904 resultados para Proinflammatory profile
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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OBJECTIVE: To evaluate clinical profiles, predictors of 30-day mortality, and the adherence to international recommendations for the treatment of myocardial infarction in an academic medical center hospital. METHODS: We retrospectively studied 172 patients with acute myocardial infarction, admitted in the intensive care unit from January 1992 to December 1997. RESULTS: Most patients were male (68%), white (97%), and over 60 years old (59%). The main risk factor for coronary atherosclerotic disease was systemic blood hypertension (63%). Among all the variables studied, reperfusion therapy, smoking, hypertension, cardiogenic shock, and age were the predictors of 30-day mortality. Most commonly used medications were: acetylsalicylic acid (71%), nitrates (61%), diuretics (51%), angiotensin-converting enzyme inhibitors (46%), thrombolytic therapy (39%), and beta-blockers (35%). CONCLUSION: The absence of reperfusion therapy, smoking status, hypertension, cardiogenic shock, and advanced age are predictors of 30-day mortality in patients with acute myocardial infarction. In addition, some medications that are undoubtedly beneficial have been under-used after acute myocardial infarction.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the World Health Organization (WHO) in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-gamma and TNF-alpha, a central factor in immune response against Mycobacterium tuberculosis, are responsible for the interaction between T lymphocytes and the infected macrophage and are also produced during this interaction. As proinflammatory cytokines have a close relationship with mycobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute-phase response as a result of homeostatic and physiological responses also induced by them. Acute-phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-gamma, TNF-alpha, IL-10 and TGF-beta production in supernatant of peripheral blood mononuclear cell (PBMC) and monocyte (MO) cultures, as well as serum acute-phase response through total protein, albumin, globulin, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (BSM-UH) were evaluated once and 28 pulmonary tuberculosis patients (G2): 13 from BSM-UH and 15 from the Bauru State Health Secretariat. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20ml of peripheral blood (ELISA), with or without activation: lipopolysaccharide (LPS) for MO culture and phytohemagglutinin (PHA) for PBMC culture. Acute-phase protein behavior in G2 throughout treatment was: Globulins: M1> M2, M1> M3 (rho < 0.001); CRP: M1> M2> M3 (.< 0.001); AGP for men: M1> M2, M1> M3 (rho < 0.001); ESR for men: M1> M2, M1> M3 (rho < 0.0016) and for women: M1> M2 (.< 0.025). Comparison between cytokine levels found in supernatant of MO and PBMC cultures, with and without stimulus, in G1 and G2 during treatment showed: TNF-alpha (with/ without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); (without LPS) at M3: G2> G1 (rho < 0.001), (with LPS) at M3: G2> G1 (rho < 0.028); IFN-. (with and without PHA) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); IL-10 (with and without LPS) at M1: G2> G1; at M2: G2> G1; at M3: G2> G1 (rho < 0.001); TGF-beta (with and without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001), (without LPS) at M3: G2> G1 (rho < 0.001). In G2, all cytokines in supernatant of MO and PBMC cultures, with and without stimulus, showed: M1> M2> M3 (rho < 0.01). Levels of globulins, CRP, AGP, and ESR in patients with pulmonary tuberculosis before treatment (M1) were significantly higher than reference values, suggesting their use as diagnostic markers and indicators of treatment. The CRP decreasing values along treatment could be taken as a marker of the regression of inflammatory process and of response to treatment in patients with pulmonary tuberculosis.Regarding cytokines, there was significant increase in TNF-alpha, IFN-gamma, IL-10, and TGF-alpha levels before and at three months treatment, with and without stimulus; in TNF-a and IL-10 lvels, with and without stimulus, as well as in TGF-alpha levels without stimulus at six months. Patients had higher levels of all studied cytokines than controls before treatment, and these values decreased along treatment. In this study, pulmonary tuberculosis patients showed a Th0 cytokine profile before treatment, with the production of both Th1 (IFN-gamma) and Th2 (IL-10) cytokines, in addition to TNF-alpha inflammatory and TGF-alpha regulatory and fibrosis-inducer cytokines. At the end of treatment, all had evolved to Th2 profile, probably in an attempt to reduce the harmful effects of the proinflammatory activity of the Th1 cytokine profile and of the still above-normal levels of TNF-alpha. The high levels of TGF-alpha, also found in these patients, are related to its important role in the extracellular matrix deposition and fibrosis induction that characterize tuberculosis healing process. IFN-gamma was the only cytokine reaching normal levels at the end of treatment, which suggests its use as a marker of response to treatment.
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In order to contribute to a better understanding of cytokine participation in borderline leprosy, in the present study we determined - by in vitro and in situ examinations - the production of these cytokine mediation in non-treated borderline tuberculoid (BT) patients and borderline lepromatous (BL) patients. Seven non-treated BT patients, 12 non-treated BL patients, besides 19 healthy individuals (control group), were evaluated. Peripheral blood mononuclear cells (PBMC) were stimulated or not with specific-M. leprae stimulus (whole and sonicated M. leprae antigens) and a non-specific stimulus. After 48 hours, supernatant was collected for TNF-alpha, IFN-gamma, IL-10 and TGF-beta1 cytokine determination by ELISA. Biopsies from cutaneous lesions were submitted to histological analysis and hematoxylin-eosin and Fite-Faraco stainings; the sections then underwent iNOS, IL-10 and TGF-beta1 in situ detection by immunohistochemistry. Cytokine quantification in PBMC supernatants from patients showed that BT patients produced higher levels of IFN-gamma. Compared to healthy individuals, both borderline patient groups produced lower levels of TGF-beta1 while BL patients generated lower IL-10 levels. The in situ iNOS expression was higher in BT patients compared to BL individuals. on the order hand, TGF-beta1 cytokine revealed a higher proportion of immunostained cells in BL patients. There was no significant difference in IL-10 level between BT and BL patients. Regarding cutaneous lesions, in BL patients there was a negative correlation between TGF-beta1 tissue expression and IL-10. Independently of the clinical form, we observed a positive correlation between TGF-beta1 and bacterial index as well as a negative correlation between the TGF-beta1 tissue expression and iNOS. The results even showed a positive correlation between iNOS tissue expression and production of IFN-gamma by PBMC stimulated with M. leprae antigens. Taken together, the histopathological and immunological observations reinforce the notion of immunological instability in borderline leprosy patients and indicating the participation of mixed cytokines profiles in these individuals, specifically a Th1 profile in BT patients and Th2 profile in BL patients, with a possible participation of T-regulatory lymphocytes.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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A hanseníase é doença infecto-contagiosa para a qual, além das condições individuais, outros fatores relacionados aos níveis de endemia e às condições socioeconômicas desfavoráveis influem no risco de adoecer. Objetivou-se reconhecer o perfil socioeconômico e demográfico e o grau de incapacidade instalado dos portadores de hanseníase, atendidos no Centro de Saúde Escola de Botucatu, São Paulo, Brasil. Fizeram parte do estudo 37 pacientes. Os dados foram obtidos por meio do instrumento de consulta de enfermagem. Os resultados mostraram predominância de indivíduos com união estável (78%), brancos (92%), com idade entre 30 e 49 anos (51%), com baixo nível de escolaridade e com renda familiar per capita menor que um salário mínimo. Mais de um terço dos pacientes investigados (35%) apresentavam algum grau de incapacidade física. A associação do baixo perfil socioeconômico com a presença de incapacidades físicas imprime maior vulnerabilidade a essa população, podendo impactar negativamente a sua qualidade de vida.