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Background Localized aggressive periodontitis (LAgP) occurs in 2% of African-American adolescents but only 0.15% of white adolescents. First molars and incisors are affected by rapid onset and progression. Methods This nonsystematic critical review evaluated published data for LAgP and chronic periodontitis (CP), focusing on potential differences in epidemiology, microbiology, immunology, genetics, and response to therapy. Results LAgP differs from CP by localization to incisors and first molars, early onset and rapid progression in adolescents and young adults, and a 10-fold higher prevalence in populations of African or Middle Eastern origin, often with strong familial aggregation. The bacterium Aggregatibacter actinomycetemcomitans and hyperresponsive neutrophils are frequently observed. Antibiotic and nonsurgical therapies are highly effective. Conclusions LAgP differs in many ways from the far more common CP that affects older adults. The substantial evidence of dissimilarities summarized in this review strongly supports the classification of LAgP as a distinct form of periodontitis. Practical Implications Classifying LAgP as a distinct subcategory of periodontitis will encourage future research and does not conflict with the newly proposed “staging and grading” system. The silent onset and rapid progression of LAgP make early diagnosis and frequent follow-up with patients essential for effective treatment.

Background In this field trial, the authors assess the feasibility of screening for diabetes and prediabetes in dental practices and in a community health center. Methods Dental patients 45 years and older who were not aware of their diabetic status underwent evaluation for diabetes risk with an American Diabetes Association Diabetes Risk Test and with hemoglobin (Hb) A 1c measurement. Participants with an HbA 1c level of 5.7 percent or greater were referred to their physicians for diagnosis. Results Of the 1,022 patients screened, 416 (40.7 percent) had an HbA 1c blood level of 5.7 percent or greater and were referred for diagnosis. The HbA 1c and the American Diabetes Association Diabetes Risk Test were correlated ( P Conclusions The study results show that screening for prediabetes and diabetes is feasible in a dental office, with acceptance by the dentist and dental office staff members, patients' physicians and patients. Patients from the community health center demonstrated good compliance with referrals to physicians; however, compliance was poor among those in the private dental offices. Practical Implications Screening for diabetes and prediabetes in the dental office may provide an important benefit to patients and encourage interprofessional collaboration to achieve a chronic care model in which health care professionals work together to care for a panel of patients.

Background Smoking is associated with tooth loss. However, smoking's relationship to the specific reason for tooth loss in postmenopausal women is unknown. Methods Postmenopausal women (n = 1,106) who joined a Women's Health Initiative ancillary study (The Buffalo OsteoPerio Study) underwent oral examinations for assessment of the number of missing teeth, and they reported the reasons for tooth loss. The authors obtained information about smoking status via a self-administered questionnaire. The authors calculated odds ratios (ORs) and 95 percent confidence intervals (CIs) by means of logistic regression to assess smoking's association with overall tooth loss, as well as with tooth loss due to periodontal disease (PD) and with tooth loss due to caries. Results After adjusting for age, education, income, body mass index, history of diabetes diagnosis, calcium supplement use and dental visit frequency, the authors found that heavy smokers (≥ 26 pack-years) were significantly more likely to report having experienced tooth loss compared with never smokers (OR = 1.82; 95 percent CI, 1.10-3.00). Smoking status, packs smoked per day, years of smoking, pack-years and years since quitting smoking were significantly associated with tooth loss due to PD. For pack-years, the association for heavy smokers compared with that for never smokers was OR=6.83 (95 percent CI, 3.40 –13.72). The study results showed no significant associations between smoking and tooth loss due to caries. Conclusions and Practical Implications Smoking may be a major factor in tooth loss due to PD. However, smoking appears to be a less important factor in tooth loss due to caries. Further study is needed to explore the etiologies by which smoking is associated with different types of tooth loss. Dentists should counsel their patients about the impact of smoking on oral health, including the risk of experiencing tooth loss due to PD.

Background This report presents weighted average estimates of the prevalence of periodontitis in the adult US population during the 6 years 2009-2014 and highlights key findings of a national periodontitis surveillance project. Methods Estimates were derived for dentate adults 30 years or older from the civilian noninstitutionalized population whose periodontitis status was assessed by means of a full-mouth periodontal examination at 6 sites per tooth on all non–third molar teeth. Results are reported according to a standard format by applying the Centers for Disease Control and Prevention/American Academy of Periodontology periodontitis case definitions for surveillance, as well as various thresholds of clinical attachment loss and periodontal probing depth. Results An estimated 42% of dentate US adults 30 years or older had periodontitis, with 7.8% having severe periodontitis. Overall, 3.3% of all periodontally probed sites (9.1% of all teeth) had periodontal probing depth of 4 millimeters or greater, and 19.0% of sites (37.1% of teeth) had clinical attachment loss of 3 mm or greater. Severe periodontitis was most prevalent among adults 65 years or older, Mexican Americans, non-Hispanic blacks, and smokers. Conclusions This nationally representative study shows that periodontitis is a highly prevalent oral disease among US adults. Practical Implications Dental practitioners should be aware of the high prevalence of periodontitis in US adults and may provide preventive care and counselling for periodontitis. General dentists who encounter patients with periodontitis may refer these patients to see a periodontist for specialty care.

Acknowledgment: This Editors' Consensus is supported by an educational grant from Colgate-Palmolive, Inc., New York, New York, and is based on a meeting of the authors held in Boston, Massachusetts, on January 9, 2009.Disclosure: Dr. Friedewald has received honoraria for speaking from Novartis, East Hanover, New Jersey. Dr. Kornman is a full-time employee and shareholder of Interleukin Genetics, Waltham, Massachusetts, which owns patents on genetic biomarkers for chronic inflammatory diseases. Dr. Genco is a consultant to Merck, Whitehouse Station, New Jersey. Dr. Ridker has received research support from AstraZeneca, Wilmington, Delaware; Novartis; Pfizer, New York, New York; Roche, Nutley, New Jersey; Sanofi-Aventis, Bridgewater, New Jersey; and Abbott Laboratories, Abbott Park, Illinois. Dr. Ridker has received non-financial research support from Amgen, Thousand Oaks, California. Dr. Ridker is a co-inventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarker...

The guest editor of this special supplement to JADA provides an overview of salivary diagnostic testing and introduces the articles presented in this supplement to The Journal of the American Dental Association.

Background Many early epidemiologic studies reported an association between periodontal disease and cardiovascular disease. However, other studies found no association or nonsignificant trends. This report summarizes the evidence from epidemiologic studies and studies that focused on potential contributing mechanisms to provide a more complete picture of the association between periodontal and heart disease. Types of Studies Reviewed The authors summarize the longitudinal studies reported to date, because they represent the highest level of evidence available regarding the connection between periodontal disease and heart disease. The authors also review many of the case-control and cross-sectional studies published, as well as findings from clinical, animal and basic laboratory studies. Results The evidence suggests a moderate association—but not a causal relationship—between periodontal disease and heart disease. Results of some case-control studies indicate that subgingival periodontal pathogenic infection may be associated with myocardial infarction. Basic laboratory studies point to the biological plausibility of this association, since oral bacteria have been found in carotid atheromas and some oral bacteria may be associated with platelet aggregation, an event important for thrombosis. Animal studies have shown that atheroma formation can be enhanced by exposure to periodontal pathogens. Conclusions The accumulation of epidemiologic, in vitro, clinical and animal evidence suggests that periodontal infection may be a contributing risk factor for heart disease. However, legitimate concerns have arisen about the nature of this relationship. These are early investigations. Since even a moderate risk contributed by periodontal disease to heart disease could contribute to significant morbidity and mortality, it is imperative that further studies be conducted to evaluate this relationship. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in heart disease resulting from the prevention or treatment of periodontal disease.

ObjectiveBile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD.DesignSerum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls.ResultsSerum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na+-taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats.ConclusionsThe serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome.

Background The authors previously suggested that an adjunctive, controlled-release chlorhexidine, or CHX, chip may reduce periodontal surgical needs at little additional cost. This article presents an economic analysis of the CHX chip in general dental practice. Methods In a one-year prospective clinical trial, 484 chronic periodontitis patients in 52 general practices across the United States were treated with either scaling and root planing, or SRP, plus any therapy prescribed by treating, unblinded dentists; or SRP plus other therapy as above but including the CHX chip. Economic data were collected from bills, case report forms and 12-month treatment recommendations from blinded periodontist evaluators. Results Total dental charges were higher for SRP + CHX chip patients vs. SRP patients when CHX chip costs were included ( P = .027) but lower when CHX chip costs were excluded ( P = .012). About one-half of the CHX chip acquisition cost was offset by savings in other charges. SRP + CHX chip patients were about 50 percent less likely to undergo surgical procedures than were SRP patients ( P = .021). At the end of the trial, periodontist evaluators recommended similar additional procedures for both groups: SRP, about 46 percent; maintenance, about 37 percent; surgery, 56 percent for SRP alone and 63 percent for SRP + CHX chip. Conclusions Adjunctive CHX chip use for general-practice patients with periodontitis increased costs but reduced surgeries over one year. At study's end, periodontists recommended similar additional surgical treatment for both groups. Clinical Implications In general practice, routine use of the CHX chip suggests that costs will be partially offset by reduced surgery over at least one year.

Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, has been implicated in the onset and development of periodontitis. The P. gingivalis fimbriae which mediate bacterial adherence to host oral sites and induce host inflammatory responses have been suggested as a potential antigen candidate. for vaccine development. This study was undertaken to generate Streptococcus gordonii vectors expressing the major subunit protein (FimA) of P. gingivalis fimbriae for testing as a potential live vaccine against periodontitis. We report here the expression of the C-terminal saliva-binding epitopes of P. gingivalis FimA on the surface of S. gordonii and demonstrate that domains containing free cysteine residues are poorly expressed on the surface of S. gordonii.

Please cite this article as: Borgnakke WS, Madianos PN, Chapple ILC, Murakami S, Genco RJ, Papapanou PN, Armitage G, Preshaw PM, Bartold PM, Rahman Au, D’Aiuto F, Sanz M, Eke PI, Slots J, Giannobile WV, Tonetti MS, Kornman KS, Van Dyke TE, Lang NP, WITHDRAWN: The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental flaws, The Journal of Evidence-Based Dental Practice (2014), doi: 10.1016/j.jebdp.2014.01.011.

P. gingivalis fimbriae play an important role in attachment of bacteria to various salivary components as well as to host cells and matrix proteins including fibronectin. In the present study, we investigated the binding domain of P. gingivalis fimbriae to fibronectin using synthetic peptides. A series of 20 mer fimbrillin peptides were used. Binding of fibronectin to purified fimbriae and synthetic peptides was assayed using polyclonal fibronectin antibodies as well as iodinated fibronectin. Purified fimbriae and peptide 126-146 (RMAFTEIKVQMSAAYDNIYTF) showed high levels of binding to fibronectin, while peptide 318-337(HLNVQCTVAEWVLVGQNATW) showed low but statistically significant binding. Our results suggest V-Q-X-X-X-A or V-X-X-X A common domain/domains present in both peptides might be involved in protein-protein interaction between P. gingivalis fimbriae and fibronectin.

Binding of Porphyromonas gingivalis to pellicle-coated teeth is mediated to a large extent by fimbrillin, a major structural subunit of fimbriae. A simple and efficient method for purifying the major fimbrial proteins from various strains of P. gingivalis was developed. The sonic extracts of crude fimbriae were prepared from P. gingivalis strains 2561, A7A1-28, EM-3, and 9-14K-1, which are representatives of different fimbrial groups. The crude fimbriae were precipitated from the extracts with 40% saturated ammonium sulfate. The dialyzed crude fimbriae were dissolved in 8 M guanidine HCl and loaded onto a Sepharose CL-6B column equilibrated with 6 M guanidine HCl. The major fimbrial protein-enriched fractions were obtained and further purified to homogeneity by repetitive gel filtration on the same column. The purity and intactness of the purified fimbrial proteins were ascertained by SDS-polyacrylamide gel electrophoresis followed by silver nitrate staining and immunoblot analysis using rabbit antisera raised against the purified fimbrial proteins. The result demonstrates the usefulness of guanidine HCl as a reliable reagent for purifying various fimbrial proteins of P. gingivalis, which are often associated strongly with other outer membrane proteins and show different physicochemical and antigenic characteristics.

FMLP-receptor DNA was expressed in Escherichia coli. The expressed product could specifically bind FMLP. This is the first-reported expression of a functional FMLP receptor in Escherichia coli. We confirm that receptor glycosylation is not essential for ligand binding. A deletion mutant did not bind FMLP, suggesting that the deleted portion plays a role in ligand binding.

Periodontal diseases are bacterial infections and anti-microbials have been shown to be useful in their treatment and prevention. State-of-the-art treatment of refractory forms of destructive periodontal disease presently includes adjunctive use of systemic antibiotics directed to eliminating or suppressing pathogenic subgingival bacteria. Also, local application of antimicrobials by subgingival deposition or their use as irrigants during periodontal therapy are soon likely to be major components of anti-infective management of periodontal diseases. A new approach to anti-infective periodontal therapy combines ultrasonic surgical debridement with antimicrobial irrigation.

The receptor for formylated peptides such as FMLP has been reported to consist of glycoprotein components ranging from 24-95 kDa, and to exhibit both high and low affinity for ligand. Controversy exists on the molecular size and number of these components, and whether the different affinities represent distinct ligand binding sites. In this study, the receptor was found to be comprised of components, of 94, 68, and approximately 40 kDa molecular size. Competitive binding inhibition experiments showed that FMLP bound to the components in the following order from highest to lowest affinity: 68 kDa greater than approximately 40 kDa greater than 94 kDa. Our findings suggest that the FMLP receptor of human neutrophils contains at least three components, and that each component has a different affinity for FMLP.

An actinomycetemcomitans can cause localized juvenile periodontitis and certain types of adult periodontitis. Optimal treatment of periodontal disease caused by this microorganism requires systemic antibiotic therapy in addition to mechanical debridement of the infected gingival tissues. Laboratory techniques are available to assist the practitioner in identifying this microorganism in dental plaque samples.

Two cases of Papillon-LeF evre are described. Both siblings demonstrated neutrophil dysfunction and severe precocious periodontal disease. The neutrophil locomotion defect was characterized by a decreased migration toward a chemotactic factor and decreased random migration. Binding of the chemotactic factor, FMLP, to the neutrophil surface was unchanged. Both patients harbored Actinobacillus actinomycetemcomitans and showed elevated serum IgG levels. Both patients also demonstrated salivary and serum antibody to A. actinomycetemcomitans. The Papillon-LeF evre syndrome is compared with the more common localized juvenile periodontitis.

The localization of IgG, IgM, IgA, and several complement components were studied in long-standing human periapical lesions. Sections of 38 Formalin-fixed and ten fast-frozen periapical lesions were stained with fluorescein-conjugated antibodies specific for IgG, IgM, IgA, C3, C4, and C3 proactivator (C3pa). IgG, IgA, and IgM were observed extracellularly as well as in plasma cells. Plasma cells containing IgG were most numerous and those containing IgM least numerous. Numerous non-Ig-containing round cells resembling lymphocytes also were found in most lesions. Five of ten lesions processed by fast freezing showed bright C3 staining of small vessel-like structures. This staining was blocked with unlabeled anti-C3 serums, but was not blocked by prior absorption of the anti-C3 conjugate with AB blood group substances. Deposits of C3 were also identified extracellularly in most of the lesions. C3pa and C4 were not observed in the ten lesions. These experiments suggest that reactions involving complement (C3) play a role in some periapical lesions.

A commercially available bacterial colony counter has been modified to allow rapid, accurate, semi-automated evaluation of cell numbers in the micropore filter assay for chemotaxis. The method is valuable for objective, rapid evaluation of cell counts at various levels through the filter, as well as counts on the distal surface of the filter. Coupled with a programmable calculator, this instrument had made feasible a new method of assessing random migration by the regression line analysis, which discriminates between migration rate and mass migration of cells. This combination of equipment may thus serve as a considerable time saving accessory to laboratories engaged in cell locomotion research, but also will allow more rigorous assessment of differences among specific populations of cells.

Myeloperoxidase (MPO) is an enzyme found in the azurophil granules of neutrophils. Cation-exchange chromatography on carboxymethyl-cellulose previously has been used to demonstrate the heterogeneity of the peroxidase enzymes isolated from human neutrophils. In this study, fast protein liquid chromatography (FPLC) was used to separate and purify three major (I, II, and III) and three minor (IIa, IIIa, IIIb) forms of MPO from isolated neutrophil granules. Purity was confirmed by polyacrylamide gel electrophoresis in the presence of cetyltrimethylammonium bromide (CETAB-PAGE), by crossed immunoelectrophoresis, and by spectral characteristics. All three major forms were indistinguishable by immunodiffusion against rabbit antiserum, scanning spectrophotometry, and amino acid composition. They differed in their elution from a cation-exchange resin, inhibition by 3-amino-1,2,4-triazole, migration rate in CETAB-PAGE, and subunit molecular weight. Subunit molecular weight was examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). All three major forms appeared to consist of heavy (H), intermediate (M), and light (L) peptides. The M peptide appeared to be derived from the H subunit. All L subunits exhibited a molecular weight of 14,500. The molecular weights for the H subunits varied, and were 60,000, 59,000, and 57,000 for MPO I, II, and III, respectively. The molecular weights for the M peptides were 44,100, 43,000, and 42,000 for MPO I, II, and III, respectively. The treatment of neutrophils, granules, and extracts with protease inhibitors and sodium azide did not block the appearance of three major forms of MPO. Thus, neither protease activity nor MPO autooxidation during extraction and purification procedures is responsible for the appearance of multiple chromatographic forms of MPO derived from human neutrophils.

Extracts of parotid glands taken from rhesus monkeys at various times after infection with mumps virus were assayed for the ability to inhibit the migration of guinea pig peritoneal macrophages. Inhibitory activity was found in extracts of glands removed 2 or 7 days after infection. Separation of a pool of these extracts by means of Sephadex G-100 chromatography yielded two active fractions, one containing substances of molecular weight between 45,000 and 65,000, and the second containing substances of approximately 12,000 molecular weight. The larger molecules occur in the same fraction in which migration inhibitory substances generated by virus-infected tissue cultures of nonlymphoid cells are found. Extracts of parotid glands from immune animals challenged with mumps virus were also analyzed for migration inhibitory activity. Positive extracts separated on Sephadex G-100 showed a band of activity in fractions covering molecular weights from 5000 to 30,000 corresponding to those obtained with human MIF produced by antigen-stimulated lymphocytes. Thus it appears that factors with MIF-like activity may be generated in vivo by both immunologic and nonimmunologic means.

Supernatants obtained from sonication of human and macaque dental plaque contained components which, when added to homologous peripheral blood lymphocytes and simultaneously cultured in vitro with suboptimal amounts of mitogen, caused a synergistic effect upon the synthesis of DNA by the lymphocytes. The component in human plaque was heat stable, predominantly non-dialysable and present exclusively in the void volume fraction after Sephadex G-150 column chromatography. A proposed mechanism for the synergism is that among the many cells non-specifically stimulated to divide in culture by the mitogen are cells which were specifically sensitized to plaque antigens; the number of these cells therefore increases and the synergism observed occurs as these sensitized cells become further stimulated by plaque antigens.

Polymorphonuclear leukocyte chemotaxis and chemokinesis, in the micropore filter assay, have been evaluated using Regression Line Analysis. The method discriminates between migration rate and the number of migrating cells by statistical comparison of the slope of the regression line and the γ -intercept, respectively. The derivation of this new method of assessment of cell migration is reported. This report also includes critical evaluation of the chemokinesis dose/ response curve and the directional component of chemotaxis. The effect of inhibitors of chemotaxis were evaluated using the new method. Colchicine was found to effect the directional component of chemotaxis, as indicated by decreased rate of locomotion in chemotaxis experiments, and had no effect on random migration and chemokinesis. Cytochalasin B had a general inhibitory effect upon cell locomotion by depressing the rate of random migration and chemotaxis. 1-Tosylamide-2-phenylethyl chloromethylketone (TPCK) had the apparent effect of uncoupling the receptor and effector mechanisms of chemotaxis, or altering the binding of the chemotactic ligand, since random migration was unaffected but the rate of chemotaxis and chemokinesis were depressed. Ionophore A23187 had a generalized inhibitory effect on the cell rate under all three conditions; however, at low concentrations it induced an increase in the number of migrating cells. These studies indicate that the method of regression line analysis is effective in differentiating in vitro the mechanisms of chemotaxis inhibition. The method may be used effectively in the assessment of defective neutrophil chemotaxis in disease states and may prove a useful adjunct to the study of cell locomotory mechanisms.