Fish Oil and Inflammation: A Perspective on the Challenges of Evaluating Efficacy in <em>Trypanosoma cruzi</em> Infection

Parasitic diseases constitute a big problem of ill health in both the tropics and subtropics as well as in more temperate climates and have been targeted by the Centers for Disease Control and Prevention (CDC) as priorities for public health in the USA. Parasitic infections can be caused by three types of organisms: protozoa, helminths and ectoparasites. They subsist on the host’s nutrients at the host’s expense. Effectively combating infections caused by parasites is essential for the survival of the organism. In this effort, cells and molecules of the immune system are susceptible to the modulating influence of fatty acids. The primary purpose of this chapter is to present a critical review of the multiple effects of fish-oil on Trypanosoma infection

Aspectos imunohistologicos das placas de Peyer de camundongos normais e infectados com Trypanosoma cruzi

Orientador : Paulo Maria Ferreira AraujoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: O estudo da atividade imunológica sob a ótica de um sistema fisiológico tem sido pouco explorado e isto fica mais evidente com respeito ao papel do tecido linfoíde associado as mucosas, que já se demonstrou ser o maior produtor espontâneo de imunoglobulinas dos mamíferos e as placas de Peyer, agregados linfóides distribuídos ao longo do intestino delgado e grosso, tomam importante papel neste processo. Paradoxalmente em ruminantes existem dois tipos de placas de Peyer; placas do jejuno e do íleo, distinguidas pela sua arquitetura, composição de linfócitos e ontogenia. Um aspecto central na abordagem de Jerne ao sistema imunológico, é que um distúrbio desencadeado pelo antígeno afeta muito mais linfócitos que aqueles capazes de interagir diretamente com o antígeno, e a ativação policlonal é um bom exemplo disso. A ativação policlonal de células B e T é muito freqüente em diferentes processos infecciosos. Este fenômeno já está bem estabelecido na infecção experimental pelo Trypanosma cruzi, onde se observa uma maciça proliferação de células B no baço e nos linfonodos. Neste trabalho, camundongos C57BL/6 infectados com T. cruzi ou não, tiveram suas placas de Peyer analisadas quanto ao número, tamanho e distribuição; submetidas a análise histológica e processadas para a determinação do número de PFC reverso, com hemácias sensibilizadas com proteína A. Os resultados do número de PFC reverso, realizado no sétimo dia de infecção, utilizando linfócitos de placas de Peyerdo duodeno - jejuno e de placas do íleo, demonstraram que estes estão aumentados e ativados, possivelmente de natureza policlonal no sétimo dia de infecção. A análise histológica deplacas de Peyer de camundongos normais não evidenciaram a existência de diferenças na arquitetura entre as mesmas, como descrito em ruminantes, embora os centros germinativos e as áreas foliculares de placas localizadas no íleo, possuam quantidade maior de grandes linfócitos em comparação aos centros germinativos e áreas foliculares das placas de Peyer do duodeno-jejuno. Os animais infectados apresentaram os centros germinativos, as áreas foliculares e parafoliculares, tanto de placas do duodeno-jejuno como do íleo, alteradas em sua citoarquitetura. As placas de Peyer destes animais apresentaram ainda, uma redução significativa no númeroMestradoImunologiaMestre em Ciências Biológica

Macrophage Polarization in Chagas Disease

Submitted by Luciane Willcox ([email protected]) on 2016-08-30T15:29:19Z No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-08-30T16:22:50Z (GMT) No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5)Made available in DSpace on 2016-08-30T16:22:50Z (GMT). No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5) Previous issue date: 2015-04-06Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunopatologia Experimental. Londrina, PR, Brasil.Macrophages are terminally differentiated cells of the mononuclear phagocytic system, which play an indispensable role in the maintenance of homeostasis and defense. Macrophages can be phenotypically polarized by the microenvironment to mount specific functional responses. Polarized macrophages can be broadly classified into two main groups: classically activated macrophages (M1), whose prototypical activating stimuli are IFN-γ and LPS, and alternatively activated macrophages (M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1β or LPS) and M2c (IL-10, TGF-β or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, while M2 macrophages support Th2- associated effector functions. Here we review the main functions of polarized macrophages in Chagas disease and discuss their potential value in evaluating disease severity

iNOS inhibition improves autonomic dysfunction and oxidative status in hypertensive obese rats

It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE2). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE2 was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity

Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats

Submitted by Luciane Willcox ([email protected]) on 2016-10-03T15:22:57Z No. of bitstreams: 1 Decreased endothelial nitric oxide.pdf: 253893 bytes, checksum: 48279c58ff340e5623f8fd3b0b140153 (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-10-03T15:31:44Z (GMT) No. of bitstreams: 1 Decreased endothelial nitric oxide.pdf: 253893 bytes, checksum: 48279c58ff340e5623f8fd3b0b140153 (MD5)Made available in DSpace on 2016-10-03T15:31:44Z (GMT). No. of bitstreams: 1 Decreased endothelial nitric oxide.pdf: 253893 bytes, checksum: 48279c58ff340e5623f8fd3b0b140153 (MD5) Previous issue date: 2014-03-14Fundo de Auxílio ao Ensino, Pesquisa e Extensão da Universidade Estadual de Londrina, Brazil, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação de Amparo a Pesquisa do Estado de São Paulo, and CNPq Conselho Nacional de Desenvolvimento Científico e TecnológicoUniversidade Estadual de Londrina. Departamento de Ciências Fisiológicas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Departamento de Ciências Patológicas. Londrina, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade de São Paulo. Escola de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Escola de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Departamento de Física e Química. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Departamento de Física e Química. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Departamento de Ciências Fisiológicas. Londrina, PR, Brasil.We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with L-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. L-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after L-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals