Sphingoid bases (sphingosine, dihydrosphingosine and phytosphingosine) have been recently found in the oral cavity where they may serve to fortify innate immunity against commensals and periodontal pathogens. In fact, sphingoid bases have potent antimicrobial activity against Gram- positive and Gram- negative bacteria including oral pathogens like Porphyromonas gingivalis. It is not known whether these lipids are cytotoxic or alter the chemokine and cytokine responses of human dendritic cells, a finding important to their future potential as a therapeutic for treatment of periodontal disease. Objectives: The objective of this study was to determine the effects of sphingoid bases on the cytotoxicity and cytokine responses of human myeloid dendritic cells. Methods: Dendritic cells were treated with sphingoid bases (0.2-80.0 μM) for 16 hours in the presence or absence of 0.02 μM hemagglutinin B, a nonfimbrial adhesin of P. gingivalis used as a pro-inflammatory stimulus. The cytotoxicity of the inocula and its ability to induce the production of chemokines and pro-inflammatory cytokines was determined after 16 hours. Results: Higher concentrations of sphingoid bases were cytotoxic (e.g., 40.0-80.0 μM), but physiologic concentrations of sphingoid bases (e.g., 0.2-20.0 μM) were not. At 5, 10, or 20 μM, sphingosine did not enhance or attenuate any HagB-induced IL-8, GM-CSF, MIP-1α, MIP-1β, or TNFα response of human myeloid dendritic cells. At 5 or 10 μM, neither phytosphingosine nor dihydrosphingosine enhanced or attenuated any HagB- induced IL-8, GM-CSF, MIP-1α, MIP-1β, or TNFα response of human myeloid dendritic cells. Conclusion: Sphingoid bases exhibit dose-dependent cytotoxicity and cytokine responses against human myeloid dendritic cells. But at physiologic concentrations sphingoid bases appear to be safe and efficacious at the doses needed to prevent or treat microbial infections in the oral cavity.

<p>Bakgrund: Diabetes är en kronisk sjukdom och mer än 150 miljoner i världen har sjukdomen. Diabetessjukdomen försämrar både den allmänna och den orala hälsan. Diabetikernas kunskaper om sjukdomens negativa effekter på munhälsan är bristfällig. Syfte: var att beskriva hur vuxna individers orala hälsa påverkas av diabetes och vad tandhygienister ska beakta vid en tandvårdsbehandling. Frågeställningar: Vilka är de orala komplikationerna hos vuxna individer med diabetes? Kan parodontitbehandling hos diabetiker ha positiva effekter på diabetessjukdomen? Vad bör tandhygienister särskilt ta hänsyn till vid behandling av diabetiker? Metod: Studien har genomförts som en systematisk litteraturstudie. Resultat: Parodontala sjukdomar är den dominerande orala komplikationen hos diabetiker. Diabetiker som är rökare har svårare parodontala sjukdomar än de som inte röker. Liksom parodontit förekommer karies hos diabetiker men är inte lika omfattande studerad som de parodontala sjukdomarna. Diabetiker med bättre metabolismkontroll har bättre oral hälsa. Många diabetiker har dåliga kunskaper om att diabetessjukdomen kan ha negativ effekt på deras orala hälsa. Konklusion: Diabetiker har behov av både parodontala behandlingar och hälsofrämjande och förebyggande insatser. Ett samarbete mellan tandvård och sjukvård är nödvändig.</p>

Bakgrund: Diabetes är en kronisk sjukdom och mer än 150 miljoner i världen har sjukdomen. Diabetessjukdomen försämrar både den allmänna och den orala hälsan. Diabetikernas kunskaper om sjukdomens negativa effekter på munhälsan är bristfällig. Syfte: var att beskriva hur vuxna individers orala hälsa påverkas av diabetes och vad tandhygienister ska beakta vid en tandvårdsbehandling. Frågeställningar: Vilka är de orala komplikationerna hos vuxna individer med diabetes? Kan parodontitbehandling hos diabetiker ha positiva effekter på diabetessjukdomen? Vad bör tandhygienister särskilt ta hänsyn till vid behandling av diabetiker? Metod: Studien har genomförts som en systematisk litteraturstudie. Resultat: Parodontala sjukdomar är den dominerande orala komplikationen hos diabetiker. Diabetiker som är rökare har svårare parodontala sjukdomar än de som inte röker. Liksom parodontit förekommer karies hos diabetiker men är inte lika omfattande studerad som de parodontala sjukdomarna. Diabetiker med bättre metabolismkontroll har bättre oral hälsa. Många diabetiker har dåliga kunskaper om att diabetessjukdomen kan ha negativ effekt på deras orala hälsa. Konklusion: Diabetiker har behov av både parodontala behandlingar och hälsofrämjande och förebyggande insatser. Ett samarbete mellan tandvård och sjukvård är nödvändig.

Chlorhexidine mouth rinses remove dental plaque from teeth, preventing dental caries, dental decay, and more serious systemic infections. Tooth discoloration due to extrinsic staining is the most prominent side effect of regular chlorhexidine use. Decreasing the concentration of chlorhexidine reduces staining area and severity. Staining can also be prevented and treated by tooth bleaching, a common cosmetic dental procedure that diminishes extrinsic staining by oxidizing chromagens adsorbed onto the tooth surface. In the proposed trial, common bleaching agents will be investigated for their efficacies in preventing chlorhexidine staining. Results of the trial could further the development of a chlorhexidine mouth rinse that is suitable for long term use.

Made available in DSpace on 2015-09-25T12:18:22Z (GMT). No. of bitstreams: 1 Salomao CuryRad Oka.pdf: 1635559 bytes, checksum: c69a9f145da6d86de4f06ad7da5b589a (MD5) Previous issue date: 2011-07-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Actinic cheilitis is the main lesion with malignant potential of the lower lip, and it is considered a precursor of squamous cell carcinoma in this region. The objective of this study was to evaluate clinical, histopathological and immunohistochemical expression of Ki67 protein in actinic cheilitis aiming better understanding its biological behavior. This research was of transversal, descriptive, analytical, observational, blinded, quantitative, clinical, histopathological and immunohistochemical kind. Thirty cases of actinic cheilitis were clinically and histologically evaluated using pre-established parameters and subjected to immunohistochemistry by streptavidin-biotin method in order to evaluate the expression of protein Ki67. Data were submitted to Mann-Whitney and Kruskal-Wallis tests. It was verified that the most affected gender was male (86.7%), median age was 52,5 years with standard deviation of ±15.75, the most prevalent occupation was farmer (43.3%) and the most affected skin color was white (76.7%). Almost the entire sample was exposed to the sun (90%), although 53.3% used to wear some kind of protection. The main forms of clinical presentation of these lesions were not ulcerated leukoplakia (43.3%), followed by not ulcerated erythroplakia (33.3%). Regarding the main histomorphological characteristics, it was observed that the hyperkeratosis became more present (43.3%) and there were no cases of carcinoma in situ. Although Ki67 protein has been expressed in all cases analyzed, there was not correlation between this protein immunohistochemical expression index and any other analyzed variable. However, it can be concluded that there were cell proliferative activity in varying degrees in these lesions. / A queilite actínica é a principal lesão com potencial de malignidade do lábio inferior, sendo considerada precursora do carcinoma de células escamosas nessa região. Assim, o objetivo deste trabalho foi realizar uma avaliação clínica, histopatológica e imunohistoquímica da expressão da proteína ki67 em queilites actínicas, com intuito de compreender melhor o seu comportamento biológico. A presente pesquisa se caracterizou como um estudo transversal, descritivo-analítico, observacional, quantitativo, cego, de cunho clínico, histopatológico e imunohistoquímico dos casos diagnosticados como queilite actínica na clínica da LINCCO (Liga Interdisciplinar de Combate ao Câncer Oral) do Departamento de Odontologia, da Universidade Estadual da Paraíba (UEPB). Assim, trinta casos de queilites actínicas foram avaliados clínica e histologicamente, usando parâmetros pré-estabelecidos, e submetidos à análise imunohistoquímica pelo método da estreptoavidina-biotina, a fim de se avaliar a expressão da proteína ki67. Os dados obtidos foram submetidos aos testes Mann-Whitney e de Kruskal-Wallis, tendo como base os níveis de significância de 5% (p<0,05). Foi verificado que o gênero mais acometido foi o masculino (86,7%), a idade média foi de 52,5 anos com desvio padrão de ±15,75, a ocupação profissional mais presente foi a de agricultor (43,3%) e a cor da pele mais acometida foi a leucoderma (76,7%). Da amostra, 90% se expunha ao sol, embora 53,3% usasse algum tipo de proteção. As principais formas de apresentação clínica destas lesões foram leucoplasias não ulceradas (43,3%), seguidas de eritroplasias não ulceradas (33,3%). Com relação às principais características histomorfológicas, pôde-se observar que as hiperceratoses se fizeram mais presentes (43,3%) e que não houve nenhum caso de carcinoma in situ. Embora a proteína Ki67 tenha se expressado em todos os casos analisados, não houve uma correlação estatisticamente significativa do índice de expressão imunohistoquímica desta proteína com nenhuma outra variável analisada. Foi possível concluir que existia atividade proliferativa celular em diversos graus nas referidas lesões.

Made available in DSpace on 2015-09-25T12:19:51Z (GMT). No. of bitstreams: 1 Francisco Jadson Lima 1.pdf: 2216015 bytes, checksum: 4aec929c1778b8fd050b7f0847082b5b (MD5) Previous issue date: 2012-07-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Background: Squamous cell carcinoma of the lower lip (SCCLL) is recognize as the oral malignancy of larger incidence, especially in populations with high exposure to solar radiation. Objective: This study aimed to analyze the immunoexpression of EGFr, Ki-67 and p27 proteins in SCCLL evaluating regions that represent distinct stages of lesion development, in order to verify the use of these proteins as markers of tumor progression. Method: We analyzed a sample of 32 SCCLL and 32 cases of normal oral epithelium represented by phenomena of extravasation of mucus as a comparative group. All cases of SCCLL were analyzed based on their clinical characteristics such as gender, age, race, occupational activity, exposure to solar radiation and clinical staging (TNM), and histologically for the presence of cellular atypia in the epithelium adjacent to the tumor and to the front invasion. In the adjacent epithelium was used the classification to degrees of epithelial dysplasia as mild, moderate and severe by Gale et al., (2005) and adapted of Warnakulasuriya et al., (2008), and to the invasive front was used the malignancy classification suggested by Bryne (1998) and adapted by Silveira et al. (2010) classifying the cases into high and low degrees of malignancy. Additionally the entire tumor area was classified according to the histological gradation by Cardesa et al.,(2005) in welldifferentiated, moderately differentiated and poorly differentiated tumors. To the analysis of the immunostaining of EGFr protein was considered the mark to the cytoplasmic membrane and its expression pattern was classified as absent, weak, moderate and intense (DINIZFREITAS et al., 2007). For p27 and Ki-67 proteins were counted the positive and negative cells in a set of 500 cells to obtain the index of positivity (ROCK, SOUZA, PINTO, 2007). Results: The results revealed that males (n = 23/71.9%), 61 years old or older (n = 19/59.3%) and Caucasians (n = 22/68.8%) were more frequent and farmers (n = 25/78.1%), exposed to solar radiation (n = 26/81.2%) and lesions clinically in the early stages I and II (28/87.5%) were the most frequent findings. The mild dysplasia (n = 18/56, 3%), the histological grading in front of low grade (n = 19/59.4%) and the well differentiated cases (n = 16/50.0%) predominated. The front grading and grading across tumor extension showed a statistical association (p = 0.004). The difference in expression between normal epithelium and SCCLL was not significant for KI-67, while the expression of p27 was significant in the adjacent epithelium (p=0.025), tumor chorion (p<0.001) and the front of invasion (p<0.001), and the staining of EGFr protein was significant only in front of invasion (p = 0.047). The analysis of the tumoral areas showed no significant difference in scores of EGFr and Ki-67 proteins,while, the p27 protein showed a progressive decrease of expression as it was performed the analysis of the adjacent epithelium to the front of invasion (p<0.001). Conclusion: The protein EGFr and p27 are involved in tumor progression, is related to the process of cellular proliferation or other signaling pathways. These findings suggest the use of proteins as p27 and EGFr markers of tumor progression in CCELI, and the protein Ki-67 as a marker of cell proliferation. / Fundamento: O carcinoma de células escamosas de lábio inferior (CCELI) é reconhecido como a neoplasia maligna oral de maior incidência, principalmente em populações com alto índice de exposição à radiação solar. Objetivo: A presente pesquisa teve como objetivo analisar a imunoexpressão das proteínas EGFr, Ki-67 e p27 em CCELI avaliando regiões que representam etapas distintas do desenvolvimento da lesão, com intuito de verificar a utilização destas proteínas como marcadores de progressão tumoral. Método: Foi analisada uma amostra de 32 CCELI, tendo como grupo comparativo 32 casos de epitélio oral normal representado por espécimes de fenômeno de retenção de muco. Todos os casos de CCELI foram analisados quanto às suas características clínicas como: sexo, idade, raça, atividade ocupacional, exposição à radiação solar e estadiamento clínico (TNM), e histologicamente quanto à presença de atipia celular em epitélio adjacente ao tumor. No epitélio adjacente foi utilizada a classificação sugerida por Gale et al., (2005) e adaptado por Warnakulasuriya et al., (2008) para graus de displasia epitelial classificando-as em leve, moderada e severa, e para front de invasão a classificação de malignidade sugerida por Bryne (1998) e adaptada por Silveira et al., (2010), classificando os casos como de alto e baixo grau de malignidade. Adicionalmente os CCELI foram classificados em tumores bem diferenciados, moderadamente diferenciados e pobremente diferenciados pelos critérios sugeridos por CARDESA et al., (2005). Para análise da imunoexpressão da proteína EGFr foi considerada a marcação em membrana citoplasmática e seu padrão de expressão foi classificado em ausente, fraco, moderado e intenso (DINIZ-FREITAS et al., 2007). Para as proteínas Ki-67 e p27 foram contadas as células positivas e negativas em um conjunto de 500 células para obtenção do índice de positividade (ROCHA, SOUZA, PINTO, 2007). Resultados: Os resultados revelaram que o sexo masculino (n=23/71,9%), com 61 anos ou mais de idade (n=19/59,3%) e da raça branca (n=22/68,8%) foram mais prevalentes, bem como agricultores (n=25/78,1%), expostos à radiação solar (n=26/81,2%) e com lesões clinicamente nos estádios iniciais I e II (28/87,5%) foram os achados mais frequentes. A displasia epitelial leve (n=18/56,3%), a gradação histopatológica de baixo grau em front de invasão tumoral (n=19/59,4%) e os casos bem diferenciados (n=16/50,0%) foram predominantes. A gradação histopatológica no front de invasão bem como a gradação em toda extensão tumoral demonstraram associação estatística (p=0,004). A diferença de expressão entre CCELI e o epitélio normal não demonstrou significância para KI-67, enquanto a expressão de p27 foi significativa em epitélio adjacente (p=0,025), cório tumoral (p<0,001) e front de invasão (p<0,001), enquanto a marcação da proteína EGFr apenas foi significativa em front de invasão (p=0,047). A análise nas áreas tumorais não mostrou diferença significativa para marcações das proteínas EGFr e Ki-67, enquanto a proteína p27 apresentou uma diminuição progressiva de expressão conforme realizada a análise de epitélio adjacente, passando pelo cório tumoral e chegando a front de invasão (p<0,001). Conclusão: As proteínas EGFr, Ki67 e p27 estão envolvidas na progressão tumoral, seja relacionadas ao processo de proliferação celular ou a outras vias de sinalizações. Estes achados sugerem utilização das proteínas EGFr e p27 como marcadores de progressão tumoral em CCELI.

Oral cancer is a major health problem, with over 500000 patients diagnosed each year. Although progress has been made in regards to both diagnosis and treatment, the overall 5-year survival rate has not changed much in the last 30 years and still relatively static at around 50 %. This high mortality rate is related to late diagnosis of oral malignancies. At stages III and IV the 5-year survival rate is as low as 30 %, however if diagnosed at stage I the survival rate increases substantially to approximately 80 %. Research in to viable methods for early detection of oral malignancies and potential malignancies has the potential to save lives and reduce suffering for many people word wide. The purpose of this systematic review is to find an effective and practical diagnostic test for early detection of malignancies and potential malignancies in the oral cavity. Electronic database searches were conducted in English on the 4th of February 2017, using PubMed medical database, publication date 2005 or later. Inclusion criteria: Diagnostic Test Accuracy studies for oral malignancies and potential malignancies in human patients with gold standard reference test. Search yielded 166 records, titles and abstracts was screened and evaluated, 19 records was included. Included studies were assessed in detail regarding methodological quality and diagnostic accuracy. 19 studies with a total of 11575 participants were included. The studies were subdivided in to groups based on the specific index test assessed in each study. Diagnostic accuracy results: 4 records assessed Tissue autofluorescence; sensitivity ranging from 65.5 % to 100 % and specificity ranging from 41.7 % to 97.4 %. 10 records assessed Brush biopsy sampling; sensitivity ranging from 45 % to 100 % and specificity ranging from 90 % to 100 %. 1 record assessed Blood sampling; sensitivity 64 % and specificity 80 %. 2 records assessed saliva sampling Saliva sampling; sensitivity 100 % and specificity 96.7 %. 1 record assessed Metachromatic dye staining; detection rate of experimental group was 5 % higher than control group. 1 record assessed Narrow-band imaging; sensitivity 95 % and specificity 97 %. The Brush biopsy sampling diagnostic test methods has a body of evidence that far exceeds any other category presented in this review. As for methodological quality, diagnostic accuracy and risk of bias, we deemed the category as a whole to be at an acceptable level.

Previous studies suggest that Medicaid-enrolled children have difficulties accessing dental care, which can lead to untreated dental disease, poor oral health, and compromised overall health status. While Medicaid-enrolled children with a chronic condition (CC) encounter additional barriers to dental care, most relevant studies on dental utilization fail to adopt risk adjustment methods. As such, the impact of CC status and CC severity on access to dental care for Medicaid-enrolled children is poorly understood. The main objectives of this dissertation were to: 1) compare dental utilization for Medicaid-enrolled children with and without a CC; 2) assess the relationship between CC severity and dental utilization; and 3) identify the other factors associated with dental utilization. The 3M Clinical Risk Grouping (CRG) Methods were applied to enrollee-level data from the Iowa Medicaid Program (2003-2008) to identify children with and without a CC and to classify children with a CC into a CC severity level. Three outcome measures were developed: 1) access to an annual dental visit; 2) use of dental services under general anesthesia (GA); and 3) time to the first dental visit after initial enrollment into the Medicaid program. We used multiple variable logistic regression models and survival analytic techniques to test our study hypotheses. Compared to Medicaid-enrolled children without a CC, those with a CC were more likely to have had an annual dental visit and earlier first dental visits. Having a CC was an important determinant of dental utilization under GA for older but not for younger Medicaid-enrolled children. In terms of CC severity, Medicaid-enrolled children with more severe CCs were less likely to have had an annual dental visit and more likely to have utilized dental services under GA. CC severity was not associated with the rate at which the first dental visit took place. Not residing in a dental Health Professional Shortage Area, previous use of dental care, and previous utilization of primary medical care were all positively associated with dental utilization. Identifying and understanding the determinants of access to dental care is an important first step in developing clinical interventions and policies aimed at improving access to dental care for all Medicaid-enrolled children. Future work should focus on identifying the socio-behavioral determinants of as well as the clinical outcomes associated with access to dental services for vulnerable children.

Background P. gingivalis, a non-motile, rod-shaped, anaerobic, Gram-negative bacterium is one of the principal sources of periodontal disease. It possesses a number of potential virulence factors thought to be important in the disease process including 5 hemagglutinins (Hag). One of these is HagB. It is a well characterized nonfimbrial adhesin expressed on the surface of P. gingivalis. HagB is very pro-inflammatory and induces robust chemokine and cytokine responses in vitro and in vivo. Since the chemokine and cytokine responses seen from single cells grown in tissue culture often are not representative of the chemokine and cytokine profiles seen in clinical samples or biopsy specimens, we devised a co-culture model of keratinocytes, dendritic cells, and T-cells to test the hypothesis that chemokine and cytokine responses from co-cultured cells would be more representative of responses seen in clinical samples from individuals with periodontal disease than single cell models. Methods and materials HagB was prepared by cloning hagb of P. gingivalis (1.4 kb) into the vector pQE31 (QIAGEN Inc., Valencia, CA); expressed in E. coli M15(pREP4)pQE31-TX1; and isolated from E. coli lysates by affinity chromatography using a Ni-charged resin (Profinity IMAC Resin, BioRad, Hercules, CA) and examined by SDS-PAGE. Co-culture models were treated with 10 µg/ml HagB (Test) or 10 µg/ml HagB diluent (Control). At 64 hours the supernatants were collected. Chemokine and cytokine biomarkers GM-CSF, CCL3 (MIP-1α), CCL4 (MIP-1β), CCL5 (RANTES), IL-1α, IL-6, IL-8, TNFα, IL-12(p40), and VEGF responses were determined using Milliplex immunoassays. HagB responses were corrected by subtracting the constitutive responses detected in supernatants incubated with HagB diluent. Statistical differences among groups were determined on Log10 transformed biomarker concentration using JMP 10 (version 10.0, SAS, CAR; NC). Results Buffers (e.g. HagB diluent) did not induce a chemokine or cytokine response, however there was a gradual increase in chemokine and cytokine responses from cells at 64 hours. These were subtracted from HagB induced responses. Responses generally fell in 2 groups; in one group containing VEGF, IL-12(p40), IL-6, RANTES and GM-CSF, there were no significant differences among groups (p>0.05). In another group containing IL-1α, IL-8, MIP-1α, MIP-1β and TNF-α, there were significant differences among groups (p< 0.05). Interestingly these resulting responses fell in 2 categories- GM-CSF, IL-12, IL-1α, IL-6 were less than 25pg/ml and IL-8, MIP-1α, MIP-1β, RANTES, TNFα and VEGF were more than 25pg/ml. Some responses were driven by a particular cell type e.g. GM-CSF produced by dendritic cells, RANTES produced by T- cells and VEGF produced by T cells. There were similar responses in HagB-induced IL-8, MIP-1β, MIP-1α and TNFα responses by dendritic cells + keratinocytes and dendritic cells + keratinocytes + T cells. Conclusions Co-culture models can more realistically produce chemokine and cytokine responses to agonists than individual cultures of cells, which is important for predicting and assessing novel therapeutic treatments of periodontal disease.

Porphyromonas gingivalis produces proteases capable of degrading cytokines, host heme proteins, and some antimicrobial peptides. In this work, I show that P. gingivalis culture supernatants fully or partially degrade human neutrophil peptide alpha-defensins and human beta-defensins after 30 minutes. This observation suggests that proteases from P. gingivalis degrade defensins and this activity could abrogate defensin-related innate immune functions.