Increased levels of circulating endothelial progenitor cells in subjects with moderate to severe chronic periodontitis.

AIM: Emerging evidence shows that periodontal disease is associated with endothelial dysfunction. The purpose of this study was to determine the association between chronic periodontitis (CP) and circulating endothelial progenitor cells (EPC). MATERIALS AND METHODS: Eighty-six non-smoking subjects (36 males and 50 females, aged 35-80 years) were recruited, including 23 subjects with no or mild CP and 63 subjects with moderate to severe CP. The levels of circulating EPC were quantitatively determined by fluorescence-activated cell analysis, including CD34+/kinase insert domain-containing receptor (KDR)+ (more mature EPC) and CD133+/KDR+ (less mature EPC). Periodontal conditions, the intima-media thickness of carotid arteries and circulating biomarkers were examined. RESULTS: Subjects with moderate to severe CP exhibited an increased risk of high EPC count, compared with those with no or mild CP: CD34+/KDR+ EPC [odds ratio (OR)=9.5, 95% confidence interval (95% CI) 1.5-61.0, p=0.018; CD133+/KDR+ EPC, OR=4.6, 95% CI 1.1-19.5, p=0.039]. C-reactive protein was significantly associated with high CD34+/KDR+ EPC count and age was inversely related with high EPC count. Age, gender and CD34+/KDR+ EPC were independent variables of increased carotid intima-media thickness (p<0.05). CONCLUSION: This study shows for the first time that moderate to severe CP is associated with an increased level of circulating EPC.

Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus.

AIM: To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. METHODS: Plasma concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. RESULTS: Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. CONCLUSION: Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes.

Periodontal therapy alters gene expression of peripheral blood monocytes.

AIMS: We investigated the effects of periodontal therapy on gene expression of peripheral blood monocytes. METHODS: Fifteen patients with periodontitis gave blood samples at four time points: 1 week before periodontal treatment (#1), at treatment initiation (baseline, #2), 6-week (#3) and 10-week post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were obtained. Periodontal therapy (periodontal surgery and extractions without adjunctive antibiotics) was completed within 6 weeks. At each time point, serum concentrations of 19 biomarkers were determined. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labelled and hybridized with AffymetrixU133Plus2.0 chips. Expression profiles were analysed using linear random-effects models. Further analysis of gene ontology terms summarized the expression patterns into biologically relevant categories. Differential expression of selected genes was confirmed by real-time reverse transcriptase-polymerase chain reaction in a subset of patients. RESULTS: Treatment resulted in a substantial improvement in clinical periodontal status and reduction in the levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probe sets differentially expressed at a false discovery rate of <0.05. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis and cell signalling. CONCLUSIONS: The data suggest that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect.

Interactions between stress, interleukin-1beta, interleukin-6 and cortisol in periodontally diseased patients.

BACKGROUND/AIMS: The aim of the present study was to measure interleukin-1beta, interleukin-6 and cortisol levels in the peripheral blood of periodontally diseased patients in order to record any interactions with psychosocial stress. MATERIAL AND METHODS: The test group comprised 16 patients with untreated and 14 with treated aggressive generalized periodontitis (AGP), five patients with untreated aggressive localized periodontitis (ALP) and five with chronic generalized periodontitis (CGP). The control group comprised 40 periodontally healthy probands. Blood was taken from the cephalic vein of all patients and controls at the same time (8 a.m.) each day. IL-1beta, IL-6 and cortisol levels were then measured with a sensitive ELISA, the 'Quantikine HS Immunoassay Kit' (Biermann Diagnostica, Bad Nauheim, FRG). The clinical examination covered probing depth, gingival recession, gingival index, plaque index and clinical attachment level. A questionnaire was used to ask the patients and controls about their attitude to life and the stress induced by their jobs and their families. Previous and current levels of tobacco consumption were also recorded. Statistical evaluation was based on the Mann-Whitney U-Wilcoxon test for comparison of blood serum values and clinical parameters between patients and controls, and the Kruskal-Wallis test for intergroup comparison. All data were correlated by means of Spearman's rank correlation coefficient, and significance levels relating to stress and smoking were determined with the chi-square test. RESULTS: With respect to cortisol, the results showed no significant differences either between the patient groups or in comparison with the controls. IL-1beta was detected only in the AGP patients and their controls, but with no significant differences. IL-6 was detected in virtually all patients and controls, but with no significant differences. Only in the untreated AGP patients was IL-6 significantly elevated (P < 0.05) and a slight correlation with attachment loss recorded. In all AGP patients a slight correlation between IL-1beta and IL-6 was recorded. Evaluation of the questionnaire revealed a higher proportion of untreated AGP patients than of controls with a pessimistic attitude to life. In all AGP patients, family-induced stress and smoking were found to correlate with attachment loss. In the untreated AGP patients, smoking correlated with IL-1beta protein content, and in the controls there was a moderate correlation between smoking and IL-6 levels. CONCLUSIONS: The present study found no correlation between the immunological mediators (IL-1beta, IL-6), glucocorticoids (cortisol) and the registered stress values. However, the patients with untreated AGP showed signs of a pessimistic attitude to life, and an elevated IL-6 level was recorded in the peripheral blood. As a restrictive factor it should be borne in mind that the number of patients investigated was too small for adequate conclusions to be drawn.

Relationship between bleeding time test and postextraction bleeding in a healthy control population.

OBJECTIVE: We sought to determine whether cutaneous bleeding time (BT) is related to bleeding outcome measures after a single tooth extraction. STUDY DESIGN: This was a prospective clinical pilot study of 30 subjects. Cutaneous BT was evaluated before a single tooth extraction. After extraction, an oral BT was determined. Subjects were contacted 3 to 7 hours and 2 days after extraction to assess further postoperative bleeding. RESULTS: The mean cutaneous BT was 5.9 minutes (range 1.5-10.0 minutes). The mean oral BT was 7.5 minutes (range 0-20 minutes). Cutaneous BT did not correlate with oral BT or any of our measures of postoperative bleeding. However, the oral BT correlated with the number of hours of bleeding after surgery (R(s) = 0.54, P =.03). The time necessary to perform the extraction correlated with the extraction site bleeding 3 to 7 hours after surgery (R(s) = 0.67, P =.0006). CONCLUSION: Cutaneous BT did not correlate with measures of postoperative bleeding in the present study, but oral BT immediately after extraction correlated with the duration of subsequent postoperative bleeding.

Serum IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis and healthy subjects.

BACKGROUND/AIMS: Established periodontal diseases may be associated with antibody responses to periodontal pathogens, but it is not known at which stage of disease this antibody response is initiated. This study aimed to characterize the host systemic response in initial periodontitis, gingivitis, and periodontal health, to evaluate whether elevated serum antibodies to subgingival species could be detected in initial periodontitis. METHOD: Human systemic immune response were evaluated to 40 subgingival bacterial species in 16 healthy, 21 gingivitis, 11 initial periodontitis and 5 progressing recession adults. Subjects had minimal periodontal attachment level (AL) loss at baseline. Disease categories were determined after 12 months monitoring at three-month intervals. Increased AL loss > or = 1.5 mm (disease activity) at interproximal sites defined initial periodontitis, recession was characterized by AL loss at buccal sites. Serum IgG antibodies were evaluated semi-quantitatively by immunoblot from blood taken at baseline, active and final visits. RESULTS: No antibody was detected from 55% of reactions. When detected, levels were below those reported for advanced periodontitis subjects. There were no major differences in serum antibody levels between healthy, gingivitis and initial periodontitis subjects, despite differences in the subgingival microbiota. Serum antibodies for more species were detected in recession subjects, compared with the other study subjects. No changes in antibody levels were detected between baseline, active, and final visits. No systematic association between species colonization and presence of systemic antibody was observed. CONCLUSIONS: This study did not detect differential elevation of mean serum antibody levels in initial periodontitis subjects, suggesting that serum antibody levels are not sensitive risk markers for initial periodontitis.