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AimTo investigate whether there is an association between subgingival microbial diversity and reduced respiratory function.Materials and MethodsA group of dentate 58–72-year-old men in Northern Ireland had a comprehensive periodontal examination including subgingival plaque sampling. DNA was extracted from plaque samples and the V1–V3 regions of the 16S rRNA gene were analysed by high-throughput sequencing and a microbial diversity index (MDI) was derived. Spirometry measurements were made using a wedge bellows spirometer. The primary outcome variable of interest was the percentage of predicted forced expiratory volume in 1 s (% predicted FEV1). Analysis included multiple linear regression with adjustment for various confounders.ResultsFive-hundred and seven men were included in the analysis. The mean age was 63.6 years (SD = 3.1). Of these, 304 (60.0%) men had no or mild periodontitis, 105 (20.7%) had moderate periodontitis and 98 (19.3%) had severe periodontitis. Multiple linear regression analysis showed that a one unit increase in MDI was associated with a 0.71% loss (95% confidence interval: 0.06%–1.35%; p = .03) in % predicted FEV1 after adjustment for all confounders.ConclusionsIn this group of dentate men from Northern Ireland, subgingival microbial diversity was associated with reduced respiratory function.

Objectives The aims of this study were to investigate neuropeptide receptor expression regulation on STRO-1 +ve periodontal ligament stem cells (PDLSCs) in response to inflammatory cytokines and to investigate a potential osteogenic effect of neuropeptides. Background Nerve fibres innervating the periodontal tissues in humans contain several neuropeptides including neuropeptide Y and substance P. The role of neuropeptide receptors on PDLSCs, including their response to the local inflammatory environment of periodontitis, is currently unknown. Methods A homogenous population of STRO-1 +ve PDLSCs was prepared by immunomagnetic separation of cells obtained by the tissue out-growth method from healthy premolar teeth from a single donor. Regulation of gene expression of the neuropeptide Y Y1 receptor and substance P receptor tachykinin receptor 1 was investigated. A potential osteogenic effect of neuropeptide Y and substance P was also investigated by measuring alkaline phosphatase (ALP) activity, Alizarin red staining and quantifying osteogenic gene expression. Results Treatment of STRO-1 +ve PDLSCs with tumour necrosis factor-alpha or interleukin 1-beta up-regulated the expression of the neuropeptide Y's Y1 receptor, but down-regulated substance P's receptor. Significantly increased ALP activity was observed in STRO-1 +ve PDLSCs treated with neuropeptide Y but not substance P. Further studies showed that neuropeptide Y had a modest osteogenic effect on cells at both a functional level and a gene level. Conclusions Expression of the neuropeptide Y Y1 receptor gene on STRO-1 +ve PDLSCs was sensitive to local inflammatory cytokines. Treatment of cells with neuropeptide Y was found to produce a modest enhanced osteogenic effect.

There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter pylori-mediated inflammation in gastric cancer and more recently Fusobacterium nucleatum-mediated inflammation in colorectal cancer. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that was first isolated from the oral cavity and identified as a periodontal pathogen. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, including F. nucleatum, which has prompted hypotheses that this bacterium could contribute to oral cancer development. Recent studies have demonstrated that F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion. This review provides an update on the association between F. nucleatum and oral carcinogenesis, and provides insights into the possible mechanisms underlying it.

AIM The aim was to investigate the role of systemic inflammation in the relationship between periodontitis, edentulism, and all-cause mortality in a group of men in Northern Ireland aged 58-72 years. MATERIALS AND METHODS A representative sample of 1558 men had a detailed dental examination between 2001 and 2003. The primary end point was death from any cause. Cox's proportional hazards model was used to assess the longitudinal relationship between periodontitis, edentulism, and all-cause mortality. Accelerated failure time modelling was performed to investigate the mediating role of systemic inflammation. RESULTS Mean age of the men at baseline was 64.3 (standard deviation 2.9) years. During a median follow-up of 17 years, 500 (32.1%) men died. After adjustment for confounding variables, compared to men with no/mild periodontitis, edentulous men had a hazard ratio for all-cause mortality of 1.52 (95% confidence interval [CI] 1.16-1.99) p

OBJECTIVE To investigate whether there was an association between chronic periodontitis (CP) and reduced respiratory function. METHODS A group of dentate 58- to 72-year-old men in Northern Ireland had a comprehensive periodontal examination. Parallel to the periodontal examination, participants completed questionnaires gathering information on their medical history, social circumstances, demographic background and tobacco use. A physical examination assessed anthropometric measures. Fasting blood samples were obtained and analysed for high-sensitivity C-reactive protein (hs-CRP). Spirometry measures were performed using a wedge bellows spirometer (Vitalograph S Model). The primary outcome variable of interest was the percentage predicted forced expiratory volume in one-second (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders and a regression-based mediation analysis. RESULTS A total of 1,380 men were included in the analysis. The mean age was 63.7 years (SD 3.0). Multiple linear regression analysis showed that a doubling in mean clinical attachment loss (CAL) equated to a -3.33% (95% CI: -4.80, -1.86), p

Background A growing body of evidence suggests a role for oral bacteria in lung infections. This systematic review aimed to analyse the association between poor periodontal status and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations. Methods PubMed, Embase, Web of Science, CINAHL and Medline were searched for studies published until May 2020, with no language restriction. Studies reporting periodontal condition, or periodontal treatment outcomes, with data on the frequency of exacerbations of COPD, were identified. The primary outcome was the frequency of exacerbations and secondary outcomes included quality of life (QoL) and hospitalisation. Quality and risk of bias assessment were carried out using the Newcastle Ottawa Scale for observational studies, Robins-1 tool for non-randomised intervention studies and Cochrane risk of bias assessment (RoB-2) tool for randomised clinical trials. Studies were assessed for eligibility and quality by two assessors independently. Results Searches identified 532 records and 8 met the inclusion criteria. Included studies were three clinical trials, one prospective cohort study, one case–control, and three cross-sectional studies. A narrative synthesis was performed. The data from intervention studies showed reduction in the frequency of exacerbations following periodontal treatment. Data from observational studies suggest association of worse plaque scores and fewer teeth with exacerbation, but not pocket depth or clinical attachment loss. Better periodontal health was also associated with reduced frequency of COPD exacerbations, hospitalisations and improved quality of life in COPD patients. Due to the high heterogeneity no meta-analysis was performed. The quality of some of the included studies was low and there was evidence of a high risk of bias. Conclusion The data supports possible association between poor periodontal health, the frequency of exacerbations, hospitalisation and quality of life in COPD patients. The evidence is of moderate to low certainty and is limited by high risk of bias suggesting the need for well-designed and adequately powered randomised controlled trials, to inform future research and clinical practice. The PROSPERO registration number CRD42020180328.

OBJECTIVE: To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland.METHODS: A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD.RESULTS: The mean age of the men at baseline was 63.7 (SD 3.0) years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p = 0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7 years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p = 0.24.CONCLUSIONS: In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Introduction Like many tissues, the dental pulp is equipped with innate and adaptive immune responses, designed to defend against infection and limit its spread. The pulp’s innate immune response includes the synthesis and release of antimicrobial peptides by several dental pulp cell types. These naturally-occurring antimicrobial peptides have broad spectrum activity against bacteria, fungi and viruses. There is a resurgence of interest in the bioactivities of naturally-occurring antimicrobial peptides, largely driven by the need to develop alternatives to antibiotics. Methods This narrative review focused on the general properties of antimicrobial peptides, providing an overview of their sources and actions within the dental pulp. Results We summarized the relevance of antimicrobial peptides in defending the dental pulp, highlighting the potential for many of these antimicrobials to be modified or mimicked for prospective therapeutic use. Conclusion Antimicrobial peptides and novel peptide-based therapeutics are particularly attractive as emerging treatments for polymicrobial infections, such as endodontic infections, because of their broad activity against a range of pathogens.

BackgroundPeriodontitis is a major cause of tooth loss globally. Risk factors include age, smoking, and diabetes. Intake of specific nutrients has been associated with periodontitis risk but there has been little research into the influence of overall diet, potentially more relevant when formulating dietary recommendations.ObjectivesWe aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.MethodsTwo 24-h dietary recalls and periodontal examination data from the cross-sectional US NHANES, 2009–2014 (n = 10,010), were used. Dietary patterns were extracted using treelet transformation, a data-driven hierarchical clustering and dimension reduction technique. Associations between each pattern [treelet component (TC)] and extent of periodontitis [proportion of sites with clinical attachment loss (CAL) ≥ 3 mm] were estimated using robust logistic quantile regression, adjusting for age, sex, ethnicity, education level, smoking, BMI, and diabetes.ResultsEight TCs explained 21% of the variation in diet, 1 of which (TC1) was associated with CAL extent. High TC1 scores represented a diet rich in salad, fruit, vegetables, poultry and seafood, and plain water or tea to drink. There was a substantial negative gradient in CAL extent from the lowest to the highest decile of TC1 (median proportion of sites with CAL ≥ 3 mm: decile 1 = 19.1%, decile 10 = 8.1%; OR, decile 10 compared with decile 1: 0.67; 95% CI: 0.46, 0.99).ConclusionsMost dietary patterns identified were not associated with periodontitis extent. One pattern, however, rich in salad, fruit, and vegetables and with plain water or tea to drink, was associated with lower CAL extent. Treelet transformation may be a useful approach for calculating dietary patterns in nutrition research.

Objectives The aim of this study was to investigate periodontitis as a risk factor for incident type 2 diabetes mellitus (T2DM) in a group of men aged 58–72 years. Methods One thousand three hundred and thirty-one dentate, diabetes-free men in Northern Ireland underwent a detailed periodontal examination during 2001–2003. Follow-up was by bi-annual questionnaire and for those reporting diabetes their general medical practitioner was contacted to validate diabetes type, treatment and diagnosis date. Cox's proportional hazard models were used to estimate the effect of periodontitis on incident diabetes. Multivariable analysis included adjustment for various known confounders. Results The mean age of the men was 63.7 (SD 3.0) years. There were 80 cases (6.0%) of incident T2DM. Follow-up was for a median period of 7.8 years (IQR 6.7–8.3). After adjusting for confounding variables, the hazard ratio (HR) for incident T2DM in men with moderate/severe periodontitis versus those with no/mild periodontitis was 1.69 (95% CI 1.06–2.69), p = 0.03. Conclusion There was evidence in this homogenous group of dentate men, that those with moderate to severe periodontitis had a significantly increased risk of incident T2DM.

Aims Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men. Methods Baseline serum levels of leptin and adiponectin were measured in 1839 non-diabetic men aged 50–60 years who were participating in the prospective population-based PRIME study. Over a mean follow-up of 14.7 years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners. Results 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67–6.83) and men in the top third of the adiponectin distribution at reduced risk (HR 0.24, 95% CI 0.14–0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin. Conclusions This study provides evidence that adipokines are associated with men’s future type 2 diabetes risk but not independently of other risk factors.

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

The transient receptor potential (TRP) channels are unique cellular sensors that are widely expressed in many neuronal and nonneuronal cells. Among the TRP family members, TRPA1 and TRPV4 are emerging as candidate mechanosensitive channels that play a pivotal role in inflammatory pain and mechanical hyperalgesia. Odontoblasts are nonneuronal cells that possess many of the features of mechanosensitive cells and mediate important defense and sensory functions. However, the effect of inflammation on the activity of the odontoblast's mechanosensitive channels remains unknown. By using immunohistochemistry and calcium microfluorimetry, we showed that odontoblast-like cells express TRPA1 and TRPV4 and that these channels were activated by hypotonicity-induced membrane stretch. Short treatment of odontoblast-like cells with tumor necrosis factor (TNF)-α enhanced TRPA1 and TRPV4 responses to their chemical agonists and membrane stretch. This enhanced channel activity was accompanied by phospho-p38 mitogen-activated protein kinase (MAPK) expression. Treatment of cells with the p38 inhibitor SB202190 reduced TNF-α effects, suggesting modulation of channel activity via p38 MAPK. In addition, TNF-α treatment also resulted in an up-regulation of TRPA1 expression but down-regulation of TRPV4. Unlike TRPV4, enhanced TRPA1 expression was also evident in dental pulp of carious compared with noncarious teeth. SB202190 treatment significantly reduced TNF-α-induced TRPA1 expression, suggesting a role for p38 MAPK signaling in modulating both the transcriptional and non-transcriptional regulation of TRP channels in odontoblasts.

BACKGROUND AND AIMS: The scope of this working group was to review: (1) the effect of professional mechanical plaque removal (PMPR) on secondary prevention of periodontitis; (2) the occurrence of gingival recessions and non-carious cervical lesions (NCCL) secondary to traumatic tooth brushing; (3) the management of hypersensitivity, through professionally and self administered agents and (4) the management of oral malodour, through mechanical and/or chemical agents. RESULTS AND CONCLUSIONS: Patients undergoing supportive periodontal therapy including PMPR showed mean tooth loss rates of 0.15 ± 0.14 teeth/year for 5-year follow-up and 0.09 ± 0.08 teeth/year (corresponding to a mean number of teeth lost ranging between 1.1 and 1.3) for 12-14 year follow-up. There is no direct evidence to confirm tooth brushing as the sole factor causing gingival recession or NCCLs. Similarly, there is no conclusive evidence from intervention studies regarding the impact of manual versus powered toothbrushes on development of gingival recession or NCCLs, or on the treatment of gingival recessions. Local and patient-related factors can be highly relevant in the development and progression of these lesions. Two modes of action are used in the treatment of dentine hypersensitivity: dentine tubule occlusion and/or modification or blocking of pulpal nerve response. Dentifrices containing arginine, calcium sodium phosphosilicate, stannous fluoride and strontium have shown an effect on pain reduction. Similarly, professionally applied prophylaxis pastes containing arginine and calcium sodium phosphosilicate have shown efficacy. There is currently evidence from short-term studies that tongue cleaning has an effect in reducing intra-oral halitosis caused by tongue coating. Similarly, mouthrinses and dentifrices with active ingredients based on Chlorhexidine, Cetylpyridinium chloride and Zinc combinations have a significant beneficial effect. ispartof: Journal of Clinical Periodontology vol:42 issue:S16 pages:S214-S220 ispartof: location:SPAIN status: published

Cationic amphipathic α-helical peptides are intensively studied classes of host defence peptides (HDPs). Three peptides, peptide glycine-leucine-amide (PGLa-AM1), caerulein-precursor fragment (CPF-AM1) and magainin-AM1, originally isolated from norepinephrine-stimulated skin secretions of the African volcano frog Xenopus amieti (Pipidae), were studied for their antimicrobial and immunomodulatory activities against oral and respiratory pathogens. Minimal effective concentrations (MECs), determined by radial diffusion assay, were generally lower than minimal inhibitory concentrations (MICs) determined by microbroth dilution. PGLa-AM1 and CPF-AM1 were particularly active against Streptococcus mutans and all three peptides were effective against Fusobacterium nucleatum, whereas Enterococcus faecalis and Candida albicans proved to be relatively resistant micro-organisms. A type strain of Pseudomonas aeruginosa was shown to be more susceptible than the clinical isolate studied. PGLa-AM1 displayed the greatest propensity to bind lipopolysaccharide (LPS) from Escherichia coli, P. aeruginosa and Porphyromonas gingivalis. All three peptides showed less binding to P. gingivalis LPS than to LPS from the other species studied. Oral fibroblast viability was unaffected by 50 μM peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with 1 or 10 μM magainin-AM1 but not following treatment with PGLa-AM1 or CPF-AM1. In conclusion, as well as possessing potent antimicrobial actions, the X. amieti peptides bound to LPS from three human pathogens and had no effect on oral fibroblast viability. CPF-AM1 and PGLa-AM1 show promise as templates for the design of novel analogues for the treatment of oral and dental diseases associated with bacteria or fungi.

BACKGROUND AND OBJECTIVES: There has been limited study of the bacterial species associated with aggressive periodontitis (AgP) in high-risk populations in Africa. The aim of this study was to investigate and quantify the presence of four putative periodontal pathogens in the subgingival plaque of Sudanese subjects with AgP. A secondary aim was to investigate the effect of varying the detection threshold on the reported prevalence of the bacterial species investigated.MATERIALS AND METHODS: Subgingival plaque samples were collected from AgP cases (n=73) and healthy controls (n=71). Bacterial DNA was extracted and analyzed by quantitative polymerase chain reaction for the detection and quantification of four putative periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia.RESULTS: At the lowest detection threshold (>10(1) cells), P. gingivalis (p70%) in AgP cases at all detection levels. While T. forsythia was significantly more frequently identified in AgP than in controls at all detection thresholds, this was only the case for T. denticola at the intermediate threshold (>10(2) cells). A. actinomycetemcomitans was identified less frequently than the other bacterial species with no difference in its prevalence between AgP cases and controls.CONCLUSION: The prevalence of the putative periodontal pathogens investigated varied considerably in Sudanese subjects with AgP and in periodontally healthy controls depending on the detection thresholds applied. T. forsythia was identified as having the strongest association with AgP.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1000 Greater Belfast (both in NI) and 2094 Republic of Ireland (ROI) volunteers and in 116 acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) vs. non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1275-5000) years. tMRCA-based simulations predicted 432 (90-5175) current carriers, including 86 affected (18-1035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically-targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. This article is protected by copyright. All rights reserved.

Background Little is known about the financial costs that smoking adds to the lifetime treatment of periodontal disease. Methods The total lifetime cost of periodontal treatment was modeled using data from private periodontal practice. The costs of initial and supportive therapy, re‐treatment and tooth replacements (with bridgework or implants) were identified using average dental charges from the American Dental Association survey. Smoking costs at $6 and $10 for 20 cigarettes were compared to the costs of lifetime periodontal treatment for stable and unstable compliant patients. Results Smoking added 8.8% to the financial cost of the lifetime cost of periodontal therapy in stable maintenance patients, 40.1% in patients who needed one extra maintenance visit, and 71.4% in patients who needed two extra maintenance visits per year in addition to added retreatment. The cost of smoking far exceeded the cost of periodontal treatment; For patients who smoked 10 to 40 cigarettes per day at the cost of $6 or $10 a pack, the cost of smoking exceeded the cost of lifetime periodontal treatment by between 2.7 and 17.9 times. Smoking 40 cigarettes at $10 a packet for 3.4 years would pay for the entire lifetime cost of periodontal treatment. Conclusion Smoking adds considerable extra financial costs to the lifetime treatment of periodontal diseases. The cost of smoking itself exceeds the cost of periodontal therapy.

Amongst the recognized classes of naturally occurring antimicrobials, human host defense peptides are an important group with an advantage (given their source) that they should be readily translatable to medicinal products. It is also plausible that truncated versions will display some of the biological activities of the parent peptide, with the benefit that they are less costly to synthesize using solid-phase chemistry. The host defense peptide, LL-37, and two truncated mimetics, KE-18 and KR-12, were tested for their inhibitory effects and antibiofilm properties against Candida albicans, Staphylococcus aureus, and Escherichia coli, microorganisms commonly implicated in biofilm-related infections such as ventilator-associated pneumonia (VAP). Using in silico prediction tools, the truncated peptides KE-18 and KR-12 were selected for minimum inhibitory concentration (MIC) and antibiofilm testing on the basis of their favorable cationicity, hydrophobic ratio, and amphipathicity compared with the parent peptide. Two methods were analyzed for determining peptide efficacy against biofilms; a crystal violet assay and an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. The biocidal activities (measured by MIC) and antibiofilm activities (measured by a crystal violet assay) appeared to be independent. LL-37 had no biocidal action against C. albicans (MIC > 250 μg/ml) but significant effects in both biofilm-prevention and biofilm-inhibition assays. KE-18 and KR-12 yielded superior MIC values against all three microorganisms. Only KE-18 had a significant effect in the biofilm-prevention assay, which persisted even at sub-MICs. Neither of the truncated peptides were active in the biofilm-inhibition assay. KE-18 was shown to bind lipopolysaccharide as effectively as LL-37 and to bind lipoteichoic acid more effectively. None of the peptides showed hemolytic activity against human erythrocytes at the concentrations tested. KE-18 should be considered for further development as a natural peptide-derived therapeutic for prevention of multi-species biofilm-related infections such as VAP.

Purpose of Review The aim was to assess recent evidence that diabetes, metabolic syndrome (MetS) and obesity impact the progression of periodontitis. Recent Findings Electronic searches using Embase, Medline, and Web of Science were carried out for epidemiological studies on humans, published between 2014 and 2016. A small number of prospective studies and systematic reviews were identified that in general provide further support for the hypothesis that diabetes, metabolic syndrome and obesity can adversely affect the periodontal condition. Summary Confounding remains the most challenging issue in the interpretation of the associations found between diabetes, MetS, obesity and periodontal disease. Recent research applying a Mendelian randomisation approach concluded that the association between obesity and periodontitis is confounded and questioned a role for obesity in causation. Further studies are warranted to assess the issue of causality.

Over the last two decades there has been a renewed interest around the possible effects of periodontal disease on both cardiovascular health and pregnancy outcome (among other diseases), a topic which has interested science for hundreds of years. These have led to a range of studies, workshops and consensus documents being published, with corresponding coverage in general and professional media. In this article the authors summarise the history and supporting theories behind such associations, whether clinical studies have been able to confirm these and what this might mean for general practitioners who are questioned on this topic by patients.

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds.

Background: The purpose of the present study is to investigate the potential link between maternal periodontitis and pregnancy outcomes, including preterm birth (

Successful periodontal treatment requires a commitment to regular lifelong maintenance and may be perceived by patients to be costly. This study calculates the total lifetime cost of periodontal treatment in the setting of a specialist periodontal practice and investigates the cost implications of choosing not to proceed with such treatment.Data from patients treated in a specialist practice in Norway were used to calculate the total lifetime cost of periodontal treatment that included baseline periodontal treatment, regular maintenance, retreatment, and replacing teeth lost during maintenance. Incremental costs for alternative strategies based on opting to forego periodontal treatment or maintenance and to replace any teeth lost with either bridgework or implants were calculated.Patients who completed baseline periodontal treatment but did not have any additional maintenance or retreatment could replace only three teeth with bridgework or two teeth with implants before the cost of replacing additional teeth would exceed the cost of lifetime periodontal treatment. Patients who did not have any periodontal treatment could replace ≤ 4 teeth with bridgework or implants before a replacement strategy became more expensive.Within the limits of the assumptions made, periodontal treatment in a Norwegian specialist periodontal practice is cost-effective when compared to an approach that relies on opting to replace teeth lost as a result of progressive periodontitis with fixed restorations. In particular, patients who have initial comprehensive periodontal treatment but do not subsequently comply with maintenance could, on average, replace ≤ 3 teeth with bridgework or two teeth with implants before this approach would exceed the direct cost of lifetime periodontal treatment in the setting of the specialist practice studied.

Background and Objective: The matrix metalloproteinases (MMPs) play a role in regulating turnover and metabolism of connective tissues in health but they have also been implicated in a wide variety of pathological conditions, including periodontal disease. MMP-8 has been extensively studied in periodontal health and disease using ELISA, although this technique is limited by its inability to determine enzyme activity. The aim was to develop an assay specifically to measure MMP-8 activity and to demonstrate its use in the analysis of gingival crevicular fluid samples.Material and Methods: A specific antibody was used to coat black 96-well microtitre plates to capture MMP-8 selectively. The activity of bound MMP-8 was measured using a fluorogenic substrate. Gingival crevicular fluid samples, from healthy and periodontally diseased sites, were collected using PerioPaper strips and tested for MMP-8 activity.Results: Significantly higher MMP-8 activity was demonstrated in gingival crevicular fluid from periodontally diseased sites compared with healthy sites that exhibited basal or no MMP-8 activity. No cross-reactivity with other MMPs was noted.Conclusion: We show, for the first time, that MMP-8 activity can be specifically detected and quantified in gingival crevicular fluid samples. Measurement of MMP-8 activity could prove to be useful in monitoring periodontal disease progression.

Exuberant gingival inflammation accompanied by periodontitis is a rare finding in a very young child and may indicate a defect in the host response. Affected children should be referred to appropriate specialists to establish a definitive diagnosis. A 5-year-old girl presented with persistent gingival inflammation and periodontal destruction. Immunological investigations identified specific polysaccharide antibody deficiency which, when treated, resulted in a significant improvement in the gingival condition. This case illustrates the need for integrated management by a wide range of dental and medical specialists. Antibody deficiency is rare but, if not identified and treated effectively, can be associated with chronic ill health and decreased life expectancy. CPD/Clinical Relevance: This article describes a rare case of gingival inflammation accompanied by periodontitis in a very young child secondary to an underlying host antibody deficiency and details the investigation, management and clinical outcomes.

International audience; Introduction: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Methods: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Results: Immunofluorescent staining revealed. TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha induced TRPA1 responses after Biodentine treatment. Conclusions: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses.

Objectives To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality. Methods Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects. Results During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality. Conclusions Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.

To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men.A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model.In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03.The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

In recent years there has been considerable interest in possible links between periodontal disease and systemic diseases. The general public are increasingly aware that such links may exist and in some cases are concerned about the implications for them as individuals. Nearly half of all adults in the United Kingdom have some form of periodontal disease,1 and as such present to dental practices every day. It is essential that all members of the dental team are aware of the periodontitis-systemic disease link, and can provide clear evidence-based advice and information to patients. The aim of this article is to summarise the current state of knowledge so that members of the dental team can convey appropriate advice and guidance to patients.

Aim: To characterize and map temporal changes in the biological and clinical phenotype during a 21-day experimental gingivitis study. Materials and Methods: Experimental gingivitis was induced over 21 days in healthy human volunteers (n = 56), after which normal brushing was resumed (resolution phase). Gingival and plaque indices were assessed. Gingival crevicular fluid was collected from four paired test and contra-lateral control sites in each volunteer during induction (Days 0, 7, 14 and 21) and resolution (Days 28 and 42) of experimental gingivitis. Fluid volumes were measured and a single analyte was quantified from each site-specific, 30s sample. Data were evaluated by analysis of repeated measurements and paired sample tests. Results: Clinical indices and gingival crevicular fluid volumes at test sites increased from Day 0, peaking at Day 21 (test/control differences all p < 0.0001) and decreased back to control levels by Day 28. Levels of four inflammatory markers showed similar patterns, with significant differences between test and control apparent at Day 7 (substance P, cathepsin G, interleukin-1b, elastase: all p < 0.03) and peaking at Day 21 (all p < 0.002). Levels of a-1-antitrypsin showed no pattern. Conclusions: Levels of substance P, cathepsin G, interleukin-1b and neutrophil elastase act as objective biomarkers of gingival inflammation induction and resolution that typically precede phenotypical changes.

International audience; Protease-activated receptors (PARs) are G-proteincoupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Chronic periodontitis (CP) is a common inflammatory disease which is characterized by progressive destruction of the tooth supporting structures and ultimately, potential tooth loss. A relationship between CP and diabetes has been recognized for some time. Both diseases share several collective risk factors, however, recent research has provided greater insight into the relationship with evidence emerging for each disease being a co-factor in the pathogenesis of the other. The aim of this review is to examine recent epidemiological evidence for the impact of diabetes on CP, and in the reverse direction, the impact of CP on diabetes. Based on the available evidence to date, it seems likely that the level of metabolic control influences future periodontal disease risk. In the reverse direction, the presence of CP has the potential to adversely affect glycemic control in both diabetes-affected and diabetes-free individuals. CP may potentially be a risk factor for the development of type 2 diabetes in diabetes-free individuals. Interventional studies show that successful treatment of CP may improve metabolic control in people with diabetes in the short term.

OBJECTIVE The aim was to investigate the association between periodontal health and the serum levels of various antioxidants including carotenoids, retinol and vitamin E in a homogenous group of Western European men. MATERIALS AND METHODS A representative sample of 1258 men aged 60-70 years, drawn from the population of Northern Ireland, was examined between 2001 and 2003. Each participant had six or more teeth, completed a questionnaire and underwent a clinical periodontal examination. Serum lipid-soluble antioxidant levels were measured by high-performance liquid chromatography with diode array detection. Multivariable analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed using two measures of periodontal status (low- and high-threshold periodontitis) as dependent variables and the fifths of each antioxidant as a predictor variable. RESULTS The levels of alpha- and beta-carotene, beta-cryptoxanthin and zeaxanthin were highly significantly lower in the men with low-threshold periodontitis (p

Introduction Neuropeptides play an important role in inflammation and repair and have been implicated in mediating angiogenesis. Pulp fibroblasts express neuropeptide receptors, and the aim of this research was to investigate whether neuropeptides could regulate angiogenic growth factor expression in vitro Methods An angiogenic array was used to determine the levels of 10 angiogenic growth factors expressed by human pulp fibroblasts. Results Pulp fibroblasts were shown to express angiogenin, angiopoietin-2, epidermal growth factor, basic fibroblast growth factor, heparin-binding epidermal growth factor, hepatocyte growth factor, leptin, platelet-derived growth factor, placental growth factor, and vascular endothelial growth factor. Furthermore, the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide Y altered angiogenic growth factor expression in vitro . Conclusions The regulation of angiogenic growth factor expression by neuropeptides suggests a novel role for neuropeptides in pulpal inflammation and repair.

AIM: The aim of this study was to investigate the factors associated with continued significant tooth loss due to periodontal reasons during maintenance following periodontal therapy in a specialist periodontal practice in Norway. MATERIAL AND METHODS: A case-control design was used. Refractory cases were patients who lost multiple teeth during a maintenance period of 13.4 (range 8-19) years following definitive periodontal treatment in a specialist practice. Controls were age- and gender-matched maintenance patients from the same practice. Characteristics and treatment outcomes were assessed, and all teeth classified as being lost due to periodontal disease during follow-up were identified. The use of implants in refractory cases and any complications relating to such a treatment were recorded. RESULTS: Only 27 (2.2%) patients who received periodontal treatment between 1986 and 1998 in a specialist practice met the criteria for inclusion in the refractory to treatment group. Each refractory subject lost 10.4 (range 4-16) teeth, which represented 50% of the teeth present at baseline. The rate of tooth loss in the refractory group was 0.78 teeth per year, which was 35 times greater than that in the control group. Multivariate analysis indicated that being in the refractory group was predicted by heavy smoking (p=0.026), being stressed (p=0.016) or having a family history of periodontitis (p=0.002). Implants were placed in 14 of the refractory patients and nine (64%) of these lost at least one implant. In total, 17 (25%) of the implants placed in the refractory group were lost during the study period. CONCLUSIONS: A small number of periodontal maintenance patients are refractive to treatment and go on to experience significant tooth loss. These subjects also have a high level of implant complications and failure. Heavy smoking, stress and a family history of periodontal disease were identified as factors associated with a refractory outcome.

Key content •Pregnancy has significant effects on the periodontal tissues and pregnancy gingivitis is a common manifestation of this. •The host response and oral flora are affected and tooth surface loss and mobility may develop. •Further research is required to establish the association between periodontal health and adverse pregnancy outcome. Learning objectives •To identify the main dental manifestations of pregnancy. •To be able to advise pregnant women on how to maintain good dental health. •To be aware of the need for effective communication between the dental and medical disciplines to ensure that pregnant women receive the best care possible for oral, obstetric and general health. Ethical issues •The treatment of gingivitis and periodontitis during pregnancy is safe and effective in treating gum disease. Please cite this article as: Pirie M, Cooke I, Linden G, Irwin C. Dental manifestations of pregnancy. The Obstetrician & Gynaecologist 2007;9:21–26.

Aim To investigate associations between periodontal disease pathogens and levels of systemic inflammation measured by C-reactive protein (CRP). Methods A representative sample of dentate 60–70-year-old men in Northern Ireland had a comprehensive periodontal examination. Men taking statins were excluded. Subgingival plaque samples were analysed by quantitative real time PCR to identify the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. High-sensitivity CRP (mg/l) was measured from fasting blood samples. Multiple linear regression analysis was performed using log-transformed CRP concentration as the dependent variable, with the presence of each periodontal pathogen as predictor variables, with adjustment for various potential confounders. Results A total of 518 men (mean age 63.6 SD 3.0 years) were included in the analysis. Multiple regression analysis showed that body mass index (p

BACKGROUND: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa.AIM: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan.METHODS: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP.RESULTS: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing.CONCLUSION: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.

Summary Objective To quantitatively measure VIP levels and to qualitatively study the distribution of VIP fibres and demonstrate the presence of the VPAC1 receptor in human dental pulp from carious and non-carious adult human teeth. Design Dental pulp samples were collected from non-carious, moderately carious and grossly carious adult human teeth. VIP levels were determined using radioimmunoassay. The distribution of VIP fibres was studied using immunohistochemistry. The VPAC1 receptor protein expression was determined by Western blotting. Results VIP levels were found to be significantly elevated in the dental pulp of moderately carious compared with non-carious ( p = 0.0032) or grossly carious teeth ( p = 0.0029). The distribution of VIP fibres was similar in non-carious and carious teeth, except that nerve bundles appeared thicker in the pulp samples from carious compared with non-carious teeth. Western blotting indicated that the VPAC1 receptor proteins were detected in similar levels in pooled dental pulp samples from both carious and non-carious teeth. Conclusion It is concluded that quantitative changes in the levels of VIP in human dental pulp during the caries process and the expression of VPAC1 receptor proteins in membrane extracts from carious and non-carious teeth suggests a role for VIP in modulating pulpal health and disease.

The aim of this study was to investigate whether an association could be demonstrated between coronary heart disease (CHD) and chronic periodontitis in a population of middle-aged males in Northern Ireland.A case-control design was used. Cases were men aged over 40 years with angiographically proven CHD. Controls were age-matched males, with no evidence of CHD, randomly drawn from the same locality as the cases. Each subject had a clinical periodontal examination and completed a detailed sociodemographic questionnaire. High sensitivity C-reactive protein (CRP) was measured in serum by immunoturbidimetry.There were 92 cases (mean age 56.7 years; SD = 6.3) and 79 controls (mean age 58.2 years; SD = 6.7). The CHD cases had an average of three teeth less than the controls (P0.0001). A higher proportion of sites examined in cases than controls had plaque (P = 0.004), bleeding on probing (P = 0.013), and probing depths ofor = 4 mm (P = 0.006) oror = 6 mm (P = 0.03). Subjects withor = 4 mm pocketing in more than 20% of their interproximal sites and those with deep pocketing (or = 6 mm) were classified as having poor periodontal status. A total of 35 cases (38%), compared to only 13 controls (16%), had a poor periodontal status (P = 0.0017). Men with a poor periodontal condition had higher levels of CRP (median 2.19 mg/l) than those with good periodontal health (median 1.42 mg/l), P = 0.007. After adjusting for smoking, academic achievement, alcohol consumption, unemployment, ability to maintain body weight, regular exercise, ability to relax daily, having a hobby or pastime, plaque, and CRP, logistic regression analysis showed that poor periodontal status was significantly associated with CHD, with an adjusted odds ratio of 3.06 and 95% confidence intervals of 1.02 to 9.17, P = 0.046.There was an association between coronary heart disease and poor periodontal status in the middle-aged males investigated. This association was independent of diabetes and all other cardiovascular risk factors investigated.

Background: Periodontal therapy coupled with active maintenance has been shown to be effective in maintaining periodontal health, however, the question of re-treatment is rarely alluded to in the literature. Aim: To quantify the type and extent of re-treatment in a group of patients who had completed a definitive course of periodontal treatment in a Norwegian specialist periodontal practice. The study also investigated factors associated with the provision of periodontal surgery as a re-treatment modality. Methods: A consecutive group of patients who had comprehensive periodontal treatment, which included periodontal surgery, and were subsequently maintained for between 10 and 17 years were studied. Results: One hundred and one patients with an average age at reassessment of 59.4 (standard deviation (SD) 9.0) years were studied. The average length of the review period was 13.1 (SD 1.9) years. In addition to routine maintenance, 50 patients had further re-treatment and 40 of those who were re-treated had periodontal surgery in the study period. Logistic regression showed that independent predictors of surgical re-treatment, with the effects adjusted for other variables in the model, were uncertain or poor prognosis at baseline, erratic or poor post baseline compliance and a family history of periodontal disease. Conclusion: Considerable amounts of re-treatment, including in many cases extensive non-surgical treatment or periodontal surgery, were provided for patients who had surgical periodontal treatment and were subsequently maintained for least 10 years in a specialist periodontal practice.

Background: Periodontal therapy coupled with careful maintenance has been shown to be effective in maintaining periodontal health; however, a small number of teeth are still lost because of progressive periodontitis. Aim:To investigate factors associated with tooth loss due to periodontal reasons during maintenance following periodontal treatment in patients in a Norwegian specialist periodontal practice. The study also examined how initial prognosis related to actual outcome as measured by periodontal tooth loss. Methods: Hundred consecutive patients (68 females, 32 males) who had comprehensive periodontal treatment and attended for 9.8 (SD: 0.7), range: 9-11 years of maintenance care, were studied. All teeth classified as being lost due to periodontal disease over the period were identified. Results: Only 36 (1.5%) of the 2436 teeth present at baseline were subsequently lost due to periodontal disease. There were 26 patients who lost at least one tooth. Logistic regression analysis showed that tooth loss was significantly related to male gender (p = 0.049; adjusted odds ratio: 2.8; confidence interval (c.i.): 1.0-8.1), older age, i.e.>60 years (p=0.012; adjusted odds ratio: 4.0; c.i.: 1.3-12.0) and smoking (p = 0.019; adjusted odds ratio: 4.2; c.i.: 1.4-13.8). The majority 27 (75%) of the teeth lost due to periodontal disease had been assigned an uncertain, poor or hopeless initial prognosis; however, nine teeth (25%) lost had been assigned a good prognosis at baseline. The prognosis for 202 teeth was judged to have worsened over the period of the study. Conclusion: Compliance with maintenance following periodontal treatment was associated with very low levels of tooth loss in a referral practice in rural Norway. Male gender, older age ( > 60 years) and smoking were predictors of tooth loss due to progressive periodontitis.

Background: The case outlined is a rare presentation of sarcoidosis intraorally associated with gingival ulceration. Methods: The diagnosis was made following a gingival biopsy. Results: The patient was subsequently referred to a physician for clinical management and the condition resolved without active treatment. Conclusions: Sarcoidosis should be considered in the differential diagnosis of persistent swellings and ulceration of the oral mucosa. Intraoral sarcoid lesions are often the first indication of systemic involvement. It is important to make the diagnosis and monitor the condition as sarcoidosis is progressive if untreated in a small number of those affected. J Periodontol 2004;75:608-612.

The immunosuppressive agent cyclosporin is associated with a number of major side-effects including the development of gingival overgrowth. Although the pathogenesis of cyclosporin-induced gingival overgrowth remains unclear, it has been suggested that the finely regulated balance between extracellular matrix synthesis and degradation may be disturbed, resulting in an accumulation of excess connective tissue components within the gingival tissue. The aim of this study was to investigate the effect of cyclosporin on matrix metalloproteinases (MMP)-1 and tissue inhibitors of MMP (TIMP)-1 expression at the mRNA, protein, and enzyme activity levels.Gingival fibroblasts were grown to confluence and then cultured in serum-free medium supplemented with cyclosporin over the concentration range of 0 to 2000 ng/ml. MMP-1 and TIMP-1 mRNA levels in cultures were determined by reverse transcription polymerase chain reaction (RT-PCR), protein levels in whole conditioned medium were assessed by enzyme-linked immunosorbent assay (ELISA), and collagenolytic activity determined using a 3H-acetylated type I collagen degradation assay. Tissue mRNA levels in normal and overgrown gingiva were also determined by RT-PCR.Results indicated that cyclosporin inhibited MMP-1 expression at both the mRNA and protein level in a dose- and time-dependent fashion. The effects on TIMP-1 expression were less clear, cyclosporin inhibiting mRNA expression, but having no effect on TIMP-1 protein levels at any concentration studied. Addition of the drug resulted in reduced levels of collagenolytic activity in the culture medium. MMP-1 mRNA expression was significantly reduced in overgrown compared to normal tissue.These results add support to the hypothesis that the accumulation of collagen seen in gingival overgrowth can be explained by a cyclosporin-induced inhibition of collagenolytic activity within the gingival tissues.