RAGE: A journey from the complications of diabetes to disorders of the nervous system – striking a fine balance between injury and repair

This is the published version. Copyright 2005 IOS Press.The Receptor for Advanced Glycation End Products (RAGE) is a multiligand member of the immunoglobulin superfamily. RAGE interacts with AGEs, the products of nonenzymatic glycation/oxidation of proteins and lipids that accumulate in diverse settings, such as diabetes, inflammation, renal failure, pro-oxidant states and natural aging. In addition, RAGE is also a receptor for amyloid-β peptide and β-sheet fibril species. Recent studies underscore the premise that RAGE interacts with pro-inflammatory molecules, including S100/calgranulins and amphoterin, the latter also known as high mobility group box 1 (HMGB1). In chronic neurodegenerative disorders as well as in nerve tissue upon acute injury, evidence points to upregulation of both RAGE and these ligand families. In this review, we will discuss the implications of transient/self-limited upregulation of RAGE and its ligands, vs sustained/chronic upregulation of this axis in neurodegeneration vs repair in both the central and peripheral nervous systems. Experimental evidence supports the premise that RAGE bears both homeostatic and injurious properties in the nervous system, thereby highlighting "yin/yang" features of this receptor and its ligand families

Periodontal manifestations of systemic diseases and developmental and acquired conditions:consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions

BACKGROUND A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly prevalent and often associated with hypersensitivity, the development of caries and non-carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations. METHODS Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants. RESULTS Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon-Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm-induced inflammation (such as neoplastic diseases); 2) diabetes-associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking - now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues - is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non-carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm-induced gingival inflammation and loss of periodontal supporting tissues. CONCLUSION An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented

Dentists’ Management of the Diabetic Patient: Contrasting Generalists and Specialists

Objectives. We measured and contrasted general dentists’ and periodontists’ involvement in 3 areas of managing diabetic patients—assessment of health status, discussion of pertinent issues, and active management of patients—and identified and contrasted predictors of active management of diabetic patients. Methods. We conducted a cross-sectional mail survey of random samples of general dentists and periodontists in the northeastern United States during fall 2002, using lists from the 2001 American Dental Directory and the 2002 American Academy of Periodontology Directory. Responses were received from 105 of 132 eligible general dentists (response rate=80%) and from 103 of 142 eligible periodontists (response rate=73%). Results. Confidence, involvement with colleagues and medical experts, and professional responsibility were influential predictors of active management for periodontists (R(2)=0.46, P<.001). Variables pertaining to patient relations were significant predictors for general dentists (R(2)=0.55, P<.001). Conclusions. Our findings permitted us to assess and compare general dentists’ and periodontists’ behavior in 3 realms—assessment of diabetic patients’ health status, discussion of pertinent issues, and active management of diabetic patients—and to identify components of potentially effective targeted interventions aimed at increasing specialists’ and generalist dentists’ involvement in the active management of diabetic patients

Receptor for advanced glycation endproducts mediates pro-atherogenic responses to periodontal infection in vascular endothelial cells

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. 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). 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

A revision of two distinct species of Rhipicephalus: R. microplus and R. australis

ABSTRACT: Rhipicephalus ( Boophilus ) species are monoxenous ticks with seasonal distribution in tropical and subtropical regions. For many years, Rhipicephalus microplus was considered as a single species; however, further analysis split these ticks into two distinct species. Because R. microplus and R. australis share similar attributes, it is hard to discriminate these two species and explain the changes in the classification of these parasites over the past decades. The reappearance of R. australis is an outcome of new research, which has afforded to better characterize these probably cryptic species. Evidence based on morphological features, the lack of conspecificity, microsatellite markers, mitochondrial 12S and 16S ribosomal DNA, and mitochondrial genome supports the re-classification of R. microplus as different species. Therefore, populations of R. microplus from Australia, Cambodia, Philippines, Indonesia, New Caledonia, Borneo, New Guinea, Tahiti and parts of Southeast Asia were recently reinstated as R. australis . Moreover, a better knowledge on the speciation between these two species could pave the way to important advances in tick control strategies