Objectives: Periodontal disease is a chronic inflammation resulting in periodontal attachment loss. Keratinocyte Growth Factor-1 (KGF-1) is upregulated in chronic inflammation and specifically stimulates epithelial cell proliferation by signaling through the epithelial-specific Keratinocyte Growth Factor Receptor (KGFR). First, we examined KGF-1 and KGFR expression and localization in human periodontal tissues. Second, we extended these studies by developing an in vitro mechanical wound model to mimic trauma to the periodontal pocket epithelium and examined ligand independent KGFR activation and cell migration. Methods: In our study of human gingival tissues, we used immunohistochemistry and laser capture microdissection with RT-PCR to analyze KGF-1 and KGFR expression and localization. To study ligand independent KGFR phosphorylation, KGFR internalization along the wound edge was imaged using immunohistochemical staining and KGFR phosphorylation confirmed using immunoprecipitation with western blotting. Wounding induced oxidative stress was detected using DCFH-DA (2',7'-dichlorofluorescin diacetate) and modulated by pretreatment with an antioxidant. Changes in migration were examined in the presence or absence of pathway specific inhibitors. Results: KGF-1 protein localized to areas of junctional and basal oral epithelial cells was significantly increased in periodontal pocket epithelium (p<0.01) and oral epithelium (p<0.05) of disease-associated tissues. KGFR localized to the junctional and the parabasal cells of oral epithelium, and was increased in disease-associated pocket epithelium (p<0.05). Laser capture microdissection with RT-PCR confirmedKGF-1 and KGFR were specifically expressed by connective tissue and epithelium, respectively. In our cell culture model, mechanical wounding induced ligand independent KGFR activation. ROS (Reactive Oxygen Species) generation along the wound edge was associated with KGFR activation and scavenging of ROS reduced KGFR phosphorylation. The c-Src family inhibitor, PP1, significantly inhibited KGFR phosphorylation. Functionally cell migration was reduced by PP1 (82.7%), SU5402(70%) and PD98059 (57%). Conclusions: KGF-1 and KGFR proteins are expressed in health but significantly induced in human diseased periodontal tissues. Microwounding associated generation of ROS mediates KGFR phosphorylation via c-Src kinase signaling and induced wound edge cell migration. Therefore, regulation of epithelial cell behavior associated with the onset and progression of periodontal disease may possibly be mediated by two related but distinct mechanisms. (1) Ligand-dependent activation of KGFR due to upregulation of KGF-1. (2) Ligand-independent activation of KGFR due to chronic microwounding. / Dentistry, Faculty of / Graduate

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / Introducción: Las enfermedades gingivales son una condición prevalente en la población. Los métodos actuales de vigilancia de enfermedades periodontales se basan en exámenes clínicos, los cuales requieren numerosos recursos para su implementación. Como alternativa se plantea el auto-reporte, opción de menor costo para estudios poblacionales, pero poco estudiado en población infantil. El objetivo de este estudio fue evaluar la relación entre sangrado gingival autoreportado, la condición clínica de salud gingival y su relación con la presencia de placa bacteriana en escolares de 6-12 años asistentes a colegios municipalizados. Material y métodos: Se examinaron 207 escolares de 6-12 años de edad asistentes a dos colegios municipalizados de la Región Metropolitana. Se registró Índice gingival de Löe y Silness simplificado (IG), Índice de higiene oral simplificado (IHO-S) y Examen Periodontal Básico simplificado (EPB), junto con una pregunta de auto-reporte sobre sangrado gingival durante el cepillado. Se determinó presencia de gingivitis mediante dos definiciones de caso (PG1=IG promedio≥0.5 y PG2=EPB>0) al igual que su severidad (SG1=según IG promedio y SG2=según índice de sangrado gingival). Se utilizaron pruebas de diferencia entre grupos, según edad y género, para los índices periodontales y test chi2 para determinar asociación entre presencia de gingivitis, severidad de gingivitis y condición de higiene oral respecto al auto-reporte. Se estimó sensibilidad (SS) y especificidad (ES) del auto-reporte, considerando buena validez si SS+ES≥ 120%. Resultados: La prevalencia de gingivitis fue PG1=98.6% y PG2=90.8%, registrándose severidades leve y moderada (SG1=54.6% y 43.9%; SG2=38.2% y 3.4%, respectivamente). El 60.9% presentó regular higiene oral. El 50.7% de los escolares con gingivitis auto-reportó sangrado a veces y el 10.6% reportó siempre, sin asociación según la condición de higiene oral. La definición PG2 fue más prevalente en quienes auto-reportaron sangrado gingival. Los mayores valores de SS+ES se obtuvieron para PG2 (127.0%) y SG2 moderada (128.7%). Conclusiones: El auto-reporte tendría capacidad para tamizar población enferma, especialmente con mayor severidad de gingivitis, pudiendo ser una prometedora herramienta para utilizar en vigilancia poblacional de gingivitis en población infantil y como método de detección precoz para instaurar medidas preventivas. / Adscrito a proyecto de investigación FONIS SA 14/D0056

Indiana University-Purdue University Indianapolis (IUPUI) / The effect of weightlessness on bone and osteoblast precursor cells has previously been studied. A marked decrease in bone formation, an increase in less differentiated committed osteogenic cells (A+A'), and a decrease in preosteoblast cells (C+D) was noted. To date, the effect of hypergravity (2g) on osteoblast histogenesis has not been studied in vivo. In vitro studies using nonphysiologic high levels of gravity (20,40g) have shown an increased proliferation of cloned osteoblast-like cells. The purpose of the present study was to evaluate the effect of hypergravity (2g) on osteoblast histogenesis in the rat periodontal ligament (PDL), on the width of the mesial PDL, and on the percentage of forming bone surface on the mesial side of the tooth. Twenty male Wistar rats (SPF: Harlan Sprague Dawley) were randomly assigned to the centrifuge (experimental) or to the stationary (control) group. The experimental group was centrifuged for 14 days at 2g and the stationary group was housed in identical cages in the centrifuge room. The PDL of the mesial and distal surface of the mesial root of the first maxillary molar was analyzed microscopically 100 μm above and below the midroot area. Nuclear volume morphometry was used to classify periodontal ligament cells as: L cells (<40 μm3), A+A' cells (40-79 μm3), B cells (80-119 μm3), C cells (120-169 μm3), and D cells (>170 μm3). The percent of forming bone surface on the mesial side and the width of the PDL were also measured. A 2x2 factorial ANOVA with repeat measures revealed a significant (p < 0.05) decrease in the C cell population and a nearly significant (p < 0.06) increase in the A+A' cell population in the centrifuge group. Comparing bone surfaces, the forming surface had a significant (p < 0.01) increase in the C and D cell populations, a significant (p < 0.01) decrease in the L and A+A' cell populations, and a significant (p < 0.05) decrease in the B cell population. The stationary group weighed significantly (p < 0.01) more than the centrifuge group post-experiment. And an unpaired t-test revealed a nearly significant (p < 0.06) increase in the percent forming bone surface on the mesial side of the maxillary first molar and no significant difference in mesial PDL width. The results showed that the centrifuge group had a trend toward a block in preosteoblast formation. This is similar to that seen with hypogravity. However, it cannot be concluded at this time if this is a direct gravitational effect or related to other factors such as physiological response to stress. Physical stress has been suggested as a potential mechanism for the observed decrease in weight seen in centrifuged animal, while the PDL width does not seem to be affected by gravitational forces, and thus may not be a sensitive marker to osteoblast differentiation inhibition. Finally, the reason for the increase in forming bone surface in the centrifuged group is unclear.

Periodontal disease is a condition in which the gums and bones surrounding the teeth are inflamed. It is a common cause of oral discomfort and tooth loss, but in recent years has been linked to a variety of systemic problems. Among them is cardiovascular disease, which is the top cause of death in the developed world. There is evidence that periodontal pathogens invade the bloodstream from the gingival pockets and contribute to the progression of disease through a variety of different mechanisms. First, they initiate the systemic inflammatory process by invading and activating vascular endothelial cells to upregulate adhesion molecules and chemokines, which then in turn activate macrophages to take up low density lipoprotein and deposit it on the luminal wall. Atherosclerotic plaque is pro-thrombotic, which increases the chances of forming blood clots and ischemic attacks. Periodontal pathogens also can induce the proliferation of antibodies that can cross-react with self-antigens, resulting in an autoimmune disease. The presence of these pathogens also causes oxidative stress through the production of reactive oxygen species, which is highly damaging. Since these pathogens have many ways of contributing to cardiovascular diseases, it has been hypothesized that treating the periodontal problems will help prevent the progression of cardiovascular disease. Several studies show that addressing periodontitis has resulted in decreased levels of inflammatory markers like C-reactive protein, interleukin-6, and fibrinogen, lower incidences of stroke, decreased blood pressure and lipid levels, and a lower left ventricular mass.

Bibliography: leaves 184-220.

Thesis (M.S.)--University of Michigan, 2004. / Includes bibliographical references.

Bibliography: leaves 107-138.

Orientador: Daniela Leal Zandim-Barcelos / Resumo: A movimentação dentária ortodôntica em pacientes adultos com histórico de doença periodontal requer um planejamento complexo, devido à reabsorção óssea, e a dificuldade de se obter uma ancoragem satisfatória por consequência da perda de elementos dentários. O objetivo deste trabalho foi avaliar as alterações longitudinais no perfil microbiológico e nos parâmetros clínicos periodontais de incisivos centrais superiores com periodonto reduzido durante e após término do movimento de intrusão dentária. Vinte pacientes com doença periodontal foram selecionados de acordo com os critérios do estudo. Estes pacientes deveriam apresentar incisivos centrais superiores vestibularizados e extruídos com perda de inserção ≥ 5 mm e indicação de intrusão dentária. Todos os sítios com atividade de doença periodontal receberam raspagem e alisamento radicular (RAR) e para o tratamento ortodôntico ser iniciado, os incisivos centrais superiores deveriam apresentar estabilidade no nível clínico de inserção após 90 dias do término do tratamento periodontal ativo. Os parâmetros clínicos Índice de placa (IP), Índice Gengival (IG), profundidade de sondagem (PS), nível clínico de inserção (NCI), recessão gengival (RG), sangramento à sondagem (SS) e tamanho de coroa clínica (TCC) foram avaliados antes do procedimento de RAR, no início do movimento de intrusão (T1- Baseline), durante o movimento de intrusão (90 e 180 dias), imediatamente após o término da intrusão ortodôntica (T2), 90 e 180 dias após o tér... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Orthodontic tooth movement in adult patients with a history of periodontal disease requires complex planning, due to bone resorption, and the difficulty of achieving satisfactory anchorage as a result of loss of dental elements. The objective of this study was to evaluate longitudinal changes in microbiology and clinical periodontal parameters of upper central incisors, in patients with reduced periodontium, before, during and after orthodontic intrusion. Twenty patients with periodontal disease were selected according to the study criteria. These patients should have vestibularized and extruded upper central incisors with insertion loss ≥ 5 mm and indication of dental intrusion. All sites with activity of periodontal disease received scaling and root planing (RAR) and for orthodontic treatment to be started, the upper central incisors should have stability in the clinical level of insertion after 90 days of the end of active periodontal treatment. Clinical parameters Plaque index (PI), Gingival index (GI), probing depth (PD), clinical level of insertion (CLI), gingival recession (GR), probing bleeding (PB) and clinical crown size (CCS) were evaluated before the RAR procedure, at the beginning of the intrusion movement (T1- Baseline), during the intrusion movement (90 and 180 days), immediately after the end of the orthodontic intrusion (T2), 90 and 180 days after the end of the intrusion treatment. Sample collections of gingival crevicular fluid (GFC) were performed during t... (Complete abstract click electronic access below) / Mestre

As doenças periodontais (DP) são precedidas em importância apenas pela cárie dentária como problema de saúde bucal coletiva no Brasil. Ambas são doenças infecciosas ainda muito prevalentes, entretanto é dada às DP uma importância questionavelmente secundária, pois não são sistematicamente investigadas e prevenidas em saúde pública. Pelo fato de sua prevalência ser atualmente desconhecida no Brasil, a alta freqüência das formas leves e moderadas das doenças periodontais na população como um todo e de suas formas mais graves em grupos ou indivíduos de risco, dentre estes os portadores de cardiopatias isquêmicas, motivou este estudo no Ambulatório de Cardiopatia Isquêmica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, cotejando os resultados com outros obtidos em grupo de pessoas não-cardiopatas atendidas na mesma instituição. Foi investigada a prevalência e gravidade das doenças periodontais, bem como a prevalência de seus fatores de risco, história médica da presença de doenças de interesse à periodontia (diabetes, hipertensão, acidente vascular cerebral) e comportamento relativo à higiene bucal. Dentre as 634 pessoas examinadas na fase de recrutamento dos participantes, 480 foram do grupo de pacientes cardiopatas isquêmicos e 154 de grupo de não-cardiopatas. Foram selecionados respectivamente de cada grupo, 58 e 62 participantes, na faixa etária de 30 a 79 anos, para a investigação periodontal. A média da idade foi de 53 anos em ambos os sexos para os pacientes cardiopatas e de 40 anos nos homens e 37 anos nas mulheres nos pacientes não-cardiopatas. Foram utilizados o Índice Periodontal Comunitário (IPC) e o índice de Perda de Inserção periodontal (PI), ambos recomendados pela OMS (1999). Os resultados mostraram um predomínio de sextantes nos escores indicativos das formas graves da DP entre os pacientes cardiopatas (74,1% contra 20,2%; p < 0,00001). Dentre os pacientes cardiopatas apenas 1,1% dos sextantes exibiram saúde periodontal, contra 32,0% nos pacientes não-cardiopatas (p < 0,00001). No tocante a história pregressa da DP, mensuradas através da perda de inserção, 6,0% dos sextantes não a exibiram entre os pacientes cardiopatas, contra 68,0% dos não-cardiopatas (p < 0,00001). Eram portadores de fatores de retenção de biofilme dental 100,0% dos pacientes cardiopatas e 82,3% dos pacientes não-cardiopatas (p < 0,001). Exigiam tratamento periodontal mais complexo, normalmente praticados por especialistas em periodontia, 94,8% dos pacientes cardiopatas contra 33,9% dos pacientes não-cardiopatas (p < 0,0001). Necessitavam de tratamento de bolsas > 6mm 79,3% dos pacientes cardiopatas contra 9,7% dos pacientes não-cardiopatas (p < 0,0001). Alguns fatores de risco comprovado e/ou provável às DP, foram investigados nos pacientes cardiopatas e pacientes não-cardiopatas: observou-se tabagismo em 10,4% e 33,9% (p < 0,01), respectivamente; alcoolismo em 44,8% e 24,2% (p < 0,02), respectivamente; diabetes em 29,3% e 1,6% (p < 0,0001), respectivamente; hipertensão arterial em 34,5% e 8,1% (p < 0,001), respectivamente. Conclusões: As DP mostraram-se muito prevalentes nos dois grupos estudados, sendo de maior gravidade nos pacientes com cardiopatia isquêmica. A elevada prevalência de fatores de risco às DP aponta para a necessidade de adoção de estratégias de intervenção para minimizá-los. / Periodontal diseases are preceded in importance only by dental caries as oral public health problem in Brazil. Both are infectious diseases and with high prevalences, however, a secondary importance is given to periodontal diseases because they are not routinely investigated and prevented at public health level. Presently its prevalence is not known in the Brazilian population. The high prevalence of mild and moderate forms of periodontal diseases in the general population, and its severe forms in specific groups or in high risk patients, as those with ischaemic coronary diseases, motivated this survey. It was carried out among patients from the Outpatient Clinic of Ischaemic Coronary Disease – Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo – and using for comparisons patients from other clinics of the same hospital. The prevalence and severity of periodontal diseases were investigated, as well as the prevalence of their risk factors, medical history of diseases with periodontic interest (diabetes, hypertension, stroke), and behaviour related to oral hygiene. During the recruitment phase, among 634 patients examined, 480 were from the group with cardiopathy and 154 from the group without cardiopathy. From each group were selected, respectively, 58 and 62 participants, aged 30 to 79 years for the periodontal investigation. Mean age was 53 years for both sexes in the group with cardiopathy and 40 years for men and 37 years for women in the group without cardiopathy. The Community Periodontal Index and the Attachment Periodontal Index, both recommended by the World Health Organization (1999), were used. Results showed a predominance of sextants in the scores indicating severe forms of periodontal diseases among patients with cardiopathy (74.1 vs. 20.2%; p< 0.00001). Among patients with cardiopathy, only 1.1% of the sextants showed periodontal health against 32.0% in the other group (p< 0.00001). Previous history of periodontal diseases, measured through lost of insertion, was present in 6.0% of the sextants in patients with cardiopathy and 68.0% in those without cardiopathy (p< 0.0001). All patients with cardiopathy and 82.3% of those without cardiopathy were carriers of retention factors of dental biofilm (p< 0.001). It was found that 94.8% of the patients with cardiopathy against 33.9% of the other group (p< 0.0001) required more complex periodontal treatment, usually performed by periodontal specialists. Treatment of sites &#8805; 6mmm was required by 79.3% of the patients with cardiopathy and by 9.7% from the other group (p< 0.0001). The frequency of confirmed or possible risk factors for periodontal diseases in the groups with and without cardiopathy were, respectively: smoking – 10.4 and 33.9% (p< 0.001); alcoholism – 44.8 and 24.2% (p< 0.02); diabetes – 29.3 and 1.6% (p< 0.0001); hypertension – 34.5 and 8.1% (p< 0.001). Conclusions: Periodontal diseases were highly prevalent in the two groups studied, but with higher severity among patients with cardiopathy. The high frequency of risk factors for periodontal diseases in both groups appointed to the need of intervention strategies towards these risk factors.

As doenças periodontais (DP) são precedidas em importância apenas pela cárie dentária como problema de saúde bucal coletiva no Brasil. Ambas são doenças infecciosas ainda muito prevalentes, entretanto é dada às DP uma importância questionavelmente secundária, pois não são sistematicamente investigadas e prevenidas em saúde pública. Pelo fato de sua prevalência ser atualmente desconhecida no Brasil, a alta freqüência das formas leves e moderadas das doenças periodontais na população como um todo e de suas formas mais graves em grupos ou indivíduos de risco, dentre estes os portadores de cardiopatias isquêmicas, motivou este estudo no Ambulatório de Cardiopatia Isquêmica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, cotejando os resultados com outros obtidos em grupo de pessoas não-cardiopatas atendidas na mesma instituição. Foi investigada a prevalência e gravidade das doenças periodontais, bem como a prevalência de seus fatores de risco, história médica da presença de doenças de interesse à periodontia (diabetes, hipertensão, acidente vascular cerebral) e comportamento relativo à higiene bucal. Dentre as 634 pessoas examinadas na fase de recrutamento dos participantes, 480 foram do grupo de pacientes cardiopatas isquêmicos e 154 de grupo de não-cardiopatas. Foram selecionados respectivamente de cada grupo, 58 e 62 participantes, na faixa etária de 30 a 79 anos, para a investigação periodontal. A média da idade foi de 53 anos em ambos os sexos para os pacientes cardiopatas e de 40 anos nos homens e 37 anos nas mulheres nos pacientes não-cardiopatas. Foram utilizados o Índice Periodontal Comunitário (IPC) e o índice de Perda de Inserção periodontal (PI), ambos recomendados pela OMS (1999). Os resultados mostraram um predomínio de sextantes nos escores indicativos das formas graves da DP entre os pacientes cardiopatas (74,1% contra 20,2%; p < 0,00001). Dentre os pacientes cardiopatas apenas 1,1% dos sextantes exibiram saúde periodontal, contra 32,0% nos pacientes não-cardiopatas (p < 0,00001). No tocante a história pregressa da DP, mensuradas através da perda de inserção, 6,0% dos sextantes não a exibiram entre os pacientes cardiopatas, contra 68,0% dos não-cardiopatas (p < 0,00001). Eram portadores de fatores de retenção de biofilme dental 100,0% dos pacientes cardiopatas e 82,3% dos pacientes não-cardiopatas (p < 0,001). Exigiam tratamento periodontal mais complexo, normalmente praticados por especialistas em periodontia, 94,8% dos pacientes cardiopatas contra 33,9% dos pacientes não-cardiopatas (p < 0,0001). Necessitavam de tratamento de bolsas > 6mm 79,3% dos pacientes cardiopatas contra 9,7% dos pacientes não-cardiopatas (p < 0,0001). Alguns fatores de risco comprovado e/ou provável às DP, foram investigados nos pacientes cardiopatas e pacientes não-cardiopatas: observou-se tabagismo em 10,4% e 33,9% (p < 0,01), respectivamente; alcoolismo em 44,8% e 24,2% (p < 0,02), respectivamente; diabetes em 29,3% e 1,6% (p < 0,0001), respectivamente; hipertensão arterial em 34,5% e 8,1% (p < 0,001), respectivamente. Conclusões: As DP mostraram-se muito prevalentes nos dois grupos estudados, sendo de maior gravidade nos pacientes com cardiopatia isquêmica. A elevada prevalência de fatores de risco às DP aponta para a necessidade de adoção de estratégias de intervenção para minimizá-los. / Periodontal diseases are preceded in importance only by dental caries as oral public health problem in Brazil. Both are infectious diseases and with high prevalences, however, a secondary importance is given to periodontal diseases because they are not routinely investigated and prevented at public health level. Presently its prevalence is not known in the Brazilian population. The high prevalence of mild and moderate forms of periodontal diseases in the general population, and its severe forms in specific groups or in high risk patients, as those with ischaemic coronary diseases, motivated this survey. It was carried out among patients from the Outpatient Clinic of Ischaemic Coronary Disease – Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo – and using for comparisons patients from other clinics of the same hospital. The prevalence and severity of periodontal diseases were investigated, as well as the prevalence of their risk factors, medical history of diseases with periodontic interest (diabetes, hypertension, stroke), and behaviour related to oral hygiene. During the recruitment phase, among 634 patients examined, 480 were from the group with cardiopathy and 154 from the group without cardiopathy. From each group were selected, respectively, 58 and 62 participants, aged 30 to 79 years for the periodontal investigation. Mean age was 53 years for both sexes in the group with cardiopathy and 40 years for men and 37 years for women in the group without cardiopathy. The Community Periodontal Index and the Attachment Periodontal Index, both recommended by the World Health Organization (1999), were used. Results showed a predominance of sextants in the scores indicating severe forms of periodontal diseases among patients with cardiopathy (74.1 vs. 20.2%; p< 0.00001). Among patients with cardiopathy, only 1.1% of the sextants showed periodontal health against 32.0% in the other group (p< 0.00001). Previous history of periodontal diseases, measured through lost of insertion, was present in 6.0% of the sextants in patients with cardiopathy and 68.0% in those without cardiopathy (p< 0.0001). All patients with cardiopathy and 82.3% of those without cardiopathy were carriers of retention factors of dental biofilm (p< 0.001). It was found that 94.8% of the patients with cardiopathy against 33.9% of the other group (p< 0.0001) required more complex periodontal treatment, usually performed by periodontal specialists. Treatment of sites &#8805; 6mmm was required by 79.3% of the patients with cardiopathy and by 9.7% from the other group (p< 0.0001). The frequency of confirmed or possible risk factors for periodontal diseases in the groups with and without cardiopathy were, respectively: smoking – 10.4 and 33.9% (p< 0.001); alcoholism – 44.8 and 24.2% (p< 0.02); diabetes – 29.3 and 1.6% (p< 0.0001); hypertension – 34.5 and 8.1% (p< 0.001). Conclusions: Periodontal diseases were highly prevalent in the two groups studied, but with higher severity among patients with cardiopathy. The high frequency of risk factors for periodontal diseases in both groups appointed to the need of intervention strategies towards these risk factors.