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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.
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Huesos , Óxido Nítrico Sintasa , Cicatrización de Heridas , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Regulación hacia Arriba , Microtomografía por Rayos X , Huesos/lesionesRESUMEN
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.
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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.
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Terapéutica , Granuloma de Células Gigantes/cirugía , Calcitonina , Corticoesteroides , DenosumabRESUMEN
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.
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COVID-19 , Neoplasias de Cabeza y Cuello , Manejo de Atención al Paciente , Atención Integral de SaludRESUMEN
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.
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Ortodoncia/métodos , Terapia por Luz de Baja Intensidad , Manejo del DolorRESUMEN
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.
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Dolor Facial , Trastornos de la Articulación Temporomandibular , Adulto , Ansiedad , Artralgia , Femenino , Humanos , Ferulas Oclusales , Trastornos de la Articulación Temporomandibular/genética , Trastornos de la Articulación Temporomandibular/terapia , Adulto JovenRESUMEN
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.
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Inflamación/genética , Umbral del Dolor , Trastornos de la Articulación Temporomandibular , Adulto , Genotipo , Humanos , Interleucina-6/genética , Músculo Masetero , Polimorfismo de Nucleótido Simple , Presión , Músculo Temporal , Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/genética , Adulto JovenRESUMEN
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.
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Benzofuranos/administración & dosificación , Cicatriz/tratamiento farmacológico , Córnea/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Cicatrización de Heridas/efectos de los fármacos , Administración Oftálmica , Animales , Benzofuranos/química , Pollos , Córnea/irrigación sanguínea , Femenino , Gelatina/administración & dosificación , Gelatina/química , Liposomas/administración & dosificación , Liposomas/química , Neovascularización Fisiológica/efectos de los fármacos , Soluciones Oftálmicas/químicaRESUMEN
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.
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Trastornos Mentales , Trastornos Relacionados con Sustancias , Anciano , Humanos , Masculino , Prevalencia , Factores de Riesgo , Intento de SuicidioRESUMEN
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.
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Manifestaciones Bucales , Displasia EctodérmicaRESUMEN
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.
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Humanos , Masculino , Anciano , Trastornos Relacionados con Sustancias , Trastornos Mentales , Intento de Suicidio , Prevalencia , Factores de RiesgoRESUMEN
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)
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Animales , Osteítis/inmunología , Ratones/genéticaRESUMEN
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 21â¯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.
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Proceso Alveolar/patología , Inflamación/patología , Cicatrización de Heridas , Proceso Alveolar/diagnóstico por imagen , Animales , Antígenos CD/metabolismo , Birrefringencia , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Inflamación/diagnóstico por imagen , Ratones , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/patología , Microtomografía por Rayos XRESUMEN
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.
RESUMEN
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.
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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.
Asunto(s)
Ortodoncia , Responsabilidad Legal , Ética Odontológica , Ortodoncistas , Legislación en OdontologíaRESUMEN
Objetivo: Reportamos la asociación entre el polimorfismo de nucleótido simple de IL-10-592C/A (rs1800872) y la detección/abundancia relativa de los periodontopatógenos Porfiromonas gingivalis, Tenerella forsythia, Treponema denticola y Aggregatibacter actinomycetemcomitans. Además investigamos la influencia de los determinantes genéticos y microbiológicos en los niveles de expresión de IL-10 en lesiones periodontales. Metodología Fueron reclutados 117 pacientes con periodontitis crónica y 58 controles. Luego del examen clínico fueron obtenidas muestras microbiológicas y la presencia/carga bacteriana de especies de periodontopatógenos fue cuantificada por RT-PCR. El genotipo para IL-10-592C/A fue determinado mediante restriction fragment length polymorphism. Resultados La distribución alélica del SNP rs1800872 en la población investigada cumplió con el equilibrio de Hardy-Weinberg (p = 0,64). Como ya ha sido reportado, los sujetos polimórficos demostraron menor expresión de IL-10 y riesgo aumentado de sufrir periodontitis crónica. El polimorfismo IL-10-592C/A no demostró relación con la detección o carga bacteriana de ninguna de las bacterias investigadas, además los niveles de expresión de IL-10 no fueron influenciados por el perfil microbiológico, sino que se correlacionaron directamente con el genotipo para el polimorfismo IL-10-592C/A.
Objective: A study was conducted to investigate the possible influence of the single nucleotide polymorphism (SNP) IL-10-592 C/A on the occurrence and load of the periodontal pathogens: P. gingivalis, T. forsythia, T. denticolaand A. Actinomycetemcomitans; as well to investigate the influence of microbial and genetic factors on the modulation of local IL-10 mRNA levels. Methodology The study included 117 cases and 58 controls. After clinical examination microbiological samples were obtained and the detection/quantification of the target bacterial species was performed by RT-PCR. SNP rs1800872 was assayed by restriction fragment length polymorphism (RFLP). Results Allele distribution of rs1800872 was in Hardy-Weinberg equilibrium (P = 64). As previously reported, polymorphic subjects demonstrated decreased IL-10 expression and increased risk of suffering chronic periodontitis. IL-10-592C/A rs1800872 SNP was not associated with the detection or the bacterial load of the investigated pathogens. Moreover, the presence/load of bacteria at periodontal sites did not influence IL-10 expression, which was determined by the genetic background of the study subjects. IL-10-592C/A SNP was not associated with detection/bacterial load of pathogenic bacteria. IL-10 expression levels were determined by the genetic background and were independent of the bacterial microenvironment.
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Humanos , Masculino , Adulto , Femenino , Enfermedades Periodontales/genética , Enfermedades Periodontales/microbiología , /genética , Carga Bacteriana , Bacterias/aislamiento & purificación , Estudios de Casos y Controles , ADN Bacteriano , Encía/microbiología , Enfermedades Periodontales/inmunología , Interacciones Huésped-Patógeno , /fisiología , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
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.
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Proceso Alveolar/fisiología , Expresión Génica , Extracción Dental , Cicatrización de Heridas , Proceso Alveolar/patología , Proceso Alveolar/cirugía , Animales , Inmunohistoquímica/métodos , Masculino , Ratones Endogámicos C57BL , Osteogénesis/genética , Microtomografía por Rayos XRESUMEN
INTRODUCTION: Previous studies describe contrasting molecular profiles of active and inactive periapical granulomas characterized by distinct expression of cytokines, osteoclastogenic factors, and wound healing markers. Although the molecular mechanisms underlying such a dichotomy remain unknown, in this study we investigated the potential involvement of mesenchymal stem cells (MSCs) in determining human and murine periapical lesion activity and outcomes. METHODS: Periapical granulomas (n = 83) and control samples (n = 24) were comparatively assessed for the expression levels of 11 mesenchymal stem cell (MSC) markers using real-time polymerase chain reaction. Experimental periapical lesions induced in mice were evaluated for MSC marker expression and the effects of AMD3100 treatment on lesion outcomes. RESULTS: MCS marker expression was prevalent in periapical granulomas compared with that in controls, whereas CD29, CD73, CD90, CD146, CD166, NANOG, Stro-1, and CXCR4 expressions were higher in inactive than in active lesions. Experimental periapical lesion inactivity was also associated with an increased expression of MSC markers. The inhibition of MSC mobilization to the periapex by AMD3100 resulted in increased lesion sizes; decreased expression of MSCs and wound healing markers; and increased expression of interleukin 1 beta (IL-17ß), interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa-B ligand (RANKL). CONCLUSIONS: Our results show that MSC markers are overexpressed in inactive human and experimental periapical lesions and that MSC mobilization results in the attenuation of experimental lesion progression associated with immunosuppressive and prohealing mechanisms.
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Inmunosupresores/farmacología , Células Madre Mesenquimatosas/fisiología , Granuloma Periapical/patología , 5'-Nucleotidasa/análisis , Molécula de Adhesión Celular del Leucocito Activado/análisis , Adulto , Animales , Antígenos de Superficie/análisis , Bencilaminas , Biomarcadores/análisis , Antígeno CD146/análisis , Ciclamas , Modelos Animales de Enfermedad , Compuestos Heterocíclicos/uso terapéutico , Proteínas de Homeodominio/análisis , Humanos , Integrina beta1/análisis , Interferón gamma/análisis , Interleucina-17/análisis , Interleucina-1beta/análisis , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Persona de Mediana Edad , Granuloma Periapical/tratamiento farmacológico , Granuloma Periapical/fisiopatología , Tejido Periapical/citología , Tejido Periapical/efectos de los fármacos , Tejido Periapical/fisiología , Ligando RANK/análisis , Receptores CXCR4/análisis , Receptores CXCR4/antagonistas & inhibidores , Antígenos Thy-1/análisis , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/fisiologíaRESUMEN
INTRODUCTION: The development of periapical granulomas is dependent on the host response and involves Th1, Th2, Th17, and Treg-related cytokines. The discovery of new Th9 and Th22 subsets, with important immunomodulatory roles mediated by interleukin (IL)-9 and IL-22, respectively, emphasizes the need for reevaluation of current cytokine paradigms in context of periapical lesions. We investigated the expression of IL-9 and IL-22 in active and stable human granulomas and throughout experimental lesion development in mice. METHODS: Periapical granulomas (N = 83) and control specimens (N = 24) were evaluated regarding the expression of IL-9 and IL-22 via real-time polymerase chain reaction. Experimental periapical lesions were induced in mice (pulp exposure and bacterial inoculation) and the lesions evolution correlation with IL-9 and IL-22 expression kinetics was evaluated. RESULTS: IL-9 and IL-22 mRNA expression was higher in periapical lesions than in control samples; higher levels of IL-9 and IL-22 were observed in inactive than in active lesions. In the experimental lesions model, increasing levels of IL-9 and IL-22 mRNA were detected in the lesions, and inverse correlations were found between IL-9 and IL-22 and the increase of lesion area in the different time point intervals. CONCLUSIONS: Our results suggest that Th9 and Th22 pathways may contribute to human and experimental periapical lesion stability.