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Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease and has a high frequency among dermatological diseases. The interaction of genetic factors, skin and environmental conditions affect the expression of the disease, developing a complex pathology. Current multimodal treatment has numerous adverse effects and variations in its efficacy and safety, demonstrating the need to develop safe and effective therapeutic resources for patients with CAD. Mesenchymal stem cells (MSCs) are multipotent cells, with special characteristics, such as self-renewal, immunomodulatory properties, and de-differentiation, making them useful for several clinical problems. The discovery of the immunosuppressive effect of MSCs on T cells has opened the potential for new perspectives with its use as a therapeutic agent for immune diseases, such as CAD. The scarce number of research using the MSC as a treatment for CAD result in the lack of knowledge about the benefits and possible protocols to be followed for the use of this cell therapy. In this review, we highlighted the clinical studies and potential biological mechanisms of MSC-based cell therapy effects attenuating canine atopic dermatitis compared to conventional treatment, which might lead to a safe improvement of the animal’s clinical condition in a short period without causing adverse effects. RESUMO A dermatite atópica canina (DAC) é uma doença inflamatória crônica da pele e tem alta frequência entre as doenças dermatológicas. A interação de fatores genéticos, pele e condições ambientais afetam a expressão da doença, desenvolvendo uma patologia complexa. O tratamento multimodal atual apresenta inúmeros efeitos adversos e variações em sua eficácia e segurança, demonstrando a necessidade de desenvolver recursos terapêuticos seguros e eficazes para pacientes com DAC. As células-tronco mesenquimais (CTM) são células multipotentes, com características especiais, como auto renovação, propriedades imunomoduladoras e desdiferenciação, tornando-se úteis para diversos problemas clínicos. A descoberta do efeito imunossupressor das CTMs sobre as células T abriu o potencial para novas perspectivas com sua utilização como agente terapêutico para doenças imunológicas, como a DAC. O escasso número de pesquisas utilizando o MSC como tratamento para DAC resulta no desconhecimento dos benefícios e dos possíveis protocolos a serem seguidos para a utilização dessa terapia celular. Nesta revisão, destacamos os estudos clínicos e os potenciais mecanismos biológicos dos efeitos da terapia celular baseada em MSC que atenuam a dermatite atópica canina em comparação com o tratamento convencional, podendo levar a uma melhora segura da condição clínica do animal em um curto período, sem causar efeitos adversos.

Submitted by Gabriella Paiva (gcarpa@stj.jus.br) on 2017-02-03T12:10:23Z No. of bitstreams: 2 juizo_admissibilidade_correcao_santos.pdf: 184703 bytes, checksum: 9dcd43a3895fae49b7ec53e5847790f8 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Approved for entry into archive by Rafaella Monterei (rcarine@stj.jus.br) on 2017-02-09T18:00:40Z (GMT) No. of bitstreams: 2 juizo_admissibilidade_correcao_santos.pdf: 184703 bytes, checksum: 9dcd43a3895fae49b7ec53e5847790f8 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Made available in DSpace on 2017-02-09T18:00:40Z (GMT). No. of bitstreams: 2 juizo_admissibilidade_correcao_santos.pdf: 184703 bytes, checksum: 9dcd43a3895fae49b7ec53e5847790f8 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Previous issue date: 2016

Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil The main pathogenic event caused by Schistosoma mansoni infection is characterized by a granulomatous inflammatory reaction around parasite eggs and fibrosis in the liver. We have previously shown that transplantation of bone marrow cells (BMC) promotes a reduction in liver fibrosis in chronically S. mansoni-infected mice. Here we investigated the presence and phenotype of bone marrow-derived cells in livers of S. mansoni-infected mice. During the chronic phase of infection, C57BL/6 mice had an increased number of circulating mesenchymal stem cells and endothelial progenitor cells in the peripheral blood when compared to uninfected controls. In order to investigate the fate of BMC in the liver, we generated bone marrow chimeric mice by transplanting BMC from transgenic green fluorescent protein (GFP) mice into lethally irradiated wild-type C57BL/6 mice. S. mansoni-infected chimeric mice did not demonstrate increased mortality and developed similar liver histopathological features, when compared to wild-type S. mansoni-infected mice. GFP(+) bone marrow-derived cells were found in the liver parenchyma, particularly in periportal regions. CD45(+)GFP(+) cells were found in the granulomas. Flow cytometry analysis of digested liver tissue characterized GFP(+) cells as lymphocytes, myeloid cells and stem cells. GFP(+) cells were also found in areas of collagen deposition, although rare GFP(+) cells expressed the myofibroblast cell marker α-SMA. Additionally GFP(+) endothelial cells (co-stained with von Willebrand factor) were frequently observed, while BMC-derived hepatocytes (GFP(+) albumin(+) cells) were sparsely found in the liver of chimeric mice chronically infected with S. mansoni. In conclusion, BMC are recruited to the liver during chronic experimental infection with S. mansoni and contribute to the generation of different cell types involved, not only in disease pathogenesis, but possibly in liver regeneration and repair

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy and induces neuronal destruction are discussed in this paper. The results suggest that autoimmunity in the chronic phase is the main cause of the progressive cardiac destruction, and that autoreactivity is restricted to the CD4+ T cell compartment. During the acute phase, the neuronal and cardiac fiber destruction occurs when ruptured parasite nests release T. cruzi antigens that bind to the cell surface in the vicinity which become targets for the cellular and humoral immune response against T. cruzi. The various factors involved in the genesis of autoimmunity in chronic T. cruzi infection include molecular mimicry, presentation of self-antigens and imbalance of immune regulation.

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ciências da Comunicação Esta dissertação parte da ideia de que o conceito de dispositivo é o operador conceptual mais decisivo para pensar a experiência contemporânea. Para tanto, tomámos com objecto o conceito de dispositivo na obra de Giorgio Agamben e assim tentámos compreender como poderia ser útil o modo pelo qual Agamben pensa o conceito de maneira a perceber a relação prioritária da técnica com política. A primeira parte desta dissertação é uma abordagem às raízes do conceito de dispositivo na obra de Martin Heidegger e na de Michel Foucault pretendendo-se compreender a tradição de pensamento na qual o próprio Agamben se insere. Na segunda parte explorámos a importância que assume na obra do filósofo italiano o dispositivo teológico e, por outro lado, como é que a relação da política com a técnica é pensada pelo mesmo autor. Chegámos a duas conclusões: (a) uma das suas principais inovações foi demonstrar como o conceito de dispositivo é também devedor de um outro conceito da teologia cristã, o de oikonomia, assim Agamben mostra como a nossa cultura apelidada de secular depende da sua herança teológica; (b) a obra de Agamben, apesar das suas inovações falha na compreensão de que o principal dispositivo na nossa cultura é agora técnico, o que o leva a uma ausência de uma filosofia da técnica substancial no seio da sua teoria do dispositivo, que não lhe permite compreender amplamente os fenómenos políticos associados às novas tecnologias de informação e comunicação no contexto da nossa sociedade do controlo.

Texto completo: acesso restrito. p. 4691-4702 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-03-27T13:07:52Z No. of bitstreams: 1 10.1096fj.13-229351.pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5) Approved for entry into archive by Alda Lima da Silva (sivalda@ufba.br) on 2014-04-22T18:45:56Z (GMT) No. of bitstreams: 1 10.1096fj.13-229351.pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5) Made available in DSpace on 2014-04-22T18:45:56Z (GMT). No. of bitstreams: 1 10.1096fj.13-229351.pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5) Previous issue date: 2013 Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony-stimulating factor (G-CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G-CSF (3 courses of 200 μg/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the hearts of vehicle-treated mice, which correlated with decreased syndecan-4, intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions in interferon-γ and tumor necrosis factor-α and increased interleukin-10 and transforming growth factor-β were found after G-CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (Treg) cells. A significant increase in CD3+Foxp3+ cells was observed in the hearts of G-CSF-treated mice. In addition, a reduction of parasitism was observed after G-CSF treatment. Our results indicate a role of Treg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease.—Vasconcelos, J. F., Souza, B. S. F., Lins, T. F. S., Garcia, L. M. S., Kaneto, C. M., Smapaio, G. P., de Alcântara, A. C., Meira, C. S., Macambira, S. G., Ribeiro-dos-Santos, R., Soares, M. B. P. Administration of granulocyte colony-stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy.

Texto completo: acesso restrito. p. 339–349 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-19T15:06:24Z No. of bitstreams: 1 Antonio Rodrigues de Freitas.pdf: 617438 bytes, checksum: cf6db99b23516a431130f0307e2e0657 (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-10-09T15:43:27Z (GMT) No. of bitstreams: 1 Antonio Rodrigues de Freitas.pdf: 617438 bytes, checksum: cf6db99b23516a431130f0307e2e0657 (MD5) Made available in DSpace on 2014-10-09T15:43:28Z (GMT). No. of bitstreams: 1 Antonio Rodrigues de Freitas.pdf: 617438 bytes, checksum: cf6db99b23516a431130f0307e2e0657 (MD5) Previous issue date: 2012 Background aims Cirrhosis, end-stage liver disease, is caused by different mechanisms of injury, associated with persistent inflammation. Galectin-3 is an important regulator of fibrosis that links chronic inflammation to fibrogenesis. We investigated the role of bone marrow cell (BMC) transplantation in chronic inflammation and hepatic fibrosis. Methods Liver cirrhosis was induced by administration of carbon tetrachloride and ethanol to wild-type C57BL/6 or bone marrow chimeric mice. Bone marrow chimeras were generated by lethal irradiation and transplantation with BMC obtained from green fluorescent protein (GFP+ )donors. Wild-type cirrhotic mice were transplanted with BMC without irradiation. Livers from chimeras and cirrhotic transplanted mice were obtained for evaluation of inflammation, fibrosis and regulatory factors [galectin-3, matrix metallopeptidase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-β]. Results The development of cirrhosis was associated with increased expression of galectin-3 by F4/80+ cells and intense migration of BMC to the liver. Furthermore, when transplanted after the establishment of cirrhosis, BMC also migrated to the liver and localized within the fibrous septa. Two months after BMC therapy, cirrhotic mice had a significant reduction in liver fibrosis and expression of type I collagen. We did not find any difference in levels of TGF-β, TIMP-1 and MMP-9 between saline and BMC groups. However, the numbers of inflammatory cells, phagocytes and galectin-3+ cells were markedly lower in the livers of cirrhotic mice treated with BMC. Conclusions Our results demonstrate an important role for BMC in the regulation of liver fibrosis and that transplantation of BMC can accelerate fibrosis regression through modulatory mechanisms.

Texto completo: acesso restrito. p. 1011–1021 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-07-15T15:53:39Z No. of bitstreams: 1 Luiz Antônio Rodrigues de Freitas.pdf: 1068341 bytes, checksum: d48e47b2f4ec8b947c4ee5717afa8049 (MD5) Rejected by Flávia Ferreira (flaviaccf@yahoo.com.br), reason: Bom dia Por favor efetue cadastro de autores na ordem em que aparece no artigo: Souza,Bruno Solano de Freitas Nascimento,Ramon Campos Oliveira,Sheilla Andrade de Vasconcelos,Juliana Fraga Kaneto,Carla Martins Carvalho,Lian Felipe Paiva Pontes de Santos,Ricardo Ribeiro dos Soares, Milena Botelho Pereira Freitas, Luiz Antonio Rodrigues de Equipe RI Gratos, on 2014-08-07T13:20:42Z (GMT) Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-11T11:32:08Z No. of bitstreams: 1 BRUNO SOLANO DE FREITAS SOUZA.pdf: 1068341 bytes, checksum: d48e47b2f4ec8b947c4ee5717afa8049 (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-10-09T15:45:53Z (GMT) No. of bitstreams: 1 BRUNO SOLANO DE FREITAS SOUZA.pdf: 1068341 bytes, checksum: d48e47b2f4ec8b947c4ee5717afa8049 (MD5) Made available in DSpace on 2014-10-09T15:45:53Z (GMT). No. of bitstreams: 1 BRUNO SOLANO DE FREITAS SOUZA.pdf: 1068341 bytes, checksum: d48e47b2f4ec8b947c4ee5717afa8049 (MD5) Previous issue date: 2012 Background aims Acute liver failure (ALF), although rare, remains a rapidly progressive and frequently fatal condition. Acetaminophen (APAP) poisoning induces a massive hepatic necrosis and often leads to death as a result of cerebral edema. Cell-based therapies are currently being investigated for liver injuries. We evaluated the therapeutic potential of transplantation of bone marrow mononuclear cells (BMC) in a mouse model of acute liver injury. Methods ALF was induced in C57Bl/6 mice submitted to an alcoholic diet followed by fasting and injection of APAP. Mice were transplanted with 107 BMC obtained from enhanced green fluorescent protein (GFP) transgenic mice. Results BMC transplantation caused a significant reduction in APAP-induced mortality. However, no significant differences in serum aminotransferase concentrations, extension of liver necrosis, number of inflammatory cells and levels of cytokines in the liver were found when BMC- and saline-injected groups were compared. Moreover, recruitment of transplanted cells to the liver was very low and no donor-derived hepatocytes were observed. Mice submitted to BMC therapy had some protection against disruption of the blood–brain barrier, despite their hyperammonemia, and serum metalloproteinase (MMP)-9 activity similar to the saline-injected group. Tumor necrosis factor (TNF)-α concentrations were decreased in the serum of BMC-treated mice. This reduction was associated with an early increase in interleukin (IL)-10 mRNA expression in the spleen and bone marrow after BMC treatment. Conclusions BMC transplantation protects mice submitted to high doses of APAP and is a potential candidate for ALF treatment, probably via an immunomodulatory effect on TNF-α production.

INTRODUÇÃO: as células-tronco (CT) possuem capacidade de induzir a regeneração tecidual e, portanto, apresentam um potencial terapêutico. Assim como a medula óssea e o cordão umbilical, a polpa dentária é uma das fontes disponíveis de CT. O seu fácil acesso e o fato de os dentes decíduos não serem órgãos vitais, que normalmente são descartados após a esfoliação, provêm um atrativo para testes de segurança e viabilidade terapêutica dessas células. OBJETIVOS: descrever a coleta, o isolamento e o cultivo de CT obtidas da polpa de dentes decíduos, assim como a sua caracterização por meio de citometria de fluxo e da indução da diferenciação em linhagens osteogênica e adipogênica. MÉTODOS: as CT foram obtidas de forma relativamente simples e apresentaram boa capacidade proliferativa, mesmo a partir de pouca quantidade de tecido pulpar. RESULTADOS: a análise por citometria de fluxo confirmou as características de CT mesenquimais, com baixos níveis de expressão dos antígenos CD34 e CD45, que são marcadores de células hematopoiéticas, e altos níveis de expressão dos antígenos CD105, CD166, CD90 e CD73, que são marcadores de CT mesenquimais. A plasticidade das células foi confirmada pela identificação de depósitos de cálcio nas culturas que receberam meio osteogênico, e de acúmulo lipídico intracelular nas culturas que receberam meio adipogênico. CONCLUSÕES: as CT de dentes decíduos têm um potencial promissor de aplicação em regeneração tecidual. Sendo assim, é importante difundir entre os cirurgiões-dentistas o conhecimento sobre a existência e as características dessa fonte de CT, discutindo a técnica utilizada, suas limitações e possíveis indicações. INTRODUCTION: Stem cells (SCs) are capable of inducing tissue regeneration and are, therefore, potentially therapeutic. Similarly to bone marrow and umbilical cords, dental pulp is one of the available sources of SCs. The fact that these cells are easily accessible and that deciduous teeth are not vital organs, and are normally discarded after exfoliation, make them particularly attractive for use in safety and viability tests. OBJECTIVE: To describe the collection, isolation and culture of SCs obtained from the pulp of deciduous teeth as well as their characterization by flow cytometry, and the induction of differentiation into osteogenic and adipogenic lineages. METHODS: SCs were obtained in a relatively straightforward manner and showed good proliferative capacity, even from a small amount of pulp tissue. RESULTS: Analysis by flow cytometry confirmed the characteristics of mesenchymal SCs with low expression of CD34 and CD45 antigens, which are markers for hematopoietic cells, and high levels of expression of CD105, CD166, CD90 and CD73 antigens, which are markers for mesenchymal SCs. Cell plasticity was confirmed by identifying calcium deposits in cultures that received osteogenic medium, and intracellular lipid accumulation in adipogenic cultures that received adipogenic medium. CONCLUSIONS: SCs collected from deciduous teeth show promising potential for application in tissue regeneration. Therefore, it is important that knowledge about the existence and characteristics of this source of stem cells be disseminated among dentists and that the technique, its limitations and possible indications are highlighted and discussed.

p. 596-602 Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2012-03-02T12:23:00Z No. of bitstreams: 1 C__Documents and Settings_rep...t.default_Cache_0_D1_CC9D1d01.pdf: 275086 bytes, checksum: 1b60c6ff0f48421176622c1ede9f1263 (MD5) Made available in DSpace on 2012-03-02T12:23:00Z (GMT). No. of bitstreams: 1 C__Documents and Settings_rep...t.default_Cache_0_D1_CC9D1d01.pdf: 275086 bytes, checksum: 1b60c6ff0f48421176622c1ede9f1263 (MD5) Previous issue date: 2011 7-Hydroxycoumarin (umbelliferone, 1), the main metabolite of coumarin, has been reported to produce potent antinociceptive effects in animal models of pain. However, the biochemical events involved in antinociception mediated by 1 are currently not well understood. In the present study, the mechanisms by which 1 exerts its pharmacological actions were investigated. Acute pretreatment of mice with 1 produced a long-lasting antinociceptive effect against complete Freund’s adjuvant (CFA)-induced hyperalgesia. The subchronic administration of 1 inhibited CFA-induced hyperalgesia and paw edema, while it did not cause any apparent toxicity. Another set of experiments showed that 1 inhibited carrageenan-induced mechanical hyperalgesia, but not mechanical hyperalgesia induced by prostaglandin E2 (PGE2), suggesting that it acts upstream of PGE2. Treatment with 1 was able to prevent the plantar tissue neutrophil influx induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-R and IL-1β) and the production of PGE2, a directly acting hyperalgesic mediator. The present results suggest that the antinociceptive effect of 1 is correlated with the inhibition of neutrophil migration, cytokine release, and PGE2 production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.

Texto completo: acesso restrito. p. 518–524 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-03-12T14:27:03Z No. of bitstreams: 1 Cristiane Flora Villarreal.pdf: 594276 bytes, checksum: b0d66da8523776a2790724667c0f6d07 (MD5) Approved for entry into archive by Alda Lima da Silva (sivalda@ufba.br) on 2014-03-12T17:55:42Z (GMT) No. of bitstreams: 1 Cristiane Flora Villarreal.pdf: 594276 bytes, checksum: b0d66da8523776a2790724667c0f6d07 (MD5) Made available in DSpace on 2014-03-12T17:55:42Z (GMT). No. of bitstreams: 1 Cristiane Flora Villarreal.pdf: 594276 bytes, checksum: b0d66da8523776a2790724667c0f6d07 (MD5) Previous issue date: 2011 Aim of study: Adiantum, one of the most widely distributed genera of the family Pteridaceae, is employed in folk medicine worldwide. Adiantum latifolium Lam. has been used in Latin American traditional medicine as anxiolytic, analgesic and antiinflammatory. The present study investigates the antinociceptive and antiinflammatory properties of the methanolic extract of Adiantum latifolium (MEA) in animal models of pain and inflammation to confirm its medicinal use. Material and methods: The antinociceptive and antiinflammatory activities of MEA were evaluated using the writhing, formalin, and tail-flick tests, carrageenan-induced paw edema and arachidonic acid-induced ear edema. Mice motor performance was evaluated in the rota rod test and the acute toxicity evaluated over 14 days. Results: Intraperitoneal (1–100 mg/kg) or oral (100–400 mg/kg) administration of MEA produced a dose-related inhibition of acetic acid-induced writhing in mouse. Furthermore, treatment with MEA (100 mg/kg) inhibited both the early and late phases of formalin-induced hypernociception. In contrast, MEA (100 mg/kg/IP) did not prevent the thermal nociception in the tail-flick test. In addition, MEA (100 and 200 mg/kg/IP) inhibited important events related to the inflammatory response induced by carrageenan or arachidonic acid, namely local edema and increase in tissue interleukin-1β levels. MEA (300 mg/kg/IP)-treated mice did not show any motor performance alterations. Over the study period of 14 days, there were no deaths or toxic signs recorded in the group of mice given 1000 mg/kg of MEA. Conclusion: The results demonstrate that Adiantum latifolium has antinociceptive and antiinflammatory activities, acting through the inhibition of IL-1β production.

Texto completo: acesso restrito. p.33-42 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-09-11T13:49:45Z No. of bitstreams: 1 00042737-201001000-00005.pdf: 262144 bytes, checksum: cd90401cc93bb9cd48cc317c3f9d7f97 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-10-31T17:42:53Z (GMT) No. of bitstreams: 1 00042737-201001000-00005.pdf: 262144 bytes, checksum: cd90401cc93bb9cd48cc317c3f9d7f97 (MD5) Made available in DSpace on 2013-10-31T17:42:53Z (GMT). No. of bitstreams: 1 00042737-201001000-00005.pdf: 262144 bytes, checksum: cd90401cc93bb9cd48cc317c3f9d7f97 (MD5) Previous issue date: 2010 Aim: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis. Methods: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model. Results: Mean age, baseline model for end-stage liver disease, and Child–Pugh score were similar in both groups. Child–Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days. Conclusion: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response.

P. 502-505,Ago./Set. Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2011-10-19T11:25:14Z No. of bitstreams: 1 v20n4a07.pdf: 692004 bytes, checksum: 9db1d9e2966bc739590d20569e5954dc (MD5) Made available in DSpace on 2011-10-19T11:25:14Z (GMT). No. of bitstreams: 1 v20n4a07.pdf: 692004 bytes, checksum: 9db1d9e2966bc739590d20569e5954dc (MD5) Previous issue date: 2010 A família Rutaceae apresenta espécies vegetais muito bem distribuídas no Semi-Árido Brasileiro e comumente usadas em medicina popular. Espécies dessa família tem diversas atividades biológicas descritas na literatura. Neste trabalho, atividades imunomoduladora e bactericida são descritas para o extrato acetato de etila e clorofórmico de três espécies da família (Esenbeckia grandiflora Mart., Pilocarpus spicatus A.St.-Hil. e Galipea simplicifolia Schult.). Todas as amostras foram inicialmente avaliadas quanto à sua citotoxicidade, com objetivo de determinar a LC50. O potencial imunomodulador foi avaliado em culturas de esplenócitos murinos estimulados ou não com concanavalina A e também em reação mista linfocitária (RML), usando também esplenócitos de camundongos BALB/c (H-2d) imunizados com esplenócitos de camundongos C57Bl/6 (H-2b). Quatro amostras tiveram os mais elevados valores percentuais de inibição da proliferação de linfócitos ativados pela concanavalina A e foram avaliados em RML. A atividade antibacteriana dos extratos foi também avaliada e a concentração mínima inibitória (CMI) para duas amostras ativas foi de 1.0 e 5.0 mg/mL, respectivamente para as espécies Esenbeckia grandiflora Mart. and Galipea simplicifolia Schult. Assim, os dados aqui apresentados reforçam informações da literatura científica relacionados à atividade biológica para muitas espécies da família Rutaceae e incentivam outros estudos com estas visando descobrir substâncias ativas, potenciais candidatas a novos fármacos. Curitiba

Trabalho completo: acesso restrito, p. 3843-3850 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-06-20T20:38:56Z No. of bitstreams: 1 (81)3843.full.pdf: 1316507 bytes, checksum: 63c35205e5bb09d4d24366fe35a602bc (MD5) Made available in DSpace on 2012-06-20T20:38:56Z (GMT). No. of bitstreams: 1 (81)3843.full.pdf: 1316507 bytes, checksum: 63c35205e5bb09d4d24366fe35a602bc (MD5) Previous issue date: 2009-11 This study investigates the effects of granulocyte colony-stimulating factor (G-CSF) therapy in experimental chronic chagasic cardiomyopathy. Chagas disease is one of the leading causes of heart failure in Latin America and remains without an effective treatment other than cardiac transplantation. C57BL/6 mice were infected with 103 trypomastigotes of Trypanosoma cruzi, and chronic chagasic mice were treated with G-CSF or saline (control). Evaluations following treatment were functional, immunological, and histopathological. Comparing hearts of G-CSFtreated mice showed reduced inflammation and fibrosis compared to saline-treated chagasic mice. G-CSF treatment did not alter the parasite load but caused an increase in the number of apoptotic inflammatory cells in the heart. Cardiac conductance disturbances in all infected animals improved or remained stable due to the G-CSF treatment, whereas all of the saline-treated mice deteriorated. The distance run on a treadmill and the exercise time were significantly greater in G-CSFtreated mice when compared to chagasic controls, as well as oxygen consumption (V˙ O2), carbon dioxide production (V˙ CO2), and respiratory exchange ration (RER) during exercise. Administration of G-CSF in experimental cardiac ischemia had beneficial effects on cardiac structure, which were well correlated with improvements in cardiac function and whole animal performance.— Macambira, S. G., Vasconcelos, J. F., Costa, C. R. S., Klein, W., Lima, R. S., Guimara˜es, P., Vidal, D. T. A., Mendez, L. C., Ribeiro-dos-Santos, R., Soares, M. B. P. Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function.

Trabalho completo: acesso restrito, p.102–107 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-07-06T19:39:44Z No. of bitstreams: 1 (109)1-s2.0-S0378874109003511-main.pdf: 353227 bytes, checksum: 0bac3212f8f9df561e8643035d74e8cb (MD5) Made available in DSpace on 2012-07-06T19:39:44Z (GMT). No. of bitstreams: 1 (109)1-s2.0-S0378874109003511-main.pdf: 353227 bytes, checksum: 0bac3212f8f9df561e8643035d74e8cb (MD5) Previous issue date: 2009-07-17 Blechnum occidentale L. is a terrestrial fern that ranges from the United States to South America, and is employed in Brazilian folk medicine. In the present study we investigated the antinociceptive and antiinflammatory activities of the methanolic extract of Blechnum occidentale L. (MEB) in animal models of pain and inflammation to support its medicinal use in treatment of inflammatory and pulmonary diseases, urinary infections and liver diseases. The antinociceptive activity of MEB was evaluated using the writhing, formalin, and tail flick tests. The antiinflammatory activity of MEB was evaluated in carrageenan-induced paw oedema and neutrophil migration. In order to discard possible non-specific muscle relaxant or sedative effects of MEB, mice motor performance was evaluated in the rota rod test and its toxicity evaluated over 14 days. Intraperitoneal (IP) administration of MEB (0.01–100 mg/kg) produced a dose-related antinociception on acetic acid-induced writhing in mice. Oral administration of MEB, at a different range of doses (100–400 mg/kg), also produced significant antinociceptive effect on the writhing test. Furthermore, treatment with MEB (100 and 200 mg/kg IP) inhibited significantly both the early and late phases of formalin-induced hypernociception in rats. In contrast, treatment with MEB (100 and 200 mg/kg IP) did not prevent the thermal nociception in the tail flick test. The IP administration of MEB (100 and 300 mg/kg) significantly reduced the paw oedema induced by carrageenan. Moreover, systemic treatment with MEB (11–300 mg/kg) reduced the neutrophil migration in the carrageenan-induced migration to the peritoneal cavity. In the rota rod test, MEB-treated mice did not show any significant motor performance alterations with the dose of 300 mg/kg. In addition, over the study duration of 14 days, there were no deaths or toxic signs recorded in the mice given 100 or 1000 mg/kg of MEB. The results described here are the first report of pharmacological studies of Blechnum occidentale L. and indicate that this plant has antinociceptive and antiinflammatory activities which support its folk medicine use.

Texto completo: acesso restrito. p. 2051-2056 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-11-26T11:48:23Z No. of bitstreams: 1 Bioinformatics-2008-Galvão-2051-6.pdf: 1422357 bytes, checksum: 04a5873b69bec93436f15b9b3f2054f5 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-26T12:57:06Z (GMT) No. of bitstreams: 1 Bioinformatics-2008-Galvão-2051-6.pdf: 1422357 bytes, checksum: 04a5873b69bec93436f15b9b3f2054f5 (MD5) Made available in DSpace on 2013-11-26T12:57:07Z (GMT). No. of bitstreams: 1 Bioinformatics-2008-Galvão-2051-6.pdf: 1422357 bytes, checksum: 04a5873b69bec93436f15b9b3f2054f5 (MD5) Previous issue date: 2008 Motivation: A significant issue in stem cell therapy is to understand the role of this type of cell in the tissue regeneration. To explain this mechanism, an experimental study has quantified that the bone marrow cell transplantation decreases the number of inflammatory cells and reduces the fibrosis area in chagasic mice. Using this experimental data, we have developed an agent-based computational model to investigate the regeneration of the chronic chagasic cardiomyopathy after bone marrow stem cell transplantation. Results: Our model includes six different types of agents: inflammatory cell, fibrosis area, cardiomyocyte, proinflammatory cytokine tumor necrosis factor-α, Trypanosoma cruzi parasite and bone marrow stem cell. This latter promotes apoptosis in inflammatory cells, reduction in the fibrosis area and can differentiate into cardiomyocyte. Proinflammatory cytokine tumor necrosis factor-α can increase the fibrosis area and T.cruzi can increase the number of inflammatory cells. Our results for both apoptosis of inflammatory cells and reduction in the fibrosis area were compared with experimental data. They suggest that the concentration pattern is the most important factor to characterize the kinetics of cardiac tissue regeneration after bone marrow stem cell transplantation.

A cardiopatia chagásica crônica é ainda uma das maiores causas de óbito por insuficiência cardíaca na América Latina e para a qual não há nenhum tratamento eficaz até o momento. Enquanto a população de indivíduos com doença de Chagas aguarda o desenvolvimento de novos quimioterápicos mais eficientes e de menor toxicidade para a eliminação do Trypanosoma cruzi, uma nova estratégia surgiu na tentativa de reparar ou diminuir os danos causados ao miocárdio de pacientes com forma crônica cardíaca. Trata-se do transplante de células de medula óssea obtidas do próprio indivíduo a ser tratado, que pode levar à melhora funcional e da qualidade de vida dos pacientes, como ocorreu em estudos utilizando esta abordagem para o tratamento de pacientes com insuficiência cardíaca de etiologia isquêmica. Os possíveis efeitos de terapias celulares e sua utilização em pacientes cardiopatas chagásicos crônicos são discutidos no presente artigo. Chronic chagasic cardiomyopathy remains a major cause of death due to heart failure in Latin American countries and for which there is currently no effective treatment. While chagasic patients wait for the development of more efficient and less toxic chemotherapeutics for the elimination of Trypanosoma cruzi, a new strategy has appeared in an attempt to repair or ameliorate the damage caused to the myocardium of patients with chronic chagasic cardiomyopathy. This therapy, involving the transplant of bone marrow cells obtained from the patient to be treated, may lead to improvement in heart function and in life quality of patients with severe chagasic cardiopathy, similar to that obtained with this approach in the treatment of patients with heart failure of ischemic etiology. The possible effects of cell therapies and its applications in chronic chagasic cardiopaths are discussed in the present report.

Apresentado o primeiro caso de transplante de célula de medula óssea para o miocárdio de um portador de insuficiência cardíaca de etiologia chagásica. Homem, 52 anos, portador de insuficiência cardíaca crônica, em classe funcional III da NYHA, apesar de terapêutica clínica otimizada. Como procedimento, foi aspirado 50 ml de medula óssea através de punção da crista ilíaca, seguidos de filtragem, separação das células mononucleares, ressuspensão e injeção intracoronariana. A fração de ejeção do ventrículo esquerdo em repouso, medida pela ventriculografia radioisotópica com hemácias marcadas, antes do transplante, era de 24% e, após 30 dias, aumentou para 32% sem alterar o esquema medicamentoso. Foram avaliados, antes e 30 dias após o procedimento, respectivamente, o diâmetro diastólico final do ventrículo esquerdo (82 mm; 76 mm); escore de qualidade de vida de Minnesota (55; 06); distância caminhada no teste de 6min (513 m; 683 m). Achados demonstraram ser possível realizar a injeção intracoronariana de célula de medula óssea, sugerindo que este procedimento é potencialmente seguro e efetivo em pacientes com insuficiência cardíaca chagásica. We report the first case of bone marrow cell transplantation to the myocardium of a patient with heart failure due to chagas' disease. The patient is a 52-year-old man with chronic heart failure, NYHA functional class III, despite the optimized clinical therapy. The procedure consisted of aspiration of 50 mL of bone marrow through puncture of the iliac crest, followed by filtration, separation of the mononuclear cells, resuspension, and intracoronary injection. The left ventricular ejection fraction at rest, measured using radionuclide ventriculography with labeled red blood cells prior to transplantation, was 24%, and, after 30 days, it increased to 32% with no change in the medicamentous schedule. The following measurements were assessed before and 30 days after transplantation: left ventricular end diastolic diameter (82 mm and 76 mm, respectively); Minnesota living with heart failure questionaire score (55 and 06, respectively); and distance walked in the 6-minute walking test (513 m and 683 m, respectively). Our findings show that intracoronary injection of bone marrow cells may be performed, suggesting that this is a potentially safe and effective procedure in patients with due to Chagas' disease heart failure.

p. 273–278 Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2012-10-23T14:19:51Z No. of bitstreams: 1 __ac.els-cdn.com_S088240...226c700c0e910395082e7788b8517.pdf: 320439 bytes, checksum: ddff06dbdb7aee3df77fcf7cc203e9fa (MD5) Made available in DSpace on 2012-10-23T14:19:51Z (GMT). No. of bitstreams: 1 __ac.els-cdn.com_S088240...226c700c0e910395082e7788b8517.pdf: 320439 bytes, checksum: ddff06dbdb7aee3df77fcf7cc203e9fa (MD5) Previous issue date: 2004 Trypanosoma cruzi is an obligate intracellular protozoan parasite that actively penetrates into non-phagocytic mammalian cells. To accomplish this, the parasite relies on the binding of cell surface ligands. It is reported herein that the T. cruzi trans-sialidase (TS), which is exposed on the parasite surface, binds to mouse heart cells, and should therefore be further studied as a possible cell penetration-related ligand. In addition, as has been proposed elsewhere, the binding of T. cruzi to tissues may turn them into targets for parasite-specific immune reactions. Washed heart sections from T. cruzi-infected mice were subjected to immunoenzymatic staining with antisera against whole T. cruzi and with polyclonal or monoclonal antibodies against TS. The anti-TS antibodies stained both parasites and uninfected heart cells in the vicinity of T. cruzi nest remains/trypomastigotes. On the other hand, an anti-T. cruzi serum, which did not recognize TS, only stained the parasites. In addition, normal heart sections from uninfected nude mice were shown to react with both enzymatically active and inactive recombinant TS molecules, probably through their amino-terminal region, since a recombinant TS lacking this region failed to bind.

Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.

Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Chronic chagasic cardiomyopathy (CChC) is characterized by an inflammatory reaction which may eventually lead to heart enlargement, arrythmia, and death. As described herein, interleukin-4-deficient mice mount increased specific T helper (Th) 1 immune responses when infected with Trypanosoma cruzi, as compared to wild-type mice. Interestingly, these mice had reduced parasitism and mortality and exacerbated inflammation in their hearts, demonstrating a clear dissociation between inflammation and parasite load. The modulation of these phenomena so as to maximize host and parasite survivals may depend on a fine balance between Th responses, in which a Th1 response will, on one hand, control parasitism and, on the other hand, enhance heart inflammation throughout the course of the infection

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy and induces neuronal destruction are discussed in this paper. The results suggest that autoimmunity in the chronic phase is the main cause of the progressive cardiac destruction, and that autoreactivity is restricted to the CD4+ T cell compartment. During the acute phase, the neuronal and cardiac fiber destruction occurs when ruptured parasite nests release T. cruzi antigens that bind to the cell surface in the vicinity which become targets for the cellular and humoral immune response against T. cruzi. The various factors involved in the genesis of autoimmunity in chronic T. cruzi infection include molecular mimicry, presentation of self-antigens and imbalance of immune regulation.

Uma paciente com síndrome de imunodeficiência adquirida (SIDA) e doença de Chagas, com xenodiagnóstico positivo, estava em uso prolongado de cetoconazol com o objetivo de suprimir a parasitemia e prevenir a reativação da doença de Chagas. O cetoconazol foi suspenso inadvertidamente após 6 meses de uso. Um mês após, a paciente foi internada com febre, cefaléia, vômitos, taquicardia e hepatoesplenomegalia. Tanto o xenodiagnóstico como o exame de sangue a fresco demonstraram a presença de Trypanosoma cruzi. O tratamento com benzonidazol foi instituído, com supressão da parasitemia. A paciente desenvolveu concomitantemente uma provável neurotoxoplasmose, evoluindo para o óbito em septicemia. À necropsia, não foram encontrados parasitas.

Uma paciente com síndrome de imunodeficiência adquirida (SIDA) e doença de Chagas, com xenodiagnóstico positivo, estava em uso prolongado de cetoconazol com o objetivo de suprimir a parasitemia e prevenir a reativação da doença de Chagas. O cetoconazol foi suspenso inadvertidamente após 6 meses de uso. Um mês após, a paciente foi internada com febre, cefaléia, vômitos, taquicardia e hepatoesplenomegalia. Tanto o xenodiagnóstico como o exame de sangue a fresco demonstraram a presença de Trypanosoma cruzi. O tratamento com benzonidazol foi instituído, com supressão da parasitemia. A paciente desenvolveu concomitantemente uma provável neurotoxoplasmose, evoluindo para o óbito em septicemia. À necropsia, não foram encontrados parasitas. A patient with AIDS and asymptomatic Chagas's disease and positive xenodiagnosis was taking ketoconazole in order to supress parasitemia and prevent reactivation of Chagas's disease. Ketoconazole was unplanned suspended after 6 months, and the patient was admitted with fever, headache, vomiting, tachycardia, postural hypotension, hepatosplenomegaly, and positive xenodiagnosis one month later. Treatment with benzonidazole was begun leading to supression of parasitemia. The patient had probabily a neurotoxoplasmosis associated and progressed to coma and death with sepsis. No parasite was found in autopsy.