Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population.

OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNP) in grainyhead-like 3 (GRHL3) and to verify its possible interactions with others genes responsible for craniofacial development in the risk of non-syndromic oral cleft (NSOC). METHODS: Applying TaqMan allelic discrimination assays, we evaluated GRHL3 SNPs (rs10903078, rs41268753, and rs4648975) in an ancestry-structured case-control sample composed of 1,127 Brazilian participants [272 non-syndromic cleft palate only (NSCPO), 242 non-syndromic cleft lip only (NSCLO), 319 non-syndromic cleft lip and palate (NSCLP), and 294 healthy controls]. Additionally, SNP-SNP interactions of GRHL3 and previously reported variants in FAM49A, FOXE1, NTN1, and VAX1 were verified in non-syndromic cleft lip with or without cleft palate (NSCL ± P). To eliminate false-positive associations, Bonferroni correction or 1,000 permutation method was applied. RESULTS: The multiple logistic regression analysis showed that the CC genotype of rs10903078 (p = .03) and the haplotype C-C formed by the SNPs rs10903078 and rs41268753 (p = .04) were associated with NSCLO, but the p-values did not withstand Bonferroni correction. However, SNP-SNP test revealed significant interactions between GRHL3 SNPs and FAM49A (rs7552), FOXE1 (rs3758249), VAX1 (rs7078160 and rs751231), and NTN1 (rs9891446). CONCLUSIONS: Our results confirm the importance of GRHL3 and its interactions with previously NSOC-associated genes, including FAM49A, FOXE1, NTN1, and VAX1, in the pathogenesis of NSOC in the Brazilian population.

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population.

BACKGROUND: Epidemiological studies have indicated a higher incidence of breast and gastric cancer in patients with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and their relatives, which can be based on similar genetic triggers segregated within family with NSCL ± P. METHODS: This multicenter study evaluated the association of 9 single nucleotide polymorphisms (SNP) in AXIN2 and CDH1, representing genes consistently altered in breast and gastric tumors, with NSCL ± P in 223 trios (father, mother and patient with NSCL ± P) by transmission disequilibrium test (TDT). RESULTS: Our results showed that the minor A allele of rs7210356 (p = 0.01) and the T-G-G-A-G haplotype formed by rs7591, rs7210356, rs4791171, rs11079571 and rs3923087 SNPs (p = 0.03) in AXIN2 were significantly under-transmitted to patients with NSCL ± P. In CDH1 gene, the C-G-A-A and A-G-A-G haplotypes composed by rs16260, rs9929218, rs7186053 and rs4783573 polymorphisms were respectively over-transmitted (p = 0.01) and under-transmitted (p = 0.008) from parents to the children with NSCL ± P. CONCLUSIONS: The results suggest that polymorphic variants in AXIN2 and CDH1 may be associated with NSCL ± P susceptibility, and reinforce the putative link between cancer and oral clefts.

Oral manifestations in patients diagnosed with psoriasis: A systematic review.

AIMS: To identify the main types of oral lesions associated with psoriasis. METHODS AND RESULTS: It was a systematic review, based on a search performed in the PubMed/Medline, and Scielo databases, and an associated manual search. Descriptors were selected from DeCs/MeSH and the PICOS strategy (population, intervention, comparison, outcomes, and study design) was applied. Randomized clinical trials and retrospective and prospective studies published from 2000 to 2022 were included, according to the PRISMA parameters (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), registered in the PROSPERO platform. The STROBE quality scale (Strengthening the Reporting of Observational studies in Epidemiology) was also used. One hundred fourteen articles were identified using the search strategy, and nine articles were found in the manual search. Of the sixty-six preselected articles, seven were included in the study. Although it was not possible to identify a specific oral lesion associated with psoriasis, there was a greater occurrence of geographic tongue, fissured tongue, and Candida sp. infection CONCLUSION: Evidence shows that although patients with psoriasis may exhibit lesions in the oral mucosa, they are not specific to this condition. Further epidemiological studies are needed to address the association of psoriasis with possible changes in the oral mucosa.

Brazilian Multiethnic Association Study of Genetic Variant Interactions among FOS, CASP8, MMP2 and CRISPLD2 in the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate.

Associations of CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) and genes belonging to its activation pathway, including FOS (Fos proto-oncogene), CASP8 (caspase 8) and MMP2 (matrix metalloproteinase 2), with nonsyndromic orofacial cleft risk, have been reported, but the results are yet unclear. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) in FOS, CASP8 and MMP2 and to determine their SNP-SNP interactions with CRISPLD2 variants in the risk of nonsyndromic cleft lip with or without cleft palate (NSCL±P) in the Brazilian population. The SNPs rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) were genotyped using TaqMan allelic discrimination assays in a case-control sample containing 801 NSCL±P patients (233 nonsyndromic cleft lip only (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)) and 881 healthy controls via logistic regression analysis adjusted for the effects of sex and genomic ancestry proportions with a multiple comparison p value set at ≤0.01. SNP-SNP interactions with rs1546124, rs8061351, rs2326398 and rs4783099 in CRISPLD2 were performed with the model-based multifactor dimensionality reduction test complemented with a 1000 permutation-based strategy. Although the association between FOS rs1046117 and risk of NSCL±P reached only nominal p values, NSCLO risk was significantly higher in carriers of the FOS rs1046117 C allele (OR: 1.28, 95% CI: 1.10-1.64, p = 0.004), TC heterozygous genotype (OR: 1.59, 95% CI: 1.16-2.18, p = 0.003), and in the dominant model (OR: 1.50, 95% CI: 1.10-2.02, p = 0.007). Individually, no significant associations between cleft risk and the SNPs in CASP8 and MMP2 were observed. SNP-SNP interactions involving CRISPLD2 variants and rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) yielded several significant p values, mostly driven by FOS rs1046117 and CASP8 rs3769825 in NSCL±P, FOS rs1046117 in NSCLO and CRISPLD2 rs8061351 in NSCLP. Our study is the first in the Brazilian population to reveal the association of FOS rs1046117 with NSCLO risk, and to support that CRISPLD2, CASP8, FOS and MMP2 interactions may be related to the pathogenesis of this common craniofacial malformation.

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only.

The identification of genetic risk factors for non-syndromic oral clefts is of great importance for better understanding the biological processes related to this heterogeneous and complex group of diseases. Herein we applied whole-exome sequencing to identify potential variants related to non-syndromic cleft palate only (NSCPO) in the multiethnic Brazilian population. Thirty NSCPO samples and 30 sex- and genetic ancestry-matched healthy controls were pooled (3 pools with 10 samples for each group) and subjected to whole-exome sequencing. After filtering, the functional affects, individually and through interactions, of the selected variants and genes were assessed by bioinformatic analyses. As a group, 399 variants in 216 genes related to palatogenesis/cleft palate, corresponding to 6.43%, were exclusively identified in the NSCPO pools. Among those genes are 99 associated with syndromes displaying cleft palate in their clinical spectrum and 92 previously related to cleft lip palate. The most significantly biological processes and pathways overrepresented in the NSCPO-identified genes were associated with the folic acid metabolism, highlighting the interaction between LDL receptor-related protein 6 (LRP6) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) that interconnect two large networks. This study yields novel data on characterization of specific variants and complex processes and pathways related to NSCPO, including many variants in genes of the folate/homocysteine pathway, and confirms that variants in genes related to syndromic cleft palate and cleft lip-palate may cause NSCPO.

Evaluation of preventive laser photobiomodulation in patients with head and neck cancer undergoing radiochemotherapy: Laser in patients with head and neck cancer.

AIMS: This study aimed to evaluate the effect of laser photobiomodulation in the prevention of oral mucositis (OM), salivary hypofunction and referred pain in patients with head and neck cancer. METHODS AND RESULTS: This randomized clinical study divided patients into two groups: the laser group (LG, n = 30) and the control group (CG, n = 24). The LG (InGaAlP, 660 nm, 86.7 mW, 2 J/cm2 ) participated in the preventive protocol, while the CG underwent a simulated procedure without light emission. The degree of OM, salivary flow, and referred pain were evaluated at five different periods of radiotherapy. Both groups showed a significant increase in the degree of OM (P < .01). Regarding OM, salivary flow, and oral pain, there were no significant differences between the groups. CONCLUSIONS: The laser photobiomodulation protocol used in this study was not effective in preventing radiochemotherapy-induced OM, salivary hypofunction, and referred pain in patients with head and neck cancer. Notably, although the development of OM did not differ significantly according to the use of laser therapy, the severity of oral mucositis was reduced in patients who underwent laser therapy compared to that in patients who did not.

Access and use of the oral health service in a reference center in oral cleft in the state of Bahia / Acesso e utilização de serviço de saúde bucal em centro de referência em fissura oral no estado da Bahia

ABSTRACT This study aimed to determine the access and utilization of dental services in a reference center for orofacial defects in the state of Bahia, Brazil. In an interview, a questionnaire was done about socio-demographic information, cleft type, specialized treatments, scheduling time and return of the consultation of 101 patients with nonsyndromic cleft lip with or without cleft palate and 101 healthy controls. In both groups the age was between 5 to 12 years old. It was observed that individuals with cleft had faster access to the dental service in relation to the control group and shorter scheduling time between the first consultation and their return. Different needs in the use of dental services were observed in the study groups with differences in relation to the specialties (p=0.000). The nonsyndromic cleft lip with or without cleft palate individuals showed socialization difficulties in the age group between 9 and 12 years and did not present difficulties in accessing primary dental care in specialized service. In conclusion, in this study NSCL±P individuals did not present difficulties in accessing the specialized dental center. To complement the comprehensive care, it is suggested the performance of educational activities of oral health, not yet fully implemented in this multidisciplinary treatment center.

RESUMO Esta pesquisa teve como objetivo determinar o acesso e a utilização de serviços odontológicos em centro de referência para pacientes com defeitos orofaciais no estado da Bahia, Brasil. Em entrevista um questionário foi preenchido sobre informações sociodemográficas, tipo de fissura, tipos de tratamentos especializados, tempo para agendamento e de retorno da consulta de 101 pacientes com fissura labial com ou sem fissura palatina não sindrômica e 101 indivíduos controles sem a malformação. Em ambos os grupos a faixa etária foi de 5 a 12 anos. Observou-se que indivíduos fissurados tiveram acesso mais rápido ao serviço odontológico em relação ao grupo controle e menor tempo de agendamento entre a primeira consulta e o retorno. Distintas necessidades na utilização de serviços odontológicos foram observadas nos grupos de estudo com diferenças em relação às especialidades (p=0,000). Indivíduos com fissura labial com ou sem fissura palatina não sindrômica mostraram dificuldades de socialização no grupo de faixa etária entre 9 e 12 anos e não tiveram dificuldades no acesso ao serviço odontológico especializado. Através desse estudo concluiu-se que os indivíduos fissurados não apresentaram dificuldades no acesso ao serviço especializado. Sugere-se a implementação de atividades educacionais básicas de saúde oral nesse centro de tratamento multidisciplinar.

Impacto da terapia nutricional em pacientes com câncer de cabeça e pescoço com desnutrição: uma revisão sistemática / Impact of nutritional therapy in patients with head and neck cancer with malnutrition: systematic review

Introdução: o câncer de cabeça e pescoço (CCP) ocupa o 5º lugar entre as neoplasias mais prevalentes no Brasil. Por acometer regiões que estão relacionadas diretamente à alimentação, os efeitos secundários ao tratamento provoca diminuição da ingesta alimentar, que favorece perda de peso acelerada e desnutrição. A terapia nutricional (TN) contribui para a minimização desses efeitos, pois visa à manutenção ou recuperação do estado nutricional. Objetivo: avaliar o impacto da TN em pacientes com CCP com desnutrição, e na minimização dos efeitos colaterais advindos do tratamento antineoplásico. Metodologia: trata-se uma revisão sistemática, utilizando-se as bases de dados eletrônicas Lilacs, Medline, Pubmed, periódicos CAPES e Scielo, através dos descritores: "nutritional therapy", "head and neck neoplasms" e "malnutrition". Os critérios de inclusão estabelecidos foram ensaios clínicos randomizados, escritos em inglês e publicados entre os anos de 2013 e 2018; participantes dos estudos deveriam apresentar idade superior a 19 anos e submetidos a qualquer tipo e fase de tratamento oncológico. Resultados: observou-se um total de 755 indivíduos com CCP que participaram dos seis ensaios clínicos selecionados. Os estudos avaliaram o impacto nutricional no uso de suplementos alimentares e na eficácia da terapia enteral. Destes, apenas quatro constataram diferença em relação a intervenção nutricional (p<0,05) e dois não relataram resultados significativos (p>0,05). O acompanhamento nutricional mostra-se necessário para reduzir os riscos de piora do estado nutricional e da qualidade de vida. Conclusão: a TN oral ou enteral podem ser implementadas, para garantir a melhora da condição nutricional e de saúde do paciente com CCP.

Introduction: head and neck cancer (HNC) ranks 5th among the most prevalent cancers in Brazil. By affecting regions that are directly related to food, the side effects of treatment may cause decreased food intak with weight loss and malnutrition. Nutritional therapy (NT) contributes to minimization this, as it aims to maintain or recover nutritional status. Aim: evaluate the impact of nutritional therapy in patients with HNC with malnutrition, and minimizing side effects from antineoplastic treatment. Methodology ­ A systematic review was carried out using Lilacs, Medline, Pubmed, periodicals CAPES and Scielo, through the descriptors: "nutritional therapy", "head and neck neoplasms" and "malnutrition". The inclusion criteria were randomized clinical trials, in English and published between 2013 and 2018. Participants in the studies should be over the age of 19 years, submitted to any type and stage of cancer treatment. Results: a total of 755 individuals with CCP who participated in the six selected clinical trials were observed. The studies evaluated the nutritional impact of dietary supplement use and the efficacy of enteral therapy. Of these, only four found a difference in relation to nutritional intervention (p <0.05) and two did not report significant results (p> 0.05). Depending on staging of the disease, only nutritional counseling is not enough to prevent weight loss. Nutritional monitoring is necessary to reduce the risks of worsening nutritional status and quality of life. Conclusions: oral or enteral NT can be implemented to ensure the improvement of the nutritional and health condition of the patient with CCP.

A retrospective study on the oral health of patients in the intesive care unit / Um estudo retrospectivo sobre a condição bucal de pacientes em unidade de terapia intensiva

Introduction: the oral condition of patients in the Intensive Care Unit (ICU) is extremely important for clinical status monitoring, as lesions in the oral mucosa may imply complications and worsening of the health status of these patients. A higher probability of adherence, colonization, and bacterial infection in the oral cavity of patients in the ICU has also been reported. The poor oral hygiene conditions of these patients may be related to the reduction of salivary flow and difficulties in maintaining oral hygiene in a hospital environment, which rarely employs dentists on staff. Objective: to analyze the dental condition of patients admitted to the ICU of Roberto Santos General Hospital, Salvador, Bahia, Brazil. Methodology: a total of 73 patients were evaluated through an oral examination performed with a wooden spatula and sterile gauze under natural light, and data were collected and analyzed. Results: The most commom oral lesions were tongue-coating (41%) and ulcerations in the oral mucosa caused by trauma or dehydration (19.1%). The occurrence of pseudomembranous candidiasis (8.2%), dehydration of the lips and mucosa (26%), and angular cheilitis (9.5%) was additionally recorded. It was observed that 31.5% patients had more than 10 days of hospitalization and of these, 26% presented pseudomembranous candidiasis. This clinical condition was not seen in patients with a shorter hospital stay. Conclusions: this study suggest a possible association between the length of stay of these patients and the clinical conditions presented. Thus, the results of this study may guide preventive and curative measures implemented by dental surgeons who may, in the future, be part of the multidisciplinary team of professionals working in the hospital environment, especially in ICUs.

Introdução: a condição oral de pacientes internados em Unidade de Terapia Intensiva (UTI) é de extrema importância na evolução do quadro clínico desta população, já que lesões na mucosa oral podem implicar em complicações e agravo do estado de saúde destes indivíduos. Tem sido relatado também maior probabilidade de aderência, colonização e infecção bacteriana na cavidade oral de pacientes que se encontram em leitos de UTI. As condições precárias de higiene oral que estes pacientes normalmente apresentam podem estar relacionadas à redução do fluxo salivar e às dificuldades de higienização oral inerentes ao ambiente hospitalar, o qual geralmente não conta com cirurgiões-dentistas integrando a equipe de profissionais da instituição. Objetivo: a presente pesquisa visou analisar a condição odontológica de pacientes internados na Unidade de Terapia Intensiva do Hospital Geral Roberto Santos. Metodologia: setenta e três foram avaliados através de um exame bucal, realizado com espátula de madeira e gaze estéril sob a iluminação de luz natural e seus dados foram coletados e analisados. Resultados: as lesões orais mais comuns foram saburra lingual (41%) e ulcerações na mucosa oral provocadas por trauma ou ressecamento (19,1%). A ocorrência de candidíase pseudomembranosa (8,2%), lábios e mucosas desidratados (26%) e queilite angular foi adicionalmente registrada. Foi observado que dos 31,5% dos pacientes com mais de 10 dias de internação, 26% apresentaram candidíase pseudomembranosa. Essa condição clínica não foi observada em pacientes com menor tempo de internação. Conclusão: o presente estudo sugere uma possível associação entre o tempo de internação destes pacientes e as condições clínicas apresentadas. Desta forma, a descrição dos resultados desta investigação pode contribuir para nortear os cuidados preventivos e curativos a serem adotados por cirurgiões-dentistas que futuramente integrem a equipe multidisciplinar de profissionais que atuam no ambiente hospitalar, em especial, nas unidades de terapia intensiva.

Evaluation of the Impact of Oral Hygiene and Chamomile Tea in the Development of Oral Mucositis: Pilot Study / Avaliação do Impacto da Higiene Oral Associada ao Uso do Chá de Camomila no Desenvolvimento de Mucosite Oral: Estudo-Piloto / Evaluación del Impacto de la Higiene Oral y el Té de Manzanilla en el Desarrollo de la Mucositis Oral: Estudio Piloto

Introduction: The oral mucositis (OM) represents a frequent inflammatory condition in cancer patients, and poor oral hygiene has been related as a predisposing factor for its onset. Chamomile tea has been studied as an adjunctive therapy in the management of OM due to its analgesic and anti-inflammatory properties. Objective: The objective of this study was to evaluate the influence of chamomile tea associated with a rigorous oral hygiene in the OM prevention. Method: Randomized pilot clinical study, with 35 patients assigned to two groups. The case-group underwent oral hygiene control associated with the use of chamomile tea before starting the first cycle of chemotherapy, while the control group, there were no previous guidelines and prescriptions. Data about sociodemographic characteristics, the type of neoplasm and the chemotherapy scheme proposed were collected. The variables OM, salivary flow and pain associated to the oral cavity were evaluated, and statistical analysis was performed with significance level p <0.05. Results: It was observed that the majority of the patients had a mean age of 50 years, breast (57%) was the most prevalent tumor site and cyclophosphamide (52%), the most frequently used drug In this sample, no statistically significant result was observed in the two groups for OM, salivary flow and pain variables (p> 0.05). Conclusion: These data suggest that the use of chamomile tea and the accuracy of oral hygiene were not sufficient to prevent OM.

Introdução: A mucosite oral (MO) representa uma condição inflamatória frequente em pacientes oncológicos e uma higiene oral insatisfatória tem sido relacionada como fator predisponente para o seu surgimento. O chá de camomila vem sendo estudado como terapia adjuvante no manejo da MO em razão das suas propriedades analgésicas e anti-inflamatórias. Objetivo: Avaliar a influência do chá de camomila associada a uma rigorosa higiene oral na prevenção de MO. Método: Trata-se de um estudo-piloto clínico randomizado, no qual 35 pacientes foram alocados em dois grupos. O grupo-caso foi submetido ao controle de higiene oral associado ao uso do chá de camomila antes de iniciar o primeiro ciclo de quimioterapia; no grupo-controle, não houve orientações e prescrições prévias. Foram coletados dados referentes às características sociodemográficas, à neoplasia em questão e ao tipo de tratamento quimioterápico proposto. Foram avaliadas as variáveis MO, fluxo salivar e dor associada à cavidade oral, e realizada análise estatística com nível de significância p<0,05. Resultados: Observou-se que a maioria dos pacientes apresentava-se na quinta década de vida, a localização do tumor mais prevalente foi a mama (57%) e a droga mais utilizada por esses pacientes foi a ciclosfamida (52%). Nesta amostra, não foi observado resultado estatisticamente significativo entre os grupos, no que diz respeito às variáveis MO, fluxo salivar e dor (p>0,05). Conclusão: Os dados sugerem que o uso do chá de camomila e o rigor na higiene oral não foram suficientes para a prevenção da MO.

Introducción: La mucositis oral (MO) representa una afección inflamatoria frecuente en pacientes con cáncer, y la mala higiene bucal se ha relacionado como un factor predisponente para su aparición. El té de manzanilla se ha estudiado como una terapia adyuvante en el tratamiento de la OM debido a sus propiedades analgésicas y antiinflamatorias. Objetivo: El objetivo de este estudio fue evaluar la influencia del té de manzannilla asociado con una hygiene oral rigurosa en la prevención de la MO. Método: Fue un estudio clínico piloto aleatorizado, en el que treinta y cinco pacientes fueron asignados en dos grupos. El grupo de casos se sometió a un control de higiene oral asociado con el uso de té de manzanilla antes de comenzar el primer ciclo de quimioterapia, mientras que en el grupo de control, no había pautas ni recetas previas. Se recopilaron datos sobre las características sociodemográficas, el tipo de neoplasia y el esquema de quimioterapia propuesto. Se evaluaron las variables MO, flujo salival y dolor asociado a la cavidad oral, y se realizó un análisis estadístico con nivel de significancia p<0,05. Resultados: Se observó que la mayoría de los pacientes tenían una edad media de 50 años, el sitio del tumor más prevalente era la mama (57%) y el fármaco utilizado con mayor frecuencia era la ciclofamida (52%). En esta muestra, no se observaron resultados estadísticamente significativos entre los grupos con respecto a las variables MO, flujo salival y dolor (p>0,05). Conclusión: Estos datos sugieren que el uso de té de manzanilla y la precisión de la higiene oral no fueron suficientes para prevenir la MO.

The influence of low-level laser therapy on biomodulation of collagen and elastic fibers.

The study of low-level laser therapy upon extracellular matrix elements is important to understand the wound healing process under this agent. However, little is known about the interference of laser light in relation to collagen and elastic fibers. Cutaneous wounds were performed on the back of 72 Wistar rats and a Ga-Al-As low-level laser was punctually applied with different energy densities. The animals were killed after 24, 48, 72 hours and 5, 7 and 14 days. Tissues were stained with hematoxilin-eosin, sirius red fast green and orcein and then analyzed. It was observed that the treated group exhibited larger reduction of edema and inflammatory infiltrate. The treated animals presented a larger expression of collagen and elastic fibers, although without statistical significance (p > 0.05). Treatment with a dosage of 4 J/cm(2) exhibited more expressive results than that with 8 J/cm(2). In this study, the authors concluded that low-level laser therapy contributed to a larger expression of collagen and elastic fibers during the early phases of the wound healing process.

[Genotoxic effect of ethanol on oral mucosa cells]. / Efeito genotóxico do etanol em células da mucosa bucal.

Ethanol is one of the chemicals related to the development of oral malignant neoplasms. Micronuclei are chromatin fragments which, after aberrant mitoses, do not become included in the main nucleus. They have been used as indicators of genotoxic damage in cells exposed to carcinogens. The aim of this study was to assess the frequency of micronuclei in exfoliated cells from the tongue and buccal mucosa of alcoholic individuals. Samples were taken from the tongue and buccal mucosa of 40 alcoholic individuals who did not smoke, and from 20 alcohol and tobacco abstainers. Cells were stained with the Feulgen reaction and counterstained with Fast Green. A significant increase in the frequency of micronuclei in tongue cells was found in the group of subjects exposed to alcohol, when compared to the control group (p < 0.01). The frequency of micronuclei in buccal mucosa cells was higher in the group of alcoholic individuals, when compared to the control group, although there was no significant difference (p > 0.05). Our results indicate that excessive alcohol consumption may induce effective alterations on oral mucosa cells, even without exposure to tobacco. These alterations are more expressive in the tongue, which is a site more exposed to the action of carcinogens, when compared to the buccal mucosa.

Immunolocalization of FGF-2 and VEGF in rat periodontal ligament during experimental tooth movement.

OBJECTIVE: This article aimed at identifying the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) in the tension and pressure areas of rat periodontal ligament, in different periods of experimental orthodontic tooth movement. METHODS: An orthodontic force of 0.5 N was applied to the upper right first molar of 18 male Wistar rats for periods of 3 (group I), 7 (group II) and 14 days (group III). The counter-side first molar was used as a control. The animals were euthanized at the aforementioned time periods, and their maxillary bone was removed and fixed. After demineralization, the specimens were histologically processed and embedded in paraffin. FGF-2 and VEGF expressions were studied through immunohistochemistry and morphological analysis. RESULTS: The experimental side showed a higher expression of both FGF-2 and VEGF in all groups, when compared with the control side (P < 0.05). Statistically significant differences were also found between the tension and pressure areas in the experimental side. CONCLUSION: Both FGF-2 and VEGF are expressed in rat periodontal tissue. Additionally, these growth factors are upregulated when orthodontic forces are applied, thereby suggesting that they play an important role in changes that occur in periodontal tissue during orthodontic movement.

Effect of low-level laser therapy (λ660 nm) on angiogenesis in wound healing: a immunohistochemical study in a rodent model.

The aim of the present investigation was to evaluate the angiogenesis on dorsal cutaneous wounds in a rodent model treated with λ660 nm laser light. New vessel formation is a multistep process involving vessel sprouting, endothelial cell migration, proliferation and tube formation. Although several in vivo studies have shown that laser phototherapy influences tissue repair, a fully understanding of angiogenesis mechanisms are not yet known. Twenty-four young adult male Wistar rats weighing between 200 and 250 g were used. Under general anesthesia, one excisional wound was created on the dorsum of each animal and they were randomly distributed into two groups: one control and one treated with laser (λ660 nm, 16 mW, 10 J/cm2). Each group was subdivided into three subgroups according to the animal death timing (2, 4 and 6 days). Laser irradiation started immediately after surgery and was repeated every other day during the experiment and marked with Sirius Red, specific for collagen, and immunomarked with anti-TGF-ß and anti-von Willebrand factor. Marked sections underwent histological analysis by light microscopy and the mean area of the wound of each animal was calculated and analyzed by ANOVA and Tukey's test (α=0.05). Although at some death periods, collagen expression and number of blood vessels on irradiated animals were higher than in the control ones, no significant differences were found at any time in relation to TGF-ß expression (p>0.05). It was concluded that laser treatment (λ660 nm) contributed to increase angiogenesis.

Influence of protein malnutrition on cutaneous wound healing in rats / Impacto da desnutrição proteica na cicatrização de feridas cutâneas em ratos

ABSTRACT Objective Investigate histological changes related to inflammatory response and collagen expression during wound healing in rats with protein malnutrition. Methods Twenty male Wistar rats underwent cutaneous surgery and were divided into two experimental groups: Malnourished (8% casein diet); Nourished (17% casein diet). Animals were euthanized after 5th and 10th days, descriptive and quantitative analyses were performed on sections stained with hematoxylin-eosin and sirius red, respectively. Statistical analysis of data using nonparametric Fisher's exact test with p<0.05 was carried out. Results At five days, increased fibroblast proliferation (p<0.01) and collagen expression (p<0.05) was observed in N5 group. After ten days, N10 and MN10 animals showed higher amount of granulation tissue and edema/inflammatory infiltrate independent of nutritional status (p>0.05), only N10 group showed fibroblast proliferation (p<0.01) and increased collagen expression (p<0.01). Conclusion Protein malnutrition seems not to influence inflammatory phase of healing, whereas it negatively effects fibroblast proliferation and collagen synthesis.

RESUMO Objetivo Investigar as alterações histológicas relacionadas à resposta inflamatória e à expressão de colágeno durante a cicatrização em ratos com desnutrição protéica. Métodos Vinte ratos Wistar machos foram submetidos à cirurgia cutânea e divididos em dois grupos experimentais: Desnutridos (dieta com caseína a 8%); Nutridos (17% de dieta com caseína). Animais foram eutanasiados após 5 e 10 dias, análises descritivas e quantitativas foram realizadas em cortes corados com hematoxilina-eosina e sirius vermelho, respectivamente. Análise estatística dos dados utilizando teste exato não paramétrico de Fisher com p<0,05 foi realizada. Resultados Aos cinco dias, observou-se aumento da proliferação fibroblástica (p<0,01) e expressão de colágeno (p<0,05) no grupo N5. Após 10 dias, animais N10 e MN10 apresentaram maior quantidade de tecido de granulação e edema/infiltrado inflamatório independente do estado nutricional (p>0,05), apenas grupo N10 apresentou proliferação fibroblástica (p<0,01) e aumento da expressão de colágeno (p<0,01). Conclusão A desnutrição protéica parece não influenciar na fase inflamatória da cicatrização, porém afeta negativamente a proliferação de fibroblastos e a síntese de colágeno.

Influence of the HPA axis on the inflammatory response in cutaneous wounds with the use of 670-nm laser photobiomodulation.

This study evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis in cutaneous wounds subjected to laser biomodulation. A total of 48 rats were divided into two groups: Group I (GI) with 24 adrenalectomized animals and Group II (GII) with 24 non-adrenalectomized animals. Each group was divided into two subgroups: the irradiated subgroup which laser was applied to four points at the edges of the wound (670 nm laser, 9 mW) and control subgroup. Rats in each subgroup were sacrificed at 24 or 72 h. Adrenal glands were only removed from GI rats. Three days after adrenalectomy, a cutaneous wound was made. An immunohistochemical analysis was performed using anti-CD45 and anti-CD8 antibodies. Flow cytometry was used to count T lymphocytes and their subpopulations in blood. Decreases in the number of CD45-positive inflammatory cells and in the total numbers of CD8- and CD45-positive cells were observed in histological sections of adrenalectomized animals subjected to laser biomodulation at 24h. Similar results were observed for distribution of total lymphocytes in blood (p<0.05). The action of 670 nm laser does not depend exclusively on HPA axis. It is believed that corticosteroid-promoting enzymes liberated in non-adrenal tissues may influence immune response under the influence of this type of phototherapy.

Parental age is related to the occurrence of cleft lip and palate in Brazilian populations

Aim: To evaluate the association of environmental risk factors, particularly paternal and maternal age, with gender and type of oral cleft in newborn with nonsyndromic cleft lip with or without cleft palate (NSCL/P). Methods: This study included 1,346 children with NSCL/P of two Brazilian Services for treatment of craniofacial deformities. Parental ages were classified into the following groups: maternal age <35, 36-39, and ≥40 years; paternal age <39 and ≥40 years. The data was analyzed with chi-square test and multinomial logistic regression analysis. The odds ratios were estimated with a 95% confidence interval. Results: Of the 1,346 children included in this study, CLP was the type of NSCL/P with highest prevalence, followed by, respectively, CL and CP. There was a greater occurrence of NSCL/P in males compared to females (55.8% versus 44.2%). CLP was more common in men, while the CL and CP were more prevalent in women (p=0.000). No association between maternal age and clefts was observed (p=0.747). However, there was evidence of association between father's aged ≥40 years old and NSCL/P (p=0.031). When patients with CP were analyzed separately, no association between the father's age and the child's gender (p=0.728) was observed, i.e. the female gender prevails among patients with CP, regardless of the father's age. Conclusions: This study showed that there were differences in the distribution of the non-syndromic cleft lip and/or palate and the gender, and fathers aged ≥40 years old may have increased risk of oral cleft. Further studies involving different populations are needed for a better understanding of the effect of maternal and paternal ages as a risk factor for the occurrence of oral clefts (Au)

Influence of 670 nm low-level laser therapy on mast cells and vascular response of cutaneous injuries.

Laser biomodulation has been getting considerable attention when it comes to its effects on the inflammatory process. Its action upon mast cells have been already studied, but none of the previous papers related the resulting effect to the inflammatory and vascular status of the wounds. Therefore, the acute inflammatory process as well as the mast cells behavior and the vascular response were analyzed under the influence of laser treatment on cutaneous wounds. Surgical procedures were performed on 60 rats divided into sham and laser groups. Low-level laser therapy was performed following surgical procedures (670 nm, 9 mW, 4 J/cm(2), 124 s). Histological specimens were analyzed for cell morphology and immunohistochemistry using anti-von Willebrand Factor and anti-Vascular Endothelial Growth Factor antibody. Laser treatment resulted in an increased acute inflammatory response in irradiated tissues; surgical wounds treated with laser therapy had increased polymorphonuclear cells, mast cells and vasodilation and lower numbers of vessels than those in control rats. Laser treatment resulted in higher expression of VEGF in irradiated tissues 6-24h post-treatment (p=0.002). It is possible to observe an amplification of acute inflammatory process during the first hours after surgical procedure in rats submitted to laser therapy.

Immunolocalization of FGF-2 and VEGF in rat periodontal ligament during experimental tooth movement

OBJECTIVE: This article aimed at identifying the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) in the tension and pressure areas of rat periodontal ligament, in different periods of experimental orthodontic tooth movement. METHODS: An orthodontic force of 0.5 N was applied to the upper right first molar of 18 male Wistar rats for periods of 3 (group I), 7 (group II) and 14 days (group III). The counter-side first molar was used as a control. The animals were euthanized at the aforementioned time periods, and their maxillary bone was removed and fixed. After demineralization, the specimens were histologically processed and embedded in paraffin. FGF-2 and VEGF expressions were studied through immunohistochemistry and morphological analysis. RESULTS: The experimental side showed a higher expression of both FGF-2 and VEGF in all groups, when compared with the control side (P < 0.05). Statistically significant differences were also found between the tension and pressure areas in the experimental side. CONCLUSION: Both FGF-2 and VEGF are expressed in rat periodontal tissue. Additionally, these growth factors are upregulated when orthodontic forces are applied, thereby suggesting that they play an important role in changes that occur in periodontal tissue during orthodontic movement. .

OBJETIVO: o objetivo desse estudo foi identificar a expressão do fator de crescimento de fibroblastos 2 (FGF-2) e do fator de crescimento vascular endotelial (VEGF) nos lados de tensão e pressão do ligamento periodontal de ratos, durante movimento ortodôntico experimental, em diferentes períodos de tempo. MÉTODOS: uma força ortodôntica de 0,5N foi aplicada no primeiro molar superior direito de 18 ratos Wistar machos, por períodos de 3 (grupo I), 7 (grupo II) e 14 dias (grupo III). O primeiro molar do lado oposto foi utilizado como controle. Os animais foram sacrificados nos períodos de tempo mencionados, sendo a arcada superior removida e fixada. Após a desmineralização, os espécimes foram processados histologicamente e embebidos em parafina. A expressão do FGF-2 e do VEGF foram estudadas por meio de análise imuno-histoquímica. RESULTADOS: o ligamento periodontal dos dentes submetidos à movimentação ortodôntica mostraram maior expressão tanto de FGF-2 quanto de VEGF, em todos os grupos experimentais, quando comparados com os dentes do lado controle (p < 0,05). Diferenças estatisticamente significativas entre os lados de tensão e pressão também foram encontradas nos dentes submetidos à movimentação ortodôntica. CONCLUSÕES: tanto o FGF-2 quanto o VEGF são expressos no tecido periodontal de ratos, e esses fatores de crescimento são aumentados quando forças ortodônticas são aplicadas, sugerindo que esses desempenham um papel importante na reorganização do periodonto durante o movimento ortodôntico. .