Influência da suplementação com citamina E(dl-alfa tocoferol) nas funções de monócitos e polimorfonucleares de eqüinos da raça Árabe submetidos ao exercício físico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da ação do hidróxido de cálcio sobre LPS de Pseudomonas aeruginosa por meio da liberação de óxido nítrico e TNF-'ALFA' em cultura de macrófagos peritoneais de camundongos

Pós-graduação em Odontologia - FOAR

Fator de necrose tumoral-α, interleucinas-8 e 10 em sangue de cordão umbilical como marcadores de infecção neonatal precoce na rotura prematura de membranas pré-termo

Pós-graduação em Pediatria - FMB

Comparative analysis of adverse events between infliximab and adalimumab in Crohn's disease management: a Brazilian single-centre experience

INTRODUCTION: Data is scarce regarding adverse events (AE) of biological therapy used in the management of Crohn's Disease (CD) among Brazilian patients. OBJECTIVES: To analyse AE prevalence and profile in patients with CD treated with Infliximab (IFX) or Adalimumab (ADA) and to verify whether there are differences between the two drugs. METHOD: Retrospective observational single-centre study of CD patients on biological therapy. Variables analysed: Demographic data, Montreal classification, biological agent administered, treatment duration, presence and type of AE and the need for treatment interruption. RESULTS: Forty-nine patients were analysed, 25 treated with ADA and 24 with IFX. The groups were homogeneous in relation to the variables studied. The average follow-up period for the group treated with ADA was 19.3 months and 21.8 months for the IFX group (p = 0.585). Overall, 40% (n = 10) of patients taking ADA had AE compared with 50% (n = 12) of IFX users (p = 0.571). There was a tendency towards higher incidence of cutaneous and infusion reactions in the IFX group and higher incidence of infections in the ADA treated group, although without significant difference. CONCLUSIONS: No difference was found in the AE prevalence and profile between ADA and IFX CD patients in the population studied.

Homogneous time resolved fluorescence: a new technique for detection and quantifications of infliximab in autoimmune patients

RESUMO:As terapias biológicas revolucionaram o tratamento das doenças autoimunes nos últimos anos. Tipicamente têm como alvos mediadores importantes no mecanismo das doenças. Os antagonistas do fator de necrose tumoral-α (TNF-α) são um grupo de agentes biológicos muito prescrito, pois estão indicados no tratamento de doenças imuno-mediadas comuns, tais como artrite reumatoide, artrite idiopática juvenil, artrite psoriática, espondilite anquilosante, doença de Crohn e colite ulcerosa. Com o uso frequente de inibidores do TNF-α, tem-se tornado evidente que estes agentes têm um potencial imunogénico importante, que pode comprometer o prognóstico a longo prazo dos doentes cronicamente tratados. A produção de anticorpos anti-fármaco parece causar falência terapêutica secundária em muitos doentes. Um dos efeitos dos anticorpos anti-fármaco é o aumento da eliminação do fármaco. A eliminação do fármaco, por sua vez, varia entre indivíduos, refletindo diferentes perfis farmacocinéticos. A determinação dos níveis séricos mínimos do agente anti-TNF-α é assim muito informativa e pode auxiliar nas decisões terapêuticas. Contudo, os testes imunológicos para determinar as concentrações séricas do fármaco não estão facilmente disponíveis na prática clínica. De forma a investigar uma nova técnica potencialmente fidedigna e prática para a deteção e quantificação dos agentes biológicos anti-TNF-α, foi testada a técnica por HTRF (homogeneous time-resolved fluorescence resonance energy transfer) para a determinação de concentrações séricas de infliximab. Apesar de apresentar algumas limitações relacionadas com as condições de leitura da fluorescência, esta técnica provou obter resultados próximos das concentrações obtidas por ELISA (enzyme-linked immunosorbent assay) bridging. Adicionalmente, tem a vantagem de ser de execução muito mais fácil e rápida. Deste modo, a técnica por HTRF poderá ser otimizada e tornar-se uma valiosa ferramenta laboratorial para orientar as decisões terapêuticas em doentes autoimunes com falência da terapêutica anti-TNF-α.--------- ABSTRACT: Biologic therapies revolutionized the treatment of autoimmune diseases in the last years. Typically, they target important disease mediators. Tumor necrosis factor-alpha (TNF-α) antagonists constitute a very prescribed group of biologic agents as they are indicated for the treatment of common immune-mediated diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. With the increasing use of TNF-α inhibitors it has been noticed that they have an important immunogenic potential that can compromise long-term outcomes in chronically treated patients. The production of anti-drug antibodies seems to cause secondary therapeutic failure in many patients. One of the effects of anti-drug antibodies is the enhancement of drug clearance. Drug clearance, in turn, varies among individuals, reflecting different pharmacokinetic profiles. Determination of serum anti-TNF-α drug trough levels is though very informative and could support treatment decisions. However, immunologic assays to determine drug serum concentrations are not readily available in clinical practice. In order to investigate a potentially reliable and practical new technique for detection and quantification of anti-TNF-α biologic agents, homogeneous time-resolved fluorescence resonance energy transfer (HTRF) technique was tested for determination of serum infliximab concentrations. Although presenting some limitations related with fluorescence reading conditions, this technique proved to give results close to the concentrations obtained by the widely used bridging enzyme-linked immunosorbent assay (ELISA). In addition, it has the advantage of being much easier and faster to perform. Thus, HTRF technique can be optimized and become a valuable laboratorial tool to guide treatment decisions in autoimmune patients with anti-TNF-α therapy failure.

Evaluation of inflammatory response induced by different types of daily contact lenses

Dissertação de mestrado em Genética Molecular

Efeitos do levosimendan sobre TNF-alfa, PNB e MMP-1 em pacientes com insuficiência cardíaca com anemia

FUNDAMENTO: O levosimendan é conhecido pelo seu efeito bilateral de fortalecimento contração das miofibrilas sem aumentar a demanda de oxigênio no miocárdio. A anemia é uma deterioração que causa aumento da dosagem de fármacos em pacientes com insuficiência cardíaca. OBJETIVO: No presente estudo comparamos a eficácia do tratamento com levosimendan em pacientes com insuficiência cardíaca descompensada com ou sem anemia. MÉTODOS: Foram incluídos no estudo 23 pacientes anêmicos com insuficiência cardíaca classe 3 ou 4, segundo a New York Heart Association (NYHA) e fração de ejeção abaixo de 35%. Outros 23 pacientes com o mesmo diagnóstico cardíaco, mas sem anemia, serviu como grupo controle. Ao tratamento da insuficiência cardíaca tradicional desses pacientes foi acrescido um tratamento de 24 horas de levosimendan. Amostras foram tomadas para dosar os níveis séricos do fator de necrose tumoral alfa sérico (TNF-alfa), peptídeo natriurético cerebral aminoterminal (NT-proPNB) e metaloproteinase da matriz 1 (MMP-1), antes e após a administração. RESULTADOS: Não houve diferença significativa entre os níveis séricos de TNF-alfa e MMP-1, antes e depois do tratamento (p > 0,05). Embora o nível de NT-proBNP tenha diminuído em ambos os grupos após o tratamento, não foi estatisticamente significativo (p = 0,531 e p = 0,913 para os grupos de anemia e de controle, respectivamente). Uma restauração significativa da capacidade funcional foi observada em ambos os grupos avaliados, de acordo com a NYHA (p < 0,001 e p = 0,001 para os grupos de anemia e controle, respectivamente). CONCLUSÃO: O tratamento com levosimendan apresenta efeitos semelhantes em pacientes com insuficiência cardíaca, com anemia e sem anemia. No entanto, o efeito precoce desse tratamento sobre os níveis de TNF-alfa, NT-proPNB e MMP-1 não é evidente. Ele oferece uma melhora significativa na capacidade funcional, sem a influência da anemia.

TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.

BACKGROUND The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. METHODS We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. RESULTS No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. CONCLUSION This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

Fármacos que inhiben el factor de necrosis tumoral α y embarazo

Pregunta: ?Es segura la administración de los fármacos que inhiben el factor de necrosis tumoral a (TNF-a) durante el embarazo? Respuesta: En los últimos años se han desarrollado medicamentos que inhiben el TNF-a, porque esta citocina tiene un efecto inflamatorio que condiciona el proceso patológico de diversas enfermedades autoinmunitarias sistémicas, como artritis reumatoide, psoriasis, enfermedades inflamatorias intestinales y otras. Actualmente existen en el mercado farmacéutico 5 fármacos que...

Comportamento do fator de necrose tumoral e da proteína C reativa em hepatectomia simultânea com colectomia em ratos

OBJETIVO: Observar o comportamento do fator de necrose tumoral-a (TNFalfa) e da proteína C reativa (PCR) em cirurgias simultâneas de fígado e intestino. MÉTODO: Para este objetivo foi desenvolvido um modelo experimental, no qual foram operados quarenta ratos da raça Wistar, divididos em quatros grupos: grupo controle, grupo 1 com ratos submetidos à hepatectomia a 70%, grupo 2 com ratos submetidos à colectomia e grupo 3 com cirurgia simultânea de hepactetomia e colectomia. Em todos os grupos foram dosados TNFalfa e PCR uma hora após o procedimento. Os animais foram mortos em seguida. RESULTADOS: Os valores encontrados mostraram alteração nas dosagens desses elementos nos diversos grupos, sendo que no grupo 3 houve aumento significativo do TNFalfa e queda de PCR. CONCLUSÃO: Quanto mais complexo se tornou o ato cirúrgico os níveis sangüíneos de TFNalfa aumentaram e os níveis sangüíneos da PCR diminuíram significativamente.

Evaluación del uso terapeutico del factor de necrosis tumoral, factor de crecimiento epidermico e insulina sobre el proceso de cicatrización en lesiones causadas por la reacción de Shwartzman en la piel de conejos diabéticos

Tesis (Maestría en Ciencias con Especialidad en Inmunología) UANL

Factor de necrosis tumoral y granulocitos neutrófilos en la producción del síndrome de insuficiencia respiratoria del adulto causado por peroxisomicina A-1

Tesis (Doctorado en Ciencias con Especialidad en Morfología) UANL

Avaliação do potencial anti-inflamatório de composto tipo heparina (cCTH) extraído do caranguejo Goniopsis cruentata em modelo experimental de peritonite

Heparin, a sulfated polysaccharide, was the first compound used as an anticoagulant and antithrombotic agent. Due to their structural characteristics, also has great potential anti-inflammatory, though such use is limited in inflammation because of their marked effects on coagulation. The occurrence of heparin-like compounds that exhibit anticoagulant activity decreased in aquatic invertebrates, such as crab Goniopsis cruentata, sparked interest for the study of such compounds as anti-inflammatory drugs. Therefore, the objective of this study was to evaluate the potential modulator of heparin-like compound extracted from Goniopsis cruentata in inflammatory events, coagulation, and to evaluate some aspects of its structure. The heparin-type compound had a high degree of N-sulphation in its structure, being able to reduce leukocyte migration into the peritoneal cavity at lower doses compared to heparin and diclofenac sodium (anti-inflammatory commercial). Furthermore, it was also able to inhibit the production of nitric oxide and tumor necrosis factor alpha by activated macrophages, inhibited the activation of the enzyme neutrophil elastase in low concentrations and showed a lower anticoagulant effect in high doses as compared to porcine mucosal heparin. Because of these observations, the compound extracted from crab Goniopsis cruentata can be used as a structural model for future anti-inflammatory agents

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition