The low quality of transplants having undergone hypoxic injury can lead to postoperative complications. The aim of the present research is to estimate, by means of mathematical modeling, how the process of oxygen uptake through the liver surface influences the metabolism of ex vivo perfused liver under hypoxia. The value of oxygen uptake through the surface was established to depend on the degree of oxygenation of the perfusion medium. A decrease in the oxygenation of the perfusion medium resulted in a decreased oxygen uptake through the liver surface. Stoichiometric modeling of the liver metabolism shows that upon the decreased oxygenation of the perfusion medium more energy is required for the process of oxygen uptake through the surface even at a lower level as compared to the normal oxygen supply. The application of the Pareto optimality allows estimating the optimum distribution of the energy resources in liver under ex vivo conditions. Both upon the normal and decreased oxygenation of the perfusion medium, the phenomenon of "free competition" for the resource was observed, with the energy being optimally distributed among all the metabolic fluxes. Moreover, this energy is also spent on the accompanying processes, e.g. for the transport of interstitial fluid.

We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.

Congenital heart diseases (CHDs) are the most common birth defects among life births, which could be presented as isolated or syndromic with other congenital malformations. The etiology of CHD largely unknown, genetic and environmental factors contribute to the disease. Recurrent copy number variants (CNVs) have been reported in the pathogenesis of CHD. The aim of this study was to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and microarray analyses on isolated and syndromic CHD cases and to explore the relationship between identified CNVs and CHD. Eighteen prenatal samples, 16 isolated and 33 syndromic patients with mild to severe CHD phenotype were tested. Prenatal and isolated CHD cases did not show pathogenic CNVs. Clinically significant CNVs were detected in 7/33 (21%) syndromic CHD patients: del 22q11.2 (n = 2), 8p23.1 duplication (n = 2), deletion 5p (n = 1), deletion 6q21q22 (n = 1), unbalanced translocation causing partial deletion of 4q34.3 and duplication of 6q25.1 (n = 1). These genomic imbalances contain genes that has been associated with human CHD before. The present study demonstrates that using microarray and MLPA analysis increase the detection rate of causal CNVs in individuals with syndromic CHD.

Математическое моделирование метаболической активности изолированной перфузируемой печени крысы в условиях сниженной оксигенации перфузионной средыШадрин К.В. 1, 2 , Пахомова В.Г. 1 , Крюкова О.В. 1 , Рупенко А.П. 1 1 ФГБНУ «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук» 2 ФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф.Войно-Ясенецкого» Министерства здравоохранения Российской Федерации

The metabolic features of the rat liver were studied in artificial homeostasis conditions, using an isolated perfused organ as a model. The metabolism of the liver isolated from an intact rat and perfused with a normobaric hypoxic medium was compared with that of a liver that was isolated from a rat preliminarily kept in a chamber to simulate hypoxia of the total body and perfused using a medium with a normal oxygen content. The functional activity of the liver was assessed by portal pressure; oxygen consumption; and carbon dioxide gas, urea, glucose, and lactate contents in the perfusion medium. Metabolic changes in the perfused liver during oxygen deficiency became detectable at the same time point after exposure regardless of the method used to experimentally simulate hypoxia. This finding directly points to the metabolic autonomy of the liver.

The goal of this work was to suggest a method for measuring the total rate of oxygen consumption by an isolated perfused rat liver. This method involves calculation of the rates of oxygen consumption by the blood stream and through the liver surface. The two independently determined values are then summed up to determine the total consumption rate. Experimental results obtained by this method are in good agreement with the results obtained previously using the manometric method of measurement of the oxygen consumption rate.

It is shown that the transport of oxygen through the surface of the isolated perfused rat liver is an energy-dependent process that requires the energy of ATP hydrolysis.

The effect of the perfusion conditions (duration of the preparatory period, noradrenaline and lactic acid) on the characteristics of isolated rat liver functioning is determined in the present research.

The research results on estimation of nitrogen-containing and carbohydrate compounds metabolism in the isolated perfused rat liver undergoing the hypoxic conditions simulated by cobalt chloride are presented in the article.

It is convenient to study liver function and metabolism on the model of isolated perfused organ. The results of the present study indicate that viability and metabolic activity of the organ largely depend on the composition of the medium. Under conditions of isolated perfusion, the known pathway of oxygen transport through capillary filtration is supplemented by oxygen delivery to cells through the organ surface making an important contribution to liver oxygenation.