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Background: Vascular endothelial growth factor (VEGF) is a master regulator and is required for the effective coupling of angiogenesis and osteogenesis supporting both skeletal development and postnatal bone repair. A direct role for VEGF in intramembranous-derived osteoblast growth and differentiation is not clear. We investigated the expression of primary alveolar osteoblast VEGF receptors and the subsequent effects on mineralization and nodule formation in vitro following VEGFR inhibition.Methods: Primary human alveolar osteoblasts (HAOBs) were cultured in the presence of VEGF receptor inhibitors, exogenous VEGF or the bisphosphonate, zoledronic acid. VEGF, VEGFR1 and VEGFR2 mRNA expression and nodule formation following 21 days of culture. VEGFR1 protein expression was examined using immunofluorescence after 48 h.Results: The HAOBs expressed high levels of VEGF and VEGFR1 protein but VEGFR2 was not detected. The VEGFR1/2 inhibitors, ZM306416 and KRN633, lead to a dose-dependent decrease in mineralization. Treatment with zoledronic acid showed no difference in HAOB VEGF receptor expression.Conclusion: VEGF/VEGFR1 pathway appears to be important for intramembranous-derived osteoblast differentiation and maturation in vitro. [ABSTRACT FROM AUTHOR]

Background and Objective: The salivary transcriptome may present as a readily available and non‐invasive source of potential biomarkers. The development of chronic periodontitis is determined by individual patient susceptibility; hence, the aim of this study was to determine the potential of the salivary transcriptome as a biomarker of disease susceptibility using chronic periodontitis as an example. Material and Methods: Using an Oragene® RNA kit, the total RNA was purified from the saliva of 10 patients with chronic periodontitis and 10 patients without chronic periodontitis. The quantity and quality of the total RNA was determined, and a measure of gene expression via cDNA was undertaken using the Affymetrix microarray system. The microarray profiling result was further validated by real‐time quantitative polymerase chain reaction. Results: Spectrophotometric analysis showed the total RNA purified from each participant ranged from 0.92 μg/500 μL to 62.85 μg/500 μL. There was great variability in the quantity of total RNA obtained from the 2 groups in the study with a mean of 10.21 ± 12.71 μg/500 μL for the periodontitis group and 15.97 ± 23.47 μg/500 μL for the control group. Further the RNA purity (based on the A260/A280 ratio) for the majority of participants (9 periodontitis and 6 controls) were within the acceptable limits for downstream analysis (2.0 ± 0.1). The study samples, showed 2 distinct bands at 23S (3800 bp) and 16S (1500 bp) characteristic of bacterial rRNA. Preliminary microarray analysis was performed for 4 samples (P2, P6, H5 and H9). The percentage of genes present in each of the 4 samples was not consistent with about 1.8%‐18.7% of genes being detected. Quantitative real‐time polymerase chain reaction confirmed that the total RNA purified from each sample was mainly bacterial RNA (Uni 16S) with minimal human mRNA. Conclusion: This study showed that minimal amounts of human RNA were able to be isolated from the saliva of patients with periodontitis as well as controls. Further work is required to enhance the extraction process of human mRNA from saliva if the salivary transcriptome is to be used in determining individual patient susceptibility. [ABSTRACT FROM AUTHOR]

Aims: This study investigated the association between the prevalence of oral health problems (caries, gingivitis, mucosal pigmentation and enamel defects in one to 5 year-old children exposed and not exposed to environmental tobacco smoke before and/or after birth. Exposure to environmental tobacco smoke (ETS) in childhood may have significant health effects. Methods: A structured questionnaire was used to collect data on a child's current and previous illnesses, oral health behaviours, dietary habits, parental smoking behaviours and parents' dental history. The intraoral examination recorded dental caries (dmfs), enamel defects, gingival health, melanin pigmentation and soft tissue health. Stimulated saliva was collected. Total sIgA levels were quantified using indirect competitive ELISA with a SalimetricsTM kit. Results: The 44 children (aged 15-69 months) recruited were divided into two groups: ETS and non-ETS (control). There were 22 children in each: 16 who were exposed to ETS during and after gestation were identified as the ETSB subgroup. Participants exposed to ETS were more likely to have had upper respiratory tract and middle ear infections during the neonatal period and had higher mean dmft, mean dmfs, mean percent of surfaces with demarcated opacities and mean GI than the non-ETS participants. The children exposed to ETS before and after birth had the highest occurrence of enamel opacities showed a higher risk for dental caries even though more children in this group used the recommended fluoride toothpaste (1000 ppm fluoride). Mothers who smoked either never breastfed their children or breastfed their children for less than the recommended period of 6 months. Children exposed to ETS were shown to have higher mean total sIgA (μg/ml) than the children in the control group. Conclusions: Associations between ETS exposure before and after gestation and oral health, including salivary changes in young children were shown in the present study. Dental health professionals should include a question about household smoking in children's dental histories, which would allow opportunities to discuss the impact of smoking on child oral health. Longitudinal oral health studies should include a history of maternal smoking during pregnancy and afterwards. [ABSTRACT FROM AUTHOR]

Several systematic reviews with meta-analyses on the effectiveness of periodontal treatment to improve glycaemic control have been published. So far no overview of these systematic reviews has been performed. The main objective of this report was to assess critically these systematic reviews to provide the reader with a high-level synthesis of research evidence. MEDLINE (via PubMed) and EMBASE databases were searched independently and in duplicate to identify systematic reviews with meta-analyses of clinical studies that assessed the relationship between diabetes mellitus and periodontitis. The last database search was performed on 10 March 2015. The reference lists of included systematic reviews were also scrutinized for further publications. The methodological quality of the included systematic reviews was assessed independently with two validated checklists ( AMSTAR and OQAQ) by two authors. Disagreements in the assessment were resolved by consensus. A total of 226 potential publications were initially retrieved. Eleven systematic reviews with meta-analyses were finally included. Glycosylated haemoglobin A1c (HbA1c) was the most commonly used clinical endpoint. Meta-analytic estimates from systematic reviews generated an average reduction of 0.46% (median 0.40%) of HbA1c in patients with diabetes mellitus who received periodontal treatment. These meta-analyses had, nevertheless, methodological limitations such as inclusion of trials with different types of risk of bias that hinder more robust conclusions. A recent meta-analysis that included recently published large randomized controlled trials did not show significant change in the level of HbA1c at the 6 mo follow-up. The AMSTAR checklist generated results that were more conservative than OQAQ. Findings from this overview do not support the information that periodontal treatment may improve glycaemic control. Methodological issues described in this overview may guide further research on this topic. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aimed to investigate treatment protocols and opinions towards direct pulp capping (DPC) amongst New Zealand (NZ) general dental practitioners (GDP) through a Practice Based Research Network (PBRN) study. DESIGN: Mixed-methods approach using qualitative thematic and quantitative analysis. METHODS: An on-line survey containing Likert scale items and open-ended questions was distributed to GDPs on the Dental Council of New Zealand (DCNZ) register (2012) to collect information on practitioner demographics, treatment protocols, continuing professional development (CPD) and philosophies towards DPC. RESULTs: Two hundred and ten GDPs from North and South Islands providing care in main centres and rural areas engaged with the PBRN and participated in the study. Almost all performed DPC treatment although it was not a common procedure. DPC was perceived as 'successful' or 'very successful' by 95% of respondents, mostly for cases of reversible pulpitis. Most provided DPC for patients of all ages but younger patients were perceived to have the best clinical outcomes. Calcium hydroxide and MTA were the most commonly used materials for DPC. MTA was believed to have the best outcome but cost and handling properties were barriers to its use. The majority of respondents had participated in CPD related to vital pulp therapy and regarded this treatment as conservative and providing time and financial benefits compared with more invasive treatment. Clinicians' timeframes for assessing healing were variable, and combined clinical and radiographic findings were considered most useful. CONCLUSION: New Zealand dentists perceive DPC as a successful and conservative treatment in selected cases. The findings have provided insights into engagement of NZ dentists in using research to inform everyday clinical practice through a PBRN study. [ABSTRACT FROM AUTHOR]

Background Systemic antimicrobials have been used as an adjunctive therapy for the treatment of periodontitis. Nevertheless, it is unclear whether the use of antimicrobials may improve tooth survival in patients with periodontitis. The main objective of this overview of systematic reviews (SRs) with meta-analyses was to assess the evidence supporting systemic antimicrobials for improving tooth survival in patients suffering from periodontitis. Information on adverse events was also extracted from SRs.Methods PubMed and EMBASE databases were searched independently (up to 1st August 2013) to identify SRs with meta-analyses on the use of systemic antimicrobials as an adjunctive treatment to scaling and root planing (SRP) in the treatment of periodontitis. Tooth survival and adverse events were assessed. Clinical effect was also assessed based on endpoints including clinical attachment level and probing depth. The methodological quality of the SRs was assessed by two authors using two checklists (AMSTAR and OQAQ).Results No data on tooth survival after treatment with SRP and antimicrobials were found. Nine SRs were included in this overview. Three SRs showed statistically significant outcome improvement with the use of antimicrobials, although the clinical relevance may be questionable. One SR showed better results based on surrogate endpoints; however, short-term adverse events were more pronounced with the use of antimicrobials. The reporting of long-term data on clinical effects, adverse events and bacterial resistance is scarce. The SRs were of heterogeneous quality.Conclusions Evidence of the efficacy of systemic antimicrobials on improving tooth survival is lacking. Further research focused on tooth survival and adverse events should be performed to provide more robust evidence of the benefits of using systemic antimicrobials for treating periodontitis. [ABSTRACT FROM AUTHOR]

Treatment planning in periodontics, as with any disease, must be based on an understanding of the aetiology and pathogenesis of the disease. In this context, it has slowly become recognized over the past three decades that while plaque is the cause of the disease, it is the innate susceptibility of the host that determines the ultimate outcome of the disease process. Innate susceptibility, in turn, is determined by the nature of the immune response to the specific periodontopathic complexes comprising the plaque biofilm. The aim of this review was to examine current understanding of the immunopathogenesis of chronic periodontitis with respect to its possible clinical implications in terms of treatment planning and risk assessment. Numerous studies have demonstrated that the periodontitis lesion itself involves predominantly B cells and plasma cells, while the gingivitis lesion is primarily a T cell mediated response. This led to the concept over 30 years ago that the development of periodontitis involves a switch from a T cell lesion to one involving large numbers of B cells and plasma cells. It is also well recognized that control of this shift is mediated by a balance between the so-called Th1 and Th2 subsets of T cells, with chronic periodontitis being mediated by Th2 cells. More recently, T regulatory (Treg) and Th17 cells have been demonstrated in periodontal tissues, raising the possibility that these cells are also important in the immunoregulation of periodontal disease. The clinical implications of these observations can be seen in the fact that identification of Th1/Th2 and Treg/Th17 cytokine gene expression in the peripheral blood and salivary transcriptomes is now being trialled as a possible marker of disease susceptibility. If this proves to be the case, a chairside salivary diagnostic could be developed within the next five to 10 years. [ABSTRACT FROM AUTHOR]

The relationship between poor oral health and systemic diseases has been increasingly recognized over the past two decades. Indeed, the clichés “You cannot have good general health without good oral health”, “The mouth is part of the body” and “Floss or die”, are gaining an increasing momentum. A large number of epidemiological studies have now linked poor oral health with cardiovascular diseases, poor glycaemic control in diabetics, low birthweight preterm babies and a variety of other conditions. The majority have shown an association, although not always strong. As a result, a number of meta-analyses have been conducted and have confirmed the associations and at the same time cautioned that further studies are required, particularly with regard to the effect of periodontal treatment in reducing risk. A number of biologically plausible mechanisms have been put forward to explain the association and there is accumulating evidence in support of them, although at this stage, insufficient to establish causality. Nevertheless, the relationship between poor oral health and systemic diseases has become a significant issue, such that adult oral health can no longer be ignored in overall health strategies. This review provides an update on current understanding of the contribution of poor oral health to systemic diseases, the possible mechanisms involved and the relevance of this for general dental practitioners. [ABSTRACT FROM AUTHOR]

Dental caries and periodontal disease are the most common oral conditions experienced by adults today. The treatment of these diseases by the dental team can only be performed when patients attend dental practices. There is recognition that the preventive measures patients perform at home between dental visits is of vital importance in the control of these diseases. Water fluoridation and fluoridated toothpastes have made enormous progress into the prevention of dental caries worldwide. However, prevention of periodontal disease is yet to enjoy the same success. A number of toothpastes have been developed for the prevention and control of periodontal disease. One such toothpaste - containing triclosan/copolymer - has been thoroughly researched. The literature pertaining to the efficacy, mode of action and safety of triclosan/copolymer toothpaste has been reviewed. A MEDLINE search identified 198 articles dated from 1989 to 2008. The findings of this body of research are discussed and conclusions regarding the efficacy of triclosan/copolymer toothpaste in the home-care management of periodontal disease are presented. [ABSTRACT FROM AUTHOR]

Background: Tannerella forsythia (previously T. forsythensis) in subgingival plaque has been recognized as a defined periodontal pathogen, but its mere presence may be insufficient for disease initiation and/or progression. The organism may produce a cysteine protease, encoded by the prtH gene, which may play a role in the transition from commensal organism to opportunistic pathogen. This study aimed to relate changes in the level of T. forsythia prtH genotype over a 5-year period to a concomitant loss of attachment. Methods: Real-time polymerase chain reaction was used to quantify the level of the prtH gene in plaque samples from subjects with and without attachment loss (≥2 mm in at least two sites) over a 5-year period. Clinical measures and subgingival plaque samples were obtained at yearly intervals. Results: Baseline levels of the prtH genotype were significantly lower in the subjects without loss of attachment compared to those who lost attachment over 1, 2, 4, or 5 years. In the subjects with loss of attachment, the higher prtH levels at baseline were not maintained until the end of the observation period Conclusion: Higher levels of the prtH genotype were associated significantly with future attachment loss. [ABSTRACT FROM AUTHOR]

Background, aim: The present study describes (i) the natural distribution of the three putative periodontopathogens Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in an Australian population and (ii) the relationship between these organisms, pocket depths and supragingival plaque scores. Methods: Subgingival plaque was collected from the shallowest and deepest probing site in each sextant of the dentition. In total, 6030 subgingival plaque samples were collected from 504 subjects. An ELISA utilising pathogen-specific monoclonal antibodies was used to quantitate bacterial numbers. Results:: A. actinomycetemcomitans was the most frequently detected organism (22.8% of subjects) followed by P. gingivalis and P. intermedia (14.7% and 9.5% of subjects respectively). The majority of infected subjects (83%) were colonised by a single species of organism. A. actinomycetemcomitans presence was overrepresented in the youngest age group but under-represented in the older age groups. Conversely, P. gingivalis and P. intermedia presence was under-represented in the youngest age group but over-represented in the older age groups. Differing trends in the distribution of these bacteria were observed between subjects depending upon the site of the infection or whether a single or mixed infection was present; however, these differences did not reach significance. Bacterial presence was strongly associated with pocket depth for both A. actinomycetemcomitans and P. gingivalis. For A. actinomycetemcomitans, the odds of a site containing this bacterium decrease with deeper pockets. In contrast, for P. gingivalis the odds of a site being positive are almost six times greater for pockets >3 mm than for pockets ≥3 mm. These odds increase further to 15.3 for pockets deeper than 5 mm. The odds of a site being P. intermedia positive were marginally greater (1.16) for pockets deeper than 3 mm. Conclusions: This cross-sectional study in a... [ABSTRACT FROM AUTHOR]

Background: Patients receiving an HLA-matched bone marrow transplant (BMT) from a relative or unrelated donor undergo a permanent alteration of their immune system, followed by a prolonged period of immunodeficiency. This study aimed to examine alterations in the periodontal status of patients over 6 months post-bone marrow transplantation. Methods: Thirty-seven patients scheduled for bone marrow transplantation participated in this study. One calibrated examiner carried out periodontal examinations (clinical and radiographic) immediately prior to and at 3 and 6 months after transplantation. All patients followed an intense oral care program. Subgingival plaque samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Prevotella intermedia. Data were subjected to statistical analyses to determine the relationships between the frequency distribution of the radiographic and clinical variables over time. Results: Gains in clinical attachment level (CAL) of > or =2 mm at 4 or more sites from baseline to 6 months post-BMT were noted in 9/16 patients (56%), while 6/16 (38%) patients experienced a loss of CAL > or =2 mm at 4 or more sites in the same period. At a site level, 4.8% of sites exhibited a gain in CAL > or =2 mm between baseline and 3 months post-BMT while 2.3% of sites showed a loss of CAL > or =2 mm in the same period. From baseline to 6 months, a gain in CAL of > or =2 mm was recorded at 3.1% of sites, and 2.4% of sites experienced a loss of > or =2 mm. A significant improvement in the gingival index occurred between all sequential time periods when assessed at a site level. At a patient level, 11/18 (61%) patients showed a significant change in gingival index between baseline and 3 months and 10/16 (63%) between baseline and 6 months. There was no significant relationship between clinical changes and the prevalence of the periodontal pathogens at the various time periods. Conclusions: An improvement in periodontal health was recorded between baseline and 6 months post-transplantation. Most of the improvement in periodontal status was noted in the first 3 months after BMT, with a slight decline in periodontal health between 3 and 6 months post-transplant. No significant alteration was noted in the prevalence of periodontal pathogens during the study period. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the jaws is recognised as a serious complication for patients receiving bisphosphonates. The anti-angiogenic effects of bisphosphonates have been implicated in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this study was to determine the effects of zoledronic acid on cultured human gingival fibroblasts in relation to the modulation of genes associated with angiogenic regulation., Methods: Primary cultures of fibroblasts were developed from gingival tissues excised during crown-lengthening surgery from three patients. Cells were cultured with and without 30μM zoledronic acid for 6, 12 and 24h and cellular proliferation and migration investigated using CellTiter-Blue and scratch wound assays, respectively. Gene expression was determined using semi-quantitative PCR array technology that allowed the analysis of 84 pathway-focused genes known to be important in the regulation of angiogenesis., Results: Zoledronic acid increased the proliferation of the gingival fibroblasts in a dose dependent manner with 12 and 24h of exposure. Scratch wounding of the human gingival fibroblasts and treatment with increasing doses and time exposure to zoledronic acid (ZA) inhibited their migration. Statistically significant increases in gene expression were found for RHOB, VEGFA, CD55 and BMP2 (p≤0.05) in response to 30μM zoledronic acid. CCL2 and IL6 genes were significantly downregulated (p≤0.05)., Conclusions: The regulation of the prenylated protein RHOB in this study was consistent with the known effects of zoledronic acid on the mevalonate pathway. The down regulation of CCL2 and IL6 and the upregulation of CD55 may be associated with suppression of inflammation. An increase in VEGFA and BMP2 gene expression suggests that fibroblasts respond to zoledronic acid by producing a proangiogenic environment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Previous studies have demonstrated variable effects on systemic inflammatory and immune responses following improved periodontal health. This study examined changes in serum levels of the inflammatory mediators IL-1β, IL-6, TNF-α and sICAM-1, and antibodies to Porphyromonas gingivalis, human heat shock protein (hHSP) 60 and P. gingivalis GroEL following improvement in periodontal health in high cardiovascular (CV) risk and low CV-risk patients., Methods: Patients retrospectively selected from a longitudinal study, had undergone yearly periodontal examinations and peripheral blood collections. They had demonstrated a quantifiable improvement in periodontal health (>60% reduction in number of sites with probing depth ≥ 4 mm from the baseline visit) and could be classified as either high CV-risk (≥ 6 classical risk factors, n = 13) or low CV-risk (≤ 1 classical risk factor, n = 14). Serum levels of the cytokines and antibodies were measured using ELISA., Results: For sICAM-1 and anti-P. gingivalis GroEL and anti-hHSP60 antibodies, most patients recorded decreased levels. Reductions in serum sICAM-1 levels were more notable in low CV-risk patients (p = 0.006); and reductions in levels of anti-P. gingivalis GroEL and anti-hHSP60 antibodies (p = 0.001 and 0.009 respectively) were more notable in high CV-risk patients., Conclusions: This study found that subsequent to improved periodontal health, the anti-HSP (HSP60 and GroEL) antibody response was reduced, particularly for high CV-risk patients. sICAM-1 levels were also lowered, more so for low CV-risk patients., (© 2011 Australian Dental Association.)

Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient's cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.

Background: Cross-sectional studies have demonstrated that a specific polymorphism (allele 2 of both IL-1A +4845 and IL-1B +3954) in the IL-1 gene cluster has been associated with an increased susceptibility to severe periodontal disease and to an increased bleeding tendency during periodontal maintenance. The aim of the present study was to investigate the relationship between IL-1 genotype and periodontitis in a prospective longitudinal study in an adult population of essentially European heritage., Methods: From an ongoing study of the Oral Care Research Programme of The University of Queensland, 295 subjects consented to genotyping for IL-1 allele 2 polymorphisms. Probing depths and relative attachment levels were recorded at baseline, 6, 12, 24, 36, 48 and 60 months using the Florida probe. Periodontitis progression at a given site was defined as attachment loss > or =2 mm at any observation period during the 5 years of the study and the extent of disease progression determined by the number of sites showing attachment loss. Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia were detected using ELISA., Results: 38.9% of the subjects were positive for the composite IL-1 genotype. A relationship between the IL-1 positive genotype and increased mean probing pocket depth in non-smokers greater than 50 years of age was found. Further, IL-1 genotype positive smokers and genotype positive subjects with P. gingivalis in their plaque had an increase in the number of probing depths > or =3.5 mm. There was a consistent trend for IL-1 genotype positive subjects to experience attachment loss when compared with IL-1 genotype negative subjects., Conclusion: The results of this study have shown an interaction of the IL-1 positive genotype with age, smoking and P. gingivalis which suggests that IL-1 genotype is a contributory but non-essential risk factor for periodontal disease progression in this population.

Background: It is generally accepted that periodontal disease progresses by a series of bursts that are interspersed by periods of stability or even gain of attachment. In order to analyze longitudinal data on a patient's disease experience, it is necessary to use models which accommodate serial dependence. Ante-dependence between the results of a series of periodontal examinations over time can be modeled using a Markov chain. This model describes temporal changes in patients' levels of disease in terms of transition probabilities, which allow for both regression and progression of the disease. The aim of the present study was to demonstrate the use of a Markov chain model to analyze data from a longitudinal study investigating the progression of periodontal disease in an adult population., Methods: The study population consisted of 504 volunteers; however, only 456 were included in the analysis because the remaining 48 subjects did not give consecutive data. Subjects were examined at baseline, 6 months, and 1, 2, and 3 years. Probing depths (PD) were recorded using an automated probe. Disease was defined as four or more sites with PD > or = 4 mm. Markov chain modeling was used to determine the effect of age, gender, and smoking on the natural progression and regression (healing) of periodontal disease., Results: Smoking and increasing age had no effect on the progression of disease in this population, but did have a significant effect (P values < or = 0.05) in reducing the regression of disease; i.e., their effect on disease appears to be inhibition of the natural healing process. Gender had no significant effects., Conclusions: These results demonstrate how ante-dependence modeling of longitudinal data can reveal effects that may not be immediately apparent from the data, with smoking and increasing age being seen to inhibit the healing process rather than promote disease progression.