Development and Validation of a Nomogram Incorporating Colloid Osmotic Pressure for Predicting Mortality in Critically Ill Neurological Patients

Backgrounds: The plasma colloid osmotic pressure (COP) values for predicting mortality are not well-estimated. A user-friendly nomogram could predict mortality by incorporating clinical factors and scoring systems to facilitate physicians modify decision-making when caring for patients with serious neurological conditions.Methods: Patients were prospectively recruited from March 2017 to September 2018 from a tertiary hospital to establish the development cohort for the internal test of the nomogram, while patients recruited from October 2018 to June 2019 from another tertiary hospital prospectively constituted the validation cohort for the external validation of the nomogram. A multivariate logistic regression analysis was performed in the development cohort using a backward stepwise method to determine the best-fit model for the nomogram. The nomogram was subsequently validated in an independent external validation cohort for discrimination and calibration. A decision-curve analysis was also performed to evaluate the net benefit of the insertion decision using the nomogram.Results: A total of 280 patients were enrolled in the development cohort, of whom 42 (15.0%) died, whereas 237 patients were enrolled in the validation cohort, of which 43 (18.1%) died. COP, neurological pathogenesis and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were predictors in the prediction nomogram. The derived cohort demonstrated good discriminative ability, and the area under the receiver operating characteristic curve (AUC) was 0.895 [95% confidence interval (CI), 0.840–0.951], showing good correction ability. The application of this nomogram to the validation cohort also provided good discrimination, with an AUC of 0.934 (95% CI, 0.892–0.976) and good calibration. The decision-curve analysis of this nomogram showed a better net benefit.Conclusions : A prediction nomogram incorporating COP, neurological pathogenesis and APACHE II score could be convenient in predicting mortality for critically ill neurological patients.

Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

The size of the nucleus scales robustly with cell size so that the nuclear-to-cell volume ratio (N/C ratio) is maintained during cell growth in many cell types. The mechanism responsible for this scaling remains mysterious. Previous studies have established that the N/C ratio is not determined by DNA amount, but is instead influenced by factors such as nuclear envelope mechanics and nuclear transport. Here, we developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in the fission yeast Schizosaccharomyces pombe. This model posits that the N/C ratio is determined by the numbers of macromolecules in the nucleoplasm and cytoplasm. Osmotic shift experiments showed that the fission yeast nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces. Inhibition of nuclear export caused accumulation of macromolecules and an increase in crowding in the nucleoplasm, leading to nuclear swelling. We further demonstrated that the N/C ratio is maintained by a homeostasis mechanism based upon synthesis of macromolecules during growth. These studies demonstrate the functions of colloid osmotic pressure in intracellular organization and size control.

Analysis of Mitochondrial Calcium Retention Capacity in Cultured Cells: Permeabilized Cells Versus Isolated Mitochondria

In response to various pathological stimuli, such as oxidative and energy stress accompanied by high Ca2+, mitochondria undergo permeability transition (PT) leading to the opening of the non-selective PT pores (PTP) in the inner mitochondrial membrane. Opening of the pores at high conductance allows the passage of ions and solutes <1.5 kD across the membrane, that increases colloid osmotic pressure in the matrix leading to excessive mitochondrial swelling. Calcium retention capacity (CRC) reflects maximum Ca2+ overload of mitochondria that occurs just before PTP opening. Quantification of CRC is important for elucidating the effects of different pathological stimuli and the efficacy of pharmacological agents on the mitochondria. Here, we performed a comparative analysis of CRC in mitochondria isolated from H9c2 cardioblasts, and in permeabilized H9c2 cells in situ to highlight the strengths and weaknesses of the CRC technique in isolated cell mitochondria vs. permeabilized cells. The cells were permeabilized by digitonin or saponin, and the Ca2+-sensitive fluorescence probe Calcium Green-5N was used in both preparations. Results demonstrated the interference of dye-associated fluorescence signals with saponin and the adverse effects of digitonin on mitochondria at high concentrations. Analysis of the CRC in permeabilized cells revealed a higher CRC in the saponin-permeabilized cells in comparison with the digitonin-permeabilized cells. In addition, the mitochondrial CRC in saponin-permeabilized cells was higher than in isolated mitochondria. Altogether, these data demonstrate that the quantification of the mitochondrial CRC in cultured cells permeabilized by saponin has more advantages compared to the isolated mitochondria.

Mathematical model of solute transfer in a permeable channel with effect of variable viscosity

This paper describes a mathematical model of solute transfer in fluid flow across a permeable channel with variable viscosity, with applications to glomerular capillary blood flow. Solute transfer through the glomerular capillary wall is controlled by the difference in transcapillary hydrostatic pressure and the analogous difference in colloid osmotic pressure (Starling’s law). Using appropriate analytical and numerical approaches, the solutions of coupled equations regulating fluid flow and solute transport are found. The current study’s hydrostatic and osmotic pressure curves are qualitatively in excellent agreement with the experimental data. The effects of variable viscosity on velocity profiles, concentration profiles, and total solute clearance are seen to be substantial, and the findings are graphically depicted.

The Colloid Osmotic Pressure Across the Glycocalyx: Role of Interstitial Fluid Sub-Compartments in Trans-Vascular Fluid Exchange in Skeletal Muscle

The primary purpose of these investigations is to integrate our growing knowledge about the endothelial glycocalyx as a permeability and osmotic barrier into models of trans-vascular fluid exchange in whole organs. We describe changes in the colloid osmotic pressure (COP) difference for plasma proteins across the glycocalyx after an increase or decrease in capillary pressure. The composition of the fluid under the glycocalyx changes in step with capillary pressure whereas the composition of the interstitial fluid takes many hours to adjust to a change in vascular pressure. We use models where the fluid under the glycocalyx mixes with sub-compartments of the interstitial fluid (ISF) whose volumes are defined from the ultrastructure of the inter-endothelial cleft and the histology of the tissue surrounding the capillaries. The initial protein composition in the sub-compartments is that during steady state filtration in the presence of a large pore pathway in parallel with the “small pore” glycocalyx pathway. Changes in the composition depend on the volume of the sub-compartment and the balance of convective and diffusive transport into and out of each sub-compartment. In skeletal muscle the simplest model assumes that the fluid under the glycocalyx mixes directly with a tissue sub-compartment with a volume less than 20% of the total skeletal muscle interstitial fluid volume. The model places limits on trans-vascular flows during transient filtration and reabsorption over periods of 30–60 min. The key assumption in this model is compromised when the resistance to diffusion between the base of the glycocalyx and the tissue sub-compartment accounts for more than 1% of the total resistance to diffusion across the endothelial barrier. It is well established that, in the steady state, there can be no reabsorption in tissue such as skeletal muscle. Our approach extends this idea to demonstrate that transient changes in vascular pressure favoring initial reabsorption from the interstitial fluid of skeletal muscle result in much less fluid exchange than is commonly assumed. Our approach should enable critical evaluations of the empirical models of trans-vascular fluid exchange being used in the clinic that do not account for the hydrostatic and COPs across the glycocalyx.

Serum Albumin

Being one of the most abundant proteins in human and other mammals, albumin plays a crucial role in transporting various endogenous and exogenous molecules and maintaining of colloid osmotic pressure of the blood. It is not only the passive but also the active participant of the pharmacokinetic and toxicokinetic processes possessing a number of enzymatic activities. A free thiol group of the albumin molecule determines the participation of the protein in redox reactions. Its activity is not limited to interaction with other molecules entering the blood: of great physiological importance is its interaction with the cells of blood, blood vessels and also outside the vascular bed. This entry contains data on the enzymatic, inflammatory and antioxidant properties of serum albumin.

Options of severe preeclampsia treatment

Background. Preeclampsia (PE) occurs in 2-8 % of all pregnancies. Every day 210 women die from PE, and neonatal losses are even greater (1380 children per day). Fatal complications of severe PE include cerebral hemorrhage, cerebral edema, pulmonary edema, placental abruption, adrenal hemorrhage, dissecting aortic aneurysm, HELLP syndrome, disseminated intravascular coagulation syndrome. Excessive intravenous fluid infusion is one of the causes of pulmonary edema in PE. Objective. To describe the options of severe PE treatment. Materials and methods. Analysis of literature data on this issue. Results and discussion. The pathogenesis of PE is based on total damage to the vascular endothelium, which leads to an increase in its permeability, including for albumin molecules. Plasma protein loss is accompanied by a drop in oncotic blood pressure and fluid leakage into the interstitial space. Thus, in patients with PE there is an associated disturbance of fluid and electrolyte balance: along with intravascular dehydration there is extravascular hyperhydration. Infusion therapy (IT) allows to overcome this imbalance and to increase the colloid-osmotic pressure. According to modern views, a restricted IT regimen improves the effects of PE treatment. There are two ways to correct this disorder: an increase in oncotic blood pressure due to infusion of albumin (indicated in case of blood albumin levels <25 g/L) and the administration of osmotically active drugs, such as Reosorbilact (“Yuria-Pharm”). The latter option prevents the loss of fluid from the vascular bed and promotes its return to the vessels from the intercellular space. The total fluid volume should be limited to physiological needs, taking into account pathological losses (not more than 1 ml/kg/h). The maximum IT volume should not exceed 800 ml per day. The drugs of choice for IT before delivery are balanced isotonic saline solutions and solutions containing 6 % sorbitol. Fresh-frozen plasma is not recommended for the correction of colloid-oncotic pressure. Influence on the redistribution of fluid in the interstitial space without the introduction of significant volumes of infusion solutions is the main principle of low-volume IT. Recommendations for the administration of Reosorbilact comply with this principle. The low osmolarity of Reosorbilact and its ability to improve the osmotic properties of blood justify the use of this drug in women with PE. Conclusions. 1. PE occurs in 2-8 % of all pregnancies. 2. Excessive intravenous fluid infusion is one of the causes of pulmonary edema in PE. 3. Restricted IT mode improves the consequences of PE treatment. 4. Osmotically active drugs (Reosorbilact) are prescribed for this purpose.