Assessment of Silver-Nanoparticles-Induced Erythrocyte Cytotoxicity through Ion Transport Studies.

BACKGROUND/AIMS: Silver nanoparticles (AgNPs) are the most frequently used nanomaterials in industrial and biomedical applications. Their functionalization significantly impacts their properties and potential applications. Despite the need to produce, investigate and apply them, not much is known about the toxicity of silver nanoparticles to and their interaction with blood components, such as erythrocytes. Here, we report on the effect of two negatively charged AgNPs (Creighton, and Lee-Meisel) on ion transport in human red blood cells (HRBCs). METHODS: HRBCs were obtained from blood of adult donors, which was either expired, fresh or refrigerated for variable lengths of time, and from fresh or refrigerated cord blood. Rb+ and K+ ions were measured by atomic emission and absorption spectrophotometry, respectively. Erythrocyte hemoglobin optical density (Hbc OD), was determined at 527 nm to estimate RBC volume in the same tubes in which Rb+ and K+ were measured. Cellular Rb+ uptake and intracellular K+ concentrations, [K]i, were calculated in mmol/L of original cells (LOC) per time. Rubidium, a potassium ion (K+) congener used to measure K+ influx, [K]i, and Hbc ODs were determined in the presence and absence of several concentrations (0-150 µg mL-1) of spherical AgNPs of an average diameter of 10 nm, at different time points (0-60 min). RESULTS: Creighton AgNPs inhibited Rb+ influx and depleted the cells of K+ independently of the source and in a time and dose-dependent manner. In contrast, Lee-Meisel AgNPs caused ~ 50 % Rb+ influx inhibition and ~ 15 % K+ loss with larger interindividual variability than Creighton AgNPs. The loss of K+ from HRBCs was entirely accounted for by an increase in extracellular K+ concentration, [K]o. Enhanced dark field optical microscopy in conjunction with CytoViva® hyperspectral imaging helped visualize AgNPs internalized by HRBCs, thus pointing to a potential cause for their cytotoxic effects. CONCLUSION: These findings indicate that HRBC K+ homeostasis is an early and sensitive biomarker for AgNPs toxicity and is a function of their surface functionalization.

US term stillbirth rates and the 39-week rule: a cause for concern?

BACKGROUND: More than a decade ago an obstetric directive called "the 39-week rule" sought to limit "elective" delivery, via labor induction or cesarean delivery, before 39 weeks 0 days of gestation. In 2010 the 39-week rule became a formal quality measure in the United States. The progressive adherence to the 39-week rule throughout the United States has caused a well-documented, progressive reduction in the proportion of term deliveries occurring during the early-term period. Because of the known association between increasing gestational age during the term period and increasing cumulative risk of stillbirth, however, there have been published concerns that the 39-week rule-by increasing the gestational age of delivery for a substantial number of pregnancies-might increase the rate of term stillbirth within the United States. Although adherence to the 39-week rule is assumed to be beneficial, its actual impact on the US rate of term stillbirth in the years since 2010 is unknown. OBJECTIVE: To determine whether the adoption of the 39-week rule was associated with an increased rate of term stillbirth in the United States. STUDY DESIGN: Sequential ecological study, based on state data, of US term deliveries that occurred during a 7-year period bounded by 2007 and 2013. The patterns of the timing of both term childbirth and term stillbirth were determined for each state and for the United States as a whole. RESULTS: A total of 46 usable datasets were obtained (45 states and the District of Columbia). During the 7-year period, there was a continuous reduction in all geographic entities in the proportion of term deliveries that occurred before 39 weeks of gestation. The overall rate of term stillbirth, when we compared 2007-2009 with 2011-2013, increased significantly (1.103/1000 vs 1.177/1000, RR 1.067, 95% confidence interval 1.038-1.096). Furthermore, during the 7-year period, the increase in the rate of US term stillbirth appeared to be continuous (estimated slope: 0.0186/1000/year, 95% confidence interval 0.002-0.035). Assuming 3.5 million term US births per year, and given 6 yearly "intervals" with this rate increase, it is possible that more than 335 additional term stillbirths occurred in the United States in 2013 as compared with 2007. In addition, during the 7-year period, there was a progressive shift in the timing of delivery from the 40th week to the 39th week. Absent this confounding factor, the magnitude of association between the adoption of the 39-week rule and the increase in rate of term stillbirth might have been greater. CONCLUSIONS: Between 2007 and 2013 in the United States, the adoption of the 39-week rule caused a progressive reduction in the proportion of term births occurring before the 39th week of gestation. During the same interval the United States experienced a significant increase in its rate of term stillbirth. This study raises the possibility that the 39-week rule may be causing unintended harm. Additional studies of the actual impact of the adoption of the 39-week rule on major childbirth outcomes are urgently needed. Pressures to enforce the 39-week rule should be reconsidered pending the findings of such studies.