Orientadores: Dagmar Ruth Stach-Machado, Hernandes Faustino de Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-06T23:10:44Z (GMT). No. of bitstreams: 1 Lorencini_Marcio_M.pdf: 2260417 bytes, checksum: a023a6cebfd812d6f2ed9c440e34ac59 (MD5) Previous issue date: 2006 / Resumo: A doença periodontal é a patologia crônica de maior incidência na dentição humana. A placa bacteriana é seu agente etiológico principal, embora uma resposta imune exacerbada seja apontada como fator preponderante para o agravamento das lesões. Já nos primeiros estágios da doença é possível notar uma grande degradação da matriz extracelular local, principalmente de fibras colágenas. Dessa forma, o envolvimento das metaloproteinases de matriz (MMPs), uma família de enzimas com atividade dependente de íons metálicos que degradam proteínas estruturais da matriz extracelular, tem sido amplamente estudado nesta patologia. Baseado nestas evidências, o objetivo deste projeto foi caracterizar as principais modificações teciduais associadas ao modelo de doença periodontal induzida em ratos com ligaduras durante três, cinco ou sete dias. Foi analisada a microbiota associada à progressão inicial da doença, a disposição de fibras colagênicas e reticulares no tecido gengival e o perfil de células inflamatórias migrantes. Também foi avaliada a expressão e atividade enzimática de MMP-2 e -9, além da expressão gênica de MMP-2, -7, -9 e -14, e do inibidor RECK. A indução da doença com ligaduras pennitiu a formação de placa bacteriana caracterizada pela substituição de microorganismos Oram-positivos por Oram-negativos. O tecido gengival apresentou uma diminuição na área ocupada por fibras colagênicas, com a deposição de fibras mais espessas, características de um processo inicial de fibrose, aos sete dias de indução da resposta inflamatória. Não foram observadas alterações na disposição de fibras reticulares próximas à membrana basal do epitélio. Aos três e cinco dias de inflamação, respectivamente, foram observados picos de migração de neutrófilos e macrófagos. A MMP-2 apresentou um aumento crescente na atividade enzimática e expressão gênica até os sete dias de inflamação induzida, com a marcação de células epiteliais e fibroblastos na imunohistoquímica. A MMP-9 apresentou um pico na atividade enzimática aos três dias e um pico na expressão gênica aos cinco dias de inflamação, com a marcação imunohistoquímica de células epiteliais, fibroblastos e células inflamatórias migrantes para o sítio gengiva!. As MMPs-7 e -14, assim como o inibidor RECK, não apresentaram mudanças significativas em suas expressões gênicas. Os amplificados derivados de RT-PCR para MMP-7 apresentaram um fragmento correspondente a um íntron, indicando um possível mecanismo de regulação relacionado ao processamento do RNA mensageiro. Podemos concluir que o modelo de doença periodontal induzida por ligadura em ratos apresentou uma dinâmica bastante similar aos resultados já descritos para a evolução da doença no homem. A degradação de matriz extracelular observada foi coerente com o aumento na expressão e atividade enzimática de MMP-2 e -9, sugerindo que estas enzimas estejam relacionadas a este processo. Os resultados obtidos para a MMP-2 sugerem uma produção vinculada predominantemente a células próprias do tecido afetado pelo processo inflamatório. A MMP-9, no entanto, parece ter um aumento diretamente relacionado com a chegada de células inflamatórias no sítio gengival. Nossos estudos foram realizados com o intuito de elucidar os mecanismos moleculares da doença periodontal, buscando encontrar caminhos para o desenvolvimento de aplicações de potencial utilização diagnóstica ou terapêutica / Abstract: Periodontal disease is the major chronic disease affecting the human dentition. Bacteri plaque is its main etiological factor, although an exacerbated immune response is point< preponderant factor to the aggravation of the lesions. In the early stages of disease there is a gre degradation of the local extracellular matrix, mainly of the collagen fibers. That way, ti involvement of matrix metalloproteinases (MMPs), a family of enzymes with activity dependir on metallic ions that can degrade structural proteins of the extracelular matrix, it has been studit thoroughly in this pathology. Based on these evidences, the aim of this project was characterize the main tissue modifications associated to the model of periodontal disease induc~ in rats with ligatures during three, five or seven days. It was analyzed the microbiota associat~ to the initial development of the disease, the arrangement of collagen and reticulin fibers in ti gingival tissue and the migration of inflammatory cells. It was also evaluated the expression ar enzymatic activity ofMMP-2 and -9, besides the gene expression ofMMP-2, -7, -9 and -14, ar of the RECK inhibitor. The induction of disease using ligatures allowed the formation I bacterial plaque, characterized by substitution of Gram-positive for Gram-negati1 microorganisms. The gingival tis sue presented a decrease in the area occupied by collagen fibel with the formation of thicker fibers at seven days on induction of inflammatory response, usual found in fibrosis processes. Alterations were not observed for the organization of reticulin fibe elose to the basement membrane of the epithelium. To the three and five days of inflammatio respectively, peaks of neutrophils and macrophages migration were observed. MMP-2 present~ an increase in the enzymatic activity and gene expression until the seven days of induc~ inflammation, with the demarcation of epithelial cells and fibroblasts by immunohistochemistr MMP-9 presented a peak of enzymatic activity at the third day of inflammation and a peak I gene expression at the fifth day, with the demarcation of epithelial cells, fibroblasts ar migrating inflammatory cells to the gingival area. MMP-7 and -14, as well as the inhibitl RECK, did not present significant changes in their gene expressions. The amplified from R.' PCR for MMP-7 presented a fragment corresponding to an intron, indicating a possib regulation mechanism related to an altemative splicing of mRNA. The degradation ( extracellular matrix was coherent with the increased gene expression and enzymatic activity I MMP-2 and -9, suggesting that these enzymes are related to this processo The results for MMI suggest that its production may be related to the resident cells grom gingival tissue. In the otl hand MMP-9 may be produced by migrating inflammatory cells. We conclude that t periodontal disease model showed similar dynamics to the human disease described I 1 literature, and it could be an important tool to understand the molecular events associated w the pathology and to support the development of diagnostic or therapeutic applications / Mestrado / Imunologia / Mestre em Genética e Biologia Molecular

A definição clara de doença periodontal é fundamental para se estabelecer critérios de risco ao desenvolvimento de outras condições sistêmicas e definir fenótipos biológicos que representem os eventos microbiológicos, moleculares e imunológicos subjacentes à manifestação clínica da doença. O objetivo deste estudo foi avaliar a prevalência dos diferentes fenótipos biológicos dentre os pacientes atendidos na Faculdade de Odontologia de Bauru-USP, correlacionando os achados clínicos às condições sistêmicas dos pacientes e aos achados microscópicos. Foram incluídos na amostra dados do prontuário clínico de 313 pacientes de ambos os sexos, com idade entre 12 e 76 anos. Após a coleta dos dados relativos à identificação, história médica e odontológica e parâmetros periodontais (profundidade de sondagem P.S.; recessão - REC ou hiperplasia HP; nível de inserção clínica NIC; índice de sangramento à sondagem SS e índice de placa IPl), a amostra foi dividida em cinco grupos: IBG-S (Interface Biofilme Gengiva - Saúde)- SS <10% e P.S. 3mm (n=24); IBG-G (Gengivite)- SS&#x2265;10% e P.S.&#x2264;3mm (n=39); IBG-LP/SL (Lesão Profunda- Sangramento Leve)- SS< 10% e 1 sítio ou mais P.S.&#x2265;4 mm (n=47); IBG-LP/SM (Lesão Profunda -Sangramento Moderado)- 10%-49% de SS e 1 sítio ou mais com P.S.&#x2265;4 mm (n=131); IBG-LP/SS (Lesão Profunda -Sangramento severo)- SS&#x2265;50% dos sítios e 1 sítio ou mais com P.S.&#x2265;4 mm (n=72). Foram obtidas biópsias de tecido mole de 25 pacientes dos diferentes grupos para análise em microscopia ótica convencional por dois examinadores experientes, desconhecedores da identificação dos pacientes. Os resultados demonstraram maior prevalência de IBG-LP/SM (41,85%) e menor prevalência de IBG-S (7,65%). A idade média foi de 42,93 ± 14,48 anos, sem diferenças entre os grupos (p=0.42; Kruskal-Wallis), com prevalência de mulheres (63,8%). A avaliação pelo teste Chi-quadrado demonstrou que IBG-LP/SL, IBG- LP/SM e IBG-LP/SS apresentaram maior número de fumantes do que IBG-S e IBG-G (p=0.015), sem diferenças entre os grupos em relação à presença de diabetes e doenças cardiovasculares (p>0.05). O risco de pacientes com SS>10% apresentarem doenças cardiovasculares foi significativamente elevado (p= 0.04, teste exato de Fischer). A P.S. média e NIC foram maiores no grupo IBG-PL/SS (2.95±1.55; 1.94±2.24, respectivamente) e menores no grupo IBG-G (1.71±0.65 e 0.51±0.99, respectivamente), com diferenças significantes entre os grupos (p<0.001; Kruskal-Wallis). O SS e IPl foram maiores nos grupos IBG-LP/SS e IBG-G, seguido pelos grupos IBG-LP/SM, IBG-LP/SL e IBG-S (p<0.001; Kruskal-Wallis). A análise microscópica demonstrou que o diagnóstico clínico foi compatível com o diagnóstico microscópico em 10 das 25 amostras investigadas (40%), observando-se correlação entre os achados clínicos e microscópicos em 100% das amostras do grupo IBG-G (n=4), 83,3% do grupo IBG-LP/SS (n=6), 50% do grupo IBG-S (n=2), 16,67% do grupo IBG-LP/SM (n=6) e 0% do grupo IBG-LP/SL (n=7). Esses achados sugerem que a manifestação clínica da doença periodontal é heterogênea, não compatível com a resposta inflamatória observada no tecido conjuntivo gengival. / A clear definition of periodontal disease is essential to establish criteria of risk of developing other systemic conditions, as well as to determine biological phenotypes that represent the microbiological, molecular and immunological features underlying clinical manifestation of the disease. The aim of this study was to evaluate the prevalence of different biological phenotypes among patients attended at School of Dentistry at Bauru-USP, correlating the clinical findings with systemic conditions and microscopic findings. It was included in the sample data collected from dental file records of 313 patients, both genders, age ranged 12-76 years. After collection of data related to the identification, medical and dental history and periodontal parameters (probing depth PD; recession REC or marginal hyperplasia HP; clinical attachment level CAL; bleeding on probing BOP; plaque índex IPl), sample was divided into Five groups: BGI-H (Health)- BOP <10% and PD&#x2264; 3mm (n=24); BGI-G (Gingivitis)- BOP&#x2265;10% and PD&#x2264;3mm (n=39); BGI-DL/LB (Deep lesion/low bleeding)- SS<10% and 1 or more sites PD&#x2265;4 mm (n=47); BGI-DP/MB (Deep lesion/moderate bleeding)- 10%-49% BOP and 1 or more sites PD&#x2265;4 mm (n=131); BGI-DL/SB (Deep lesion/severe bleeding)- BOP 50% and 1 ore more sites PD&#x2265;4 mm (n=72). Soft tissue excisional biopsies were removed from 25 patients of all groups for analysis in optical microscopy by two expertise blinded examiners. The results showed more prevalence of BGI-DP/MB (41.85%) and lesser prevalence of BGI-H (7.65%). Mean age was 42.93±14.48 years, without significant differences among groups (p=0.42; Kruskal-Wallis), and prevalence of women (63.8%). Evaluation by Chi-squared test showed that BGI-DL/LB, BGI-DL/MB and BGI-DL/SB presented more smokers than BGI-H and BGI-G (p=0.015), without significant differences in diabetes and cardiovascular diseases (p>0.05). The risk of patients with BOP> 10% present CVD was significantly higher (p= 0.04, Fischers exact test). Mean PD and CAL were deeper in BGI-DL/SB (2.95±1.55; 1.94±2.24, respectively) and shallower in BGI-G (1.71±0.65; 0.51±0.99, respectively), with significant differences among groups (p<0.001; Kruskal-Wallis). BOP and IPl were higher at BGI-DL/SB and BGI-G, followed by BGI-DL/MB, BGI-DL/LB and BGI-H (p<0.001; Kruskal-Wallis). Clinical diagnosis was compatible with microscopic diagnosis in 10 out of 25 samples (40%), noticing correlation between clinical and microscopic finding in 100% of BGI-G samples (n=4), 83.3% of BGI-DL/SB samples (n=6), 50% of BGI-H samples (n=2), 16,67% of BGI-DL/MB (n=6) and 0% of BGI-DL/LB (n=7). These findings suggest that clinical manifestation of periodontal diseases is heterogeneous, not corresponding to the inflammatory response observed at gingival connective tissue.

Hipótese do estudo: O presente estudo parte do pressuposto de que a terapia periodontal não cirúrgica é eficaz no tratamento da doença periodontal. Objetivos: este estudo de intervenção avaliou a eficácia dos procedimentos de raspagem e aplainamento radicular utilizando como ferramenta de validação parâmetros clínicos, microbianos e salivares em indivíduos diagnosticados com gengivite e periodontite comparando-os a controles saudáveis. Método: Foram alocados no presente estudo 89 indivíduos assim caracterizados: 31 periodontalmente saudáveis (K), 27 com gengivite (G) e 31 com periodontite crônica (P). Avaliou-se os seguintes parâmetros clínicos: índice de placa, índice de sangramento, profundidade de sondagem e nível de inserção clínica. Avaliou-se ainda a presença dos periodontopatógenos Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tanerella forsythia, Treponema denticola e Prevotella intermedia por meio da reação em cadeia da polimerase (PCR). Finalmente, a presença salivar de arginase e proteína total por meio de espectrofotometria foi também considerada. Todos estes parâmetros foram mensurados em pré e pós terapia periodontal. Tratamento estatístico dos dados intragrupo foi realizada pelo teste de Wilcoxon, enquanto os dados intergrupos foram avaliados pelos testes Mann-Witney e Kruskal-Wallis, adotando-se significância estatística quando p<0,05. Resultados: Verificou-se melhora dos parâmetros clínicos nos grupos G e P após o tratamento (p<0,05). Houve redução da atividade de arginase e proteína total salivares nos grupos P (p<0,05) e G, equiparando-se ao grupo controle (K). T. forsythia reduziu no grupo G (p<0,05), enquanto P. gingivalis, T. denticola, P. intermedia e T. forsythia apresentaram redução no grupo P (p<0,05). Conclusão: O pressuposto apresentado neste estudo foi confirmado, tendo como validação a utilização dos parâmetros clínicos, microbiológicos e salivares. / Hypothesis of the study: the present study assumes that non-surgical periodontal therapy is efficient on the periodontal disease treatment. Aims: this interventional study evaluated the efficacy of the scaling and root planing procedures by using as a tool of validation, clinical, microbiological and salivary parameters in subjects diagnosed with gingivitis and periodontitis comparing them with healthy controls. Methods: In the present study, 89 subjects were characterized as follows: 31 periodontal healthy (K), 27 with gingivitis (G), and 31 with chronic periodontitis (P). The following parameters were evaluated: plaque index, bleeding index, probing depth, and clinical attachment level. The presence of the periodontalpathogens Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tanerella forsythia, Treponema denticola, and Prevotella intermedia were also evaluated by polymerase chain reaction (PCR). Finally, the presence of salivary arginase and total protein by spectrophotometry were also considered. All these parameters were measured before and after periodontal treatment. Intra-group statistical analysis were performed by Wilcoxons test while the inter-group analysis were evaluated by Mann-Witney and Kruskal-Wallis tests, adopting a statistical significance when p<0,05. Results: An improvement of the clinical parameters was verified in the G and P groups after treatment (p<0,05). There was a significant reduction of the salivary arginase activity and protein content in the P and G groups compared to the control group (K). T. forsythia was diminished in the G group (p<0,05), while P. gingivalis, T. denticola, P. intermedia and T. forsythia showed a decrease in the P group (p<0,05). Conclusion: the hypothesis of the present study was confirmed being validated by clinical, microbiological and salivary parameters.

Speichelglykane können einerseits spezifisch an bakterielle Lektine binden und damit deren Adhäsion an orale Oberflächen vermitteln, andererseits eine Antiadhäsion bedingen. Sie stellen ein Schutzsystem für orale Oberflächen dar. Bei vorhandener Karies bzw. Parodontitis ist die Konzentration bestimmter Glykokonjugate verändert. Ziel dieser Studie war es, die Reaktivität der Glandulae majores bzgl. ihrer Sekretion von Glykanen in Abhängigkeit einer experimentellen Gingivitis zu ermitteln. 14 gesunde Probanden enthielten sich 9 Tage der Mundhygiene. Neben der Erhebung des PBI und QH wurde drüsenspezifisch Speichel gewonnen. Die Konzentrationen an die Lektine PNA, GS1, VVA, SNA und AAA bindender Komponenten und deren drüsenspezifische Sekretionsraten wurden bestimmt. Bei allen Probanden stiegen PBI und QH im Versuchsverlauf signifikant an. Gleiches galt für die Speichelmenge nach Stimulation sowie zum Ende der Kontrollreihe. Die Konzentrationen der verschiedenen Glykane verhielten sich unabhängig von der Speichelmenge und unabhängig voneinander. Meist ergab sich eine erhöhte Glykansekretion spezifisch für das untersuchte Lektin. Neben dem Konzentrationsgefälle der einzelnen Drüsen war auch eine Verschiebung nach erfolgter Stimulation zu beobachten. Da genetische und externe Einflüsse für diese Studie weitgehend ausgeschlossen werden konnten bzw. als konstant einzuordnen waren, darf die Veränderung als Reaktion auf die orale Bakterienbelastung angesehen werden. Der Rückgang bestimmter terminaler Strukturen könnte als Folge der vermehrten Synthese anderer, in Bezug auf die veränderte Bakterienflora effektiverer Speichelbestandteile eingeordnet werden. Basierend auf dem Modell, dass freie Glykane die Adhäsion von Mikroorganismen inhibieren können, ließe sich die gemessene Reaktion der Speicheldrüsensekretion als ein gesteigerter Schutzmechanismus im Sinne einer ´first line of defence´ interpretieren. Dieser könnte z.B. in Bezug auf Prophylaxe und Therapie genutzt werden. / Salivary glycans can bind specificly to bacterial lectins. Consequently, bacterial adhesion to oral surfaces is mediated or inhibited by glycans. It is known that the concentration of certain glycans changes in the presence of caries or periodontitis. Therefore this study examines the reactivity of the major salivary glands with respect to the secretion of glycans as conditioned by an experimentally induced gingivitis. 14 healthy subjects refrained from all oral hygiene measures for 9 days. On 5 days a plaque and bleeding index as well as pure glandula saliva with and without stimulation were obtained. The collected salivary samples were examined for their concentration of certain structures that bind to the lectins ´PNA´, ´GS1´, ´VVA´, ´SNA´ and ´AAA´. All subjects developed a gingivitis as measured by the plaque and bleeding index. Salivary flow increased after stimulation and compared to baseline at the end of the trial. The concentration of glycans was neither related to one of the glands nor to the salivary flow. Besides to the differentials of concentration after stimulation there was no symmetrical development between the concentrations of salivary lectin-specific components compared one lectin to another. Genetic and external influences could be largely excluded or considered to be stable during the trial. Therefore the observed results can be regarded as a reaction to the increased bacterial load. The decrease of certain terminal structures in saliva might be explained by a raised synthesis of other components, which are more effective in defending the body against bacterial adhesion. The observed changes in salivary secretion might be interpreted as a mechanism in order to protect the human organism within the meaning of a ´first line of defence´. This mechanism would be able to respond more quickly than the immune system and might be used in future, for example, for preventive and therapeutical strategies.

Bakgrund: Övervikt/fetma är ett hälsoproblem som snabbt ökar i Sverige och hela världen. Övervikt/fetma, karies och parodontit är alla kroniska och multifaktoriella sjukdomar. Dessa sjukdomar är vanligt förekommande hos både barn och ungdomar. De orala sjukdomarna är förknippade med ohälsosamma kostvanor som påverkar både orala- och allmänna hälsan och som i sin tur kan påverka vikten hos barn och ungdomar. Syfte: Att studera om det finns ett eventuellt samband mellan övervikt/fetma och orala sjukdomar hos barn och ungdomar. Metod: Detta arbete var en litteraturöversikt. För sökning av vetenskapliga artiklar användes DOSS och PubMed. Totalt genererades 393 träffar varav 50 artiklar valdes ut till fulltextgranskning. Med hjälp av en modifierad granskningsmall granskades sedan artiklarnas bevisvärde och analyserades för att avgöra om graden på artiklarna var svag, måttlig eller stark. Slutligen inkluderades 19 artiklar i studien. Resultat: Socioekonomi, BMI hos barn och föräldrar, utbildningsnivå, etnicitet, hygien- kostvanor och hälsotillstånd var av stor betydelse till utvecklingen av övervikt/fetma samt karies. Övervikt/fetma hade en direkt inverkan på parodontit men då studierna inom detta område var få anser författarna till denna litteraturstudie att ytterligare forskning inom detta område krävs. Slutsats: Merparten av dessa 19 studier har visat ett statistiskt signifikant samband mellan övervikt/fetma och orala sjukdomar och detta samband visades vara beroende av flera faktorer. / The link between overweight/obesity and oral diseases in children and adolescents   Background: Overweight/obesity is a health problem that is increasing rapidly in Sweden and around the world. Overweight/obesity, dental caries and periodontitis are all chronic and multifactorial diseases. These diseases are common in both children and adolescents. The oral diseases are linked to unhealthy dietary habits that affect both oral- and general health, which in turn may affect the weight of children and adolescents. Aim: To study whether there is a possible link between overweight/obesity and oral diseases in children and adolescents. Me-thod: This work was a literature review. DOSS and PubMed were used for search of scientific articles. Total generated hits were 393 of which 50 articles were selected for fulltext review. Using a modified review the articles were then examined for probative value and analyzed to determine if the the articles are weak, moderate or strong. Finally, 19 articles were included in the study. Results: Socioeconomi, BMI in children and parents, level of education, ethnicity, hygiene, nutrition and health status was of great importance in the development of overweight/obesity and dental caries. Overweight/obesity had a direct impact on periodontal disease but because of the studies in this area being few the authors of this study believe that further research in this area is required. Conclusion: The majority of these 19 studies have shown a statistically significant association between overweight/obesity and oral diseases and the relationship was shown to be dependent on several factors.

Protein identification and quantitation using mass spectrometry has evolved as the dominant technique for studying the protein complement of a system: cell, tissue or organism. The proteomics of body fluids is a very active research area as there is great potential for protein biomarker discovery; application of such technologies would revolutionise medical practice and treatment. Saliva, through its non intrusive nature of sampling, is an ideal body fluid for disease diagnosis, screening and monitoring. Gingivitis is a gum disease with symptoms including bleeding, swollen, and receding gums. After dental decay, gingivitis is estimated to be the most common disease worldwide, and around 40% of the population in the US are reported to have gingivitis. The end point goal of this project was to identify salivary biomarkers for gingivitis. This dissertation presents an investigation of: 1) the salivary proteome; 2) developments and applications of a mass spectrometry kinase assay; and 3) salivary biomarkers for gingivitis using proteomics and kinase activities. The soluble portion of the human salivary proteome (saliva supernatant) has been studied by several research groups but very few proteomic studies have been performed on the insoluble, cellular and bacterial portion of saliva. Presented here, is the first global proteomics study performed on the saliva residue and supernatant from the same test subject. A total of 834 and 1426 proteins were identified in the saliva supernatant and residue, respectively. A global analysis of protein complexes in saliva was also performed and is the first study, to date, of such an analysis. KAYAK (‘Kinase ActivitY Assay for Kinome analysis’) was further developed for its application on a number of cell types, tissue types, and a variety of organisms. Proof of concept work for in-gel kinase activity/kinase abundance correlation profiling using blue native gels was performed, and experiments using anion exchange chromatographic kinase activity/kinase abundance correlation profiling were performed to identify kinase-substrate pairs. KAYAK applications included the analysis of kinase activities in Saccharomyces cervisiae, Drosophila, mouse, and human saliva in which significant kinase activity was detected in the saliva supernatant, a novel finding. Finally, gingivitis was induced in patients, and the saliva samples were analysed using proteomics and kinase activity profiling. Although this work is ongoing, preliminary data indicate that there are increases in various inflammatory proteins, certain bacteria and also in the activity of particular kinases as a result of the induction of gingivitis. The overall study provided insights into the salivary proteome for both the human and bacterial complement, as well as discovering the presence of significant kinase activity in saliva. In the induced gingivitis study, almost half of all the proteins identified in the residue were from bacteria (1274 bacterial proteins, 198 species identified) and there may be more potential for biomarker discovery for certain diseases in the saliva residue than in the supernatant. A very large overlap was observed between the human proteins in the saliva supernatant and residue, indicating that many of the salivary proteins originate from lysed cells. The origin of the kinase activity in the saliva supernatant is not known but is also proposed to originate predominantly from lysed cells. A range of novel KAYAK applications have been investigated, demonstrating that KAYAK has a wide variety of future uses ranging from target compound evaluation in Pharmaceutical companies to patient testing in the clinic.

Magnesidin is a magnesium chelate of the 3-hexanoyl and 3-octanoyl tetramic acid derivatives isolated from Psuedomonas magensiorubra. Its activity against grampositive bacteria was found to be a specific target for Gingivitis, a dental plaque.Although the synthesis of magnesidin has been reported earlier, it was not reproducible. The highly polar nature and it’s ability to exhibit tautomerization makes their chemical behavior complex and difficult to predict its structure. A variety of reactions and an in depth understanding of the chemical structure is necessary to attain the synthesis of these compounds. This dissertation focuses on addressing the attempts towards the synthesis of Magnesidin by identifying the important intermediates necessary for the synthesis as β- keto esters, α,β-unsaturated amino esters. The focus of the work has been addressed by developing a TAG molecule approach, which is similar to the concept of solid phase synthesis except for the fact that the TAG molecule can be identified under UV and also can be detected using various spectroscopic techniques. Microwave synthesis has been explored and applied in to the synthesis of benzyl mono and di bromination, 1,3- benzodioxoles have been established. The benzyl mono bromination is applied to synthesize the TAG molecule, which is then applied in developing a method of synthesis for β-keto esters. The azide approach was used to synthesize the α,β- unsaturated amides, which are another essential class of compounds in the synthesis of magnesidin.

Memoria para optar al Título Profesional de Médico Veterinario / Con el propósito de conocer si existe asociación entre la presentación de gingivitis con la seropositividad a Bartonella henselae en felinos domésticos, se analizaron 144 gatos en la ciudad de Santiago, provenientes de los Hospitales Clínicos Veterinarios de la Universidad de Chile, de ambos sexos, mayores de un año, negativos a las pruebas de Inmunodeficiencia Viral Felina y Leucemia Viral Felina. Todos los gatos fueron clasificados, según la presencia o ausencia de gingivitis, en dos grupos de 72 gatos cada uno. Para la determinación clínica de gingivitis se utilizó una adaptación del índice descrito por Loe y Silness. Para el diagnóstico serológico de Bartonella henselae se utilizó una prueba comercial de inmunofluorescencia indirecta (SLIDE ®). De los todos gatos analizados, el 73,6% fue seropositivo a Bartonella henselae y de los 72 gatos con gingivitis, el 87,5% de ellos fueron seropositivos. Mediante la prueba de Chi cuadrado, se determinó que no hay independencia entre la presentación de gingivitis y la seropositividad a Bartonella henselae (p<0,05)

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / Autor no autoriza el acceso a texto completo de su documento / Introducción: Los niños y adolescentes con parálisis cerebral (PC) se encuentran gran parte del día en centros educacionales y/o de rehabilitación. Las políticas de salud y prácticas de higiene oral pueden variar entre establecimientos según nivel socioeconómico (NSE). El presente estudio evalúa y compara prevalencia de caries, gingivitis y estado de higiene oral de niños y adolescentes con PC, según el NSE del establecimiento. Material y métodos: 59 pacientes con PC (36 hombres, 23 mujeres) de tres centros educacionales, ambos géneros, entre 2 y 19 años, fueron examinados por dentistas calibrados, previa obtención de consentimiento informado. Se evaluó prevalencia de niños libres de caries, índice de caries (COP-D/ceo-d), presencia/ausencia de gingivitis e índice de higiene oral simplificado (IHO-S). Un establecimiento (Fundación Alter Ego) fue clasificado como NSE alto y los otros dos (Colegio Amapolas y Cedros del Líbano) como NSE bajo. Los resultados fueron analizados según la naturaleza de las variables mediante análisis T test (paramétricas) y MannWhitney U Test (no paramétricas), considerando diferencias significativas cuando p<0,05. Resultados: El total de examinados presentó un 49,1% de niños libres de caries, COP-D=2,1, ceo-d=0,2; 78,0% de gingivitis e IHO-S=2,2. Se encontraron diferencias significativas en la prevalencia de niños libres de caries y en el índice de caries entre niños y adolescentes del grupo NSE alto (n=30, 66,7% libre de caries, COP-D=1,3, ceo-d=0) respecto de los del grupo NSE bajo (n=29, 31,0% libre de caries, COPD=2,7, ceo-d=0,5). El 76,6% de los examinados del grupo NSE alto presentó gingivitis, con un IHO-S=2,2, mientras que el 79,3% presentó gingivitis en el NSE bajo con un IHO=2,3. No se encontró diferencia significativa en la prevalencia de gingivitis e IHO-S entre ambos grupos. Conclusiones: Existen diferencias en la salud bucal e higiene oral de niños y adolescentes con PC según el NSE del establecimiento al que asisten. En el NSE bajo se observó menor porcentaje libre de caries y mayores índices de caries; sin embargo, el NSE fue indiferente en cuanto a la alta prevalencia de gingivitis y mala higiene oral observada en los diferentes establecimientos.

Syfte: Syftet med litteraturstudien var att sammanställa evidens kring diabetes typ 1 och dess påverkan på barn och ungdomars orala hälsa. Metod: Studien var en allmän litteraturstudie. Inklusionskriterier var att de skulle ha publicerats mellan år 2008 till 2018, vara peer-reviewed granskade samt ha ett åldersspann på deltagare från 3  till 18 år. Efter en kvalitetsgranskning bedömdes 21 artiklar uppfylla kriterier till grund för studien. Artiklarna som användes har samtliga studerat diabetes typ 1 och dess påverkan på barn och ungdomars orala hälsa. Resultat: Resultatet påvisade att sjukdomen diabetes typ 1 har en påverkan på barn och ungdomars orala hälsa. Gingivit, karies, parodontit, oral candidos, plack samt tandsten är orala besvär som har visat sig ha en högre prevalens hos barn med diabetes i jämförelse med friska barn, enligt tidigare evidens. Resultatet i studierna varierade i en viss utsträckning beroende på olika utfallsmått och metoder. Slutsats: En sammanställning av studier visade ett samband mellan barn och ungdomar med diabetes typ 1 och en försämrad oral hälsa, där plack och gingivitförekomsten var som högst. Mer forskning generellt krävs kring hur diabetes typ 1 påverkar den orala hälsan hos barn och ungdomar, i syfte om att få en heltäckande bild. / Purpose: The purpose of the literature overview was to study evidence for type 1 diabetes impact on children and adolescents oral health. Method: The study was a general literature study. The inclusion criteria were that they should have been published between 2008 until 2018, peer-reviewed and have an age range of children up to 18 years. After a quality review, 21 articles were used in this study. The articles that was used, have all studied diabetes type 1 and its impact on children and adolescents oral health. Result: The result showed that the disease type 1 diabetes has an effect on the oral health of children and adolescents. Gingivitis, caries, periodontitis, oral candidos, plaque and calculus are oral disorders that has been shown having a higher prevalence in children with diabetes in comparison to healthy children. The results in the studies varied to a certain extent due to different outcome measures and methods. Conclusion: Previous studies have shown a relationship between children and adolescents with type 1 diabetes and their impaired oral health, where plaque and gingivitis were most prevalent. More research is generally required on how diabetes type 1 affects the oral health of children and adolescents in general.