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.

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.

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.

The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies: a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition.

AIM: Current literature on chronic periodontitis genetics encompasses numerous single nucleotide polymorphisms-focused case-control studies with inconsistent and controversial results, which typically disregards the exposure concept embraced by case-control definition. Herein, we propose a case-control design reappraisal by clear phenotype selection, where chronic gingivitis represents a genetically resistant phenotype/genotype opposing the susceptible cohort. MATERIAL AND METHODS: The hypothesis was tested in healthy, chronic periodontitis and gingivitis groups through Real-time PCR-based allelic discrimination of classic variants IL1B-3954, IL6-174, TNFA-308, IL10-592 and TLR4-299. RESULTS: Observed allele/genotype frequencies characterize the healthy group with an intermediate genetic profile between periodontitis and gingivitis cohorts. When comparing genotype/allele frequencies in periodontitis versus healthy and periodontitis versus gingivitis scenarios, the number of positive associations (2-4) and the degree of association (p and odds ratio values) were significantly increased by the new approach proposed (periodontitis versus gingivitis), suggesting the association of IL1B-3954, TNFA-308, IL10-592 and TLR4-299 with periodontitis risk. Power study was also significantly improved by the new study design proposed when compared to the traditional approach. CONCLUSIONS: The data presented herein support the use of new case-control study design based on the case-control definition and clear resistance/susceptibility phenotypes selection, which can significantly impact the study power and odds of identification of genetic factors involved in PD.

Functional interferences in host inflammatory immune response by airway allergic inflammation restrain experimental periodontitis development in mice.

AIMS: periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. MATERIAL AND METHODS: Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. RESULTS: PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, interferon-γ, IL-17A, receptor activator of nuclear factor κ-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor γ and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. CONCLUSION: our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.

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.

Role of inflammatory and pain genes polymorphisms in temporomandibular disorder and pressure pain sensitivity.

OBJECTIVE: The aim of this study was to assess the correlation of inflammatory and pain genes polymorphisms with the presence of temporomandibular disorder (TMD) patients and with pressure pain sensitivity. DESIGN: Data was collected from 268 consecutive subjects at Bauru School of Dentistry. Subjects aged younger than 20 years, with dental and neuropathic pain, sinusitis, cognitive and neurologic disorder were excluded. Included subjects were evaluated using the Research Diagnostic Criteria for Temporomandibular disorders and divided into two groups: TMD cases and healthy controls. Groups were submitted to pressure pain threshold (PPT) test for the temporomandibular joint, anterior temporalis and masseter muscles and genotyped for Val158Met, IL6-174, IL-1ß-3954 and TNFA-308. Student's t-test and Pearson chi-square test were used to comparisons between groups. A linear multiple regression was used to evaluate the influence of genetics variables on the PPT and a bivariate analysis was used to assesses the influence of genetics variables on pain sensitivity below the PPT cut off of the structures in TMD group. RESULTS: TMD group showed significantly lower PPT values for all structures when compared with control group (p < 0.001). SNP IL6-174 predicted higher pain sensitivity in the temporomandibular joint (p < 0.005) and in anterior temporalis muscle (p < 0.044) and SNP Val158Met in the masseter muscle (p < 0.038); when TMD group was divided according to PPT cut-off values the SNP Val158Met influenced increase pain sensibility in the masseter muscle. CONCLUSION: TNFA-308 was associated with TMD and SNP IL6-174 and SNP Val158Met influenced pain sensitivity of patients with TMD.

Gelatin-based membrane containing usnic acid-loaded liposomes: A new treatment strategy for corneal healing.

PURPOSE: To evaluate the safety and potential healing efficacy of the topical ocular administration of a gelatin membrane containing usnic acid/liposomes (UALs) for corneal cicatrization. UALs have shown healing activity in animal models of dermal burn lesions. We evaluated the safety of topical ocular administration of UAL and its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes. METHOD: The Draize test was used to check for ocular toxicity and the score was zero at each observation, indicating the ocular safety of a gelatin membrane containing usnic acid/liposome. Its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes was also assessed. RESULTS: After epithelial removal and treatment with UAL, there was a 49.4 % reduction in injury under in vivo conditions compared with a 36.6 % reduction in the control, a gelatin membrane containing liposome without usnic acid. Histological analysis of ocular surface chemical injury-tissue sections after treatment with UAL supported these observations. The corneal expression of VEGF and TGF-ß1increased by 70 % and 50 % respectively following treatment with UAL gelatin membrane. CONCLUSION: These results indicate the potential therapeutic application of UAL gelatin membranes as an ophthalmic treatment that may be used for corneal cicatrization.

Strong and persistent microbial and inflammatory stimuli overcome the genetic predisposition to higher matrix metalloproteinase-1 (MMP-1) expression: a mechanistic explanation for the lack of association of MMP1-1607 single-nucleotide polymorphism genotypes with MMP-1 expression in chronic periodontitis lesions.

AIMS: Our objective was to evaluate the association between the MMP1-1607 single-nucleotide polymorphism (SNP), periodontopathogens and inflammatory cytokines with matrix metalloproteinase-1 (MMP-1) mRNA levels in vitro and in vivo. MATERIALS AND METHODS: This study investigated the influence of genetic (MMP1-1607 SNP), microbial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Actinobacillus actinomycetemcomitans) and inflammatory [tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)] factors on the determination of MMP-1 mRNA levels in periodontal tissues of non-smoker chronic periodontitis (CP, N=178) and control (C, N=190) groups. The effects of single and repeated lipopolysaccharide (LPS) and inflammatory cytokine stimulation of macrophages with distinct MMP1-1607 SNP genotypes were also investigated. RESULTS: In healthy tissues, the MMP1-1607 2G allele was associated with higher MMP-1 levels while in CP MMP-1 levels were associated with the presence and load of periodontopathogens, and also with TNF-alpha and IL-1beta expression irrespective of the MMP1-1607 genotype. In vitro data demonstrate that in 2G macrophages low- and intermediate-dose LPS and TNF-alpha+IL-1beta stimulation was associated with increased MMP-1 expression, while strong and repeated stimulation resulted in higher MMP-1 levels irrespective of the MMP1-1607 genotype. CONCLUSION: Our data demonstrate a limited role for MMP1-1607 SNP in periodontitis, where the extensive chronic antigenic challenge exposure overcomes the genetic control and plays a major role in the determination of MMP-1 expression.

Differential expression of osteoblast and osteoclast chemmoatractants in compression and tension sides during orthodontic movement.

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading, and is supposed to be mediated by several host mediators, such as chemokines. In this study we investigated the pattern of mRNAs expression encoding for osteoblast and osteoclast related chemokines, and further correlated them with the profile of bone remodeling markers in palatal and buccal sides of tooth under orthodontic force, where tensile (T) and compressive (C) forces, respectively, predominate. Real-time PCR was performed with periodontal ligament mRNA from samples of T and C sides of human teeth submitted to rapid maxillary expansion, while periodontal ligament of normal teeth were used as controls. Results showed that both T and C sides exhibited significant higher expression of all targets when compared to controls. Comparing C and T sides, C side exhibited higher expression of MCP-1/CCL2, MIP-1alpha/CCL3 and RANKL, while T side presented higher expression of OCN. The expression of RANTES/CCL5 and SDF-1/CXCL12 was similar in C and T sides. Our data demonstrate a differential expression of chemokines in compressed and stretched PDL during orthodontic tooth movement, suggesting that chemokines pattern may contribute to the differential bone remodeling in response to orthodontic force through the establishment of distinct microenvironments in compression and tension sides.

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.

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.

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.

Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization.

Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h), the development of a provisional immature granulation tissue is evident (7 d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFß1,VEGFa), cytokines (TNFα, IL-10), chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4), matrix (Col1a1-2, ITGA4, VTN, MMP1a) and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146) markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14 d), characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9), bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST) markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2). No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21 d) when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the histomorphometric events and the potential participation of MCSs and immune cells in the healing process, supporting the forthcoming application of the model for the better understanding of the bone healing process.

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.