O estudo dos efeitos do estresse em modelos animais contribui para investigar os mecanismos de sinalização envolvidos nas enfermidades humanas. O projeto foi dividido em duas partes. Primeiramente investigou-se o efeito do estresse crônico imprevisível (ECI) na evolução clínica da encefalomielite autoimune experimental (EAE) e as concentrações circulantes de corticosterona (CORT). O ECI agravou os sinais clínicos da EAE em ratos, mas as concentrações plasmáticas de CORT durante o desenvolvimento da doença pareceram depender unicamente do desafio imunológico. Posteriormente investigaram-se os mediadores inflamatórios e o estresse oxidativo em diversas áreas do SNC de ratos submetidos à isquemia e reperfusão mesentérica. Foram observadas alterações distintas, conforme o tecido analisado, na expressão gênica de NOS e COX, atividade da NOS Ca2+-dep e da arginase e no conteúdo de TBARS. Conclui-se que, nas primeiras horas de reperfusão intestinal, as estruturas analisadas reagem diferentemente ao estresse oxidativo. / The study of stress effects in different animal models help to clarify signalization mechanisms involved in human diseases. The present project was divided in two parts. Firstly, we investigated the effects of chronic unpredictable stress (CUS) on the course of experimental autoimmune encephalomyelitis (EAE) and circulating corticosterone (CORT) concentrations. CUS aggravated the clinical signs of the disease in Lewis rats. However, plasma CORT during the development of clinical signs seemed to be solely dependent on the immunological challenge. Secondly, we investigated the oxidative and defense mechanisms in several CNS regions of rats submitted to an intestinal ischemia-reperfusion model. There were distinct results, as tissue analysis, in genic expression of NOS and COX, calcium-dependent nitric oxide synthase and arginase activities and TBARs content. Based on these results, we concluded that, at least during the first two hours of intestinal reperfusion, CNS lesions may be efficiently prevented by defense mechanisms able to modulate the oxidative injury.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-27T18:12:44Z No. of bitstreams: 1 alyriateixeiradias.pdf: 10088679 bytes, checksum: 54e2cba2e92e9707b5c8813c456ca1cb (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-06-28T12:50:27Z (GMT) No. of bitstreams: 1 alyriateixeiradias.pdf: 10088679 bytes, checksum: 54e2cba2e92e9707b5c8813c456ca1cb (MD5) / Made available in DSpace on 2016-06-28T12:50:27Z (GMT). No. of bitstreams: 1 alyriateixeiradias.pdf: 10088679 bytes, checksum: 54e2cba2e92e9707b5c8813c456ca1cb (MD5) Previous issue date: 2012-03-01 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A esclerose múltipla (EM) é uma doença autoimune que acomete o sistema nervoso central (SNC) promovendo inflamação, desmielinização e subsequente comprometimento neurológico. A encefalomielite autoimune experimental (EAE) é o modelo animal mais amplamente utilizado para o estudo da EM, podendo ser induzida por uma grande diversidade de protocolos. Porém, o resultado da doença pode ser diferente em cada modelo, dependendo das características genéticas dos animais utilizados, da fonte e concentração do material antigênico e do modo de aplicação do antígeno, refletindo, em parte, a heterogeneidade encontrada nas diversas formas clínicas da EM. Portanto, devido à diversidade de modelos de indução de EAE, vários fatores relacionados à resposta imunológica, permanecem pouco conhecidos. O presente trabalho buscou avaliar a diferença entre duas concentrações antigênicas, utilizadas na indução, sobre o desenvolvimento clínico da EAE e em diversos parâmetros da resposta imunológica. Para isto, a EAE foi induzida em camundongos da linhagem C57BL/6, utilizando-se a glicoproteína mielínica de oligodendrócitos (MOG35-55), em duas concentrações diferentes (100 ou 300 μg do peptídeo MOG35-55) e mantendo-se as concentrações de Mycobacterium tuberculosis (4 mg/mL) e toxina pertussis (300 ng) constantes. Foi então acompanhado o curso clínico da doença, nos dois protocolos utilizados, durante um período de 58 dias. Além disso, parâmetros da resposta imunológica, como avaliação do infiltrado celular no cérebro e dosagem de citocinas e quimiocinas no SNC e linfonodos inguinais foram acompanhados no 7°, 10°, 14°, 21° e 58° dias após a indução. Observou-se que embora não tenha ocorrido diferença significativa entre os grupos de animais imunizados em relação à pontuação do escore clínico, ocorreram diferenças importantes entre estes dois protocolos no que diz respeito ao perfil de citocinas, quimiocinas e infiltrado celular no cérebro. O aumento das citocinas pró-inflamatórias e quimiocinas no SNC ocorreu de forma precoce no grupo imunizado com 100 μg do peptídeo MOG35-55, que também exibiu infiltrado celular precoce e mais intenso do que o grupo imunizado com 300 μg do peptídeo MOG35- 55. Além disso, o nível das quimiocinas CCL5 e CCL20 e das citocinas de perfil Th1 e Th17 foram, de forma geral, mais elevados no grupo imunizado com 100 μg do peptídeo MOG35-55. Os resultados sugerem que somente a variação na concentração antigênica do MOG35-55, no momento da indução, não é capaz de induzir diferentes cursos clínicos de EAE e que a concentração mais elevada do antígeno (300 μg do peptídeo MOG35-55) parece promover algum mecanismo regulador ou de tolerância, que deve ser melhor estudado. / Multiple sclerosis (MS) is an inflammatory autoimmune disease of central nervous system (CNS) that causes demyelination and neurological deficit. The experimental autoimmune encephalomyelitis (EAE) is the most common model for study this disease. The EAE can be induced by different protocols and the score of the disease is related to the genetic background of the animals, the concentration of antigen and the way of induction, reproducing the heterogeneity of the MS. Thus, due to the diversity of EAE induction, different factors related to immune response are still unclear. The aim of this study was evaluate the difference between two antigen concentrations in the development of EAE and the parameters of immune response. The EAE was induced in C57BL/6 female mice with the myelin oligodendrocyte glycoprotein (MOG35-55) in two different concentrations (100 or 300μg of MOG35-55), but keeping the same concentrations of Mycobacterium tuberculosis (4 mg/mL) and pertussis toxin (300 ng). The disease clinical signs were followed until the 58th day after induction in both protocols, and the immunological parameters, such as cellular infiltrate at brain and levels of cytokines and chemokines at CNS and lymph nodes, were evaluated at 7th, 10th, 14th, 21st and 58th days post induction. In relation to the clinical score, were not observed significant differences between the different protocols, however the cytokines, chemokines and cellular infiltrate profile at brain showed interesting results. The release of Th1 and Th17 cytokines and the CCL5 and CCL20 chemokines at CNS occurred early and more intense at 100μg MOG35-55 group, in accordance with the earlier and intense cellular infiltrate than 300μg MOG35- 55 group. In conclusion, the results suggest that only the differences in the MOG35-55 concentration at induction, is not capable of induce different clinical signs of EAE and that the 300 μg of MOG35-55 seems to promote a regulatory or tolerance mechanism that deserves further studies.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-20T18:17:08Z No. of bitstreams: 1 adrianakarlagaviosilva.pdf: 1087827 bytes, checksum: c5a343cea0fe929422a92846e99a422c (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:24:59Z (GMT) No. of bitstreams: 1 adrianakarlagaviosilva.pdf: 1087827 bytes, checksum: c5a343cea0fe929422a92846e99a422c (MD5) / Made available in DSpace on 2016-09-26T20:24:59Z (GMT). No. of bitstreams: 1 adrianakarlagaviosilva.pdf: 1087827 bytes, checksum: c5a343cea0fe929422a92846e99a422c (MD5) Previous issue date: 2010-03-26 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / A Esclerose Múltipla (EM) é uma doença inflamatória, crônica e desmielinizante do sistema nervoso central (SNC). Embora ela seja, ainda, de etiologia desconhecida, é considerada uma doença auto-imune mediada por linfócitos T “helper” 1 (Th1) e T “helper” 17 (Th17) e com predominância em mulheres. Contudo, as bases para esta predominância ainda não estão bem elucidadas. Os primeiros sintomas da EM, normalmente, surgem após a maturidade sexual. Por outro lado, níveis elevados de hormônios sexuais durante o período de gravidez parecem reduzir os sinais e sintomas, os quais aumentam no período pós-parto. A Encefalomielite auto-imune experimental (EAE) é o modelo animal mais usado para estudar a EM. Assim, este estudo teve como objetivo avaliar os efeitos do tratamento com 17 β-Estradiol na prevenção da EAE murina. Os resultados indicaram que o tratamento com este hormônio melhorou o curso clínico da doença, diminuiu a concentração de citocinas pró-inflamatórias, como interferon-gama (IFN-γ), fator de necrose tumoral-alfa (TNF-α) e interleucina 17 (IL-17), e a infiltração de leucócitos no SNC, além de aumentar os níveis da interleucina 10 (IL-10). Houve, também, um aumento de linfócitos B no cérebro e baço dos animais submetidos ao tratamento. Portanto, o 17 β-Estradiol parece desempenhar um papel imunomodulador na EAE. / Multiple Sclerosis (ME) is an inflammatory, chronic and demyelinating disease of the central nervous system (CNS). Although the etiology of it is still unclear, it is considered a CD4+ T Helper-1-mediated and CD4+ T Helper-17-mediated autoimmune disease and the highest prevalence of it is in women. However, the basis for this prevalence isn´t still well clear. The first symptoms of ME, often, appear after sexual maturity. On the other hand, high levels of sexual hormones during pregnancy seems to low signs and symptoms, which to be high after childbirth. Experimental autoimmune encephalomyelitis (EAE) is an animal model to study ME. Therefore, the aim of this study was to investigate the effects of treatment with 17 β-Estradiol on murine EAE. Results indicated that the treatment with this hormone ameliorated the clinical course of the disease, decreased pró-inflammatory cytokines levels, like interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) e interleucine 17 (IL-17), and infiltration of white blood cells on CNS, further on increased interleucine 10 (IL-10) levels. There was also an increased of B cells in brain and spleen of treated animals. In conclusion, 17 β-Estradiol may play an immunomodulatory role in EAE.

Orientadores: Wanderley Dias da Silveira, Leonilda Maria Barbosa dos Santos / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-20T04:05:25Z (GMT). No. of bitstreams: 1 QuispeCabanillas_JuanGuzman_D.pdf: 2170255 bytes, checksum: 1536168e140f26af8e2fe11a63ef15ae (MD5) Previous issue date: 2012 / Resumo: A Acupuntura é uma das mais antigas formas de tratamento que tem sobrevivido e evoluido não só no Extremo Oriente (China), mas em todo o mundo. A técnica consiste na inserção de agulhas em vários níveis de profundidade da pele em pontos específicos chamados de "Acupontos", podendo ser estimuladas manualmente ou com uma corrente de baixa tensão elétrica (Eletroacupuntura). Faz parte ainda de um conjunto de técnicas com fins terapêuticos da Medicina Tradicional Chinesa, sendo, atualmente, praticada como terapia primária e adjuvante para uma variedade de doenças e condições crônicas. De outro lado a Esclerose Múltipla é uma doença inflamatória crônica do sistema nervoso central, caracterizada pela infiltração de células do sistema imune neste compartimento, com destruição de mielina e perda de oligodendrócitos, é a mais comum das doenças auto-imunes do sistema nervoso central. Trata-se de uma doença que acomete principalmente adultos jovens, sendo mais frequente nas mulheres, causando múltiplos sinais e sintomas de disfunção neurológica. Aproximadamente 85% dos pacientes apresentam a forma recorrente - remitente (surto/remissão), que é caraterizada por apresentar manifestações sintomatológicas de disfunção neurológica (exacerbação, relapso ou ataque) com períodos de estabilização ou melhora (remissão). Terapias imunomoduladoras modernas vêm sendo empregadas no tratamento da Esclerose Múltipla, no entanto, não aliviam muitos dos sintomas, como dor e depressão, levando a uma piora na qualidade de vida. Pacientes, assim, procuram tratamentos alternativos, como a acupuntura, embora os benefícios desses tratamentos não tenham sido objetivamente avaliados. O emprego do modelo experimental, a Encefalomielite Autoimune (alérgica) Experimental, tem trazido grandes contribuições para a compreensão dos mecanismos envolvidos e o esclarecimento da patogênese de doenças autoimunes, tais como a Esclerose Múltipla. Este estudo foi, portanto, concebido para avaliar o efeito da eletroacupuntura sobre a qualidade de vida de pacientes com Esclerose Múltipla tratados com imunomoduladores e na modulação da resposta imune na encefalomielite autoimune experimental. No final do estudo foi observado que a Eletroacupuntura promove a melhora em vários aspectos da qualidade de vida dos pacientes com Esclerose Múltipla, especialmente a dor, e na Encefalomielite Autoimune (alérgica) Experimental foi observado que existe uma modificação da resposta imunológica. Além disso, os resultados também sugerem que o uso rotineiro de um questionário de autoavaliação da qualidade da vida deve ser incluído nas avaliações clínicas regulares dos pacientes / Abstract: Acupuncture is one of the oldest forms of treatment that has survived and evolved not only in the Far East (China), but around the world. The technique involves inserting needles at various levels of depth of the skin at specific points called "Acupoints" and can be stimulated manually or with a low voltage electrical current (electroacupuncture). It is part of a set of therapeutic techniques the traditional chinese medicine and is currently practiced as primary therapy and adjuvant for a variety of diseases and chronic conditions. On the other hand the MS is a chronic inflammatory disease of the central nervous system characterized by infiltration of immune cells in this compartment, with destruction of myelin and oligodendrocytes loss. It is the most common of the autoimmune diseases of the central nervous system and is a disease that mostly affects young adults, being more common in women, causing multiple signs and symptoms of neurological dysfunction. Approximately 85% of patients present form recurrent-remitting MS (relapsing/remitting), which presenting symptom of neurological events (exacerbation, relapse or attack) with periods of stabilization or improvement (remission). Modern immunomodulatory therapies have been employed in the treatment of Multiple Sclerosis, however, do not alleviate many of the symptoms such as pain and depression, leading to deterioration in quality of life. Patients, therefore, seek alternative treatments such as acupuncture, although the benefits of these treatments have not been objectively evaluated. The use of model experimental autoimmune encephalitis has brought large contributions to the understanding of mechanisms and understanding the pathogenesis of autoimmune diseases such as MS. This study was therefore designed to evaluate the effect of electro on the quality of life of patients with multiple sclerosis treated with immunomodulators and modulation of immune response in experimental autoimmune encephalomyelitis. At the end of the study it was observed that electroacupuncture improved in various aspects of quality of life of patients with multiple sclerosis, especially pain, and it was observed that electroacupuncture modifies the immune response in the Autoimmune Encephalomyelitis Experimental. Moreover, the results also suggest that the routine use of a self-assessment of quality of life should be included in regular clinical evaluations of patients / Doutorado / Farmacologia / Mestre em Farmacologia

M.A. (Psychology) / Please refer to full text to view abstract

Le système nerveux central est un site particulier vis-à-vis du système immunitaire, en raison de la présence de la barrière hémato-encéphalique et de la barrière sang-liquide céphalorachidien. Les plexus choroïdes ont été considérés comme une voie d’entrée de certains lymphocytes dans le système nerveux central. Et le liquide céphalo-rachidien a été considéré comme une voie préférentielle de circulation des cellules immune au cours de la surveillance neuro-immunitaire de l’ensemble des compartiments cérébraux, puisque le LCR circule des ventricules, aux espaces sous-arachnoïdiens ainsi qu’aux velum et citernes internes. L’implication du système plexus choroïdes-liquide céphalorachidien dans l’infiltration cellulaire et la distribution des différents effecteurs immuns a été évaluée. Premièrement, nous avons analysé la relation entre le LCR et la répartition des différentes cellules immune au sein du système nerveux central, dans deux modèles d’encéphalite autoimmune expérimentale, utilisé comme modèle de la sclérose en plaque. Deuxièmement, nous avons recherché les partenaires moléculaires pouvant être impliqués dans la mise en place d’une inflammation, tels que les molécules d’adhésion exprimés par l’épithélium choroïdien, et les chimiokines pouvant être sécrétées dans le liquide céphalorachidien. Nos résultats identifient les plexus choroïdes comme une source de chimiokines sécrétées dans le liquide céphalorachidien, ce dernier orchestrant la distribution des différents effecteurs immunitaire au cours de l’inflammation / The central nervous system is an immunologically specialized site, because of the blood-brain barrier and the blood-cerebrospinal fluid barrier. The choroid plexuses had been considered as a preferential site for the entry of lymphocytes into the CNS. And the cerebrospinal fluid has been considered as a preferential pathway of circulation for immune cells during physiological neuroimmune surveillance, in all cerebral compartments, as the cerebrospinal fluid circulates from the ventricles to the subarachnoid spaces as well as the velum and internal cisterns. We evaluate the involvement of the choroid plexus-cerebrospinal fluid system in the cerebral infiltration and distribution of immune cells in CNS inflammation. First we realized a time course analysis of the different type of immune cell association with the CSF-containing compartments in two experimental autoimmune encephalomyelitis, models of multiple sclerosis. Secondly, we analyzed the molecular partners that could be involved in CNS inflammation development, such as adhesion molecules expressed on the choroid plexus, and chemokines secreted into the cerebrospinal fluid. Results identified the choroid plexuses as a source of chemokines, released into the cerebrospinal fluid that orchestrates the immune cell invasion during CNS inflammation

Orientadores: Leonilda Maria Barbosa dos Santos, Alessandro dos Santos Farias / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-27T11:48:04Z (GMT). No. of bitstreams: 1 Santos_MarianaPeresAlmeida_M.pdf: 3287854 bytes, checksum: 80bab808b4f3e83a5512a78140733089 (MD5) Previous issue date: 2014 / Resumo: O Resumo poderá ser visualizado no texto completo da tese digital / Abstract: The Abstract is available with the full electronic digital document / Mestrado / Imunologia / Mestra em Genética e Biologia Molecular

Bakgrund: ME/CFS är en allvarlig, kronisk och komplex multisystemsjukdom som ofta och dramatiskt begränsar de drabbade personernas aktivitet. De vetenskapliga beläggen gällande effekten av interventioner riktade mot funktion och funktionsnedsättning är begränsade. Nuvarande kunskapsläge indikerar att arbetsterapeuten kan bidra i vården av personer med ME/CFS, men behov av vidare forskning finns. Syfte: Att med denna litteraturöversikt kartlägga och beskriva aktuell forskning gällande arbetsterapeutens roll för personer med diagnosen ME/CFS. Metod: Datainsamling för litteraturöversikten genomfördes baserat på utarbetade urvalskriterier i tre relevanta databaser; PubMed, CINAHL och PsycINFO och resulterade i tio artiklar, sju kvantitativa och tre kvalitativa studier. Studiernas kvalitet granskades och sedan utfördes en latent innehållsanalys. Resultat: Analysen resulterade i fyra kategorier: Att ge klientcentrerat stöd för strategier i aktivitet, Att justera terapeutiskt förhållningssätt vid aktivitetsanpassning, Att beakta gruppbehandlingens terapeutiska värde samt Att bidra till professionernas teamsamverkan. Slutsats: Arbetsterapeutens kompetens är ett viktigt bidrag i rehabiliteringen på grund av den komplexa aktivitetssituation som diagnosen innebär. / Background: ME/CFS is a serious, chronic and complex systemic disease which often and dramatically limits the activity of the affected. The existing scientific evidence of interventions regarding function and disability is limited. The current level of knowledge indicates that the occupational therapist can contribute to the care for people with ME/CFS, but there is a need for further research. Aim: The aim of this literature overview was to map out and describe current research regarding the role of the occupational therapist for people diagnosed with ME/CFS. Method: Data collection for the literature overview was conducted based on developed selection criterias in three relevant databases; PubMed, CINAHL and PsycINFO which resulted in ten articles, seven quantitative and three qualitative studies. The quality of the included studies were assessed and finally a latent content analysis was completed which resulted in four categories. Result: The content analysis resulted in four categories: to supply a client centered support for strategies in activity, to adjust therapeutic approach in occupational adaptation, to consider the therapeutic value of the group treatment, and to contribute to the professional team collaboration. Conclusion: The expertise of the occupational therapist is an important contribution to rehabilitation due to the complex occupational situation for people diagnosed with ME/CFS.

Experimental autoimmune encephalomyelitis (EAE) is the rodent model of multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease that has a devastating impact on various neurological functions of the patients. The hallmarks of both, MS and EAE, are neuroinflammation, demyelination and neuroaxonal degeneration. Various types of lymphoid and myeloid cells were shown to infiltrate the central nervous system and to participate in disease pathology. However, the role of eosinophil granulocytes has been less explored thus far. An early study showed that eosinophils infiltrate into the spinal cord of EAE mice and suggested their role in the disease progression. Recently, it was reported that eosinophils can play a protective role against EAE when mice are treated with an extract from helminths. Furthermore, it was shown that EAE development is not altered in mice deficient for interleukin-5, an important eosinophil pro-survival factor. Taken together, the role of eosinophils in EAE is currently unclear and needs to be investigated in detail. In the present study, we use the active model of EAE, whereby we immunized the C57BL/6 mouse strain with MOG35-55 peptide emulsified in the complete Freund’s adjuvant, in order to study a possible contribution of eosinophils to the disease pathology. Using the flow cytometry and RT-qPCR analysis of the spinal cord, we show that eosinophils infiltrate into the tissue in the course of EAE. The infiltration is likely driven by eosinophil chemoattractants, such as eotaxin-1, as the concentration of the latter was increased in the spinal cord during EAE, as shown on mRNA and protein level. Moreover, detailed flow cytometry analysis of spinal cord eosinophils revealed that they show signs of activation, namely an increase in CD11b and decrease in CCR-3 surface expression. Furthermore, we observed signs of degranulation of spinal cord eosinophils in EAE which was measured as a decrease of the side scatter parameter and an upregulation of CD63 surface expression. These data suggest a potential role of eosinophils in the pathology of EAE. In order to elucidate whether eosinophils are important for the disease development, eosinophil-deficient mice were subjected to EAE and the clinical development of the disease was observed. For this purpose, we used two independent models of eosinophil deficiency - ΔdblGATA1 and interleukin-5-depleted mice. ΔdblGATA1 mice are a genetically manipulated mouse strain bearing a deletion in GATA1 promoter that causes a specific depletion of eosinophils. Interestingly, clinical development of EAE was not affected in these mice when compared to their wild-type controls. As a next step, we depleted eosinophils by injecting wild-type mice with an antibody against the eosinophil pro-survival factor interleukin-5 in order to reduce eosinophil numbers in the effector phase of EAE. In accordance with the result from the experiment with ΔdblGATA1 mice, EAE progression was not altered in the eosinophil-depleted mice when compared to mice that were injected with an isotype control antibody. Further, we analyzed the neuroinflammation and demyelination in the spinal cord of 4ΔdblGATA1 mice subjected to EAE. Specifically, the infiltration of inflammatory cell populations, including CD4 and CD8 T cells, neutrophils and macrophages, was assessed by flow cytometry. In agreement with the unchanged clinical EAE development, inflammatory cell infiltration was not affected in ΔdblGATA1 mice. Furthermore, we analyzed expression of pro-inflammatory cytokines in the spinal cord of ΔdblGATA1 mice subjected to EAE in order to better characterize the inflammatory status. No significant changes were detected further confirming that eosinophils do not contribute to neuroinflammation in EAE. Finally, we assessed the demyelination in the spinal cord of ΔdblGATA1 EAE mice using luxol fast blue staining to detect myelin. In accordance with the unaffected clinical development and inflammatory status, we did not observe any difference in the spinal cord demyelination in ΔdblGATA1 mice when compared to their wild-type littermates. Taken together, although eosinophils infiltrate into the spinal cord of EAE mice and are activated and degranulate therein, they are dispensable for EAE development.

No description available.