Orientador: Oslei Paes de Almeida / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-25T08:18:42Z (GMT). No. of bitstreams: 1 DellaColetta_Ricardo_D.pdf: 6321143 bytes, checksum: fee6575189b6054e21beeaa54cc06f5a (MD5) Previous issue date: 1999 / Resumo: Fibromatose gengival hereditária (FGH) é uma condição rara caracterizada por um aumento gengival generalizado com crescimento lento e progressivo. Para elucidar algumas das características regulatórias que resultam nesta condição, quatro linhagens celulares de fibroblastos provenientes de indivíduos de uma mesma família com FGH foram isoladas e caracterizadas em relação ao comportamento prol proliferativo, produção, e expressão de colágeno e suas proteínas chaperones, expressão de MMPs e TIMPs e produção de citocinas. Fibroblastos de gengiva normal (GN) e FGH em condições de subconfluência celular apresentaram típicas características morfológicas, mas em condições de saturação da densidade, os fibroblastos de FGH apresentaram dimensões menores que as células controle. Cinco diferentes ensaios de proliferação celular mostraram que a relação de proliferação foi significantemente maior em fibroblastos de FGH. A produção e expressão de Hsp47 é também aumentada em fibroblastos de FGH em paralelo com o aumento na produção de colágeno. Em adição, a expressão de Hsp47 é regulada por estresse celular e pró-peptídeos correspondendo as regiões da porção N-terminal das cadeias 'alfa'1 (I). A produção de citocinas foi detectada por ELlSA utilizando anticorpos específicos para TGF-' beta '31, IL-6, IL-1 ' beta ' e TNF- 'alfa '. Em fibroblastos de FGH a produção de TGF-' beta ' 1 e IL-6 foi estatisticamente maior que em fibroblastos normais (p<0,013 e p< 0,0035 respectivamente), enquanto que IL-' beta ' 1 e TNF- 'alfa ' não foram detectadas em todos as linhagens celulares. A expressão e produção de MMP-1 e MMP-2, como revelada por RT -PCR e zimografia, foram significantemente menores em fibroblastos de FGH comparando com células de GN. Por outro lado, a expressão de TIMP-1 e TIMP-2 foi ligeiramente maior em fibroblastos de GN. A neutralização de TGF- ' beta ' 1 com anticorpos específicos elevou os níveis de expressão e produção de MMP-1 e dramaticamente reduziu os níveis de MMP-2, enquanto que os de níveis de TIMPs não foram alterados. Estes resultados sugerem que a pato gênese do aumento gengival de indivíduos com FGH é possivelmente resultado de uma associação de fatores incluindo alterado comportamento proliferativo, exacerbada síntese de colágeno e Hsp47, desregulação no balanço proteolítico e elevada produção de citocinas / Abstract: Characterization of cellular proliferation and expression of collagen and its molecular chaperones, cytokines and matrix metalloproteinases and its tissue inhibitors in gingival fibroblasts from pacients with hereditary gingival fibromatosis Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxillaand mandible. To further elucidate some of the regulatory features resulting in this condition, the culture characteristics of the four cell lines of gingival fibroblasts derived from patients of the some family with HGF were isolated and characterized on proliferation index, collagen and its molecular chaperones production and expression, MMPs and TIMPs expression, and cytokines production. HGF and normal gingiva (NG) fibroblasts in subcofluent culture densities showed typical morphologic characteristics, but in saturation density, HGF fibroblasts were shorter than NG cells. Five different cell proliferation assays showed that the cell proliferation rate was significantly higher in HGF fibroblasts. The production and expression of Hsp47 were significantly higher in HGF fibroblasts than in NG fibroblasts, along with increased producto?n of collagen. In addition, Hsp47 is coordinately regulated by stress and by feedback mechanism mediated by N-terminal procollagen propeptides corresponding to residues of a1 (I)-chains. The cytokines production was detected by ELlSA using specific antibodies for TGF-' beta ' 1 , IL-6, IL-1 ' beta ' and TNF- 'alfa '. In HGF fibroblasts, the production of TGF-' beta ' 1 and IL-6 was higher than fibroblasts from normal tissues (p<0.013 and p<0.0035 respectively), whereas IL-1' beta ' and TNF-'alfa ' were not detected in ali cell lines. RT-PCR and enzymographic analysis clearly demonstrated that the expression and production of MMP-1 and MMP-2 were significantly lower in fibroblasts from HGF than from NG. Interestingly, TIMP-1 and TIMP-2 expression from NG cells was shown to be slightly higher than those from HGF. The use of neutralizing antibodies to TGF-' beta ' 1 caused a slight increase in MMP-1 and a decrease in MMP-2 expression, whereas that no change TIMPs levels. These results suggest that the pathogenesis of gingival outgrowth in HGF patients is possibly resulted of a association of factors such as increased proliferative potential, altered synthesis of collagen and Hsp47, dysregulated proteolytic balance and increased cytokines production / Doutorado / Biologia e Patologia Buco-Dental / Doutor em Odontologia

Abstract Both immunosuppressive and nifedipine medication have been associated with drug-induced gingival overgrowth. There are several hypothetical mechanisms for drug-induced gingival overgrowth, such as the influence of genetic predisposition, alterations in gingival tissue homeostasis, especially in the function of fibroblasts, and drug-induced action on growth factors. Clinical studies have also shown that, those with poor oral hygiene status drug-induced gingival overgrowth is more prevalent and severe than those with good oral hygiene status. The working hypothesis was that immunosuppressive medication and/or nifedipine medication affects inflammatory cell profile and mitotic activity of keratinocytes in human overgrown gingiva. We studied gingival samples, collected from nifedipine-medicated cardiac outpatients and immunosuppression-medicated organ-transplant recipients. Patients were placed into four groups: 1) the immunosuppression group, patients receiving cyclosporin-A (CsA), azathioprine (AZA) and prednisolone (Pred) 2) the immunosuppression plus nifedipine group, patients receiving CsA, AZA, Pred. and nifedipine 3) the nifedipine group patients receiving only nifedipine and 4) the non-medicated control group. All of the samples related to moderate to severe degrees of gingival overgrowth, covering half to two thirds of the clinical crown. The aim of the study was to investigate the occurrence of Langerhans cells, macrophages, mast cells and mitotic activity of keratinocytes in human drug-induced overgrown gingiva, and consequently to assess their possible role in the pathogenesis of drug-induced gingival overgrowth. We found that immunosuppressive medication increased the numbers of reparative macrophages (RM3/1) and decreased the numbers of tryptase- and chymase-positive mast cells (MCTC) cells. We have also shown that immunosuppressive and nifedipine medication decreased the numbers of Langerhans cells (CD1a) and increased the numbers of 27E10-macrophages parallelly. Additionally we found increase in the mitotic activity of gingival keratinocytes and even two-fold thickening of gingival epithelium in immunosuppressive and nifedipine medication-induced gingival overgrowth as compared with healthy gingiva. Immunosuppressive medication activated gingival epithelium (27E10 expression in gingival keratinocytes) more than nifedipine medication. In conclusion, our results suggest that gingival overgrowth among immunosuppressive- and nifedipine-medicated patients is related to alteration of tissue homeostasis. First, this suggestion is supported by changes found in the numbers of cells that directly affect connective tissue turnover, e.g. reparative macrophages (RM3/1) and mast cells. Changes in the numbers of these cells could alter the cytokine- and growth factor-profile, which affects fibroblast function. Secondly, we found changes in the numbers of cells involved in regulation of inflammation, e.g. Langerhans cells and monocytes as compared with healthy controls. Immunosuppressive medication could directly activate gingival keratinocytes. We suggest that our findings mainly reflect the effects of immunosuppressive medication, but the role of inflammation cannot be excluded. The changes observed above represent differences of the pathogenesis of drug-induced gingival overgrowth between immunosuppressive and nifedipine medication. It must be however remembered that drug-induced gingival overgrowth is a result of multicausal intrinsic and extrinsic factors. Age, gender, concomitant medication with multiple drugs, plaque accumulation, and genetic disposition are additional risk factors. The abnormal distribution of specific immune system cell subpopulations does not alone prove a functional relationship to gingival overgrowth.

No description available.

Orientador: Antonio Wilson Sallum / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-26T23:46:04Z (GMT). No. of bitstreams: 1 Santana_AnaLiviaFileto_M.pdf: 1784469 bytes, checksum: 2e0765eeda22d929d35779199871496b (MD5) Previous issue date: 2015 / Resumo: O aumento do biofilme e a ocorrência de gengivite é um achado comum durante o tratamento ortodôntico. O objetivo do presente estudo foi avaliar se o uso de terapia fotodinâmica (TFD), como coadjuvante ao controle mecânico do biofilme supragengival, tem eficácia no tratamento de pacientes com aparelhos ortodônticos fixos apresentando gengivite, em relação aos parâmetros clínicos e marcadores inflamatórios. Um estudo clínico cego, paralelo, randomizado e controlado foi realizado em pacientes ortodônticos com diagnóstico de gengivite, apresentando sangramento à sondagem em pelo menos um par de incisivos contralaterais e um par de molares ou pré-molares contralaterais (com bráquetes colados). Os pacientes selecionados foram alocados em dois grupos distintos para receber (1) TFD + profilaxia (pTFD; n=12) ou (2) profilaxia (PA; n=12). Nos sítios tratados com pTFD, o sistema incluiu um diodo emissor de luz (LED) com comprimento de onda igual a 450nm, 310mW de potência e 122,04mW/cm2 poder de densidade, associado a curcumina 10% como fotossensibilizador. No baseline, 1 e 3 meses após, parâmetros clínicos tais como nível de inserção clínica (NIC), profundidade de sondagem (PS), índice gengival (IG), índice de placa (IP), sangramento à sondagem (SS) foram mensurados e o padrão de citocinas [interferon (IFN)-y. interleucina (IL)-10, IL-17, IL-1?, IL-4, IL-6, IL-8 e fator de necrose tumoral (TNF)-?] no fluído gengival crevicular (FGC) foi determinado. Os parâmetros clínicos relacionados a inflamação, como IP e SS reduziram para ambos os grupos (p<0,05), porém sem diferenças estatísticas entre eles (p>0,05). Em relação as citocinas, aos 3 meses, menores concentrações de pró-inflamatórias como IFN-y, IL-1? e IL-8 foram encontradas na região anterior das arcadas do grupo pTFD quando comparadas com o grupo que só recebeu profilaxia (p<0,05). Adicionalmente, houve uma redução em IL-8 no grupo teste ao longo do tempo nesta mesma região (p<0,05) e um aumento em IL-1? na região posterior ao longo do tempo no grupo controle (p<0,05). A TFD como coadjuvante a remoção mecânica do biofilme demonstrou benefícios imunológicos adicionais em pacientes com gengivite e talvez seja uma importante alternativa durante o tratamento ortodôntico / Abstract: The increase in the biofilm and gingivitis occurrence are common findings during orthodontic treatment. The aim of the present study was to evaluate the use of photodynamic therapy (PDT), as an adjunct to mechanical control of supragingival biofilm, is effective in treating patients with fixed orthodontic appliances presenting gingivitis in terms of clinical parameters and inflammatory markers. A blind, parallel, randomized, controlled clinical trial was performed in orthodontic patients with gingivitis diagnosis presenting bleeding on probing in at least one pair of contralateral incisors and one more pair of contralateral molars or pre molars (with glued bráquetes). The selected patients were assigned to receive (1) PDT + prophylaxis (pPDT; n=12) or (2) prophylaxis alone (PA; n=12). In sites treated by pPDT, the laser system included an emitted blue light (LED) of wavelength 450nm, 310mW power and power density 122.04mW/cm2, with 10% curcumin as photosensitizer. At baseline, 1 and 3 months after, changes in clinical attachment level (CAL), in probing pocket depth (PPD), gingival index (GI), plaque index (PI), bleeding on probing (BoP) was performed and cytokine levels [interferon (IFN)-y. interleukin (IL)-10, IL-17, IL-1?, IL-4, IL-6, IL-8 and tumor necrosis factor (TNF)-?] in gingival crevicular fluid (GCF) were determined. The clinical parameters related to inflammation, such as PI and BoP reduced for both groups (p<0.05), but no statistical differences between them (p>0.05). Regarding cytokines, at 3-months, lower concentrations of pro-inflammatory IFN-y, IL-1? and IL-8 were found in anterior segment of pPDT group compared with PA group (p<0.05). Additionally, there was a reduction in IL-8 for the test group over time in the same part (p<0.05), and an increase in IL-1? in the posterior segment over time for the control group (p<0.05). PDT as an adjunctive to mechanical biofilm removal demonstrated additional immunological benefits in gingivitis patients and maybe be an alternative therapeutic strategy during orthodontic treatment / Mestrado / Periodontia / Mestra em Clínica Odontológica

O diabetes mellitus (DM) é caracterizado por uma deficiência no transporte de glicose da corrente sanguínea para o interior da célula, elevando os níveis de glicose no sangue. Isso ocorre pela deficiência e até mesmo resistência à insulina, e é controlada por agentes hipoglicêmicos orais e/ou dieta, associada a exercícios físicos. É classificada em tipo I e II, sendo que o segundo é a forma mais comum da doença e tem a idade como um dos fatores predisponentes. O periodonto é formado por estruturas de suporte e proteção ao elemento dentário e seu aspecto de saúde tem uma importância significante na cavidade bucal. A doença periodontal (DP) é um processo inflamatório crônico caracterizado por inflamação do tecido gengival e/ou perda de estruturas que compõem o periodonto, causando danos à estrutura dentária ou até perda do dente. É reconhecida como a sexta maior complicação do diabetes. Esse estudo teve como objetivo comparar as alterações periodontais em indivíduos diabéticos tipo II e não diabéticos residentes no município de Araguaína Tocantins (TO). Para isso, foram examinados 34 pacientes divididos em dois grupos: diabéticos e não diabéticos, que foram submetidos a exames periodontais para determinar a Profundidade de Sondagem (PS), Perda de Inserção Clínica (PIC), Índice Gengival (IG), Índice de Placa (IP), Índice de Higiene Oral (IHO) e exames laboratoriais para os diabéticos tipo II. Para a análise estatística foi usado o teste t no intuito de obter as correlações dos índices entre os diabéticos e o teste U para analisar as alterações periodontais entre os grupos. Foram encontrados PIC e IHO maiores em diabéticos, sendo os demais índices maiores no grupo dos não diabéticos. Só IP não apresentou diferença estatística significante (p>0,05). Também foi verificada uma correlação entre IP e IG, não ocorrendo entre os demais índices. Concluiu-se que os diabéticos têm doença periodontal mais severa que os não diabéticos. / Diabetes Melitus (DM) is characterized by a deficiency in the glicose transport from the blood stream to the inside of cells, raising the glicose leves in the blood. This occurs due to the deficiency or even resistance to insulin, and it is controlled by oral hypoglicemic agents and/or diet, associated with physical exercises. It is classified in types I and II, in such a way the second type in the most common and its predisponent factor is age. The periodonto is made of structures that support and protect the dental element and its health aspect has a significant importance to the bucal cavity. The periodontal disease (PD) is a chronic inflammatory process characterized by inflammation of the gingival tissue and /or loss of structures that compose the periodonto, causing damage to the dental structure or even loss of teeth. Its known as the sixth biggest complication derived from diabetes. This work had the purpose of comparing periodontal modifications in diabetic type II and non diabetic patients who lived in Araguaína Tocantins (TO). Therefore, 34 patients were examined and separated in two groups with PD: diabetics and non diabetics. They were submitted to periodontal examination in order to measure the Depth Proof (PPD), Clinical Attachment Loss (CAL), Gingival Index (GI), Plaque Index (PII), Oral Hygiene Index (OHI) indices. Also, laboratorial tests were made for type II - diabetic patients. The statistical analysis was made using the t-test to obtain the indices of correlation in diabetic group and the u-test to evaluate periodontal modifications between the groups. The CAL and the indices were higher in diabetic group and the other indices were higher in non diabetic group. Only the PII index show no significant statistic difference (p>0,05). It was also verified a correlation between PII and GI indices, yet it was not true in other indices. It was possible the conclude that the diabetics have more severe periodontal disease than the non diabetics.

In der Literatur wird die kieferorthopädische Bewegung auch als ätiologischer Faktor für die Entstehung gingivaler Rezessionen gesehen (Dorfman 1978; Toker und Ozdemir 2009). Bereits 1942 beschäftigte sich Oppenheim mit dem Einfluss der Kieferorthopädie auf das parodontale Gewebe und stellte bereits damals fest, dass selbst bei größter Sorgfalt negative Einflüsse auf das Parodont nicht vermieden werden können (Oppenheim 1942). Nach derzeitiger Datenlage scheint folgende Antwort gerechtfertigt zu sein. Im Zuge einer kieferorthopädischen Therapie kann es zu Rezessionen der marginalen Gingiva kommen und dies kann auch teilweise nicht verhindert werden. Die fachlich korrekt durchgeführte kieferorthopädische Therapie scheint per se kein erhöhtes Risiko für die Entstehung von Rezessionen zu sein. Dies setzt eine sorgfältige prätherapeutische Diagnostik, geeignete Kräfte und Verankerungselemente, Beibehaltung einer suffizienten Mundhygiene und die Beachtung anatomischer Limits voraus.:Einleitung 3 Material und Methodik 5 Ergebnis 6 Häufigkeit und Verteilung von Rezessionen 6 Attached Gingiva 8 Biomechanik der kieferorthopädischen Zahnbewegung 11 Plaque, Gingivitis 15 Kraft 20 Intrusion 21 Extrusion 23 Expansion/Dehnung 23 Labial und Lingualbewegung/Labialstand 29 Proklination/Inklination 34 Knochendehiszenz/Knochenbedeckung 43 Systematische Literaturübersicht 59 Vorbeugende Maßnahmen 61 Diskussion 63 Zusammenfassung 68 Literaturverzeichnis 69

2-Hydroxy-ethyl methacrylate (HEMA) is the major component released from resin-modified glass ionomer cements and dental adhesives. Human tissues mainly affected by HEMA are oral epithelium and dental pulp. We treated human gingival epithelial S-G cells and pulp fibroblasts (HPF) with various concentrations of HEMA, to evaluate its effects on cell growth, cell cycle progression, intracellular glutathione (GSH) level and reactive oxygen species (ROS) production. HEMA-induced growth inhibition in HPF and S-G cells in a dose-dependent manner, which may be partially explained by induction of cell cycle perturbation. G2/M phase arrest was noted after exposure of HPF to 5 and 10mM of HEMA, concomitant with glutathione depletion and ROS production. S-phase arrest occurred in S-G cells when treated with 2.5 and 5mM, while at 10mM a sub-G0/G1 peak was noted, indicating the potential induction of apoptosis. GSH depletion was marked in S-G cells only at concentrations of 5 and 10mM, but excessive ROS production was noted at concentration of 1mM and rose with dose increase between 1 and 5mM, then lessened at 10mM. This suggested that the increase of ROS in S-G cells was not mainly caused by GSH depletion. These results helped to define the mechanism of the cytotoxicity caused by HEMA.

No description available.

No description available.

Background: The aim of this study was to compare the direct impact of different agents for immunosuppressive therapy on mouse fibroblasts as a possible cause of drug-induced gingival overgrowth (DIGO). Methods: 3T3 mouse fibroblasts were cultivated in cell-specific media (2 × 104 cells/mL) and treated for 6, 24, 48 and 72 h with one of three immunosuppressive drugs (IsDs): cyclosporin a (CsA), tacrolimus (TaC) and sirolimus (SiR). Different concentrations (10–750 ng/mL) were used to mimic serum levels under active immunosuppressive therapy conditions. Cell population characteristics (cell number, viability and morphology) were assessed using computer-assisted cell analysis. Expression of pro-collagen type I carboxy-terminal propeptide (PICP) was identified using an ELISA assay. Results: The influence of IsDs on the biological status of 3T3 fibroblasts was time- and dose-dependent. Comparing CsA and TaC, the total cell amount was enhanced using concentrations in the range of 10–150 ng/mL (p > 0.05). In contrast, treatment with SiR resulted in a decrease in the average cell number (p < 0.01). PICP and cell diameter of fibroblasts were not susceptible to IsD treatment (p > 0.05). Conclusions: Our results revealed time-dependent effects of IsDs, with distinct influences on cell number. The cell morphology and the PICP balance of the investigated fibroblast cell line remained unaffected. Hence, the potential role of IsDs is not a unilateral mechanism of action but rather a multifactorial process.