Mabel Brunotto

Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer.

BACKGROUNDnOral cancer represents 2%-5% of all cancers, being one of the 10 most frequent ones. Apart from oral cancer risk factors already described in literature, such as tobacco and alcohol consumption, others emerging risk factors have been proposed, such as chronic irritation from dental factors. The aim of this work was to assess the influence of chronic trauma of the oral mucosa (CTOM) in patients with oral potentially malignant disorders (OPMD) and cancer.nnnMETHODSnA retrospective study of 406 patients (both sexes; aged between 18 and 80 years; with OPMD and cancer) who attended the Department of Clinical Stomatology A of the National University of Cordoba was performed by non-probabilistic sampling. The association of variables and outcome variable diagnosis, with levels control, OPMD, oral cancer, was evaluated by multinomial regression model.nnnRESULTSnPopulation under study was represented by 72% of control patients, 16% patients with OPMD and 11% of patients with oral cancer. It was observed a significant association between diagnosis and CTOM (P = 0.000), after adjustment of confounding factors (smoking and drinking habits, sex, cancer inheritance and denture use).nnnCONCLUSIONSnOur results suggest that CTOM is, together with other factors, an important risk factor in patients with oral cancer diagnosis, but not for patients with OPMD.

Risk genes in head and neck cancer: a systematic review and meta-analysis of last 5 years

The aim of this work was to identify risk genes related to the development and progression of squamous cell carcinoma head and neck (SCCHN) and do a meta-analysis of available estimates. Eligible gene/polymorphism studies were identified by electronic searches. Individual participant data of 8540 patients with HNC and 9844 controls from 19 genetic studies were analyzed, yielding adjusted (tobacco, gender, age and alcohol) odds ratios (OR) and 95% confidence intervals (CIs) comparing cases with controls. A meta-analysis was done on the studies that applied fixed and random models. People have an increase of polymorphism expression related to inflammation (NFKB1-294-ATTG, TNFα308-A2A2/A2A1, and TNFβ252- B2B2/B2B1) or carcinogenic metabolism (GSTM1 null, and CYP1A1 m1/m1), representative of malignancy development. Furthermore, the increased expression of genes associated with the stabilization and repair of the cellular (OGG1-Asp267Asn, Ser279Gly Ile253Phe, 1578A>T, 1582C>T Ala399Glu (1542C>A) 1582insG 1543_1544delCT), and genes associated with the regulation of proliferation, apoptosis or tumor survival (miRNA499-CT/CC, CRYABC802G-CG/GG) are considered as risk factors. In this scheme, only the polymorphisms of ADH7A92G-GG and DEC1606-T/C genes are protective against malignancy transformation. The TP53, GSTM1 and CYPA1genes have been evaluated in more than one study and analyzed for homogeneity in each genotype. The meta-analysis showed no significant association between different allelic variants of Arg72Pro rs1042522 and SCCHN risk. In a model of tumorigenesis, an increased risk of SCCHN is associated with DNA repair and DNA stabilization genes. In addition, the polymorphisms involved in inflammation and carcinogenic metabolism processes represent an increased risk of SCCHN.

Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.

The organizational action of testosterone during critical periods of development is the cause of numerous sex differences in the brain. However, sex differences in neuritogenesis have been detected in primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expression of Ngn3 than male neurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation of female neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex differences in neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.

Salivary factors associated to the prevalence and increase of dental caries in rural schoolchildren

OBJECTIVEnTo evaluate the association between saliva and prevalence of dental caries.nnnMETHODSnTwo-year longitudinal study in rural schoolchildren at Cruz del Eje, Argentina between 2000 and 2002. The study population comprised all schoolchildren (N=196) aged 5 to 14 years of both sexes attending eight rural schools. They were assessed at three different time points (N=46): baseline, 12 and 24 months. Salivary components and DMFT and dmft indexes were used. Nominal variables, decay and new decay, were created to assess risk of decay at baseline, 12, and 24 months, respectively. Principal component analysis was applied to select salivary factors associated to decay and then they were categorized according to the median as a cutoff value.nnnRESULTSnHigh prevalence of decay (50%-90%) was found at the three time points of study. There was significantly increase in caries at 12 months (p=0.000) compared to that seen at 24 months. At baseline there were homogeneous low levels of calcium and phosphate and a significant association (p<0.050) between calcium and phosphorus and calcium/phosphorus molar ratio and decay.nnnCONCLUSIONSnPhosphorus levels and calcium/phosphorus molar ratio can be considered risk factors for the development of caries in populations with characteristics similar to those studied.OBJETIVO: Avaliar a associacao entre saliva e prevalencia de caries. METODOS: Estudo longitudinal de dois anos, em populacao de escolares de Cruz del Eje, Cordoba-Argentina, entre os anos 2000 e 2002. A populacao de estudo compreendeu todos os escolares matriculados (N=196) em oito escolas rurais, de cinco a 14 anos de idade, ambos sexos, analisados em tres momentos (N=46): base, 12 e 24 meses. Avaliaram-se os componentes salivares e os indices CPOD e ceod. As variaveis nominais caries e caries novas foram criadas para avaliar o risco de caries no momento base e aos 12 e 14 meses, respectivamente. A analise dos componentes principais foi aplicada para selecionar os fatores salivares relacionados com a presenca de caries e em seguida foram caracterizadas segundo a mediana como ponto de corte. RESULTADOS: Observou-se alta prevalencia de caries (50%-90%) nos tres momentos de estudo. O incremento de caries foi significativamente maior aos 12 meses (p=0,000), comparado com o observado aos 24 meses. No estudo base se observou concentracao baixa e homogenea dos ions fosfato e calcio, e associacao significativa (p<0,050) entre os calcio e fosforo e relacao calcio/fosforo com a presenca de caries. CONCLUSOES: Concentracoes de ions fosfato e a relacao calcio/fosforo poderiam ser considerados como fatores de risco para o desenvolvimento de caries em populacoes com caracteristicas particulares como a estudada.

Oral ecosystem alterations in celiac children: A follow-up study

OBJECTIVEnThe aims of this work were (1) to assess the oral health status of children with celiac disease (CD) with or without compliance with a gluten-free diet and in non-celiac children in a follow-up study and (2) to identify oral ecosystem changes that could be used as non-invasive monitoring methods for CD patients.nnnSTUDY DESIGNnAn 18-month follow-up study in children of both genders, who were 4-12 years old during the study period, was performed. Decayed-missing-filled in temporary (dmft) and permanent teeth (DMFT), enamel alterations, oral hygiene, and gingival index were measured. Oral smears were collected by brushing. Flow rate, calcium, phosphate, pH, buffer capacity, fluoride, and Ca/P ratio were measured in saliva. Salivary protein profiles were performed.nnnRESULTSnMost CD patients (80%) presented typical symptoms between 12 and 24 months old. Children with CD had a significantly low frequency of enamel alterations (30%) (p=0.0001). A high percentage of patients (63.15%) reported having had aphthous ulcers at several times. The celiac group showed significantly more polymorphonuclear neutrophils (PMNs) in smears (20% PMNs per area, p=0.0459) than the control group (0% PMNs per area) at baseline. In CD children, 90% of the samples that showed PMNs at baseline did not present them after 18 months. However, 10% of the smears of CD patients presented PMNs at the end of this study. Compliance with the gluten-free diet was controlled to detect the maintenance or worsening of signs and symptoms during the medical controls.nnnCONCLUSIONSnThe main differences amongst CD children who did or did not comply with a gluten-free diet and control children are the presence of PMNs in oral mucosa and protein salivary patterns; these findings could be considered as markers for CD, in conjunction with other signs and symptoms.

Graph models for phenotype and genotype association between oral mucosa and submandibular gland tumorigenesis in rat

BACKGROUNDnIn recent years, success of statistics in field of genetics has been the identification of genes that affect the process of disease. Experimental models using animals enable early stages of tumor development to be studied. The aim of this study was to apply graph models to assess the association between the observed phenotypic changes in rat oral mucosa and induced tumorigenesis in the submandibular gland (SMG).nnnMATERIALS AND METHODSnWe studied changes in oncogenes TP53 and bcl-2, histopathological and immunomarker variables in samples of oral mucosa and SMG of Wistar male rats, 60 days old and 180 g in weight, in which tumorigenesis was induced in their SMG by a 0.5% solution of 9,10-dimethyl-1,2-benzanthracene in acetone. A set of linear structural equations were defined, with each formula indicating the response variables and the direct influences. In graph models, saliva was considered as a latent variable. The association was analyzed using Graphical Gaussian Markov models and odd ratios.nnnRESULTSnAbout 40% of animals treated with 9, 10-dimethyl-1, 2-benzanthracene showed histological alterations in the epithelial basal strata of their oral mucosa only at 150 days. Statistical models indicated a relationship between gene alteration in gene bcl-2 in the SMG and histological changes observed in the oral mucosa (P = 0.04).nnnCONCLUSIONnGraph statistical model with one latent variable allows to conclude that these results associated with other clinical parameters may be useful in detecting early changes in SMG tumorigenesis. Furthermore, the design of randomized sampling of oral mucosa allows to validate these results and establish a reliable methodology for presumptive diagnosis or screening in the future.

Factores salivales asociados a prevalencia e incremento de caries dental en escolares rurales

OBJECTIVEnTo evaluate the association between saliva and prevalence of dental caries.nnnMETHODSnTwo-year longitudinal study in rural schoolchildren at Cruz del Eje, Argentina between 2000 and 2002. The study population comprised all schoolchildren (N=196) aged 5 to 14 years of both sexes attending eight rural schools. They were assessed at three different time points (N=46): baseline, 12 and 24 months. Salivary components and DMFT and dmft indexes were used. Nominal variables, decay and new decay, were created to assess risk of decay at baseline, 12, and 24 months, respectively. Principal component analysis was applied to select salivary factors associated to decay and then they were categorized according to the median as a cutoff value.nnnRESULTSnHigh prevalence of decay (50%-90%) was found at the three time points of study. There was significantly increase in caries at 12 months (p=0.000) compared to that seen at 24 months. At baseline there were homogeneous low levels of calcium and phosphate and a significant association (p<0.050) between calcium and phosphorus and calcium/phosphorus molar ratio and decay.nnnCONCLUSIONSnPhosphorus levels and calcium/phosphorus molar ratio can be considered risk factors for the development of caries in populations with characteristics similar to those studied.OBJETIVO: Avaliar a associacao entre saliva e prevalencia de caries. METODOS: Estudo longitudinal de dois anos, em populacao de escolares de Cruz del Eje, Cordoba-Argentina, entre os anos 2000 e 2002. A populacao de estudo compreendeu todos os escolares matriculados (N=196) em oito escolas rurais, de cinco a 14 anos de idade, ambos sexos, analisados em tres momentos (N=46): base, 12 e 24 meses. Avaliaram-se os componentes salivares e os indices CPOD e ceod. As variaveis nominais caries e caries novas foram criadas para avaliar o risco de caries no momento base e aos 12 e 14 meses, respectivamente. A analise dos componentes principais foi aplicada para selecionar os fatores salivares relacionados com a presenca de caries e em seguida foram caracterizadas segundo a mediana como ponto de corte. RESULTADOS: Observou-se alta prevalencia de caries (50%-90%) nos tres momentos de estudo. O incremento de caries foi significativamente maior aos 12 meses (p=0,000), comparado com o observado aos 24 meses. No estudo base se observou concentracao baixa e homogenea dos ions fosfato e calcio, e associacao significativa (p<0,050) entre os calcio e fosforo e relacao calcio/fosforo com a presenca de caries. CONCLUSOES: Concentracoes de ions fosfato e a relacao calcio/fosforo poderiam ser considerados como fatores de risco para o desenvolvimento de caries em populacoes com caracteristicas particulares como a estudada.

Characterization of Chronic Mechanical Irritation in Oral Cancer

Objective. Oral mucosa could host many lesions originated by chronic mechanical irritation (CMI) from teeth or dentures, and it has been proposed as risk factor for oral cancer. Nevertheless, the features of CMI factors in oral cancer and other lesions are not assessed. The aim of this study is to describe CMI features regarding type (dental, prosthetic, and/or functional), localization, and time span. Materials and Methods. Three groups were studied in this cross-sectional study: Oral Cancer (OC); Chronic Traumatic Ulcer (CTU); and Benign Irritative Mechanical Lesions (BIML). All sources of mechanical irritation were included: dental, prosthetic, and functional. Results. 285 patients (176 females, 109 males) were studied: OC = 38, CTU = 44, and BIML = 203. The most frequent CMI factor was dental, followed by functional and prosthetic in all groups; 76.5% (n = 218) presented functional factors. Buccal mucosa (45%) and tongue (42%) were the most affected sites. Time of action of CMI displayed statistically significant differences between BIML, CTU, and OC groups, with a mean of 21, 33, and 49 months, respectively. Conclusions. CMI should be properly recorded with as much detail as alcohol and tobacco consumption. CMI associated lesions are produced by dental or prosthetic factors, usually in relation to functional factors, involving mainly tongue and buccal mucosa.

Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques

BACKGROUNDnPrevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up.nnnMETHODSnAgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated.nnnRESULTSnThe diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio.nnnCONCLUSIONSnThe total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.

Characterization of maxillary central incisor: novel crown-root relationships

ObjectivesThe periodontal biotype includes crown features of the maxillary central incisor (MCI), whereas root measures have been less studied. The aim of our study was to morphologically characterize MCI and search relationships between crown and root measures.Material and methodsOne hundred-fifty MCIs were used. On each tooth, several crown and root reference points were marked and the following measures were done: On crown: mesio-distal (MDu2009=u2009major, mdu2009=u2009minor), axial (crown length, cervical convexity) and buccolingual diameters (Cbl); On root: mesio-distal (Rmd) and buccolingual diameters (Rbl); and tooth length. A ratio between md and MD was made in order to assess dental forms. Root diameter prediction was assessed by means of multiple and single linear regression analyses, with variable selection by backward method. Reliability of measurements was estimated by the Pearson correlation coefficient.ResultsDental form groups were: Stout type 56.67xa0%, Intermediate type 22.67xa0%, and Strangled type 20.67xa0%. A significative association was found between Rbl and Cbl (pu2009=u20090,000), Rmd with md (pu2009=u20090.000), and Rmd with MD (pu2009=u20090.000). The results allow predicting root diameters through crown measures.ConclusionsThere is a direct relationship between crown and root features, which allows the prediction of root diameters with a high accuracy (95xa0%), regardless of tooth form.Clinical relevanceThe morphometric data assess tooth diameters more accurately and could improve treatment planning, offering a more comprehensive approach to the periodontal biotype concept.