Alex W. Ho

A Proposed Model Linking Inflammation to Obesity, Diabetes, and Periodontal Infections

BACKGROUND Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFα) and its soluble receptors (sTNFα) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections. METHODS The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNFα and sTNFα were assessed in subsets of 1,221 adults from Erie County, New York, who represented the highest and lowest quartile of BMI. These subjects had extensive periodontal and medical evaluations. RESULTS In the NHANES III portion of the study, BMI was positively related to severity of periodontal attachment loss (P <0.001). Weighted multiple logistic regressions showed that this relationship is likely mediated by insulin resistance, since overweight individuals (with BMI ≥27 kg/m2 ) with high levels of insulin resistance (IR) exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe periodontal disease as compared to overweight subjects with low IR. In the Erie County adult population, the highest levels of TNFα and sTNFα receptors were found in those individuals in the highest quartile of BMI. A positive correlation of TNFα levels with periodontal disease was found only in those in the lowest quartile of BMI. CONCLUSIONS Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNFα and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.

Cigarette Smoking Increases the Risk for Subgingival Infection With Periodontal Pathogens

Cigarette smoking has been found to increase the risk for periodontitis. The present study examined the association between cigarette smoking and subgingival infection with periodontal pathogens to determine if smokers are more likely to be infected with certain periodontal pathogens than non-smokers. Self-reported data on 1,426 subjects, aged 25 to 74, from the Erie County Study were obtained including data on 798 subjects who were current or former smokers. Mean clinical attachment loss was used to estimate the severity of periodontal destruction. Subgingival infection with target periodontal pathogens was determined by indirect immunofluorescence microscopy. Smokers harbored significantly higher levels and were at significantly greater risk of infection with Bacteroides forsythus than non-smokers. Adjusting for disease severity, the risk of subgingival infection with B. forsythus in current smokers was 2.3 times that of former smokers or non-smokers. The relative risk of B. forsythus infection also increased 1.18 times for every category of smoking as the amount of smoking measured in packyears increased from very light to heavy. Adjusting for disease severity, Porphyromonas gingivalis was also more likely to subgingivally infect smokers than non-smokers; however, there was not a significantly higher relative risk for infection with this bacterium. The data from this study indicate that cigarette smoking increases the likelihood of subgingival infection with certain periodontal pathogens. This may partly explain the increased risk for periodontitis seen in smokers. J Periodontol 1996;67:1050-1054.

Systemic Inflammation in Cardiovascular and Periodontal Disease: Comparative Study

ABSTRACT Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, α1-acid-glycoprotein (AAG), α1-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.

Environmental lead exposure induces changes in the heme biosynthetic pathway

Lead is ubiquitous in the environment today. Lead enters our body from a variety of sources such as urban environments and food. All humans have lead in their bodies primarily as a result of exposure to man-made sources. Children show a greater sensitivity to leads effects than adults do. In this study, the concentration of metabolites of heme biosynthesis in school children from a group of volunteers with various blood lead contents and a group of lead-intoxicated children were reported. Also, the measurement of free erythrocyte porphyrins (FEP) as a microscreening test for lead toxicity was performed, and the blood lead levels of the school children were determined as well. The results show that the concentrations of the metabolites of heme biosynthesis are affected by the blood lead level. FEP level shows a small change as the blood lead level slightly increases. Elevation of blood lead level and the increase of the metabolite concentration are a good indication of lead-induced heme metabolic changes. FEP is an excellent screening test for the heme metabolic imbalances. Because of differences in individual susceptibility, symptoms of lead intoxication and their onset may vary. With increasing exposure, the severity of symptoms can be expected to change with varying degrees of lead toxicity. ©1997 by John Wiley & Sons, Inc. Environ Toxicol Water Qual 12: 245–248, 1997

Inhibition of proton transport through spinach thylakoid membranes by 5,5'-dithiobis(2-nitrobenzoate).

In both oxidative phosphorylation and photo‐phosphorylation, electron flow through a carrier is linked to the generation of ATP. The energy released by electron transport is converted to potential energy forming a proton gradient across the membranes in chloroplasts. The proton gradient can be measured by a pH microelectrode. In this report, pH changes produced by photo‐induced proton transport through spinach chloroplast membranes were measured by a glass microelectrode. The effect of 5,5′‐dithiobis(2‐nitrobenzoate) (DTNB) on the kinetics of proton movement across the thylakoid membranes was studied. The results showed that the rate of proton uptake was reduced with increasing DTNB concentration. The rate of leakage of accumulated protons through thylakoid membranes also decreased. The results support the notion that cysteinyl residue is involved in proton translocation. The inhibition of proton transport would subsequently affect the chemical reactions of the Calvin Cycle that takes place in the stroma which is the soluble compartment surrounding the thylakoid membranes.