Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro

Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.

Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

Rendering peacekeeping instrumental? The Brazilian approach to United Nations peacekeeping during the Lula da Silva years (2003-2010)

The article analyses how Brazilian state actions and policies regarding peace operations during the Presidency of Lula da Silva relate to the country's positions and attitudes towards United Nations peacekeeping. It argues that the inconsistencies identified on the Brazilian positions reflect the lack of a clear strategic horizon guiding the country's participation in UN peacekeeping, which consequentially hinders the country emergence as a great power.

Security issues during Lula's administration: from the reactive to the assertive approach

Brazil's security agenda during Lula's administration was not homogeneous through the two mandates: the first tenure (2002-2006) revealed a reactive approach towards security topics, while the second one (2006-2010) was more assertive. More specifically, the shift occurred in terms of both its geographical scope - once it incorporated global issues in a more systematic way -, and instruments through which the security agenda was exercised, given the multilateral initiative of Unasur's CDS

The rights approach to local public management: experiences from Brazil

The Fundação Getulio Vargas, São Paulo, Public Management and Citizenship Program was set up in 1996 with Ford Foundation support to identify and disseminate Brazilian subnational government initiatives in service provision that have a direct effect on citizenship. Already, the program has 2,500 different experiences in its data bank, the results of four annual cycles. The article draws some initial conclusions about the possibilities of a rights-based approach to public management and about the engagement of other agencies and civil society organizations.

Budgeting and resource allocation in universities: a public choice approach

The calls for colleges and universities to improve their productivity are coming thick and fast in Brazil. Many studies are suggesting evaluation systems and external criteria to control the quality of teaching and research in universities. Since universities and colleges are not profit-oriented organizations (considering only the legitimate and serious research and teaching organizations, of course), the traditional microeconomics and administrative variables used to measure efficiency do not have any direct function. An alternative would be to create an "as if" market control system to evaluate performance in universities and colleges. Internal budget and resources allocation mechanism can be used as incentive instruments to improve quality and productivity. It will be the main issue of this article.

Teaching and learning production and operations management: the journey from identity crisis to a cross, disciplinary approach

Este artigo tem suas raízes em algumas questões relacionadas à "forma" e ao "conteúdo" do que nós, professores, ensinamos na área de Administração da Produção e Operações. Inicialmente, descrevo a evolução histórica desse campo no Brasil. Em seguida, discuto a crise de identidade que o campo está sofrendo. Com o objetivo de apresentar respostas para essa situação, apresento seis propostas para o desenvolvimento e consolidação do campo. Finalmente, descrevo uma iniciativa prática, envolvendo uma disciplina específica da área, ensinada para alunos de pós-graduação. Essa iniciativa enfatiza a "dimensão do conteúdo" (de uma abordagem técnico-operacional para uma abordagem estratégico-gerencial) como também a "dimensão da forma" (do foco no ensino para o foco no aprendizado). O sucesso dessa experiência em curso confirma a coerência da agenda proposta e induz futuros aperfeiçoamentos.

Intensidade tecnológica e sistemas de trabalho de alto desempenho: a contingent approach

Este artigo analisa o efeito moderador que a intensidade tecnológica do ambiente no qual a empresa atua exerce na relação entre os Sistemas de Trabalho de Alto Desempenho (STAD) e o desempenho operacional da empresa. Estudamos esse efeito moderador potencial em uma amostra de 593 empresas industriais espanholas divididas em duas sub-amostras: empresas industriais de alta (n1=301) e baixa (n2=292) tecnologia. Os resultados mostram que os STAD realmente influenciam o desempenho operacional das empresas de alta intensidade tecnológica, enquanto nas empresas de baixa intensidade tecnológica nenhum efeito é observado.

Theory of reasoned action for continuous improvement capabilities: a behavioral approach

The importance of interaction between Operations Management (OM) and Human Behavior has been recently re-addressed. This paper introduced the Reasoned Action Theory suggested by Froehle and Roth (2004) to analyze Operational Capabilities exploring the suitability of this model in the context of OM. It also seeks to discuss the behavioral aspects of operational capabilities from the perspective of organizational routines. This theory was operationalized using Fishbein and Ajzen (F/A) behavioral model and a multi-case strategy was employed to analyze the Continuous Improvement (CI) capability. The results posit that the model explains partially the CI behavior in an operational context and some contingency variables might influence the general relations among the variables involved in the F/A model. Thus intention might not be the determinant variable of behavior in this context.

A new approach for measuring corporate reputation

This study describes the concept of corporate reputation and reviews some of the major points that exist when it comes to measuring it. It thus suggests a new index for measurement and its advantages and disadvantages are pointed out. The consistency of the seven key variables for the collecting indicator is described by the results of a factor analysis and correlations. Finally, the indicator is put to test by gathering the perception of corporate reputation of 1500 individuals for 69 companies belonging to 15 different industrial sectors, in Peru. The results indicate that the proposed index variables are not necessarily of greatest interest to the study sample in which companies have a better performance. Also greater memorial companies aren't necessarily those that enjoy a greater corporate reputation. Managerial implications for the organizations in the process of managing and monitoring the dimensions involved of this key asset are also referenced.