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1.
Nat Biomed Eng ; 2(5): 304-317, 2018 05.
Article in English | MEDLINE | ID: mdl-30936449

ABSTRACT

Systemic injection into blood vessels is the most common method of drug administration. However, targeting drugs to the heart is challenging, owing to its dynamic mechanical motions and large cardiac output. Here, we show that the modification of protein and peptide therapeutics with tannic acid-a flavonoid found in plants that adheres to extracellular matrices, elastins and collagens-improves their ability to specifically target heart tissue. Tannic-acid-modified (TANNylated) proteins do not adsorb on endothelial glycocalyx layers in blood vessels, yet they penetrate the endothelium to thermodynamically bind to myocardium extracellular matrix before being internalized by myoblasts. In a rat model of myocardial ischaemia-reperfusion injury, TANNylated basic fibroblast growth factor significantly reduced infarct size and increased cardiac function. TANNylation of systemically injected therapeutic proteins, peptides or viruses may enhance the treatment of heart diseases.


Subject(s)
Cardiotonic Agents , Heart/drug effects , Myocardial Reperfusion Injury/drug therapy , Tannins , Animals , Cardiotonic Agents/chemistry , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Disease Models, Animal , Drug Delivery Systems , Fibroblast Growth Factors , Male , Mice, Inbred BALB C , Myocardial Reperfusion Injury/pathology , Rats , Rats, Sprague-Dawley , Tannins/chemistry , Tannins/pharmacology , Tannins/therapeutic use
2.
Nutr Res Pract ; 3(2): 128-33, 2009.
Article in English | MEDLINE | ID: mdl-20016713

ABSTRACT

Few studies have examined short term responses to the different contents of carbohydrate or fat in the meal, although long term effects of the high fat meal have been considered as compound risk factor for metabolic disorders. The aim of this study was to investigate the postprandial changes of plasma glucose, insulin and lipids upon intakes of high carbohydrate or high fat meal in young healthy women. Subjects were randomly assigned to either the high carbohydrate meal (HCM, 75% carbohydrate, n=13) or the high fat meal (HFM, 60% fat, n=12) groups. The meals were prepared as isocaloric typical Korean menu. Blood samples were obtained prior to and 30, 60, 90, 120, 180 and 240 minute after the meal. There were no significant differences on fasting blood parameters including glucose, insulin, lipids concentrations between the groups prior to the test. The HCM had higher blood glucose and insulin concentrations, reached the peak at 30 min and maintained for 240 min compared to the HFM (P<0.05). The HFM had higher plasma triglyceride (TG) and free fatty acid (FFA) concentrations, reached the peak at 120 min and maintained for 240 min compared to the HCM (P<0.05). It is concluded that macronutrients content in the meal may be an important determinant of postprandial substrate utilization in healthy women.

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