Clopidogrel Enhances Periodontal Repair in Rats Through Decreased Inflammation

Aim We hypothesized that platelet inactivation induced by drugs might interfere with periodontal repair in experimental periodontitis by suppressing the release of biological mediators from platelets at the site of injury. Material and Methods 60 rats were randomly assigned to 6 groups (n=10) and ligatures were placed around lower first molars of three groups. The other three groups were used as negative controls. Ligatures were removed after 10 days of periodontitis induction and all groups were submitted to treatment with aspirin (Asp) (30 mg/kg), clopidogrel (Clop) (75 mg/kg) or NaCl 0.9% intragastrically once daily for 3 days. Periodontal tissue was assessed by the measurement of CXCL12, CXCL4, CCL5 and PDGF by ELISA; histomorphometric analysis of PMN infiltration, attachment loss, bone loss and osteoclast numbers and quantification of blood vessels by imunnohistochemistry. Results During periodontal repair and treatment with NaCl 0.9%, CCL5 was decreased and CXCL12 increased when compared to negative control groups. Asp and Clop did not affect CCL5 expression, decreased CXCL12 but only Clop decreased CXCL4 and PDGF content compared to saline-treated animals. Clop increased blood vessel number, reduced PMN count, and decreased attachment and bone loss, also decreased osteoclast number in animals submitted or not to periodontal repair. Conclusion Systemic administration of Clop during 3 days improved the repair process associated with experimental periodontal disease, suggesting that it may have therapeutic value under situations where tissues undergo a transition from inflammation to repair

Relatório de estágio profissional

Este trabalho encontra-se estruturado em quatro capítulos. Inicialmente será abordada a importância da elaboração do relatório, a metodologia utilizada, a caracterização do Jardim-Escola, assim como do meio em que se insere e a pertinência deste relatório. O primeiro capítulo é composto pelos relatos diários que refletem os momentos mais pertinentes dos dias de estágio, nas várias turmas. Após cada relato diário seguem- -se as inferências, em que são mencionados pontos de vista pessoais ou explicações que permitam uma melhor compreensão dos relatos antecedidos. Como conclusão, de cada dia mencionado, fundamentar-se-á os temas e metodologias vividas em sala de aula. No segundo capítulo dá-se relevância à planificação de aulas dadas durante o estágio, especificamente em cada área e domínio curricular: Conhecimento do Mundo, Matemática (pré-escolar), Linguagem oral e abordagem à escrita, Língua Portuguesa, Matemática (1.º Ciclo) e Estudo do Meio. Em seguida serão igualmente abordadas as planificações elaboradas para a Prova Prática de Avaliação da Capacidade Profissional. Cada fundamentação será devidamente fundamentada. O terceiro capítulo explorará a avaliação, introduzindo seis dispositivos de avaliação elaborados para as várias áreas curriculares. O quarto capítulo é constituído por uma reflexão final sobre este relatório, em que serão apresentadas algumas limitações, bem como sugestões para novas pesquisas

The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis

Abstract\ud \ud Background\ud In experimental periodontitis, non-steroidal antiinflammatory drugs (NSAIDs) effectively inhibit the resultant alveolar bone loss. However, their deleterious gastric effects, observed in both animals and humans, dramatically limit their long-term use. It has been proven that the addition of a hydrogen sulfide (H2S)-releasing moiety to classical NSAID structures results in antiinflammatory compounds with improved gastric safeness. In this way, we decided to compare the effects of naproxen with its H2S-releasing derivative ATB-346 on ligature-induced periodontitis in rats.\ud \ud \ud Methods\ud Male Holtzman rats had a cotton ligature placed subgingivally around the lower right first molar during 7 days. During this period, groups of animals were daily treated with Na2S (a spontaneous H2S donor) or equimolar oral doses of naproxen (10 mg/kg) or ATB-346 (16 mg/kg). The mandibles were finally collected for histological analysis, radiographical measurements of alveolar bone loss and micro-computed tomography (μCT) analysis. Interleukin (IL)-1β, IL-6 and IL-10 were quantified in gingiva samples, and the stomachs were also collected for scoring of tissue damage and measurement of myeloperoxidase (MPO, a marker of granulocyte infiltration).\ud \ud \ud Results\ud Ligature-induced bone loss was significantly inhibited by all the treatments, although only ATB-346 treatment resulted in significant inhibition of bone defect and other histological characteristics (such as flatness of the gingival epithelium, chronic inflammatory cell infiltration and loss of connective tissue in the gingival papillae). Both naproxen and ATB-346 inhibited the increase of gingival IL-1β and IL-6 secondary to periodontitis, but IL-10 was unaffected. Significant damage and increased MPO contents were only found in the stomachs of the naproxen-treated animals.\ud \ud \ud Conclusion\ud The H2S-releasing moiety in the ATB-346 compound not only does not impair the effects of the parent naproxen on periodontitis, but also improves bone quality and prevents the gastric mucosa damage due to prostaglandin inhibition, thus configuring a potentially new adjuvant therapy for periodontal diseases.This study has been supported by the State of São Paulo Research\ud Foundation (FAPESP); LCS, SKPC and MNM are recipients of fellowships from the Brazilian National Council for Scientific and Technological Development (CNPq)

Porphyromonas endodontalis in chronic periodontitis: a clinical and microbiological cross-sectional study

Although previous studies have shown the presence of Porphyromonas endodontalis in chronic periodontitis associated with periapical lesions, the occurrence of this pathogen in diseased periodontal sites without periapical lesions has been poorly investigated.The aims of this study were to quantify P. endodontalis in patients with chronic periodontitis without periapical lesions, to evaluate the potential correlation of P. endodontalis with Porphyromonas gingivalis and Tannerella forsythia, and to evaluate the ability of periodontal treatment to reduce these pathogens.Patients with generalized chronic periodontitis were selected by recording clinical attachment level (CAL), probing depth (PD), and bleeding on probing (BOP). Subgingival samples from 30 diseased nonadjacent sites (CAL ≥ 5 mm, PD between 5 and 7 mm and positive BOP) and 30 healthy nonadjacent sites (PD ≤ 3 mm and negative BOP) were collected and subjected to microbial analysis by quantitative polymerase chain reaction (qPCR) The variables of age, PD, CAL and BOP of all individuals were analyzed using the paired t-test (GrapPad Prism5®). Data of bacteria quantification were subjected to a normality test (D'Agostino-Pearson Test). For bacterial correlation analysis, the Spearman correlation was used.Our results showed that diseased sites had significantly higher levels of P. endodontalis compared to healthy sites, similar to the results obtained for P. gingivalis and T. forsythia. The numbers of all bacterial species were reduced significantly after mechanical periodontal treatment. P. endodontalis was significantly correlated with the presence of T. forsythia and P. gingivalis in the diseased group.Our results suggest that there is a high prevalence of P. endodontalis, P. gingivalis and T. forsythia in periodontitis sites and that mechanical periodontal treatment is effective at reducing the pathogens studied

Eco-epidemiological analysis of rickettsial seropositivity in rural areas of Colombia: A multilevel approach

ABSTARCT: Rickettsiosis is a re-emergent infectious disease without epidemiological surveillance in Colombia. This disease is generally undiagnosed and several deadly outbreaks have been reported in the country in the last decade. The aim of this study is to analyze the eco-epidemiological aspects of rickettsial seropositivity in rural areas of Colombia where outbreaks of the disease were previously reported. A cross-sectional study, which included 597 people living in 246 households from nine hamlets in two municipalities of Colombia, was conducted from November 2015 to January 2016. The survey was conducted to collect sociodemographic and household characteristics (exposure) data. Blood samples were collected to determine the rickettsial seropositivity in humans, horses and dogs (IFA, cut-off = 1/128). In addition, infections by rickettsiae were detected in ticks from humans and animals by real-time PCR targeting gltA and ompA genes. Data was analyzed by weighted multilevel clog-log regression model using three levels (person, household and hamlets) and rickettsial seropositivity in humans was the main outcome. Overall prevalence of rickettsial seropositivity in humans was 25.62% (95%CI 22.11-29.12). Age in years (PR = 1.01 95%CI 1.01-1.02) and male sex (PR = 1.65 95%CI 1.43-1.90) were risk markers for rickettsial seropositivity. Working outdoors (PR = 1.20 95%CI 1.02-1.41), deforestation and forest fragmentation for agriculture use (PR = 1.75 95%CI 1.51-2.02), opossum in peridomiciliary area (PR = 1.56 95%CI 1.37-1.79) and a high proportion of seropositive domestic animals in the home (PR20-40% vs 40% vs <20% = 3.14 95%CI 2.43-4.04) were associated with rickettsial seropositivity in humans. This study showed the presence of Rickettsia antibodies in human populations and domestic animals. In addition, different species of rickettsiae were detected in ticks collected from humans and animals. Our results highlighted the role of domestic animals as sentinels of rickettsial infection to identify areas at risk of transmission, and the importance of preventive measures aimed at curtailing deforestation and the fragmentation of forests as a way of reducing the risk of transmission of emergent and re-emergent pathogens

Aspectos morfometricos e estererometricos do aumento gengival induzido pela ciclosporina

Orientador: Oslei Paes de AlmeidaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A csa é a principal droga imunossupressora, usada na prevenção da rejeição de enxertos em transplantes alogênicos. Aumento gengival é um dos efeitos colaterais da csa, e o principal na boca. O objetivo deste trabalho foi avaliar o aumento gengival de ratos tratados diariamente com 10 mg/kg de peso corporal de csa, durante 60 dias, por via subcutânea, assim como a regressão do aumento gengival após a interrupção do tratamento. Também foi verificado os efeitos da dieta cariogênica e xerostomia no aumento gengival. Todos os ratos tratados com csa desenvolveram aumento gengival, com aumento da espessura do epitélio bucal, da altura e largura do tecido conjuntivo, e da densidade volumétrica de fibroblastos e fibras colágenas. A dieta cariogênica e a xerostomia não modificaram as características da gengiva dos ratos normais dos tratados com csa. Cinco a 90 dias após a interrupção do tratamento com csa, houve diminuição progressiva do volume gengival e da densidade de fibras e fibroblastos. A diminuição foi mais acentuada nos períodos iniciais (10 dias), mas mesmo após 90 dias não retomou aos valores normaisAbstract: Cycloporin is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Csa can cause various side effects including gingival overgrowth. The aim of this work was to evaluate the gingival overgrowth of rats treated daily with 10mg/kg of body weight of csa, during 60 days, subcutaneosly, as well as the regression of gingival overgrowth after the interruption of treatment. The efects of a cariogenic diet and xerostomia were also considered. All rats treated with csa developed gingival overgrowth, with increased thickness of the epithelium, height and wideness of the connective tissue. The density of fibroblasts and collagen fibers, also increased. The cariogenic diet and xerostomia did not modify the characteristics of the gingiva of either normal and csa treated rats 5 to 90 days after the interruption of treatment with cyclosporin, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblasts densities. The reduction was more exuberant in the initial periods, but after 90 days did not return to the normal valuesDoutoradoBiologia e Patologia Buco-DentalDoutor em Odontologi

Cyclosporin A-induced new cementum formation: a morphometric evaluation in the periapical region of rats

Cyclosporin A (CsA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Recent studies have shown that CsA stimulates deposition of cementum on root surfaces. The aim of this study was to evaluate the periapical cementum thickness and the apical foramen width in CsA-treated rats. Rats weighing 50 g were treated with a daily injection of 10 mg/kg body weight of CsA in the chow for 60 days. The cementum of the mandibular 1st molars was histologically and morphometricaly examined by analysis of 5-microm-thick serial buccolingual paraffin sections stained with hematoxylin and eosin. Histometric and stereologic analyses revealed the presence of large amounts of cementum in all root surfaces, particularly abundant in the periapical region and obliterating the foramen. The volume density of cementoblasts did not increase. Five to 90 days after the termination of CsA therapy, there was no reduction of cementum thickness. These results suggest that cementum deposition is not reversible after cessation of CsA treatment.Ciclosporina A (CsA) é um potente imunossupressor usado no transplante de órgãos e no tratamento de várias doenças autoimunes. Recentes estudos têm demonstrado que a CsA estimula a deposição de cemento na superfície radicular. O objetivo deste estudo foi de avaliar a espessura do cemento periapical e largura do forame apical em ratos tratados com CsA. Os ratos pesavam 50 g e foram tratados com doses diárias de 10 mg/kg de peso corporal de CsA no período de 60 dias. O cemento do primeiro molar inferior foi examinado histologicamente e morfometricamente por análises de cortes em parafina com 5µm de espessura no sentido vestíbulo-lingual e corados com hematoxilina e eosina. As análises histométricas e estereológicas revelaram a presença de largos depósitos de cemento em todas as superfícies radiculares, particularmente maior na região periapical e obliterando o forame. A densidade volumétrica dos cementoblastos não foi aumentada. No período de 5 a 90 dias após o término da terapia com CsA, não houve redução na espessura do cemento. Estes resultados sugerem que o depósito de cemento não é reversível após o tratamento com CsA ser cessado