Gamma-delta T lymphocytes coordinate eosinophil influx during allergic responses

Tissue eosinophil infiltration, which is a hallmark of allergic and helminthic diseases, is mainly coordinated by T lymphocytes, via the production of eosinophilotactic chemokines. Among T lymphocyte subsets, lymphocytes expressing gamma delta TCR have been determined as a key factor for eosinophil accumulation via direct and indirect mechanisms. This knowledge is strongly supported by the fact that, in different experimental models of eosinophilic airway inflammation and helminth-induced Th2 lung inflammation, an evident tissue accumulation of gamma delta T lymphocytes is observed. In addition, the depletion of gamma delta T lymphocytes is correlated with the impairment of eosinophil accumulation in inflamed tissue. Gamma delta T lymphocytes are non-conventional T lymphocytes, which comprise a minor T lymphocyte subset, mainly distributed in the tissue, and present crucial roles in innate and acquired immune responses. Gamma delta T lymphocytes recognize several danger- and pathogen-associated molecular pattern molecules and stress antigens in a MHC-independent fashion and can provide rapid tissue-specific responses, via the production of a wide range of chemical mediators capable to modulate other cell populations. These mediators include chemoattractant cytokines and chemokines that attract eosinophils into the tissue by either direct recognition (such as IL-5, CCL11/eotaxin), or indirect mechanisms via the modulation of alpha beta T lymphocytes and macrophages (through the production of interferon-γ, IL-4 and CCL2/MCP-1, for example). The present review presents an overview of how gamma delta T lymphocytes coordinate eosinophil accumulation in allergy, by focusing on their role in airway inflammation and by discussing the involvement of cytokines and chemokines in this phenomenon

Plantas Medicinais e Medicamentos Fitoterápicos no Combate a Doenças Negligenciadas: uma Alternativa Viável?

Made available in DSpace on 2017-06-01T18:21:23Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 10.pdf: 89441 bytes, checksum: 03754340473ee8de89bce0dba757f579 (MD5) Previous issue date: 7Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Consultora da Organização Mundial da Saúde.Atualmente, há falta de medicamentos efetivos, seguros e viáveis do ponto de vista da produção industrial, voltada para as doenças infectoparasitárias, responsáveis por uma alta mortalidade entre a população mais pobre. A indústria farmacêutica argumenta que a pesquisa e o desenvolvimento de novas drogas são muito caros, e o baixo retorno financeiro muitas vezes não compensa os riscos dos investimentos. A busca de novas drogas para estas doenças infecto-parasitárias, “não lucrativas”, denominadas Doenças Negligenciadas, exige novas estratégias para os investimentos em P&D, que passam pelo estabelecimento de novos paradigmas para as políticas públicas, num esforço em integrar ao mercado as importantes questões sociais; ao mesmo tempo em que requerem a busca incessante de alternativas viáveis aos tratamentos dessas enfermidades. Neste contexto, deve ser levada em conta, tanto a exploração de novas moléculas e alvos terapêuticos para a pesquisa de novos medicamentos como o uso das plantas medicinais e de fitoterápicos. Estes últimos podem tornar-se uma alternativa terapêutica viável, tornando a abordagem da fitoterapia uma ferramenta auxiliar para a melhora na qualidade de vida destas populações.Nowadays, there is a lack of effective, safe and affordable pharmaceuticals to control infectious diseases that cause high mortality among the poorer people of the world. The international pharmaceutical industry argues that research and development is too costly and risky to invest in such low return “non-profitable” Neglected Diseases as they are called. The search for new drugs for neglected diseases requires new strategies of R&D investments, these being established in new paradigms of public policies, which contemplates social questions and not just market value and provide for a continual search for viable alternatives for the treatment of these diseases. This search should not be limited only to the examination of new molecules as new effective pharmacological targets, but also take in account the use of medicinal plants and phytopharmaceuticals, which can offer equally effective tools for improving the quality of life of these underprivileged populations

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-α, IFN-α, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-α, IFN-α and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

Submitted by Sandra Infurna ([email protected]) on 2019-10-29T13:54:10Z No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-10-29T14:02:20Z (GMT) No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5)Made available in DSpace on 2019-10-29T14:02:20Z (GMT). No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5) Previous issue date: 2007Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Farmacologia Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Farmacologia Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune etiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applied for dengue fever

Management methodology for product-oriented R&D projects: a proposal

Submitted by Fabricia Pimenta ([email protected]) on 2017-12-27T17:23:39Z No. of bitstreams: 1 Pizarro_etal_2006.pdf: 466173 bytes, checksum: 2cb13d1ef451596265eb3401090153e9 (MD5)Approved for entry into archive by Fabricia Pimenta ([email protected]) on 2018-01-29T16:15:29Z (GMT) No. of bitstreams: 1 Pizarro_etal_2006.pdf: 466173 bytes, checksum: 2cb13d1ef451596265eb3401090153e9 (MD5)Made available in DSpace on 2018-01-29T16:15:29Z (GMT). No. of bitstreams: 1 Pizarro_etal_2006.pdf: 466173 bytes, checksum: 2cb13d1ef451596265eb3401090153e9 (MD5) Previous issue date: 2006Fundação Oswaldo Cruz.. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional em Saúde Pública Sérgio Arouca. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.As atividades de pesquisa e desenvolvimento (P&D) realizadas nos institutos públicos de pesquisa (IPPs) têm como característica uma gestão arraigada nas premissas acadêmicas, que priorizam a geração e difusão do conhecimento. Em contrapartida, a necessidade de competitividade tecnológica no mercado e a pressão pela participação, como instrumentos da política pública do esforço nacional rumo à inovação, têm pressionado os IPPs para a busca por resultados mais concretos. Esse fato acarreta a geração de grandes lacunas nos processos relacionados à gestão, induzindo a uma constante necessidade de aperfeiçoamento gerencial, no sentido de criar e melhorar ferramentas que contribuam para adequá-la à nova realidade. Este artigo propõe uma metodologia de gestão de projetos de P&D, que se baseia no direcionamento dos projetos de pesquisa para a obtenção de produtos, e considera suas características multidisciplinares e interdisciplinares e a incerteza inerentes a esse processo. Essa metodologia foi desenvolvida no Instituto de Tecnologia de Fármacos da Fiocruz e é proposta como um modelo original para instituições semelhantes.The Research and Development (R&D) activities carried out at public research institutes have a strongly rooted academic-like management which focuses on knowledge improvement. On the other hand, the need for technological competitiveness and contribution in the national effort towards innovation has lead Brazilian organizations to search for more concrete results: products. This fact accounts for huge gaps in management-related processes and a constant need for managerial improvements in order to generate and perfect tools suitable to a new reality. This article proposes a R&D project management methodology focused on research projects that aim at new technological products taking into consideration the multidiscip linary and interdisciplinary aspects and the uncertainty inherent to this process. It presents the case of the Pharmaceutical Technology Institute, a unit of the Oswaldo Cruz Foundation, and proposes an original m odel for similar institutes

Article Synthesis and Trypanocidal Activity of Novel 2,4,5-Triaryl-N-Hydroxylimidazole Derivatives

Herein, we report the design, synthesis and trypanocidal activity of some novel trisubstituted imidazole derivatives. These heterocyclic derivatives were structurally planned by exploring the concept of molecular hybridisation between two arylhydrazones derived from megazol, which has potent trypanocidal activity. The trypanocidal activity of these triarylimidazole derivatives was evaluated against infective trypomastigote forms of T. cruzi and the derivative 2'-(4-bromophenyl)-1-methyl-5'-phenyl-1H,3'H-2,4'-biimidazol-3'-ol showed moderate biological activity (IC50 = 23.9 µM) when compared to benznidazole, a standard trypanocidal drug. These compounds did not present cytotoxic effects at concentrations near the trypanocidal IC50, being considered a good starting point for the development of new anti-Chagas drug candidates