ABSTRACT
Glycoside hydrolases (GHs) are enzymes that hydrolyze glycosidic bonds, but some of them can also catalyze the synthesis of glycosides by transglycosylation. However, the yields of this reaction are generally low since the glycosides formed end up being hydrolyzed by these same enzymes. For this reason, mutagenic variants with null or drastically reduced hydrolytic activity have been developed, thus enhancing their synthetic ability. Two mutagenic variants, a glycosynthase engineered from a ß-glucosidase (BGL-1-E521G) and a thioglycoligase from a ß-xylosidase (BxTW1-E495A), both from the ascomycete Talaromyces amestolkiae, were used to synthesize three novel epigallocatechin gallate (EGCG) glycosides. EGCG is a phenolic compound from green tea known for its antioxidant effects and therapeutic benefits, whose glycosylation could increase its bioavailability and improve its bioactive properties. The glycosynthase BGL-1-E521G produced a ß-glucoside and a ß-sophoroside of EGCG, while the thioglycoligase BxTW1-E495A formed the ß-xyloside of EGCG. Glycosylation occurred in the 5â³ and 4â³ positions of EGCG, respectively. In this work, the reaction conditions for glycosides' production were optimized, achieving around 90% conversion of EGCG with BGL-1-E521G and 60% with BxTW1-E495A. The glycosylation of EGCG caused a slight loss of its antioxidant capacity but notably increased its solubility (between 23 and 44 times) and, in the case of glucoside, also improved its thermal stability. All three glycosides showed better antiproliferative properties on breast adenocarcinoma cell line MDA-MB-231 than EGCG, and the glucosylated and sophorylated derivatives induced higher neuroprotection, increasing the viability of SH-S5Y5 neurons exposed to okadaic acid.
ABSTRACT
Objetivo. Determinar la compatibilidad física de la amiodarona administrada en «Y» con fármacos en perfusión continua con el fin de asegurar su estabilidad y garantizar una administración segura para el paciente. Método. Estudio experimental in vitro. Se determinó la compatibilidad física de la amiodarona con los fármacos más usados en la unidad de cuidados intensivos en perfusión continua, simulando las mismas condiciones que en la práctica diaria: envase, diluyente, temperatura ambiental y luz fluorescente. Todas las muestras se evaluaron mediante inspección visual, observando formación de color, turbidez, precipitación o formación de gas; medición del pH y lectura de las absorbancias a dos longitudes de onda: 450nm y 620nm para detectar cambios de color, turbidez y precipitación respectivamente. Se consideraron compatibles las mezclas que no presentaron cambios físicos, variabilidad del pH <0,50 y del rango espectral <0,010. Resultados. Se realizaron un total de 39 muestras: 14 simples, 13 dobles, 6 triples y 6 cuádruples, que se examinaron a diferentes intervalos de tiempo: 0, 15, 30, 60 y 120min. Las mezclas incompatibles presentaron cambios visuales inmediatos y valores de absorbancias superiores a 0,010nm. No hubo cambios significativos de pH durante el estudio. Conclusiones. La amiodarona es físicamente compatible con cisatracurio, esmolol, haloperidol, insulina, midazolam, morfina, nimodipino, nitroglicerina y urapidil e incompatible con el bicarbonato, furosemida, heparina y tiopental (AU)
Objective. To determine the physical compatibility of amiodarone administered in Y-site with other continuous infusion drugs, in order to ensure stability and safe delivery to the patient. Method. Experimental in vitro study. We determined the physical compatibility of amiodarone with drugs commonly used in the intensive care unit as a continuous infusion, simulating the same conditions as in daily practice: container, solvent, temperature and fluorescent light. All samples were evaluated by visual observation procedures, looking for colour changes, turbidity, precipitation or gas formation, pH measurement and spectrophotometer absorption at wavelengths: 450nm and 620nm to detect colour changes, cloudiness and precipitation, respectively. Compatible mixtures were considered as those that showed no physical changes, variability in pH <0.50 and the spectral range <0.010. Results. We analysed 39 samples: 14 single, 13 doubles, 6 triples and 6 quadruples, which were examined at different time intervals: 0, 15, 30, 60 and 120min. Non-compatible mixtures showed immediate visual changes and higher absorbance values of 0.010nm. There were no significant changes in pH during the study. Conclusions. Amiodarone is physically compatible with cisatracurium haloperidol, insulin, midazolam, morphine, nimodipine, nitroglycerin and urapidil and incompatible with bicarbonate, furosemide, heparin and thiopental (AU)
Subject(s)
Humans , Amiodarone/pharmacokinetics , Instillation, Drug , Drug Interactions , Drug Incompatibility , Infusion Pumps , Critical Care/methods , Drug ContaminationABSTRACT
OBJECTIVE: To determine the physical compatibility of amiodarone administered in Y-site with other continuous infusion drugs, in order to ensure stability and safe delivery to the patient. METHOD: Experimental in vitro study. We determined the physical compatibility of amiodarone with drugs commonly used in the intensive care unit as a continuous infusion, simulating the same conditions as in daily practice: container, solvent, temperature and fluorescent light. All samples were evaluated by visual observation procedures, looking for colour changes, turbidity, precipitation or gas formation, pH measurement and spectrophotometer absorption at wavelengths: 450 nm and 620 nm to detect colour changes, cloudiness and precipitation, respectively. Compatible mixtures were considered as those that showed no physical changes, variability in pH < 0.50 and the spectral range < 0.010. RESULTS: We analysed 39 samples: 14 single, 13 doubles, 6 triples and 6 quadruples, which were examined at different time intervals: 0, 15, 30, 60 and 120 min. Non-compatible mixtures showed immediate visual changes and higher absorbance values of 0.010 nm. There were no significant changes in pH during the study. CONCLUSIONS: Amiodarone is physically compatible with cisatracurium haloperidol, insulin, midazolam, morphine, nimodipine, nitroglycerin and urapidil and incompatible with bicarbonate, furosemide, heparin and thiopental.
