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1.
Pharmacol Res ; 152: 104621, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31891788

RESUMO

Statins, as the most common treatment for hyperlipidemia, exert effects beyond their lipid-lowering role which are known as pleiotropic effects. These effects are mainly due to the inhibition of isoprenoids synthesis and consequently blocking prenylation of proteins involved in the cellular signaling pathways regulating cell development, growth, and apoptosis. Statins target cholesterol synthesis in the liver as the major source of cholesterol in the body and so reduce whole-body cholesterol. The reduced level of cholesterol forces other organs to an adaptive homeostatic reaction to increase their cholesterol synthesis capacity, however, this only occurs when statins have unremarkable access to the extra-hepatic tissues. In order to reduce the adverse effects of statin on the skeletal muscle, most recent efforts have been towards formulating new statins with the highest level of hepatoselectivity rank and the least level of access to the extra-hepatic tissues; however, the inaccessibility of statins for the extra-hepatic tissues may induce several biological reactions. In this review, we aim to evaluate the effects of statins on the extra-hepatic tissues when statins have unremarkable access to these tissues.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Animais , Colesterol/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Fígado/metabolismo , Ácido Mevalônico/metabolismo
2.
Appl Biochem Biotechnol ; 191(2): 824-837, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31872336

RESUMO

The development of low fouling membranes to minimize protein adsorption has relevance in various biomedical applications. Here, electrically neutral peptoids containing 2-methoxyethyl glycine (NMEG) side chains were attached to polysulfone hollow fiber membranes via polydopamine. The number of side chains and grafting density were varied to determine the effect on coating properties and the ability to prevent fouling. NMEG peptoid coatings have high hydrophilicity compared to unmodified polysulfone membranes. The extent of biofouling was evaluated using bovine serum albumin, as well as platelet adhesion. The results suggest that both the number of side chains and grafting density play a role in the surface properties that drive biofouling. Protein adsorption decreased with increasing peptoid grafting density and is lowest above a critical grafting density specific to peptoid chain length. Our findings show that the optimization of grafting density and hydration of the surface are important factors for achieving the desired antifouling performance.


Assuntos
Membranas Artificiais , Peptoides/química , Polímeros/química , Sulfonas/química , Adsorção , Incrustação Biológica/prevenção & controle , Plaquetas , Indóis , Soroalbumina Bovina/química , Propriedades de Superfície
3.
Colloids Surf B Biointerfaces ; 149: 23-29, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27716528

RESUMO

Biofouling is a persistent problem for membranes exposed to blood or other complex biological fluids, affecting surface structure and hindering performance. In this study, a peptoid with 2-methoxyethyl (NMEG5) side chains was immobilized on polysulfone hollow fiber membranes to prevent protein fouling. The successful attachment of NMEG5 to the polysulfone surface was confirmed by X-ray photoelectron spectroscopy and an increase in hydrophilicity was confirmed by contact angle analysis. The NMEG5-modified surface was found to resist fouling with bovine serum albumin, lysozyme, and adsorbed significantly less fibrinogen as compared with other published low-fouling surfaces. Due to the low fouling nature and increased biocompatibility of the NMEG5 coated membranes, they have potential applicability in numerous biomedical applications including artificial lungs and hemodialysis.


Assuntos
Incrustação Biológica/prevenção & controle , Peptidomiméticos/síntese química , Polímeros/química , Sulfonas/química , Adsorção/efeitos dos fármacos , Alquilação , Fibrinogênio/química , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Muramidase/química , Peptidomiméticos/farmacologia , Espectroscopia Fotoeletrônica , Polímeros/farmacologia , Soroalbumina Bovina/química , Sulfonas/farmacologia , Propriedades de Superfície
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