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Background The application of orthodontic forces causes root resorption of variable severity with potentially severe clinical ramifications. Objective To systematically review reports on the pathophysiological mechanisms of orthodontically induced inflammatory root resorption (OIIRR) and the associated risk factors based on in vitro , experimental, and in vivo studies. Search methods We undertook an electronic search of four databases and a separate hand-search. Selection criteria Studies reporting on the effect of orthodontic forces with/without the addition of potential risk factors on OIIRR, including (1) gene expression in in-vitro studies, the incidence root resorption in (2) animal studies, and (3) human studies. Data collection and analysis Potential hits underwent a two-step selection, data extraction, quality assessment, and systematic appraisal performed by duplicate examiners. Results One hundred and eighteen articles met the eligibility criteria. Studies varied considerably in methodology, reporting of results, and variable risk of bias judgements. In summary, the variable evidence identified supports the notion that the application of orthodontic forces leads to (1) characteristic alterations of molecular expression profiles in vitro, (2) an increased rate of OIIRR in animal models, as well as (3) in human studies. Importantly, the additional presence of risk factors such as malocclusion, previous trauma, and medications like corticosteroids increased the severity of OIIRR, whilst other factors decreased its severity, including oral contraceptives, baicalin, and high caffeine. Conclusions Based on the systematically reviewed evidence, OIIRR seems to be an inevitable consequence of the application of orthodontic forces—with different risk factors modifying its severity. Our review has identified several molecular mechanisms that can help explain this link between orthodontic forces and OIIRR. Nevertheless, it must be noted that the available eligible literature was in part significantly confounded by bias and was characterized by substantial methodological heterogeneity, suggesting that the results of this systematic review should be interpreted with caution. Registration PROSPERO (CRD42021243431). [ABSTRACT FROM AUTHOR]

Quorum sensing molecules (QSMs) in the oral cavity regulate biofilm formation, the acquisition of iron, stress responses, and the expression of virulence factors. However, knowledge of the direct QSM–host interactions in the oral environment is limited, although their understanding could provide greater insight into the cross-kingdom communication occurring during oral disease development. This review aims to explore the literature on oral QSM–host interactions and to highlight areas of advancement in this field. The studies included in this review encompass an array of cell types and oral QSMs, with particular emphasis on immune cells and their relationship to periodontal diseases. It can be inferred from the current literature that QSMs are utilised by host cells to detect bacterial presence and, in the majority of cases, elicit an immune response towards the environmental QSMs. This may provide a base to target QSMs as a novel treatment of oral diseases. However, N-acyl homoserine lactone (AHL) detection methods remain an area for development, through which a greater understanding of the influence of oral QSMs on host cells could be achieved. [ABSTRACT FROM AUTHOR]

Background and Objective: Plaque‐induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat‐killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. Methods: H400 oral epithelial cell line was pre‐conditioned with curcumin and the production of cytokines was measured by enzyme‐linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO‐1) expression and molecules that HO‐1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. Results: Pre‐conditioning of H400 cells with a sub‐apoptotic concentration of curcumin (20 μM) attenuated secretion of Granulocyte‐Macrophage – Colony‐Stimulating Factor (GM‐CSF) and reduced NFkB nuclear translocation. This pre‐conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO‐1) expression. Inhibition of HO‐1 by SnPPIX prevented the curcumin‐induced attenuation of GM‐CSF production. HO‐1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO‐1/CO anti‐inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule‐2 (CORM2) treatment alone abrogated F. nucleatum‐induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. Conclusion: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide. [ABSTRACT FROM AUTHOR]

The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. The non-specific plaque hypothesis was the first attempt to explain the role of the dental biofilm in the pathogenesis of periodontal diseases. However, the introduction of sophisticated diagnostic and laboratory assays has led to the realisation that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the host’s immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis. This review aims to highlight the development and structure of the dental plaque biofilm and to explore current literature on the transition from a healthy (symbiotic) to a diseased (dysbiotic) biofilm in periodontitis and the associated immune-inflammatory responses that drive periodontal tissue destruction and form mechanistic pathways that impact other systemic non-communicable diseases. [ABSTRACT FROM AUTHOR]

Aim: To discover and validate differential protein biomarker expression in saliva and gingival crevicular fluid (GCF) to discriminate objectively between periodontal health and plaque‐induced periodontal disease states. Materials and Methods: One‐hundred and ninety participants were recruited from two centres (Birmingham and Newcastle upon Tyne, UK) comprising healthy, gingivitis, periodontitis, and edentulous donors. Samples from the Birmingham cohort were analysed by quantitative mass spectrometry proteomics for biomarker discovery. Shortlisted candidate proteins were then verified by enzyme‐linked immunosorbent assay in both cohorts. Leave‐one‐out cross validation logistic regression analysis was used to identify the best performing biomarker panels. Results: Ninety‐five proteins were identified in both GCF and saliva samples, and 15 candidate proteins were selected based upon differences discovered between the donor groups. The best performing panels to distinguish between: health or gingivitis and periodontitis contained matrix metalloproteinase‐9 (MMP9), S100A8, alpha‐1‐acid glycoprotein (A1AGP), pyruvate kinase, and age (area under the curve [AUC] 0.970); health and gingivitis contained MMP9, S100A8, A1AGP, and pyruvate kinase, but not age (AUC 0.768); and mild to moderate and advanced periodontitis contained MMP9, S100A8, A1AGP, pyruvate kinase, and age (AUC 0.789). Conclusions: Biomarker panels containing four proteins with and without age as a further parameter can distinguish between periodontal health and disease states. [ABSTRACT FROM AUTHOR]

Background: The British Society of Periodontology (BSP) implemented a simplified version of the 2017 World Workshop Classification (WWC) on staging and grading of periodontitis, for use in UK clinical practice. The aim of this study was to assess the long-term (>10 years) prognostic capability of BSP's implementation (BSP-i) compared with the 2017 WWC, using periodontal-related tooth loss (TLP) as a disease outcome.Methods: Data on medical history, smoking status, and clinical periodontal parameters were retrieved from 270 patients who received non-surgical and surgical periodontal therapy from 1966 to 2007. Each patient received a baseline diagnosis according to the 2017 WWC and the BSP-i guidelines for implementation. Univariate multilevel Cox regression frailty models were performed to analyze the association between variables with TLP. A post-hoc comparison with Bonferroni correction was performed to analyze interclass comparisons. The prognostic performance of both systems was analyzed using Harrell C index.Results: The prognostic performance of both systems was very similar (0.922 for the 2017 WWC and 0.925 for the BSP-i). The singular prognostic performance of BSP stage was slightly higher than that of 2017 WWC stage (0.9212 versus 0.9188), while the 2017 WWC grade showed a slightly better performance than BSP grade (0.9175 versus 0.9155). BSP-i's extent performed better than the 2017 WWC extent (0.9203 versus 0.9098); however, in the 2017 WWC extent, the class "localized" was associated with a better prognosis than "generalized."Conclusion: The overall prognostic performance of the two systems was excellent, with both systems having a Harrell C index score of >0.92. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases [NCDs] are the major cause of mortality globally and are increasing in prevalence. Different healthcare professionals' access different population groups; and engaging allied healthcare professionals in risk-driven early case detection of certain NCDs may be beneficial, especially those who have not been tested for NCDs within the previous 12 months. The objectives of this study were to determine: whether NCD case finding in dental/community pharmacy settings is feasible in terms of patient acceptability, barriers to recruitment, impact on the existing service. Determine time taken to test for: type 2 diabetes risk [T2DM], chronic obstructive pulmonary disease [COPD], hypertension, vitamin D deficiency and chronic kidney disease [CKD]. Determine whether there is added benefit of point of care testing [POCT] to identify diabetes risk compared to a validated screening questionnaire alone.Methods: An exploratory study was undertaken to explore issues associated with NCD assessment in one dental practice and one community pharmacy within the West-Midlands, UK. Fifty patients > 40 years-of-age were recruited per site. Participants undertook: a questionnaire providing demographic data, any previous NCD diagnosis or positive family history. Validated questionnaires for determining NCD risk [T2DM/COPD]. Chair-side capillary blood [finger-prick] samples for HbA1C, creatinine/eGFR, Vitamin-D. Prior work had been undertaken to measure the agreement between point of care testing [POCT] devices and a central laboratory method, and to gauge the opinions of participants regarding discomfort experienced using venous (antecubital fossa) and capillary (finger-prick) blood collection, via a 10 cm Visual-Analogue-Scale. The POCT devices demonstrated good concordance with laboratory testing and were acceptable methods of blood collection for participants.Results: Recruitment rates demonstrated that 8 days were needed to recruit 50 participants and 60% of those approached opted to participate. The principal barrier to participation was time, with average time taken to test being 19mins. Utilising dental and pharmacy settings identified potential cases of previously undiagnosed disease.Conclusions: Risk-targeted testing for NCDs in high street dental and community pharmacies is both attractive and acceptable to patients. [ABSTRACT FROM AUTHOR]

Maintenance of oral health is in part managed by the immune-surveillance and antimicrobial functions of polymorphonuclear leukocytes (PMNs), which migrate from the circulatory system through the oral mucosal tissues as oral PMNs (oPMNs). In any microorganism-rich ecosystem, such as the oral cavity, PMNs migrate toward various exogenous chemoattractants, phagocytose bacteria, and produce neutrophil extracellular traps (NETs) to immobilize and eliminate pathogens. PMNs obtained from the circulation through venipuncture (hereafter called cPMNs) have been widely studied using various functional assays. We aimed to study the potential of oPMNs in maintaining oral health and therefore compared their chemotactic and antimicrobial functions with cPMNs. To establish chemotactic, phagocytic, and NET forming capacities, oPMNs and cPMNs were isolated from healthy subjects without obvious oral inflammation. Directional chemotaxis toward the chemoattractant fMLP was analyzed using an Insall chamber and video microscopy. fMLP expression was assessed by flow cytometry. Phagocytosis was analyzed by flow cytometry, following PMN incubation with heat-inactivated FITC-labeled micro-organisms. Furthermore, agar plate-based killing assays were performed with Escherichia coli (Ec). NET formation by oPMNs and cPMNs was quantified fluorimetrically using SYTOX™ Green, following stimulation with either PMA or RPMI medium (unstimulated control). In contrast to cPMNs, the chemotactic responses of oPMNs to fMLP did not differ from controls (mean velocity ± SEM of cPMNs: 0.79 ± 0.24; of oPMNs; 0.10 ± 0.07 micrometer/min). The impaired directional movement toward fMLP by oPMNs was explained by significantly lower fMLP receptor expression. Increased adhesion and internalization of various micro-organisms by oPMNs was observed. oPMNs formed 13 times more NETs than stimulated cPMNs, in both unstimulated and stimulated conditions. Compared to cPMNs, oPMNs showed a limited ability for intracellular killing of Ec. In conclusion, oPMNs showed exhausted capacity for efficient chemotaxis toward fMLP which may be the result of migration through the oral tissues into the oral cavity, being a highly "hostile" ecosystem. Overall, oPMNs' behavior is consistent with hyperactivity and frustrated killing. Nevertheless, oPMNs most likely contribute to maintaining a balanced oral ecosystem, as their ability to internalize microbes in conjunction with their abundant NET production remains after entering the oral cavity. [ABSTRACT FROM AUTHOR]

Objectives: Nupharidine (6,6′‐Dihydroxythiobinupharidine), purified from the aquatic plant Nuphar lutea leaves (Water lily) prompts antimicrobial activity of immune cells. The aim of the study was to test the effect of Nupharidine on neutrophil function against Aggregatibacter actinomycetemcomitans, JP2 clone (Aa‐JP2). Methods: Neutrophils derived from the human cell line HL60 and human peripheral blood derived from aggressive periodontitis and periodontally healthy subjects were incubated with Nupharidine or vehicle and inoculated with JP2. Bacterial survival was tested using viable counts on blood agar (CFU's). Neutrophils' necrosis/apoptosis, reactive oxygen species (ROS) production, phagocytosis and neutrophil extracellular traps (NET) production following infection were tested, as well as markers of neutrophil priming. Results: Nupharidine had no direct bactericidal effect on JP2, but it enhanced Aa‐JP2 clearance by neutrophils. Nupharidine enhanced neutrophil phagocytosis, ROS production and NET formation during JP2 infection. Furthermore, Nupharidine enhanced the expression of certain markers of neutrophils priming, specifically iCAM1, DECTIN‐2 and intracellular IL‐1β. Conclusion: Nupharidine was shown to promote neutrophil effector bactericidal functions, boosting Aa‐JP2 clearance. The results point to the potential of Nupharidine as an adjunctive agent in the treatment of Aa‐JP2 periodontitis, but this should be tested initially using pre‐clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non‐periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non‐dental plaque biofilm–induced gingival diseases and dental plaque‐induced gingivitis. Non‐dental plaque biofilm‐induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque‐induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque‐induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non‐periodontitis patient or in a currently stable “periodontitis patient” i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient‐centered approach to care, and therefore, creates differences in the way in which a “case” of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This review proposes revisions to the current classification system for gingival diseases and provides a rationale for how it differs from the 1999 classification system. Importance: Gingival inflammation in response to bacterial plaque accumulation (microbial biofilms) is considered the key risk factor for the onset of periodontitis. Thus, control of gingival inflammation is essential for the primary prevention of periodontitis. Findings: The clinical characteristics common to dental plaque–induced inflammatory gingival conditions include: a) clinical signs and symptoms of inflammation that are confined to the gingiva: b) reversibility of the inflammation by removing or disrupting the biofilm; c) the presence of a high bacterial plaque burden to initiate the inflammation; d) systemic modifying factors (e.g., hormones, systemic disorders, drugs) which can alter the severity of the plaque‐induced inflammation and; e) stable (i.e., non‐changing) attachment levels on a periodontium which may or may not have experienced a loss of attachment or alveolar bone. The simplified taxonomy of gingival conditions includes: 1) introduction of the term “incipient gingivitis;” 2) a description of the extent and severity of gingival inflammation; 3) a description of the extent and severity of gingival enlargement and; 4) a reduction of categories in the dental plaque–induced gingival disease taxonomy. Conclusions: Dental plaque–induced gingival inflammation is modified by various systemic and oral factors. The appropriate intervention is crucial for the prevention of periodontitis. [ABSTRACT FROM AUTHOR]

Abstract: A classification scheme for periodontal and peri‐implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri‐implant Diseases and Conditions. The workshop was co‐sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri‐implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri‐implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri‐implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri‐implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table  ). [ABSTRACT FROM AUTHOR]

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. [ABSTRACT FROM AUTHOR]

A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table 1). [ABSTRACT FROM AUTHOR]

Objective: This review proposes revisions to the current classification system for gingival diseases and provides a rationale for how it differs from the 1999 classification system.Importance: Gingival inflammation in response to bacterial plaque accumulation (microbial biofilms) is considered the key risk factor for the onset of periodontitis. Thus, control of gingival inflammation is essential for the primary prevention of periodontitis.Findings: The clinical characteristics common to dental plaque-induced inflammatory gingival conditions include: a) clinical signs and symptoms of inflammation that are confined to the gingiva: b) reversibility of the inflammation by removing or disrupting the biofilm; c) the presence of a high bacterial plaque burden to initiate the inflammation; d) systemic modifying factors (e.g., hormones, systemic disorders, drugs) which can alter the severity of the plaque-induced inflammation and; e) stable (i.e., non-changing) attachment levels on a periodontium which may or may not have experienced a loss of attachment or alveolar bone. The simplified taxonomy of gingival conditions includes: 1) introduction of the term "incipient gingivitis;" 2) a description of the extent and severity of gingival inflammation; 3) a description of the extent and severity of gingival enlargement and; 4) a reduction of categories in the dental plaque-induced gingival disease taxonomy.Conclusions: Dental plaque-induced gingival inflammation is modified by various systemic and oral factors. The appropriate intervention is crucial for the prevention of periodontitis. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the impact of weight loss following gastric band surgery on multiple measures of peripheral blood neutrophil (PBN) function.Material and Methods: Twenty-three obese patients undergoing gastric band surgery were recruited to a longitudinal intervention study, alongside non-obese, healthy gender- and age-matched controls. Eighteen pairs of patients and controls completed all stages of the study. PBNs were isolated by density centrifugation and a comprehensive analysis of PBN function was undertaken at various stages of the patients’ bariatric surgical care pathway.Results: Obese patients exhibited exaggerated PBN activity in response to various stimuli, characterised by higher reactive oxygen species (ROS) generation (n = 18, p < 0.001) and release of pro-inflammatory cytokines (n = 10, p < 0.05) and lower PBN extracellular trap (NET) formation (n = 18, p < 0.01). PBN chemotactic accuracy was also impaired prior to surgery (n = 18, p < 0.01). Weight loss was associated with normalised NET production and lower ROS production and cytokine release relative to healthy controls. However, chemotactic accuracy remained impaired in patients.Conclusions: Weight loss following gastric band surgery was associated with a decrease in the pro-inflammatory activities of peripheral blood neutrophils (PBNs). A hyper-inflammatory PBN phenotype, involving excess ROS and cytokine release, reduced NET formation and chemotaxis, may lead to a reduced ability to eliminate infection, alongside inflammation-mediated tissue damage in obese individuals. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) exhibit increased morbidity and mortality which is associated with an increased systemic inflammatory burden. Identifying and managing comorbid diseases that contribute to this load may inform novel care pathways that could have a beneficial impact on the morbidity/mortality associated with CKD. Periodontitis, a highly prevalent, chronic inflammatory disease affecting the supporting structures of teeth, is associated with an increased systemic inflammatory and oxidative stress burden and the successful treatment of periodontitis has been shown to reduce both. This pilot study aims to gather data to inform a definitive study into the impact of successful periodontal treatment on the cardio-renal health of patients with CKD.Methods/design: This pilot study will employ a randomised, controlled, parallel-group design. Sixty adult patients, with CKD with a high risk of progression and with periodontitis, from the Queen Elizabeth Hospital, Birmingham, will be randomised to receive either immediate, intensive periodontal treatment (n = 30) or treatment at a delay of 12 months (n = 30). Patients will be excluded if they have reached end-stage renal disease or have received specialist periodontal treatment in the previous year. Periodontal treatment will be delivered under local anaesthetic, on an outpatient basis, over several visits by a qualified dental hygienist at the Birmingham Dental Hospital, UK. Patients in the delayed-treatment arm will continue to receive the standard community level of periodontal care for a period of 12 months followed by the intensive periodontal treatment. Randomization will occur using a centralised telephone randomisation service, following baseline assessments. The assessor of periodontal health will be blinded to the patients' treatment allocation. Patients in either arm will be followed up at 3-monthly intervals for 18 months. Aside from the pilot outcomes to inform the practicalities of a larger trial later, data on cardio-renal function, periodontal health and patient-reported outcomes will be collected at each time point.Discussion: This pilot randomised controlled trial will investigate the viability of undertaking a larger-scale study investigating the effect of treating periodontitis and maintaining periodontal health on cardio-renal outcomes in patients with CKD.Trial Registration: National Institute of Health Research (NIHR) Clinical Research Network (UKCRN ID: 18458), ID: ISRCTN10227738 . Registered retrospectively to both registers on 23 April 2015. [ABSTRACT FROM AUTHOR]

Aim To determine peripheral blood neutrophil superoxide release and C-reactive protein ( CRP) concentration in chronic periodontitis patients, before and after non-surgical periodontal treatment. Materials and Methods Neutrophils were isolated from patient and control volunteers ( n = 20) and superoxide measured by lucigenin-enhanced chemiluminescence with and without stimulation with unopsonized Porphyromonas gingivalis, unopsonized Fusobacterium nucleatum and phorbol 12-myristate 13-acetate ( PMA) before and 2-months following non-surgical therapy. Corresponding high-sensitivity plasma CRP concentrations were also determined. Results At pre-treatment baseline, patient neutrophils released more superoxide in the absence ( p ≤ 0.032) and presence of periodontal bacteria ( p ≤ 0.013) and after PMA stimulation ( p = 0.041) compared to control cells. Post-therapy, patient neutrophil superoxide release was reduced to control cell levels. Median patient plasma CRP concentrations were non-significantly higher than control values and were reduced after therapy (1.80-1.36 mg/l). Patient pre-treatment baseline, unstimulated neutrophil superoxide release showed a significant, positive correlation with plasma CRP concentration ( p = 0.01). Conclusions Chronic periodontitis is characterized by peripheral neutrophils exhibiting superoxide hyperactivity and hyper-reactivity to periodontal pathogens that is not a constitutive feature of periodontitis patients. The positive, pre-therapy relationship between unstimulated neutrophil superoxide release and plasma CRP is consistent with a protective role for CRP in reducing oxidative stress and systemic inflammation in vivo. [ABSTRACT FROM AUTHOR]

Aim Inflammatory periodontal disease is widespread in dogs. This study evaluated site-specific changes in the canine gingival crevicular fluid ( GCF) proteome during longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires general anaesthesia with associated risks and costs; our ultimate aim was to develop a periodontitis diagnostic for application in conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in dogs. Material and Methods Gingival crevicular fluid was sampled from a total of 10 teeth in eight dogs at three different stages of health/disease and samples prepared for quantitative mass spectrometry (data available via ProteomeXchange; identifier PXD003337). A univariate mixed model analysis determined significantly altered proteins between health states and six were evaluated by ELISA. Results Four hundred and six proteins were identified with 84 present in all samples. The prevalence of 40 proteins was found to be significantly changed in periodontitis relative to gingivitis. ELISA measurements confirmed that haptoglobin was significantly increased. Conclusions This study demonstrates for the first time that proteins detected by mass spectrometry have potential to identify novel biomarkers for canine periodontal disease. Further work is required to validate additional biomarkers for a periodontitis diagnostic. [ABSTRACT FROM AUTHOR]

Carbamylation of lysine residues and protein N-termini is an ubiquitous, non-enzymatic post-translational modification. Carbamylation at sites of inflammation is due to cyanate formation during the neutrophil oxidative burst and may target lysine residues within the antimicrobial peptide LL-37. The bactericidal and immunomodulatory properties of LL-37 depend on its secondary structure and cationic nature, which are conferred by arginine and lysine residues. Therefore, carbamylation may affect the biological functions of LL-37. The present study examined the kinetics and pattern of LL-37 carbamylation to investigate how this modification affects the bactericidal, cytotoxic and immunomodulatory function of the peptide. The results indicated that LL-37 undergoes rapid modification in the presence of physiological concentrations of cyanate, yielding a spectrum of diverse carbamylated peptides. Mass spectrometry analyses revealed that the N-terminal amino group of Leu-1 was highly reactive and was modified almost instantly by cyanate to generate the predominant form of the modified peptide, named LL-37C1. This was followed by the sequential carbamylation of Lys-8, Lys-12, and Lys-15 to yield LL-37C8, and Lys-15 to yield LL-37C12,15. Carbamylation had profound and diverse effects on the structure and biological properties of LL-37. In some cases, anti-inflammatory LL-37 was rapidly converted to pro-inflammatory LL-37. [ABSTRACT FROM AUTHOR]

Aims The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome ( pSS) and comparator groups of patients with rheumatoid arthritis ( RA) and osteoarthritis ( OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. Materials and Methods Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and 'In-house' antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. Results Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. Conclusion This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokine release (IL-8, IL-6, TNF-α, IL-1β) by peripheral blood neutrophils, isolated from periodontitis patients (before/after therapy) and matched controls, was determined after 18 h culture in the presence/absence of Escherichia coli LPS, opsonised Staphylococcus aureus, heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis. All cultures demonstrated differences in the amounts of each cytokine detected (P < 0.0001), with a clear release pattern (IL-8 > IL-6 > TNF-α = IL-1β). Median cytokine release from unstimulated patient neutrophils was consistently, but non-significantly, higher than from control cells. Stimulated cytokine release from untreated patient neutrophils was also consistently higher than from control cells. This hyper-reactivity was significant for all tested cytokines when data for all stimuli were combined (P < 0.016). In terms of individual stimuli, significant hyper-reactivity was detected with LPS (IL-8), F. nucleatum (IL-8, TNF-α), opsonised S. aureus (IL-8, TNF-α, IL-1β) and P. gingivalis (IL-8, IL-1β). Cytokine production by patient neutrophils did not reduce following successful non-surgical periodontal therapy and, except for responses to F. nucleatum, the cytokine hyper-reactivity detected pre-therapy was retained. These data demonstrate that chronic periodontitis is characterised by neutrophils that constitutively exhibit cytokine hyper-reactivity, the effects of which could modulate local and systemic inflammatory-immune responses and influence the risk and severity of periodontitis-associated systemic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Intrabony periodontal defects are a frequent complication of periodontitis and, if left untreated, may negatively affect long-term tooth prognosis. The optimal outcome of treatment in intrabony defects is considered to be the absence of bleeding on probing, the presence of shallow pockets associated with periodontal regeneration (i.e. formation of new root cementum with functionally orientated inserting periodontal ligament fibers connected to new alveolar bone) and no soft-tissue recession. A plethora of different surgical techniques, often including implantation of various types of bone graft and/or bone substitutes, root surface demineralization, guided tissue regeneration, growth and differentiation factors, enamel matrix proteins or various combinations thereof, have been employed to achieve periodontal regeneration. Despite positive observations in animal models and successful outcomes reported for many of the available regenerative techniques and materials in patients, including histologic reports, robust information on the degree to which reported clinical improvements reflect true periodontal regeneration does not exist. Thus, the aim of this review was to summarize, in a systematic manner, the available histologic evidence on the effect of reconstructive periodontal surgery using various types of biomaterials to enhance periodontal wound healing/regeneration in human intrabony defects. In addition, the inherent problems associated with performing human histologic studies and in interpreting the results, as well as certain ethical considerations, are discussed. The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials. Periodontal regeneration has been observed following the use of a variety of bone grafts and substitutes, guided tissue regeneration, biological factors and combinations thereof. Combination approaches appear to provide the best outcomes, whilst implantation of alloplastic material alone demonstrated limited, to no, periodontal regeneration. [ABSTRACT FROM AUTHOR]

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase. [ABSTRACT FROM AUTHOR]

Periodontitis is a ubiquitous and irreversible inflammatory condition and represents a significant public health burden. Severe periodontitis affects over 11% of adults, is a major cause of tooth loss impacting negatively upon speech, nutrition, quality of life and self-esteem, and has systemic inflammatory consequences. Periodontitis is preventable and treatment leads to reduced rates of tooth loss and improved quality of life. However, successful treatment necessitates behaviour change in patients to address lifestyle risk factors (e.g. smoking) and, most importantly, to attain and sustain high standards of daily plaque removal, lifelong. While mechanical plaque removal remains the bedrock of successful periodontal disease management, in high-risk patients it appears that the critical threshold for plaque accumulation to trigger periodontitis is low, and such patients may benefit from adjunctive agents for primary prevention of periodontitis. Aim The aims of this working group were to systematically review the evidence for primary prevention of periodontitis by preventing gingivitis via four approaches: 1) the efficacy of mechanical self-administered plaque control regimes; 2) the efficacy of self-administered inter-dental mechanical plaque control; 3) the efficacy of adjunctive chemical plaque control; and 4) anti-inflammatory (sole or adjunctive) approaches. Methods Two meta-reviews (mechanical plaque removal) and two traditional systematic reviews (chemical plaque control/anti-inflammatory agents) formed the basis of this consensus. Results Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit. Re-chargeable power toothbrushes provide small but statistically significant additional reductions in gingival inflammation and plaque levels. Flossing cannot be recommended other than for sites of gingival and periodontal health, where inter-dental brushes ( IDBs) will not pass through the interproximal area without trauma. Otherwise, IDBs are the device of choice for interproximal plaque removal. Use of local or systemic anti-inflammatory agents in the management of gingivitis has no robust evidence base. We support the almost universal recommendations that all people should brush their teeth twice a day for at least 2 min. with fluoridated dentifrice. Expert opinion is that for periodontitis patients 2 min. is likely to be insufficient, especially when considering the need for additional use of inter-dental cleaning devices. In patients with gingivitis once daily inter-dental cleaning is recommended and the adjunctive use of chemical plaque control agents offers advantages in this group. [ABSTRACT FROM AUTHOR]

Background Periodontitis prevalence remains high. Peri-implantitis is an emerging public health issue. Such a high burden of disease and its social, oral and systemic consequences are compelling reasons for increased attention towards prevention for individuals, professionals and public health officials. Methods Sixteen systematic reviews and meta-reviews formed the basis for workshop discussions. Deliberations resulted in four consensus reports. Results This workshop calls for renewed emphasis on the prevention of periodontitis and peri-implantitis. A critical element is the recognition that prevention needs to be tailored to the individual's needs through diagnosis and risk profiling. Discussions identified critical aspects that may help in the large-scale implementation of preventive programs: (i) a need to communicate to the public the critical importance of gingival bleeding as an early sign of disease, (ii) the need for universal implementation of periodontal screening by the oral health care team, (iii) the role of the oral health team in health promotion and primary and secondary prevention, (iv) understanding the limitations of self-medication with oral health care products without a diagnosis of the underlying condition, and (v) access to appropriate and effective professional preventive care. Conclusions The workshop provided specific recommendations for individuals, the oral health team and public health officials. Their implementation in different countries requires adaptation to respective specific national oral health care models. [ABSTRACT FROM AUTHOR]

Introduction Chronic kidney disease ( CKD) is associated with significant morbidity and mortality. There is a need to identify novel and modifiable risk factors in such patients. The periodontal component of the Renal Impairment In Secondary Care ( RIISC) study aims to evaluate the association between chronic periodontitis and CKD progression. Methods The RIISC study is a prospective, observational cohort study of patients with CKD from a renal clinic at a hospital in the West Midlands region of the UK. Patients undergo a periodontal examination and plaque and saliva sampling. To benchmark the oral health status of the RIISC cohort, we compared it to the Adult Dental Health Survey 2009 ( ADHS), a representative survey of the oral health of community dwelling adults in the UK. Results Of the first 500 patients recruited into the RIISC study, 469 patients underwent a dental examination and 80 (17%) were edentulous. Among dentate subjects, patients within RIISC were significantly more likely to have any ( OR 4.0 95% CI 2.7-5.9) or severe ( OR 3.8 95% CI 2.5-5.6) periodontitis compared to the ADHS sample. Conclusion The prevalence and severity of chronic periodontitis in this cohort of CKD patients is markedly higher than a geographically matched control population. [ABSTRACT FROM AUTHOR]

Background Studies suggest that periodontitis may be a risk factor for rheumatoid arthritis (RA). The purpose of this study was to determine whether periodontitis is associated with autoantibodies characteristic of RA. Methods Serum samples were tested for anti-cyclic citrullinated peptide (CCP), anti-mutated citrullinated vimentin (MCV), anti-citrullinated α-enolase peptide-1 (CEP-1), anti-citrullinated vimentin (cit-vim), anti-citrullinated fibrinogen (cit-fib) and their uncitrullinated forms anti-CParg (negative control for anti-CCP), anti-arginine-containing α-enolase peptide-1 (REP-1), anti-vimentin and anti-fibrinogen antibodies in patients with and without periodontitis, none of whom had RA. Results Periodontitis, compared with non-periodontitis, was associated with a normal frequency of anti-CCP and anti-MCV (~1%) but a higher frequency of positive anti-CEP-1 (12% vs 3%; p=0.02) and its uncitrullinated form anti-REP-1 (16% vs 2%; p<0.001). Positive antibodies against uncitrullinated fibrinogen and CParg were also more common among those with periodontitis compared to non-periodontitis patients (26% vs 3%; p<0.001, and 9% vs 3%; p=0.06). After adjusting for confounders, patients with periodontitis had 43% (p=0.03), 71% (p=0.002) and 114% (p<0.001) higher anti-CEP-1, anti-REP-1 and anti-fibrinogen titres, compared with non-periodontitis. Non-smokers with periodontitis, compared with non-periodontitis, had significantly higher titres of anti-CEP-1 (103%, p<0.001), anti-REP-1 (91%, p=0.001), anti-vimentin (87%, p=0.002), and anti-fibrinogen (124%, p<0.001), independent of confounders, confirming that the autoantibody response in periodontitis was not due to smoking. Conclusions We have shown that the antibody response in periodontitis is predominantly directed to the uncitrullinated peptides of the RA autoantigens examined in this study. We propose that this loss of tolerance could then lead to epitope spreading to citrullinated epitopes as the autoimmune response in periodontitis evolves into that of presymptomatic RA. [ABSTRACT FROM AUTHOR]

The discovery of neutrophil extracellular traps in 2004 opened a fascinating new chapter in immune-mediated microbial killing. Brinkman et al. demonstrated that neutrophils, when catastrophically stimulated, undergo a novel form of programmed cell death (neutrophil extracellular trap formation) whereby they decondense their entire nuclear chromatin/ DNA and release the resulting structure into the cytoplasm to mix with granule-derived antimicrobial peptides before extruding these web-like structures into the extracellular environment. The process requires the activation of the granule enzyme peptidyl arginine deiminase-4, the formation of reactive oxygen species (in particular hypochlorous acid), the neutrophil microtubular system and the actin cytoskeleton. Recent work by Yousefi et al. demonstrated that exposure to different agents for shorter stimulation periods resulted in neutrophil extracellular trap release from viable granulocytes, and that such neutrophil extracellular traps comprised mitochondrial DNA rather than nuclear DNA and were also capable of microbial entrapment and destruction. Deficiency in NADPH-oxidase production (as found in patients with chronic granulomatous disease) results in an inability to produce neutrophil extracellular traps and, along with their failure to produce antimicrobial reactive oxygen species, these patients suffer from severe, and sometimes life-threatening, infections. However, conversely the release of nuclear chromatin into tissues is also potentially autoimmunogenic and is now associated with the generation of anti-citrullinated protein antibodies in seropositive rheumatoid arthritis. Other neutrophil-derived nuclear and cytoplasmic contents are also pathogenic, either through direct effects on tissues or via autoimmune processes (e.g. autoimmune vasculitis). In this review, we discuss the plant origins of a highly conserved innate immune method of microbial killing, the history and biology of neutrophil extracellular traps and their role in defence and in human diseases. We attempt to resolve areas of controversy and propose roles for excess neutrophil extracellular trap release from hyperactive/reactive neutrophils and for the unique peptidyl arginine deiminase enzyme of Porphyromonas gingivalis in the pathogenesis of periodontitis, and subsequently a role for periodontitis/the peptidyl arginine deiminase enzyme of P. gingivalis in the causal pathway of autoimmune diseases such as rheumatoid arthritis. We propose that neutrophil extracellular trap and peptidyl arginine deiminase release may propagate tissue-destructive mechanisms rather than provide protection in susceptible individuals and that release of host-derived DNase may play an important role in the digestion and removal of neutrophil extracellular traps within tissues. [ABSTRACT FROM AUTHOR]

Background Diabetes and periodontitis are complex chronic diseases with an established bidirectional relationship. There is long-established evidence that hyperglycaemia in diabetes is associated with adverse periodontal outcomes. However, given the ubiquity of periodontal diseases and the emerging global diabetes epidemic, the complications of which contribute to significant morbidity and premature mortality, it is timely to review the role of periodontitis in diabetes. Aims To report the epidemiological evidence from cross-sectional, prospective and intervention studies for the impact of periodontal disease on diabetes incidence, control and complications and to identify potential underpinning mechanisms. Epidemiology Over the last 20 years, consistent and robust evidence has emerged that severe periodontitis adversely affects glycaemic control in diabetes and glycaemia in non-diabetes subjects. In diabetes patients, there is a direct and dose-dependent relationship between periodontitis severity and diabetes complications. Emerging evidence supports an increased risk for diabetes onset in patients with severe periodontitis. Biological mechanisms Type 2 diabetes is preceded by systemic inflammation, leading to reduced pancreatic β-cell function, apoptosis and insulin resistance. Increasing evidence supports elevated systemic inflammation (acute-phase and oxidative stress biomarkers) resulting from the entry of periodontal organisms and their virulence factors into the circulation, providing biological plausibility for the effects of periodontitis on diabetes. AGE (Advanced Glycation Endproducts)- RAGE (Receptor for AGEs) interactions and oxidative-stress-mediated pathways provide plausible mechanistic links in the diabetes to periodontitis direction. Interventions Randomized controlled trials ( RCTs) consistently demonstrate that mechanical periodontal therapy associates with approximately a 0.4% reduction in HbA1C at 3 months, a clinical impact equivalent to adding a second drug to a pharmacological regime for diabetes. RCTs are needed with larger numbers of subjects and longer term follow-up, and if results are substantiated, adjunctive periodontal therapies subsequently need to be evaluated. There is no current evidence to support adjunctive use of antimicrobials for periodontal management of diabetes patients. Guidelines Given the current evidence, it is timely to provide guidelines for periodontal care in diabetes patients for medical and dental professionals and recommendations for patients/the public. [ABSTRACT FROM AUTHOR]

Abstract: Background: Diabetes and periodontitis are complex chronic diseases with an established bidirectional relationship. There is long‐established evidence that hyperglycaemia in diabetes is associated with adverse periodontal outcomes. However, given the ubiquity of periodontal diseases and the emerging global diabetes epidemic, the complications of which contribute to significant morbidity and premature mortality, it is timely to review the role of periodontitis in diabetes. Aims: To report the epidemiological evidence from cross‐sectional, prospective and intervention studies for the impact of periodontal disease on diabetes incidence, control and complications and to identify potential underpinning mechanisms. Epidemiology: Over the last 20 years, consistent and robust evidence has emerged that severe periodontitis adversely affects glycaemic control in diabetes and glycaemia in non‐diabetes subjects. In diabetes patients, there is a direct and dose‐dependent relationship between periodontitis severity and diabetes complications. Emerging evidence supports an increased risk for diabetes onset in patients with severe periodontitis. Biological mechanisms: Type 2 diabetes is preceded by systemic inflammation, leading to reduced pancreatic b‐cell function, apoptosis and insulin resistance.Increasing evidence supports elevated systemic inflammation (acute‐phase and oxidative stress biomarkers) resulting from the entry of periodontal organisms and their virulence factors into the circulation, providing biological plausibility for the effects of periodontitis on diabetes. AGE (Advanced Glycation Endproducts)–RAGE (Receptor for AGEs) interactions and oxidative‐stress‐mediated pathways provide plausible mechanistic links in the diabetes to periodontitis direction. Interventions: Randomized controlled trials (RCTs) consistently demonstrate that mechanical periodontal therapy associates with approximately a 0.4% reduction in HbA1C at 3 months, a clinical impact equivalent to adding a second drug to a pharmacological regime for diabetes. RCTs are needed with larger numbers of subjects and longer term follow‐up, and if results are substantiated, adjunctive periodontal therapies subsequently need to be evaluated. There is no current evidence to support adjunctive use of antimicrobials for periodontal management of diabetes patients. Guidelines: Given the current evidence, it is timely to provide guidelines for periodontal care in diabetes patients for medical and dental professionals and recommendations for patients/the public. [ABSTRACT FROM AUTHOR]

Aim To determine the effect of cigarette smoke extract, nicotine and cotinine on lucigenin-detectable neutrophil superoxide production. Materials & Methods Neutrophils from periodontally healthy individuals were treated with aqueous smoke extract, nicotine and cotinine, prior to stimulation or at the same time as stimulation with Fusobacterium nucleatum, IgG-opsonized Staphylococcus aureus and Escherichia coli Lipopolysaccharide (LPS). Superoxide generation was determined by lucigenin chemiluminescence. Results Smoke extract induced superoxide release from neutrophils ( p <0.0001) in a dose-dependent manner. By contrast, superoxide generation by neutrophils in response to pathologically relevant stimuli was inhibited by pre-treatment with smoke extract ( p <0.01). This inhibition did not require the continued presence of the extract. A similar reduction in stimulated superoxide production by smoke extract was detected when neutrophils were simultaneously exposed to the extract and stimuli. Nicotine and cotinine (0-10 μg/ml) had no effect on superoxide release from unstimulated or stimulated neutrophils. Conclusions Stable water-soluble components of cigarette smoke directly induce superoxide generation by otherwise unstimulated neutrophils, but reduce superoxide responses of cells to pathologically relevant stimuli. These data suggest potential neutrophil-mediated mechanisms by which smoking may initiate and maintain oxidative stress at periodontally healthy sites and participate in disease progression, by reducing innate immune responses. [ABSTRACT FROM AUTHOR]

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-1β, elastase: all p < 0.03) and peaking at Day 21 (all p < 0.002). Levels of α-1-antitrypsin showed no pattern. Conclusions Levels of substance P, cathepsin G, interleukin-1β and neutrophil elastase act as objective biomarkers of gingival inflammation induction and resolution that typically precede phenotypical changes. [ABSTRACT FROM AUTHOR]

Aim A double-blind randomized controlled trial to determine whether dietary supplementation with fruit/vegetable/berry juice powder concentrates, simultaneously with non-surgical periodontal therapy, improved 2-month treatment outcomes. Methods Volunteers with chronic periodontitis were randomly assigned to one of three groups: fruit/vegetable (FV), fruit/vegetable/berry (FVB) or placebo. Supplements were taken daily during non-surgical debridement and maintenance and outcomes assessed at 2, 5 and 8 months after completion. Primary outcomes were mean probing pocket depth (PPD), clinical attachment gain, % sites bleeding on probing (% BOP) at 2 months. Adherence and plasma β-carotene were determined. Results Sixty-one nutritionally replete (by serum biochemistry) volunteers enrolled and 60 ( n = 20 per arm) completed the 2-month review. Clinical outcomes improved in all groups at 2 months, with additional improvement in PPD versus placebo for FV ( p < 0.03). Gingival crevicular fluid volumes diminished more in supplement groups than placebo (FVB; p < 0.05) at 2 months, but not at later times. The % BOP (5 months) and cumulative plaque scores (8 months) were lowered more in the FV group ( p < 0.05). Conclusions Adjunctive juice powder concentrates appear to improve initial pocket depth reductions in nutritionally replete patients, where plasma micronutrient bioavailability is attainable. Definitive multicentre studies in untreated and treated patients are required to ascertain the clinical significance of such changes. [ABSTRACT FROM AUTHOR]

Periodontitis remains a major public health issue and current management approaches have failed to impact upon the most high-risk proportion of the population and those with the most severe disease. The objective of this session was to assess if and how, current understanding of periodontitis provides the opportunity to develop new preventive and therapeutic strategies. Based on the current understanding of the pathophysiology of periodontal diseases, the Workshop discussed the potential of antimicrobial peptides, probiotics, pro-resolving lipid mediators, and micronutritional approaches. Evidence-based position papers and expert discussions formed the basis of deliberations. Current preventive and treatment approaches are only partially effective, and this appears due to the therapeutic focus remaining primarily upon biofilm management rather than embracing a pivotal role for inflammation as a driver of biofilm composition as well as tissue damage. There is a need to develop new, more effective, and efficient preventive and treatment approaches for gingivitis and periodontitis, which embrace recent advances in understanding of host modulation and inflammation resolution, as well as direct management of the microbiota. [ABSTRACT FROM AUTHOR]

The article offers information about a study which analyzes the impact of nicotine, cotinine, and cigarette smoke extract (CSE) on the neutrophil respiratory burst and their effect on activated nuclear factor-kB (NFkB) pathway in oral epithelium. Based on the results, there was an increase in neutrophil extracellular isoluminol-dependent chemiluminescence caused by smoke extract alone. Researchers realized that smoke extract can affect the ability of neutrophils to produce reactice oxygen species after simulation with the bacteria involved in the study.

Aim: To determine the effect of periodontitis patients' plasma on the neutrophil oxidative burst and the role of albumin, immunoglobulins (Igs) and cytokines. Materials and Methods: Plasma was collected from chronic periodontitis patients (n = 11) and periodontally healthy controls (n = 11) and used with/without depletion of albumin and Ig or antibody neutralization of IL-8, GM-CSF or IFN-α to prime/ stimulate peripheral blood neutrophils, isolated from healthy volunteers. The respiratory burst was measured by lucigenin-dependent chemiluminescence. Plasma cytokine levels were determined by ELISA. Results: Plasmas from patients were significantly more effective in both directly stimulating neutrophil superoxide production and priming for subsequent formyl-metleu-phe (fMLP)-stimulated superoxide production than plasmas from healthy controls (p<0.05). This difference was maintained after depletion of albumin and Ig. Plasma from patients contained higher mean levels of IL-8, GM-CSF and IFN-α. Individual neutralizing antibodies against IL-8, GM-CSF or IFN-α inhibited the direct stimulatory effect of patients' plasma, whereas the ability to prime for fMLP-stimulated superoxide production was only inhibited by neutralization of IFN-α. The stimulating and priming effects of control plasma were unaffected by antibody neutralization. Conclusions: This study demonstrates that plasma cytokines may have a role in inducing the hyperactive (IL-8, GM-CSF, IFN-α) and hyper-reactive (IFN-α) neutrophil phenotype seen in periodontitis patients. [ABSTRACT FROM AUTHOR]

Background: There is an inverse relationship between pocket depth and pocket oxygen tension with deep pockets being associated with anaerobic bacteria. However, little is known about how the host tissues respond to bacteria under differing oxygen tensions within the periodontal pocket. Aim: To investigate the effect of different oxygen tensions upon nuclear factor-kappa B (NF-κB) activation and the inflammatory cytokine response of oral epithelial cells when exposed to nine species of oral bacteria. Materials and Methods: H400 oral epithelial cells were equilibrated at 2%, 10% or 21% oxygen. Cells were stimulated with heat-killed oral bacteria at multiplicity of infection 10:1, Escherichia coli lipopolysaccharide (15 µg/ml) or vehicle control. Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) levels were measured by enzyme-linked immunosorbent assay and NF-κB activation was measured by reporter vector or by immunohistochemical analysis. Results: Tannerella forsythensis, Porphyromonas gingivalis and Prevotella intermedia elicited the greatest epithelial NF-κB activation and cytokine responses. An oxygen-tension-dependent trend in cytokine production was observed with the highest IL-8 and TNF-α production observed at 2% oxygen and lowest at 21% oxygen. Conclusions: These data demonstrate a greater pro-inflammatory host response and cell signalling response to bacteria present in more anaerobic conditions, and hypersensitivity of epithelial cells to pro-inflammatory stimuli at 2% oxygen, which may have implications for disease pathogenesis and/or therapy. [ABSTRACT FROM AUTHOR]

Aim: To quantify reduced and oxidized glutathione (GSH and GSSG) levels in gingival crevicular fluid (GCF) of periodontitis patients pre-therapy ( versus periodontally healthy controls) and ascertain whether successful non-surgical therapy alters glutathione levels. Materials and Methods: Thirty-second GCF samples (6/subject) were collected on Periopaper™ strips from starved, non-smokers ( n=20; mean age 43.6 years) with chronic periodontitis, before and 3 months after non-surgical therapy, and periodontally healthy, age- and gender-matched controls ( n=20). GSH and GSSG levels were determined using reversed-phase high-performance liquid chromatography with fluorescence detection. Results: Lower concentrations of GSH ( p<0.01) and GSSG ( p<0.05) were detected in GCF from patients (pre- and post-therapy) than controls and treatment had no significant effect. Amounts per 30-second sample did not differ between patients and controls. However, the amount of GSSG per 30-second sample decreased in patients after therapy ( p<0.05). Consequently, therapy increased the GSH:GSSG ratio ( p<0.05) in patients compared with the controls ( p=0.8). Conclusion: These data demonstrate high concentrations of GSH within GCF, which are compromised in chronic periodontitis. While therapy does not appear to fully restore GSH concentrations in GCF, it does restore the redox balance (GSH:GSSG ratio), suggesting that the abnormal redox balance arises secondary to oxidative stress resulting from periodontal inflammation. [ABSTRACT FROM AUTHOR]

The article examines the methods of periodontal diagnosis. It notes that periodontitis is a site-specific disease that is unpredictable at patient-level and site-level. It suggests that medical team members should develop a more rapid and objective screening tests to improve diagnosis rates in the dental surgery.

Chronic periodontitis is an inflammatory disease that affects the supporting tissues of the teeth. It is initiated by specific bacteria within the plaque biofilm and progresses due to an abnormal inflammatory-immune response to those bacteria. Periodontitis is the major cause of tooth loss and is also significantly associated with an increased risk of stroke, type-2 diabetes and atheromatous heart disease. Oxidative stress is reported in periodontitis both locally and peripherally (serum), providing potential mechanistic links between periodontitis and systemic inflammatory diseases. It is therefore important to examine serum antioxidant concentrations in periodontal health/disease, both at an individual species and total antioxidant (TAOC) level. To determine whether serum antioxidant concentrations were associated with altered relative risk for periodontitis, we used multiple logistic regression for dual case definitions (both mild and severe disease) of periodontitis in an analysis of 11,480 NHANES III adult participants (>20 y of age). Serum concentrations of vitamin C, bilirubin, and TAOC were inversely associated with periodontitis, the association being stronger in severe disease. Vitamin C and TAOC remained protective in never-smokers. Higher serum antioxidant concentrations were associated with lower odds ratios for severe periodontitis of 0.53 (CI, 0.42,0.68) for vitamin C, 0.65 (0.49,0.93) for bilirubin, and 0.63 (0.47,0.85) for TAOC. In the subpopulation of never-smokers, the protective effect was more pronounced: 0.38 (0.26,0.63, vitamin C) and 0.55 (0.33,0.93, TAOC). Increased serum antioxidant concentrations are associated with a reduced relative risk of periodontitis even in never-smokers. [ABSTRACT FROM AUTHOR]

The article focuses on the role of reactive oxygen and antioxidant defense systems in the periodontal tissue destruction. The study is done to identify the specific therapeutic targets for host-modulating therapies. Research papers on reactive oxygen species, free radicals, antioxidants and others linked with periodontitis were traced from the database. The gist is presented in detail with charts and diagrams.

Drug therapy and hereditary factors are two of the main causes of gingival overgrowth (GO). Both of these forms of GO are associated with increased extracellular matrix production by fibroblasts. Transforming growth factor beta (TGF-β) is an important mediator of wound healing and tissue regeneration, which stimulates fibroblasts to produce extracellular matrix materials. The aim of this immunohistochemical study was to determine whether there is any altered expression of TGF-β isoforms or its receptors in tissue from patients with drug-induced GO (DIGO; n=10) and hereditary gingival fibromatosis (n=10) when compared to non-overgrowth tissue (n-10). Compared to control tissues, significantly more fibroblasts expressed TGF-β in both DIGO and hereditary gingival fibromatosis tissues (P<0.03). Cells expressing TGF-β2 were present at control levels in DIGO but were significantly reduced in hereditary gingival fibromatosis (P<0.02). By contrast, the number of TGF-β3-positive cells was the same in overgrowth tissues and controls. However, because of differences in total fibroblast densities between groups, there was a proportional increase in TGF-β3 as well as TGF-β1 expressing cells within both overgrowth populations (P<0.0001). Furthermore, representation of the TGF-β2-positive phenotype was reduced in hereditary gingival fibromatosis (P<0.01) but increased in DIGO (P<0.005) compared to controls. Absorbance measurements of the positive cell populations showed that the level of expression was significantly higher for TGF-β1 in hereditary gingival fibromatosis (P<0.002) and significantly lower for TGF-β3 in DIGO (P<0.03). No significant differences in the numbers of TGF-βRl- or RU-positive cells were detected between overgrowth tissues and controls. However, there were increases in the proportion of receptor-positive cells in the total cell population analyzed in overgrowth tissues (P<0.0001). These results indicate qualitative and quantitative differences in TGF-β isoform and receptor expression by fibroblasts in gingival overgrowth that may contribute to disease pathogenesis. [ABSTRACT FROM AUTHOR]

AbstractBackground, aims: Early onset periodontal diseases (EOP) are a group of inflammatory disorders characterised by a rapid rate of periodontal tissue destruction, in young individuals who are otherwise healthy. There is now substantial evidence to suggest that genetic factors play a rôle in the pathogenesis of EOP but the precise nature of these factors remains unclear. Polymorphisms in cytokine genes which may underpin inter-individual differences in cytokine synthesis and secretion have been associated with other diseases which have an inflammatory pathogenesis, including chronic adult periodontal disease (CAPD). Method: We therefore investigated the frequency of polymorphisms in the genes encoding interleukin-1β (IL-1β) and its receptor antagonist (IL-1RA) in 70 EOP patients, including a subgroup of 21 localised EOP (L-EOP) patients and 72 periodontally healthy controls. All subjects were of Caucasian heritage and systemically healthy. A single nucleotide polymorphism (SNP) in exon 5 of the IL-1β gene (IL-1β+3953) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis. Results: The frequency of IL-1β genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL-1β+3953 SNP was found to be significantly increased in EOP patients (χ2 test, p=0.025). Upon stratification for smoking status a significant difference was found in the IL-1β genotype distribution between EOP smokers compared to control smokers (F-exact test, p=0.02), but not between EOP non-smokers and control non-smokers. The IL-1β 1/1 genotype occurred at a higher frequency in EOP smokers (odds ratio=4.9) compared to control smokers. A variable number tandem repeat polymorphism (VNTR) in intron 2 of the IL-1RA gene was analysed by amplifying the polymorphic region using PCR and fragment size analysis by gel electrophoresis. There was no evidence for an association of an IL-1RA genotype with EOP. However the combination of IL-1β allele 1 and IL-1RA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p=0.01). Conclusions: These findings suggest that an IL-1β genotype in combination with smoking, and a combined IL-1β and IL-1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP. [ABSTRACT FROM AUTHOR]

Myelodysplasia syndrome (MDS) presenting as spontaneous gingival hemorrhage is described. Gingival hemorrhage is recognized as a symptom of MDS, a rare group of potentially fatal hematological disorders, but it has not previously been documented as a presenting sign. The diagnostic pitfalls are discussed with the case, and the need for careful interpretation of laboratory findings in conjunction with clinical signs is emphasized. Finally, the MDSs are defined, classified and discussed with respect to their relevance to the clinical periodontist, from a diagnostic, therapeutic, and management standpoint. [ABSTRACT FROM AUTHOR]