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Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:00:17Z No. of bitstreams: 0 Made available in DSpace on 2014-02-26T17:00:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-09-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:23:23Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T15:23:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-09-01 In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57Bl/6 mice, fastuosain and bromelain injected intraperitoneally were protective, and very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, and became round and detached, forming strongly bound cell clusters in suspension. Peritoneal cells recruited and activated by fastuosain treatment ( mainly monocytic cells and lymphocytes) migrated to the lung, where pulmonary melanoma metastases grew. Adoptive transference of peritoneal cells recruited by fastuosain had no protective effect against lung metastases in recipient mice. Treatment of green fluorescent protein - chimeric animals with fastuosain did not change the number of cells that migrated to the lung, compared to PBS-injected control mice, but the number of positive major histocompatibility complex class II cells increased with fastuosain treatment. Murine antibodies against fastuosain, bromelain, and cathepsins B and L cross-reacted in ELISA and recognized surface and cytoplasmic components expressed on B16F10-Nex2 cells. Anti-fastuosain antibodies were cytotoxic/lytic to B16F10-Nex2 cells. Antitumor effects of fastuosain involve mainly the direct effect of the enzyme and elicitation of protective antibodies. Univ Fed São Paulo, UNONEX, Unidade Oncol Expt, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Univ Fed São Paulo, Discipline Parasitol, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Univ Fed São Paulo, IBILCE, Dept Quim & Ciências Ambientais, BR-04023062 São Paulo, Brazil Fiocruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil Univ Fed São Paulo, IBILCE, Dept Quim & Ciências Ambientais, BR-04023062 São Paulo, Brazil

p. 1067-1073 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-03-11T13:40:25Z No. of bitstreams: 1 Andre Lyra.pdf: 427085 bytes, checksum: a87be2bae6ef02116a97eae504b96768 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2014-09-09T16:05:03Z (GMT) No. of bitstreams: 1 Andre Lyra.pdf: 427085 bytes, checksum: a87be2bae6ef02116a97eae504b96768 (MD5) Made available in DSpace on 2014-09-09T16:05:03Z (GMT). No. of bitstreams: 1 Andre Lyra.pdf: 427085 bytes, checksum: a87be2bae6ef02116a97eae504b96768 (MD5) Previous issue date: 2007 Aim: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. Methods: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. Results: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 ± 0.9) and 4 mo (2.10 ± 1.0) after cell transplantation that baseline levels (2.78 ± 1.2). Albumin levels 4 mo after BMC infusion (3.73 ± 0.5) were higher than baseline levels (3.47 ± 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. Conclusion: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease. © 2007 The WJG Press. All rights reserved.

Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

Orientadores: Rodolfo Jardim de Azevedo, Guido Costa Souza de Araujo Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Computação Resumo: Anúncios recentes sobre os limites do desempenho dos processadores devido ao alcance da barreira térmica têm motivado a pesquisa sobre novas organizações arquiteturais e modelos de execução que visam continuar o aumento de desempenho dos processadores. Este trabalho propõe uma nova arquitetura de processador denominada 2D-VLIW. A arquitetura possui uma organização arquitetural baseada em uma matriz bidimensional de unidades funcionais e de registradores distribuídos ao longo dessa matriz. O modelo de execução 2D-VLIW possibilita que instruções longas, formadas por operações simples, sejam buscadas na memória e executadas sobre a matriz de unidades funcionais. Além disso, são propostos algoritmos para geração de código para extrair o paralelismo e preparar o código para ser executado sobre a arquitetura. Algumas contribuições deste trabalho são a concepção de uma nova arquitetura de processador que explora paralelismo em nível de instruções através de um novo arranjo dos elementos arquiteturais, a adoção de um modelo de execução que captura a geometria dos DAGs e associa os vértices e arestas desses DAGs aos recursos do hardware, um conjunto de algoritmos para escalonamento de instruções, a alocação de registradores e a codificação de instruções na arquitetura 2D-VLIW. Os resultados experimentais comparam o desempenho do modelo de execução dessa arquitetura com o modelo EPIC adotado pelo processador HPL-PD. O speedup obtido por 2D-VLIW foi de 5% at'e 63%. A estratégia de escalonamento adotada por 2D-VLIW foi também avaliada e os ganhos obtidos através do OPC e OPI foram até 4 vezes melhores que aqueles obtidos por um algoritmo de escalonamento baseado em list scheduling Abstract: Recent announcements on processor performance limits due to the thermal barrier have motivated research into innovative architectural organizations and execution models to sustain the increase of performance. This work proposes a new architecture named 2D-VLIW. The architecture provides a new architectural organization of the processing elements by using a two-dimensional functional units matrix and registers spread out along this matrix. The 2D-VLIW execution model fetches long instructions comprised of simple operations in the memory and dispatches these operations to the matrix. Moreover, the work presents new algorithms for code generation which are the responsible for extracting the parallelism of the applications and preparing the code for the 2D-VLIW architecture. Some contributions of this work are a new high performance architecture that exploits instruction level parallelism by a new arrangement of the architectural elements, the adoption of an execution model that captures the geometry of the DAGs and matches them to the hardware resources, a set of algorithms for code generation that make them possible to schedule instructions, allocate registers and encode long instructions of the 2D-VLIW architecture. Experimentos were used for comparing the performance of the 2D-VLIWexecution model to the EPIC execution model of the HPL-PD architecture. The speedup obtained by 2D-VLIW ranges from 5%-63% for all the evaluated programs. The scheduling strategy based on subgraph isomorphism was also evaluated and the OPC and OPI gains were up to 4× better than that of the list scheduling algorithm Doutorado Doutor em Ciência da Computação

The failure of neutrophils to migrate to an infection focus during severe sepsis is an important determinant of the inability of a host to deal with an infectious insult. Our laboratory has shown that inducible nitric oxide synthase (iNOS) induction and NO production contribute to the failure of neutrophils to migrate in the context of sepsis.We investigated whether CXCR2 expression contributed to the failure of neutrophils to migrate during severe sepsis and the role of NO in modulating CXCR2 expression on neutrophils in mice subjected to nonsevere (NS) or severe (S) cecal ligation and puncture (CLP).Neutrophil migration to the infection focus was deficient in S-CLP mice, a phenomenon prevented by pharmacologic (aminoguanidine, l-canavanine) or genetic (iNOS gene deletion) inhibition of iNOS. The expression of CXCR2 on neutrophils from S-CLP mice was significantly reduced when compared with neutrophils from NS-CLP or sham-operated mice. CXCR2 expression was reestablished by pharmacologic and genetic inhibition of iNOS. Immunofluorescence and confocal analysis revealed that iNOS blockade reduced neutrophil CXCR2 internalization. Adhesion and emigration of neutrophils in macrophage inflammatory protein-2-stimulated mesentery microcirculation were reduced in S-CLP mice, compared with NS-CLP mice, and reestablished by pretreatment with aminoguanidine or l-canavanine. The NO donor S-nitroso-N-acetyl-d,l-penicillamine inhibited CXCL8-induced human neutrophil chemotaxis and CXCR2 expression on human and murine neutrophils.These results highlight evidences that the failure of neutrophils to migrate to an infection focus during severe sepsis is associated with excessive NO production and NO-dependent regulation of the expression of CXCR2 on the neutrophil surface.

OBJETIVO: Avaliar efeitos precoces do transplante de células de medula óssea para o miocárdio de pacientes com insuficiência cardíaca (IC) de etiologia chagásica. MÉTODOS: A amostra consistiu de 28 pacientes, idade média 52,2±9,9 anos, 24 masculinos, 25 em classe NYHA III e 3 em NYHA IV, apesar de tratamento otimizado. O procedimento consistiu na aspiração de 50ml de medula óssea, separação da fração mononuclear e injeção intracoronariana. Foram avaliados os efeitos sobre a fração de ejeção ventricular esquerda (FEVE), distância no teste de 6 minutos, qualidade de vida, classe NYHA, efeitos arritmogênicos e bioquímicos. RESULTADOS: Não houve complicações relacionadas diretamente ao procedimento. A fração de ejeção ventricular esquerda em repouso antes do transplante era 20,1±6,8% e, após 60 dias, aumentou para 23,0±9,0%, p = 0,02. Houve melhora da classe NYHA (3,1±0,3 para 1,8±0,5; p

To evaluate early effects of bone marrow cell transplantation to the myocardium of patients with heart failure (CHF) due to Chagas disease.We studied 28 patients (mean age 52.2 +/- 9.9), of whom 24 were male. Despite optimized treatment, 25 patients were in NYHA class III and three patients, in NYHA class IV. The procedure consisted of aspiration of 50 mL of bone marrow, separation of the mononuclear fraction, and intracoronary injection. Effects on left ventricle ejection fraction (LVEF), distance walked in the six-minute walking test, quality-of-life, NYHA class, arrhythmogenic and biochemical parameters, were all evaluated.There were no complications directly related to the procedure. Baseline left ventricular ejection fraction was 20.1 +/- 6.8%, and 60 days after transplantation it increased to 23.0 +/- 9.0%, p = 0.02. Significant improvements were observed in the NYHA class (3.1 +/- 0.3 to 1.8 +/- 0.5; p0.0001); quality-of-life (50.9 +/- 11.7 to 21.8 +/- 13.4; p0.0001); and distance walked in six minutes (355 +/- 136 m to 443 +/- 110 m; p = 0,003). The number of ventricular premature beats in 24 hours tended to increase (5,322 +/- 4,977 to 7,441 +/- 7,955; p = 0,062), but without increase in ventricular tachycardia episodes (61 +/- 127 to 54 +/- 127; p = 0.27).Our data demonstrate for the first time that intracoronary injection of bone marrow mononuclear cells is feasible and suggest that it may be potentially safe and effective in patients with CHF due to Chagas disease.

Circulating antibodies in chagasic patients interact with myocardial beta adrenergic and muscarinic cholinergic receptors, triggering intracellular signals that alter cardiac function along the course of the disease. However, until now, experimental data in models of chronically infected chagasic mice linking the effects on myocardial beta adrenergic and muscarinic receptors to cardiopulmonary dysfunction is lacking. Thus, we studied C57BL/6 mice 8 months after intraperitoneal injection of 100 trypomastigote forms of the Colombian strain of T. cruzi. Uninfected mice, matched in age, were used as controls. Histopathological analyses (inflammation and fibrosis) and radio-ligand binding assays for estimation of muscarinic and adrenergic receptor density were performed in myocardium tissue samples. When compared to controls, infected mice had electrical conduction disturbances, diastolic dysfunction, lower O2 consumption and anaerobic threshold. In addition, hearts of chronic chagasic mice had intense inflammation and fibrosis, and decreased beta adrenergic and increased muscarinic receptor densities than normal controls. Our data suggest that chronic T. cruzi infection causes alterations in cardiac receptor density and fibrosis deposition which can be associated with cardiac conduction abnormalities, diastolic dysfunction and lower exercise capacity, associating for the first time all these functional and histopathological alterations in chagasic mice

In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by proinflammatory cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, profoundly lowers levels of TNF, interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either betaadrenoreceptors or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone, azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored. © 2006 Elsevier B.V. All rights reserved.

Different individuals, when infected with the same parasite, rarely produce antibodies against the same set of antigens. Indeed, unless a particular antigen happens to be recognized by antibodies in all individuals, the use of a single antigen in the serodiagnosis of parasitic diseases leads, invariably, to false-negative results. A straightforward method for pin-pointing, in genetic libraries, the precise antigens that would increase serodiagnostic assay sensitivities is presented. The method is based on the utilization of sera that produced false-negative results against previously available antigens. Employing this false-negative serum-selection methodology for the identification of new Leishmania infantum recombinant antigens (rAgs), the sensitivity of a dipstick assay for anti-Leishmania antibodies in a panel of sera from patients with visceral leishmaniasis was increased from 83.3% to 98.1%, without affecting its specificity, by the inclusion of a fifth and a sixth L. infantum rAg.

O desenvolvimento de tecnicas de transplante de orgaos solidos e de medula ossea foi um dos mais fascinantes avancos da medicina no seculo XX. A virada do seculo XXI testemunha um desdobramento tambem fascinante e promissor desta modalidade terapeutica: o uso de celulas-tronco para regenerar tecidos lesados outrora considerados irreparaveis. Resultados encorajadores de inumeros estudos com animais de experimentacao impulsionaram grupos de diversos centros no mundo a iniciar estudos clinicos com transplante de celulas-tronco em varias doencas, particularmente as doencas cardiovasculares e neurologicas. Embora ainda estejamos algo distante de entender o mecanismo preciso pelo qual as celulas-tronco regeneram orgaos lesados, os estudos publicados ate o presente momento, incluindo varios estudos envolvendo seres humanos, sugerem haver um beneficio real com esta terapia. O presente artigo pretende abordar os aspectos relevantes da terapia celular em doencas cardiovasculares, incluindo conceitos basicos sobre celulas-tronco, e os principais estudos de animais de experimentacao e clinicos publicados ate o presente.

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.

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.

Postinfarct congestive heart failure is one of the leading causes of morbidity and mortality in developed and developing countries. The main purpose of this study was to investigate whether transplantation of bone marrow stromal cells (BMSC) directly into the myocardium could improve the performance of healed infarcted rat hearts. Cell culture medium with or without BMSC was injected into borders of cardiac scar tissue 4 wk after experimental infarction. Cardiac performance was evaluated 2 wk after cellular (n = 10) or medium (n = 10) injection by electro- and echocardiography. Histological study was performed 3 wk after treatment. Electrocardiography of BMSC-treated infarcted rats showed electrical and mechanical parameters more similar to those in control than in medium-treated animals: a normal frontal QRS axis in 6 of 10 BMSC-treated and all control rats and a rightward deviation of the QRS axis in all 10 medium-treated animals. BMSC treatment, assessed by echocardiography, improved fractional shortening (39.00 +/- 4.03%) compared with medium-treated hearts (18.20 +/- 0.74%) and prevented additional changes in cardiac geometry. Immunofluorescence microscopy revealed colocalization of 4',6-diamidino-2-phenylindole-labeled nuclei of transplanted cells with cytoskeletal markers for cardiomyocytes and smooth muscle cells, indicating regeneration of damaged myocardium and angiogenesis. These data provide strong evidence that BMSC implantation can improve cardiac performance in healed infarctions and open new promising therapeutic opportunities for patients with postinfarction heart failure.

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.

BACKGROUND: Schistosoma mansoni-infected mice tend to present with either one of two different hepatic pathological patterns during chronic infection: periportal fibrosis (PF) with portal concentration of periovular granulomas and fibrosis or isolated granulomas (IG), with scattered periovular granulomas within the liver. These are models for the two clinical presentations of schistosomiasis, the severe hepatosplenic and the mild intestinal forms. In the present work, we examined the relationship between the development of these histopathological aspects and immunological markers in S. mansoni-infected mice. Although BALB/c mice with PF and IG had similar egg numbers in the liver, PF mice had higher liver collagen contents than mice with IG. Cultured spleen cells from mice with PF and IG had similar proliferation 20 and 40 weeks after S. mansoni infection upon stimulation with parasite egg antigen (SEA) or mitogen (Con A). Production of IL-4 upon SEA stimulation was higher in cell cultures from mice with PF, whereas IL-5 and IFN-gamma levels were not statistically different between PF and IG groups. Mice with IG had similar serum concentrations of total IgE and anti-SEA IgG1, IgG2a, IgG2b and IgG3 compared to sera from PF mice. Levels of IgG1 and IgG2a antibodies were the highest and the lowest detected, respectively. In conclusion, isogenic BALB/c mice infected with S. mansoni that develop periportal fibrosis or isolated granulomas have similar immunological patterns despite the two pathologic forms of schistosomal liver fibrosis.

We previously demonstrated that mice subjected to a hypoproteinic diet showed milder chronic lesions on infection with Schistosoma mansoni than normally fed mice. Here we compare the immune response of well-nourished and undernourished mice with chronic S. mansoni infection. The proliferative response and cytokine (IFN-gamma and IL-5) production of splenocytes from undernourished mice against the soluble egg antigen (SEA) of S. mansoni or concanavalin A was similar to that of well-nourished mice. The levels of SEA-specific IgG1, IgG2b and IgG3 antibodies were significantly higher in the sera of well-nourished mice in comparison with undernourished mice. Undernourished animals also exhibited diminished periovular granuloma size compared to well-nourished infected controls. Our results support the importance of host nutritional status in the humoral immune response of mice and its effects on the development of periovular granulomas in malnourished animals infected with S. mansoni.

Espécies nativas ou endêmicas do semi-árido brasileiro foram investigadas com o intuito de se descobrir novas drogas antimicrobianas. Os ensaios foram realizados contra cepas padrões de Staphylococcus aureus e Escherichia coli através do método de difusão em disco. Dos 137 extratos de vegetais avaliados, sete apresentaram atividade significativa contra o Staphylococcus aureus. Os extratos ativos foram preparados a partir de espécies pertencentes às famílias Leguminosae e Rutaceae e serão futuramente fracionados com o intuito de se chegar às moléculas ativas. Species native or endemic of the Brazilian semi-arid were investigated with the intention of discovering new antibacterial drugs. The rehearsals were accomplished against standard strains of Staphylococcus aureus and Escherichia coli through the diffusion method in disk. Of the 137 extracts of appraised vegetables, seven presented significant activity against the Staphylococcus aureus. The active extracts were prepared starting from species belonging to the Leguminosae and Rutaceae families and they will be fractional hereafter with the intention of arriving to the active molecules.

Physalis angulata L. is an annual herb widely used in popular medicine for the treatment of a variety of pathologies. Here, we tested immunomodulatory activities of physalins, seco-steroids purified from P. angulata extracts. Addition of physalins B, F or G, but not D, caused a reduction in nitric oxide production by macrophages stimulated with lipopolysaccaride and interferon-gamma. In the presence of physalin B, macrophages stimulated with lipopolysaccaride, alone or in combination with interferon-gamma, produced lower levels of tumour necrosis factor (TNF)-alpha, interleukin-6 and interleukin-12. The inhibitory activity of physalin B, unlike that of dexamethasone, was not reversed by RU486 [(4-dimethylamino) phenyl-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], an antiglucocorticoid. Physalin B-treated mice had lower levels of serum TNF-alpha than control mice after lipopolysaccaride challenge. More importantly, mice injected with physalins B, F or G survived after a lethal lipopolysaccaride challenge. These results demonstrate that seco-steroids from P. angulata are potent immunomodulatory substances and act through a mechanism distinct from that of dexamethasone.

Este trabalho apresenta o projeto e implementação de uma interface de comunicação entre o ambiente de escalonamento AMIGO e TAO, que é uma implementação da especificação CORBA. Essa interface permite que aplicações desenvolvidas com TAO utilizem os serviços de escalonamento providos pelo AMIGO. O ambiente AMIGO oferece uma maneira flexível e dinâmica de escalonamento, possibilitando um melhor desempenho para aplicações do usuário. A ferramenta TAO possibilita o desenvolvimento de aplicações distribuídas em conformidade com a especificação CORBA e, também, aplicações paralelas distribuídas através do modelo callback de mensagens assíncronas. Em trabalhos anteriores realizados no grupo de Sistemas Distribuídos e Programação Concorrente do ICMC-USP, foram implementadas com sucesso interfaces para os softwares PVM e LAM-MPI. Os resultados alcançados por esses trabalhos motivaram a implementação de uma nova interface, entre o AMIGO e uma ferramenta CORBA, com o objetivo de explorar o desenvolvimento de aplicações paralelas distribuídas na arquitetura CORBA e, conseqüentemente, oferecer serviços aprimorados de escalonamento para essas aplicações. Após a implementação da interface CORBA-AMIGO neste trabalho, foi possível verificar os ganhos que o uso de técnicas aprimoradas de escalonamento podem trazer sobre o desempenho final da aplicação. Além disso, os resultados obtidos mostraram que a ferramenta TAO é uma solução viável para o desenvolvimento de algumas classes d2 aplicações paralelas distribuídas podendo, inclusive, alcançar desempenho comparável ao desempenho observado com ferramentas construídas especificamente para essas classes de aplicações. This work presents the design and implementation of a communication interface between the AMIGO scheduling environment and TAO, that is an implementation of CORBA specification. This interface ailows applications developed with TAO to use the scheduling services provided by AMIGO. The AMIGO environment offers a flexible and dynamic scheduling, aiming at providing a better performance to user applications. TAO aliows the development of distributed applications in compliance with the CORBA specification and parailel distributed applications through the callback asynchronous messaging model. In previous works developed in the Concurrent Programming and Distributed Systems Group of the ICMC-IJSP, interfaces to PVM and LAM-MPI softwares have been successfully implemented. The results reached by these works motivated the building of a new interface between the AMIGO and a CORBA tool, aiming at exploring the development of paraliel distributed applications within the CORBA architecture and consequentely to offer better scheduling services to these applications. After the implementation of the CORBA-AMIGO interface in this work, it was possible to assess the gains that enhanced scheduling techniques can bring to the final application performance. Moreover, the results obtained showed that TAO is a viable solution to the development of some distributed parallel application classes, being able to reach performance comparable to those observed for others tools built specifically to deal with these classes of applications.

Associacao Beneficente de Coleta de Sangue da Fundacao de Apoio a Pesquisa- UNIFESP (FAP-Colsan) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-alpha after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells.Results: Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels.Conclusions: Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies. Universidade Federal de São Paulo, UNIFESP, Dept Fisiol, Lab Neurofisiol, BR-04023066 São Paulo, Brazil Universidade Federal de São Paulo, Disciplina Imunol, Dept Microimunoparasitol, São Paulo, Brazil Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil Hosp Sao Rafael, Ctr Biotecnol & Terapia Celular, Salvador, BA, Brazil Universidade Federal de São Paulo, UNIFESP, Dept Fisiol, Lab Neurofisiol, BR-04023066 São Paulo, Brazil Universidade Federal de São Paulo, Disciplina Imunol, Dept Microimunoparasitol, São Paulo, Brazil Web of Science

We have previously demonstrated that both parasite genetic variability and host genetic background were important in determining the differential tissue distribution of the Col1.7G2 and JG T. cruzi monoclonal strains after artificial infections in mice. We observed that the JG strain was most prevalent in hearts of mouse lineages with the MHC haplotype H-2(d) (BALB/c and DBA2), while Col1.7G2 was predominant in hearts from C57BL/6 mice, which have the H-2(b) haplotype. To assess whether the MHC gene region indeed influenced tissue tropism of T. cruzi, we used the same two parasite strains to infect C57BL/6 (H-2(b)) and C57BLKS/J (H-2(d)) mice; the latter strain results from the introgression of DBA2 MHC region into the C57BL/6 background. We also performed ex vivo infections of cardiac explants from four congenic mice lineages with the H-2(b) and H-2(d) haplotypes arranged in two different genetic backgrounds: C57BLKS/J (H-2(d)) versus C57BL/6 (H-2(b)) and BALB/c (H-2(d)) versus BALB/B10-H2(b) (H-2(b)). In agreement with our former observations, Col1.7G2 was predominant in hearts from C57BL/6 mice (H-2(b)), but we observed a clear predominance of the JG strain in hearts from C57BLKS/J animals (H-2(d)). In the ex vivo experiments Col1.7G2 also prevailed in explants from H-2(b) animals while no predominance of any of the strains was observed in H-2(d) mice explants, regardless of the genetic background. These observations clearly demonstrate that the MHC region influences the differential tissue distribution pattern of infecting T. cruzi strains, which by its turn may be in a human infection the determinant for the clinical forms of the Chagas disease.

Immunohistochemical studies showed that immunoglobulins from sera of patients with Chagas' disease bind specifically to endothelial cells in cryostat sections of the rodent brain. In monolayer cultures of 8-day-old rat cerebella both surface and internal labelling of the endothelial cells was detected. The contrast immune sera raised against cold-insoluble globulin (which cross-reacts with fibronectin) also labelled the surface of fibroblasts as well as the endothelial cells. It would appear that Chagasic immunoglobulins are a useful marker for endothelial cells in neural cell culture.

The family Boraginaceae is widely distributed in Brazil and in the Northeastern region some species are popularly used to treat symptoms of rheumatism, painful menstruation and dyspepsia. In this work we studied Cordia superba Cham. and C. rufescens A. DC., native from Brazilian Semi-arid region, in order to investigate their immunomodulatory activity. Six extracts were prepared from aerial parts of C. superba and C. rufescens. The cytotoxicity was evaluated using splenocytes from BALB/c mice. The immunomodulatory activity was determined by in vitro assays using activated mouse macrophages and lymphocytes. Peritoneal macrophages obtained from BALB/c mice were stimulated with IFN-gamma and LPS in the presence/absence of the samples. The NO production was measured indirectly through Griess method. Three samples inhibited the production of nitric oxide in values near 50% at a concentration of 100 µg/mL. To evaluate the effects of the extracts on lymphocytes, splenocytes from BALB/c mice were incubated with the samples and concanavalin A. Proliferation inhibition was determined by analysis of ³H-thymidine uptake. Samples from the two species had a strong inhibitory activity on lymphocyte proliferation and IL-2 production. Two chloroform extracts prepared from aerial parts of C. rufescens had the lowest IC50 values (7.6 and 11.0 µg/mL).

In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP+ cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.

The aim of the present investigation was to evaluate the effect of rabbit anti-rat macrophage serum (AMS) on the oedema and cell migration induced by a preparation of M. tuberculosis. Inflammation induced by M. tuberculosis is known to recruit macrophages, and anti-macrophage serum was found to affect macrophages in vitro as well in vivo, and is becoming a valuable tool to study their various functions1–4.