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Redispersible powders based on soft core-hard shell polymer particles can be used as additives in polymer-cement mortars. The role of this morphology on the spray-drying production of these powders and on the crack-bridging properties of the corresponding cement-based membranes is investigated. Different polymer latexes at high solid content with varied core-shell ratio, shell thickness and chemical composition (hardness) were prepared from styrene and 2-ethylhexyl acrylate monomers via semi-batch emulsion polymerization. The latexes were characterized in terms of size, composition, and glass transition temperature (T g ), and spray-dried to obtain redispersible polymer powders (RPPs) using poly (vinyl alcohol) and limestone powder as anti-caking agents. The polymer powders were mixed with a mortar mixture and redispersed in water to produce cement-based membranes, which were tested for crack-bridging properties at different temperatures. The results showed that it was not possible to spray-dry a dispersion of homogeneous polymer particles with T g of -25 ∘ C, unless these particles are protected by much harder (high T g ) shell. In particular, it was observed that a thicker shell improved the spray-ability, but lowered the crack-bridging properties of the produced membrane. A trade-off between these two was revealed to be the key for the optimal design of the polymer nanoparticles, as proven by the systematic study of the core-shell morphology reported in this work. The best compromise was shown to consist of particles larger than 300 nm, shell thickness of about 5 nm, and core-shell ratio of 97%, with styrene content in the shell not larger than 80% to avoid excessive hydrophobicity.
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BACKGROUND#ENTITYSTARTX02014;: Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naïve CD4(+)T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4(+)T-cell subsets and atherosclerosis. METHODS AND RESULTS#ENTITYSTARTX02014;: We analyzed 57 subsets of circulating CD4(+)T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (T(EM): CD3(+)CD4(+)CD45RA(-)CD45RO(+)CCR7(-) cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between T(EM) and low-density lipoproteins was observed. In the second cohort (n=130), T(EM) levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR(+)T(EM) were the T(EM) subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, T(EM) (identified as CD4(+)CD44(+)CD62L(-)) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01). CONCLUSIONS#ENTITYSTARTX02014;: Circulating T(EM) cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4(+)T-cell subset related to the atherosclerotic process. (J Am Heart Assoc. 2012;1:27-41.).
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OBJECTIVES: This study sought to assess the prevalence of normal levels of high sensitivity C-reactive protein (hsCRP) at the very onset of ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Levels of hsCRP ≥2 mg/l identify individuals who benefit from lipid lowering and possibly anti-inflammatory agents, but how many patients develop infarction in spite of hsCRP levels <2 mg/l and thus would be ineligible for these treatments? METHODS: We studied 887 patients with unequivocally documented STEMI as the first manifestation of coronary disease and 887 matched control subjects from urban areas of Italy, Scotland, and China. Blood samples were obtained before reperfusion strategies <6 h from symptoms onset in order to limit acute event-related increases. RESULTS: hsCRP values were similar in samples obtained <2 h, 2 to 4 h, and 4 to 6 h from symptoms onset in all ethnic groups, consistent with the delayed hsCRP elevation after myocardial necrosis and thus indicative of pre-infarction levels. Median hsCRP values were significantly higher in patients than in control subjects: 2.49 (interquartile range [IQR]: 1.18 to 5.55) mg/l versus 1.32 (IQR: 0.58 to 3.10) mg/l (p < 0.0001), which is consistent with previous findings. However, 41% of patients had hsCRP levels <2 mg/l and conversely, 37% of control subjects had values ≥2 mg/l. CONCLUSIONS: The measurement of hsCRP, with a 2 mg/l cutoff, would not have predicted 41% of unequivocally documented STEMIs in 3 ethnic groups without evidence of previous coronary disease, thus indicating both its limitations as an individual prognostic marker and as an indicator of a generalized inflammatory pathogenetic component of STEMI. New specific prognostic and therapeutic approaches should be found for such a large fraction of patients at risk.
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Proteína C-Reactiva/análisis , Infarto del Miocardio/sangre , Infarto del Miocardio/etnología , Anciano , Estudios de Casos y Controles , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Valor Predictivo de las Pruebas , PrevalenciaRESUMEN
OBJECTIVE: Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. METHODS AND RESULTS: We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3(+)CD4(+)CD25(high)CD127(low)) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (n=65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). CONCLUSIONS: The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis.
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Enfermedades de las Arterias Carótidas/inmunología , Enfermedad de la Arteria Coronaria/inmunología , Subunidad alfa del Receptor de Interleucina-7/sangre , Linfocitos T Reguladores/inmunología , Síndrome Coronario Agudo/inmunología , Anciano , Angina de Pecho/inmunología , Biomarcadores/sangre , Recuento de Linfocito CD4 , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/genética , Humanos , Inmunofenotipificación , Mediadores de Inflamación/sangre , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , ARN Mensajero/sangre , Índice de Severidad de la Enfermedad , UltrasonografíaRESUMEN
OBJECTIVE: The T-cell receptor zeta (TCR zeta)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR zeta-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR zeta(dim) T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR zeta(dim) T cells in coronary artery disease. METHODS AND RESULTS: We examined the expression of TCR zeta-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4(+) TCR zeta(dim) T cells were found in patients with acute coronary syndromes (ACS, n=66; median 5.3%, interquartile 2.6 to 9.1% of total CD4(+) T cells; P<0.0001) compared to chronic stable angina (CSA, n=32; 1.6%; 1.0 to 4.1%) and controls (n=42; 1.5%; 0.5 to 2.9%). Such increase was significantly greater in ACS patients with elevated levels of C-reactive protein, and it persisted after the acute event. Moreover, TCR zeta(dim) cells were also more represented within CD8(+) T cell, NK, and CD4(+)CD28(null) T cell subsets in ACS compared to CSA and controls. Finally, CD4(+) and CD8(+) TCR zeta(dim) T cells isolated from ACS displayed an enhanced transendothelial migratory capacity. CONCLUSIONS: TCR zeta(dim) T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.