Francisco H Nociti

National Institute of Arthritis and Musculoskeletal and Skin Diseases, 베서스다, Maryland, United States

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Publications (140)369.6 Total impact

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    ABSTRACT: Eukaryotic translation elongation factor 1 delta (EEF1D) is a subunit of the elongation factor 1 complex of proteins that mediates the elongation process during protein synthesis via enzymatic delivery of aminoacyl tRNAs to the ribosome. While the functions of EEF1D in the translation process are recognized, EEF1D expression was found to be unbalanced in tumors. Here we demonstrated the overexpression of EEF1D in oral squamous cell carcinoma (OSCC), and revealed that EEF1D and protein interaction partners promote the activation of cyclin D1 and vimentin proteins. EEF1D knockdown in OSCC reduced cell proliferation and induced epithelial-to-mesenchymal transition (EMT) phenotypes, including cell invasion. Taken together, these results define EEF1D as a critical inducer of OSCC proliferation and EMT.
    No preview · Article · Jan 2016 · Clinical Science
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    ABSTRACT: Objective: This study aims to clinically evaluate the treatment of mandibular class II furcation defects with enamel matrix derivative (EMD) and/or a bone substitute graft made of β-tricalcium phosphate/hydroxyapatite (βTCP/HA). Materials and methods: Forty-one patients, presenting a mandibular class II buccal furcation defect, probing pocket depth (PPD) ≥4 mm and bleeding on probing, were included. They were randomly assigned to the groups: 1-EMD (n = 13); 2-βTCP/HA (n = 14); 3-EMD + βTCP/HA (n = 14). Plaque index (PI), gingival index (GI), relative gingival margin position (RGMP), relative vertical and horizontal attachment level (RVCAL and RHCAL), and PPD were evaluated at baseline and 6 and 12 months. The mean horizontal clinical attachment level gain was considered the primary outcome variable. Results: No significant intragroup differences were observed for RGMP, but significant changes were observed for RVCAL, RHCAL, and PPD for all groups (p < 0.05). After 12 months, the mean horizontal clinical attachment level gain was 2.77 ± 0.93 mm for EMD, 2.64 ± 0.93 mm for βTCP/HA, and 2.93 ± 0.83 mm for EMD + βTCP/HA, with no significant differences among the groups. At the end of the study, 85.3 % of the sites were partially closed; however, no complete closure was observed. Conclusion: EMD + βTCP/HA does not provide a significant advantage when compared to the isolated approaches. All three tested treatments promote significant improvements and partial closure of class II buccal furcation defects. Based on its potential to induce periodontal regeneration, EMD may be considered an attractive option for this type of defect, but complete closure remains an unrealistic goal. Clinical relevance: The partial closure of buccal furcation defects can be achieved after the three tested approaches. However, the combined treatment does not provide a significant benefit when compared to the isolated approaches.
    No preview · Article · Nov 2015 · Clinical Oral Investigations
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    ABSTRACT: Aim: Generalized aggressive periodontitis (GAP) is a severe and multifactorial disease in which a familial aggregation and a specific microbiological profile has been suggested. Thus, this case-control study evaluated the clinical and subgingival microbial profile of GAP subjects and their families compared to healthy families. Methods: Fifteen families with parents presenting periodontal health and 15 with parents with a history of GAP were selected. Each family should have at least one child between 6-12 years old. Plaque index (PI), gingival index (GI), and periodontal probing depth (PPD), as well as Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Aggregatibacter actinomycetemcomitans (Aa) amounts (by qPCR), were assessed from all subjects. Results: Children of GAP families showed a higher PI, GI and PPD when compared to children of healthy families (p≤0.05). A higher frequency of detection and amounts of A. actinomycetemcomitans was observed in GAP children compared to children of healthy families (p≤0.05). Moreover, a significant association between A. actinomycetemcomitans amounts and gingival bleeding was observed in children (p≤0.05, r=0.37). Conclusion: Children from GAP families have worst clinical conditions, i.e. higher levels of PI, GI and PPD, a more pathogenic microbiological profile and the amount of A. actinomycetemcomitans are associated with a higher marginal inflammation. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Journal Of Clinical Periodontology
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    ABSTRACT: The dental cementum covering the tooth root is similar to bone in several respects, but remains poorly understood in terms of development and differentiation of cementoblasts, as well as the potential function(s) of cementocytes residing in the cellular cementum. It is not known if the cementocyte is a dynamic actor in cementum metabolism, comparable to the osteocyte in the bone. Cementocytes exhibit irregular spacing and lacunar shape, with fewer canalicular connections compared to osteocytes. Immunohistochemistry and quantitative PCR (qPCR) revealed that the in vivo expression profile of cementocytes paralleled that of osteocytes, including expression of dentin matrix protein 1 (Dmp1/DMP1), Sost/sclerostin, E11/gp38/podoplanin, Tnfrsf11b (osteoprotegerin; OPG), and Tnfsf11 (receptor activator of NF-kB ligand; RANKL). We used the Immortomouse(+/-) ; Dmp1-GFP(+/-) mice to isolate cementocytes as Dmp1-expressing cells followed by immortalization using the interferon (IFN)-γ-inducible promoter driving expression of a thermolabile large T antigen to create the first immortalized line of cementocytes, IDG-CM6. This cell line reproduced the expression profile of cementocytes observed in vivo, including alkaline phosphatase activity and mineralization. IDG-CM6 cells expressed higher levels of Tnfrsf11b, and lower levels of Tnfsf11 compared to IDG-SW3 osteocytes, and under fluid flow shear stress, IDG-CM6 cells significantly increased OPG while decreasing RANKL, leading to a significantly increased OPG/RANKL ratio, which would inhibit osteoclast activation. These studies indicate similarities yet potentially important differences in the function of cementocytes as compared to osteocytes and support cementocytes as mechanically responsive cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: This study evaluated the clinical, immunological and microbiological results of full-mouth ultrasonic debridement (FMUD) with 10 % povidone iodine (PVPI) as the cooling liquid in the treatment of generalised aggressive periodontitis (GAgP). Twenty-eight patients presenting GAgP were randomly assigned to one of the following groups for evaluation: FMUD + SS (n = 14)-single session of FMUD with 0.9 % saline solution as cooling agent and FMUD + PVPI (n = 14)-single session of FMUD with PVPI solution as cooling agent. Probing depth (PD), relative clinical attachment level (RCAL), relative position of gingival margin, plaque index (FMPI) and bleeding score (FMBS), immunological (interleukin-10 and interleukin-1β concentrations in gingival crevicular fluid) and microbiological (Aa and Pg amounts) parameters were evaluated at baseline, first, third and sixth months after treatment. The two groups presented reduction of FMPI and FMBS and had statistically significant PD reductions, RCAL gains and gingival recession (p < 0.05). Both therapies reduced Pg levels in deep and in moderate pockets (p < 0.05). FMUD + PVPI reduced Aa levels in deep pockets. However, no inter-group differences in clinical, immunological and microbiological parameters were observed (p > 0.05). It could be concluded that 10 % PVPI used as an irrigant solution in FMUD decreased Aa levels in deep pockets but had no additional benefits when compared with saline solution irrigation in terms of clinical, microbiological and immunological results. The FMUD is a valid option for the treatment of GAgP, but the use of 10 % PVPI did not improve the results of the periodontal therapy.
    No preview · Article · Apr 2015 · Clinical Oral Investigations
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    ABSTRACT: Tissue engineering is an emerging field of science that focuses on creating suitable conditions for the regeneration of tissues. The basic components for tissue engineering involve an interactive triad of scaffolds, signaling molecules, and cells. In this context, stem cells (SCs) present the characteristics of self-renewal and differentiation capacity, which make them promising candidates for tissue engineering. Although they present some common markers, such as cluster of differentiation (CD)105, CD146 and STRO-1, SCs derived from various tissues have different patterns in relation to proliferation, clonogenicity, and differentiation abilities in vitro and in vivo. Tooth-derived tissues have been proposed as an accessible source to obtain SCs with limited morbidity, and various tooth-derived SCs (TDSCs) have been isolated and characterized, such as dental pulp SCs, SCs from human exfoliated deciduous teeth, periodontal ligament SCs, dental follicle progenitor cells, SCs from apical papilla, and periodontal ligament of deciduous teeth SCs. However, heterogeneity among these populations has been observed, and the best method to select the most appropriate TDSCs for regeneration approaches has not yet been established. The objective of this review is to outline the current knowledge concerning the various types of TDSCs, and discuss the perspectives for their use in regenerative approaches.
    Full-text · Article · Mar 2015
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    ABSTRACT: Periodontal ligament mesenchymal stem cells (PDLMSCs) are an important alternative source of adult stem cells and may be applied for periodontal tissue regeneration, neuroregenerative medicine, and heart valve tissue engineering. However, little is known about the impact of bacterial toxins on the biological properties of PDLSMSCs, including self-renewal, differentiation, and synthesis of extracellular matrix. This study investigated whether proliferation, expression of pro-inflammatory cytokines, and osteogenic differentiation of CD105-enriched PDL progenitor cell populations (PDL-CD105+ cells) would be affected by exposure to bacterial lipopolysaccharide from Escherichia coli (EcLPS). Toll-like receptor 4 (TLR4) expression was assessed in PDL-CD105+ cells by the immunostaining technique and confirmed using Western blotting assay. Afterwards, these cells were exposed to EcLPS, and the following assays were carried out: (i) cell viability using MTS; (ii) expression of the interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) genes; (iii) osteoblast differentiation assessed by mineralization in vitro, and by mRNA levels of run-related transcription factor-2 (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN) determined by quantitative PCR. PDL-CD105+ cells were identified as positive for TLR4. EcLPS did not affect cell viability, but induced a significant increase of transcripts for IL-6 and IL-8. Under osteogenic condition, PDL-CD105+ cells exposed to EcLPS presented an increase of mineralized matrix deposition and higher RUNX2 and ALP mRNA levels when compared to the control group. These results provide evidence that CD105-enriched PDL progenitor cells are able to adapt to continuous Escherichia coli endotoxin challenge, leading to an upregulation of osteogenic activities.
    Preview · Article · Mar 2015 · Journal of applied oral science: revista FOB
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    Francisco H. Nociti · Marcio Z. Casati · Poliana Mendes Duarte
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    ABSTRACT: This literature review provides an overview of the current scenario regarding the impact of smoking on the progression and treatment of periodontitis; clinical, microbiological and immunological data from studies from our and other groups are presented. In general, preclinical and clinical data are unanimous in demonstrating that smokers present increased susceptibility, greater severity and faster progression of periodontal disease compared with nonsmokers. The evidence further demonstrates that smokers lose more teeth and have a less favorable response to therapy than do nonsmokers. Although it is well established that smoking significantly impacts on the onset, progression and outcome of periodontal disease, the mechanisms involved remain unclear. More importantly, some of the reported deleterious effects of smoking on periodontal tissues have been reported to be reversible upon participation in smoking-cessation programs. Therefore, clinicians should strongly advise smokers to enroll in cessation strategies, even temporarily, in order to improve the overall outcome.
    Preview · Article · Feb 2015 · Periodontology 2000
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    ABSTRACT: Background Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by immunodeficiency, oculocutaneous albinism, neurological dysfunction, and early death. Individuals with CHS present with increased susceptibility to infections of the skin, upper-respiratory tract, gastrointestinal tract, and oral tissues. Classical CHS is caused by mutations in the gene encoding lysosomal trafficking regulator (LYST). Although defects in cytotoxic T cell lytic secretory granule secretion and neutrophil phagocytosis are suggested to contribute to the immunodeficiency in CHS, the underlying molecular mechanisms are unknown. We hypothesized that skin fibroblasts from CHS subjects exhibit impaired immune response due to defective trafficking of inflammatory factors.Methods and resultsPrimary skin fibroblasts from CHS subjects or healthy controls were assessed for genes encoding inflammatory response factors using PCR array. At baseline, we found CD14, IL1R1 and TLR-1 were down-regulated significantly (¿2 fold change) and the genes encoding TLR-3, IL-1ß and IL-6 were up-regulated in CHS cells compared to control cells. When challenged with E. coli lipopolysaccharide (LPS), CHS cells were less responsive than control cells, with only 8 genes significantly up-regulated (3¿68 fold change) compared to baseline values, whereas 28 genes in control cells were significantly up-regulated at a much higher magnitude (3¿4,629 fold change). In addition, 50% of the genes significantly up-regulated in LPS-treated control cells were significantly lower in LPS-treated CHS cells. IL-6, a fibroblast-derived proinflammatory cytokine essential for fighting infections was significantly lower in culture media of CHS cells with or without LPS. Furthermore, Western blot and immunofluorescent staining revealed that TLR-2 and TLR-4 were diminished on cell membranes of CHS cells and dissociated from Rab11a.Conclusions For the first time, results from our study indicate defective trafficking of TLR-2 and TLR-4 contributes to the hyposensitive response of CHS skin fibroblasts to immunogenic challenge, providing a potential therapeutic target for clinical intervention in CHS.
    Full-text · Article · Dec 2014 · Orphanet Journal of Rare Diseases
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    ABSTRACT: Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate (Pi) to mineral inhibitor pyrophosphate (PPi), where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.
    Full-text · Article · Dec 2014 · International Journal of Oral Science
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    ABSTRACT: Background: It is known that periodontal ligament (PDL) harbors a heterogeneous progenitor cell population at different stages of lineage commitment. However, characterization of PDL stem cells committed to osteoblast/cementoblast (O/C) differentiation remains to be elucidated. The present study is carried out to isolate single cell-derived, cluster of differentiation (CD)105-positive PDL clones and to characterize the clones that present high potential to differentiate toward O/C phenotype in vitro. Methods: Isolation of single cell-derived colonies (clones) from a CD105-enriched PDL progenitor cell population was performed by the ring-cloning technique. Cell clones were evaluated for their O/C differentiation potential, metabolic activity, and expression of STRO-1 protein. Additionally, the clones that showed potential to O/C differentiation were characterized by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for expression of runt-related transcriptor factor 2 (RUNX2), alkaline phosphatase, CD105, and CD166 during osteogenic induction. Results: Six PDL-CD105(+) clones were obtained, three being highly O/C clones (C-O) and three others that did not have the ability to produce mineralized matrix in vitro (C-F). The C-O group showed lower metabolic activity compared with the C-F group, and both cell groups were positively immunostained for STRO-1. qRT-PCR analysis demonstrated an increased expression of transcripts for RUNX2 and CD166 during the maturation of C-O cells toward O/C phenotype. Conclusions: These results provide evidence that PDL-CD105(+) purified progenitor cells comprise a heterogeneous cell population that presents a cell subset with high O/C potential and, further, that surface antigen CD166 is modulated during the O/C maturation of this cell subset.
    No preview · Article · Feb 2014 · Journal of Periodontology
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    ABSTRACT: Background: Psychologic stress and clinical hypercortisolism have been related to direct effects on bone metabolism. However, there is a lack of information regarding the outcomes of regenerative approaches under the influence of chronic stress (CS). Enamel matrix derivative (EMD) has been used in periodontal regenerative procedures, resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of CS in the rat model. Methods: Twenty Wistar rats were randomly assigned to two groups; G1: CS (restraint stress for 12 hours/day) (n = 10), and G2: not exposed to CS (n = 10). Fifteen days after initiation of CS, fenestration defects were created at the buccal aspect of the first mandibular molar of all animals from both groups. After the surgeries, the defects of each animal were randomly assigned to two subgroups: non-treated control and treated with EMD. The animals were euthanized 21 days later. Results: G1 showed less bone density (BD) compared to G2. EMD provided an increased defect fill (DF) in G1 and higher BD and new cementum formation (NCF) in both groups. The number of tartrate-resistant acid phosphatase-positive osteoclasts was significantly higher in G1 when compared to G2 and in EMD-treated sites of both groups. Conclusions: CS may produce a significant detrimental effect on BD. EMD may provide greater DF compared to non-treated control in the presence of CS and increased BD and NCF in the presence or absence of CS.
    No preview · Article · Nov 2013 · Journal of Periodontology
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    ABSTRACT: Unlabelled: Dental cementum (DC) is a bone-like tissue covering the tooth root and responsible for attaching the tooth to the alveolar bone (AB) via the periodontal ligament (PDL). Studies have unsuccessfully tried to identify factors specific to DC versus AB, in an effort to better understand DC development and regeneration. The present study aimed to use matched human DC and AB samples (n=7) to generate their proteomes for comparative analysis. Bone samples were harvested from tooth extraction sites, whereas DC samples were obtained from the apical root portion of extracted third molars. Samples were denatured, followed by protein extraction reduction, alkylation and digestion for analysis by nanoAcquity HPLC system and LTQ-FT Ultra. Data analysis demonstrated that a total of 318 proteins were identified in AB and DC. In addition to shared proteins between these tissues, 105 and 83 proteins exclusive to AB or DC were identified, respectively. This is the first report analyzing the proteomic composition of human DC matrix and identifying putative unique and enriched proteins in comparison to alveolar bone. These findings may provide novel insights into developmental differences between DC and AB, and identify candidate biomarkers that may lead to more efficient and predictable therapies for periodontal regeneration. Biological significance: Periodontal disease is a highly prevalent disease affecting the world population, which involves breakdown of the tooth supporting tissues, the periodontal ligament, alveolar bone, and dental cementum. The lack of knowledge on specific factors that differentiate alveolar bone and dental cementum limits the development of more efficient and predictable reconstructive therapies. In order to better understand cementum development and potentially identify factors to improve therapeutic outcomes, we took the unique approach of using matched patient samples of dental cementum and alveolar bone to generate and compare a proteome list for each tissue. A potential biomarker for dental cementum was identified, superoxide dismutase 3 (SOD3), which is found in cementum and cementum-associated cells in mouse, pig, and human tissues. These findings may provide novel insights into developmental differences between alveolar bone and dental cementum, and represent the basis for improved and more predictable therapies.
    No preview · Article · Sep 2013 · Journal of proteomics
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    ABSTRACT: The aim of this study was to evaluate, clinically and histometrically, the effects of subgingival placement of a resin-modified glass-ionomer restoration during flap surgery. Nine dogs were included in this study. The mandibular canines were randomly assigned to receive either a transgingival resin-modified glass-ionomer restoration (test group) or no restoration (control group). The apical margins of the restorations in the test group and a reference notch on those in the control group were placed at the level of the bone crest. Clinical parameters were recorded 7 days before sacrifice. The dogs were sacrificed after 107 days, and undecalcified sections were obtained for histologic evaluation. Clinically, both groups presented significant clinical attachment loss and an increase in probing depth, but differences between groups were not statistically significant (P > .05). Histologically, a significant difference between groups was observed for length of epithelium (test, 4.05 ± 0.57 mm; control, 3.36 ± 0.63 mm; P = .01). The test group showed more bone resorption (2.02 ± 1.47 mm) when compared with the control group (0.74 ± 0.37 mm) (P = .048). It can be concluded that even with the claimed favorable properties of resin-modified glass ionomer, the presence of the restoration within the biologic width causes increased migration of the apical epithelium and bone resorption.
    No preview · Article · Sep 2013
  • Brian L Foster · Francisco H Nociti · Martha J Somerman
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    ABSTRACT: Teeth are mineralized organs comprised of three unique hard tissues, enamel, dentin, and cementum, and supported by the surrounding alveolar bone. While odontogenesis differs from osteogenesis in several respects, tooth mineralization is susceptible to similar developmental failures as bone. Here we discuss conditions fitting under the umbrella of "rickets," which traditionally referred to skeletal disease associated with vitamin D deficiency, but has been more recently expanded to include newly identified factors involved in endocrine regulation of vitamin D, phosphate, and calcium, including phosphate regulating endopeptidase homolog, X-linked (PHEX), fibroblast growth factor 23 (FGF23), and dentin matrix protein 1 (DMP1). Systemic mineral metabolism intersects with local regulation of mineralization, and factors including tissue nonspecific alkaline phosphatase (TNAP) are necessary for proper mineralization, where rickets can result from loss of activity of TNAP. Individuals suffering from rickets often bear the additional burden of a defective dentition, and transgenic mouse models have aided in understanding the nature and mechanisms involved in tooth defects, which may or may not parallel rachitic bone defects. This report reviews dental effects of the range of rachitic disorders, including discussion of etiologies of hereditary forms of rickets, a survey of resulting bone and tooth mineralization disorders, and a discussion of mechanisms, known and hypothesized, involved in the observed dental pathologies. Descriptions of human pathology are augmented by analysis of transgenic mouse models, and new interpretations are brought to bear on questions of how teeth are affected under conditions of rickets. In short, the "rachitic tooth" will be revealed.
    No preview · Article · Aug 2013 · Endocrine reviews
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    ABSTRACT: The aim of this clinical trial was to assess the performance of a full-mouth ultrasonic debridement protocol in the treatment of severe chronic periodontitis in comparison with scaling and root planing in a quadrant-wise procedure in smokers. The trial consisted of 30 participants presenting with periodontitis divided into 3 groups: Group FMUD - full-mouth ultrasonic debridement, i.e., one session of 45 minutes of ultrasonic instrumentation for smokers (n = 10), Group SRP- scaling and root planing performed in a quadrant-wise manner for smokers (n = 10), and Group Control - SRP for nonsmokers (n = 10), treated following the same protocol as the SRP group. The parameters evaluated were: plaque/bleeding on probing indices, probing pocket depth, relative recession, and relative probing attachment level at baseline, 45, 90 and 180 days after therapy. Full-mouth ultrasonic debridement and scaling and root planing resulted in comparable gain of attachment 6 months after therapy. Both groups exhibited probing pocket depth reduction at all experimental periods as compared to baseline. Smokers, however, had less probing pocket depth reduction and relative probing attachment level gain compared to non-smokers, despite the mechanical protocol used (p < 0.05). Moreover, at 180 days, nonsmokers presented with fewer sites requiring re-treatment (probing pocket depth > 5 mm and bleeding on probing) than smokers (p < 0.05). Full-mouth ultrasonic debridement and scaling and root planing result in comparable clinical outcomes for the treatment of smokers with severe chronic periodontitis. Despite the non-surgical technique used, smokers had a less favorable clinical response than non-smokers.
    No preview · Article · Jul 2013 · Journal of the International Academy of Periodontology
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    ABSTRACT: Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.454C>T, leading to change of arginine 152 to cysteine (p.R152C), and a novel heterozygous gene deletion c.1318_1320delAAC, leading to the loss of an asparagine residue at codon 440 (p.N440del). Clinical identification of low serum TNAP activity, dental abnormalities, and pedigree data strongly suggest a genotype-phenotype correlation between p.N440del and odonto-HPP in this family. Computational analysis of the p.N440del protein structure revealed an alteration in tertiary structure affecting the collagen-binding site (loop 422-452), which could potentially impair the mineralization process. Nevertheless, the Probands (compound heterozygous: p.[N440del];[R152C]) feature early-onset and severe odonto-HPP phenotype, whereas the father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose to a more severe dental phenotype in combination with the deletion. These results assist in defining the genotype-phenotype associations for odonto-HPP, and further identify the collagen-binding site as a region of potential structural importance for TNAP function in the biomineralization.
    Full-text · Article · Jun 2013 · Bone
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    ABSTRACT: To investigate the effect of photodynamic therapy (PDT) as adjunct to mechanical therapy in furcations. A double-blind, parallel, randomized controlled clinical trial was conducted in subjects presenting class II furcations. The subjects were randomly allocated to a test (PDT; n = 16) or control group (non-activated laser/only photosensitizer; n = 21). At baseline, 3 and 6 months, clinical, microbiological and cytokine pattern evaluation was performed. Clinical attachment level was defined as the primary outcome variable. Clinical parameters improved after both therapies (p < 0.05) with no differences between groups at any time point (p > 0.05). At 6 months, real-time PCR evaluation showed a decrease in Porphyromonas gingivalis and Tannerella forsythia only in the PDT group (p < 0.05) with no inter-group differences. Regarding cytokines, IL-4 and IL-10 levels increased in both groups at 6 months. GM-CSF, IL-8, IL-1β and IL-6 levels decreased only in the PDT group after 3 months (p < 0.05). At 3 months, inter-group analyses showed that GM-CSF, IFN-γ, IL-6 and IL-8 levels were lower in the PDT group. At 6 months, lower IL-1β levels were also observed in the PDT group (p < 0.05). Photodynamic therapy did not promote clinical benefits for class II furcations; however, advantages in local levels of cytokines and a reduction in periodontopathogens were demonstrated.
    No preview · Article · May 2013 · Journal Of Clinical Periodontology
  • Brian L. Foster · Francisco H. Nociti · Martha J. Somerman
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    ABSTRACT: This chapter is organized into three main sections, providing a broad overview of what is currently known about the structure and composition of tooth root tissues, the developmental processes in formation of these tissues, and the signals and influences directing root development. The chapter is intended not only as a primer for what is known about root development, but aims to identify areas requiring focused research in order to reach our ultimate goal: development of modalities for repair, regeneration, or engineering of tooth root tissues. It is outlined that much progress has been made in elucidating tooth root formation, although fundamental questions remain about the cells, signals, and events that contribute to this process.
    No preview · Chapter · Mar 2013
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    ABSTRACT: Background: Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in impaired periodontal repair. There is a lack of information about the outcomes of regenerative approaches under the influence of DM. Enamel matrix derivatives (EMDs) have been used in periodontal regenerative procedures, resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of DM. Methods: Twenty Wistar rats were randomly assigned to two groups: group 1 (G1): DM was induced with a single intraperitoneal injection of streptozotocin (STZ) (n = 10); group 2 (G2): rats were not exposed to STZ (n = 10). Seven days after DM induction, bilateral fenestration defects were created at the buccal aspect of the first mandibular molar. After the surgeries, the defects of each animal were randomly assigned to two subgroups: non-treated (control) and treated with EMD. The animals were euthanized 21 days later, and the percentage of defect fill (DF), newly formed bone density (BD), and new cementum formation (NCF) were histometrically assessed. The number of osteoclasts was determined by tartrate-resistant acid phosphatase. Weight and blood glucose were also analyzed. Mann-Whitney U test was used for comparison among groups and Wilcoxon test for comparison between the start and end times (weight and blood glucose) and between treatments (NCF and number of osteoclasts). One-way analysis of variance was used to assess DF and BD. Tukey test was used when the analysis of variance test detected significant differences (α = 5%). Results: G1 (DM) showed less DF and BD compared with G2. EMD provided an increased DF in both groups and enhanced BD and NCF only in G2. The number of TRAP-positive osteoclasts was significantly higher in EMD-treated sites of G1. Conclusions: DM may produce a significant detrimental effect on BD. EMD may provide greater DF under diabetic or normal conditions; however, it may not significantly increase NCF in animals with DM.
    No preview · Article · Nov 2012 · Journal of Periodontology

Publication Stats

2k Citations
369.60 Total Impact Points


  • 2011-2015
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases
      베서스다, Maryland, United States
  • 2000-2015
    • University of Campinas
      • Faculty of Dentistry from Piracicaba
      Conceição de Campinas, São Paulo, Brazil
  • 2004-2012
    • University of Washington Seattle
      • Department of Periodontics
      Seattle, Washington, United States
  • 2009
    • Laval University
      • Department of Microbiology and Immunology
      Quebec City, Quebec, Canada
  • 2008
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2002-2007
    • CEP America
      Емеривил, California, United States
  • 2003
    • University of Michigan
      • School of Dentistry
      Ann Arbor, MI, United States