The results of this study indicate the presence of a significant relationship between periodontitis, hyperlipidemia, and serum antibodies against P. gingivalis LPS that warrants further examination in a larger patient population. Furthermore, these studies indicate that elevated triglycerides are able to modulate IL-1beta production by PMNs stimulated with P. gingivalis LPS.

Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/or increased inflammatory mediators. These cytokines can produce an insulin resistance syndrome similar to that observed in diabetes and initiate destruction of pancreatic beta cells leading to development of diabetes. Thus, there is potential for periodontitis to exacerbate diabetes-induced hyperlipidemia, immune cell alterations, and diminished tissue repair capacity. It may also be possible for chronic periodontitis to induce diabetes.

Periodontitis has been traditionally regarded as a chronic inflammatory oral infection. However, recent studies indicate that this oral disease may have profound effects on systemic health. The search for cellular/molecular mechanisms linking periodontitis to changes in systemic health and systemic physiology has resulted in the evolution of a new area of lipid research establishing linkages between existing multidisciplinary biomedical literature, recent observations concerning the effects of serum lipids on immune cell phenotype/function, and a heightened interest in systemic responses to chronic localized infections. There appears to be more than a casual relationship between serum lipid levels and systemic health (particularly cardiovascular disease, diabetes, tissue repair capacity, and immune cell function), susceptibility to periodontitis, and serum levels of pro-inflammatory cytokines. In terms of the potential relationship between periodontitis and systemic disease, it is possible that periodontitis-induced changes in immune cell function cause metabolic dysregulation of lipid metabolism through mechanisms involving proinflammatory cytokines. Sustained elevations of serum lipids and/or pro-inflammatory cytokines may have a serious negative impact on systemic health. The purpose of this paper is to present the background, supporting data, and hypotheses related to this concept. As active participants in this emerging and exciting area of investigation, we hope to stimulate interest and awareness among biomedical scientists and practitioners.

The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50488%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age-and sex-matched controls yielded significant decreases (60488%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.There has been much interest in the 28-kDa calbindin-D

This confirms our earlier work in the diabetic rat model. These studies indicate that decreased metabolic control in type 2 diabetics results in increased serum triglycerides and has a negative influence on all clinical measures of periodontal health, particularly in patients without preexisting periodontitis. Levels of the cytokine IL- 1beta showed a trend for increasing as diabetic control diminished. In contrast, levels of the growth factor PDGF, which normally increase in periodontitis, decreased in poorly controlled diabetics with periodontitis. These studies suggest a possible dysregulation of the normal cytokine/growth factor signaling axis in poorly controlled type 2 diabetics that may contribute to periodontal breakdown/diminished repair.

READ THESE TERMS AND CONDITIONS CAREFULLY BEFORE USING THIS WEBSITE.Access and use of this website and the material on it are subject to the Terms and Conditions set forth at http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/jsp/nparc_cp.jsp?lang=en An Update on Novel Non-Invasive Approaches for Periodontal DiagnosisXiang, Xiaoming; Sowa, Michael G.; Iacopino , Anthony M.; Maev, Roman G.; Hewko, Mark D.; Man, Angela; Liu, Kan-Zhi Abstract For decades there has been an ongoing search for clinically acceptable methods for the accurate, non-invasive diagnosis and prognosis of periodontitis. There are several well-known inherent drawbacks with current clinical procedures. The purpose of this review is to summarize some of the newly emerging diagnostic approaches, namely, infrared spectroscopy, optical coherence tomography (OCT), and ultrasound. The history and attractive features of these new approaches are briefly illustrated, and the interesting and significant inventions related to dental applications are discussed. The particularly attractive aspects for the dental community are that some of these methods are totally non-invasive, do not impose any discomforts to the patients during the procedure, and require no tissue to be extracted. For instance, multiple inflammatory indices withdrawn from near infrared spectra have the potential to identify early signs of inflammation leading to tissue breakdown. Morphologically, some other non-invasive imaging modalities, such as OCT and ultrasound, could be employed to accurately measure probing depths and assess the status of periodontal attachment, the front-line of disease progression. Given that these methods reflect a completely different assessment of periodontal inflammation, if clinically validated, these methods could either replace traditional clinical examinations for the diagnosis of periodontitis or at least serve as attractive complementary diagnostic tools. However, the potential of these techniques should be interpreted more cautiously given the multifactorial character of periodontal disease. In addition to these novel tools in the field of periodontal inflammatory diseases, other alternative modalities like microbiologic and genetic approaches are only briefly mentioned in this review because they have been thoroughly discussed in other comprehensive reviews.Periodontitis is an endemic infectious disease of the tissues surrounding the teeth occurring in 50% of the population and may result in significant debilitation for about half of these persons. 1As the leading cause of edentulism, periodontitis may also have important implications for systemic health including an increased risk for cardiovascular disease and low birth weight/preterm delivery.2 According to a report by the World Health Organization, 3 severe periodontitis leading to tooth loss was found in 5% to 15% of most populations worldwide. Therefore, it is considered one of the most important global oral health burdens.Periodontitis is a multifactorial disease with microbial dental plaque as the in...

Advances in all aspects of science and discovery continue to occur at an exponential rate, leading to a wealth of new knowledge and technologies that have the potential to transform dental practice. This "new science" within the areas of cell/ molecular biology, genetics, tissue engineering, nanotechnology, and informatics has been available for several years; however, the assimilation of this information into the dental curriculum has been slow. For the profession and the patients it serves to benefit fully from modern science, new knowledge and technologies must be incorporated into the mainstream of dental education. The continued evolution of the dental curriculum presents a major challenge to faculty, administrators, and external constituencies because of the high cost, overcrowded schedule, unique demands of clinical training, changing nature of teaching/assessment methods, and large scope of new material impacting all areas of the educational program. Additionally, there is a lack of personnel with adequate training/experience in both foundational and clinical sciences to support the effective application and/or integration of new science information into curriculum planning, implementation, and assessment processes. Nonetheless, the speed of this evolution must be increased if dentistry is to maintain its standing as a respected health care profession. The influence of new science on dental education and the dental curriculum is already evident in some dental schools. For example, the Marquette University School of Dentistry has developed a comprehensive model of curriculum revision that integrates foundational and clinical sciences and also provides a dedicated research/scholarly track and faculty development programming to support such a curriculum. Educational reforms at other dental schools are based on addition of new curricular elements and include innovative approaches that introduce concepts regarding new advances in science, evidence-based foundations, and translational research. To illustrate these reforms, the Marquette curriculum and initiatives at the University of Connecticut and the University of Texas Health Science Center at San Antonio dental schools are described in this article, with recognition that other dental schools may also be developing strategies to infuse new science and evidence-based critical appraisal skills into their students' educational experiences. Discussion of the rationale, goals/objectives, and outcomes within the context of dissemination of these models should help other dental schools to design approaches for integrating this new material that are appropriate to their particular circumstances and mission. For the profession to advance, every dental school must play a role in establishing a culture that attaches value to research/discovery, evidence-based practice, and the application of new knowledge/technologies to patient care.

Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of seizures. A common side effect of PHT therapy is gingival hyperplasia, occasionally so severe that it requires surgical intervention. Cyclosporine A (CSA) is a drug widely used for the control of rejection phenomena following solid organ and bone marrow transplantation. A frequent side effect of CSA administration is gingival overgrowth. As yet, the molecular mechanisms of drug-induced gingival hyperplasia are unknown although it has been postulated that certain drugs increase fibroblastic activity through alterations in levels of various growth factors and cytokines. The purpose of this study was to: 1) evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and interleukin (IL)-1 beta production in vitro after exposure to CSA; 2) determine the levels of PDGF-B and IL-1 beta gene expression in minimally inflamed gingival tissues of control patients and PHT-treated patients exhibiting gingival overgrowth as well as patients with severe gingival inflammation; and 3) combine characterization of macrophage phenotype with clinical presentation and expression of PDGF-B and IL-1 beta in gingival tissues from the control and PHT-treated patients. For the in vitro studies, commercial ELISA kits were used to measure PDGF-A/PDGF-B and IL-1 beta levels in conditioned media from rat and human monocyte/macrophage cell cultures. CSA caused a significant elevation of PDGF but did not cause any changes in IL-1 beta levels. For the in vivo studies, quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B and IL-1 beta mRNA levels in experimental groups. PHT-treated patients exhibiting gingival overgrowth demonstrated a significant increase in PDGF-B mRNA compared with minimally inflamed controls. Patients with severe gingival inflammation also demonstrated a significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is approximately 6 times larger than PDGF-B upregulation produced by inflammation alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no significant increase in IL-1 beta mRNA; however, IL-1 beta mRNA levels in the severely inflamed gingival samples demonstrated a significant increase. Additionally, for the clinical samples, macrophage phenotype was characterized immunohistochemically in adjacent sections using specific monoclonal antibodies for inflammatory and reparative/proliferative phenotypes. There were no significant differences in the numbers of either macrophage phenotype in minimally inflamed gingival tissues; however, in the severely inflamed tissue, there was a significant increase in the inflammatory macrophage phenotype and in the hyperplastic gingival tissue, there was a significant increase in the reparative/proliferative macrophage phenotype. The results of this investigation indicate that the clinical presentation of inflamed and hyperplastic gingival tissues is associated with specific macrophages phenotyp...