Esta dissertação analisa o Sanatório São José, uma instituição psiquiátrica particular criada no ano de 1934 na cidade de Porto Alegre, Rio Grande do Sul. O recorte temporal proposto para a pesquisa inicia com o contexto de criação do referido estabelecimento e encerra no decorrer da década de 1950 quando ocorre a introdução e a disseminação do uso de medicamentos para o tratamento psiquiátrico, o que imprime uma mudança no cotidiano e na prática institucional. Parte-se desta instituição para examinar a prática psiquiátrica de forma ampla, examina-se nesse sentido o contexto que legitimava o funcionamento de estabelecimentos desta natureza, a atuação dos psiquiatras como profissionais autorizados pela sociedade e as práticas terapêuticas desenvolvidas na instituição. Utilizam-se como fonte, sobretudo, as pastas dos pacientes internados neste estabelecimento, sendo estas de responsabilidade do Arquivo da Clínica São José. A pesquisa que segue esta dividida em três capítulos: no primeiro capítulo analisa-se o contexto da assistência psiquiátrica no Rio Grande do Sul durante as décadas de 1920 e 1930, compondo o ambiente no qual se desenvolveu a ideia da criação de um Sanatório particular. Os agentes envolvidos na criação desta instituição e os profissionais que atuaram naquele espaço – os psiquiatras e as religiosas – são analisados ainda neste espaço. No segundo capítulo, a partir dos dados presentes nos questionários iniciais – Boletins de internamento – e nas anotações clínicas presentes nas pastas dos pacientes, examinamos as concepções de alienação mental que compartilhavam aqueles que procuravam este estabelecimento, as formas como se justificava a internação, as atitudes e hábitos flagrantes de alienação mental. No decorrer do terceiro capítulo, que conclui este trabalho, ocupamo-nos dos tratamentos desenvolvidos pelos psiquiatras do Sanatório São José, traçando os referenciais teóricos e ideológicos que orientavam estas práticas, as resistências a estas terapêuticas e conclui-se esta dissertação com a análise das concepções de cura da alienação mental a partir da ação de uma instituição privada. / This dissertation analyzes the São José Sanatorium, a private psychiatric institution created in 1934 in Porto Alegre, Rio Grande do Sul. The time proposed for the survey starts with the context of the creation of that establishment and closes during the decade 1950 when occurs the introduction and use of drugs for psychiatric treatment, which prints a change in daily life and in institutional practice. Starting of this institution is to examine the psychiatric practice broadly; it examines that effect the context that legitimized the operation of establishments of this nature, the actions of psychiatrists as licensed professionals by society and therapeutic practices developed in the institution. Use’s as a source above all the folders of patients admitted at this property, which are the responsibility of the Archive of São José Sanatorium. The research that follows is divided into three chapters:, in the first chapter analyzes the context of psychiatric care in Rio Grande do Sul during the 1920s and 1930s, making the environment in which they developed the idea of creating a private sanatorium. Agents involved in the creation of this institution and the professionals who worked in that space - the psychiatrists and religious - are also analyzed in this space. In the second chapter, from the data present in the initial questionnaires - inpatient Bulletins - and the clinical notes present in the folders of patients, we examine the mental alienation concepts they shared those seeking this establishment, the ways in which he justified hospital admission, attitudes and blatant insanity habits. During the third chapter, which concludes this work we deal with the treatments developed by psychiatrists in the São José Sanatorium, tracing the theoretical and ideological references that guided these practices, resistance to these therapies and concludes this essay with the analysis of healing conceptions of mental illness from the action of a private institution.

English Abstract Crohn's disease together with ulcerative colitis, is a type of inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. IBD is an immunologically mediated multifactorial disease and it's mechanism of action is still unknown. Current well- established treatment targets the inflammation with corticosteroids and immunosuppressive drugs. Apart from the intestinal inflammation, which is the primary target of the treatment, patients are characteristically afflicted with intestinal dysbiosis. Therefore, possible interventions might be an adjuvant or biological therapy. Adjuvant therapy directly aims the microbiota with probiotics, whereas the target of biological therapy is TNF-α, a pro- inflammatory cytokine excessively secreted by macrophages. The aim of this thesis is to evaluate intestinal microbiota composition changes in IBD patients with regard to courses of adjuvant and biological therapy. Bacterial diversity was analyzed using three different DNA extraction techniques. Rapid beat beating + column (RBB+C) was chosen for analyzing patient samples, as it showed the highest DNA yield and the highest DNA purity. Primarily the bacterial diversity was analyzed using degradation gradient gel electrophoresis (DGGE) with subsequent sequencing of bands of...

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Doenças crônicas sistêmicas, em especial o diabetes mellitus, favorecem o aparecimento e a continuidade de lesões dermo-epidérmicas, sendo o impacto econômico e social significativo. No âmbito da medicina regenerativa para o tratamento de lesões cutâneas crônicas, o emprego clínico da bioengenharia de tecidos associada à terapia celular tem sido considerado uma promissora alternativa terapêutica. Neste contexto, o estudo tem como objetivo avaliar a eficácia terapêutica no tratamento de úlceras cutâneas de pacientes diabéticos, empregando células-tronco mesenquimais do tecido adiposo (CT-TA) associadas a plasma rico em plaquetas (PRP) obtido de sangue autólogo. A pesquisa aplicada foi composta por seis pacientes diabéticos e portadores de úlceras cutâneas crônicas. A reepitelização total ocorreu em 5 das 9 lesões tratadas, sendo o índice de cicatrização médio superior a 70% após 3 meses da aplicação. Desta forma, é possível concluir que a terapia com CT-TA associadas a PRP proporciona uma redução na área ulcerosa de lesões cutâneas crônicas em pacientes diabéticos. / Systemic chronic diseases, especially diabetes mellitus, favor the emergency and continuity of dermal-epidermal lesions, being significant the economic and social impact. Within the regenerative medicine field for treatment of cutaneous chronic wounds, the clinical use of tissue bioengineering and cell therapy has been considered as a promising therapeutic alternative. In this context, the present study aims to evaluate the therapeutic efficiency, using adipose-derived mesenchymal stem cells (ADSC) associated with platelet-rich plasma (PRP) obtained from autologous blood, for the treatment of cutaneous ulcers from diabetic patients. The applied research was composed of six diabetic patients with chronic skin ulcers. The total re-epithelialization occurred in 5 of the 9 lesions treated, and the average wound healing index greater than 70% after 3 months of application. In this way, it can be concluded that ADSC therapy associated with PRP provides a reduction in ulcer area of chronic skin lesions in diabetic patients.

Em sua maioria, estratégias de transferência gênica utilizam arranjos com promotores e transgenes funcionando de maneira independente entre si, como é o caso do amplamente utilizado promotor CMV. Nosso grupo foge dessa linha de promotores/transgenes independentes. Desenvolvemos uma nova estratégia de transferência gênica que combina estrategicamente a atividade do transgene e o do promotor de expressão gênica, onde o promotor foi modificado com a inserção do elemento PG, responsívo a p53. Neste trabalho construímos um novo vetor adenoviral (AdPGp53) contendo o gene da proteína supressora de tumor p53 cuja expressão é controlada por ela própria através do elemento PG. Em comparação com um vetor adenoviral que possui o gene da p53 sob ação do promotor tradicional CMV (AdCMVp53), o vetor AdPGp53 apresentou expressão superior de p53 em células humanas de carcinoma de próstata PC3, maior morte celular in vitro e parece ter diminuído o ritmo de crescimento tumoral in vivo em um modelo xenográfico de células PC3 em camundongos atímicos. / The majority of gene therapy strategies in use today are based on promoters and transgenes that work independently, and an example of this is the widely used CMV promoter. Our group breaks way from the use of independent promoter/transgene activity. We developed a new gene transfer strategy which combines the transgene activity and the promoter of gene expression. This was achieved by the insertion of the PG element, which is a p53-responsive enhancer, in the promoter. In the present work we built a new adenoviral vector (AdPGp53) containing the p53 tumor suppressor gene, whose expression is controlled by the p53 protein itself through the PG element. In comparative experiments, in which we used our AdPGp53 vector and another adenoviral vector, with a p53 gene and a traditional CMV promoter (AdCMVp53), our vector showed superior p53 expression in PC3 human prostate cancer cells, superior cell death in vitro and a tendency in diminishing tumor growth in an in vivo xenograft model in nude mice injected with PC3 cells.

Em sua maioria, estratégias de transferência gênica utilizam arranjos com promotores e transgenes funcionando de maneira independente entre si, como é o caso do amplamente utilizado promotor CMV. Nosso grupo foge dessa linha de promotores/transgenes independentes. Desenvolvemos uma nova estratégia de transferência gênica que combina estrategicamente a atividade do transgene e o do promotor de expressão gênica, onde o promotor foi modificado com a inserção do elemento PG, responsívo a p53. Neste trabalho construímos um novo vetor adenoviral (AdPGp53) contendo o gene da proteína supressora de tumor p53 cuja expressão é controlada por ela própria através do elemento PG. Em comparação com um vetor adenoviral que possui o gene da p53 sob ação do promotor tradicional CMV (AdCMVp53), o vetor AdPGp53 apresentou expressão superior de p53 em células humanas de carcinoma de próstata PC3, maior morte celular in vitro e parece ter diminuído o ritmo de crescimento tumoral in vivo em um modelo xenográfico de células PC3 em camundongos atímicos. / The majority of gene therapy strategies in use today are based on promoters and transgenes that work independently, and an example of this is the widely used CMV promoter. Our group breaks way from the use of independent promoter/transgene activity. We developed a new gene transfer strategy which combines the transgene activity and the promoter of gene expression. This was achieved by the insertion of the PG element, which is a p53-responsive enhancer, in the promoter. In the present work we built a new adenoviral vector (AdPGp53) containing the p53 tumor suppressor gene, whose expression is controlled by the p53 protein itself through the PG element. In comparative experiments, in which we used our AdPGp53 vector and another adenoviral vector, with a p53 gene and a traditional CMV promoter (AdCMVp53), our vector showed superior p53 expression in PC3 human prostate cancer cells, superior cell death in vitro and a tendency in diminishing tumor growth in an in vivo xenograft model in nude mice injected with PC3 cells.

Doenças crônicas sistêmicas, em especial o diabetes mellitus, favorecem o aparecimento e a continuidade de lesões dermo-epidérmicas, sendo o impacto econômico e social significativo. No âmbito da medicina regenerativa para o tratamento de lesões cutâneas crônicas, o emprego clínico da bioengenharia de tecidos associada à terapia celular tem sido considerado uma promissora alternativa terapêutica. Neste contexto, o estudo tem como objetivo avaliar a eficácia terapêutica no tratamento de úlceras cutâneas de pacientes diabéticos, empregando células-tronco mesenquimais do tecido adiposo (CT-TA) associadas a plasma rico em plaquetas (PRP) obtido de sangue autólogo. A pesquisa aplicada foi composta por seis pacientes diabéticos e portadores de úlceras cutâneas crônicas. A reepitelização total ocorreu em 5 das 9 lesões tratadas, sendo o índice de cicatrização médio superior a 70% após 3 meses da aplicação. Desta forma, é possível concluir que a terapia com CT-TA associadas a PRP proporciona uma redução na área ulcerosa de lesões cutâneas crônicas em pacientes diabéticos. / Systemic chronic diseases, especially diabetes mellitus, favor the emergency and continuity of dermal-epidermal lesions, being significant the economic and social impact. Within the regenerative medicine field for treatment of cutaneous chronic wounds, the clinical use of tissue bioengineering and cell therapy has been considered as a promising therapeutic alternative. In this context, the present study aims to evaluate the therapeutic efficiency, using adipose-derived mesenchymal stem cells (ADSC) associated with platelet-rich plasma (PRP) obtained from autologous blood, for the treatment of cutaneous ulcers from diabetic patients. The applied research was composed of six diabetic patients with chronic skin ulcers. The total re-epithelialization occurred in 5 of the 9 lesions treated, and the average wound healing index greater than 70% after 3 months of application. In this way, it can be concluded that ADSC therapy associated with PRP provides a reduction in ulcer area of chronic skin lesions in diabetic patients.

Optimization of biologic therapy in children with inflammatory bowel disease (IBD) using modern biomarkers Abstract to thesis Study programme: Biochemistry and Pathobiochemistry Introduction: In adults, infliximab (IFX) levels correlate with disease activity and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in paediatric population. Methods: This study was performed as a prospective observational study. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). We used multivariate analysis to identify the predictors of IFX levels. IFX and ATIs levels were meassured using ELISA. Results: Lower levels of IFX were associated with ATIs positivity (OR [odds ratio] 0.027, CI [confidence interval] 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and CPT levels were found in patients with lower IFX levels. The optimal combination of specificity (50%) and sensitivity (74%) for disease activity was calculated for IFX levels ≥ 1.1 µg/ml using CRP level < 5 mg/l as a marker of laboratory remission. In a model that used CPT ≤...

The submitted thesis deals with the theme of a neurodegenerative autoimmune disease, the sclerosis multiplex. Although this serious disease has become an object of intensive research in recent decades and there is an inexhaustible quantity of literature available, we haven't yet fully identified the causes of this disease as well as we haven't found such kind of effective treatment that would lead to the permanent recovery of patients. I focused my interest on two main spheres: first, the description and comparison of practices in terms of pharmacotherapy giving priority to its benefits to patients, second, the view of another important but not always appreciated part of therapy, physiotherapy or rehabilitation; the main point is studying of processes and actions from the pedagogical point of view.

INTRODUÇÃO: Diversos ensaios clínicos randomizados (ECR) foram realizados nos últimos anos sobre a eficácia dos agentes biológicos no tratamento da artrite reumatóide (AR). Porém, as revisões sistemáticas sobre o tema ainda geram dúvidas sobre a real eficácia relacionada à capacidade funcional e qualidade de vida. MÉTODOS: O presente estudo sintetizou as evidências geradas pelas revisões sistemáticas que compararam o tratamento realizado com a utilização dos agentes biológicos e o tratamento convencional com a utilização das drogas anti-reumáticas modificadoras da doença de síntese química (DARMDq), considerando a capacidade funcional e qualidade de vida dos pacientes com AR, além de avaliar a qualidade metodológica das revisões sistemáticas recuperadas. Utilizamos as bases de dados PubMed (Medline), EMBASE e Cochrane para realizar o levantamento de revisões sistemáticas com ou sem meta-análises de ECR. Dois pesquisadores de maneira independente realizaram a seleção das revisões sistemáticas, avaliaram a qualidade metodológica utilizando a ferramenta AMSTAR e classificaram a qualidade das evidências pelo GRADE. RESULTADOS: Esta overview incluiu 10 revisões sistemáticas e meta-análises de ECR que avaliaram a capacidade funcional mensurada pelo HAQ e a qualidade de vida mensurada pelo SF-36 (PCF e PCM) em pacientes com AR que utilizaram a terapia com os agentes biológicos comparada a terapia convencional com a utilização das DARMDq. A maioria da revisões sistemáticas apresentaram alta qualidade metodológica avaliada pela ferramenta AMSTAR e a qualidade da evidência variou entre baixa a alta qualidade pelo GRADE. A melhora da capacidade funcional e qualidade de vida observada no período inicial do tratamento (24 semanas) com a terapia biológica, foi de pequena relevância clínica. Esta diferença entre os tratamentos não foi observada no longo prazo (52 semanas), principalmente com os agentes biológicos na forma de monoterapia. CONCLUSÃO: Evidências que variam entre baixa a alta qualidade mostraram que os agentes biológicos apresentaram melhora de baixa relevância clínica na capacidade funcional e qualidade de vida no período inicial do tratamento em comparação à terapia convencional com as DARMDq. Entretanto, não há diferenças entre a utilização da terapia biológica e da terapia convencional a longo prazo / INTRODUCTION: Several randomized clinical trials (RCTs) have been conducted in recent years on the efficacy of biological agents in the treatment of rheumatoid arthritis (RA). However, systematic reviews on this topic still raise doubts about the real efficacy related to functional capacity and quality of life. METHODS: This study synthesized the evidence generated by systematic reviews comparing the treatment with biological agents and the conventional treatment with disease-modifying antirheumatic drugs (DMARD), considering the functional capacity and quality of life of patients with RA, also evaluating the methodological quality of the systematic reviews retrieved. PubMed (Medline), EMBASE and Cochrane databases were searched for systematic reviews with or without RCT meta-analyzes. Two researchers independently carried out the selection of systematic reviews, assessed the methodological quality using the AMSTAR tool and classified the quality of the evidence by GRADE. RESULTS: This overview included 10 systematic reviews and meta-analyzes of RCTs that assessed functional capacity measured by HAQ and quality of life measured by SF-36 (PCS and MCS) in RA patients who used therapy with biological agents compared to conventional therapy with DMARDq. Most of the systematic reviews presented high methodological quality evaluated by the AMSTAR tool and the quality of the evidence ranged from low to high quality by GRADE. The improvement in functional capacity and quality of life observed in the initial period of treatment (24 weeks) with biological therapy presented low clinical relevance. This difference between the treatments was not observed in the long term (52 weeks), mainly with the biological agents in the form of monotherapy. CONCLUSION: Evidence that varied between low to high quality demonstrated that biological agents presented improvement with low clinical relevance of the functional capacity and quality of life during the initial period of treatment compared to conventional therapy with DMARDq. However, there are no differences in the long term between the use of biological therapy and conventional therapy