Terapêutica adjuvante na modulação da resposta imune no tratamento da doença periodontal: uma revisão de literatura / Adjuvant therapeutic in the modulation of the immune response in the treatment of periodontal disease: a literature review

Introdução: A Doença Periodontal tem caráter multifatorial, já que depende de condições microbiológicas, imunogenéticas e sistêmicas do hospedeiro. Representa inflamação crônica das estruturas de suporte e proteção dental. Desencadeia uma complexa estimulação imunológica, bem como a produção de citocinas inflamatórias, que mediam a destruição óssea e de tecido conjuntivo, provocando perda dental e complicações à distância. A compreensão da etiopatogênese, permitiu os conceitos de modulação, que referem-se às modificações dos aspectos danosos da resposta inflamatória. Objetivo: O presente artigo tem como objetivo realizar uma revisão dos estudos sobre as principais terapêuticas adjuvantes na modulação da resposta imune frente à doença periodontal. Revisão de Literatura: Foi realizada uma revisão da literatura, onde foram selecionados artigos científicos em inglês, publicados entre os anos 2005 a 2020, por meio das bases de dados PubMed e ScienceDirect. No decorrer das buscas, foram utilizadas as palavraschaves "Inflamation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Resultados e Conclusão: A literatura é bem promissora em relação à terapia de controle complementar da doença periodontal. Dessa forma, novas pesquisas nessa área podem trazer inúmeros beneficos aos pacientes, sendo, assim, um novo caminho para o contorno da resistência bacteriana(AU)

Introduction: Periodontal disease has a multifactorial character, depending on the host's microbiological, immunogenetic and systemic conditions. It represents chronic inflammation of dental support and protection structures. It triggers a complex immune stimulation, as well as the production of inflammatory cytokines, which mediate bone and connective tissue destruction, causing tooth loss and complications at a distance. The understanding of etiopathogenesis allowed the concepts of modulation, which refers to the modifications of the harmful aspects of the inflammatory response. This article has the escape of conducting a review of studies on the main mechanisms of modulation against periodontal disease. Objective: This article aims to rev iew the studies on the main modulation mechanisms in the face of periodontal disease. Literature Review: A literature review was carried out in which scientific articles were selected in English, published between 2005 and 2020, through the PubMed and ScienceDirect databases. During the searches, the keywords "Inflammation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Results and Conclusion: The literature is very promising with complementary control therapy for periodontal disease. Thus, new research in this area can bring countless benefits to patients, thus being a new way to bypass bacterial resistance(AU)

Ellagic acid on the quality of the adhesive interface of class I composite resin restorations after aging

To evaluate the effect of ellagic acid on the inhibition of matrix metalloproteinase by analyzing the quality of the adhesive interface with bond strength measures in periods of 24 hours and six months of storage. Method: 40 healthy human third molars were prepared with class I cavities (5x4x3mm). The teeth were divided into four experimental groups: Group 1- without application of ellagic acid and storage time of 24 hours; Group 2- with ellagic acid/24 hours; G3- without ellagic acid/six months; Group 4- with ellagic acid/six months. Then, the cavities were restored with Single Bond Universal adhesive and Z350 composite resin, with and without the previous application of ellagic acid. Subsequently, hourglass-shaped specimens were obtained and subjected to the bond strength (BS) test (n = 10) in a universal testing machine. The bond test was performed after 24 hours and six months of storage. For the standard evaluation (n = 3) the samples were infiltrated with silver nitrate and placed in a developing solution for analysis in a Scanning Electron Microscope (SEM). The data obtained were analyzed with the Kruskal-Wallis non-parametric test, showing a statistically significant difference. Results: The highest bond strength values were found for the 24-hour groups followed by the groups with six months of storage. For nano-infiltration, groups G1 and G2 showed lower infiltration than groups G3 and G4. Conclusion: The previous application of ellagic acid did not affect the BS of the adhesive interface of the adhesive system analyzed, regardless of storage time.

Perfil inflamatório e microbiológico de pacientes com infecção endodôntica primária e periodontite apical: estudo observacional / Inflammatory and microbiological profile of patients with primary endodontic infection and apical periodontitis: observational study

O objetivo deste estudo foi avaliar o perfil microbiológico e identificar padrões de agregação bacteriana, avaliar a associação desses padrões com os níveis de mediadores inflamatórios, MMPs e sinais e sintomas clínicos e ainda correlacionar os mediadores inflamatórios entre si e com os sinais e sintomas clínicos em dentes com infecção endodôntica primária e periodontite apical (PA). Para isso, 40 dentes uniradiculares, de pacientes com infecção endodôntica primária e PA, foram submetidos à avaliação clínica, com registro de sinais e sintomas, e tomográfica através do cálculo de volumetria das lesões periapicais com o software ITK Snap. Em seguida os dentes foram submetidos ao tratamento endodôntico. Logo após a abertura coronária, amostras foram coletadas de cada canal radicular utilizando cones de papel (S1) e submetidas ao método Checkerboard DNA-DNA hybridization para investigação de espécies bacterianas presentes. Foi realizado o preparo biomecânico (PBM) e em seguida o fluído intersticial da PA foi coletado (SF1) para a quantificação dos mediadores inflamatórios (IL1-ß, IL-6, TNF-α, IL-10, MMPs -2 e -9) através do ensaio multiplex e a quantificação de RvD2 através de ensaio imunoenzimático ELISA. Para a análise de correlação o teste de correlação de Spearman foi utilizado. A análise fatorial foi usada para identificar padrões de agregação bacteriana e regressão linear foi realizada para associar os escores fatoriais, mediadores e características clínicas dos pacientes (P=0,05). Correlação positiva foi encontrada entre MMP-2, -9, IL-10, IL-1ß, IL-6 e TNF-α, e entre RvD2, MMP-9, IL-10, IL-1ß, IL-6 e TNF-α (P<0,05), e correlação negativa foi encontrada entre IL-1ß e sensibilidade a percussão (P<0,05). A análise microbiológica revelou presença de DNA bacteriano em 100% das amostras analisadas com presença de pelo menos 2 das 40 espécies bacterianas investigadas (média = 24,62) por canal. As espécies mais frequentemente detectadas foram P. gingivalis, E. nodatum, F. nucleatum spp. vicentii, S. mitis, L. bucallis e A. actinomycetemcomitans. Das 6 espécies mais detectadas, 4 delas eram gram negativas, destacando o predomínio de gram-negativos das infecções endodônticas primárias com PA. A análise fatorial determinou 2 padrões de associação bacteriana e os resultados de regressão para o fator 1 revelaram uma associação com aumento de dor a percussão (coeficiente (coef) ß=0,788) e redução de dor a palpação (coefß=-0,753) e exsudato (coefß=- 0,479). Níveis mais altos de exsudato e menores de dor a palpação foram associados a bactérias do fator 2 (coefß=0,460 e -0,546, respectivamente). Concluímos que os mediadores inflamatórios formam uma rede inter-relacionada e que as periodontites apicais assintomáticas e sintomáticas tem uma etiologia bacteriana heterogênea e com combinações de espécies diferentes (AU)

The aim of this study was to evaluate the microbiological profile and identify patterns of bacterial aggregation, evaluate the association of these patterns with the levels of inflammatory mediators, MMPs and clinical signs and symptoms, and also correlate the inflammatory mediators with each other and with the clinical signs and symptoms in teeth with primary endodontic infection and apical periodontitis (AP). For this, 40 single-rooted teeth, from patients with primary endodontic infection and PA, were submitted to clinical evaluation, with registration of signs and symptoms, and tomography through the calculation of volumetry of periapical lesions with the ITK Snap software. Then the teeth were submitted to endodontic treatment. Immediately after the coronal opening, samples were collected from each root canal using paper cones (S1) and submitted to the Checkerboard DNA-DNA hybridization method to investigate bacterial species present. Biomechanical preparation (BMP) was performed and then the AP interstitial fluid was collected (SF1) for the quantification of inflammatory mediators (IL1-ß, IL-6, TNF-α, IL-10, MMPs -2 and -9) by the multiplex assay and the quantification of RvD2 by enzyme immunoassay ELISA. For correlation analysis, Spearman's correlation test was used. Factor analysis was used to identify bacterial aggregation patterns and linear regression was performed to associate factor scores, mediators and patients' clinical characteristics (P=0.05). Positive correlation was found between MMP-2, -9, IL-10, IL-1ß, IL-6 and TNF-α, and between RvD2, MMP-9, IL-10, IL-1ß, IL-6 and TNF- α (P<0.05), and a negative correlation was found between IL-1ß and sensitivity to percussion (P<0.05). The microbiological analysis revealed the presence of bacterial DNA in 100% of the samples analyzed with the presence of at least 2 of the 40 bacterial species investigated (mean = 24.62) per root canal. The most frequently detected species were P. gingivalis, E. nodatum, F. nucleatum spp. vicentii, S. mitis, L. buccallis and A. actinomycetemcomitans. Of the 6 most detected species, 4 of them were gram negative, highlighting the predominance of gram-negative primary endodontic infections with AP. Factor analysis determined 2 patterns of bacterial association and regression results for factor 1 revealed an association with increased pain on percussion (coefficient (coef) ß=0.788) and reduced pain on palpation (coefß=-0.753) and exudate (coefß=-0.479). Higher levels of exudate and lower levels of pain on palpation were associated with factor 2 bacteria (coefß=0.460 and -0.546, respectively). We conclude that inflammatory mediators form an interrelated network and that asymptomatic and symptomatic apical periodontitis has a heterogeneous bacterial etiology and combinations of different species (AU)

Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption / 国际口腔科学杂志·英文版

Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap+ and Ctsk+ multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions.

Study on the mechanism of Wuzi-Yanzong-Wan-medicated serum interfering with the mitochondrial permeability transition pore in the GC-2 cell induced by atractyloside / 中国天然药物

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.

Does oral lichen planus aggravate the state of periodontal disease? A systematic review and meta-analysis

OBJETIVO: O objetivo desta revisão sistemática e metanálise (SRM) foi avaliar as evidências entre a associação de líquen plano oral (OLP) e doença periodontal, avaliando os parâmetros clínicos periodontais e os níveis de biomarcadores. MATERIAIS E MÉTODOS: Esta revisão sistemática e meta-análise seguiu PRISMA e foi registrada no PROSPERO (CRD42020181513). Foram realizadas buscas em bases de dados de artigos publicados até junho de 2021. A metanálise foi realizada com as variáveis: índice de placa (PI), índice gengival (GI), profundidade de sondagem (PD) e perda de inserção clínica (CAL). A diferença média foi aplicada com intervalo de confiança de 95%. RESULTADOS: 6 artigos foram incluídos. A análise qualitativa mostrou que os níveis de biomarcadores (metaloproteinases de matriz, interleucinas e perfil microbiológico periodontal) estão aumentados em indivíduos com doença periodontal e líquen plano oral. Na metanálise, esses indivíduos também apresentaram aumentos em todos os parâmetros clínicos periodontais avaliados: GI­ gengivite 0,22 [0,14, 0,31] p< 0,0001 e periodontite 0,12 [0,06, 0,19] p=0,0003; PI­ gengivite 0,22 [0,12, 0,31] p< 0,0001 e periodontite 0,15 [0,08, 0,23] p< 0,0001; PD­ gengivite 0,27 [0,06; 0,48] p=0,0107 e periodontite 0,11 [0,01; 0,21] p=0,0299; e CA ­ periodontite 0,06 [0,01, 0,12] p=0,0176. CONCLUSÕES: Evidências sugerem uma relação significativa entre a gravidade da doença periodontal e a presença de líquen plano oral. RELEVÂNCIA CLÍNICA: Este SRM fornece informações sobre a interação entre OLP e a doença periodontal e orienta os médicos a tomar decisões baseadas em evidências e sugere recomendações para estudos adicionais de alta qualidade(AU)

BACKGROUND: The objective of this systematic review and meta-analysis (SRM) was to assess the evidence between the association of oral lichen planus (OLP) and periodontal disease, evaluating the periodontal clinical parameters and biomarkers levels. METHODS: This systematic review and meta-analysis followed PRISMA and was registered in PROSPERO (CRD42020181513). Searches were accomplished in databases for articles published until June 2021. The meta-analysis was performed with the variables: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). The mean difference was applied with a 95% confidence interval. RESULTS: 6 articles were included. Qualitative analysis showed the levels of biomarkers (matrix metalloproteinases, interleukins, and periodontal microbiological profile) are increased in subjects with periodontal disease and oral lichen planus. In the meta-analysis, these subjects also presented increases in all periodontal clinical parameters evaluated: GI­ gingivitis 0.22 [0.14, 0.31] p < 0.0001 and periodontitis 0.12 [0.06, 0.19] p =0.0003; PI­ gingivitis 0.22 [0.12, 0.31] p < 0.0001 and periodontitis 0.15 [0.08, 0.23] p < 0.0001; PD­ gingivitis 0.27 [0.06; 0.48] p=0.0107 and periodontitis 0.11 [0.01; 0.21] p=0.0299; and CA ­ periodontitis 0.06 [0.01, 0.12] p=0.0176. CONCLUSIONS: Evidence suggests a significant relationship between the severity of periodontal disease and the presence of oral lichen planus. CLINICAL RELEVANCE: This SRM provides information on the interaction between OLP and periodontal disease and guides clinicians to make evidence-based decisions and suggests recommendations for further high-quality studies(AU)

Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination

Meta-Analysis of association between single nucleotide polymorphisms with sports injuries in soccer / Metaanálisis de asociación entre polimorfismos de nucleótido único y lesiones deportivas en fútbol

Abstract Introduction: The high incidence of sports injuries in elite athletes is a concern in sports medicine. A broad vision of sport injuries in Colombia and its pathophysiology can be achieved in the scope of genomics, which could respond to numerous sports injuries from the Identification of single nucleotide polymorphism that lead to disabilities that affect the health of athletes and often distance them from the field of play. Objective: To determine the association of single nucleotide polymorphisms in various genes with sports injuries in soccer. Material and methods: We searched in the databases PubMed, ScienceDirect and EBSCO for studies published in the last 6 years to January 2020, including studies in English and Portuguese, corresponding to case-control clinical studies, where the experimental group were soccer practitioners and controls were supposedly healthy people. The final papers were assessed for quality and bias using the Jadad scoring scale or Oxford quality scoring system. From the data obtained, heterogeneity was identified with the I2 test and the Q statistic, for the estimation of the effect in the cohort studies the odds ratio and p value <0.05 were used, obtaining the forest plots of each gen. Results: 10 out of 1928 studies were selected, finding a degree of heterogeneity in all studies, such as the risk of injury to ACNT3 SNP (OR = 0.98, 95% CI 0.64-1.50), MMP (OR = 1.16, 95% CI 0.86 - 1.58, p = 0.33), TIMP2 (OR 1.03 95% CI 0.65-1.63), VEFGA (OR 0.98 95% CI 0.70-1.37). Conclusion: The studies showed moderate heterogeneity with statistical significance for the ACTN3 and TIM SNPs, providing a pathway for future studies that relate to sports injuries. MÉD.UIS.2021;34(3): 9-18.

Resumen Introducción: La alta incidencia de lesiones deportivas en atletas de élite es una preocupación en medicina deportiva. Se puede lograr una visión amplia sobre las lesiones deportivas en Colombia y sobre su fisiopatología desde el ámbito de la genómica, la cual podría responder a numerosas lesiones deportivas a partir de la Identificación de polimorfismos de nucleótido único que conducen a discapacidades que afectan la salud de los deportistas y frecuentemente los distancian del campo de juego. Objetivo: Determinar la asociación entre polimorfismos de nucleótido único en varios genes con lesiones deportivas en el fútbol. Materiales y métodos: Se realizó búsqueda en las bases de datos PubMed, ScienceDirect y EBSCO de estudios publicados en los últimos 6 años hasta enero de 2020, incluyendo estudios en inglés y portugués, correspondientes a estudios clínicos de casos y controles, donde el grupo experimental fueran practicantes de fútbol y los controles fueran personas presumiblemente saludables. Se evaluó la calidad y el sesgo de los artículos finales mediante la escala de puntuación de Jadad o el sistema de puntuación de calidad de Oxford. A partir de los datos obtenidos se identificó la heterogeneidad con la prueba de I2 y el estadístico Q, para la estimación del efecto en los estudios de cohorte se utilizaron odds ratio y valor p <0.05, obteniendo los forest plot de cada gen. Resultados. 10 de los 1928 estudios fueron seleccionados, se encontró un grado de heterogeneidad en todos los estudios, como el riesgo de lesión de los polimorfismos de nucleótido único para ACNT3 (OR = 0,98; IC del 95%: 0.64-1.50), MMP (OR = 1.16; IC del 95%: 0.86-1.58, p = 0.33), TIMP2 (OR = 1,03; IC del 95%: 0,65-1,63), VEFGA (OR = 0,98; IC del 95%: 0,70-1,37). Conclusión. Los estudios mostraron una heterogeneidad moderada con significancia estadística para los polimorfismos de nucleótido único de ACTN3 y TIM, lo que proporciona una vía para futuros estudios en relación con lesiones deportivas. MÉD.UIS.2021;34(3): 9-18.

Expression of Matrix Metalloproteinases-8 and Myeloperoxidase in Pulp Tissue after Pulpotomy with Calcium Silicate Cements

ABSTRACT Objective: To evaluate the pulp tissue of rat molars after pulpotomies with mineral trioxide aggregate (MTA), BiodentineTM (BDT) and calcium hydroxide (CH) mixed with sterile saline solution (24 hours, 72 hours, 7 days and 15 days), through correlating MPO activity with active neutrophils and MMP8 activity with tissue remodeling. Material and Methods: Thirty-eight Wistar rats were randomly distributed into groups (control, I (MTA gray), II (BDT), and III (CH)) and subdivided according to the study period of 24 hours, 72 hours, 7 days or 15 days after pulpotomy. MMP8 activity was assessed through fluorescence technique, and MPO activity was determined using the MPO assay. Results: A gradual decrease of MPO and MM8 activity occurred in the group MTA over the experimental periods (p<0.05). Groups BDT and CH exhibited an increase in the activity at 7 and 15 days (p<0.05). Conclusion: MTA demonstrated a decrease in the values of MPO e MMP8. BDT and CH showed high neutrophilic and collagenase activity over the experimental periods.

Análise in vitro da capacidade de soluções contendo fluoreto e/ou trimetafosfato na remineralização da dentina e na inibição da atividade de metaloproteinases da matriz dentinária / In vitro analysis of the capacity of solutions containing fluoride and/or trimetaphosphate in the remineralization of dentin and in the inhibition of the activity of dentin matrix metalloproteinases

Objetivo: O objetivo deste estudo foi investigar o potencial anti-proteolítico contra MMP-2 e MMP-9 e a capacidade de induzir a remineralização da dentina, através de soluções contendo diferentes concentrações de TMP (na sua forma cíclica), diferentes concentrações de F e associação TMP/F. Métodos: Blocos de dentina radicular (6mmx4mmx2mm, n = 130) foram selecionados e divididos aleatoriamente em 13 grupos/soluções experimentais (n = 10): 1) Placebo (sem F/TMP); 2) 0,3% TMP hidrolisado; 3) 1% TMP hidrolisado; 4) 3% TMP hidrolisado; 5) 0,3% TMP; 6) 1% TMP; 7) 3% TMP; 8) 250 ppm F; 9 500 ppm F; 10) 1100 ppm F; 11) 250 ppm F associado a 0,3% TMP; 12) 500 ppm F associado a 1% TMP e 13) 1100 ppm F associado a 3% TMP. A avaliação do potencial anti-proteolítico das soluções experimentais contra as metaloproteinases da matriz dentinária (- 2 e -9) foi realizado por meio da análise zimográfica. Para as análises mecânicas, três áreas foram determinadas para cada espécime: 1- controle (sem tratamento); 2- desmineralizado (cárie artificial); 3- tratado (desmineralizado e submetido a ciclagem de pH por 7 dias, e tratado por 1 min com as soluções experimentais). Os espécimes de dentina foram analisados quanto à porcentagem de recuperação de dureza superficial (%SHR), em dureza transversal (%CSHR) e por microtomografia computadorizada (IMC). Para os dados de dureza e Micro-CT, os resultados foram analisados por ANOVA de medidas repetidas seguida do teste de Student-Newman-Keuls (p <0,05). Resultados: A análise zimográfica mostrou que 1100 ppm F + 3% de TMP promoveu inibição completa da atividade gelatinolítica (MMP-2; MMP-9). Os grupos com TMP não hidrolisados apresentaram efeito remineralizador (% SHR e % CSHR) superior aos grupos hidrolisados. O grupo 1100F + TMP promoveu a maior %SHR e %CSHR entre todos os grupos (p <0,001), sendo respectivamente 15,4 e 10,5%, superior ao grupo 1100F. Os grupos contendo 1100F e 1100F + 3%TMP apresentaram maior concentração mineral. Conclusão: Com base nos resultados, 3% TMP atua como um agente antiproteolítico contra metaloproteinases da matriz dentinária. Além disso, quando suplementado com 1100F, 3% TMP potencializa a remineralização, aumentando significativamente as propriedades mecânicas da dentina tratada. Os tratamentos com TMP não hidrolisado e associado ao F maior que as soluções fluoretadas sem o TMP. Significância clínica: Dessa forma, uma potencial estratégia preventiva e terapêutica pode ser considerada na clínica odontológica, principalmente na terapia da cárie radicular, como também para método preventivo de lesões iniciais de cárie dentinária ou no pré-tratamento da dentina, utilizando-os como agentes cross-linker em procedimentos restauradores(AU)

Objective: The aim of this study was to investigate the anti-proteolytic potential against MMP-2 and MMP-9 and the ability to induce dentin remineralization, through solutions containing different concentrations of TMP (in its cyclic form), different concentrations of F and TMP / F association. Methods: Root dentin blocks (6mmx4mmx2mm, n = 130) were selected and randomly divided into 13 groups / experimental solutions (n = 10): 1) Placebo (without F / TMP); 2) 0.3% hydrolyzed TMP; 3) 1% hydrolyzed TMP; 4) 3% hydrolyzed TMP; 5) 0.3% TMP; 6) 1% TMP; 7) 3% TMP; 8) 250 ppm F; 9,500 ppm F; 10) 1100 ppm F; 11) 250 ppm F associated with 0.3% TMP; 12) 500 ppm F associated with 1% TMP and 13) 1100 ppm F associated with 3% TMP. The evaluation of the antiproteolytic potential of experimental solutions against dentin matrix metalloproteinases (- 2 and -9) was carried out by means of zymographic analysis. For mechanical analysis, three areas were determined for each specimen: 1- control (without treatment); 2- demineralized (artificial caries); 3- treated (demineralized and subjected to pH cycling for 7 days, and treated for 1 min with the experimental solutions). The dentin specimens were analyzed for the percentage of recovery of superficial hardness (% SHR), in crosssectional hardness (% CSHR) and by computed microtomography (∆IMC). For the hardness and Micro-CT data, the results were analyzed by repeated measures ANOVA followed by the Student-Newman-Keuls test (p <0.05). Results: The zymographic analysis showed that 1100 ppm F + 3% TMP promoted complete inhibition of gelatinolytic activity (MMP-2; MMP-9). The groups with non-hydrolyzed TMP showed a remineralizing effect (% SHR and % CSHR) superior to the hydrolyzed groups. The 1100F + TMP group promoted the highest % SHR and % CSHR among all groups (p <0.001), being 15.4 and 10.5%, respectively, higher than the 1100F group. The groups containing 1100F and 1100F + 3% TMP showed higher mineral concentration. Conclusion: Based on the results, 3% TMP acts as an antiproteolytic agent against dentinal matrix metalloproteinases. In addition, when supplemented with 1100F, 3% TMP enhances remineralization, significantly increasing the mechanical properties of the treated dentin. Treatments with non-hydrolyzed TMP and associated with F greater than fluoridated solutions without TMP. Clinical significance: Thus, a potential preventive and therapeutic strategy can be considered in the dental clinic, mainly in the treatment of root caries, as well as for the preventive method of initial lesions of dental caries or in the pretreatment of dentin, using them as agents cross-linker in restorative procedures(AU)

Metaloproteinases da matriz: papel no desenvolvimento das lesões periapicais e modulação após tratamento endodôntico / Matrix metalloproteinases: role in the development of apical periodontitis and modulation after endodontic treatment

Introduction: Apical periodontitis represents a local immune response directed against the progression of microorganisms from the dental pulp to the apical foramen and periapical tissues, which results in bone and dental resorption. The aim of this review is to describe the expression of this group of proteases in apical periodontitis and its modulation during the periapical healing phase following root canal treatment. Literature review: The pathogenesis of apical periodontitis involves degradation of several extracellular matrix components. Matrix metalloproteinases (MMPs) are expressed in response to specific stimuli by resident cells of connective tissue during tissue remodeling and by inflammatory cells that arrive into the surrounding tissues during inflammatory events. MMPs have been reported in apical periodontitis, either experimentally induced or obtained from humans and there is evidence that these enzymes show diff erent expression patterns in granulomas and periapical cysts. Root canal therapy is important for the reduction of periapical inflammation as well as the synthesis of MMPs, especially when using a calcium hydroxide-based dressing. Conclusion: Apical periodontitis show high expression of matrix metalloproteinases and root canal treatment results in less expression of MMPs when compared to untreated apical periodontitis.

Introdução: A lesão periapical representa a resposta imunoinflamatória devido ao aumento do número e progressão de micro-organismos advindos dos canais radiculares contaminados em direção aos tecidos apicais e periapicais, resultando em reabsorção óssea. O objetivo desta revisão será abordar a importância das metaloproteinases da matriz no desenvolvimento das lesões periapicais e sua modulação durante a fase de reparação tecidual depois de instituído o tratamento endodôntico. Revisão da literatura: A patogênese da lesão periapical envolve a degradação progressiva de diversos componentes da matriz extracelular. Dentre as proteases responsáveis pela degradação destes componentes estão as metaloproteinases da matriz (MMPs). Estas proteinases são expressas em resposta a estímulos específicos pelas células residentes do tecido conjuntivo durante o processo de remodelação tecidual e por células inflamatórias que invadem os tecidos durante eventos inflamatórios. As MMPs foram descritas em lesões periapicais experimentais e em humanos e existem evidências de que estas enzimas apresentam padrões de expressões diferentes em granulomas e cistos periapicais. A terapia endodôntica é importante para a redução da inflamação periapical assim como da síntese das MMPs, principalmente quando utilizado um curativo de demora à base de hidróxido de cálcio. Conclusão: As lesões periapicais apresentam alta expressão de metaloproteinases da matriz e o tratamento endodôntico em dentes com lesão periapical resulta em menor expressão de MMPs quando comparado às lesões periapicais não tratadas.

Biomarcadores para la evaluación y diagnóstico del síndrome de ojo seco: una revisión / Biomarkers for the evaluation and diagnosis of the dry eye syndrome: a review

Resumen Introducción: El síndrome de ojo seco es una enfermedad en la que se generan signos y síntomas que conducen a alteraciones oculares prolongadas, por lo tanto, es relevante establecer con precisión la etiología de la enfermedad con la finalidad de establecer el tratamiento más efectivo, de allí, la importancia del desarrollo de exámenes innovadores como son los biomarcadores, los cuales permiten identificar con mayor precisión el cuadro clínico. Por esta razón, el presente trabajo pretende describir los principales avances de los biomarcadores de la superficie ocular y reconocer su aplicación clínica para el diagnóstico de ojo seco entre los años 2013 a 2018. Metodología: Se analizó literatura sobre biomarcadores empleados para el diagnóstico del ojo seco, mediante una revisión sistemática tipo narrativa de 2013 a 2018 por medio de los descriptores controlados "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" seleccionados en DeCS y Pubmed; la búsqueda arrojó 48 estudios, de los cuales seleccionamos 21 para el análisis. Resultados: Son diversas las proteínas lagrimales que pueden ser relacionadas con la presencia y ausencia de la enfermedad, es vital que los biomarcadores sean valorados como una herramienta alternativa para diagnosticar con facilidad y precisión la enfermedad del ojo seco. Discusión: Los biomarcadores permiten reconocer los procesos patógenos y biológicos del síndrome de ojo seco, al reflejar el estado de la superficie ocular en presencia o ausencia de signos y síntomas, facilitando el diagnóstico precoz, seguimiento, tratamiento y control de la enfermedad.

Abstract Introduction: Dry eye syndrome is a disease in which signs and symptoms that lead to prolonged ocular alterations occur, therefore, it is relevant to accurately establish the etiology of the disease with the configuration of establishing the most effective treatment, hence the development of innovative exams such as biomarkers selected with greater precision the clinical picture. For this reason, the present work aims to describe the main advances of biomarkers of the ocular surface and to recognize their clinical application for the diagnosis of dry eye between 2013 and 2018. Metodology: Literature on biomarkers used for the diagnosis of dry eye was analyzed, by means of a systematic narrative review from 2013 to 2018 by means of the controlled descriptors "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" selected in DeCS and Pubmed; The search yielded 48 studies and 21 studies were selected for the analysis. Results: There are several tear proteins that can be related to the presence and absence of the disease, it is vital that biomarkers are evaluated as an alternative tool to easily and accurately diagnose dry eye disease. Discussion: Biomarkers allow to recognize the pathogenic and biological processes of dry eye syndrome, reflecting the state of the ocular surface in the presence or absence of signs and symptoms, facilitating early diagnosis, monitoring, treatment and control of the disease.

Cytotoxicity of chelating agents used in endodontics and their influence on mmps of cell membranes

Abstract This study evaluated the cytotoxic effect and the ability to inhibit matrix metalloproteinases (MMP-2 and MMP-9) of 0.2% chitosan (CH) and 1% acetic acid (AA) compared with 17% ethylenediaminetetraacetic acid (EDTA). Cell viability assay was performed according to ISO 10993-5 with mouse fibroblasts (L929). The culture was exposed to 0.2% CH, 1% AA, and 17% EDTA. The chelating agents were evaluated immediately after contact with the cells and after 6 h, 12 h, and 24 h of incubation. Cell viability was analyzed using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inhibition of the gelatinolytic activity of MMP-2 and MMP-9 was evaluated by gelatin zymography. Different concentrations of CH were evaluated: 50 mM, 5 mM, 0.5 mM, and 0.05 mM. EDTA (0.5 mM) was used as a positive control. The results demonstrated that CH and AA had an initial cytotoxic effect, which decreased after 6 h, 12 h, and 24 h, being statistically similar to EDTA (P > 0.05). Additionally, CH at concentrations of 50 mM, 5 mM, and 0.5 mM had an inhibitory effect on MMP-2 and MMP-9, similar to that of the control with EDTA. The chelating agents had no cytotoxic effects after 24 h. MMP-2 and MMP-9 were inhibited by the experimental solutions.

Resumo Este estudo avaliou o efeito citotóxico e a capacidade de inibição das metaloproteinases da matriz extracelular (MMP-2 e MMP-9) pela quitosana 0,2%(CH) e o ácido acético 1% (AA) em comparação com o ácido etilenodiaminotetracético 17% (EDTA). O ensaio de viabilidade celular foi realizado de acordo com a ISO 10993-5 com fibroblastos de camundongo (L929). A cultura foi exposta a CH 0,2%, AA 1% e EDTA 17%. Os agentes quelantes foram avaliados imediatamente após o contato com as células e após 6 h, 12 h e 24 h de incubação. A viabilidade celular foi analisada utilizando o ensaio de brometo de 3- (4,5-dimetitiazol-2-il) -2,5-difeniltetrazólio (MTT). A inibição da atividade gelatinolítica de MMP-2 e MMP-9 foi avaliada por zimografia de gelatina. Diferentes concentrações de CH foram avaliadas: 50 mM, 5 mM, 0,5 mM e 0,05 mM. EDTA (0,5 mM) foi usado como controlo positivo. Os resultados demonstraram que CH e AA apresentaram um efeito citotóxico inicial, que diminuiu após 6 h, 12 h e 24 h, sendo estatisticamente similar ao EDTA (P> 0,05). Adicionalmente, CH a concentrações de 50 mM, 5 mM e 0,5 mM tiveram um efeito inibidor sobre MMP-2 e MMP-9, semelhante ao controlo com EDTA. Os agentes quelantes apresentaram efeitos não citotóxicos após 24 h. MMP-2 e MMP-9 foram inibidas pelas soluções experimentais.

Resistance training improves the lipid profile, combat oxidative stress and inhibit MMP-2 activity in the left ventricle diet-induced obese rats

Abstract Aims: The purpose of the present study was to evaluate the effects of the resistance training (RT) on the lipid profile and metabolism, oxidative stress, and activity of metalloproteinase-2 (MMP-2) in the left ventricle (LV) of diet-induced obesity rats. Methods: Forty males Wistar rats 90 days-old were grouped into four groups (n=10): i) Sedentary group (SED); ii) Obese sedentary group, feed with high-fat diet (Ob-SED); iii) Resistance Trained group (RT), and iv) Obese Resistance trained group (Ob-RT). The LV was assayed to Obesity index, LV lipid content, citrate synthase activity, lipid peroxidation (TBARS), enzymatic and non-enzymatic antioxidant systems, lipid profile, cardio-metabolic parameters, and activity of MMP-2. Results: High-fat diet was associated with manifestations of the obesity, body mass gain, and increased obesity index, accompanied by an alteration in the lipid profile. On the other hand, RT was able to prevent body weight gain, to reduce the obesity index and to improve the lipid profile, to elevate the activation of the citrate synthase, and to decrease MMP-2 activity in the LV of obese rats. Conclusion: RT positively modulated blood lipid profile and antioxidant enzymes preventing the increased activity of MMP-2 in the left ventricle from rats fed with high-fat diet.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters

Abstract Purpose: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. Methods: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. Results: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). Conclusions: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Effect of chitosan nanoparticles on microtensile bond strength of resin composite to dentin: an in vitro study / Efeito de nanopartículas de quitosana na resistência a união por microtração da resina composta à dentina: um estudo in vitro

Objective: The purpose of this study was to evaluate the effect of chitosan nanoparticles on microtensile bond strength of resin composite to dentin using self etch adhesive after aging. Material and Methods: A total number of 90 freshly extracted, sound human molar teeth. Flat tooth surface was gained after cut of the occlusal surface. Three main groups according to pretreatment of dentin before adhesive application; 0.2 % chitosan, 2.5 % chitosan and no treatment control group. Universal self etch adhesive were applied according to manufacture instruction and 4 mm of Feltik Z250 xt composite. Storage of specimens for 1 day, 3 months and 6 months in 37O C distilled water. After that, the tooth was sectioned to beams of 1 mm x8 mm sticks for microtensile bond strength test using universal testing machine. Scanning electron microscope (SEM) was used to evalute the effect of chitosan nanoparticles on dentin and smear layer. Kruskal-Wallis test was used to compare between the three groups as well as the three aging periods. Dunn's test was used for pair-wise comparisons. The significance level was set at P ≤ 0.05. Results: chitosan 0.2% is statistically significant increase in bond strength than chitosan 2.5% and control in one day group. Three months chitosan 0.2 % groups have statistically significant increase in bond strength than chitosan 2.5%. It was found in 6 months that control and chitosan 0.2 % have statistically significant increase in bond strength than chitosan 2.5%. There was statistically significant difference found between the three studied groups regarding bond strength at different storage times . Conclusion: Microtensile bond strength was influenced by different chitosan concentration. Different aging periods had no effect on the microtensile bond strength without application of chitosan and with application of 2.5% chitosan concentration. (AU)

Introdução: O objetivo deste estudo foi avaliar o efeito das nanopartículas de quitosana na resistência da microtração de união do compósito de resina à dentina usando adesivo autocondicionante após o envelhecimento. Material e Métodos: Foram utilizados um total de 90 dentes molares humanos extraídos e sadios. A superfície plana do dente foi obtida após o corte da superfície oclusal. Os dentes foram divididos em três grupos principais de acordo com o pré-tratamento da dentina e antes da aplicação do adesivo: 0,2% de quitosana, 2,5% de quitosana e nenhum tratamento foi utilizado no grupo controle. O adesivo autocondicionante universal foi aplicado de acordo com as instruções do fabricante e 4 mm de composito Feltik Z250 xt foi inserido. O armazenamento de amostras foi realizado por 1 dia, 3 meses e 6 meses em água destilada a 37 °C. Depois disso, o dente foi seccionado em peças de 1 mm x 8 mm para teste de resistência de união por microtração, utilizando máquina de teste universal. Microscópio eletrônico de varredura (MEV) foi usado para avaliar o efeito das nanopartículas de quitosana na dentina e na camada de smear layer. O teste de Kruskal-Wallis foi utilizado para comparar os três grupos e os três períodos de envelhecimento. O teste de Dunn foi usado para comparação pareada dos grupos. O nível de significância foi estabelecido em P ≤ 0,05. (AU)

In vivo evaluation of inflammation and matrix metalloproteinase expression in dental pulp induced by luting agents in dogs

Objectives: To evaluate the inflammatory tissue response and matrix metalloproteinase (MMP)-2 and -9 expression in the pulp-dentin complex in response to RelyX TM Unicem (RU) and Ketac Cem TM Easymix (KC) cements. Methods : Class V cavities were prepared in 56 teeth from six dogs, and indirect pulp capping was performed using RU (n=20), KC (n=20), zinc oxide, and eugenol cement (control, n=16). At 7 and 70 days following indirect pulp capping, the animals were euthanized, and tissues were removed for histological evaluation. The distance from the cavity floor to the odontoblastic layer was measured, and the numbers of inflammatory cells, fibroblasts, and odontoblasts were counted in pulp tissue. MMP-2 and -9 expression levels were immunohistochemically assessed. Statistical analyses were performed for all experiments (significance level=5%). Results : The dentin remnant thickness between the cavity floor and the pulp chamber was similar for all materials, ranging from 469 to 739 µm (p>0.05). At 7 days, KC and RU induced a small inflammatory response in the pulp-dentin complex, similar to the control (p>0.05). At 70 days, RU induced a tissue response characterized by fewer odontoblasts and more mononuclear cells (p<0.05), whereas KC induced a response similar to the control (p>0.05). Lutingagents induced low levels of MMP-2 and MMP-9 expression, similar to the control (p>0.05). Conclusion : KC and RU luting agents are compatible materials for use in deep cavities close to dental pulp tissue, although RU led to a slightly diminished odontoblastic population with a higher percentage of mononuclear cells.

Objetivo : Avaliar a resposta tecidual inflamatória e a expressão de metaloproteinase de matriz (MMP) -2 e -9 no complexo polpa-dentina em resposta aos cimentos RelyX TM Unicem (RU) e Ketac Cem TM Easymix (KC). Métodos : Cavidades classe V foram preparadas em 56 dentes de seis cães, e capeamento pulpar indireto foi realizado com cimento de RU (n = 20), KC (n = 20), óxido de zinco e eugenol (controle, n = 16). Aos 7 e 70 dias após o capeamento pulpar indireto, os animais foram eutanasiados, e os tecidos foram removidos para avaliação histológica. A distância entre o assoalho da cavidade e a camada odontoblástica foi medida, e os números de células inflamatórias, fibroblastos e odontoblastos foram contados no tecido pulpar. Os níveis de expressão de MMP-2 e -9 foram avaliados por imuno-histoquímica. Análises estatísticas foram realizadas para todos os experimentos (nível de significância = 5%). Resultados : A espessura da dentina remanescente entre o assoalho da cavidade e a câmara pulpar foi semelhante para todos os materiais, variando de 469 a 739 µm (p> 0,05). Aos 7 dias, KC e RU induziram uma pequena resposta inflamatória no complexo polpa-dentina, semelhante ao controle (p> 0,05). Aos 70 dias, a RU induziu uma resposta tecidual caracterizada por menos odontoblastos e mais células mononucleares (p <0,05), enquanto o KC induziu uma resposta semelhante ao controle (p> 0,05). Os agentes cimentantes induziram baixos níveis de expressão de MMP-2 e MMP-9, semelhantes ao controle (p> 0,05). Conclusão : Os agentes cimentantes KC e RU são materiais compatíveis para uso em cavidades profundas próximas ao tecido da polpa dentária, embora a UR tenha levado a uma população odontoblástica levemente diminuída, com maior porcentagem de células mononucleares.

Inmunopatología de la brucelosis osteoarticular / Immunopathology of osteoarticular brucelosis

La brucelosis es una de las enfermedades zoonóticas más importantes a nivel mundial capaz de producir enfermedad crónica en los seres humanos. La localización osteoarticular es la presentación más común de la enfermedad activa en el hombre. Sin embargo, algunos de los mecanismos moleculares implicados en la enfermedad osteoarticular han comenzado a dilucidarse recientemente. Brucella abortus induce daño óseo a través de diversos mecanismos en los cuales están implicados TNF-α y RANKL. En estos procesos participan células inflamatorias que incluyen monocitos/macrófagos, neutrófilos, linfocitos T del tipo Th17 y linfocitos B. Además, B. abortus puede afectar directamente las células osteoarticulares. La bacteria inhibe la deposición de la matriz ósea por los osteoblastos y modifica el fenotipo de estas células para producir metaloproteinasas de matriz (MMPs) y la secreción de citoquinas que contribuyen a la degradación del hueso. Por otro lado, la infección por B. abortus induce un aumento en la osteoclastogénesis, lo que aumenta la resorción de la matriz ósea orgánica y mineral y contribuye al daño óseo. Dado que la patología inducida por Brucella afecta el tejido articular, se estudió el efecto de la infección sobre los sinoviocitos. Estos estudios revelaron que, además de inducir la activación de estas células para secretar quemoquinas, citoquinas proinflamatorias y MMPs, la infección inhibe la muerte por apoptosis de los sinoviocitos. Brucella es una bacteria intracelular que se replica en el retículo endoplásmico de los macrófagos. El análisis de los sinoviocitos infectados con B. abortus indicó que las bacterias también se multiplican en el retículo endoplasmático, lo que sugiere que la bacteria podría usar este tipo celular para la multiplicación intracelular durante la localización osteoarticular de la enfermedad. Los hallazgos presentados en esta revisión intentan responder a preguntas sobre los mediadores inflamatorios implicados en el daño osteoarticular causado por Brucella. (AU)

Brucellosis is one of the most important zoonotic diseases that can produce chronic disease in humans worldwide. Osteoarticular involvement is the most common presentation of human active disease. The molecular mechanisms implicated in bone damage have started to be elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and RANKL are implicated. These processes are driven by inflammatory cells, including monocytes/macrophages, neutrophils, Th17 lymphocytes and B cells. Also, Brucella abortus (B. abortus) can directly affect osteoarticular cells. The bacterium inhibits bone matrix deposition by osteoblast and modifies the phenotype of these cells to produce matrix methalloproteinases (MMPs) and cytokine secretion that contribute to bone matrix degradation. B. abortus also affects osteoclast increasing mineral and organic bone matrix resorption and contributing to bone damage. Since the pathology induced by Brucella species involves joint tissue, experiments conducted in sinoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits sinoviocyte apoptosis. Brucella is an intracellular bacterium that replicate in the endoplasmic reticulum of macrophages. The analysis of B. abortus infected sinoviocytes indicated that bacteria also replicate in their reticulum suggesting that the bacterium could use this cell type for intracellular replication during the osteoarticular localization of the disease. The findings presented in this review try to answer key questions about the inflammatory mediators involved in osteoarticular damage caused by Brucella. (AU)

Host response and peri-implantitis

Abstract Considering the absence of predictable and effective therapeutic interventions for the treatment of peri-implantitis, scientific evidence concerning the host response profile around dental implants could be important for providing in the future a wider preventive and/or therapeutic window for this peri-implant lesion, indicating biomarkers that provide quantifiable measure of response to peri-implant therapy. Moreover, a better knowledge of pattern of host osteo-immunoinflammatory modulation in the presence of peri-implantitis could either benefit the early diagnostic of the disease or to cooperate to prognostic information related to the status of the peri-implant breakdown. Finally, new evidences concerning the host profile of modulators of inflammation and of osseous tissue metabolism around dental implants could explain the individual susceptibility for developing peri-implant lesions, identifying individuals or sites with increased risk for peri-implantitis. The focus of this chapter was, based on a systematically searched and critically reviewed literature, summarizing the existing knowledge in the scientific research concerning the host osteo-immunoinflammatory response to the microbiological challenge related to periimplantitis.

Effect of gallic acid addition on some mechanical properties of self-adhesive resin cements

Abstract Self-adhesive resin cements (RCs) activate matrix metalloproteinase (MMP) and cathepsin-related collagen degradation, and gallic acid (GA) inhibits the activity of both MMPs and cysteine cathepsins. The purpose of this study was to evaluate the setting time, biaxial flexural strength, and Vickers hardness of self-adhesive RCs after the addition of two different concentrations of GA. RelyX U200 (3M ESPE) and Panavia SA (Kuraray) were modified with 0.5 and 1 wt% GA. The setting time of five samples in each RC group was assessed using a thermocouple apparatus as described in the ISO 4049 test. Biaxial flexure strength was measured using a universal testing machine until failure. Vickers hardness was measured with three randomized indentations on the surface of each resin disc. RCs without GA were used as control. Data were analyzed using a one-way analysis of variance and Tukey's HSD test (α = 0.05). The setting times ranged from 2.4 to 4.6 min for RelyX and from 4.9 to 6.0 min for Panavia. The biaxial flexure strength ranged from 76.5 to 109.7 MPa for RelyX and from 73.3 to 108.2 MPa for Panavia. Vickers hardness values ranged from 41.6 to 58.6 for RelyX and 27.2 to 33.6 for Panavia. The addition of 0.5 and 1 wt% GA to improve durability of resin-dentin bonds had no adverse effects on setting time, whereas the biaxial flexure strength and Vickers hardness values for the tested materials were significantly reduced.