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Purpose: The retinal pigment epithelium (RPE) is a barrier to Klebsiella pneumoniae infection in endogenous endophthalmitis. Nevertheless, the inflammatory response of RPE cells upon interaction with this pathogen has not been studied. Here we tested the hypothesis that K. pneumoniae induces an inflammatory response in human retinal epithelial cells., Methods: In this study we set out to investigate the effects of whole K. pneumoniae and of its lipopolysaccharide on RPE cells in vitro using bacterial invasion and cytotoxicity assays, fluorescent microscopy and ELISA. For that, we utilized K. pneumoniae strain ATCC 43816 and the continuous human retinal-pigmented epithelial cell line ARPE-19., Results: Stimulation of ARPE-19 with live K. pneumoniae for 24h induced a 31.5-fold (p=0.0132) increase in IL-6 and 6.5-fold (p=0.0004) increase in MCP-1 levels compared to the non-infected control cells. Purified K. pneumoniae LPS (1μgml(-1)) also induced cytokine levels, MCP-1 (1.7-fold upregulation; p=0.0006) and IL-6 (1.3-fold upregulation, p=0.065). The tested K. pneumoniae strain ATCC 43816 did not have a significant effect on the viability of ARPE-19 cells (11% decrease, p=0.096) and showed a low ability to invade the cells., Conclusions: Both whole live K. pneumoniae and K. pneumoniae LPS exert a strong pro-inflammatory effect on retinal pigmented epithelial cells, consistent with clinical manifestations of disease. Bacterial pro-inflammatory effects are not likely related to host cell invasion. This is the first investigation of the interactions of a major endogenous endophthalmitis pathogen, K. pneumoniae with human retinal pigmented epithelial cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: A link between periodontal infections and an increased risk for vascular disease has been demonstrated. Porphyromonas gingivalis, a major periodontal pathogen, localizes in human atherosclerotic plaques, accelerates atherosclerosis in animal models and modulates vascular cell function. The receptor for advanced glycation endproducts (RAGE) regulates vascular inflammation and atherogenesis. We hypothesized that RAGE is involved in P. gingivalis's contribution to pro-atherogenic responses in vascular endothelial cells., Methods and Results: Murine aortic endothelial cells (MAEC) were isolated from wild-type C57BL/6 or RAGE-/- mice and were infected with P. gingivalis strain 381. P. gingivalis 381 infection significantly enhanced expression of RAGE in wild-type MAEC. Levels of pro-atherogenic advanced glycation endproducts (AGEs) and monocyte chemoattractant protein 1 (MCP-1) were significantly increased in wild-type MAEC following P. gingivalis 381 infection, but were unaffected in MAEC from RAGE-/- mice or in MAEC infected with DPG3, a fimbriae-deficient mutant of P. gingivalis 381. Consistent with a role for oxidative stress and an AGE-dependent activation of RAGE in this setting, both antioxidant treatment and AGE blockade significantly suppressed RAGE gene expression and RAGE and MCP-1 protein levels in P. gingivalis 381-infected human aortic endothelial cells (HAEC)., Conclusion: The present findings implicate for the first time the AGE-RAGE axis in the amplification of pro-atherogenic responses triggered by P. gingivalis in vascular endothelial cells., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The term "diabetes mellitus" describes a group of disorders characterized by elevated levels of glucose in the blood and abnormalities of carbohydrate, fat and protein metabolism. A number of oral diseases and disorders have been associated with diabetes mellitus, and periodontitis has been identified as a possible risk factor for poor metabolic control in subjects with diabetes., Methods: The authors reviewed the literature to identify oral conditions that are affected by diabetes mellitus. They also examined the literature concerning periodontitis as a modifier of glycemic control., Results: Although a number of oral disorders have been associated with diabetes mellitus, the data support the fact that periodontitis is a complication of diabetes. Patients with long-standing, poorly controlled diabetes are at risk of developing oral candidiasis, and the evidence indicates that periodontitis is a risk factor for poor glycemic control and the development of other clinical complications of diabetes. Evidence suggests that periodontal changes are the first clinical manifestation of diabetes., Conclusions: Diabetes is an important health care problem. The evidence suggests that oral health care providers can have a significant, positive effect on the oral and general health of patients with diabetes mellitus.

Background: As a link between periodontal infections and an increased risk for vascular disease has been demonstrated, we assessed the ability of the Gram-negative periodontal pathogen Porphyromonas gingivalis to modulate properties of endothelial cells linked to inflammation and proatherogenic pathways., Methods and Results: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis strain 381 or its non-invasive fimbriae-deficient mutant, DPG3, and incubated with U-937 monocytes, or Jurkat T cells. P. gingivalis-infected HAEC demonstrated significantly increased adhesion of immune cells compared to non-infected cells or those infected with DPG3. Heat-killed bacteria had no effect on mononuclear cell adhesion and P. gingivalis LPS had only a minimal effect. P. gingivalis infection significantly increased HAEC expression of VCAM-1, ICAM-1 and E-selectin, and enhanced production of IL-6, IL-8 and MCP-1., Conclusion: These data demonstrate that live invasive P. gingivalis 381 elicits a pro-atherogenic response in HAEC.

Background: Advances in understanding the relationship between oral disease and systemic conditions need to be translated into clinical practice. Relevant here is assessing dentists' active involvement in in-office smoking-cessation activities and management of the patient with type 1 or type 2 diabetes., Methods: The authors mailed a survey to a net sample of 132 active general practitioners (GPs) in the northeastern United States during fall 2002. They drew a random sample of GPs listed in the designated states from the 2001 American Dental Association directory. They received 105 responses, for a response rate of 80 percent., Results: With regard to smoking-cessation activities and management of diabetic patients, a majority of GPs reported having a lack of knowledge, viewed such activities as peripheral to their role and disagreed that colleagues and/or patients expected them to perform such activities. More GPs performed both activities on an assessing/advising basis than on an active management basis., Conclusion: Results suggest that approaches to changing dentists' behavior should aim not only at increasing knowledge but at overcoming attitudes and orientations associated with actively managing patients who smoke and patients who have diabetes., Practice Implications: The profession's growing evidence base supports an increased primary and preventive care role for dentists. This role affords them opportunities to expand the bounds of dental practice, improve therapeutic outcomes and promote patients' overall health.

The glycation and oxidation of proteins/lipids leads to the generation of a new class of biologically active moieties, the advanced glycation endproducts (AGEs). Recent studies have elucidated that carboxymethyllysine (CML) adducts of proteins/lipids are a highly prevalent AGE in vivo. CML-modified adducts are signal transduction ligands of the receptor for AGE (RAGE), a member of the immunoglobulin superfamily. Importantly, CML-modified adducts accumulate in diverse settings. In addition to enhanced formation in settings of high glucose, these adducts form in inflammatory milieu. Studies performed both in vitro and in vivo have suggested that the proinflammatory/tissue destructive consequences of RAGE activation in the diabetic/inflamed environment may be markedly attenuated by blockade of the ligand-RAGE axis. Here, we will summarize the known consequences of RAGE activation in the tissues and highlight novel areas for therapeutic intervention in these disease states.