Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice

Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult Schistosoma mansoni worms in vitro. In the first phase of this study, S. mansoni-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-γ, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process

Immunoregulatory properties of soluble extracts from Ascaris suum worms or eggs.

O extrato de Ascaris suum (Asc total), preparado a partir de uma mistura de vermes machos e fêmeas (albergando ovos), suprime a resposta imune específica a ovalbumina (OA). A partir do fracionamento deste extrato por gel filtração demonstrou-se que componentes protéicos de alto peso molecular (PM), eluídos no primeiro pico (PI), eram supressores da resposta a OA e os eluídos no terceiro pico (PIII) estimularam uma resposta maior de anticorpos IgE anti-Asc. Uma resposta do tipo Th2 foi preferencialmente estimulada por este extrato, sendo as citocinas IL-4 e IL-10 atuantes na supressão dos parâmetros da resposta anti-OA mediados por células Th1. Em algumas espécies de helmintos a resposta Th2 é estimulada de forma estágio-específica. Assim, analisamos neste trabalho quais dos componentes do Asc total seriam responsáveis pelo efeito supressor. Verificamos que os extratos dos vermes adultos apresentaram perfis cromatográficos semelhantes ao do extrato total. O perfil cromatográfico do Asc O foi distinto, com um segundo pico (PII) mais evidente e apresentou um quarto pico de menor PM. O fracionamento eletroforético confirmou uma concentração de proteínas com PM entre 107 e 52 kDa e a presença de proteínas adicionais entre 27,2 e 19 kDa neste extrato. Os extratos de vermes e dos ovos suprimiram a resposta imune celular específica a OA, avaliada por reações de hipersensibilidade tardia, resposta proliferativa de células de linfonodos drenantes e secreção de citocinas por estas células. A produção de anticorpos IgG1 e IgG2a anti-OA foi também diminuída acentuadamente pelos mesmos extratos. Observamos, ainda, que as citocinas predominantes na resposta aos extratos dos vermes e dos ovos foram diferentes, com maior secreção de IL-4 e IL-10 nos primeiros e IFN-g no segundo. Com relação às diferentes frações do Asc O, a produção de anticorpos IgE anti-OA foi suprimida por componentes de PI e PIII, enquanto que os de PII estimularam a síntese maior de IgE anti-Asc O. Os componentes de PIV não tiveram nenhum efeito. Nossos resultados indicam que o efeito supressivo do Asc total é uma propriedade que pode ser atribuída aos vermes machos e fêmeas. No entanto, o extrato preparado a partir dos ovos também apresenta este efeito, o qual parece ser mediado por mecanismos diferentes.The extract of Ascaris suum (whole Asc), prepared from male and female worms (with stored eggs) suppress the specific immune response to ovalbumin (OA). This extract was fractionated by gel filtration and high and low molecular weight (MW) proteins were obtained in the first (PI) and third peak (PIII), respectively. PI suppressed the OA-specific cellular and humoral responses and PIII stimulated more anti-Asc IgE antibodies. The whole Asc stimulated a Th2 response predominantly, with high levels of IL-4 and IL-10. These cytokines had an important role in the down-regulation of the Th1 response to OA. In some helminthic infections the Th2 response is stimulated by specific stages of the life cycle. Thus, in this work we investigated which components of whole Asc were responsible for immunosuppression. The worm extracts presented similar chromatographic profiles. The profile of Asc O was distinct, with the second peak being more evident and showing a fourth peak with much lower MW components. By polyacrylamide gel electrophoresis we observed a high concentration of proteins between 107 and 52 kDa. In addition, some bands between 27,2 and 19 kDa were only present in this extract. The extracts from worms and eggs suppressed the cell-mediated immune response to OA, measured by delayed-type hypersensitivity, proliferative response of draining lymph node cells and cytokine secretion. The anti-OA IgG1 and IgG2a antibody production were as drastically reduced by these extracts. The cytokines IL-4 and IL-10 were mainly secreted in response to worm extracts, whereas the egg extract stimulated more IFN-g. Regarding the different fraction of Asc O, PI and PIII components diminished the anti-OA IgE antibody production, whereas PII components stimulated higher anti-Asc O IgE synthesis. PIV components did not display any effect. Our results indicate that the immunosuppressive effect of whole Asc is due to male and female body components. However, extracts prepared from eggs do also display this effect, that seems to be mediated by different mechanisms

Immunoregulatory properties of soluble extracts from Ascaris suum worms or eggs.

O extrato de Ascaris suum (Asc total), preparado a partir de uma mistura de vermes machos e fêmeas (albergando ovos), suprime a resposta imune específica a ovalbumina (OA). A partir do fracionamento deste extrato por gel filtração demonstrou-se que componentes protéicos de alto peso molecular (PM), eluídos no primeiro pico (PI), eram supressores da resposta a OA e os eluídos no terceiro pico (PIII) estimularam uma resposta maior de anticorpos IgE anti-Asc. Uma resposta do tipo Th2 foi preferencialmente estimulada por este extrato, sendo as citocinas IL-4 e IL-10 atuantes na supressão dos parâmetros da resposta anti-OA mediados por células Th1. Em algumas espécies de helmintos a resposta Th2 é estimulada de forma estágio-específica. Assim, analisamos neste trabalho quais dos componentes do Asc total seriam responsáveis pelo efeito supressor. Verificamos que os extratos dos vermes adultos apresentaram perfis cromatográficos semelhantes ao do extrato total. O perfil cromatográfico do Asc O foi distinto, com um segundo pico (PII) mais evidente e apresentou um quarto pico de menor PM. O fracionamento eletroforético confirmou uma concentração de proteínas com PM entre 107 e 52 kDa e a presença de proteínas adicionais entre 27,2 e 19 kDa neste extrato. Os extratos de vermes e dos ovos suprimiram a resposta imune celular específica a OA, avaliada por reações de hipersensibilidade tardia, resposta proliferativa de células de linfonodos drenantes e secreção de citocinas por estas células. A produção de anticorpos IgG1 e IgG2a anti-OA foi também diminuída acentuadamente pelos mesmos extratos. Observamos, ainda, que as citocinas predominantes na resposta aos extratos dos vermes e dos ovos foram diferentes, com maior secreção de IL-4 e IL-10 nos primeiros e IFN-g no segundo. Com relação às diferentes frações do Asc O, a produção de anticorpos IgE anti-OA foi suprimida por componentes de PI e PIII, enquanto que os de PII estimularam a síntese maior de IgE anti-Asc O. Os componentes de PIV não tiveram nenhum efeito. Nossos resultados indicam que o efeito supressivo do Asc total é uma propriedade que pode ser atribuída aos vermes machos e fêmeas. No entanto, o extrato preparado a partir dos ovos também apresenta este efeito, o qual parece ser mediado por mecanismos diferentes.The extract of Ascaris suum (whole Asc), prepared from male and female worms (with stored eggs) suppress the specific immune response to ovalbumin (OA). This extract was fractionated by gel filtration and high and low molecular weight (MW) proteins were obtained in the first (PI) and third peak (PIII), respectively. PI suppressed the OA-specific cellular and humoral responses and PIII stimulated more anti-Asc IgE antibodies. The whole Asc stimulated a Th2 response predominantly, with high levels of IL-4 and IL-10. These cytokines had an important role in the down-regulation of the Th1 response to OA. In some helminthic infections the Th2 response is stimulated by specific stages of the life cycle. Thus, in this work we investigated which components of whole Asc were responsible for immunosuppression. The worm extracts presented similar chromatographic profiles. The profile of Asc O was distinct, with the second peak being more evident and showing a fourth peak with much lower MW components. By polyacrylamide gel electrophoresis we observed a high concentration of proteins between 107 and 52 kDa. In addition, some bands between 27,2 and 19 kDa were only present in this extract. The extracts from worms and eggs suppressed the cell-mediated immune response to OA, measured by delayed-type hypersensitivity, proliferative response of draining lymph node cells and cytokine secretion. The anti-OA IgG1 and IgG2a antibody production were as drastically reduced by these extracts. The cytokines IL-4 and IL-10 were mainly secreted in response to worm extracts, whereas the egg extract stimulated more IFN-g. Regarding the different fraction of Asc O, PI and PIII components diminished the anti-OA IgE antibody production, whereas PII components stimulated higher anti-Asc O IgE synthesis. PIV components did not display any effect. Our results indicate that the immunosuppressive effect of whole Asc is due to male and female body components. However, extracts prepared from eggs do also display this effect, that seems to be mediated by different mechanisms

Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice

Submitted by Ana Beatriz Oliveira ([email protected]) on 2019-04-16T13:49:32Z No. of bitstreams: 1 Maternal schistosomias.pdf: 1018997 bytes, checksum: c1ec1c407e05afe150263743a6abdda8 (MD5)Approved for entry into archive by Ana Beatriz Oliveira ([email protected]) on 2019-04-16T14:19:17Z (GMT) No. of bitstreams: 1 Maternal schistosomias.pdf: 1018997 bytes, checksum: c1ec1c407e05afe150263743a6abdda8 (MD5)Made available in DSpace on 2019-04-16T14:19:17Z (GMT). No. of bitstreams: 1 Maternal schistosomias.pdf: 1018997 bytes, checksum: c1ec1c407e05afe150263743a6abdda8 (MD5) Previous issue date: 2018Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Imunologia. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil / Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Medicina Tropical. Recife, PE, Brasil. ​Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Imunologia. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil / Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Medicina Tropical. Recife, PE, Brasil. ​Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil / Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined

Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice

Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Submitted by Adagilson Silva ([email protected]) on 2017-09-01T13:38:24Z No. of bitstreams: 1 26872339 2016 san-ges.oa.pdf: 1698870 bytes, checksum: e40dfc9f32e48eb9116565e13d2317d7 (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-09-01T13:58:39Z (GMT) No. of bitstreams: 1 26872339 2016 san-ges.oa.pdf: 1698870 bytes, checksum: e40dfc9f32e48eb9116565e13d2317d7 (MD5)Made available in DSpace on 2017-09-01T13:58:39Z (GMT). No. of bitstreams: 1 26872339 2016 san-ges.oa.pdf: 1698870 bytes, checksum: e40dfc9f32e48eb9116565e13d2317d7 (MD5) Previous issue date: 2016-02Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, BrasilSchistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants

TST conversions and systemic interferon-gamma increase after methotrexate introduction in psoriasis patients.

BackgroundTuberculosis screening in psoriasis patients is complex due to the immunological alterations associated with psoriasis, the presence of comorbidities, and the effect of immunosuppressive treatment. However, it is not established whether the results of screening tests are affected by these factors in psoriasis patients.ObjectivesTo determine whether there is a change in the results of the tuberculin skin test (TST) or the interferon-gamma release assay (IGRA) in psoriasis patients living in tuberculosis (TB)-endemic area after 12 weeks of methotrexate (MTX) treatment and to investigate the association of the test results with clinical and inflammatory markers.MethodsForty-five patients were selected for a prospective single-arm self-controlled study and followed for at least 18 months. The TST, IGRA, Psoriasis Area and Severity Index (PASI), and inflammatory factors (erythrocyte sedimentation rate (ESR), C-reactive protein, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha levels), were determined before and after 12 weeks of oral 15 mg per week MTX administration and compared. The associations between the IGRA and TST results were verified before and after treatment according to inflammatory factors and clinical characteristics (age, blood glucose, weight, body mass index, disease duration, and PASI).ResultsWe collected data on 25 patients who completed the full course of therapy and the follow-up. None of the patients developed TB. TST positivity was significantly elevated at week 12 (25% baseline vs 44% at week 12, P ConclusionsIn addition to the classic booster effect, TST conversions in patients using MTX can occur due to an increase in IFN-γ. However, it is not possible to exclude true TST conversions. Therefore, other diagnostic methods, like IGRA or chest tomography, should be used when the TST has intermediate results

Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes

Moreira, Diogo Rodrigo de Magalhães. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. A. C. L. Leite (&) F. F. Barbosa M. V. O. Cardoso D. R. M. Moreira L. C. D. Coêlho E. B. da Silva G. B. O. Filho V. M. O. de Souza Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE 50740-520, Brazil e-mail: [email protected] V. R. A. Pereira L. de C. Reis Departamento de Imunologia, Centro de Pesquisas Ageu Magalhães-FIOCRUZ, Recife, PE, Brazil P. M. P. Ferreira Departamento de Ciências Biológicas, Universidade Federal do Piauí, Picos, Piauí 64607-670, Brazil C. Pessoa Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, CE 60430-270, Brazil A. G. Wanderley Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE 50740-520, Brazil F. V. B. Mota T. G. da Silva Departamento de Antibio´ticos, Universidade Federal de Pernambuco, Recife, PE 50740-520, BrazilSubmitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-13T16:17:18Z No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-13T16:30:02Z (GMT) No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5)Made available in DSpace on 2018-06-13T16:30:02Z (GMT). No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5) Previous issue date: 2014Brazilian National Research Council (CNPq), FACEPE, and FIOCRUZMúltipla – ver em NotasAbstract A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a ‘‘one pot’’ condensation reaction to a-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide.Most of the compounds effectively suppressed nitric oxide production inmurine cells stimulatedwith lipopolysaccharide.Nphthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-a and IL-1b production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity