Platelet transfusions are routine procedures in clinical treatment aimed at preventing bleeding in critically ill patients, including those with cancer, undergoing surgery, or experiencing trauma. However, platelets are susceptible blood cells that require specific storage conditions. The availability of platelet concentrates is limited to five days due to various factors, including the risk of bacterial contamination and the occurrence of physical and functional changes known as platelet storage lesions. In this article, the problems related to platelet storage lesions are categorized into four groups depending on research areas: storage conditions, additive solutions, new testing methods for platelets (proteomic and metabolomic analysis), and extensive data modeling of platelet production (mathematical modeling, statistical analysis, and artificial intelligence). This article provides extensive information on the challenges, potential improvements, and novel perspectives regarding platelet storage.

Fluorescein-PE is a fluorescence probe that is used as a membrane label or a sensor of surface associated processes. Fluorescein-PE fluorescence intensity depends not only on bulk pH, but also on the local electrostatic potential, which affects the local membrane interface proton concentration. The pH sensitivity and hydrophilic character of the fluorescein moiety was used to detect conformational changes at the lipid bilayer surface. When located in the dipalmitoylphosphatidylcholine (DPPC) bilayer, probe fluorescence depends on conformational changes that occur during phase transitions. Relative fluorescence intensity changes more at pretransition than at the main phase transition temperature, indicating that interface conformation affects the condition in the vicinity of the membrane. Local electrostatic potential depends on surface charge density, the local dielectric constant, salt concentration and water organisation. Initial increase in fluorescence intensity at temperatures preceding that of pretransition can be explained by the decreased value of the dielectric constant in the lipid polar headgroups region related in turn to decreased water organisation within the membrane interface. The abrupt decrease in fluorescence intensity at temperatures between 25 degrees C and 35 degrees C (DPPC pretransition) is likely to be caused by an increased value of the electrostatic potential, induced by an elevated value of the dielectric constant within the phosphate group region. Further increase in the fluorescence intensity at temperatures above that of the gel-liquid phase transition correlates with the calculated decreased surface electrostatic potential. Above the main phase transition temperature, fluorescence intensity increase at a salt concentration of 140 mM is larger than with 14 mM. This results from a sharp decline of the electrostatic potential induced by the phosphocholine dipole as a function of distance from the membrane surface.

Obese people differ from the people of normal weight in gall bladder motility and have a higher risk of cholesterol stone formation. In this study, using a mathematical model of cholesterol homeostasis, which also considers the enterohepatic circulation of bile as well as cholesterol, we investigated the risk of cholesterol stone formation in obese and normal-weight groups who had normal blood cholesterol levels. We associated the risk of stone formation with the amount of cholesterol released into bile and the amount of de novo-synthesized cholic acid. For both groups, we determined the conditions of low and high risk. In addition, we analyzed the potential effects of changes in gall bladder motility with increased weight. The results showed that the obese group exhibited increased kinetics of enterohepatic circulation, leading to a significant increase in blood cholesterol levels, which can be reduced by increasing the amount of cholesterol in bile. Based on this finding, we suggest that for obese people, it is beneficial to reduce the amount and change the composition of circulating bile through the inhibition of cholic acid synthesis along with cholesterol synthesis. Furthermore, obese people should maintain a triglyceride-lowering diet and consume small meals containing fat, preferably in combination with agents that can reduce bile output from the gall bladder.

This study aimed to build a mathematical model describing the pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) in a stable setting with concomitant administration of morphine. The model consists of a set of four differential equations prepared upon the available knowledge regarding the biological processes in the pharmacokinetics of ticagrelor. The set of equations was solved numerically using the Runge–Kutta method. The data were obtained in a double-blind, randomized, placebo-controlled, crossover trial. Twenty-four healthy volunteers received a 180-mg ticagrelor loading dose together with either 5-mg morphine or placebo. Blood samples were analyzed with liquid chromatography–tandem mass spectrometry to assess plasma concentrations of ticagrelor and AR-C124910XX before ticagrelor loading dose and after that 1, 2, 3, 4, and 6 h. The model allowed us to reproduce the experimental results accurately and led us to conclusions consistent with clinical observations that morphine delays the time of maximum drug concentration and that the morphine effect occurs due to decreased gastrointestinal motility. Based on the model, we were able to predict the effect of drug dose on receptor blocking efficacy.

Cholesterol is a vital structural and functional molecule in the human body that is only slightly soluble in water and therefore does not easily travels by itself in the bloodstream. To enable cholesterol's targeted delivery to cells and tissues, it is encapsulated by different fractions of lipoproteins, complex particles containing both proteins and lipids. Maintaining cholesterol homeostasis is a highly regulated process with multiple factors acting at both molecular and tissue levels. Furthermore, to regulate the circulatory transport of cholesterol in lipoproteins, the amount of cholesterol present depends on and is controlled by cholesterol dietary intake, de novo synthesis, usage, and excretion; abnormal and/or unbalanced cholesterol levels have been shown to lead to severe outcomes, e.g., cardiovascular diseases. To investigate cholesterol transport in the circulatory system, we have previously developed a two-compartment mathematical model. Here, we show how this model can be used as a teaching tool for cholesterol homeostasis. Using the model and a hands-on approach, students can familiarize themselves with the basic components and mechanisms behind balanced cholesterol circulatory transport as well as investigate the consequences of and countermeasures to abnormal cholesterol levels. Among others, various treatments of high blood cholesterol levels can be simulated, e.g., with commonly prescribed de novo cholesterol synthesis inhibitors.