Faculty Bibliography

BACKGROUND: Destructive periodontal diseases have been associated with an increased risk of atherosclerotic complications; however, the potential mechanisms are yet to be defined. Inflammation plays a central role in atherosclerosis since C-reactive protein (CRP), an acute-phase protein monitored as a marker of inflammatory status, has been identified as a major risk factor for atherosclerotic complications. Recent reports that destructive periodontal diseases can increase CRP values present the possibility that the acute-phase response may link these 2 disease processes. The objective of the present investigation was to determine the effect of destructive periodontal disease status, severity, and progression on components of the acute-phase response in an urban minority population. METHODS: Clinical measurements recorded included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration, and plaque. Disease progression was defined as a >2 mm loss of attachment 2 months post-baseline. Serum antibody was measured by enzyme-linked immunosorbent assay. CRP was measured using a high-sensitivity CRP (hsCRP) assay. A commercial laboratory measured serum glucose (non-fasting), albumin, cholesterol, high-density lipoprotein (HDL), triglycerides, low-density lipoprotein (LDL), and iron. RESULTS: Increased serum IgG antibody to Porphyromonas gingivalis, but not to 5 other species, was associated with periodontal disease status, increased severity, and progression as were age, male gender, and smoking. Cholesterol and LDL were increased in disease, and HDL and iron were increased in health. hsCRP, glucose, and cholesterol increased with disease progression. By regression analysis, IgG antibody to P. gingivalis correlated with age, probing depth, and hsCRP, and negatively correlated with albumin and iron. By logistic regression, subjects who experienced multiple sites of disease progression and elevated antibody to P. gingivalis increased the odds ratio of hsCRP>2.08 mg/l by 14.1 and 5.6, respectively. CONCLUSION: These results suggest that destructive periodontal disease and disease progression are associated with changes in serum components consistent with an acute-phase response

Disparities in the prevalence and severity of destructive periodontal diseases have been reported for American minority populations and have raised the following questions. Are differences in destructive periodontal disease prevalence and severity due to genetic or other confounding variables associated with ethnicity race? Do risk factors for destructive periodontal diseases differ among American minority populations or differ from the population at large? Answers to these questions will have profound impact on the direction of future research and the allocation of resources to address disparities in destructive periodontal diseases in American minority populations. Risk assessment studies that examined a set of clinical, demographic, immunologic, and microbiologic parameters of Asian Americans, African Americans, and Hispanic Americans resident in the greater New York City region suggest that occupational status, monitored as a surrogate variable for socioeconomic status, may be a more robust risk factor than ethnicity/race for destructive periodontal diseases in these populations

BACKGROUND: Hemodialysis (HD) patients face a 25% annual mortality rate, with 50% of reported deaths attributed to cardiovascular disease. All-cause and cardiovascular mortality correlate with such acute-phase proteins as C-reactive protein (CRP). Hepatic CRP synthesis is upregulated by inflammation; however, elevated CRP values frequently are found in the absence of apparent infection or inflammation. Because destructive periodontal diseases have been associated with elevated CRP levels, we questioned whether destructive periodontal diseases could contribute to elevated CRP values in HD populations. METHODS: Sera from 86 consecutive dentate HD patients were assayed for levels of immunoglobulin G (IgG) antibody to six periodontal species by means of an enzyme-linked immunosorbent assay. RESULTS: CRP values for the subject population ranged from less than 6.9 to 159 mg/L (median, 8.2 mg/L). Univariate comparisons between subjects with or without elevated CRP levels (>10 mg/L) showed that CRP level elevation was associated significantly (P < 0.05) with greater doses of human recombinant erythropoietin and lower levels of hemoglobin, serum iron, transferrin saturation (TSat), albumin averaged over the 3 preceding months, total cholesterol, and triglycerides. Log serum IgG antibody levels to Porphyromonas gingivalis also were significantly greater in the group with elevated CRP levels (P = 0.013). Subsequent multivariate logistic regression showed that log serum antibody levels to P gingivalis remained significant (P = 0.02) after controlling for nonperiodontal sources of elevated CRP, hemoglobin, TSat, and triglyceride values. CONCLUSION: These results suggest that elevated levels of IgG antibody to bacterial species associated with destructive periodontal diseases are associated with elevated CRP values in HD populations.

Differences in periodontal disease prevalence, severity, subgingival microflora and host immune response have been reported for various ethnic/racial groups, which implies that risk factors for destructive periodontal disease progression may also vary in these populations. As it is possible that these differences may be due to confounding variables other than ethnicity/race, we have measured serum IgG antibody response to six periodontal pathogens, and compared these data with microbiological, clinical and demographic parameters in three urban minority populations. The study population consisted of 23 Asiatic, 48 African-American and 37 Hispanic subjects, who were resident in the greater New York region. Clinical indices that were recorded included pocket depth, attachment level, gingival erythema, bleeding upon probing, suppuration and supragingival plaque. Attachment level measurements were taken twice at each visit, and the difference between the means of pairs of measurements taken at baseline and two months later was used to determine disease progression. Subgingival microbiological species were identified and enumerated using DNA-DNA checkerboard hybridization. Serum IgG antibody levels to Actinobacillus actinomycetemcomitans serotyopes a and b, Bacteroides forsythus, Campylobacter rectus, Porphyromonas gingivalis and Prevotella intermedia were measured by enzyme-linked immunosorbant assay (ELISA). Mean serum IgG antibody to P. gingivalis was found to be higher in the African-American group, while IgG antibody to B. forsythus was lower in the Hispanic group. However, the African-American group also had greater mean probing depth, attachment loss, number of missing teeth and numbers of individuals within the unskilled occupational group. When the data were analyzed by occupational status, mean serum IgG antibody to P. gingivalis increased from professional to skilled to unskilled groups. For the entire study population, prior disease and subsequent attachment loss were associated with elevated serum IgG antibody to P. gingivalis. Increasing pocket depth, attachment level, gingival erythema and age were also positively correlated with serum IgG antibody to P. gingivalis, but not with serum IgG antibody to the other five subgingival species. No correlation was found between whole-mouth bacterial levels and homologous serum IgG antibody levels. These results suggest that elevated serum IgG antibody to P. gingivalis reflects destructive periodontal disease status, and may be considered a risk factor for disease progression in these ethnic/racial populations. In addition, although differences in serum IgG antibody profiles to subgingival species were found among the three ethnic/racial groups, environmental and socioeconomic variables may have a greater influence on serum IgG antibody levels in these populations

End-stage renal disease (ESRD) patients on hemodialysis experience a greatly increased rate of atherosclerotic complications. In both hemodialysis and general populations, it has become evident that inflammation plays a central role in the pathogenesis of atherosclerotic complications. C-reactive protein (CRP), the major acute phase protein in man, has been found to predict all-cause and cardiovascular mortality in ESRD patients on hemodialysis maintenance therapy. Hepatic CRP synthesis is upregulated by proinflammatory cytokines released locally at sites of infection or inflammation, although many patients experience elevated CRP values in the absence of overt infection or inflammation. Destructive periodontal diseases in the general population have been associated with both an increased prevalence of atherosclerotic complications and an elevation in serum CRP values. In view of the prevalence of destructive periodontal diseases in the general population, and since periodontal evaluations are normally not performed as part of a medical assessment, destructive periodontal diseases may be an over looked source of inflammation in ESRD patients on hemodialysis therapy. The intent of this report is to review the possible role destructive periodontal diseases and associated periodontal infections may play in the management of the ESRD patient on hemodialysis maintenance therapy

BACKGROUND, AIMS: Destructive periodontal diseases have been reported disproportionately more prevalent and severe in African-Americans relative to other American populations. Differences in subgingival microbiota and host immune response have also been reported for African-Americans, implying that risk factors for disease progression may also differ for these populations. Since it is not clear whether these differences are truly genetic or due to confounding variables such as social economic status, we examined a series of clinical, environmental, demographic, and microbiologic features associated with periodontal disease status in a group of 185 urban minority subjects resident within the greater New York metropolitan area. METHODS: The study population consisted of 56 Asian-American, 71 African-American and 58 Hispanic subjects. Clinical data recorded included pocket depth, attachment level, gingival erythema, bleeding upon probing, suppuration, and the presence of supragingival plaque. Environmental and demographic data recorded included smoking history, years resident in the United States, whether the subject reported a private dentist and occupational status. Subgingival plaque was sampled from the mesial aspect of all teeth exclusive of third molars and the levels of 40 subgingival species enumerated using checkerboard DNA-DNA hybridization. RESULTS: The African-American group had more missing teeth, deeper periodontal pocket depth and more attachment loss than the Asian-American or Hispanic groups. However, the African-American group were less likely to report having a private dentist, had a greater proportion of smokers and a greater proportion of unskilled individuals. The profile of subgingival species differed among the three ethnic/racial groups with A. actinomycetemcomitans, N. mucosa, S. noxia and T. socranskii significantly elevated in the Asian-American group and P. micros significantly elevated in the African-American group. When subset by occupational status, numbers of missing teeth, pocket depth, attachment level and prior disease activity were all found increased in the unskilled relative to the professional group. Local factors including the mean % of sites with plaque, marginal gingival erythema, bleeding upon probing and suppuration were also elevated in the unskilled group. The microbial profile differed among the 3 occupational groups with the unskilled group having elevated numbers of species associated with destructive periodontal diseases. CONCLUSIONS: Although greater destructive periodontal disease prevalence and severity were found in the African-American group, these results suggest that environmental and demographic variables, such as occupational status, may have a greater influence on risk indicators associated with disease prevalence and progression in these populations

Endosseous dental implants can support at least three types of biomaterial/connective tissue interfaces: osseointegration, fibro-osseous integration, and periodontal connective tissue attachment. Although a periodontal connective tissue attachment offers distinct advantages, only osseointegration and fibro-osseous integration are at present clinically achievable. Recent studies indicate a periodontal regeneration-competent cell population and an appropriate biomaterial substrate both are required for periodontal connective attachment formation on biomaterial surfaces. We therefore have developed an in vitro model to characterize the effects of various biomaterial substrates on the early events of periodontal connective tissue attachment formation. Primary cultures of periodontal ligament and gingival connective tissue cells were cultured on uncoated (control) and coated (titanium- and hydroxyapatite-coated) tissue culture plastic, and the level of cell proliferation, collagen, and noncollagen protein synthesis, alkaline phosphatase activity, and expression of a 42 kD cementum extracellular matrix protein were measured over 5, 7, and 9 days in culture. While all three substrates supported cell attachment, proliferation, and protein synthesis, only uncoated and titanium-coated tissue culture plastic supported expression of the cementum extracellular matrix protein after 9 days of culture. In addition, the levels of cell proliferation and collagen and noncollagen protein synthesis for cells grown on hydroxyapatite-coated surfaces lagged behind cells cultured on the control or titanium-coated surfaces at each of the three time points. These data suggest that biomaterial substrates markedly can influence the temporal sequence of extracellular matrix proteins associated with periodontal connective tissue attachment formation. In addition to surface composition (titanium versus hydroxyapatite), surface properties (e.g., topography) also may have an effect on periodontal connective tissue attachment formation. This model may be of use in designing biomaterials to support the formation of periodontal connective tissue attachment in vivo.

The developments in biomaterials over the past 40 years were listed in a questionnaire. Groups of dentists with and without a Master's degree ranked each development on the basis of the impact they believed it has had on the practice of dentistry. The results of the questionnaires were analysed and the rankings were discussed and used as a guide to the projection of the probable future needs and developments in biomaterials, based on the needs of current and future dental patients.

Past attempts to detect tropomyosin in electron micrograph images of frozen-hydrated troponin-regulated thin filaments under relaxing conditions have not been successful. This raised the possibility that tropomyosin may be disordered on filaments in the off-state, a possibility at odds with the steric blocking model of muscle regulation. By using cryoelectron microscopy and helical image reconstruction we have now resolved the location of tropomyosin in both relaxing and activating conditions. In the off-state, tropomyosin adopts a position on the outer domain of actin with a binding site virtually identical to that determined previously by negative staining, although at a radius of 3.8 nm, slightly higher than found in stained filaments. Molecular fitting to the atomic model of F-actin shows that tropomyosin is localized over sites on actin subdomain 1 required for myosin binding. Restricting access to these sites would inhibit the myosin-cross-bridge cycle, and hence contraction. Under high Ca(2+) activating conditions, tropomyosin moved azimuthally, away from its blocking position to the same site on the inner domain of actin previously determined by negative staining, also at 3.8 nm radius. These results provide strong support for operation of the steric mechanism of muscle regulation under near-native solution conditions and also validate the use of negative staining in investigations of muscle thin filament structure.

Wasting of connective tissues including skin, bone, and cartilage have been closely associated with elevated matrix metalloproteinase (MMP) activity and depressed collagen content in the streptozotocin (STZ)-induced diabetic rat, while tetracyclines have been reported to normalize total body weight, skin hydroxyproline and collagen content in this model, in part through inhibition of MMPs. In the present study, we report the effect of CMT-1, a chemically modified tetracycline that lacks antimicrobial properties but retains divalent cation binding and MMP inhibitory activity, on diabetic skin collagen synthesis and steady-state levels of procollagen alpha 1(I) mRNA. Male, 4-month old Sprague-Dawley rats received a single injection of 75 mg/kg STZ or citrate vehicle alone and diabetic status was confirmed by positive glucosuria. Some diabetic animals received 10 mg/day of CMT-1 by oral gavage and, 28 days after STZ treatment, body weight, blood glucose values and the in vivo rates of skin collagen production were measured using the pool-expansion technique. Steady-state levels of procollagen alpha 1(I) mRNA were analyzed 21 days after STZ treatment by hybridization of total RNA with a 32P labelled cDNA to rat type I procollagen alpha 1(I) mRNA in a dot-blot assay. STZ treatment was found to significantly depress body weight, skin collagen hydroxyproline content, the in vivo rate of collagen production, and hybridizable levels of type I procollagen alpha 1(I) mRNA. CMT-1 administered daily to STZ-treated rats inhibited the diabetic depression of these parameters but had little or no effect on non-diabetic controls or on STZ-induced hyperglycemia. Thus, in addition to the inhibition of MMP mediated extracellular collagen degradation, these results suggest CMT-1 also acts to inhibit diabetic connective tissue breakdown in STZ-induced diabetes by increasing both steady-state levels of type I procollagen mRNA and collagen synthesis through mechanism(s) that are independent of the antibacterial properties of tetracyclines.