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1.
Heart Lung Circ ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33229241

RESUMO

BACKGROUND: The best approach for aortic root disease remains controversial. Composite valve-graft conduit (CVG) replacement offers good results at short-term and long-term follow-up; on the other hand, valve-sparing aortic root replacement (VSARR) has proven to be an excellent treatment alternative. This study aimed to analyse the outcomes after VSARR and compare whether preoperative moderate or severe aortic regurgitation (AR) and or the need for aortic valve repair (AVR) during this procedure influenced survival and freedom from reoperation rates. METHODS: From September 2005 to June 2018, 104 patients underwent VSARR using the reimplantation technique: 64% presented with preoperative moderate or severe AR, concomitant AVR was performed in 43.3%, Marfan syndrome was present in 16.3%, and 12.5% had a bicuspid aortic valve. Complete follow-up was obtained in 91% of the sample, echocardiographic results were available for 86% and the mean follow-up time was 1,893 days. RESULTS: In-hospital mortality was 2.9% and one death occurred 42 days after hospital discharge. In the latest echocardiographic assessment, 88.3% presented with mild AR or better. Freedom from reoperation at 8 years was 95.4%. There was no case of endocarditis and one patient had a stroke 2 years after the operation. There were no between-group differences in morbidity, mortality and complications during the follow-up. CONCLUSION: VSARR can be performed with low mortality rates and reasonable durability of the aortic valve. Neither moderate or severe AR nor the need for aortic valve repair during the procedure altered survival and freedom from reoperation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33113317

RESUMO

INTRODUCTION: The objective of this study was to evaluate whether a surgery with the use of valved conduit is capable of leading to better immediate and late results than those obtained by the valve-sparing aortic root reconstruction technique. METHODS: Between January 2002 and June 2016, 448 patients underwent aortic root reconstruction. These were divided into three groups according to the technique used: 319 (71.2%) patients received mechanical valved conduits, 49 (10.9%) received biological valved conduits, and 80 (17.9%) underwent the valve-sparing aortic root reconstruction technique. The results were examined by univariate and multivariate analyses of Cox proportional hazards models with multiple logistic regression. RESULTS: The hospital mortality rate was 7.5%. The mortality rates were 8.2%, 12%, and 2.5% in the mechanical valved conduit, biological valved conduit, and aortic valve-sparing groups, respectively, with no significant difference between groups (P=0.1). Thromboembolic complications and reoperationfree survival were also similar (P=0.169 and P=0.688). However, valve-sparing aortic root replacement was superior in terms of long-term survival (P<0.001), hemorrhagic-free survival (P<0.001), and endocarditis-free survival (P=0.048). Multivariate analysis showed that the following aspects had an impact on mortality: age > 70 years (P<0.001; hazard ratio [HR] 1.05), preoperative acute kidney injury (P<0.0042; HR 2.9), diagnosis of dissection (P<0.01; HR 2.0), previous cardiac surgery (P<0.027; HR 2.3), associated coronary artery bypass grafting (P<0.038; HR 1.8), reoperation for postoperative tamponade (P<0.004; HR 2.2) and postoperative acute kidney injury (P<0.02; HR 3.35). CONCLUSION: Valve-sparing technique seems to be the operation of choice, whenever possible, for aortic root reconstruction.

4.
Molecules ; 25(17)2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32858905

RESUMO

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor but ubiquitous component of the inner leaflet of the plasma membrane of eukaryotic cells. However, due to its particular complex biophysical properties, it stands out from its neighboring lipids as one of the most important regulators of membrane-associated signaling events. Despite its very low steady-state concentration, PI(4,5)P2 is able to engage in a multitude of simultaneous cellular functions that are temporally and spatially regulated through the presence of localized transient pools of PI(4,5)P2 in the membrane. These pools are crucial for the recruitment, activation, and organization of signaling proteins and consequent regulation of downstream signaling. The present review showcases some of the most important PI(4,5)P2 molecular and biophysical properties as well as their impact on its membrane dynamics, lateral organization, and interactions with other biochemical partners.

5.
J Mech Behav Biomed Mater ; 111: 103976, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32750673

RESUMO

Traumatic brain injury is one of the major causes of death and disability in the world. One of the most frequent and deadly injury resulted from a head trauma is acute subdural haematoma (ASDH), which consists on the rupture of a bridging vein (BV). Given the importance of this type of injury, it is necessary to correctly assess thresholds and damage criteria, which is difficult to perform on human cadavers or animals, due to ethical and economical issues. Finite element (FE) models are a very good and cost-effective alternative. Once properly validated, a finite element head model (FEHM) becomes a valuable tool, that can be used in the development of head protective gear as a design tool and in the reconstruction of head traumas by predicting brain injuries under impact conditions. The YEt Another Head Model (YEAHM) is one example of a FE model that can be used to assist/replace the experimental tests. In this study, the bridging veins model from YEAHM was improved and validated by comparing its results with others reported in literature and estimating the success rate. At the end, it was developed a pressurised tubular shaped FE model of BVs, considering the blood pressure in cerebral veins. Results showed a maximum success rate of 90%, which in comparison with other FE models available in the literature, presents an equal or even better ASDH prediction success rate.

6.
Chemistry ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627856

RESUMO

Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a "boron hot spot" based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (Ka of 58128±2 m-1 ). The reaction is selective in the presence of competing lysine ϵ-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.

7.
Eur J Med Chem ; 201: 112418, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590115

RESUMO

A series of highly active hybrids were discovered as novel antiparasitic agents. Two heterocyclic scaffolds (1,2,4-oxadiazole and 3-hydroxy-2-oxindole) were linked, and the resulting compounds showed in vitro activities against intracellular amastigotes of two protozoan parasites, Trypanosoma cruzi and Leishmania infantum. Their cytotoxicity was assessed using HFF-1 fibroblasts and HepG2 hepatocytes. Compounds 5b, 5d, 8h and 8o showed selectivity against L. infantum (IC50 values of 3.89, 2.38, 2.50 and 2.85 µM, respectively). Compounds 4c, 4q, 8a and 8k were the most potent against T. cruzi, exhibiting IC50 values of 6.20, 2.20, 2.30 and 2.20 µM, respectively. Additionally, the most potent anti-T. cruzi compounds showed in vitro efficacies comparable or superior to that of benznidazole. These easy-to-synthesize molecules represent novel chemotypes for the design of potent and selective lead compounds for Chagas disease and leishmaniasis drug discovery.

8.
Rev Assoc Med Bras (1992) ; 66(3): 345-352, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32520156

RESUMO

Cardiac amyloidosis is an infiltrative disease which requires a high degree of clinical suspicion for appropriate diagnosis. Early diagnosis and the definition of the type of amyloidosis play a key role in the early treatment and prognosis of this disease. In this context, the use of cardiac biomarkers such as troponins and NT-proBNT associated with analysis by multimodality imaging methods like echocardiographic techniques such as strain, nuclear medicine, and cardiovascular resonance imaging have an increasing role in patients with cardiac amyloidosis. This article details the role of non-invasive diagnostic methods in patients with cardiac amyloidosis.


Assuntos
Amiloidose/diagnóstico , Biomarcadores , Ecocardiografia , Humanos , Espectroscopia de Ressonância Magnética , Prognóstico , Cintilografia , Tomografia Computadorizada por Raios X
9.
Arq Bras Cardiol ; 114(4): 683-689, 2020 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32491013

RESUMO

Background Galectin-3 (Gal-3) is a proinflammatory, profibrotic molecule implicated in the pathogenesis of heart failure. The role of Gal-3 in patients with chronic constrictive pericarditis (CCP) is not clear. Objective The aim of this study was to assess plasma Gal-3 in patients with CCP and correlate it with clinical, functional and histologic parameters. Methods We prospectively evaluated 25 symptomatic patients with CCP referred for pericardiectomy and 21 healthy controls. Patients underwent clinical assessment, Gal-3 and B-type natriuretic peptide (BNP) measurements, echocardiography, cardiac magnetic resonance imaging and cardiopulmonary exercise test (CPET) at baseline. Six months after pericardiectomy CPET was repeated. An alpha error < 5% was considered statistically significant, with a confidence interval of 95%. Results Twenty-five patients with a median age of 45 years were included. Etiology was mainly idiopathic (n = 19, 76%); and 14 (56%) patients had NYHA functional class III/IV. Median BNP and Gal-3 were 143 (89-209) pg/dL and 14.8 (9.7-17.2) ng/mL, respectively. Gal-3 levels were not significantly higher in CCP patients than in control (p = 0.22). There were no significant correlations of Gal-3 with BNP, echocardiographic and cardiac magnetic resonance measures and histological findings. After pericardiectomy, it was found a statistically significant correlation between Gal-3 and the CPTE measures test duration (r = -0.79; p < 0.001) and exercise time (r = -0.79; p < 0.001). Conclusions Patients with CCP had normal levels of Gal-3 as compared to the controls. Gal-3 did not correlate with morphological and functional measures before pericardiectomy. However, the associations between Gal-3 and exercise intolerance after pericardiectomy may suggest a role of Gal-3 in prognosis prediction after pericardiectomy. (Arq Bras Cardiol. 2020; 114(4):683-689).


Assuntos
Pericardite Constritiva , Doença Crônica , Galectina 3 , Humanos , Pessoa de Meia-Idade , Pericardiectomia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
10.
ESC Heart Fail ; 7(4): 1744-1752, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383349

RESUMO

AIMS: Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. METHODS AND RESULTS: In GENIUS-HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3-1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. CONCLUSIONS: This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.

11.
Arq. bras. cardiol ; 114(4): 683-689, Abr. 2020. ilus, tab
Artigo em Português | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1100302

RESUMO

FUNDAMENTO: A galectina-3 (Gal-3) é uma molécula pró-inflamatória e pró-fibrótica, envolvida na patogênese da insuficiência cardíaca. O papel da Gal-3 em pacientes com pericardite constritiva crônica (PCC) não está claro. OBJETIVO: O objetivo deste estudo foi avaliar os níveis de Gal-3 em pacientes com PCC e correlacioná-los com parâmetros clínicos, funcionais e histológicos. MÉTODOS: Nós avaliamos prospectivamente 25 pacientes sintomáticos com PCC agendados à pericardiectomia e 21 controles sadios. Os pacientes foram submetidos à avaliação clínica, medidas de Gal-3 e peptídeo natriurético do tipo B (BNP), ecocardiografia, ressonância magnética cardíaca e teste cardiopulmonar de exercício (TCPE) no período basal. Seis meses após a pericardiectomia, repetiu-se o TCPE. Um erro alfa < 5% foi considerado estatisticamente significativo, com um intervalo de confiança de 95%. RESULTADOS: Foram incluídos 25 pacientes com idade mediana de 45 anos. A etiologia foi principalmente idiopática (n = 19, 76%), e 14 (56%) apresentaram classe funcional New York Heart Association (NYHA) III/IV. Os valores medianos de BNP e Gal-3 foram 143 (89-209) pg/dL e 14,8 (9,7-17,2) ng/mL, respectivamente. Os níveis de Gal-3 não foram estatisticamente maiores nos pacientes com PCC que em controles (p = 0,22). Não foram encontradas correlações significativas da Gal-3 com BNP, medidas ecocardiográficas e de ressonância magnética cardíaca, e achados histológicos. Após a pericardiectomia, encontrou-se uma correlação estatisticamente significativa entre Gal-3 e medidas do TCPE ­ duração do teste (r = ­0,79; p < 0,001) e tempo de exercício (r = ­0,79; p < 0,001). CONCLUSÕES: Pacientes com PCC apresentaram níveis normais de Gal-3, quando comparados aos indivíduos controles. A Gal-3 não se correlacionou com medidas morfológicas e funcionais antes da pericardiectomia. No entanto, associações entre Gal-3 e intolerância ao exercício após pericardiectomia pode sugerir um papel da Gal-3 na predição de prognóstico após a pericardiectomia.


Assuntos
Humanos , Pessoa de Meia-Idade , Pericardite Constritiva , Galectina 3
13.
Mater Sci Eng C Mater Biol Appl ; 109: 110528, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228970

RESUMO

Thermally activated delayed fluorescence (TADF) has revolutionized the field of organic light emitting diodes owing to the possibility of harvesting non-emissive triplet states and converting them in emissive singlet states. This mechanism generates a long-lived delayed fluorescence component which can also be used in sensing oxygen concentration, measuring local temperature, or on imaging. Despite this strong potential, only recently TADF has emerged as a powerful tool to develop metal-free long-lived luminescent probes for imaging and sensing. The application of TADF molecules in aqueous and/or biological media requires specific structural features that allow complexation with biomolecules or enable emission in the aggregated state, in order to retain the delayed fluorescence that is characteristic of these compounds. Herein we demonstrate a facile method that maintains the optical properties of solvated dyes by dispersing TADF molecules in nanoparticles. TADF dye-doped silica nanoparticles are prepared using a modified fluorescein fluorophore. However, the strategy can be used with many other TADF dyes. The covalent grafting of the TADF emitter into the inorganic matrix effectively preserves and transfers the optical properties of the free dye into the luminescent nanomaterials. Importantly, the silica matrix is efficient in shielding the dye from solvent polarity effects and increases delayed fluorescence lifetime. The prepared nanoparticles are effectively internalized by human cells, even at low incubation concentrations, localizing primarily in the cytosol, enabling fluorescence microscopy imaging at low dye concentrations.

18.
Arq Bras Cardiol ; 113(5): 1006-1056, 2019 11.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31800728
19.
BMC Cardiovasc Disord ; 19(1): 251, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706288

RESUMO

BACKGROUND: Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge. We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort. METHODS: We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use. RESULTS: We screened 2314 consecutive patients for eligibility and enrolled 700 participants. The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008-1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347-2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969-0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies. CONCLUSIONS: High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample. TRIAL REGISTRATION: Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.

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