BackgroundRecent studies have suggested that periodontal disease increases the risk of atherothrombotic disease. Atherosclerosis has been characterized as a chronic inflammatory response to cholesterol deposition in the arteries. Although several studies have suggested that certain periodontopathic bacteria accelerate atherogenesis in apolipoprotein E-deficient mice, the mechanistic link between cholesterol accumulation and periodontal infection-induced inflammation is largely unknown.Methodology/Principal FindingsWe orally infected C57BL/6 and C57BL/6.KOR-Apoeshl (B6.Apoeshl) mice with Porphyromonas gingivalis, which is a representative periodontopathic bacterium, and evaluated atherogenesis, gene expression in the aorta and liver and systemic inflammatory and lipid profiles in the blood. Furthermore, the effect of lipopolysaccharide (LPS) from P. gingivalis on cholesterol transport and the related gene expression was examined in peritoneal macrophages. Alveolar bone resorption and elevation of systemic inflammatory responses were induced in both strains. Despite early changes in the expression of key genes involved in cholesterol turnover, such as liver X receptor and ATP-binding cassette A1, serum lipid profiles did not change with short-term infection. Long-term infection was associated with a reduction in serum high-density lipoprotein (HDL) cholesterol but not with the development of atherosclerotic lesions in wild-type mice. In B6.Apoeshl mice, long-term infection resulted in the elevation of very low-density lipoprotein (VLDL), LDL and total cholesterols in addition to the reduction of HDL cholesterol. This shift in the lipid profile was concomitant with a significant increase in atherosclerotic lesions. Stimulation with P. gingivalis LPS induced the change of cholesterol transport via targeting the expression of LDL receptor-related genes and resulted in the disturbance of regulatory mechanisms of the cholesterol level in macrophages.Conclusions/SignificancePeriodontal infection itself does not cause atherosclerosis, but it accelerates it by inducing systemic inflammation and deteriorating lipid metabolism, particularly when underlying hyperlidemia or susceptibility to hyperlipidemia exists, and it may contribute to the development of coronary heart disease.

Increasing evidence suggests that distinct inflammatory cytokines convert forkhead box protein P3 (FOXP3(+)) regulatory T-cells (Tregs) into IL-17-producing cells (Th17 cells) in vitro. However, this functional plasticity has not been examined in the pathogenesis of periodontal disease. In this study, we analyzed the IL-17A(+)FOXP3(+) cells present in periodontitis lesions to determine the association between Treg conversion and the pathogenesis of periodontitis. The immunohistochemical analysis of gingival tissues demonstrated that the numbers of Th17 cells (IL-17A(+)FOXP3(-)) and Tregs (IL-17A(-)FOXP3(+)) were greater in periodontitis lesions than in gingivitis lesions. We further identified a small number of IL-17A(+)FOXP3(+) cells in periodontitis lesions but not in gingivitis lesions. The flow cytometry analysis of CD4(+) T-cell lines established from gingival tissues and the peripheral blood of periodontitis patients showed that the proportion of Tregs was reduced and the proportion of IL-17A(+)FOXP3(+) cells among all FOXP3(+) cells was elevated in gingival tissue T-cell lines relative to the proportions in peripheral blood T-cell lines. Our findings indicate that Treg-Th17 conversion may occur in periodontitis lesions. Further studies addressing the role of Treg conversion during inflammatory responses against periodontopathic bacteria are needed.

The results suggest that in hypertensive patients, PWV and SDPTG provide different information about arterial properties at central and peripheral sites.

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The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.

These data demonstrate that oral infection with P. gingivalis induces alterations in systemic cytokine production. These cytokines could play roles in the development not only of periodontitis but also of atherosclerosis.

The results suggest that evening administration of the central alpha(2)-agonists guanabenz and clonidine effectively suppresses the morning BP elevation in treated hypertensive patients.

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