The essential role of toll like receptor-4 in the control of Aggregatibacter actinomycetemcomitans infection in mice

Objective: Aggregatibacter actinomycetemcomitans is an oral Gram-negative bacterium that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll-like receptors (TLRs). In this study, we evaluated the role of TLR4 in the control of A. actinomycetemcomitans infection. Material and Methods: We examined the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR4(-/-) mice. The production of cytokines was evaluated by ELISA. The bacterial load was determined by counting the number of colony-forming units per gram of tissue. Results: The results showed that TLR4-deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. However, the absence of TLR4 facilitated the A. actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in the periodontal tissue of TLR4(-/-) mice. We observed a significant reduction in the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta in the periodontal tissue of TLR4(-/-) mice. Conclusion: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.

Absence of TLR2 influences survival of neutrophils after infection with Candida albicans

Candida albicans is an opportunistic pathogen, which causes local and/or disseminated diseases in immunosuppressed humans. Phagocytic cells play a critical role in the immune response against C. albicans. Toll like receptors (TLR) are important in the identification of invading microorganisms and in the regulation of neutrophil survival. TLR2 has been shown to participate in the response against pathogenic yeasts and to increase the functional life span of neutrophils. In view of these observations, we studied the involvement of TLR2 in neutrophil function after C. albicans infection. The absence of TLR2 resulted in lower chemotaxis of neutrophils to the site of infection. This in turn was associated with lower levels of chemokines from neutrophils, facilitating the dissemination of the pathogen to the lymph nodes and spleen. A high frequency of apoptotic neutrophils and macrophages in the inflammatory exudates from TLR2(-/-) mice was found. In addition, the phagocytic activity of neutrophils and macrophages, nitric oxide production and myeloperoxidase, activity were diminished in cells from TLR2(-/-) mice. Together, these data demonstrate the importance of TLR2 signals for neutrophils activation and survival after C albicans infection.

The Role of Toll-Like Receptor 2 in the Recognition of Aggregatibacter actinomycetemcomitans

Background: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) is a Gram-negative bacterium present in the oral cavity and is usually associated with localized aggressive periodontitis. Isolated antigens from A. actinomycetemcomitans can activate innate immune cells through Toll-like receptors (TLRs), which are molecules that recognize structural components conserved among microorganisms. In this study, we evaluate the role of TLR2 in the recognition of A. actinomycetemcomitans. Methods: Macrophages and neutrophils from knockout mice with targeted disruption of TLR2 (TLR2(-/-) mice) and wild-type mice were collected and used for the subsequent assays. The production of cytokines and chemokines was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of apoptotic cells was determined by flow cytometry. In addition, the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR2(-/-) mice were examined. Results: The results show that TLR2-deficient mice developed more severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly higher bone loss and inflammatory cell migration to periodontal tissues. The inflammatory cell influx into the peritoneal cavities of TLR2(-/-) mice was three-fold lower than that observed for the littermate controls. A significantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1 beta as well as the chemokine CC-ligand-5 in the peritoneal cavities of TLR2(-/-) mice was observed. In addition, a high frequency of apoptotic cells in the inflammatory exudates from TLR2(-/-) mice was observed. Phagocytosis and nitric oxide production was diminished in cells from TLR2(-/-) mice, facilitating the dissemination of the pathogen to the spleen. Conclusion: The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection. J Periodontot 2009,80:2070-2019.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8(+)PD1(+) in PBMC when compared with controls. On the other hand, increased frequency of CD4(+) and CD8(+) T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-gamma and higher levels of TGF-beta were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

Inducible nitric oxide synthase-deficient mice show exacerbated inflammatory process and high production of both Th1 and Th2 cytokines during paracoccidioidomycosis

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by fungus Paracoccidioides brasiliensis. To analyze the influence of inducible nitric oxide synthase (iNOS) in this disease, iNOS-deficient (iNOS(-/-)) and wild-type (WT) mice were infected intravenously with P. brasiliensis 18 isolate. We found that, unlike WT mice, iNOS(-/-) mice did not control fungal proliferation, and began to succumb to infection by day 50 after inoculation of yeast cells. Typical inflammatory granulomas were found in WT mice, while, iNOS(-/-) mice presented incipient granulomas with intense inflammatory process and necrosis. Additionally, splenocytes from iNOS(-/-) mice did not produce nitric oxide, however, their proliferative response to Con-A was impaired, just like infected WT mice. Moreover, infected iNOS(-/-) mice presented a mixed pattern of immune response, releasing high levels of both Th1 (IL-12, IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines. These data suggest that the enzyme iNOS is a resistance factor during paracoccidioidomycosis by controlling fungal proliferation, by influencing cytokines production, and by appeasing the development of a high inflammatory response and consequently formation of necrosis. However, iNOS-derived nitric oxide seems not being the unique factor responsible for immunosuppression observed in infections caused by P. brasiliensis. (c) 2008 Elsevier Masson SAS. All rights reserved.

Characterization of CD4(+)CD25(+) natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis

Periodontitis is an infectious disease, where putative periodontopathogens trigger chronic inflammatory and immune responses against periodontal structures, in which an unbalanced host response is also determinant to the disease outcome. It is reasonable to assume that patient susceptibility to periodontal tissue destruction could be determined by the balance between the response against periodontopathogens and regulatory mechanisms of these events mediated by suppressive T cells. In the present study, we identified and characterized natural regulatory T cells ( Tregs) in the inflammatory infiltrate of human chronic periodontitis ( CP) with emphasis on phenotypic analyses that were carried out to address the participation of Tregs in CP. Results showed that patients with CP presented increased frequency of T lymphocytes and CD4(+)CD25(+) T cells in the inflammatory infiltrate of gingival tissues. These cells exhibited the phenotypic markers of Tregs such as forkhead box p3 ( Foxp3), CTLA- 4, glucocorticoidinducible TNFR, CD103, and CD45RO and seemed to be attracted to the inflammation site by the chemokines CCL17 and CCL22, as their expression and its receptor CCR4 were increased in CP patients. Moreover, besides the increased detection of Foxp3 mRNA, diseased tissues presented high expression of the regulatory cytokines IL-10 and TGF-beta. In addition, the inflammatory infiltrate in CP biopsies was composed of CD25(+)Foxp3(+) and CD25(+)TGF-beta(+) cells, thus corroborating the hypothesis of the involvement of Tregs in the pathogenesis of CP. Finally, these results indicate that Tregs are found in the chronic lesions and must be involved in the modulation of local immune response in CP patients.

Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. To investigate the role of interleukin (IL)-12 in this disease, IL-12p40(-/-) deficient mice (IL-12p40(-/-)) and wild type mice (WT) were infected intravenously with viable yeast cells of P. brasiliensis 18 isolate. We found that, unlike WT mice, IL-12p40(-/-) mice did not control fungal proliferation and dissemination and succumbed to infection by day 21 after inoculation. Additionally, IL-12p40(-/-) mice presented a higher number of granulomas/mm(2) in lung tissue than WT mice, and showed unorganized granulomas containing high numbers of yeast cells. Moreover, IL-12p40(-/-) mice did not release detectable levels of IFN-gamma, but they produced high levels of IL-10, as well as IgG1 antibody. Additionally, splenocytes from both infected IL-12p40(-/-) and WT mice exhibited a suppressed Con-A-induced T cell proliferative response. Our findings suggest that the IL-12p40 subunit mediates resistance in paracoccidioidomycosis by inducting IFN-gamma production and a Th1 immune response

Orthodontic-surgical treatment of Class III malocclusion with extraction of an impacted canine and multi-segmented maxillary surgery

Establishment of a treatment plan is based on efficacy and easy application by the clinician, and acceptance by the patient. Treatment of adult patients with Class III malocclusion might require orthognathic surgery, especially when the deformity is severe, with a significant impact on facial esthetics. Impacted teeth can remarkably influence treatment planning, which should be precise and concise to allow a reasonably short treatment time with low biologic cost. We report here the case of a 20-year-old man who had a skeletal Class III malocclusion and impaction of the maxillary right canine, leading to remarkable deviation of the maxillary midline; this was his chief complaint. Because of the severely deviated position of the impacted canine, treatment included extraction of the maxillary right canine and left first premolar for midline correction followed by leveling, alignment, correction of compensatory tooth positioning, and orthognathic surgery to correct the skeletal Class III malocclusion because of the severe maxillary deficiency. This treatment approach allowed correction of the maxillary dental midline discrepancy to the midsagittal plane and establishment of good occlusion and optimal esthetics. (Am J Orthod Dentofacial Orthop 2010;137:840-9)

Projeto porto sem papel

O setor portu??rio envolve uma grande diversidade de usu??rios e ??rg??os intervenientes, cada um com suas normas e processos pr??prios. Tal situa????o, associada ao fato de que todo o fluxo de informa????es e documentos solicitados pelos ??rg??os aos usu??rios era realizado em papel, n??o permitia clareza e efici??ncia na troca de informa????es. A falta de dados confi??veis e tempestivos tamb??m n??o permitia efetividade na gest??o e planejamento do setor. Nesse contexto, foi implantado, na fase inicial do Porto Sem Papel, um sistema que permitia a troca de informa????es e documentos digitais entre os usu??rios e os diversos ??rg??os intervenientes. Assim, os fluxos de informa????es e documentos, que antes eram realizados em papel, passaram a ser realizados digitalmente, dando agilidade e transpar??ncia aos processos. Cabe destacar que todas as informa????es est??o presentes agora em uma base ??nica de dados, o que permite a realiza????o de an??lises que subsidiem a gest??o e a melhoria de processos no setor portu??rio

Log??stica de distribui????o e entrega dos objetos do Programa Nacional do Livro Did??tico (PNLD)

O Programa Nacional do Livro Did??tico ??? PNLD, administrado pelo Fundo Nacional de Desenvolvimento da Educa????o ??? FNDE, utiliza, desde 1994, os servi??os da Empresa Brasileira de Correios e Tel??grafos - ECT, para levar ??s escolas p??blicas mais de uma centena de milh??es de livros did??ticos. V??rios eram os problemas a serem resolvidos. Antes de a ECT assumir os servi??os, somente 25% dos livros eram entregues antes do in??cio do ano letivo e o restante entregue durante ano, prejudicando de uma sobre maneira, n??o s?? alunos e professores, mas todo o planejamento de ensino. A aus??ncia de um controle efetivo da entrega dos livros, aliado ao endere??amento incorreto, gerava um de alto ??ndice de reclama????o quanto ao n??o recebimento dos objetos. Com as a????es descritas nesse relato, foi poss??vel aumentar o n??mero de crian??as/adolescentes estudantes de escolas p??blicas, com cobertura de todos os munic??pios brasileiros, os quais s??o na realidade os grandes clientes de todo o processo. Certamente que o sucesso da opera????o envolve a FNDE e a ECT, sendo que nesta ??ltima ?? imprescind??vel a perfeita sintonia entre todas as ??reas

Sa??de e preven????o: um passo para a melhoria da qualidade de vida

Com o objetivo de desenvolver uma pol??tica de qualidade total, o INSS percebeu a necessidade de melhorar a qualidade de vida dos servidores de modo a obter a melhoria da qualidade do trabalho. Com esta finalidade, foi proposto o Programa ???Sa??de e Preven????o???, focado no diagn??stico biopsicossocial dos servidores, com o planejamento de a????es que contemplam aspectos da sa??de f??sica, ps??quica e social e dimens??es educacionais associadas ?? valoriza????o do indiv??duo no trabalho e do seu desenvolvimento pessoal e profissional. A iniciativa alcan??ou a melhoria da qualidade de vida e de trabalho dos servidores, a viabiliza????o de uma pol??tica integrada, voltada para a????es preventivas, orientadoras e curativas, contemplando as necessidades das unidades e subunidades, a elimina????o de a????es pulverizadas, otimizando a rela????o de custo/benef??cio do investimento em sa??de no trabalho e uma maior efici??ncia no atendimento m??dico dos servidores, mediante a informatiza????o e a atua????o a partir do diagn??stico biopsicossocial

Concess??o de bolsas de doutorado no CNPq: o primeiro julgamento sem papel

A experi??ncia consistiu na implementa????o de esquema de recep????o e tratamento de formul??rios de solicita????o de bolsas de doutorado no CNPq eliminando totalmente o uso de papel. Fazendo uso do software de gerenciamento de imagens KeyFile, acoplado ao sistema de ger??ncia de bancos de dados Oracle, e de um conjunto de softwares desenvolvidos no CNPq e por empresas contratadas, o fluxo de julgamento de bolsas de doutorado, desde a recep????o do formul??rio de solicita????o at?? a implementa????o e pagamento das bolsas, passando por todas as etapas intermedi??rias de forma????o de processo e julgamento de m??rito, foi montado em ambiente inteiramente virtual. Mesas virtuais de trabalho, acomodando processos virtuais, organizados em caixas e arquivos virtuais, est??o dispon??veis aos t??cnicos do CNPq e membros da comunidade cient??fica envolvidos nos fluxos de concess??o de bolsas. Os formul??rios de solicita????o podem ser conseguidos e enviados pelos interessados por meio da Internet (ou em disquetes por correio normal),sendo que todo o processo de montagem de processos ?? feito virtual e automaticamente. Utilizando-se t??cnicas de refer??ncias a imagens, os processos tramitam sem sair do arquivo virtual em que s??o armazenados

Pergunte ao prefeito: divulga????o e controle de verbas p??blicas na educa????o

O Fundo Nacional de Desenvolvimento da Educa????o (FNDE) ?? o respons??vel pela capta????o e administra????o do sal??rio-educa????o, contribui????o de 2,5% que incide sobre as folhas de pagamento das empresas p??blicas e privadas. Entretanto, nem sempre os recursos chegavam integralmente ??s salas de aula. A solu????o foi encontrada na divulga????o da informa????o. Em coopera????o com o FNDE, a Radiobr??s passou a anunciar, nos intervalos da ???Voz do Brasil???, diariamente de segunda a sexta-feira, a lista de munic??pios contemplados, mesclada com spots de curta dura????o que explicavam a natureza dos conv??nios e estimulavam a a????o da comunidade com o slogan: ???Pergunte aos vereadores. Pergunte ao prefeito???. A iniciativa aumentou a efici??ncia na aplica????o dos recursos destinados ?? educa????o. O n??mero de den??ncias, encaminhadas ?? auditoria do FNDE, cresceu de 100 por ano para 20 por dia. Praticamente desapareceram as solicita????es de audi??ncias de prefeitos ao FNDE, a fim de influenciar a libera????o das verbas. A partir de junho de 1995, os recursos passaram a ser alocados diretamente ??s escolas em todo o Pa??s, o que aumentou o alcance do programa, sendo que o n??mero de cartas tipo contracheque expedidas cresceu de 100 mil para um milh??o

Caf?? com debate: federalismo e integra????o nacional

Servidores p??blicos de diferentes ??rg??os do governo federal participaram na manh?? desta ter??a-feira (17) de mais uma edi????o do Caf?? com Debate. Para analisar o tema ???Federalismo e Integra????o Nacional???, estiveram na ENAP o presidente do F??rum das Federa????es, o canadense George Anderson, a cientista pol??tica Marta Arretche e o soci??logo Vicente Trevas. A experi??ncia profissional dos convidados possibilitou analisar diferentes aspectos do tema. George Anderson fez um apanhado sobre o desenvolvimento do federalismo no contexto mundial, destacando alguns pontos caracter??sticos do modelo brasileiro. Marta Arretche, que ?? docente na Universidade de S??o Paulo, abordou a quest??o sob a ??tica da Academia. A apresenta????o do ponto de vista do governo federal ficou a cargo de Vicente Trevas, que coordenou a Subchefia de Assuntos Federativos da Secretaria de Rela????es Institucionais da Presid??ncia da Rep??blica e atualmente assessora a Presid??ncia da Caixa Econ??mica Federal