Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Imageamento Tridimensional , Procedimentos de Cirurgia Plástica/métodos , Choque Cardiogênico/diagnóstico por imagem , Choque Cardiogênico/etiologia , Anormalidades Múltiplas/cirurgia , Determinação da Pressão Arterial/métodos , Canal Arterial/anormalidades , Canal Arterial/cirurgia , Ecocardiografia Doppler em Cores , Feminino , Seguimentos , Humanos , Recém-Nascido , Artéria Pulmonar/anormalidades , Artéria Pulmonar/cirurgia , Artéria Subclávia/anormalidades , Artéria Subclávia/cirurgia , Tomografia Computadorizada por Raios X/métodos , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Enulosides, carbohydrate derivatives containing an α,ß-unsaturated carbonyl unit, were designed and obtained in high yields and isomeric purity. All synthesized compounds exhibited antitumoral activity in micromolar range against four tested tumor cells lines, being the best results observed for HL-60 cells. These compounds open new possibilities to prepare an array of more active, site-specific or selective antitumor agents. 2016 Elsevier Ltd. All rights reserved.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Carboidratos/química , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Produtos Biológicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
BACKGROUND: Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct. METHODS AND RESULTS: Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (n=14) or bare metal (n=14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct-derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [(3)H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (P=0.009), 54% (P=0.004), and 77% (P=0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (P=0.18), 5% (P=0.25), and 61% (P=0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (P<0.001). CONCLUSIONS: Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.