71 research outputs found

    Polypeptide-grafted macroporous polyHIPE by surface-initiated N-Carboxyanhydride (NCA) polymerization as a platform for bioconjugation

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    A new class of functional macroporous monoliths from polymerized high internal phase emulsion (polyHIPE) with tunable surface functional groups was developed by direct polypeptide surface grafting. In the first step, amino-functional polyHIPEs were obtained by the addition of 4-vinylbenzyl or 4-vinylbenzylphthalimide to the styrenic emulsion and thermal radical polymerization. The obtained monoliths present the expected open-cell morphology and a high surface area. The incorporated amino group was successfully utilized to initiate the ring-opening polymer- ization of benzyl-L-glutamate N-carboxyanhydride (BLG NCA) and benzyloxycarbonyl-L-lysine (Lys(Z)) NCA, which resulted in a dense homogeneous coating of polypeptides throughout the internal polyHIPE surfaces as confirmed by SEM and FTIR analysis. The amount of polypeptide grafted to the polyHIPE surfaces could be modulated by varying the initial ratio of amino acid NCA to amino-functional polyHIPE. Subsequent removal of the polypeptide protecting groups yielded highly functional polyHIPE-g-poly(glutamic acid) and polyHIPE-g- poly(lysine). Both types of polypeptide-grafted monoliths responded to pH by changes in their hydrohilicity. The possibility to use the high density of function (−COOH or −NH2) for secondary reaction was demonstrated by the successful bioconjugation of enhanced green fluorescent protein (eGFP) and fluorescein isocyanate (FITC) on the polymer 3D-scaffold surface. The amount of eGFP and FITC conjugated to the polypeptide-grafted polyHIPE was significantly higher than to the amino- functional polyHIPE, signifying the advantage of polypeptide grafting to achieve highly functional polyHIPEs

    Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

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    Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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    This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisĂŁo enfatiza a expressĂŁo e a função dos receptores muscarĂ­nicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressĂŁo dos receptores muscarĂ­nicos e adrenoceptores α1 em compartimentos especĂ­ficos de dĂșctulos eferentes, epidĂ­dimo, ductos deferentes, vesĂ­cula seminal e prĂłstata de vĂĄrias espĂ©cies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do mĂșsculo liso, incluindo efeitos na fertilidade masculina. AlĂ©m disso, a ativação dos receptores muscarĂ­nicos leva Ă  transativação do receptor para o fator crescimento epidermal e proliferação das cĂ©lulas de Sertoli. Os receptores para relaxina estĂŁo presentes no testĂ­culo, RXFP1 nas espermĂĄtides alongadas e cĂ©lulas de Sertoli de rato e RXFP2 nas cĂ©lulas de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogĂȘnico. A localização de ambos os receptores na porção apical das cĂ©lulas epiteliais e no mĂșsculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo Ă  Pesquisa do Estado de SĂŁo Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientĂ­fico e TecnolĂłgico (CNPq)Universidade Federal de SĂŁo Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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