Microtomographic, histomorphometric, and molecular features show a normal alveolar bone healing process in iNOS-deficient mice along a compensatory upregulation of eNOS and nNOS isoforms.

METHODOLOGY: Inducible nitric oxide synthase (iNOS) is one of the enzymes responsible for the synthesis of nitric oxide (NO), which is an important signaling molecule with effects on blood vessels, leukocytes, and bone cells. However, the role of iNOS in alveolar bone healing remains unclear. This study investigated the role of iNOS in alveolar bone healing after tooth extraction in mice. C57Bl/6 wild type (WT) and iNOS genetically deficient (iNOS-KO) mice were subjected to upper incision tooth extraction, and alveolar bone healing was evaluated by micro-computed tomography (µCT) and histological/histomorphometric, birefringence, and molecular methods. RESULTS: The expression of iNOS had very low control conditions, whereas a significant increase is observed in healing sites of WT mice, where iNOS mRNA levels peak at 7d time point, followed by a relative decrease at 14d and 21d. Regarding bone healing, both WT and iNOS-KO groups showed the usual phases characterized by the presence of clots, granulation tissue development along the inflammatory cell infiltration, angiogenesis, proliferation of fibroblasts and extracellular matrix synthesis, bone neoformation, and remodeling. The overall micro-computed tomography and histomorphometric and birefringence analyses showed similar bone healing readouts when WT and iNOS-KO strains are compared. Likewise, Real-Time PCR array analysis shows an overall similar gene expression pattern (including bone formation, bone resorption, and inflammatory and immunological markers) in healing sites of WT and iNOS-KO mice. Moreover, molecular analysis shows that nNOS and eNOS were significantly upregulated in the iNOS-KO group, suggesting that other NOS isoforms could compensate the absence of iNOS. CONCLUSION: The absence of iNOS does not result in a significant modulation of bone healing readouts in iNOS-KO mice. The upregulation of nNOS and eNOS may compensate iNOS absence, explaining the similar bone healing outcome in WT and iNOS-KO strains.

Microtomographic, histomorphometric, and molecular features show a normal alveolar bone healing process in iNOS-deficient mice along a compensatory upregulation of eNOS and nNOS isoforms

Abstract Inducible nitric oxide synthase (iNOS) is one of the enzymes responsible for the synthesis of nitric oxide (NO), which is an important signaling molecule with effects on blood vessels, leukocytes, and bone cells. However, the role of iNOS in alveolar bone healing remains unclear. This study investigated the role of iNOS in alveolar bone healing after tooth extraction in mice. Methodology C57Bl/6 wild type (WT) and iNOS genetically deficient (iNOS-KO) mice were subjected to upper incision tooth extraction, and alveolar bone healing was evaluated by micro-computed tomography (μCT) and histological/histomorphometric, birefringence, and molecular methods. Results The expression of iNOS had very low control conditions, whereas a significant increase is observed in healing sites of WT mice, where iNOS mRNA levels peak at 7d time point, followed by a relative decrease at 14d and 21d. Regarding bone healing, both WT and iNOS-KO groups showed the usual phases characterized by the presence of clots, granulation tissue development along the inflammatory cell infiltration, angiogenesis, proliferation of fibroblasts and extracellular matrix synthesis, bone neoformation, and remodeling. The overall micro-computed tomography and histomorphometric and birefringence analyses showed similar bone healing readouts when WT and iNOS-KO strains are compared. Likewise, Real-Time PCR array analysis shows an overall similar gene expression pattern (including bone formation, bone resorption, and inflammatory and immunological markers) in healing sites of WT and iNOS-KO mice. Moreover, molecular analysis shows that nNOS and eNOS were significantly upregulated in the iNOS-KO group, suggesting that other NOS isoforms could compensate the absence of iNOS. Conclusion The absence of iNOS does not result in a significant modulation of bone healing readouts in iNOS-KO mice. The upregulation of nNOS and eNOS may compensate iNOS absence, explaining the similar bone healing outcome in WT and iNOS-KO strains.

Comparação entre métodos cirúrgicos e conservadores para o tratamento de granuloma central de células gigantes descritos na literatura / Comparison between surgical and conservative methods for the treatment of central granuloma of giant cells described in the literature

Objetivo: Apresentar, através de uma revisão de literatura, métodos de tratamento do Granuloma mais conservadores, estabelecendo comparações entre estes, afim de fornecer à comunidade científica mais clareza e opções mais efi-cazes e seguras para o paciente. Revisão da literatura:O Granuloma Central de Células Gigantes (GCCG) é uma lesão proliferativa benigna intraóssea de etiologia incerta e comportamento clínico variável que possui como forma de tratamento mais utilizado os métodos cirúrgicos, entretanto, observou-se que os métodos cirúrgicos apresentam alta taxa de recidiva e um grande comprometimento estético e funcional. Em contrapartida, métodos mais conserva-dores mostram regressão completa da lesão e baixa taxa de recidiva, porém com a desvantagem de apresentar um longo período de tratamento e alguns efeitos adversos. Discussão: Ainda não existe um protocolo de gerenciamento de GCCG, seu manejo clínico deve levar em consideração a possibilidade de combinação de duas ou mais terapias objetivando melhores resultados. Conclusão: Os métodos conservadores são promissores por diminuir o tempo de tratamento e preservar a estética e função, além de ter a possibilidade de serem empregados juntos conforme a necessidade do paciente, apesar de nenhuma forma de tratamento individual ser a ideal.

Aim: To present, through a literature review, more conservative methods of treatment for Granuloma, establishing comparisons between them, in order to provide the scientific community with more clarity and more effective and safer options for the patient. Literature review: The Central Giant Cell Granuloma (GCCG) is a benign proliferative intraosseous lesion of uncertain etiology and variable clinical behavior that has surgical methods as the most used form of treatment, however, it was observed that surgical methods have a high recurrence rate and a great aesthetic and functional compromise. On the other hand, more conservative methods show complete regression of the lesion and a low recurrence rate, but with the disadvantage of presenting a long period of treatment and some adverse effects. Discussion: There is no protocol for managing GCCG, its clinical management should consider the possibility of com-bining two or more therapies aiming at better results. Conclusion: Conservative methods are promising for reducing treatment time and preserving aesthetics and function, in addition to having the possibility of being used together according to the patient's need, although no individual treatment is ideal.

The new paradigms in the time of care to patients with head and neck cancer during the Covid-19 pandemic: a literature review / Os novos paradigmas no tempo de atendimento em pacientes com câncer de cabeça e pescoço durante a pandemia Covid-19: revisão de literatura

Introduction: SARS-CoV2 is a worldwide health threat, which has as its main risk group patients with head and neck cancer. In the time being and in the chance of an emerging second wave of infection, a new protocol based on when to treat patients with head and neck cancer must be implemented. Aim: Reporting the handling protocols for patients with head and neck cancer, facilitating the clinician's decision in the pandemic scenario. Materials and Methods: A bibliographic search was performed in PubMed. A search strategy with descriptors was applied to the database, aiming at reaching scientific articles. The articles reached in such database had their titles and abstracts read in search for the adequacy to the objective proposed. Only scientific articles published between De-cember 1st 2019, and July 10th 2020, were chosen. There was no restriction either on country or language. Literature review: New protocols were created based on the type and stage of cancer, classifying them in order to identify the ideal time to operate safely. Thus, the protocol has levels from initial to advanced, where the initial level comprises benign neoplasms, skin cancers smaller than 2 mm and cases in asymptomatic early stages, and the advanced level comprises malignant, aggressive neoplasms, with painful symptoms and/or that are compromising the other systems and organs. Conclusion: It is necessary to follow the detailed care protocol to guide the progress of head and neck cancer services, by operating patients immediately or postponing surgery, depending on the case and seriousness.

Introdução: O novo coronavirus SARS-CoV2 é uma ameaça de saúde mundial que tem como um de seus principais grupo de risco os pacientes com câncer de cabeça e pescoço. Na atual conjuntura e em caso de uma segunda onda de infecção, há necessidade de um novo protocolo de quando tratar esses pacientes. Objetivo: Relatar os protocolos de manejo e atendimento dos pacientes com câncer de cabeça e pescoço, facilitando a decisão do clínico no cenário de pandemia. Materiais e Métodos: Uma busca bibliográfica foi realizada no PubMed. Uma estratégia de busca com descritores foi aplicada, onde os artigos alcançados tiveram seus títulos e resumos lidos em busca da adequação ao objetivo proposto. Foram selecionados artigos científicos publicados entre 1 de dezembro de 2019 e 10 de julho de 2020, sem restrição de país ou idioma. Revisão da literatura: Novos protocolos foram criados baseados no tipo e estágio de câncer, classificando-os para saber o momento ideal de intervir com segurança. O protocolo se dá em níveis de inicial ao avançado onde o inicial compreende as neoplasias benignas, ou seja, cânceres de pele menores de 2 mm e casos em estágios iniciais assintomáticos, e o nível avançado compreende neoplasias malignas, agressivas, com sintomatologia dolorosa e/ou que estejam comprometendo os outros sistemas e órgãos. Conclusão: Há necessidade de seguir o protocolo de atendimento detalhado que norteie o andamento dos serviços oncológicos de cabeça e pescoço, atendendo os pacientes imediatamente ou adiando o tratamento dependendo do caso e severidade.

Laserterapia de baixa intensidade no manejo da dor provocada por separadores elastoméricos: uma revisão integrativa / Low-level laser therapy in the management of pain evoked by elastomeric separators: an integrative review

Introdução: O uso de separadores elastoméricos durante o tratamento ortodôntico pode provocar dor e a laserterapia de baixa intensidade tem sido empregada no manejo deste desfecho. Objetivo: Apresentar as evidências sobre o efeito da laserterapia de baixa intensidade no manejo da dor provocada pelo uso de separadores elastoméricos. Métodos: Foi desenvolvida uma revisão integrativa de estudos clínicos nas bases de dados PubMed, Web of Science, Scopus, BVS, SciELO e clinicaltrials.gov utilizando uma estratégia PICo elaborada com descritores, incluindo estudos publicados nos últimos dez anos, sem restrição de idioma. Foram rastreados 68 artigos e 12 foram revisados. Revisão de literatura: Considerando a laserterapia, a maioria dos estudos utilizou arsenieto de gálio e alumínio (Ga-Al-As), com comprimento de onda entre 808nm e 940nm, bem como a potência entre 40.6mW e 200mW. A escala visual analógica (EVA) foi utilizada pela maioria dos estudos para mensurar a dor. Dois estudos não verificaram diferenças significativas da laserterapia de baixa intensidade na dor provocada pelos separadores elastoméricos, oito estudos encontraram diferenças significantes entre os grupos de intervenção, de controle e o placebo (quando utilizado) e dois estudos não foram totalmente conclusivos e apontaram diferenças estatística parciais entre os grupos em questão. As técnicas de aplicação foram demasiadamente heterogêneas nos estudos incluídos nesta revisão e não permitem uma síntese quantitativa. Conclusão: O laser de baixa intensidade pode demonstrar efeitos benéficos na redução da dor provocada por separadores elastoméricos. Entretanto, ainda não é possível determinar qual a melhor técnica de aplicação.

Introduction: The use of elastomeric separators during orthodontic treatment can cause pain and low-level laser therapy has been used to manage this outcome. Objective:To present the evidence on the effect of low-level laser therapy in the management of pain caused by the use of elastomeric separators. Methods: An integrative review of clinical studies was carried out in the PubMed, Web of Science, Scopus, BVS, SciELO and clinicaltrials.gov data-bases using a PICo strategy developed with descriptors, including studies published in the last ten years, without language restriction. 68 articles were tracked and 12 were reviewed. Literature review: Considering laser therapy, most studies used gallium and aluminum arsenide (Ga-Al-As), with a wavelength between 808nm and 940nm, as well as power between 40.6mW and 200mW. The visual analog scale (VAS) was used by most studies to measure the pain. Two studies did not find significant differences in low-level laser therapy in pain caused by elastomeric separators, eight studies found significant differences between the intervention, control and placebo groups (when used) and two studies were not fully conclusive and pointed out partial statistical differences between the groups in question. The application techniques were too heterogeneous in the studies included in this review and do not allow a quantitative synthesis. Conclusion: The low-level laser therapy can demonstrate beneficial effects in reducing pain caused by elastomeric separators. However, it is not yet possible to determine the best application technique.

Insights for temporomandibular disorders management: From psychosocial factors to genetics-A case report.

AIMS: This case report aimed to discuss the multifactorial etiology and also the management of temporomandibular disorders (TMD) by addressing important associated psychosocial and biological factors, emphasizing the interaction between these factors and a probable genetic predisposition. METHODS AND RESULTS: A 21-year-old female patient was evaluated according to Research Diagnostic Criteria for TMD and diagnosed with arthralgia, myofascial pain, disc displacement without reduction, and temporomandibular joint (TMJ) degenerative disease. TMJ alterations were confirmed through magnetic resonance imaging and cone-beam computed tomography. Pressure pain threshold of masticatory structures was evaluated using a pressure algometer. Sleep bruxism, poor sleep quality, migraine with aura, mild anxiety, and history of facial trauma were also identified through anamnesis and clinical examination. Following this, genetic analysis was performed to evaluate the presence of single nucleotide polymorphisms (SNPs) already associated with TMD: SNP COMT Val158 Met (rs4680), MMP1-1607 (rs1799750), and tumor necrosis factor alpha-308 (rs1800629), which were all present. A personalized treatment for TMD management was performed, and it included self-management programs, occlusal appliance therapy, pharmacotherapy, anxiety management, and stress control. An 8-year follow-up demonstrated long-term stabilization of TMJ degenerative disease. CONCLUSION: Genetic evaluation, added to anamnesis and clinical examination, could be useful for TMD prognosis and management.

Prevalence of mental disorders among elderly men: a systematic review and meta-analysis.

BACKGROUND: Elderly men have been characterized as a group vulnerable to suicide, motivated by loneliness, loss of loved ones and feelings of uselessness to family members. OBJECTIVES: To ascertain the prevalence of different mental disorders among elderly men who attempted suicide. DESIGN AND SETTING: Systematic review of observational studies developed as a result of a partnership between two postgraduate schools (Lagarto and Uberlândia). METHODS: An electronic search was performed in eight electronic databases, including "grey literature", in January 2019. Observational studies that assessed mental disorders among men older than 60 years who attempted suicide were eligible for inclusion. RESULTS: Among the disorders evaluated, mood disorders had the highest prevalence (42.0%; 95% confidence interval, CI: 31.0-74.0%; I2: 0.0%; P = 0.763), followed by substance use-related disorders (41.0%; 95% CI: 8.0-74.0%; I2: 96.4; P < 0.001) and, lastly, schizophrenic disorders (5.0%; 95% CI: 0.0%-14.0%; I2: 80.3%; P = 0.024). CONCLUSIONS: It seems that mood disorders and substance use-related disorders are quite prevalent among elderly men with mental disorders who attempted suicide. It is important to consider the role of healthcare services in making early diagnoses of mental disorders among elderly men, in order to diminish the chances of suicide attempts among them. SYSTEMATIC REVIEW REGISTRATION: CRD42018105981.

Prevalence of mental disorders among elderly men: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Elderly men have been characterized as a group vulnerable to suicide, motivated by loneliness, loss of loved ones and feelings of uselessness to family members. OBJECTIVES: To ascertain the prevalence of different mental disorders among elderly men who attempted suicide. DESIGN AND SETTING: Systematic review of observational studies developed as a result of a partnership between two postgraduate schools (Lagarto and Uberlândia). METHODS: An electronic search was performed in eight electronic databases, including "grey literature", in January 2019. Observational studies that assessed mental disorders among men older than 60 years who attempted suicide were eligible for inclusion. RESULTS: Among the disorders evaluated, mood disorders had the highest prevalence (42.0%; 95% confidence interval, CI: 31.0-74.0%; I2: 0.0%; P = 0.763), followed by substance use-related disorders (41.0%; 95% CI: 8.0-74.0%; I2: 96.4; P < 0.001) and, lastly, schizophrenic disorders (5.0%; 95% CI: 0.0%-14.0%; I2: 80.3%; P = 0.024). CONCLUSIONS: It seems that mood disorders and substance use-related disorders are quite prevalent among elderly men with mental disorders who attempted suicide. It is important to consider the role of healthcare services in making early diagnoses of mental disorders among elderly men, in order to diminish the chances of suicide attempts among them. SYSTEMATIC REVIEW REGISTRATION: CRD42018105981.

Tricho-dento-osseous syndrome: a brief review for dentistry / Síndrome trico-dento-óssea: uma breve revisão para odontologia

Introduction: Tricho-dento-osseous syndrome is a ultra-rare ectodermal dysplasia related to genetic alterations in the DLX3 gene of interest to the health sciences due to its clinical manifestations. Aim: To synthesize the scientific evidence about tricho-dento-osseous syndrome, especially for den-tistry. Methods: A bibliographic search was performed in the MEDLINE / PubMed, Web of Science and Scopus databases. A search strategy with descriptors was applied to all databases mentioned to reach scientific articles. The articles reached in all databases had their titles and abstracts read in search of adaptation to the proposed objective. There was no restriction on the year of publication, country or language. Literature review: Patients diagnosed with this syndrome have dental enamel defects and severe taurodontism, especially in the permanently lower first molars. In addition to these signs, other manifestations may be associated, such as curly hair, increased bone density and changes in craniofacial bones. The diagnosis of tricho-dento-osseous syndrome can be challenging due to the heterogeneity and wide phenotypic variation presented by patients with DLX3 mutations, since this gene is associated with several functions, especially related to cell differentiation and biomineralization. In addi-tion, it is necessary to consider that other dental anomalies may be confused with tricho-dento-osseous syndrome, especially cases of imperfect amelogenesis associated with taurodontism. Conclusion: For dentistry, oral manifestations caused by this syndrome become relevant for diagnostic and therapeutic purposes, although there are no clinical protocols for dental management of this patients.

Introdução: A síndrome trico-dento-óssea é uma displasia ectodérmica ultra-rara relacionada a alterações genéticas no gene DLX3de interesse para as ciências da saúde de-vido à suas manifestações clínicas. Objetivo: Sintetizar as evidências científicas sobre a síndrome trico-dento-óssea, especialmente para odontologia. Materiais e métodos: Uma pesquisa bibliográfica foi realizada nas bases de dados ME-DLINE/PubMed, Web of Science e Scopus. Uma estratégia de busca com descritores foi aplicada em todas as bases de dados mencionadas para alcançar os artigos científicos. Os artigos alcançados em todas as bases de dados tiveram seus títulos e resumos lidos em busca da adequação ao objetivo proposto. Não houve restrição quanto ao ano de publicação, país ou idioma. Revisão de literatura: Os pacientes diagnos-ticados com essa síndrome apresentam defeitos no esmalte dentário e taurodontismo severo, principalmente nos pri-meiros molares permanentemente inferiores. Além desses sinais, outras manifestações podem estar associadas, como cabelos crespos, aumento da densidade óssea e alterações nos ossos craniofaciais. O diagnóstico da síndrome trico-dento-óssea pode ser desafiador devido à heterogeneidade e ampla variação fenotípica apresentada pelos pacientes com mutações em DLX3, uma vez que esse gene está associado a várias funções, principalmente relacionadas à diferenciação e biomineralização celular. Além disso, é necessário considerar que outras anomalias dentárias podem ser confundidas com a síndrome trico-dento-óssea, principalmente nos casos de amelogênese imperfeita associada ao taurodontismo. Con-clusão: Para a odontologia, as manifestações orais causadas por essa síndrome tornam-se relevantes para fins diagnós-ticos e terapêuticos, embora não existam protocolos clínicos para o tratamento odontológico específico destes pacientes.

Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction

The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21?days after upper incision extraction by micro-computed tomography (µCT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1+ cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80+ cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while M1 macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation 'sterile' inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and M1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome.(AU)

Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction

The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21?days after upper incision extraction by micro-computed tomography (µCT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1+ cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80+ cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while M1 macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation ‘sterile’ inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and M1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome.

Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction

The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21?days after upper incision extraction by micro-computed tomography (µCT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1+ cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80+ cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while M1 macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation ‘sterile’ inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and M1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome.

The influence of teriparatide in induced tooth movement: A systematic review.

BACKGROUND: Teriparatide is a synthetic drug similar than PTH (parathyroid hormone), which is currently used as long-term treatment option for patients with bone chronic diseases, as osteoporosis; and this drug can interfere in a positive way in orthodontic movement. Objectives: The medical literature was assessed in the present systematic review in order to determine the level of scientific evidence supporting the influence of teriparatide in induced tooth movement. MATERIAL AND METHODS: The PRISMA Checklist was followed in this systematic review. Four electronic databases (PubMed; Scopus; ScienceDirect; OpenGrey) were searched without implementing restrictions of year, status, and language of publications. The inclusion criteria consisted of selecting only experimental studies comparing the influence of teriparatide in tooth movement of male Wistar rats. The exclusion criteria consisted of experiments with female rats or other experimental animals, and animals with pathologic conditions. The eligible studies were evaluated based on methodological quality. Two trained examiners performed all the research steps. RESULTS: The initial sample comprised 700 studies, which was reduced to 664 after the exclusion of duplicates (n=36). Three articles were selected for the final qualitative analysis. The local administration of parathyroid hormone (PTH) 1-34 or PTH 1-84 revealed major effectiveness when compared with control groups and systematic administration. Additionally, the dilution of PTH 1-34 within methyl cellulose (MC) gel increased the time range for drug release, enabling to reduce the drug concentration without decreasing the effectiveness of tooth movement. CONCLUSIONS: Teriparatide demonstrated potential acceleration of tooth movement in Wistar rats depending on the drug concentration; drug administration; and time for drug release. Key words:Teriparatide, tooth movement, parathyroid hormone, orthodontics.

Influence of TNF-α-308 G/A gene polymorphism on temporomandibular disorder.

INTRODUCTION: Tumor necrosis factor alpha (TNF-α) levels are significantly upregulated in the synovial fluid of patients with temporomandibular joint disorder (TMD). The TNF-α influences pain generation and maintenance. Therefore, the aim of this study was to investigate the influence of single nucleotide polymorphism TNFA-308 (rs1800629) on TMD risk and on the pressure pain threshold. METHODS: The genotypic and allelic frequencies of candidate single nucleotide polymorphisms were compared among 152 TMD patients and 91 sex- and age-matched healthy subjects in the control group using the real-time polymerase chain reaction technique. The pressure pain threshold in the temporomandibular joint, anterior fascicle of the temporal muscle, masseter muscle, and Achilles tendon were recorded with an algometer. After the pressure test, all participants received a complete physical examination, including masticatory muscle evaluation, temporomandibular joint palpation, and assessment of mandibular range of motion. RESULTS: The TNFA-308 polymorphism is positively associated with TMD. Subjects with TMD had a 2.87 (95% confidence interval, 1.256-6.569) times greater chance of having the GA genotype than did the control group. Rare A-allele homozygotes demonstrated decreased pain sensitivity for the temporomandibular joint and anterior fascicle of the temporal muscle in the pressure pain threshold test compared with ancestral allele homozygotes. CONCLUSIONS: This study presents an unprecedented association between the TNFA-308 (rs1800629) polymorphism and TMD. Future studies are needed to enlighten the association between TNFA-308 G/A single nucleotide polymorphism and mechanical pain sensitivity.

Professional profile, legal obligations, and conduct of orthodontists in terms of litigation prevention / Perfil profissional, obrigações jurídicas e condutas dos ortodontistas frente à prevenção de litígios

Orthodontic treatment requires ethical and legal attitudes from professionals since the first contact with the patient. Thus, this study assessed professional profile, legal obligations in provision of care, and the conduct of orthodontists in terms of litigation prevention during their professional practice. Questionnaires were emailed to 1653 Brazilian orthodontists, asking for information such as: age, gender, graduate orthodontic education, time of work in orthodontics, place of graduate education, time since graduation, and information regarding the legal criteria involved in the orthodontic treatment. Data were tabulated using absolute and relative frequencies. The chi-square test (p<0.05) was used to verify the association among nominal qualitative variables. Only 163 orthodontists participated in the study, wherein men represented 60.5% and women 39.5% of the sample. It was clear that professionals most recently graduated are the ones that mostly use the care provision contract, and the ones that mostly request teleradiographs. The female gender offered more treatment options, clarified the estimated treatment time more often, and was less involved in legal issues. On the other hand, the male gender requested cephalometry more often. Most professionals request the control radiograph, and all of them file the medical records of patients. Few professionals use the professional liability insurance. The results of the present study indicate a highly heterogeneous professional profile. The female gender dominates the field of expertise, and they seem to be more careful regarding legal obligations.

O tratamento ortodôntico requer atitudes éticas e legais dos profissionais desde o primeiro contato com o paciente. Assim, este estudo avaliou o perfil profissional, as obrigações jurídicas na prestação de serviços e as condutas dos ortodontistas frente à prevenção de litígios durante o exercício da profissão. Foram enviados questionários para e-mails de 1653 ortodontistas brasileiros, solicitando informações como: idade, gênero, formação ortodôntica, tempo de atuação na Ortodontia, local e tempo de formação e informações quanto aos critérios legais envolvidos no tratamento ortodôntico. Os dados foram tabulados com a utilização de frequência absoluta e relativa. Para verificar a associação entre variáveis qualitativas nominais foi utilizado o teste do qui-quadrado (p<0,05). Somente 163 ortodontistas participaram desse estudo, com os homens correspondendo a 60.5% e as mulheres a 39.5% da amostra. Ficou evidente que os profissionais com menor tempo de formação são os que mais utilizam o contrato de prestação de serviço odontológico e são os que mais solicitam telerradiografias. O gênero feminino mostrou oferecer mais opções de tratamento, esclarecer mais frequentemente a estimativa do tempo de tratamento e se mostrou menos envolvido em problemas jurídicos. Enquanto que o gênero masculino mostrou maior frequência na solicitação de cefalometria. A maioria dos profissionais solicita a radiografia de controle e todos arquivam o prontuário do paciente. Poucos profissionais utilizam o seguro de responsabilidade profissional. Os resultados do presente estudo apontam para um perfil profissional bastante heterogêneo. A especialidade tem predomínio do gênero feminino e este parece ser mais cauteloso em relação às obrigações jurídicas.

Cinética de expressão de moléculas co-estimulatórias de osteoclastos no desenvolvimento da doença periodontal experimental e sua modulação por citocinas / Kinetics of osteoclast co-stimulatory molecules throughout experimental periodontitis and mice and its modulation by cytokines

O processo de diferenciação e ativação de osteoclastos, essencial para a manutenção da homeostasia do tecido ósseo e também envolvido na patogênese de diversas patologias caracterizadas pela atividade osteolítica, depende de um sistema central de controle que envolve a ligação das moléculas RANK/RANKL. Além do sistema RANK/RANKL, moléculas co-estimulatórias de osteoclastos, tais como os complexos DAP-12, TREM-2 e SIRP1, e FcR, OSCAR e PIR-A, também apresentam um papel importante na geração e ativação de osteoclastos. Entretanto, a possível contribuição de tais moléculas para a progressão da doença periodontal (DP) permanece desconhecida, assim como o possível impacto de citocinas na modulação de sua expressão no microambiente periodontal. Nosso objetivo foi investigar, por RealTimePCR, o padrão de expressão de moléculas co-estimulatórias de osteoclastos (DAP-12, TREM-2 e SIRP1, e FcR, OSCAR e PIR-A) na periodontite crônica em humanos, além de avaliar a cinética de expressão destas moléculas e a sua modulação por citocinas (TNF-, IFN-, IL-17 e IL-10) ao longo do curso da DP em camundongos em camundongos C57Bl/6 wild-type (WT) e geneticamente modificados (TNFp55KO, IFNKO, IL17KO, IL10KO. Nossos resultados demonstram que nas lesões periodontais crônicas a expressão de todas as moléculas co-estimulatórias de osteoclastos apresentaram-se significativamente aumentadas quando comparadas às amostras controle. Com relação à periodontite experimental, verificamos que todas as moléculas co-estimulatórias alvo apresentavam aumento em sua expressão após a indução de doença quando comparado aos controles. Nos camundongos para TNFp55KO, IFNKO e IL17KO, observamos uma redução na severidade da DP (reabsorção óssea e quantidade de células inflamatórias) e na expressão de moléculas co-estimulatórias, ao contrário do observado nos camundongos IL10KO. Entretanto, ao normalizarmos os níveis...

The osteoclast differentiation and activation are essential to bone tissue homeostasis and in the development of bone pathologies, which RANK/RANKL signaling molecules are the major osteoclastogenic factor. However, osteoclast co-stimulatory molecules, such as DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A, also present an important role in the osteoclastogenesis. However, the exact role and regulation of these molecules in human and mice periodontal diseases (PD) development have not completely known. Our aim was to investigate the pattern of osteoclast co-stimulatory expression (DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A) in human chronic periodontitis (CP), apart from analyze the kinetic of these molecules and their regulation by cytokines (TNF-, IFN-, IL-17 and IL-10) in the development of experimental periodontal disease in mice C57Bl/6 and knockout. Our results demonstrated that all osteoclast co-stimulatory molecules presented highly expressed in CP patients when compared with control. Similar results are presented about experimental PD, where all co-stimulatory molecules was presented highly expressed in infected mice when compared with control mice. We observed in TNFp55KO, IFNKO and IL17KO mice a decrease in PD scores and co-stimulatory molecules expression, the opposite of IL10KO mice. However, when we standardized the co-stimulatory molecules levels by the number of inflammatory cells, we found that TNF- and IL-17 are associated with increased expression of co-stimulatory molecules, while IFN- and IL-10 appear to negatively regulate the expression of such molecules. In conclusion, we demonstrated that osteoclast co-stimulatory molecules shown increased in human and experimental PD, and cytokines appear to modulate their expression by direct and indirect mechanisms, such as inflammatory cells migration to the PD infected tissue.

Cinética de expressão de moléculas co-estimulatórias de osteoclastos no desenvolvimento da doença periodontal experimental e sua modulação por citocinas / Kinetics of osteoclast co-stimulatory molecules throughout experimental periodontitis and mice and its modulation by cytokines

O processo de diferenciação e ativação de osteoclastos, essencial para a manutenção da homeostasia do tecido ósseo e também envolvido na patogênese de diversas patologias caracterizadas pela atividade osteolítica, depende de um sistema central de controle que envolve a ligação das moléculas RANK/RANKL. Além do sistema RANK/RANKL, moléculas co-estimulatórias de osteoclastos, tais como os complexos DAP-12, TREM-2 e SIRP1, e FcR, OSCAR e PIR-A, também apresentam um papel importante na geração e ativação de osteoclastos. Entretanto, a possível contribuição de tais moléculas para a progressão da doença periodontal (DP) permanece desconhecida, assim como o possível impacto de citocinas na modulação de sua expressão no microambiente periodontal. Nosso objetivo foi investigar, por RealTimePCR, o padrão de expressão de moléculas co-estimulatórias de osteoclastos (DAP-12, TREM-2 e SIRP1, e FcR, OSCAR e PIR-A) na periodontite crônica em humanos, além de avaliar a cinética de expressão destas moléculas e a sua modulação por citocinas (TNF-, IFN-, IL-17 e IL-10) ao longo do curso da DP em camundongos em camundongos C57Bl/6 wild-type (WT) e geneticamente modificados (TNFp55KO, IFNKO, IL17KO, IL10KO. Nossos resultados demonstram que nas lesões periodontais crônicas a expressão de todas as moléculas co-estimulatórias de osteoclastos apresentaram-se significativamente aumentadas quando comparadas às amostras controle. Com relação à periodontite experimental, verificamos que todas as moléculas co-estimulatórias alvo apresentavam aumento em sua expressão após a indução de doença quando comparado aos controles. Nos camundongos para TNFp55KO, IFNKO e IL17KO, observamos uma redução na severidade da DP (reabsorção óssea e quantidade de células inflamatórias) e na expressão de moléculas co-estimulatórias, ao contrário do observado nos camundongos IL10KO. Entretanto, ao normalizarmos os níveis...

The osteoclast differentiation and activation are essential to bone tissue homeostasis and in the development of bone pathologies, which RANK/RANKL signaling molecules are the major osteoclastogenic factor. However, osteoclast co-stimulatory molecules, such as DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A, also present an important role in the osteoclastogenesis. However, the exact role and regulation of these molecules in human and mice periodontal diseases (PD) development have not completely known. Our aim was to investigate the pattern of osteoclast co-stimulatory expression (DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A) in human chronic periodontitis (CP), apart from analyze the kinetic of these molecules and their regulation by cytokines (TNF-, IFN-, IL-17 and IL-10) in the development of experimental periodontal disease in mice C57Bl/6 and knockout. Our results demonstrated that all osteoclast co-stimulatory molecules presented highly expressed in CP patients when compared with control. Similar results are presented about experimental PD, where all co-stimulatory molecules was presented highly expressed in infected mice when compared with control mice. We observed in TNFp55KO, IFNKO and IL17KO mice a decrease in PD scores and co-stimulatory molecules expression, the opposite of IL10KO mice. However, when we standardized the co-stimulatory molecules levels by the number of inflammatory cells, we found that TNF- and IL-17 are associated with increased expression of co-stimulatory molecules, while IFN- and IL-10 appear to negatively regulate the expression of such molecules. In conclusion, we demonstrated that osteoclast co-stimulatory molecules shown increased in human and experimental PD, and cytokines appear to modulate their expression by direct and indirect mechanisms, such as inflammatory cells migration to the PD infected tissue.

Papel da quimiocina MIP-1α na imunomodulação da severidade da doença periodontal experimental / The role of MIP-1α on the immunomodulation of experimental periodontal disease in mice

O desenvolvimento da doença periodontal (DP) é influenciado pela resposta imunológica do hospedeiro frente ao desafio bacteriano. Apesar da função protetora de tal resposta frente à infecção, a mesma leva à destruição dos tecidos periodontais. Neste estudo, analisamos o papel de MIP-1a na imunomodulação da DP experimental em camundongos. Camundongos C57Bl/6 (WT) infectados com A. actinomycetemcomitans desenvolveram uma intensa reação inflamatória e severa reabsorção óssea alveolar, associada a uma alta expressão de MIP-1a e uma intensa migração de células CCR5+ e CCR1+ para os tecidos periodontais. Além disso, verificamos que uma intensa expressão de citocinas inflamatórias (TNF-'alfa') e do tipo Th1 (IFN-'gama'), RANKL e MMPs estava associada à progressão da doença. Entretanto, camundongos geneticamente modificados para não expressar MIP-1'alfa'(MIP-1'alfa'KO), quando infectados com A. actinomycetemcomitans, apresentaram um padrão de resposta muito semelhante aos animais WT. De fato, a ausência de MIP-1'alfa' não interferiu na migração de células inflamatórias para os tecidos periodontais e na reabsorção óssea alveolar nos camundongos infectados. Semelhantemente, a expressão de citocinas (TNF-'alfa', IFN-'gama' e IL-10), dos fatores osteoclastogênicos (RANKL e OPG) e das MMPs e seus inibidores (MMP-1, MMP-2, MMP-3, TIMP-1 e TIMP-3) foram similares entre os camundogos das linhagens WT e MIP-1'alfa'KO.

Além disso, a ausência de MIP-1a não interferiu no controle da infecção por A. actinomycetemcomitans como demonstrado pela similaridade na quantidade de carga bacteriana presente nos tecidos e nos níveis de MPO e iNOS. Os resultados obtidos podem ser explicados pela relativa redundância no sistema quimiocinas/receptores de quimiocinas, onde mais de uma quimiocina pode ligar-se ao mesmo receptor. De fato quimiocinas como MIP-1ß e RANTES, que utilizam os mesmos receptores de MIP-1'alfa' (CCR5 e CCR1), presentaram-se intensamente expressas nos tecidos periodontais dos camundongos infectados com A. actinomycetemcomitans, independentemente da ausência de MIP-1'alfa'. De fato, camundongos tratados com Met-RANTES, um antagonista específico dos CCR5 e CCR1, resultou em uma redução significativa no influxo de células inflamatórias e perda óssea alveolar quando comparados com os camundongos não tratados. Nossos resultados demonstraram que a ausência de MIP-1'alfa' não afeta o desenvolvimento da doença periodontal experimental em camundongos, provavelmente pela presença de quimiocinas homólogas que suprem sua ausência.

Periodontal disease (PD) development is highly influenced by the host immune response to the bacterial challenge. Despite the protective role of this response against infectious agents it leads to periodontal tissues destruction. In this study, we analyzed the role of chemokine MIP-1'alfa' on the immunomodulation of experimental PD in mice. C57Bl/6 (WT) mice infected with A. actinomycetemcomitans developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of MIP-1'alfa' and the migration of CCR5+ and CCR1+ cells to the periodontal tissues. In addition, an intense expression of Th1 (IFN-'gama') and inflammatory (TNF-'alfa') cytokines, RANKL and MMPs are associated with the disease progression. However, mice genetically deficient of MIP-1'alfa' (MIP-1'alfa'KO), when infected with A. actinomycetemcomitans, developed a very similar response pattern to that observed for WT strain. Indeed, the absence of MIP-1'alfa' does not interfere in inflammatory cells migration to periodontal tissues and alveolar bone resorption in response to A. actinomycetemcomitans infection. Similarly, the expression of cytokines (TNF- 'alfa', IFN-'gama' and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs and its inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3) was similar between WT and MIP-1'alfa'KO strains.

Furthermore, the lack of MIP-1'alfa' does not interfere in the control of A. actinomycetemcomitans infection as demonstrated by the similar bacterial load, and similar levels of the antimicrobial MPO and iNOS. Such results can be explained by the relative redundancy of chemokine system, where more than one chemokine can bind to the same receptor. Indeed, chemokines, such as MIP-1ß and RANTES, which use the same receptors used by MIP-1a (CCR1 and CCR5), are intensely expressed in periodontal tissues of mice infected with A. actinomycetemcomitans, regardless of the absence of MIP-1'alfa'. In accordance, the treatment of mice with Met-RANTES, a specific antagonist of the receptors CCR5 and CCR1, resulted in a significant reduction in the influx of inflammatory cells and alveolar bone loss when compared with untreated mice. Our results demonstrate that the absence of MIP-1a does not affect the development of experimental periodontitis in mice, probably due to the presence of homologous chemokines that overcome the absence of this chemokine.