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1.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678311

RESUMO

Carbohydrate (CHO) intake in oral and enteral nutrition is regularly reduced in nutritional support of older patients due to the high prevalence of diabetes (usually type 2-T2DM) in this age group. However, CHO shortage can lead to the lack of building blocks necessary for tissue regeneration and other anabolic processes. Moreover, low CHO intake decreases CHO oxidation and can increase insulin resistance. The aim of our current study was to determine the extent to which an increased intake of a rapidly digestible carbohydrate-maltodextrin-affects blood glucose levels monitored continuously for one week in patients with and without T2DM. Twenty-one patients (14 T2DM and seven without diabetes) were studied for two weeks. During the first week, patients with T2DM received standard diabetic nutrition (250 g CHO per day) and patients without diabetes received a standard diet (350 g of CHO per day). During the second week, the daily CHO intake was increased to 400 in T2DM and 500 g in nondiabetic patients by addition of 150 g maltodextrin divided into three equal doses of 50 g and given immediately after the main meal. Plasma glucose level was monitored continually with the help of a subcutaneous sensor during both weeks. The increased CHO intake led to transient postprandial increase of glucose levels in T2DM patients. This rise was more manifest during the first three days of CHO intake, and then the postprandial peak hyperglycemia was blunted. During the night's fasting period, the glucose levels were not influenced by maltodextrin. Supplementation of additional CHO did not influence the percentual range of high glucose level and decreased a risk of hypoglycaemia. No change in T2DM treatment was indicated. The results confirm our assumption that increased CHO intake as an alternative to CHO restriction in type 2 diabetic patients during oral and enteral nutritional support is safe.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Humanos , Glicemia , Nutrição Enteral/efeitos adversos , Insulina , Carboidratos da Dieta
2.
Int J Pharm ; 613: 121392, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34933083

RESUMO

Inflammatory bowel disease (IBD) is a relapsing and remitting inflammatory disease affecting millions of people worldwide. The active phase of IBD is characterized by excessive formation of reactive oxygen species (ROS) in the intestinal mucosa, which further accelerates the inflammatory process. A feasible strategy for the IBD treatment is thus breaking the oxidation-inflammation vicious circle by scavenging excessive ROS with the use of a suitable antioxidant. Herein, we have developed a novel hydrogel system for oral administration utilizing sterically hindered amine-based redox polymer (SHARP) incorporating covalently bound antioxidant SHA groups. SHARP was prepared via free-radical polymerization by covalent crosslinking of 2-hydroxyethyl methacrylate (HEMA), poly(ethylene oxide) methyl ether methacrylate (PEGMA) and a SHA-based monomer, N-(2,2,6,6-tetramethyl-piperidin-4-yl)-methacrylamide. The SHARP hydrogel was resistant to hydrolysis and swelled considerably (∼90% water content) under the simulated gastrointestinal tract (GIT) conditions, and exhibited concentration-dependent antioxidant properties in vitro against different ROS. Further, the SHARP hydrogel was found to be non-genotoxic, non-cytotoxic, non-irritating, and non-absorbable from the gastrointestinal tract. Most importantly, SHARP hydrogel exhibited a statistically significant, dose-dependent therapeutic effect in the mice model of dextran sodium sulfate (DSS)-induced acute colitis. Altogether, the obtained results suggest that the SHARP hydrogel strategy holds a great promise with respect to IBD treatment.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Aminas , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Hidrogéis , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos , Oxirredução , Polímeros
3.
Macromol Biosci ; 20(12): e2000254, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32954629

RESUMO

Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved; however, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron. Macroporous polymer beads are synthesized with three different iron-chelating moieties (benzene-1,2-diol, benzene-1,2,3-triol, and 1,10-phenanthroline). The polymers rapidly chelate iron ions from aqueous solutions in vitro in the course of minutes, and are noncytotoxic and nonprooxidant. Moreover, the in vivo biodistribution and pharmacokinetics show a negligible uptake from the gastrointestinal tract (using 125 I-labeled polymer and single photon emission computed tomography/computed tomography), which generally prevents them from having systemic side effects. The therapeutic efficacy of the prepared polymers is successfully tested in vivo, and exhibits a significant inhibition of iron uptake from the gastrointestinal tract without any noticeable signs of toxicity. Furthermore, an in silico method is developed for the prediction of chelator selectivity. Therefore, this paradigm can be applied to the next-generation maintenance/preventive treatment for hemochromatosis and/or other diseases of similar pathophysiology.


Assuntos
Hemocromatose/tratamento farmacológico , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Modelos Teóricos , Benzeno/química , Benzeno/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Hemocromatose/diagnóstico por imagem , Hemocromatose/patologia , Humanos , Quelantes de Ferro/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Polímeros/química , Polímeros/farmacologia , Tomografia Computadorizada de Emissão
4.
Membranes (Basel) ; 9(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434248

RESUMO

Stable, cross-linked, liquid crystalline polymer (LCP) films for membrane separation applications have been fabricated from the mesogenic monomer 11-(4-cyanobiphenyl-4'-yloxy) undecyl methacrylate (CNBPh), non-mesogenic monomer 2-ethylhexyl acrylate (2-EHA), and cross-linker ethylene glycol dimethacrylate (EGDMA) using an in-situ free radical polymerization technique with UV initiation. The phase behavior of the LCP membranes was characterized using differential scanning calorimetry (DSC) and X-ray scattering, and indicated the formation of a nematic liquid crystalline (LC) phase above the glass transition temperature. The single gas transport behavior of CO2, CH4, propane, and propylene in the cross-linked LCP membranes was investigated for a range of temperatures in the LC mesophase and the isotropic phase. Solubility of the gases was dependent not only on the condensability in the LC mesophase, but also on favorable molecular interactions of penetrant gas molecules exhibiting a charge separation, such as CO2 and propylene, with the ordered polar mesogenic side chains of the LCP. Selectivities for various gas pairs generally decreased with increasing temperature and were discontinuous across the nematic-sotropic transition. Sorption behavior of CO2 and propylene exhibited a significant change due to a decrease in favorable intermolecular interactions in the disordered isotropic phase. Higher cross-link densities in the membrane generally led to decreased selectivity at low temperatures when the main chain motion was limited by the lack of mesogen mobility in the ordered nematic phase. However, at higher temperatures, increasing the cross-link density increased selectivity as the cross-links acted to limit chain mobility. Mixed gas permeation measurements for propylene and propane showed close agreement with the results of the single gas permeation experiments.

5.
Int J Pharm ; 558: 268-283, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30611748

RESUMO

Currently, chemotherapy is the most common treatment for oncological diseases. Systemic administration of chemotherapeutics provides an easy and effective distribution of the active agents throughout the patient's body, however organs may be severely impaired by serious life-threatening side effects. In many oncological diseases, particularly solid tumors, the local application of chemotherapeutics would be advantageous. Recently, nanofibrous materials as local drug delivery systems have attracted much attention. They have considerable potential in the treatment of various cancers as they can provide a high concentration of the drug at the target site for a prolonged time, thereby lowering total exposure and adverse effects. The present review describes the specifics of drug delivery to the tumor microenvironment, basic characteristics of nanofibrous materials and their preparation, and comprehensively summarizes recent scientific reports concerning in vivo experiments with drug-loaded electrospun nanofibrous systems designed for local anticancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanofibras/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Humanos , Microambiente Tumoral
6.
Eur J Med Chem ; 144: 300-317, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29275230

RESUMO

Polymeric bile acid sequestrants (BAS) have recently attracted much attention as lipid-lowering agents. These non-absorbable materials specifically bind bile acids (BAs) in the intestine, preventing bile acid (BA) reabsorption into the blood through enterohepatic circulation. Therefore, it is important to understand the structure-property relationships between the polymer sequestrant and its ability to bind specific BAs molecules. In this review, we describe pleiotropic effects of bile acids, and we focus on BAS with various molecular architectures that result in different mechanisms of BA sequestration. Here, we present 1) amphiphilic polymers based on poly(meth)acrylates, poly(meth)acrylamides, polyalkylamines and polyallylamines containing quaternary ammonium groups, 2) cyclodextrins, and 3) BAS prepared via molecular imprinting methods. The synthetic approaches leading to individual BAS preparation, as well as results of their in vitro BA binding activities and in vivo lipid-lowering activities, are discussed.


Assuntos
Anticolesterolemiantes/farmacologia , Ácidos e Sais Biliares/farmacologia , Desenho de Fármacos , Hipercolesterolemia/tratamento farmacológico , Polímeros/farmacologia , Animais , Anticolesterolemiantes/síntese química , Anticolesterolemiantes/química , Ácidos e Sais Biliares/síntese química , Ácidos e Sais Biliares/química , Sítios de Ligação/efeitos dos fármacos , Humanos , Estrutura Molecular , Polímeros/síntese química , Polímeros/química
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