Coagulation at the blood-electrode interface: the role of electrochemical desorption and degradation of fibrinogen

The influence of electrochemistry on the coagulation of blood on metal surfaces was demonstrated several decades ago. In particular, the application of cathodic currents resulted in reduced surface thrombogenicity, but no molecular mechanism has been so far proposed to explain this observation. In this article we used for the first time the quartz crystal microbalance with dissipation monitoring technique coupled with an electrochemical setup (EQCM-D) to study thrombosis at the blood-electrode interface. We confirmed the reduced thrombus deposition at the cathode, and we subsequently studied the effect of cathodic currents on adsorbed fibrinogen (Fg). Using EQCM and mass spectrometry, we found that upon applying currents Fg desorbed from the electrode and was electrochemically degraded. In particular, we show that the flexible N-terminus of the α-chain, containing an important polymerization site, was cleaved from the protein, thus affecting its clottability. Our work proposes a molecular mechanism that at least partially explains how cathodic currents reduce thrombosis at the blood-electrode interface and is a relevant contribution to the rational development of medical devices with reduced thrombus formation on their surface

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.

Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors

GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK: SUMMARY OF A RECENT EXERCISE

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop theircollective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency. A recent exercise was conductedto test the participating laboratories for their capabilities in screening and in vitro assay of biological samples, performinginternal dose assessment and providing advice on medical intervention, if necessary, using a urine sample spiked with a singleradionuclide, 241Am. The laboratories were required to submit their reports according to the exercise schedule and using pre-formattedtemplates. Generally, the participating laboratories were found to be capable with respect to rapidly screening samplesfor radionuclide contamination, measuring the radionuclide in the samples, assessing the intake and radiation dose, and providingadvice on medical intervention. However, gaps in bioassay measurement and dose assessment have been identified. Thenetwork may take steps to ensure that procedures and practices within this network be harmonised and a follow-up exercise beorganised on a larger scale, with potential participation of laboratories from the networks coordinated by the InternationalAtomic Energy Agency and theWorld Health Organization