No abstract

Folic acid (FA) is a vitamin essential for normal cellular functions, growth, and development. Because humans cannot synthesize this micronutrient, it must be obtained from dietary sources through intestinal absorption. The intestinal tract is a major target for oxidative stress. Our aim was to investigate the effect of oxidative stress upon the uptake of FA by Caco-2 cells. Oxidative stress was induced by exposure of the cells to tert-butyl hydroperoxide (TBH) for 1 h. TBH (3,000 μM) induced an increase in biomarkers of oxidative stress, while maintaining cell viability and proliferation. In relation to the apical uptake of (3)H-FA, TBH (3,000 μM) reduced the cellular accumulation of (3)H-FA (10 nM), although the characteristics (kinetics, pH dependence, and inhibitory profile) of (3)H-FA uptake were not changed. This effect was associated with a decrease in the mRNA steady-state levels of proton-coupled folate transporter and folate receptor alpha and of the efflux transporter multidrug resistance protein 2. Moreover, TBH (3,000 μM) did not affect the noncarrier-mediated apical uptake of (3)H-FA. Finally, the effect of TBH upon (3)H-FA apical uptake was not dependent on protein kinase A, protein kinase C, mitogen-activated protein kinases, phosphoinositide 3-kinase, nuclear factor kappa B, and protein tyrosine kinases, but was completely prevented by dietary polyphenols (resveratrol, quercetin, and EGCG). These results suggest that oxidative stress at the intestinal level may result in a reduction in the intestinal absorption of dietary FA and that polyphenolic dietary components may offer protection against oxidative stress-induced inhibition of intestinal FA absorption.

Objectives Rocuronium is a muscle relaxant with increased use, because of the binding relation with the reversal agent sugammadex. Its continuous infusion benefits the maintenance of deeper levels of neuromuscular blockade (NMB) ensuring an improved and stable solution for daily surgical anesthesia. This is systematic review on current approaches on rocuronium infusion and monitoring parameters when using rocuronium continuous infusion for profound muscle relaxation (0–2 posttetanic count). Methods Database search included publications worldwide until February 28, 2019. Main outcomes studied were the amount of rocuronium used, surgical conditions, and time of recovery after standard sugammadex dose. Secondary assessments include methodological features of rocuronium administration and blockade monitoring. Meta-analysis was conducted to assess the effect means difference of surgical conditions, followed by heterogeneity and sensitive analysis. Results Eight randomized trials were identified as eligible. Three studies allowed to account that maintenance of profound muscle relaxation a mean difference of 0.251 mg/kg per hour (95% confidence interval = 0.169–0.334) of rocuronium is required, in relation to moderate NMB, significantly improving surgical conditions (mean difference = 0.653, 95% confidence interval = 0.451–0.856, in a 5-point scale, including data from 6 trials). Only 2 studies presented results on reversal after sugammadex; therefore, no significant results were yielded regarding the time required to complete NMB recovery. Conclusions Rocuronium continuous infusion for profound neuromuscular blockade presents inherent advantages in terms of maintenance and stability of the paralysis. Further studies should address the methodological approaches and benefits/drawbacks of this approach. Registration number: CRD42018106626