Expression of inflammatory mediators in periodontitis and T2D patients: a systematic review and meta-analysis

Abstract The high concentration of glucose in the blood in Type 2 diabetes (T2D) may be related to either insulin resistance or insulin deficiency. Moreover, the literature points to periodontitis as the main oral disease caused by glycemia imbalance. The quantification of inflammatory markers in blood or saliva samples of T2D patients may represent a valuable tool in revealing how well an individual's immune system can respond to injuries and periodontal treatment. In addition, an evaluation of the cytokine expression is extremely relevant to help understand the connection between periodontitis and T2D. This systematic review and meta-analysis aimed to evaluate the expression of inflammatory markers in T2D patients with periodontitis, compared with non-diabetic patients with periodontitis. A total of 3,894 studies were retrieved after a systematic literature search, 15 of which were included in the systematic review, and 4 of these 15, in the meta-analysis. The results did not indicate any statistical difference between the groups regarding TNF-α and IL-6 markers. T2D patients with periodontitis had increased levels of IL-10, compared with non-diabetic individuals with periodontitis (p = 0.003). On the other hand, the IL-4 concentration in non-diabetic individuals with periodontitis was high, compared with the T2D group (p< 0.001). Several studies did not include quantitative results and were excluded from the meta-analysis. The high IL-10 expression and low IL-4 expression in the T2D group suggest an association between the level of these markers and the impairment of the immune response in T2D patients with periodontitis.

Cimento biocerâmico no tratamento conservador de perfuração radicular em molar inferior / Bioceramic sealer in conservative treatment of mandibular molar root perforation

Introdução: A perfuração radicular é um acidente técnico-operatório que resulta em comunicação da cavidade pulpar com os tecidos periodontais. Esse tipo de acidente pode apresentar prognóstico desfavorável, por afetar significativamente o soalho da câmara coronária ou os terços cervical, médio e apical do canal radicular. Entre os fatores que interferem no prognóstico das perfurações radiculares, destacam-se: localização, extensão, presença ou ausência de bolsa periodontal; tempo decorrido entre a perfuração e o tratamento; e tipo de material obturador. Nesse contexto, os cimentos obturadores de canais denominados biocerâmicos surgiram como uma proposta inovadora para tratamento de perfurações antes consideradas de prognóstico desfavorável. Objetivo: O presente trabalho teve por objetivo relatar o tratamento de uma perfuração radicular em molar inferior com o cimento biocerâmico EndoSequence BC Sealer, com três anos de acompanhamento. Resultados: As imagens radiográficas e os dados clínicos do paciente evidenciaram o sucesso no tratamento da perfuração, com reparo da lesão perirradicular. Conclusão: O cimento endodôntico biocerâmico EndoSequence BC Sealer associado com a retomada do trajeto original do conduto e sua instrumentação favoreceram o reparo dos tecidos perirradiculares, sugerindo propriedades biológicas promissoras de compatibilidade e bioativida (AU).

Introduction: Root perforation is a technical-surgical accident that results in communication of the pulp cavity with periodontal tissues. This type of accident may have an unfavorable prognosis because it significantly affects the floor of the coronary chamber or the cervical, middle and apical thirds of the root canal. Factors that interfere with the prognosis of root perforations include location, extension, presence or absence of periodontal pocket, time elapsed between perforation and treatment, and type of obturator material. In this context, bioceramic canal sealers have emerged as an innovative proposal for treatment of perforations previously considered to have an unfavorable prognosis. Objective: The aim of this study was to report the treatment of a lower molar root perforation with the EndoSequence BC Sealer bioceramic sealer after a 3-year follow up. Results: Radiographic images and patient clinical data showed success in the treatment of perforation with repair of the periradicular lesion. Conclusion: Endo-Sequence BC Sealer bioceramic endodontic sealer associated with the resumption of the original conduit path and its instrumentation favored the repair of periradicular tissues, suggesting promising biological properties of compatibility and bioactivity (AU).

Biocompatibility and bioactivity of calcium silicate-based endodontic sealers in human dental pulp cells

Mineral Trioxide Aggregate (MTA) is a calcium silicate-based material. New sealers have been developed based on calcium silicate as MTA Fillapex and MTA Plus.Objective The aim of this study was to evaluate biocompatibility and bioactivity of these two calcium silicate-based sealers in culture of human dental pulp cells (hDPCs).Material and Methods The cells were isolated from third molars extracted from a 16-year-old patient. Pulp tissue was sectioned into fragments with approximately 1 mm3 and kept in supplemented medium to obtain hDPCs adherent cultures. Cell characterization assays were performed to prove the osteogenic potential. The evaluated materials were: MTA Plus (MTAP); MTA Fillapex (MTAF) and FillCanal (FC). Biocompatibility was evaluated with MTT and Neutral Red (NR) assays, after hDPCs exposure for 24 h to different dilutions of each sealer extract (1:2, 1:3 and 1:4). Unexposed cells were the positive control (CT). Bioactivity was assessed by alkaline phosphatase (ALP) enzymatic assay in cells exposed for one and three days to sealer extracts (1:4 dilution). All data were analyzed by ANOVA and Tukey post-test (p≤0.05%).Results MTT and NR results showed suitable cell viability rates for MTAP at all dilutions (90-135%). Cells exposed to MTAF and FC (1:2 and 1:4 dilutions) showed significant low viability rate when compared to CT in MTT. The NR results demonstrated cell viability for all materials tested. In MTAP group, the cells ALP activity was similar to CT in one and three days of exposure to the material. MTAF and FC groups demonstrated a decrease in ALP activity when compared to CT at both periods of cell exposure.Conclusions The hDPCs were suitable for the evaluation of new endodontic materialsin vitro. MTAP may be considered a promising material for endodontic treatments.

Radiopacity and cytotoxicity of Portland cement associated with niobium oxide micro and nanoparticles

Objective Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC) and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbµ) or nanoparticles (Nbη) may improve radiopacity and bioactivity. The aim of this study was to evaluate the radiopacity and cytotoxicity of the materials: 1) PC; 2) White MTA; 3) PC+30% Nbµ; 4) PC+30% Nbη. Material and Methods For the radiopacity test, specimens of the different materials were radiographed along an aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB-85) were used. Cell viability was evaluated through MTT assay, and bioactivity was assessed by alkaline phosphatase activity assay. Results The results demonstrated higher radiopacity for MTA, followed by Nbµ and Nbη, which had similar values. Cell culture analysis showed that PC and PC+NbO associations promoted greater cell viability than MTA. Conclusions It was concluded that the combination of PC+NbO is a potential alternative for composition of MTA. .

Incomplete vertical root fracture associated with lateral compactiontechnique: a microscopic analysis / Fratura radicular vertical incompleta associada com a técnica de condensação lateral: Análise microscópica

Objective: This study evaluated the effects of root canal obturation employing lateral compaction technique and spreader load of 1.5 kg on the incidence of complete (CVRF) or incomplete vertical root fractures (IVRF). Material and Methods: Twenty-seven distal roots of extracted human mandibular molars were used. All root canals were prepared by biomechanical step-back technique and obturated by lateral compaction technique. The prepared roots were distributed into two groups: G1- experimental (n = 17)= and G2- control (n = 10). During obturation, load of 1.5 kg was applied to a size # 30 finger spreader. Pre- and post-obturation images of the coronal portion of the roots were captured by inverted digital microscopy and analyzed by one trained examiner. Data were evaluated by Fisher’s test (p < 0.05) using GrapH Pad Prism 5.0. Results: No roots exhibited CVRF. All fractures observed before and after obturation were IVRF or “other defects”. In G2 (control group), there was no increase of IVRF number. Interestingly, G1 presented an increase in the IVRF number to 70.59% in the 12 teeth out of 17 teeth studied. The statistical analysis showed that the mean of IVRF increased significantly in G1 when compared to G2 (p < 0.05). Conclusion: The application of a 1.5 kg spreader load during lateral compaction technique does not produce complete vertical root fractures, but may produce incomplete fractures or “other defects”.

Objetivo: Este estudo avaliou os efeitos da obturação dos canais radiculares, empregando a técnica de condensação lateral com uma força do espaçador de 1,5 kg, na incidência de fraturas radiculares verticais completas (FRVC) ou incompletas (FRVI). Material e Métodos: Foram usadas 27 raízes distais de dentes molares mandibulares humanosextraídos. Todas as raízes foram instrumentadas por meio da técnica clássica ápice-coroa e obturadas pela técnica de condensação lateral. Após o preparo biomecânico, as raízes foram distribuídas em 2 grupos: G1- experimental (n = 17) e G2- controle (n = 10). Durante a obturação, uma força de 1,5 kg foi aplicada ao espaçador digital # 30. As imagens pré- e pós-obturação da superfície coronal das raízes foram capturadas por meio de um microscópio digital invertido e analisadas por um examinador treinado. Os dados obtidos foram avaliados por meio do teste de Fisher (p < 0,05) usando o programa GrapH Pad Prism 5.0. Resultados: Não foram detectadas FRVC. Todas as fraturas observadas antes e após a obturação foram FRVI ou “outros defeitos”. No G2 (grupo controle), não houve um aumento no número de FRVI. Curiosamente, G1 apresentou um aumento das FRVI em 70,59% (12/17 raízes). A análise estatística mostrou que a média de FRVI aumentou significativamente no G1 quando comparado ao G2 (p < 0,05). Conclusão: A aplicação de uma força de 1,5 kg ao espaçador durante a realização da técnica de condensação lateral não produz fraturas radiculares verticais completas, mas pode produzir fraturas incompletas ou “outros defeitos”.

Aspectos biológicos e bioatividade de materiais a base de MTA em cultura de células / Biological aspects and bioactivity of MTA based materials in cell culture systems

O objetivo deste estudo foi analisar as respostas biológicas `a materiais utilizados em Endodontia que apresentam na formulação Mineral Trióxido Agregado (MTA) ou cimento Portland (PC) utilizando sistemas de cultura de células. O estudo foi dividido em três capítulos: No capitulo 1 foram avaliados bioatividade e biocompatibilidade de dois novos cimentos endodônticos comercialmente disponíveis; MTA Fillapex (MTA-F, cimento endodôntico à base de MTA, Ângelus) e Ephiphany SE (EP-SE, cimento endodôntico a base de resina metacrilato, SybronEndo). A linhagem de osteoblastos humanos (Saos-2) foi utilizada como modelo de estudo. Os resultados de MTT mostraram uma taxa significante de morte celular nas primeiras horas de exposição para todos os materiais avaliados. Entretanto, o grupo MTA-F apresentou aumento de células viáveis após 7 dias de presa. As imagens de microscopia eletrônica de varredura e o resultado de EDS (energia de dispersão atômica) mostraram diferenças na morfologia dos nódulos minerais formados pelos osteoblastos expostos ao MTA-F. No capítulo 2, células de folículo dental humanos (hDFCs) de dois terceiros molares inclusos indicados para exodontia por razões ortodônticas foram isoladas para avaliação da bioatividade e da biocompatibilidade do PC associado a diferentes agentes radiopacificadores em cultura primária de células. Os materiais estudados foram o cimento Portland branco (PC) e as associações de PC com: óxido de bismuto (CPBi), óxido de zircônio (CPZir) e tungstato de cálcio (CPCa). Além dos resultados de viabilidade celular e atividade de fosfatase alcalina, a biocompatibilidade do PC e das associações com agentes radiopacificadores foi analisada por imagens de microscopia eletrônica de varredura, que mostraram as hDFCs aderidas aos materiais. O capítulo 3 apresenta um estudo original de pesquisa básica, no qual foi avaliada a hipótese de ativação do fator de transcrição gênica NFATc1 em células de linhagem de osteoblastos humanos após exposição ao PC. O NFATc1 é um fator de transcrição essencial para a diferenciação celular de osteoclastos, o qual é ativado por calcineurina. Curiosamente, estudos recentes demonstraram que os fatores NFAT também desempenham um papel importante na diferenciação e atividade dos osteoblastos. Os resultados obtidos no capítulo 3 com ensaios de western blotting, microscopia confocal, expressão gênica de marcadores moleculares de osteogênese e a co-localização de Osterix com NFATc1 no núcleo de Saos-2 expostas ao eluído de PC forneceram evidências que comprovaram a hipótese proposta. O PC estimulou a ativação de NFATc1 em Saos-2, devido ao influxo de Ca+2 para o ambiente intracelular

The aim of this study was to analyze the biological responses to new endodontic materials based on Portland cement (PC) and the PC itself in cell culture systems. The study was divided into three chapters as follows: The first chapter describes a research in which the bioactivity and biocompatibility of two new commercially available sealers; MTA Fillapex (MTA-F, PC-based sealer, Angelus) and Ephiphany SE (EP-SE, resin-based sealer, SybronEndo); were evaluated in human osteoblast-like cells (Saos-2). The MTT results showed a significant cell death rate during the first hours of exposure to all test materials. After 7 days of exposure, MTA-F group showed a suitable increasing rate of cell viability. Interestingly, the images of scanning electron microscopy and the result of EDS (energy-dispersive X-ray spectroscopy) showed morphological differences in the mineralized nodules formed by osteoblasts exposed to MTA-F. In Chapter 2, human dental follicle cells (hDFCs) were isolated from two included third molars, which were extracted for orthodontic reasons. The hDFCs were suitable to assess the bioactivity and biocompatibility of PC associated with different radiopacifying agents in primary cell culture system. The materials tested were the white Portland cement (PC) and PC associations with radiopacifying agents: bismuth oxide (PCBi), zirconium oxide (PCZir) and calcium tungstate (PCCa). Besides the results of cell viability and alkaline phosphatase activity, the biocompatibility of the PC was corroborated by the images of scanning electron microscopy, which allowed us to visualize the hDFCs adhered to the material surfaces. Chapter 3 presents an original study of basic research, aimed to evaluate the hypothesis of the transcription factor NFATc1 activation in human osteoblast-like cells as a result of exposure to PC. The NFATc1 is a transcription factor essential for osteoclasts differentiation, which is activated by Calcineurin. Curiously, recent studies have shown that NFAT transcription factors play an important role in differentiation and activity of osteoblasts as well. The results obtained with western blotting assay, confocal microscopy, expression of molecular markers of osteoblasts differentiation and the co-location of NFATc1 with Osterix in the nuclei of Saos-2 exposed to PC elute provided evidences that supported the hypothesis proposed. PC stimulated the activation of NFATc1 in Saos-2 due to the influx of Ca+2 to the intracellular environment