RESUMO
BACKGROUND & AIMS: The quality of carbohydrates has an essential role in nutritional management of type 2 diabetes mellitus (T2DM) because of its substantial impact on glucose homeostasis. Alcohol-free beer has beneficial bioactive components but it has a relatively high glycemic-index so its consumption is restricted in diabetic subjects. We aimed to explore the effect of an alcohol-free beer with modified carbohydrate composition almost completely eliminating maltose and adding isomaltulose (16.5 g/day) and a resistant maltodextrin (5.28 g/day) in comparison to a regular alcohol-free beer on glycemic control of diabetic subjects with overweight or obesity. DESIGN: We randomized 41 subjects into two groups: a) consumption of 66 cL/day of; regular alcohol-free beer for the first 10 weeks and 66 cL/day of alcohol-free beer with modified carbohydrate composition for the next 10 weeks; b) the same described intervention in opposite order. There was a washout period for 6-8 weeks between the two interventions. Participants were counseled to adhere to a healthy diet for cardiovascular health and to increase physical activity. Clinical, biochemical, anthropometric, lifestyle and satiety assessments were performed at the beginning and at the end of each period. RESULTS: Subjects showed significantly weight loss after the two ten weeks periods (-1.69 ± 3.21% and -1.77 ± 3.70% after experimental and regular alcohol-free beers, respectively, P = 0.881). Glucose and glycated hemoglobin did not significantly change after any period. Insulin concentrations and HOMA-IR significantly decreased (-11.1 [-21.3-4.64]% and -1.92 ± 32.8% respectively) after the intake of experimental alcohol-free beer but not after regular alcohol-free beer. Reductions remained statistically significant after adjusting for weight loss, energy intake, physical activity and intervention order. Subjects reported higher satiety scores after consuming experimental alcohol-free beer. CONCLUSIONS: An alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and the addition of a resistant maltodextrin within meals led to an improvement in insulin resistance in subjects with T2DM and overweight or obesity. CLINICAL TRIAL REGISTRATION: The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT03337828).
Assuntos
Cerveja , Dextrinas/sangue , Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Isomaltose/análogos & derivados , Sobrepeso/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dextrinas/farmacologia , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Humanos , Isomaltose/sangue , Isomaltose/farmacologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Sobrepeso/complicações , Adulto JovemRESUMO
To improve oral absorption and patient compliance when using amlodipine, novel coated dextrin microcapsules incorporable into orally disintegrating tablets (ODT's) were investigated. Amlodipine-loaded dextrin microcapsules (ADM) were prepared by spray-drying a mixture of amlodipine free base dissolved in ethanol and aqueous dextrin solution. The ADM were suspended in Eudragit(®) EPO solution in ethanol and subsequently spray-dried to collect coated ADM (CADM). The ADM or CADM were blended with ODT excipients and then directly compressed into ODTs. The ADM and CADM used were both spherical with smooth surfaces and had mean particle sizes of 13.3 and 18.5µm, respectively. Amlodipine was dispersed in an amorphous state and was readily encapsulated within ADM or CADM. Unlike the ADM, the tableted CADM remained intact without rupture during tableting, which was consistent with no loss of ethanol (0.82%) entrapped in the ODTs containing the CADM (ODTs-CADM). The amlodipine content appeared to be uniformly maintained as designed in all the dextrin microcapsules and ODTs. The ODTs-CADM compressed with 3kp of hardness showed acceptable ODT characteristics: fast disintegration time (29.8s) and low friability (0.1%). Drug dissolution from the ODTs-CADM was much faster than that of amlodipine free base itself at both pH 1.2 and 6.8 over the tested time. CADM demonstrated significantly higher plasma concentrations (2.7 fold in AUC0-24h and 2.5 fold in Cmax) in SD rats than did amlodipine free base. These results indicate that CADM substantially increased the oral absorption of amlodipine and can be incorporated into ODTs while maintaining their original physicochemical features. The dextrin microcapsules coated using Eudragit(®) EPO may be applied to the development of an amlodipine ODT formulation for improving geriatric patient compliance.
Assuntos
Anlodipino/administração & dosagem , Anlodipino/sangue , Química Farmacêutica/métodos , Dextrinas/administração & dosagem , Dextrinas/sangue , Geriatria , Administração Oral , Animais , Cápsulas , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Solubilidade , Comprimidos com Revestimento EntéricoRESUMO
The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a gamma-emitting (153)Sm(3+) radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.
Assuntos
Dextrinas/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas , Animais , Técnicas de Química Combinatória , Dextrinas/sangue , Dextrinas/química , Compostos Heterocíclicos com 1 Anel/química , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Wistar , Samário/química , Compostos de Sulfidrila/química , Distribuição TecidualRESUMO
BACKGROUND: Average dietary fiber intake in the United States is roughly half of the recommended amount. As new dietary fiber products are introduced to increase fiber intake, it is critical to evaluate the physiological effects of such fibers. AIMS: This study examined the effect of 4 fibers derived from maize or tapioca on fecal chemistry, gastrointestinal (GI) symptoms and serum markers of chronic disease. METHODS: Twenty healthy subjects completed the single-blind crossover study in which 12 g/day of fiber (pullulan, Promitor Resistant Starch, soluble fiber dextrin or Promitor Soluble Corn Fiber) or placebo (maltodextrin) were consumed for 14 days followed by a 21-day washout. GI symptom surveys were completed (days 3 and 14), stools were collected (days 11-14), diet was recorded (days 12-14) and fasting blood samples were obtained (day 15). RESULTS: The 4 test fibers were well tolerated, with mild to moderate GI symptoms. Total short-chain fatty acid (SCFA) concentrations did not differ among the treatments. Fecal pH and individual SCFAs were affected by some treatments. Stool weight and serum markers of chronic disease did not change with these treatments. CONCLUSION: Increasing fiber intake by 12 g/day was well tolerated and may have a positive impact on colon health due to fermentation.
Assuntos
Defecação/efeitos dos fármacos , Fibras na Dieta/metabolismo , Fibras na Dieta/farmacologia , Fezes/química , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Adulto , Biomarcadores/sangue , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Cólica , Estudos Cross-Over , Dextrinas/sangue , Dextrinas/farmacologia , Ácidos Graxos Voláteis/sangue , Feminino , Flatulência , Grelina/sangue , Glucanos/sangue , Glucanos/farmacologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Lipídeos/sangue , Masculino , Manihot , Polissacarídeos/sangue , Polissacarídeos/farmacologia , Valores de Referência , Método Simples-Cego , Zea mays/metabolismoRESUMO
The uptake of nanoparticles by cells of the mononuclear phagocytic system limits its use as colloidal drug carriers, reducing the blood circulation time and the ability to reach biological targets. In this work, the interaction between dextrin nanoparticles--recently developed in our laboratory--and murine bone marrow-derived macrophages was evaluated. Cytotoxicity and nitric oxide production were studied, using the MTT assay and the Griess method, respectively. FITC labelled nanoparticles were used to assess the phagocytic uptake and blood clearance after intravenous injection. The phagocytic uptake was analysed in vitro by confocal laser scanning microscopy and fluorescence activated cell sorting. The results show that the nanoparticles are not cytotoxic and do not stimulate the production of nitric oxide by macrophages, in the range of concentrations studied. Nanoparticles are phagocytosed by macrophages and are detected inside the cells, concentrated in cellular organelles. The blood clearance study showed that the blood removal of the nanoparticles occurs with a more pronounced rate in the first 3 h after intravenous administration, with about 30% of the material remaining in systemic circulation at this stage. Given the fairly high blood circulation time and biocompatibility, the dextrin nanoparticles are promising carriers for biomedical applications. Both applications targeting phagocytic, antigen-presenting cells (for vaccination purposes) and different tissues (as drug carriers) may be envisaged, by modulation of the surface properties.
Assuntos
Dextrinas/sangue , Dextrinas/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura , Feminino , Fluoresceína-5-Isotiocianato , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Microscopia de Fluorescência , Nanopartículas/ultraestrutura , Óxido Nítrico/biossíntese , Tamanho da PartículaRESUMO
The aim of this study was to investigate a newly synthesized dextrin-zidovudine (AZT) conjugate designed as a sustained release prodrug of AZT for parenteral administration. AZT was first reacted with succinic anhydride to form a succinoylated AZT which was subsequently coupled with dextrin to yield the dextrin-AZT conjugate. The structure of the conjugate was characterized by FT-IR and (1)H-NMR spectroscopy. The drug content of the conjugate was 18.9 wt.%. The release in vitro of free AZT and succinoylated AZT was investigated in buffer solutions at pH 5.5 and 7.4 and in human plasma. AZT and succinoylated AZT release from the conjugate was 1.4% (pH 5.5), 41.7% (pH 7.4) and 78.4% in human plasma after 24 h. Release was complete in human plasma after 48 h. A pharmacokinetic study in rats following intravenous administration of the conjugate showed prolonged plasma levels of AZT compared to free AZT. The use of the conjugate extended the plasma half-life of AZT from 1.3 to 19.3 h and the mean residence time from 0.4 to 23.6 h. Furthermore, the conjugate provided a significant greater area under the plasma concentration-time curve and reduced the systemic clearance of AZT. This study suggested the potential of this novel dextrin-AZT conjugate as a new intravenous preparation of AZT.
Assuntos
Fármacos Anti-HIV/farmacocinética , Dextrinas/farmacocinética , Pró-Fármacos/farmacocinética , Zidovudina/farmacocinética , Animais , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/síntese química , Dextrinas/sangue , Dextrinas/síntese química , Combinação de Medicamentos , Humanos , Injeções Intravenosas , Masculino , Pró-Fármacos/síntese química , Ratos , Ratos Sprague-Dawley , Zidovudina/sangue , Zidovudina/síntese químicaRESUMO
A female patient suffering from the after-effects of an intracerebral hemorrhage, inadvertently received approximately 50 ml of enteral feed containing high molecular weight dextrin intravenously and died 6 h later despite intensive emergency resuscitation attempts. The total quantity of enteral feed received was calculated from the amounts of dextrin measured in the blood. This is the first report describing how the total quantity of enteral feed administered intravenously was determined using biochemical analysis.
Assuntos
Autopsia/métodos , Dextrinas/sangue , Nutrição Enteral , Infusões Intravenosas/efeitos adversos , Erros Médicos , Idoso , Biomarcadores , Cromatografia em Gel , Evolução Fatal , Feminino , Ionização de Chama , HumanosRESUMO
A high-performance liquid chromatographic method has been developed for the determination of cyclodextrins (CDs) and branched CDs. The method involves their separation on a reversed-phase column using a mixture of water and acetonitrile as an eluant, eluant pH modification with a cation-exchange membrane reactor surrounded by 1.5 M sodium hydroxide solutions, and pulsed amperometric detection with a gold working electrode. The calibration graphs constructed by peak height versus injected amount were linear over the ranges 50-1000 pmol. The detection limits for CDs and branched CDs were about 1-5 pmol at a signal-to-noise ratio of 3. The method was successfully applied to the assay of beta-CD in serum samples.
Assuntos
Ciclodextrinas/sangue , Dextrinas/sangue , Amido/sangue , Cromatografia Líquida de Alta Pressão , EletroquímicaRESUMO
Procedures for the micro-determination of beta-cyclodextrin (beta-CyD) in plasma were investigated by four methods using high-performance liquid chromatography (HPLC). In methods A and B, underivatized beta-CyD was detected with a refractive index detector and determined by the absolute calibration graph method. An NH2-bonded silica/acetonitrile-water system was used in A and a C18-bonded silica/methanol-water system in B. In method C, the percarbanilate of beta-CyD was separated on a C8-bonded silica column with acetonitrile-water and determined using gamma-CyD as the internal standard with a UV detector at 231 nm. In method D, the per[1-14C]acetate of beta-CyD was fractionated on a silica column with n-hexane-ethanol containing 1% of water and the radioactivity of each fraction was measured with a liquid scintillation counter. gamma-CyD was used as the internal standard. Interfering plasma proteins were removed by centrifugal ultrafiltration with an MPS-1 micro-partition system. Method B was superior to the other methods with respect to ease of sample preparation, sensitivity and time required for analysis. The cumulative amount of beta-CyD in the mesenteric vein absorbed from the rat intestinal lumen after administration of phenobarbital-beta-CyD complex in a closed loop method was determined by the use of method B.