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ABSTRACT Introduction: Vitamin E supplementation may protect against exercise-induced muscle damage (EIMD) through possible inhibition of free radical formation and cell membrane stabilization. However, there is no systematic review of this topic. This fact maintains academic stalemates that may have a resolution. Objective: This systematic review with meta-analysis aims to provide a comprehensive literature review on the hypothesis of the benefit of vitamin E supplementation on oxidative stress and muscle damage induced by aerobic exercise. Methods: A random-effects model was used, weighted mean difference (WMD) and 95% confidence interval (CI) were applied to estimate the overall effect. Results: The results revealed a significant effect of vitamin E supplementation on reducing creatine kinase (CK) and lactate dehydrogenase (LDH). In addition, a subgroup analysis resulted in a significant decrease in CK concentrations in trials with immediate and <24 hours post-exercise CK measurement; <1000 at daily vitamin E intake; ≤1 at weekly intake; 1 at six weeks and >6 weeks experimental duration, studies on aerobic exercise and training were part of the crossover study. Conclusion: Vitamin E can be seen as a priority agent for recovery from muscle damage. Evidence Level II; Therapeutic Studies - Investigating the results.
RESUMO Introdução: A suplementação de vitamina E pode ter um efeito protetor contra danos musculares induzidos pelo exercício (EIMD) através da possível inibição da formação radical livre e estabilização da membrana celular. Todavia, não há uma revisão sistemática sobre esse tema. Tal fato mantém empasses acadêmicos que podem ter uma resolução. Objetivo: Esta revisão sistemática com meta-análise objetiva fornecer uma análise bibliográfica abrangente na hipótese do benefício na suplementação de vitaminas E sobre o estresse oxidativo e os danos musculares induzidos pelo pelo exercício aeróbico. Métodos: Foi utilizado um modelo com efeitos aleatórios, diferença média ponderada (ADM) e intervalo de confiança de 95% (IC) foram aplicados para estimar o efeito geral. Resultados: Os resultados revelaram um efeito significativo da suplementação de vitamina E na redução da creatina-quinase (CK) e lactato-desidrogenase (LDH). Além disso, uma análise do subgrupo resultou em uma diminuição significativa das concentrações de CK em ensaios com medição imediata e <24 horas de CK após o exercício; <1000 no consumo diário de vitamina E; ≤1 no consumo semanal; 1 em 6 semanas e >6 semanas de duração experimental, estudos sobre exercício aeróbico e treinamento fizeram parte do estudo cruzado. Conclusão: A vitamina E pode ser vista como um agente prioritário de recuperação de danos musculares. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.
RESUMEN Introducción: La suplementación con vitamina E puede tener un efecto protector contra el daño muscular inducido por el ejercicio (EIMD) a través de la posible inhibición de la formación de radicales libres y la estabilización de la membrana celular. Sin embargo, no existe ninguna revisión sistemática sobre este tema. Este hecho mantiene un impasse académico que puede tener resolución. Objetivo: Esta revisión sistemática con meta-análisis tiene como objetivo proporcionar una amplia revisión de la literatura sobre la hipótesis del beneficio de la suplementación con vitamina E sobre el estrés oxidativo y el daño muscular inducido por el ejercicio aeróbico. Métodos: Se utilizó un modelo de efectos aleatorios, se aplicó la diferencia de medias ponderada (DMP) y el intervalo de confianza (IC) del 95% para estimar el efecto global. Resultados: Los resultados revelaron un efecto significativo de la suplementación con vitamina E en la reducción de la creatina quinasa (CK) y la lactato deshidrogenasa (LDH). Además, un análisis de subgrupos dio como resultado una disminución significativa de las concentraciones de CK en los ensayos con medición de CK inmediata y <24 horas después del ejercicio; <1000 en la ingesta diaria de vitamina E; ≤1 en la ingesta semanal; 1 en 6 semanas y >6 semanas de duración experimental, los estudios sobre el ejercicio aeróbico y el entrenamiento formaron parte del estudio cruzado. Conclusión: La vitamina E puede resultar un agente prioritario para la recuperación del daño muscular. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.
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With increasing efficiency, accuracy, and speed we can access complete genome sequences from thousands of infectious microorganisms; however, the ability to predict antigenic targets of the immune system based on amino acid sequence alone is still needed. Here we use a Leptospira interrogans microarray expressing 91% (3359) of all leptospiral predicted ORFs (3667) and make an empirical accounting of all antibody reactive antigens recognized in sera from naturally infected humans; 191 antigens elicited an IgM or IgG response, representing 5% of the whole proteome. We classified the reactive antigens into 26 annotated COGs (clusters of orthologous groups), 26 JCVI Mainrole annotations, and 11 computationally predicted proteomic features. Altogether, 14 significantly enriched categories were identified, which are associated with immune recognition including mass spectrometry evidence of in vitro expression and in vivo mRNA up-regulation. Together, this group of 14 enriched categories accounts for just 25% of the leptospiral proteome but contains 50% of the immunoreactive antigens. These findings are consistent with our previous studies of other Gram-negative bacteria. This genome-wide approach provides an empirical basis to predict and classify antibody reactive antigens based on structural, physical-chemical, and functional proteomic features and a framework for understanding the breadth and specificity of the immune response to L. interrogans.
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Antígenos Bacterianos/sangre , Leptospira interrogans/inmunología , Leptospira interrogans/metabolismo , Leptospirosis/sangre , Proteoma/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Humanos , Leptospira interrogans/genética , Espectrometría de Masas , Análisis por Micromatrices , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Proteoma/genética , Análisis de Secuencia de ADNRESUMEN
Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Resistencia a la Enfermedad/inmunología , Esquistosomiasis/inmunología , Vacunas/inmunología , Adolescente , Adulto , Anticuerpos Antihelmínticos/inmunología , Brasil/epidemiología , Enfermedad Crónica , Análisis por Conglomerados , Enfermedades Endémicas , Femenino , Ensayos Analíticos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Desatendidas/inmunología , Análisis por Matrices de Proteínas , Esquistosomiasis/sangre , Esquistosomiasis/epidemiología , Adulto JovenRESUMEN
Brucella melitensis, one of the causative agents of human brucellosis, causes acute, chronic, and relapsing infection. While T cell immunity in brucellosis has been extensively studied in mice, no recognized human T cell epitopes that might provide new approaches to classifying and prognosticating B. melitensis infection have ever been delineated. Twenty-seven pools of 500 major histocompatibility complex class II (MHC-II) restricted peptides were created by computational prediction of promiscuous MHC-II CD4(+) T cell derived from the top 50 proteins recognized by IgG in human sera on a genome level B. melitensis protein microarray. Gamma interferon (IFN-γ) and interleukin-5 (IL-5) enzyme-linked immunospot (ELISPOT) analyses were used to quantify and compare Th1 and Th2 responses of leukapheresis-obtained peripheral blood mononuclear cells from Peruvian subjects cured after acute infection (n = 9) and from patients who relapsed (n = 5). Four peptide epitopes derived from 3 B. melitensis proteins (BMEI 1330, a DegP/HtrA protease; BMEII 0029, type IV secretion system component VirB5; and BMEII 0691, a predicted periplasmic binding protein of a peptide transport system) were found repeatedly to produce significant IFN-γ ELISPOT responses in both acute-infection and relapsing patients; none of the peptides distinguished the patient groups. IL-5 responses against the panel of peptides were insignificant. These experiments are the first to systematically identify B. melitensis MHC-II-restricted CD4(+) T cell epitopes recognized by the human immune response, with the potential for new approaches to brucellosis diagnostics and understanding the immunopathogenesis related to this intracellular pathogen.
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Brucella melitensis/inmunología , Brucelosis/inmunología , Linfocitos T CD4-Positivos/inmunología , Epítopos de Linfocito T/inmunología , Enfermedad Aguda , Antígenos Bacterianos/análisis , Proteínas Bacterianas/análisis , Enfermedad Crónica , Estudios de Cohortes , Humanos , Inmunidad Celular/inmunología , Inmunoglobulina G/inmunología , Interferón gamma/metabolismo , Interleucina-5/metabolismo , Análisis por Micromatrices/métodos , PerúRESUMEN
In order to understand the mechanisms of poor osseointegration following dental implants in type 2 diabetics, it is important to study the biological properties of alveolar bone osteoblasts isolated from these patients. We collected alveolar bone chips under aseptic conditions and cultured them in vitro using the tissue explants adherent method. The biological properties of these cells were characterized using the following methods: alkaline phosphatase (ALP) chemical staining for cell viability, Alizarin red staining for osteogenic characteristics, MTT test for cell proliferation, enzyme dynamics for ALP contents, radio-immunoassay for bone gla protein (BGP) concentration, and ELISA for the concentration of type I collagen (COL-I) in the supernatant. Furthermore, we detected the adhesion ability of two types of cells from titanium slices using non-specific immunofluorescence staining and cell count. The two cell forms showed no significant difference in morphology under the same culture conditions. However, the alveolar bone osteoblasts received from type 2 diabetic patients had slower growth, lower cell activity and calcium nodule formation than the normal ones. The concentration of ALP, BGP and COL-I was lower in the supernatant of alveolar bone osteoblasts received from type 2 diabetic patients than in that received from normal subjects (P < 0.05). The alveolar bone osteoblasts obtained from type 2 diabetic patients can be successfully cultured in vitro with the same morphology and biological characteristics as those from normal patients, but with slower growth and lower concentration of specific secretion and lower combining ability with titanium than normal ones.
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Humanos , Masculino , Persona de Mediana Edad , Proceso Alveolar/citología , Calcificación Fisiológica/fisiología , Implantes Dentales , /fisiopatología , Osteoblastos/fisiología , Osteocalcina/análisis , Fosfatasa Alcalina/análisis , Colágeno Tipo I/análisis , Oseointegración/fisiología , Osteoblastos/citología , Osteoblastos/patología , Cultivo Primario de Células/métodosRESUMEN
In order to understand the mechanisms of poor osseointegration following dental implants in type 2 diabetics, it is important to study the biological properties of alveolar bone osteoblasts isolated from these patients. We collected alveolar bone chips under aseptic conditions and cultured them in vitro using the tissue explants adherent method. The biological properties of these cells were characterized using the following methods: alkaline phosphatase (ALP) chemical staining for cell viability, Alizarin red staining for osteogenic characteristics, MTT test for cell proliferation, enzyme dynamics for ALP contents, radio-immunoassay for bone gla protein (BGP) concentration, and ELISA for the concentration of type I collagen (COL-I) in the supernatant. Furthermore, we detected the adhesion ability of two types of cells from titanium slices using non-specific immunofluorescence staining and cell count. The two cell forms showed no significant difference in morphology under the same culture conditions. However, the alveolar bone osteoblasts received from type 2 diabetic patients had slower growth, lower cell activity and calcium nodule formation than the normal ones. The concentration of ALP, BGP and COL-I was lower in the supernatant of alveolar bone osteoblasts received from type 2 diabetic patients than in that received from normal subjects (P < 0.05). The alveolar bone osteoblasts obtained from type 2 diabetic patients can be successfully cultured in vitro with the same morphology and biological characteristics as those from normal patients, but with slower growth and lower concentration of specific secretion and lower combining ability with titanium than normal ones.
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Proceso Alveolar/citología , Calcificación Fisiológica/fisiología , Implantes Dentales , Diabetes Mellitus Tipo 2/fisiopatología , Osteoblastos/fisiología , Osteocalcina/análisis , Fosfatasa Alcalina/análisis , Colágeno Tipo I/análisis , Humanos , Masculino , Persona de Mediana Edad , Oseointegración/fisiología , Osteoblastos/citología , Osteoblastos/patología , Cultivo Primario de Células/métodosRESUMEN
BACKGROUND/AIMS: A relationship between decreased propositional density (p-density) in young adulthood and future risk for Alzheimer's disease (AD) has been postulated, but multiple interpretations of the nature of this relationship are possible. This study explored the relationship between familial AD (FAD) mutation status, apolipoprotein E (APOE) genotype, and p-density. METHODS: Thirty-five non-demented persons at risk for FAD mutations were recruited. Subjects wrote brief biographical essays from which p-density, the ratio of the number of unique ideas to the number of words in the text, was calculated. mixed-effects regression models were used to examine the relationship of p-density and fad mutation status and apoe genotype. RESULTS: FAD mutation status was not significantly associated with p-density. However, results from both models indicated that the presence of the APOE ε4 allele was significantly associated with p-density (p < 0.0001), with APOE ε4 carriers having lower p-density than non-carriers. CONCLUSIONS: Our results are consistent with an influence of APOE status on p-density in young adulthood that is independent of the AD risk per se and suggest the previous finding of increased risk for the development of AD in persons with decreased p-density may be related to APOE genotype.
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Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Adulto , Envejecimiento/fisiología , Precursor de Proteína beta-Amiloide/genética , Escolaridad , Femenino , Genotipo , Heterocigoto , Humanos , Lenguaje , Masculino , Americanos Mexicanos , México , Persona de Mediana Edad , Mutación/genética , Presenilina-1/genética , Presenilina-2/genética , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Riesgo , Estados Unidos/etnologíaRESUMEN
AIMS: To characterize geographic differences in clinical characteristics and care of patients hospitalized with heart failure and preserved ejection fraction (HF-PEF). METHODS AND RESULTS: Using data on 61 182 admissions in 307 US hospitals from March 2004 to March 2006 from the Acute Decompensated Heart Failure National Registry (ADHERE)-United States (US) database and 10 904 admissions in 70 hospitals from 10 countries from March 2005 to January 2009 from the ADHERE-International (I) database composed of countries in Asia-Pacific and Latin-American regions, we compared characteristics, treatments, length of stay, and in-hospital mortality between patients with PEF (left ventricular EF ≥ 40%). There were 26 258 (49.6%) admissions with HF-PEF in the ADHERE-US and 4206 (45.7%) in ADHERE-I. The USA cohort was older [median 77.2 years (25th, 75th, 66.5, and 84.4) vs. 71.0 (59.0, 79.0), P< 0.001] and more likely to be female (61.8 vs. 54.7%, P< 0.001). The international cohort had a longer length of stay [median 6.0 days (4.0, 10.0)] vs. 4.0 days [3.0, 7.0], P< 0.001) and higher use of inotropes (12.5 vs. 4.8%, P< 0.001). At discharge, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and diuretics were prescribed more in the USA (57.6 vs. 54.4%, P< 0.001; 63.0 vs. 35.5%, P< 0.001; 78.2 vs. 76.2%, P< 0.001); digoxin was prescribed more outside the USA (26.0 vs. 17.7%, P< 0.001). After adjusting for baseline characteristics, 7-day inpatient mortality was similar between the international and the USA cohorts [hazard ratio 0.80, 95% CI (0.61-1.05); P= 0.11]. CONCLUSIONS: Clinical characteristics, inpatient interventions, discharge therapies, and length of stay vary significantly for HF-PEF patients across geographic regions. This has important implications for global clinical trials and outcome studies in HF.
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Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Sistema de Registros , Anciano , Anciano de 80 o más Años , Asia Sudoriental/epidemiología , Australia/epidemiología , Cardiología , Atención a la Salud , Femenino , Insuficiencia Cardíaca/fisiopatología , Hong Kong/epidemiología , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , América del Sur/epidemiología , Volumen Sistólico , Taiwán/epidemiología , Estados Unidos/epidemiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.