels of von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), plasminogen activator inhibitor-1 (PAI-1) activity and D-dimer were measured as markers of a prothrombotic state., Results: The erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP) and leucocyte counts (WBC) were significantly higher in patients with periodontitis. No statistically significant difference was found among the three groups for vWF (p=0.264), F1+2 (p=0.295) and D-dimer (p=0.572). However, PAI-1 was clearly elevated in the severe periodontitis group (p=0.001), even after adjusting for potential confounding factors (p(adj)=0.004). Moreover, more patients than controls were having vWF and PAI-1 levels above the respective population medians., Conclusions: In periodontitis, elevated levels of PAI-1 activity are observed compared with healthy controls. This may increase the potential for impaired fibrinolysis, a condition that results in a prothrombotic state. We suggest that this state, if left untreated, may contribute to an increased risk for CVD.

Objective: To study the relationship between vitamin C and the severity of periodontitis., Material and Methods: The study population consisted of subjects from the Malabar/Purbasari tea estate on West Java, Indonesia. In 2002, clinical measurements were performed in 128 subjects, including evaluation of plaque, bleeding on probing, pocket depth and attachment loss. In 2005, 123 out of 128 subjects could be retrieved who were present at the examination of 2002. Blood samples were taken to measure plasma vitamin C levels. Information about the subject's dietary habit was obtained by means of a personal interview guided by a questionnaire., Results: Plasma levels of vitamin C ranged from 0.02 to 34.45 mg/l with a mean of 7.90 mg/l (+/-5.35). The correlation coefficient between plasma vitamin C level and periodontal attachment loss was -0.199 (p<0.05); stepwise linear regression revealed that vitamin C levels explained 3.9% of the variance in periodontal attachment loss. Subjects with vitamin C deficiency (14.7% of the study population) had more attachment loss compared with those with depletion or normal plasma vitamin C values., Conclusion: The negative association between plasma vitamin C levels and periodontal attachment loss suggests that vitamin C deficiency may contribute to the severity of periodontal breakdown.

Objective: To identify risk factors, risk predictors and risk determinants for onset and progression of periodontitis., Material and Methods: For this longitudinal, prospective study all subjects in the age range 15-25 years living in a village of approximately 2000 inhabitants at a tea estate on Western Java, Indonesia, were selected. Baseline examination was carried out in 1987 and follow-up examinations in 1994 and 2002. In 2002, 128 subjects could be retrieved from the original group of 255. Baseline examination included evaluation of plaque, bleeding on probing, calculus, pocket depth, attachment loss and presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, spirochetes and motile microorganisms., Results: The mean attachment loss increased from 0.33 mm in 1987 to 0.72 mm in 1994 and 1.97 mm in 2002. Analysis identified the amount of subgingival calculus and subgingival presence of A. actinomycetemcomitans as risk factors, and age as a risk determinant, for the onset of disease. Regarding disease progression, the number of sites with a probing depth > or = 5 mm and the number of sites with recession were identified as risk predictors and male gender as a risk determinant., Conclusion: Screening of these parameters early in life could be helpful in the prevention of onset and progression of periodontal diseases.

Objectives: The purpose of this split-mouth study was to evaluate the clinical response of enamel matrix proteins (EMPs, Emdogain Gel in intra-osseous defects with or without a combined application of a tetracycline-coated expanded polytetrafluoroethylene barrier membrane (e-PTFE, Gore-Tex)., Methods: Twelve pairs of intra-osseous periodontal defects in 11 patients received the application of EMPs on the exposed root surface (EMP). One of the two defects received randomly, as an adjunct to EMP treatment, a tetracycline-coated e-PTFE membrane (MEMP). At baseline, 6- and 12-month probing pocket depth (PPD), clinical attachment level (CAL) and probing bone level (PBL) were measured., Results: After 12 months, the EMP defects showed a significant mean PPD reduction of 2.86+/-0.75 mm, a mean gain in CAL of 1.28+/-2.04 mm, a mean PBL gain of 1.63+/-1.21 mm and a mean increase of recession (REC) of 1.56+/-2.30 mm. The MEMP defects showed a significant mean PPD reduction of 3.02+/-1.55 mm, a mean gain in CAL of 1.65+/-1.29 mm, a mean PBL gain of 1.58+/-1.92 mm and a mean increase of REC of 1.38+/-1.63 mm. Except for significantly more post-operative discomfort at the MEMP sites, no significant differences were found between EMP and MEMP defects., Conclusion: Within the limits of this study, it is concluded that in the treatment of intra-osseous defects with EMP, the adjunctive use of a tetracycline-coated e-PTFE membrane failed to show more gain of CAL and PBL.

Background: A major aspect of the adaptive host response in periodontitis is the production of antibodies. Several risk and susceptibility factors for periodontitis, including smoking, age and composition of the subgingival microflora, have also been suggested to influence antibody production., Aim: The present study was conducted to investigate plasma levels of immunoglobulin (Ig) G, A and M antibodies in periodontitis patients of Caucasian European heritage in relation to disease severity, smoking, diagnosis and prevalence of periodontopathogens., Methods: In this study, 29 patients with severe periodontitis, 51 with moderate periodontitis and 55 controls without periodontal destruction were enrolled. From the total of 80 patients, 18 were diagnosed with aggressive periodontitis and 62 with chronic periodontitis. Total IgG, IgA and IgM as well as IgG isotypes were analyzed in plasma samples., Results: Levels of total IgG, IgA and IgM were not different between patients and controls; however, in periodontitis, higher levels of IgG1 and IgG2 were observed. Smoking appeared to be significantly and inversely related to antibody levels in periodontitis, in particular for total IgG and IgG2. The absence of an elevated total IgG and IgG2 in smoking patients was irrespective of severity, prevalence of periodontal pathogens and diagnosis. The elevation of total IgG and IgG1 and IgG2 in non-smoker periodontitis patients was observed in patients with moderate periodontitis and even greater in patients with severe periodontitis, but was independent whether patients were infected with Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis and independent of diagnosis. Clinically, it was observed that patients who smoked had more periodontal bone loss; the current findings on antibody levels may be one of several mechanisms related to more extensive periodontal breakdown in smoker patients., Conclusion: The current study shows that non-smoker periodontitis patients have higher levels of total IgG and IgG2 than smoker periodontitis patients.

Objectives: It has been suggested that periodontal inflammation may result in an altered immune response. The peripheral immune capacity in periodontitis patients can be investigated using lipopolysaccharide (LPS)-stimulated whole blood cell cultures (WBCC), known to reflect the behavior of monocytes in particular. A previous study in our laboratory revealed that monocytes in the stimulated cultures from periodontitis patients behaved functionally different compared with controls. The present study investigated whether this different response of periodontitis patients' monocytes is intrinsic or acquired., Material and Methods: The release of inflammatory mediators was measured in Escherichia coli LPS-stimulated WBCC from 12 periodontitis patients before and after periodontal therapy. In addition, the total leukocyte and leukocyte differentiation counts were also determined in the patients before and after therapy., Results: The levels of interleukin (IL)-12p70 in cell culture supernatants increased two times and those of prostaglandin E2 showed a trend towards reduction after therapy, whereas the levels of IL-1beta, IL-6, IL-8, IL-10, IL-12p40 and tumor necrosis factor-alpha did not change. The total number of white blood cells was decreased after periodontal therapy., Conclusions: After periodontal therapy, the functional phenotype of the peripheral blood monocytes from patients was reconstituted, resembling that of subjects without periodontitis.

Objectives: Evidence suggests functional relevance for polymorphisms in FcgammaR in relation to inflammatory and infectious diseases. The present aim was to investigate genetic polymorphisms in three FcgammaR in relation to susceptibility and severity of periodontitis., Material and Methods: The study population consisted of 68 periodontitis patients and 61 controls (Northern European Caucasian background, mean ages 44 and 42 years, respectively). Among the patients, 12 subjects were diagnosed with aggressive periodontitis (AgP) and 56 individuals were diagnosed with chronic periodontitis (CP). Radiographic bone levels were scored for all teeth in the patients. Subjects were typed for the following genes (alleles): FcgammaRIIa (R131 or H131), FcgammaRIIIa (V158 or F158) and FcgammaRIIIb (NA1 or NA2)., Results: Hardy-Weinberg equilibrium criteria were fulfilled for the different genotypes at the three genes investigated. The frequency of the FcgammaRIIIa-V158 allele in the patient population (53%) was higher than in the control group (39%) (OR 1.73 [1.06-2.85], p=0.034). The V158 carriage rate in AgP was even higher (63%). The frequency of the FcgammaRIIa-H131 allele in the total periodontitis population was 58%; for AgP this was 79%, compared with 51% in the control population (OR 3.68 [1.29-10.5], p=0.013). Also, the frequency of the FcgammaRIIa-H/H131 genotype was significantly higher in AgP patients than in controls (OR 9.07 [1.29-63.56], p=0.026, adjusted for smoking status and other potential confounders). Moreover, patients with the FcgammaRIIa-H/H131 genotype had more severe radiographic bone loss than patients with the other FcgammaRIIa genotypes., Conclusion: The current study of relative small sample size suggests that the FcgammaRIIa-H/H131 genotype may be a putative susceptibility and severity factor, and the FcgammaRIIIa-V158 allele a putative susceptibility factor for periodontitis in Northern European Caucasians. These results need further verification and the biological importance of these findings needs further investigation.

Background: The effect of smoking on the prevalence of periodontal pathogens after periodontal treatment is still not clear. Some studies found no effect of the smoking status on the prevalence of periodontal pathogens after therapy, whereas others did. The aim of this retrospective study was to investigate the influence of smoking on the treatment of periodontitis and the composition of the subgingival microflora., Method: The study included 59 periodontitis patients (mean age 41.5 years): 30 smokers and 29 nonsmokers. The treatment consisted of initial periodontal therapy and, if necessary, surgery and/or antibiotics. Clinical and microbiological data were obtained before and after treatment at the deepest site in each quadrant. A pooled sample was analysed for the presence of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotalla intermedia (Pi), Bacteroides forsythus (Bf), Fusobacterium nucleatum (Fn) and Peptostreptococcus micros (Pm)., Results: For smokers and nonsmokers a significant improvement of the clinical condition was found after treatment. A decrease could be assessed for bleeding on probing (smokers: 0.46; nonsmokers: 0.52) and probing pocket depth (PPD) (smokers: 1.64 mm; nonsmokers: 2.09 mm). Furthermore, both groups showed gain of attachment (smokers: 0.68 mm; nonsmokers: 1.46 mm). No significant difference in bleeding on probing and PPD reduction was found between smokers and nonsmokers. In contrast, nonsmokers showed significantly more gain of attachment than smokers. The microbiological results revealed no differences in the prevalence of the various bacteria between smokers and nonsmokers before treatment. After treatment in nonsmokers, a significant decrease was found in the prevalence of Aa (11-3), Pg (17-7), Pi (27-11), Bf (27-11), Fn (28-20) and Pm (27-17). In smokers, a significant decrease could be shown only for the prevalence of Pg (15-5)., Conclusions: Nonsmokers showed more gain of attachment and a greater decrease in the prevalence of periodontal bacteria as compared to smokers. The phenomenon that among smokers, more patients remain culture positive for periodontal pathogens after therapy, may contribute to the often observed unfavourable treatment results in smoker periodontitis patients.

Bacteria colonizing tooth surfaces are essential in the induction of an inflammatory response in the periodontal tissues, but do not cause periodontitis in everyone, implicating differences in the host immune response. These possible differences were studied using lipopolysaccharide (LPS)-stimulated whole blood cell cultures (WBCC), which revealed a down regulation of monocyte derived interleukin-12 (IL-12p70) in untreated periodontitis patients and an up regulation after therapy. IL-12p70 is a crucial factor in the differentiation of Th1 cell responses. Since CC chemokines are able to influence the T cell differentiation via cytokine secretion in antigen-presenting cells, the production of CC chemokines in periodontitis was evaluated. Therefore WBCC were stimulated with LPS from Escherichia coli for 18 h and the levels of IL-12p70 and CC chemokines were measured in the supernatants by ELISA. Untreated periodontitis patients released 2 fold more RANTES (regulated on activation normal T cell expressed and secreted) (P = 0.01) and lower levels of IL-12p70 in comparison to controls (P < 0.05). A trend towards higher levels of macrophage chemoattractant protein-1 (MCP-1) (P = 0.07) was also seen in untreated periodontitis patients; while similar levels of monocyte derived chemokine (MDC) and macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha and -1 beta) were found. After periodontal therapy no changes were seen with regard to MDC, MIP-1 alpha, MIP-1 beta and RANTES, whereas the MCP-1 levels decreased (P < 0.05) and the IL-12p70 levels strongly increased (P < 0.01). The data showed a consistent inverse correlation between the levels of MCP-1 and IL-12p70, and their proportional changes after therapy correlated with the clinical inflammatory response after therapy. This indicates that the disease state regulates the release of IL-12p70 and MCP-1 in E. coli LPS-stimulated WBCC. In contrast, the persistent augmented levels of RANTES after therapy are suggestive for an intrinsic behaviour.