Polimorfismos de nucleotídeo único em genes de metalotioneína e o risco de carcinoma epidermoide oral em uma população brasileira

Squamous cell carcinoma is the most common malignancy of the oral cavity. The main risk factors for this disease are chronic consumption of tobacco and alcohol, but the cellular response against carcinogens depends on several factors, including genetic variations. Metallothionein are proteins that have been implicated in a number of functions, including cellular protection against heavy metal toxicity and free radicals, and it is important in cell proliferation and apoptosis. The aim of this study was to investigate the possible influence of single nucleotide polymorphisms (SNP) in genes metallothionein (MT) on the risk of oral squamous cell carcinoma (OSCC). The study case- control hospital-based demonstrated that SNP rs11076161, located in intron region of MT1A, was associated with the risk of OSCC. Carriers of AA genotype of this polymorphism seem more prone to the occurrence of this tumor. It was verified paucity of information about the OSCC occurence in women. Then, further investigation was carried out, to describe on this topic. Peculiarities in the analyzed sample were identified, especially the lowest proportion of brown skinned women and in the sixth decade of life than expected, as well as increased number of women among patients with gums lesions. The survival comparative analysis between men and women showed higher survival rate for women, but this difference was not significant. These features should be better evaluated in future studies to further clarify their biological and clinical importance. Finally, it was also carried out a literature review in search of studies that have investigated the influence of SNP on the risk of salivary gland tumors in order to facilitate further research on the subject. The currently available information on the frequency and relevance of the genetic variants involved in susceptibility to salivary gland tumors is still very restricted, but seen promising because several potential genetic risk factors have been identified. On the other hand, the molecular pathogenesis of salivary gland tumors will be better understood by analyzing the genetic polymorphisms combined with various environmental factors. In addition, the results showed that susceptibility of one population may not be the same in another population, justifying the necessity of studies in the Brazilian population.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorTese (Doutorado)O carcinoma epidermoide é a neoplasia maligna mais comum da cavidade oral. O consumo crônico de cigarro e bebidas alcoólicas são os principais fatores de risco para essa doença, porém a resposta celular frente à presença de carcinógenos depende de diversos fatores, inclusive de variações genéticas. Metalotioneínas são proteínas que atuam na proteção celular contra toxicidade de metais pesados e radicais livres, e ainda considerada importante na proliferação celular e na apoptose. O objetivo principal desse estudo foi investigar a possível influência de polimorfismos de nucleotídeo único (SNP) em genes de metalotioneína (MT) sobre o risco de carcinoma epidermoide oral (CEO). O estudo tipo caso-controle de base hospitalar demonstrou que o SNP rs11076161, localizado na região de intron de MT1A, apresentou associação com o risco de CEO. Os indivíduos portadores do genótipo AA desse polimorfismo aparentam maior predisposição à ocorrência desse tumor. Ao se verificar também uma óbvia escassez de informações sobre o CEO em mulheres, foi realizada uma investigação complementar, de natureza descritiva, sobre esse tema. Foram identificadas peculiaridades na casuística avaliada, em especial a menor proporção frente ao esperado de mulheres pardas e na sexta década de vida, bem como maior número de casos em mulheres dentre os pacientes com lesões em gengiva. A análise comparativa de sobrevida entre homens e mulheres mostrou sobrevida superior para as mulheres, porém essa diferença não se mostrou significativa. Tais características devem ser melhor avaliadas em estudos posteriores para que sua importância biológica e clínica seja melhor esclarecida. Finalmente, foi realizada também uma revisão da literatura em busca de trabalhos que já tenham investigado a influência de SNP sobre o risco dos tumores de glândula salivar, de forma a favorecer a realização de investigações posteriores sobre o tema. A informação disponível atualmente sobre a frequência e a relevância das variações genéticas envolvidas na susceptibilidade aos tumores de glândula salivar ainda é muito restrita, porém promissora visto que diversos potenciais fatores genéticos de risco já foram identificados. Por outro lado, a patogênese molecular dos tumores de glândula salivar provavelmente será melhor compreendida ao analisar os diversos polimorfismos genéticos combinados com fatores ambientais. Além disso, os resultados mostram que o fator de susceptibilidade de uma população pode não se repetir em outra, justificando a necessidade de estudos na população brasileira

Differential metallothionein expression in oral lichen planus and amalgam-associated oral lichenoid lesions

Oral lichen planus (OLP) is a chronic inflammatory disease mediated by T cells, which manifests as reticular (white) or erosive (red) lesions, that are eventually painful. Oral lichenoid lesion (OLL) are distinguished from OLP by the presence of precipitating factors. The aim of this study was to evaluate whether the presence of metallothionein, which is involved in anti-apoptotic pathways and the anti-oxidative response, could serve as a differential diagnostic for OLP and OLL. We evaluated the expression of metallothionein in 40 cases of OLP and 20 cases of OLL using immunohistochemistry. White OLP has higher concentrations of metallothionein than red OLP in basal and parabasal layers. Moreover, metallothionein was more frequently observed in the cytoplasm and nuclei of basal cells in OLP patients compared to the same regions of OLL cases. Metallothionein levels are related to OLP severity and may contribute to a differential diagnosis between OLP and OLL

Simple bone cyst : description of 60 cases seen at a Brazilian School of Dentistry and review of international literature

The aim of this study was to describe the relative frequency and the main demographic and clinic-radiographic features related to patients diagnosed with Simple bone cyst (SBC) in an Oral Diagnosis Service in Southeast Brazil and present a review and discussion of international literature on this topic. SBC cases from our service encompassing the period between 1978 and 2017 were selected. In addition, a literature search was performed in the Pubmed/MEDLINE online electronic database published between 1951 and 2019. A total of 2,459 cystic lesions were documented in our service, thus 60 patients were diagnosed with the SBC representing 2.4% of all jaw cystic. Most of cases were asymptomatic. Multiple SBC lesions were seen in two patients (3.4%) and association with cemento-osseous dysplasia was seen in one female patient (1.7%). A total of 793 cases were enrolled in this literature review. The SBC is an asymptomatic lesion often discovered in routine image exams in young patients. The unilocular, well defined margin with scalloped appearance is characteristic and helps the definition of diagnosis. This review suggests a different epidemiologic trend concerning to the sex and it confirms the posterior region of mandible as the more frequent location. The conservative treatment with limited exploration and curettage remains as the gold-standard treatment

Revisiting the metallothionein genes polymorphisms and the risk of oral squamous cell carcinoma in a Brazilian population

Metallothioneins (MTs) gene polymorphisms have been associated with the ability of free radical scavenging and detoxification of heavy metals leading to cancer development. Our aim was to revisit, in a Brazilian population, single-nucleotide polymorphisms (SNPs) of the MT gene family previously associated with oral squamous cell carcinoma (OSCC). A case-control investigation with 28 OSCC patients and 45 controls was conducted, using conventional risk factors (tobacco use and alcohol consumption) as covariates. SNPs genotyping for rs8052334 (MT1B), rs964372 (MT1B), and rs1610216 (MT2A) was performed by PCR-RFLP, and SNPs for rs11076161 (MT1A) were analyzed by TaqMan assay. The only SNP associated with increased risk for OSCC was the MT-1A AA genotype (OR = 4.7; p = 0.01). We have also evidenced for the first time a significant linkage disequilibrium between the SNPs of MT-2A and MT-1A in this population with the highest frequency (30%) of the unfavorable haplotype G/A/C/T (rs1610216 / rs11076161 / rs964372 / rs8052334) of MT gene polymorphisms (OR = 6.2; p = 0.04). Interestingly, after removing the effects of conventional risk factors, we have uncovered the significance of the AA genotype of the rs11076161 with increased odds of 19-fold higher towards OSCC development. This is the first demonstration that a significant linkage disequilibrium among gene polymorphisms of the MT family may affect susceptibility to oral cancer, which is conditioned by the G/A/C/T haplotype (rs1610216/rs11076161/rs964372/ rs8052334) and the MT-1A gene polymorphism has a potential clinical utility for the OSCC risk assessment

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reavaliação dos pacientes com Líquen Plano Oral atendidos no período de 1997 a 2010

Oral Lichen Planus (OLP) is an chronic autoimune mucocutaneous disease, of a relatively high prevalence in the population. This retrospective study is about OLP patients, treated between 1997 and 2010. The aim was to present the clinical aspects of these lesions and improve the knowledge about the biological behavior of this disease, in addition to the potential of malignant transformation. The clinical data such as age, gender, location of the lesions, and symptomatology were recorded. There were 76 (1,65%) patients with OLP trough 4593 medical records. 21 attended the telephone calling for clinical review. In the 21 subjects sample, 17(81%) were females and 4(19%) males, within mean age of 46 years-old, at the diagnosis. Most lesions were localized in the buccal mucosa. Two patients showed leukoplakia concomitant with OLP. There are no malignant transformation, even no relationship between tobacco and alcohol with symptoms or clinical manifestation. In this study, it was possible to follow up the alterations between OLP clinical forms and the symptomatology, which probably does not have relationship with drinking or smoking. Our study did not show any malignant transformation.Mestre em OdontologiaLíquen Plano Oral (LPO) é uma alteração mucocutânea crônica imunologicamente mediada, com uma prevalência relativamente alta. Esse é um estudo retrospectivo que avalia as características dos pacientes com LPO, atendidos entre 1997 e 2010 com o objetivo de apresentar os aspectos clínicos das lesões e compreender o comportamento biológico dessa alteração, principalmente seu potencial de transformação maligna. Através do levantamento de 4593 prontuários, foram encontrados 76 (1,65%) pacientes com LPO e desses, 21 responderam ao contato telefônico e compareceram para uma reavaliação clínica. Foram avaliados os dados clínicos como idade, gênero, localização da lesão, presença ou ausência de sintomatologia. Dos 21 pacientes, 17 (81%) eram mulheres e 4 (19%) homens, com média de idade, no diagnóstico, de 46 anos. A maioria das lesões estava em mucosa jugal. Dois pacientes apresentaram lesões compatíveis com leucoplasia do tabagista concomitante com LPO. Não foram encontradas transformações malignas, nem relação entre o consumo de tabaco e álcool com sintomatologia ou manifestação clínica. Nesse estudo retrospectivo, foi possível acompanhar a mudança entre as formas clínicas juntamente com a variação de sintomatologia do LPO, que aparentemente, não apresentam relações com o consumo de álcool ou de tabagismo. O nosso estudo não mostrou nenhum caso de transformação maligna de LPO em carcinoma espinocelular