Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Distribution of biotypes and leukotoxic activity of Aggregatibacter actinomycetemcomitans isolated from Brazilian patients with chronic periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protective effects of Tacrolimus, a calcineurin inhibitor, in experimental periodontitis in rats

Objective: Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease.Design: Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1 mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days.Results: Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1 beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1 beta, TNF-alpha and IL-6.Conclusions: the effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease. (C) 2007 Elsevier Ltd. All rights reserved.

iNOS-Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The role of IL-6 on apical periodontitis: a systematic review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Apical periodontitis and periodontal disease increase serum IL-17 levels in normoglycemic and diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Elevated micronucleus frequency in patients with type 2 diabetes, dyslipidemia and periodontitis

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.

Exogenous Administration of 15d-PGJ(2)-Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

New genes of Xanthomonas citri subsp citri involved in pathogenesis and adaptation revealed by a transposon-based mutant library

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pathogenesis II: Fungal responses to host responses: interaction of host cells with fungi

Most of our knowledge concerning the virulence determinants of pathogenic fungi comes from the infected host, mainly from animal models and more recently from in vitro studies with cell cultures. The fungi usually present intra- and/or extracellular host-parasite interfaces, with the parasitism phenomenon dependent on complementary surface molecules. Among living organisms, this has been characterized as a cohabitation event, where the fungus is able to recognize specific host tissues acting as an attractant, creating stable conditions for its survival. Several fungi pathogenic for humans and animals have evolved special strategies to deliver elements to their cellular targets that may be relevant to their pathogenicity. Most of these pathogens express surface factors that mediate binding to host cells either directly or indirectly, in the latter case binding to host adhesion components such as extracellular matrix (ECM) proteins, which act as 'interlinking' molecules. The entry of the pathogen into the host cell is initiated by fungal adherence to the cell surface, which generates an uptake signal that may induce its cytoplasmic internalization. Once this is accomplished, some fungi are able to alter the host cytoskeletal architecture, as manifested by a rearrangement of microtubule and microfilament proteins, and this can also induce epithelial host cells to become apoptotic. It is possible that fungal pathogens induce modulation of different host cell pathways in order to evade host defences and to foster their own proliferation. For a number of pathogens, the ability to bind ECM glycoproteins, the capability of internalization and the induction of apoptosis are considered important factors in virulence. Furthermore, specific recognition between fungal parasites and their host cell targets may be mediated by the interaction of carbohydrate-binding proteins, e.g., lectins on the surface of one type of cell, probably a parasite, that combine with complementary sugars on the surface of host-cell. These interactions supply precise models to study putative adhesins and receptor-containing molecules in the context of the fungus-host interface. The recognition of the host molecules by fungi such as Aspergillus fumigatus, Paracoccidioides brasiliensis and Histoplasma capsulatum, and their molecular mechanisms of adhesion and invasion, are reviewed in this paper.

Spontaneous Periodontitis Development in Diabetic Rats Involves an Unrestricted Expression of Inflammatory Cytokines and Tissue Destructive Factors in the Absence of Major Changes in Commensal Oral Microbiota

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Traumatic subdural hygromas: Proposed pathogenesis based classification

Background: Traumatic subdural hygroma (TSHy) is an accumulation of cerebrospinal fluid (CSF) in the subdural space after head injury. It appears to be relatively common, but its onset time and natural history are not well defined. Considered a benign epiphenomenon of trauma, the pathogenesis of TSHy is still unclear and many questions remain unanswered. This study adds to the information on TSHy, and proposes a classification based on pathogenesis.Methods: Thirty-four consecutive adult patients with TSHy were analyzed for clinical evolution and serial CT scan, during a period of several months. TSHy diagnosis was based on published CT scan criteria of hypodense subdural collection after trauma, without enhancement and neomembrane, with a minimum distance of 3 mm between the skull and brain. Ventricle size was analyzed by calculating the bicaudate index (BCI). For comparison, the BCI was measured from CT scan at three moments: admission, at time of TSHy diagnosis, and from last CT scan.Results: There were 34 patients, aged between 16 and 85 years (mean 40), half of them were below 40 years. Road traffic crashes were the main cause of head injury. The mean time for hygroma diagnosis was 9 days. Twenty-one patients (61.8%) underwent conservative treatment for TSHy and 13 (38.2%), surgical treatment. TSHy are early lesions and can be detected in the first 24 hours after trauma, usually as small subdural effusion (SSEff). Based on clinical and CT scan findings, we divided the 34 patients into 3 groups, (Ia and Ib) without evident mass effect and (II) with evident mass effect. Group Ia includes patients without ventricle dilation; Ib, patients with associated ventricle dilations.Conclusions: SSEff detected in the first 24 hours posttrauma in our series evolved into TSHy suggesting that this is an early lesion; all THSy were divided in three groups according to the pathophysiologic mechanism. These three groups probably represent a continuum of CSF absorption impairment. Group la represents what most authors consider a simple hygroma, with no impairment on CSF absorption. Group Ib represent the external hydrocephalus form with various degrees of CSF imbalance, and group II were the cases presenting marked mass effect.