Effects of aging on apoptosis gene expression in oral mucosal tissues.

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca(+2)-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.

Treatment of periodontal disease and the risk of preterm birth.

BACKGROUND: Maternal periodontal disease has been associated with an increased risk of preterm birth and low birth weight. We studied the effect of nonsurgical periodontal treatment on preterm birth. METHODS: We randomly assigned women between 13 and 17 weeks of gestation to undergo scaling and root planing either before 21 weeks (413 patients in the treatment group) or after delivery (410 patients in the control group). Patients in the treatment group also underwent monthly tooth polishing and received instruction in oral hygiene. The gestational age at the end of pregnancy was the prespecified primary outcome. Secondary outcomes were birth weight and the proportion of infants who were small for gestational age. RESULTS: In the follow-up analysis, preterm birth (before 37 weeks of gestation) occurred in 49 of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodontitis measures (P<0.001), it did not significantly alter the risk of preterm delivery (P=0.70; hazard ratio for treatment group vs. control group, 0.93; 95% confidence interval [CI], 0.63 to 1.37). There were no significant differences between the treatment and control groups in birth weight (3239 g vs. 3258 g, P=0.64) or in the rate of delivery of infants that were small for gestational age (12.7% vs. 12.3%; odds ratio, 1.04; 95% CI, 0.68 to 1.58). There were 5 spontaneous abortions or stillbirths in the treatment group, as compared with 14 in the control group (P=0.08). CONCLUSIONS: Treatment of periodontitis in pregnant women improves periodontal disease and is safe but does not significantly alter rates of preterm birth, low birth weight, or fetal growth restriction. (ClinicalTrials.gov number, NCT00066131 [ClinicalTrials.gov].).

Use of saliva-based nano-biochip tests for acute myocardial infarction at the point of care: a feasibility study.

BACKGROUND: For adults with chest pain, the electrocardiogram (ECG) and measures of serum biomarkers are used to screen and diagnose myocardial necrosis. These measurements require time that can delay therapy and affect prognosis. Our objective was to investigate the feasibility and utility of saliva as an alternative diagnostic fluid for identifying biomarkers of acute myocardial infarction (AMI). METHODS: We used Luminex and lab-on-a-chip methods to assay 21 proteins in serum and unstimulated whole saliva procured from 41 AMI patients within 48 h of chest pain onset and from 43 apparently healthy controls. Data were analyzed by use of logistic regression and area under curve (AUC) for ROC analysis to evaluate the diagnostic utility of each biomarker, or combinations of biomarkers, in screening for AMI. RESULTS: Both established and novel cardiac biomarkers demonstrated significant differences in concentrations between patients with AMI and controls without AMI. The saliva-based biomarker panel of C-reactive protein, myoglobin, and myeloperoxidase exhibited significant diagnostic capability (AUC = 0.85, P < 0.0001) and in conjunction with ECG yielded strong screening capacity for AMI (AUC = 0.96) comparable to that of the panel (brain natriuretic peptide, troponin-I, creatine kinase-MB, myoglobin; AUC = 0.98) and far exceeded the screening capacity of ECG alone (AUC approximately 0.6). En route to translating these findings to clinical practice, we adapted these unstimulated whole saliva tests to a novel lab-on-a-chip platform for proof-of-principle screens for AMI. CONCLUSIONS: Complementary to ECG, saliva-based tests within lab-on-a-chip systems may provide a convenient and rapid screening method for cardiac events in prehospital stages for AMI patients.

Effects of caloric restriction on inflammatory periodontal disease.

OBJECTIVE: Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. METHODS: The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. RESULTS: Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. CONCLUSION: Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females.

Systemic immune responses in pregnancy and periodontitis: relationship to pregnancy outcomes in the Obstetrics and Periodontal Therapy (OPT) study.

BACKGROUND: Our previous studies reported on the obstetric, periodontal, and microbiologic outcomes of women participating in the Obstetrics and Periodontal Therapy (OPT) Study. This article describes the systemic antibody responses to selected periodontal bacteria in the same patients. METHODS: Serum samples, obtained from pregnant women at baseline (13 to 16 weeks; 6 days of gestation) and 29 to 32 weeks, were analyzed by enzyme-linked immunosorbent assay for serum immunoglobulin G (IgG) antibody to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), and Treponema denticola. RESULTS: At baseline, women who delivered live preterm infants had significantly lower total serum levels of IgG antibody to the panel of periodontal pathogens (P = 0.0018), to P. gingivalis (P = 0.0013), and to F. nucleatum (P = 0.0200) than women who delivered at term. These differences were not significant at 29 to 32 weeks. Changes in IgG levels between baseline and 29 to 32 weeks were not associated with preterm birth when adjusted for treatment group, clinical center, race, or age. In addition, delivery of low birth weight infants was not associated with levels of antibody at baseline or with antibody changes during pregnancy. CONCLUSIONS: Live preterm birth is associated with decreased levels of IgG antibody to periodontal pathogens in women with periodontitis when assessed during the second trimester. Changes in IgG antibody during pregnancy are not associated with birth outcomes.

Redefining the biologic width in severe, generalized, chronic periodontitis: implications for therapy.

BACKGROUND: Previous studies demonstrated significant variability in the histologic biologic width in periodontal health and mild periodontitis. The purpose of this study was to determine whether the previously established dimensions of the biologic width applied to subjects with severe, generalized, chronic periodontitis. METHODS: Twenty-eight subjects, aged 29 to 45 years, with severe, generalized, chronic periodontitis were included in the study. There were 18 males and 10 females, and 19 (68%) of the patients were smokers. Clinical and radiographic measures were taken by calibrated examiners. The clinical biologic width was determined from the most coronal level of clinical attachment to the crest of the alveolar bone for proximal surfaces only and compared to the histologic biologic width previously reported. RESULTS: The clinical biologic width in subjects with severe, generalized periodontitis was significantly greater than previously reported (P <0.001). For all evaluable proximal sites, the mean clinical biologic width was 3.95 mm versus the mean histologic biologic width of 2.04 mm. The greatest clinical biologic widths were seen with pockets <2 mm (5.02 +/- 2.48 mm; range: 1.60 to 9.00 mm) and 2 to 4 mm (4.16 +/- 1.32 mm; range: 0.20 to 6.40 mm). CONCLUSIONS: The mean clinical biologic width in subjects with severe, generalized, chronic periodontitis seemed to be significantly greater than the histologic biologic width previously reported for subjects not demonstrating significant periodontal pathology. In addition, sites with shallow probing depths demonstrated the greatest biologic width, suggesting that these sites may be at increased risk for losing clinically significant attachment during surgical procedures.

Periodontal disease in Hispanic Americans with type 2 diabetes.

BACKGROUND: Diabetes is a major risk factor for the development of periodontal disease in certain populations. The prevalence of type 2 diabetes is increased in Hispanic Americans, but its impact on the extent and severity of periodontal disease in this population has not been determined. METHODS: Sixty-three Hispanic Americans, aged 33 to 72 years, from South Texas were grouped based on the presence or absence of type 2 diabetes. Past medical histories, including smoking, were obtained. Periodontal status was evaluated by measuring probing depth (PD), clinical attachment level (CAL), plaque, bleeding on probing, visual gingival inflammation, and calculus. RESULTS: Type 2 diabetes was associated frequently with major medical complications in this population. Diabetes was associated with significantly more calculus formation and tooth loss and an increased extent and severity of periodontitis. Subjects with diabetes had nearly three times the mean CAL and frequency of PD >6 mm than subjects without diabetes and nearly twice the frequency of moderate to advanced attachment loss (> or =3 mm). Smoking and diabetes had significant independent effects on mean CAL and the frequency of deep pockets. Diabetes and smoking combined were associated with a significantly higher frequency of sites with CAL > or =3 mm compared to healthy non-smokers, healthy smokers, and non-smokers with diabetes. CONCLUSIONS: Hispanic Americans with type 2 diabetes had more supra- and subgingival calculus, an increased extent and severity of periodontal destruction, and an increased frequency of tooth loss due to periodontitis. An additive/synergistic contribution of type 2 diabetes and smoking for increasing the extent of periodontal disease was observed.

Microbiologic and immunologic characteristics of periodontal disease in Hispanic americans with type 2 diabetes.

BACKGROUND: The microbiology of periodontitis in type 1 diabetes has been reported, but less is known about type 2 diabetes. Moreover, these data have not linked microbial colonization, host response, and clinical presentation in type 1 or type 2 diabetes. The objectives of this study were to relate periodontal status, periodontal microorganisms, and host-response characteristics in Hispanic Americans with type 2 diabetes. METHODS: Plaque and serum samples were obtained from 63 Hispanic American subjects with and without type 2 diabetes. The microbiology of subgingival plaque samples was evaluated using DNA checkerboard hybridization, and serum antibody to a battery of oral microorganisms was determined using an enzyme-linked immunosorbent assay. RESULTS: In general, similar pathogens were present in periodontitis sites from subjects with and without type 2 diabetes, although the periodontitis sites in diabetes showed a higher frequency of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), and Campylobacter spp. Serum antibody to Campylobacter rectus was elevated in type 2 diabetes, whereas antibody to P. gingivalis and C. rectus were elevated in subjects with periodontitis, irrespective of diabetes status. Stratification of the population based upon antibody to P. gingivalis or C. rectus suggested a linkage between elevated antibody to P. gingivalis, increased frequency of diabetes, and significantly worse periodontitis. CONCLUSION: The increased severity of periodontal disease with type 2 diabetes may reflect an alteration of the pathogenic potential of periodontal bacteria and/or a modification of the characteristics of the host's inflammatory response that may contribute to a breakdown in the homeostasis of the periodontium.

Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease.

BACKGROUND: Previous studies showed that adjunctive subantimicrobial dose doxycycline (SDD; 20 mg, twice daily) provides significant clinical benefits to scaling and root planing (SRP). A modified-release SDD formulation containing 40 mg doxycycline (SDD-40) to be taken once daily has been developed. The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis. METHODS: A 9-month, double-masked, randomized, placebo-controlled, multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis. Subjects were treated by SRP and randomized to receive SDD-40 or placebo for 9 months with evaluations at 3, 6, and 9 months. RESULTS: Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points. At month 9, at sites with baseline probing depths (PD) > or =6 mm, 72% to 76% of sites in the SDD-40 group demonstrated clinically significant PD reductions and clinical attachment level (CAL) gains > or =2 mm compared to 56% to 58% of sites in the placebo group (P <0.0001); 48% to 52% of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32% of sites in the placebo group (P <0.0001). In moderate sites (baseline PD 4 to 6 mm), adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL (all time points: P <0.05), PD (3 months: P = 0.002; 6 and 9 months: P = 0.001), and bleeding on probing (BOP) (3 months: P <0.01; 6 months: P <0.02; 9 months: P <0.05). In deep sites (baseline PD > or =7 mm), SDD-40 provided significant benefits over control for mean CAL (3 months: P <0.05; 6 and 9 months: P <0.01), PD (all time points: P <0.001), and BOP (3 months: P <0.05; 6 months: not statistically significant; 9 months: P <0.05). Compliance with study medication was high (>92%) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group. CONCLUSION: SDD-40 used as an adjunct to SRP resulted in significantly greater clinical benefits than SRP alone in the treatment of periodontitis.

The effects of a calorie-reduced diet on periodontal inflammation and disease in a non-human primate model.

BACKGROUND: Low-calorie diets are commonplace for reducing body weight. However, no information is available on the effects of a reduced-calorie diet on periodontal inflammation and disease. The purpose of this study was to evaluate the clinical effects of a long-term calorie-restriction (CR) diet on periodontitis in an animal model of periodontitis. METHODS: Periodontitis was induced in 55 young, healthy, adult rhesus monkeys (Macaca mulatta) by tying 2.0 silk ligatures at the gingival margins of maxillary premolar/molar teeth. Animals on a CR diet (30% CR; N = 23) were compared to ad libitum diet controls (N = 32). Clinical measures, including the plaque index (PI), probing depth (PD), clinical attachment level (CAL), modified gingival index (GI), and bleeding on probing (BOP) were recorded at baseline and 1, 2, and 3 months after ligature placement. RESULTS: Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. Compared to controls, CR resulted in a significant reduction in ligature-induced GI (P <0.0001), BOP (P <0.0015), PD (P <0.0016), and CAL (P <0.0038). Periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (P <0.001). CONCLUSIONS: These clinical findings are consistent with available evidence that CR has anti-inflammatory effects. Moreover, these experimental findings are the first observations, to the best of our knowledge, that CR dampens the inflammatory response and reduces active periodontal breakdown associated with an acute microbial challenge.

Combining host modulation and topical antimicrobial therapy in the management of moderate to severe periodontitis: a randomized multicenter trial.

BACKGROUND: Previous studies showed that host modulation therapy (HMT) or topical antimicrobial therapy (TAT) provided significant adjunctive benefits to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). The purpose of this study was to evaluate a combination therapy involving SRP, HMT, and TAT in the treatment of moderate to severe CP. METHODS: A 6-month, randomized, multicenter, placebo-controlled, examiner-masked study was undertaken to evaluate the clinical usefulness of a combination treatment of systemically delivered doxycycline hyclate (HMT; 20 mg, twice a day) plus locally delivered doxycycline hyclate gel (TAT; 10%, in pockets > or =5 mm) in combination with SRP versus SRP plus placebo. Clinical outcomes included mean changes in probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and gingival index (GI) at baseline and at 3 and 6 months. RESULTS: In 171 subjects, combination therapy provided significantly greater clinical benefits than control therapy for all clinical measures at 3 and 6 months. In moderate CP (PD of 4 to 6 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.03), BOP (3 months: P <0.02; 6 months: P <0.05), and GI (3 months: P <0.01; 6 months: P <0.03). In severe CP (PD > or =7 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.02), BOP (3 months: P <0.01; 6 months: P >0.05), and GI (3 months: P <0.01; 6 months: P <0.01). CONCLUSION: Combination therapy, including SRP, HMT, and TAT, provided significantly greater clinical benefits than SRP alone in the treatment of moderate to severe CP.

Periodontal bacterial profiles in pregnant women: response to treatment and associations with birth outcomes in the obstetrics and periodontal therapy (OPT) study.

BACKGROUND: A recent clinical trial (Obstetrics and Periodontal Therapy [OPT] Study) demonstrated that periodontal therapy during pregnancy improved periodontal outcomes but failed to impact preterm birth. The present study evaluated seven target bacteria, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia (previously T. forsythensis), Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum, in subgingival dental plaque of pregnant women in the OPT Study and their association with birth outcomes. METHODS: Pregnant women were randomly assigned to receive periodontal treatment before 21 weeks' gestation or after delivery. Subgingival plaque was sampled at baseline (13 to 16 weeks; 6 days of gestation) and at 29 to 32 weeks. We analyzed subgingival plaque samples from women who experienced fetal loss, delivered a live preterm infant (preterm women), or delivered a full-term infant (full-term women). Samples were analyzed using quantitative polymerase chain reaction. Associations between preterm birth and bacterial counts and percentages were tested using multiple linear regression. RESULTS: No significant differences were observed at baseline between preterm and full-term women for any measured bacterial species or group of species, after accounting for multiple comparisons. Changes in bacterial counts and proportions during pregnancy also were not associated with birth outcomes. In full-term and preterm women, periodontal therapy significantly reduced (P <0.01) counts of all target species except for A. actinomycetemcomitans. CONCLUSIONS: In pregnant women with periodontitis, non-surgical periodontal therapy significantly reduced levels of periodontal pathogens. Baseline levels of selected periodontal pathogens or changes in these bacteria resulting from therapy were not associated with preterm birth.

Examining the safety of dental treatment in pregnant women.

BACKGROUND: Although clinicians generally consider it safe to provide dental care for pregnant women, supporting clinical trial evidence is lacking. This study compares safety outcomes from a trial in which pregnant women received scaling and root planing and other dental treatments. METHODS: The authors randomly assigned 823 women with periodontitis to receive scaling and root planing, either at 13 to 21 weeks' gestation or up to three months after delivery. They evaluated all subjects for essential dental treatment (EDT) needs, defined as the presence of moderate-to-severe caries or fractured or abscessed teeth; 351 women received complete EDT at 13 to 21 weeks' gestation. The authors used Fisher exact test and a propensity-score adjustment to compare rates of serious adverse events, spontaneous abortions/stillbirths, fetal/congenital anomalies and preterm deliveries (<37 weeks' gestation) between groups, according to the provision of periodontal treatment and EDT. RESULTS: Rates of adverse outcomes did not differ significantly (P> .05) between women who received EDT and those who did not require this treatment, or between groups that received both EDT and periodontal treatment, either EDT or periodontal treatment alone, or no treatment. Use of topical or local anesthetics during root planing also was not associated with an increased risk of experiencing adverse outcomes. CONCLUSIONS: EDT in pregnant women at 13 to 21 weeks' gestation was not associated with an increased risk of experiencing serious medical adverse events or adverse pregnancy outcomes. Data from larger studies and from groups with other treatment needs are needed to confirm the safety of dental care in pregnant women. CLINICAL IMPLICATIONS: This study provides evidence that EDT and use of topical and local anesthetics are safe in pregnant women at 13 to 21 weeks' gestation.

Gene expression analysis of neuropeptides in oral mucosa during periodontal disease in non-human primates.

BACKGROUND: Neuropeptides (NPs) are innate pivotal regulators of the immunoinflammatory response. Nevertheless, their role in the pathogenesis of periodontal disease remains unknown. Changes in gene expression of 10 NPs and 16 NP receptors (NPRs) coincident with the initiation, progression, and resolution of periodontitis were determined. METHODS: The ligature-induced periodontitis model was used in rhesus monkeys (n = 18). Gingival tissue samples were taken at baseline (preligatures), at 2 weeks and at 1 month (initiation), and at 3 months (progression) postligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated from tissues and NP/NPR gene expression microarray analysis was performed. Gene expression changes were validated by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: Unexpectedly, the expression of pro-inflammatory NPs/NPRs did not change during periodontitis or with resolution. However, increased expression of the anti-inflammatory NPs adrenomedullin (ADM) and galanin (GAL), and the NPRs calcitonin receptor-like (CALCRL) and receptor activity-modifying protein-2 and -3 (RAMP2 and RAMP3) were observed during initiation and progression of disease. The expression of the same NPs/NPRs exhibited a significant positive correlation with both molecular (interleukin-1ß, matrix mettaloproteinase-9, and receptor activator of nuclear factor-kappa B ligand) and clinical measures of gingival inflammation and tissue destruction. CONCLUSION: Initiation and progression of periodontitis involve significant overexpression of ADM, GAL, CALCRL, RAMP2, and RAMP3. These anti-inflammatory NPs/NPRs could play a role in the unresolved infection and inflammation that normally drives tissue destruction in periodontitis. Both ADM and GAL potentially are new candidates to consider as biomolecules associated with periodontal disease activity.

Evaluation of the effect of subgingival placement of chlorhexidine chips as an adjunct to scaling and root planing.

BACKGROUND: The purpose of this 9-month study was to compare the effect of scaling and root planing alone (control) to that of scaling and root planing plus application of chlorhexidine chips (test). METHODS: Twenty-six subjects having two non-adjacent sites in non-molar teeth with probing depth > or =5 mm and bleeding on probing participated in this split-mouth trial. At baseline, the patients received full-mouth scaling and root planing followed by placement of chlorhexidine chips secured by cyanoacrylate at test sites and placement of cyanoacrylate alone at control sites. Test sites still > or =5 mm deep at 3 and 6 months were retreated with renewed chlorhexidine chip application. Recordings of bleeding on probing, probing depths, and clinical attachment levels were performed at baseline, after 6 weeks, and after 3, 6, and 9 months. RESULTS: Improvements of bleeding scores, probing depths and clinical attachment levels were observed for both test and control sites at 6 weeks compared to baseline. Subsequently, all three measurements remained comparatively stable throughout the study. No differences in improvements were found comparing test and control sites. CONCLUSION: This study failed to observe any adjunctive effect of subgingival placement of chlorhexidine chips after scaling and root planing.

Periodontitis and gestational diabetes mellitus: exploring the link in NHANES III.

OBJECTIVES: The authors hypothesized that women with a history of gestational diabetes mellitus (GDM) during pregnancy would exhibit more severe periodontal disease than controls without a history of diabetes during pregnancy. METHODS: Data from NHANES Ill provided information for 4,244 women ages 20-59. One hundred and thirteen had a history of GDM (GDM+), while 4,131 had no history of diabetes before or during their pregnancies (GDM-). Women were further classified by the presence or absence of diabetes mellitus (DM+ or DM-) at the time of their NHANES Ill examination. Periodontal disease (PD) was defined as one or more teeth with one or more sites with probing depth > or = 4mm, loss of attachment > or = 2mm, and bleeding on probing. RESULTS: The PD prevalence among women who were GDM+DM- was 9.0% and 4.8% for those who were GDM-DM-. PD prevalence for women who were GDM+DM+ was 30.5% and 11.6% for GDM-DM+ subjects, respectively. A logistic regression model, controlling for age, calculus, smoking, and income estimated women who were GDM+DM+ were more likely to have periodontal disease than women who were GDM-DM- and women who were GDM-DM+. The GDM+DM- group also tended to be more likely to have PD than the GDM-DM- and GDM-DM+ groups. However, the odds ratios were not statistically significant. CONCLUSIONS: These results support the hypothesis that women with gestational diabetes mellitus (GDM) during pregnancy may be at greater risk for developing more severe periodontal disease than pregnant women without GDM.

Transcriptome Analysis of B Cell Immune Functions in Periodontitis: Mucosal Tissue Responses to the Oral Microbiome in Aging.

Evidence has shown activation of T and B cells in gingival tissues in experimental models and in humans diagnosed with periodontitis. The results of this adaptive immune response are noted both locally and systemically with antigenic specificity for an array of oral bacteria, including periodontopathic species, e.g., Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. It has been recognized through epidemiological studies and clinical observations that the prevalence of periodontitis increases with age. This report describes our studies evaluating gingival tissue transcriptomes in humans and specifically exploiting the use of a non-human primate model of naturally occurring periodontitis to delineate gingival mucosal tissue gene expression profiles focusing on cells/genes critical for the development of humoral adaptive immune responses. Patterns of B cell and plasmacyte genes were altered in aging healthy gingival tissues. Substantial increases in a large number of genes reflecting antigen-dependent activation, B cell activation, B cell proliferation, and B cell differentiation/maturation were observed in periodontitis in adults and aged animals. Finally, evaluation of the relationship of these gene expression patterns with those of various tissue destructive molecules (MMP2, MMP9, CTSK, TNFα, and RANKL) showed a greater frequency of positive correlations in healthy tissues versus periodontitis tissues, with only MMP9 correlations similar between the two tissue types. These results are consistent with B cell response activities in healthy tissues potentially contributing to muting the effects of the tissue destructive biomolecules, whereas with periodontitis this relationship is adversely affected and enabling a progression of tissue destructive events.

Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis.

BACKGROUND: Severe, generalized periodontitis is a form of chronic periodontitis that appears to be associated with an exaggerated host response. Little information is available on the benefits of using adjunctive host modulation in the management of this form of periodontal disease. METHODS: Thirty subjects < or = 45 years of age with severe, generalized periodontitis received subgingival debridement and oral hygiene instructions each week for 4 weeks, plus 6 months of adjunctive subantimicrobial doxycycline (SDD) or placebo. Periodontal status was monitored at baseline, and at 1, 3, 5.25, and 8.25 months following completion of the hygiene sessions. Maintenance therapy was performed at 3, 5.25, and 8.25 months for both groups. RESULTS: Ten subjects in each group completed all phases of the study. Subgingival debridement plus adjunctive SDD reduced deep pockets (> or =7 mm at baseline) by an average of 3.02 mm after 9 months versus 1.42 mm for the placebo group. A significant clinical response was seen in both groups as soon as 1 month, but the response was always clinically and statistically greater in the SDD group. In the SDD group, nearly 40% of 237 pockets > or =7 mm were reduced by > or =4 mm, and 55% were reduced by > or =3 mm. In addition, only 2 pockets deepened by > or =4 mm in the SDD group versus 10 in the placebo group. CONCLUSIONS: The supplementation of hygienist-delivered full mouth subgingival and supragingival debridement with a host-modulating agent, SDD, provides clinically and statistically significant benefits in the reduction of deep pockets in patients with severe, generalized periodontitis. In addition, adjunctive SDD is more effective than a placebo in preventing further increases in probing depth.

Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis: a multicenter trial.

BACKGROUND: Previous studies have shown that subantimicrobial dose doxycycline (SDD) is of clinical benefit in the treatment of chronic periodontitis (CP). The aim of this study was to further assess the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of CP. METHODS: A double-blind, randomized, placebo-controlled, multicenter clinical study was conducted to test the efficacy of SDD (20 mg doxycycline B.I.D.) in combination with SRP in subjects with moderate to severe CP. Two-hundred ten subjects were treated with a standardized episode of SRP and randomized to receive either adjunctive SDD or placebo for 9 months. Efficacy parameters included per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, and the total number of sites with attachment gains and probing depth reductions > or = 2 mm and > or = 3 mm from baseline. RESULTS: In periodontal sites with PD 4 to 6 mm and > or = 7 mm (N = 209, intent-to-treat population), mean improvements in CAL and PD were greater following SRP with adjunctive SDD than SRP with placebo, achieving statistical significance in all baseline disease categories at month 9 (P < 0.05). At month 9, 42.3% of sites in the SDD group demonstrated CAL gain > or = 2 mm compared to 32.0% of sites in the placebo group (P < 0.01). CAL gain > or = 3 mm was seen in 15.4% of sites in the SDD group compared to 10.6% of sites in the placebo group (P < 0.05). When considering the same thresholds of change in PD, 42.9% of sites in the SDD group compared to 31.1% of sites in the placebo group demonstrated PD reduction > or = 2 mm (P < 0.01), and 15.4% of sites in the SDD group compared to 9.1% of sites in the placebo group demonstrated PD reduction > or = 3 mm (P < 0.01). CONCLUSION: Adjunctive subantimicrobial dose doxycycline enhances scaling and root planing. It results in statistically significant attachment gains and probing depth reductions over and above those achieved by scaling and root planing with placebo.

Using host response modifiers in the treatment of periodontal disease.

Periodontal disease is the result of a complex interaction between microbial plaque, the host's inflammatory response to the plaque, and host modifying factors (e.g., smoking, diabetes, genetics) that may have an impact on the disease process. It is known that plaque initiates periodontal disease but that the host response is responsible for the destruction of periodontal tissues. This article describes why host response modifiers may be used to help control inflammation and tissue destruction as part of the initial phase of periodontal therapy in selected patient groups.