Periodontopathogens levels and clinical response to periodontal therapy in individuals with the interleukin-4 haplotype associated with susceptibility to chronic periodontitis

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

Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

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

Non-destructive thermal wave method applied to study thermal properties of fast setting time endodontic cement

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Non-destructive equations to estimate the leaf area of Styrax pohlii and Styrax ferrugineus

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

Análise microbiológica e imunologica do fluido gengival e proteoma salivar de individuos com Sindrome de Down com doença periodontal

Pós-graduação em Odontologia - FOAR

Synergistic Anti-Inflammatory Activity of the Antimicrobial Peptides Human Beta-Defensin-3 (hBD-3) and Cathelicidin (LL-37) in a Three-Dimensional Co-Culture Model of Gingival Epithelial Cells and Fibroblasts

Given the spread of antibiotic resistance in bacterial pathogens, antimicrobial peptides that can also modulate the immune response may be a novel approach for effectively controlling periodontal infections. In the present study, we used a three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) to investigate the anti-inflammatory properties of human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) and to determine whether these antimicrobial peptides can act in synergy. The 3D co-culture model composed of gingival fibroblasts embedded in a collagen matrix overlaid with gingival epithelial cells had a synergistic effect with respect to the secretion of IL-6 and IL-8 in response to LPS stimulation compared to fibroblasts and epithelial cells alone. The 3D co-culture model was stimulated with non-cytotoxic concentrations of hBD-3 (10 and 20 mu M) and LL-37 (0.1 and 0.2 mu M) individually and in combination in the presence of A. actinomycetemcomitans LPS. A multiplex ELISA assay was used to quantify the secretion of 41 different cytokines. hBD-3 and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IP-10, IL-6, and MCP-1, but only had an additive effect on reducing the secretion of IL-8 in response to A. actinomycetemcomitans LPS stimulation. The present study showed that hBD-3 acted in synergy with LL-37 to reduce the secretion of cytokines by an LPS-stimulated 3D model of gingival mucosa. This combination of antimicrobial peptides thus shows promising potential as an adjunctive therapy for treating inflammatory periodontitis.

Doença periodontal em pacientes com Diabetes Mellitus: influência de polimorfismos genéticos?

Currently it is clear that there are several factors that can act as modifiers of diseases, without causing them directly, but having the potential to make these conditions to progress faster and more severe. There is a growing number of studies investigating the relationship between Diabetes Mellitus (DM) and Periodontal Disease (PD), including some studies focusing on the influence of genetic factors in this process. The aim of this study was to verify through a literature review, the influence of genetic polymorphisms in the development of PD in patients with DM. PubMed and BIREME were used as databases and the terms Periodontitis or Periodontal Disease, Polymorphism, Diabetes Mellitus were searched. After a refinement in the literature, five studies were selected and they were related to chronic PD with DM and polymorphisms in cytokine genes, especially interleukin 1 (IL1) e IL6. Polymorphisms were associated with a higher concentration of pro-inflammatory cytokines in the gingival crevicular fluid of diabetic patients when compared to non-diabetic. In conclusion, it is necessary to confirm this association with longitudinal studies that must investigate a larger number of cytokine genes in order to understand the cause-effect relationship between genetic polymorphisms, DM and PD.

RANKL expression is differentially modulated by TLR2 and TLR4 signaling in fibroblasts and osteoblasts

Resident, non-immune cells express various pattern-recognition receptors and produce inflammatory cytokines in response to microbial antigens, during the innate immune response. Alveolar bone resorption is the hallmark of destructive periodontitis and it is caused by the host response to bacteria and their mediators present on the biofilm. The balance between the expression levels of receptor activator of nuclear factorkappa B ligand (RANKL) and osteoprotegerin (OPG) is pivotal for osteoclast differentiation and activity and has been implicated in the progression of bone loss in periodontitis. To assess the contribution of resident cells to the bone resorption mediated by innate immune signaling, we stimulated fibroblasts and osteoblastic cells with LPS from. Escherichia coli (TLR4 agonist), Porphyromonas gingivalis (TLR2 and -4 agonist), and interleukin-1 beta (as a control for cytokine signaling through Toll/IL-1receptor domain) in time-response experiments. Expression of RANKL and OPG mRNA was studied by RT-PCR, whereas the production of RANKL protein and the activation of p38 MAPK and NF-kB signaling pathways were analyzed by western blot. We used biochemical inhibitors to assess the relative contribution of p38 MAPK and NF-kB signaling to the expression of RANKL and OPG induced by TLR2, -4 and IL1β in these cells. Both p38 MAPK and NFkB pathways were activated by these stimuli in fibroblasts and osteoblasts, but the kinetics of this activation varied in each cell type and with the nature of the stimulation. E. coli LPS was a stronger inducer of RANKL mRNA in fibroblasts, whereas LPS from P. gingivalis downregulated RANKL mRNA in periodontal ligament cells but increased its expression in osteoblasts. IL-1β induced RANKL in both cell types and without a marked effect on OPG expression. p38 MAPK was more relevant than NF-kB for the expression of RANKL and OPG in these cell types.

Haplotypes of susceptibility to chronic periodontitis do not influence MMP-8 levels or the outcome of non-surgical periodontal therapy

Introduction: Chronic periodontitis (CP) is a multifactorial condition, presenting immunoinflammatory reaction, in which a myriad of molecules including cytokines and matrix metalloproteinases (MMPs) interplays, making the system extremely intricate. There is scarce information regarding interconnections of biological influence among IL-4, IL-8 and MMP-8, mainly considering genetic polymorphisms, and also, whether this can influence the outcome of periodontal therapy. Previously, we reported that variants in the interleukin 4 (IL4) and interleukin 8 (IL8) genes were associated with CP in Brazilians. The aim of this study was to investigate, in individuals with different genetic backgrounds with regard to the IL4 or IL8 haplotypes, differences in the immunological levels of MMP-8 in gingival crevicular fluid (GCF) before and after non-surgical periodontal treatment. A total of 141 patients participated of this study, classified as susceptible or not to CP, according to the presence of haplotypes formed by polymorphysms in the IL4 or IL8 genes. All individuals received non-surgical periodontal therapy and follow–up continued for 45 days. The GCF samples were collected at baseline and on the 45th day. The MMP-8 levels were determined by ELISA. Results: No association was found between genetic backgrounds and MMP-8 levels in GCF or the outcome of non-surgical periodontal therapy. Conclusions: In this longitudinal clinical study, the presence of IL4 or IL8 haplotypes previously associated with CP did not influence the outcome of non-surgical periodontal therapy and the MMP-8 levels in the GCF. Additional studies are necessary to determine the mechanisms by which the IL4 or IL8 haplotypes affect individual susceptibility to CP.

Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts

Objectives: The human antimicrobial peptide cathelicidin (LL-37) possesses anti-inflammatory properties that may contribute to attenuating the inflammatory process associated with chronic periodontitis. Plant polyphenols, including those from cranberry and green tea, have been reported to reduce inflammatory cytokine secretion by host cells. In the present study, we hypothesized that A-type cranberry proanthocyanidins (AC-PACs) and green tea epigallocatechin-3-gallate (EGCG) act in synergy with LL-37 to reduce the secretion of inflammatory mediators by oral mucosal cells. Methods: A three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts treated with non-cytotoxic concentrations of AC-PACs (25 and 50 mg/ml), EGCG (1 and 5 mg/ml), and LL-37 (0.1 and 0.2 mM) individually and in combination (AC-PACs + LL-37 and EGCG + LL-37) were stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). Multiplex ELISA assays were used to quantify the secretion of 54 host factors, including chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). Results: LL-37, AC-PACs, and EGCG, individually or in combination, had no effect on the regulation of MMP and TIMP secretion but inhibited the secretion of several cytokines. ACPACs and LL-37 acted in synergy to reduce the secretion of CXC-chemokine ligand 1 (GRO-a), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6), and had an additive effect on reducing the secretion of interleukin-8 (IL-8), interferon-g inducible protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) in response to LPS stimulation. EGCG and LL-37 acted in synergy to reduce the secretion of GRO-a, G-CSF, IL-6, IL-8, and IP-10, and had an additive effect on MCP-1 secretion. Conclusion: The combination of LL-37 and natural polyphenols from cranberry and green tea acted in synergy to reduce the secretion of several cytokines by an LPS-stimulated 3D coculture model of oral mucosal cells. Such combinations show promising results as potential adjunctive therapies for treating inflammatory periodontitis.

Efeitos de drogas antiplaquetárias na doença periodontal

The association between platelets, angiogenesis and progression or repair of periodontal disease has been little explored and, consequently, the results are inconclusive. The pathogenic bacteria present in the periodontal pocket release endotoxins that affect the endothelial integrity and are able to induce the production of chemical mediators derived from plasma proteins and blood clotting while altering platelet function. There is great interest in the modulation of platelet activity in vascular disorders, especially cardiovascular diseases. For this reason, antiplatelet drugs, that are commonly used in the prevention of thromboembolic diseases, such as myocardial infarction, ischemic stroke and peripheral arterial disease, have been used. Aspirin is the only non-steroidal antiinflammatory agent with antiplatelet activity. In the periodontium, instead of only reduces levels of inflammatory cytokines, also significantly affects bleeding on probing, suggesting a dose-dependent modulation of periodontitis. In contrast, clopidogrel and ticlopidine are thienopyridine drugs with no known antiinflammatory action, suggesting that this benefit is related to an antiinflammatory effect indirectly correlated to their antiplatelet activity already established. In the literature there is limited information about the effect of these drugs on periodontium and periodontal disease development. Antiplatelet drugs hypothetically can change both the pathogenesis of periodontitis and subsequent periodontal tissue repair by blocking the secretion of chemical mediators which in general are important in modulating inflammation and tissue repair.

Associação de prótese fixa, implantes e estética periodontal para reabilitação de pacientes parcialmente edêntulos

Periodontitis is a chronic inflammatory disease that results in the destruction of teeth and their supporting tissues with subsequent tooth loss. The replacement of missing teeth for implant-supported restorations has proven to be a highly predictable treatment method with good long-term prognosis. However, some consequences of tooth loss prevents dental implant placement in an ideal position, where regenerative procedures are necessary for this type of rehabilitation. Less invasive procedures such as conventional prosthesis emerge as a therapeutic option in cases where there is enough bone structure for implants and patient´s non-acceptance for invasive procedures. Thus, this paper aims to present the resolution of rehabilitation through a noninvasive and multidisciplinary treatment. One female patient referred to the clinic presented maladaptive bilateral mandibular fixed prostheses, endodontic lesions, gingival recession, and root sensitivity. For proper resolution of this case, an association among osseointegrated implants, fixed partial prosthesis, tooth extraction, and aesthetic periodontal procedures with the use of subepithelial connective tissue graft was proposed. After two years, the patient shows excellent aesthetics and chewing. Within the limits of this scenario, this paper discusses the various factors that may affect the choice of a particular treatment modality for the rehabilitation of edentulous single spaces.

Non-destructive linear model for leaf area estimation in Vernonia ferruginea Less

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

In vitro mucus transportability, cytogenotoxicity, and hematological changes as non-destructive physiological biomarkers in fish chronically exposed to metals

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)