RESUMEN
AIMS: Weight management seems to be beneficial for obese atrial fibrillation (AF) patients; however, randomized data are sparse. Thus, this study aimed to investigate the influence of weight reduction on AF ablation outcomes. METHODS AND RESULTS: SORT-AF is an investigator-sponsored, prospective, randomized, multicentre, and clinical trial. Patients with symptomatic AF (paroxysmal or persistent) and body mass index (BMI) 30-40 kg/m2 underwent AF ablation and were randomized to either weight-reduction (group 1) or usual care (group 2), after sleep-apnoea-screening and loop recorder (ILR) implantation. The primary endpoint was defined as AF burden between 3 and 12 months after AF ablation. Overall, 133 patients (60 ± 10 years, 57% persistent AF) were randomized to group 1 (n = 67) and group 2 (n = 66), respectively. Complications after AF-ablation were rare (one stroke and no tamponade). The intervention led to a significant reduction of BMI (34.9 ± 2.6-33.4 ± 3.6) in group 1 compared to a stable BMI in group 2 (P < 0.001). Atrial fibrillation burden after ablation decreased significantly (P < 0.001), with no significant difference regarding the primary endpoint between the groups (P = 0.815, odds ratio: 1.143, confidence interval: 0.369-3.613). Further analyses showed a significant correlation between BMI and AF recurrence for patients with persistent AF compared with paroxysmal AF patients (P = 0.032). CONCLUSION: The SORT-AF study shows that AF ablation is safe and successful in obese patients using continuous monitoring via ILR. Although the primary endpoint of AF burden after ablation did not differ between the two groups, the effects of weight loss and improvement of exercise activity were beneficial for obese patients with persistent AF demonstrating the relevance of life-style management as an important adjunct to AF ablation in this setting. TRIAL REGISTRATION NUMBER: NCT02064114.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
Classical approaches to strain improvement and metabolic engineering rely on rapid qualitative and quantitative analyses of the metabolites of interest. As an analytical tool, mass spectrometry (MS) has proven to be efficient and nearly universally applicable for timely screening of metabolites. Furthermore, gas chromatography (GC)/MS- and liquid chromatography (LC)/MS-based metabolite screens can often be adapted to high-throughput formats. We recently engineered a Saccharomyces cerevisiae strain to produce taxa-4(5),11(12)-diene, the first pathway-committing biosynthetic intermediate for the anticancer drug Taxol, through the heterologous and homologous expression of several genes related to isoprenoid biosynthesis. To date, GC/MS- and LC/MS-based high-throughput methods have been inherently difficult to adapt to the screening of isoprenoid-producing microbial strains due to the need for extensive sample preparation of these often highly lipophilic compounds. In the current work, we examined different approaches to the high-throughput analysis of taxa-4(5),11(12)-diene biosynthesizing yeast strains in a 96-deep-well format. Carbon plasma coating of standard 96-deep-well polypropylene plates allowed us to circumvent the inherent solvent instability of commonly used deep-well plates. In addition, efficient adsorption of the target isoprenoid product by the coated plates allowed rapid and simple qualitative and quantitative analyses of the individual cultures.
Asunto(s)
Antineoplásicos Fitogénicos/metabolismo , Cromatografía de Gases y Espectrometría de Masas/instrumentación , Ensayos Analíticos de Alto Rendimiento/instrumentación , Paclitaxel/metabolismo , Saccharomyces cerevisiae/metabolismo , Terpenos/metabolismo , Antineoplásicos Fitogénicos/análisis , Carbono/química , Fermentación , Cromatografía de Gases y Espectrometría de Masas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Paclitaxel/análisis , Terpenos/análisisRESUMEN
Polyphenols are widely abundant dietary constituents in plants that are associated with health-promoting effects. This review summarizes factors influencing the bioavailability of polyphenols, specifically flavanols, flavonols, flavanones, flavones, and hydroxycinnamic (phenolic) acids. Most factors tested so far indicate that bioaccessibility, defined as the amount of compound reaching the enterocyte in a form suitable for absorption, is the most important factor determining the absorption in the gut. Factors leading to an improved absorption of flavonols, notably quercetin and its metabolites, are primarily the nature of the attached sugar, and secondly, the solubility as modified by ethanol, fat, and emulsifiers. The absorption of flavanols, notably green tea catechins, is affected by epimerization reactions occurring during processing, the presence of lipid and carbohydrate, and is improved by the presence of piperine and tartaric acid. Flavanones, such as hesperidin, are strongly affected by the type of attached sugar. Phenolic acids are affected by the attached sugar, which can covalently link these compounds to the cereal bran matrix. In the few examples tested, absorption of polyphenols is dependent on release from the food matrix. There are only a few examples reported, but where information is available, the absorption increases with dose but is sometimes linear and sometimes saturated. The lack of systematic information on the effects of other components on the bioavailability of polyphenols needs to be addressed, and more human studies should be conducted in this field to establish general principles affecting absorption in vivo. Information derived from such experiments could be useful for the optimal design of future bioefficacy studies.