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In North America, red blood cells (RBCs) are currently cryopreserved in a solution of 40% glycerol. While glycerol is not inherently toxic to humans, it must be removed prior to transfusion to prevent intravascular osmotic hemolysis. The current deglycerolization procedure requires about 45 min per RBC unit. We previously presented predictions suggesting that glycerol could be safely removed from RBCs in less than 1 min. However, experimental evaluation of these methods resulted in much higher hemolysis than expected. Here we extend our previous study by considering both concentration-dependence of permeability and variability in permeability values in the mathematical optimization algorithm. To establish a model for the concentration dependence of glycerol permeability, we combined literature data with new measurements of permeability in the presence of 40% glycerol. To account for cell-dependent variability we scaled the concentration-dependent permeability model to define a permeability range for optimization. Methods designed using a range extending to 50% of the model-predicted glycerol permeability had a duration of less than 3 min and resulted in hemolysis ranging from 34% to 83%; hemolysis values were highly dependent on the blood donor. Extending the permeability range to 5% of the model-predicted value yielded a 30 min method that resulted in an average hemolysis of 12%. Our results suggest high variability in the glycerol permeability between donors and within a population of cells from the same donor. Such variability has broad implications for design of methods for equilibration of cells with cryoprotectants.
This article was published in the following journal.
A number of small inhibitors have been developed in recent years to target the cancer driving protein, K-Ras. In this study we propose and design a novel way of targeting oncogenic K-Ras4B.G12D with m...
Stapled peptides recapitulate the binding affinity and specificity of α-helices in proteins, resist proteolytic degradation, and may provide a novel modality against challenging drug targets such as ...
Bivalent chemical degraders provide a catalytic route to selectively remove disease-associated proteins. By linking target-specific ligands with E3 ubiquitin ligase recruiting ligands, these modular c...
Promoting drug delivery across the biological membrane is a common strategy to improve bioavailability. Inspired by the observation that carbonated alcoholic beverages can increase the absorption rate...
The RPMI 2650 cell line has been a subject of evaluation as a physiological and pharmacological model of the nasal epithelial barrier. However, its suitability for drug permeability assays has not yet...
In China, the estimated prevalence of patients with ESRD receiving peritoneal dialysis (PD) or maintenance hemodialysis (HD) increased from 51.7 per million population (pmp) at the end of ...
This study was designed to determine if an ingredient in milk fat can prevent gut leakiness induced by running at 80% maximum oxygen consumption (VO2max). In mouse studies, the milk fat in...
An epiretinal membrane is scar tissue on the retina that can cause blurring and distortion of vision and lead to swelling, or macular edema. Despite surgery to remove the scar tissue(membr...
Peritoneal Dialysis (PD) is a technique for treating kidney failure where fluid is instilled into the body's peritoneal cavity. Fluid and solutes travel across the peritoneal membrane, and...
The investigators to establish whether early microvascular permeability parameter evaluated by perfusion-CT could be good biomarkers for severity in acute pancreatitis. Therefore the inve...
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane.
Methods of creating machines and devices.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...