Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material.

Sialic acids (SA) are neuraminic acid derivatives, located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role: they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be considered as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme impact on the body and inflammatory processes are accompanied by an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include: (i) activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, (ii) impaired membrane integrity and destruction of body cells, (iii) high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and sialoglycoconjugate half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, consists in establishing the causes and mechanisms of biochemical changes in the body in certain diseases. In combination with the measurement of existing markers, they can be used to improve diagnosis, staging and monitoring of therapeutic response in some pathological conditions where the need for specificity is less than for specific diagnostics.

[Clinical and diagnostic significance of sialic acids determination in biological material]. / Kliniko-diagnosticheskoe znachenie opredeleniia sialovykh kislot v biologicheskikh ob"ektakh.

Sialic acids (SA) are derivatives of neuraminic acid; they are located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role, they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be viewed as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme effects on the body and inflammatory processes lead to an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, violation of the membrane integrity and destruction of body cells, and also high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Nevertheless, determining blood SA level and measuring concentration of existing biomarkers can be used to improve diagnostic indicators, to stage and monitor therapeutic response in some types of cancer, when the need for specificity is less than for diagnosis. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, lies in establishing the causes and mechanisms of biochemical changes in the body in certain diseases.

Prospects for the use of indicators of sialic acid metabolism in medicine (review of literature).

Sialic acids (SA) determine the degree of molecular hydrophilia, relieve binding together and their transportation, they increase mucin viscosity, stabilize the protein and membrane structure. Apart from that, SA are structural components of gangliosides participating in the formation of the outer layer of the plasma membrane. The degree of silyliation of glycoproteins and glycolipids is an important factor of molecular recognition in the cell, between the cells, between a cell and territorial matrix, as well as between a cell and some outer pathogenic factors. They can either mask the sites of recognition or be determinants of recognition. The most well-studied enzymes taking part in the SA metabolism and sialo-containing compounds are N-acetylneuraminate, cythydiltransferase, sialyltransferase, sialydase, aldolase SA and sialyl-O-acetylesterase. Numerous investigations have shown that aberrant sialylation is a specific feature of various changes and disorders of metabolism. Besides that, sialic acids are the first point of contact for different pathogenic microorganisms and the host's body due to their presence on the external surface of the cells and tissue of the mucous membrane. That is why the study of the above-mentioned various sialic acids fractions as well as of the activity of the enzymes participating in their metabolism in the blood plasma and tissues, and of the influence on the activity of these enzymes with the help of medicine can make an essential contribution to the diagnosis and treatment of many diseases.

[Influence of high-fructose diet on fibronectin level in rat blood serum].

In recent years, the consumption of diets containing a large amount of fructose has increased sharply, which is associated with the observed increase in the incidence of obesity, diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Changes in lipid and carbohydrate metabolism due to increased consumption of fructose are one of the causes of destructive processes in the tissues and cells of the organism. Fibronectin, which is an adhesive and regulatory protein of the intercellular matrix, can serve as one of the markers of these processes. The aim of the research was to study the effect of a high-fructose diet on rat serum fibronectin level. Material and methods. The experiment was performed on 50 outbred male rats aged 5-6 months. Rats from the control group (n=25) received a balanced diet of vivarium. Animals of the experimental group (n=25) for 35 days were fed a diet containing 60% fructose, 20% protein, 14% fiber, 6% fat. From the 36th to the 60th day, all rats were fed usual vivarium diet. On the 60th day, the formation of metabolic changes in the long-term period was evaluated. The animals of each group were weighed before and when removed from the experiment on the 21st, 35th and 60th day. Serum was obtained from blood samples collected during decapitation on an empty stomach under short-term ether anesthesia. The concentration of cholesterol, high and low density lipoproteins, triglycerides, glucose, insulin and fibronectin were determined in serum. The atherogenic index and insulin resistance indices were calculated using the corresponding formulas. Results and discussion. The experiment revealed a significant increase in glucose concentration from 6.52±0.35 (in control) to 7.74±0.73, 7.97±1.91 and 7.87±0.65 mmol/l and in insulin level from 1.6±0.6 to 2.3±0.4, 2.6±0.6 and 3.1±0.9 µU/ml on the 21nd, 35th and 60th days of the experiment, respectively, in animals of the experimental group, which is possibly associated with a sharp rise in the concentration of free fatty acids due to the special metabolism of fructose and the occurring oxidative stress, which causes cell damage and the formation of insulin resistance. This is reflected by insulin resistance indices that are different from the control: HOMA by 42.3, 49.2 and 81.3% higher, CARO by 13.3, 16.0 and 28.8% less than the control in the dynamics of the experiment. There was a tendency to an increase in cholesterol level with a significant rise on the 35th day of the experiment by 58.9% relative to the control. A statistically significant increase in the content of low-density lipoproteins was also observed by 158, 141 and 229% compared with the control. Such a rise can be associated with both increased formation of free fatty acids and lipogenetic activity of insulin. In addition, we revealed a significant increase in the content of fibronectin on days 21, 35 and 60 of the experiment, respectively, from 56.5±2.8 (in control) to 74±8.1, 79±3.8 and 98±2.1 µg/ml. Fibronectin plays a significant role in tissue repair processes, providing cell migration and adhesion. Its blood level can correlate with the degree of destructive and reparative processes in the cells of liver and vascular endothelium. Conclusion. A high-fructose diet in rats causes an increase in the studied biochemical parameters of carbohydrate and lipid metabolism, as well as an increase in blood level of the main regulatory protein of the intercellular matrix - fibronectin.

[Surfactant system of lung in rats with different resistance to stress under alloxan diabetes].

It is shown that the surface active properties of lung under experimental diabetes mellitus was decreased on the background of increased LPL content in alveolar space. Surfactant changes correlated with the level of glucose, glycosylated hemoglobin and 11-oxycorticosteroids in blood. The obtained results indicate that the degree of impairment in the pulmonary surfactant system in alloxan diabetes depends on the resistance or susceptibility of animals to stress.

[Metabolism of sialoglycoproteins of the stomach of rats with experimental diabetes]. / Pokazateli obmena sialoglikoproteinov zheludka krys s éksperimental'nym diabetom.

Experiments on white non-inbred male rats studied gastric sialoglycoprotein metabolism. It was found that rats with experimental (alloxan) diabetes exhibit enhanced catabolic processes in sialoglycoprotein metabolism characterized by elevated concentrations of free, oligobound sialic acids and sialidase activity in insignificantly elevated concentrations of protein-bound sialic acids.

[Changes in metabolism of sialoglycoproteins of the rat stomach during long-term immobilization stress and glucocorticoid hormone deficiency]. / Izmeneniia v obmene sialoglikoproteinov zheludka krys pri dlitel'nom immobolizatsionnom stresse v usloviiakh defitsita gliukokortikoidnykh gormonov.

The effect of glucocorticoid hormone deficiency (caused by administration of chlordithane) on the methabolism of gastric sialoglycoproteins at the prolonged immobilized stress was investigated in male albino rats. Under conditions of prolonged deficit of glucocorticoid hormones (> 10 days) the imobilised stress caused higher increase of catabolic processes of sialoglycoproteins than in rats with normal level of glucocorticoids.

[Changes in the fractional collagen composition of the kidneys in rats under immobilization stress and alloxan diabetes]. / Izmenenie fraktsionnogo sostava kollagena pochek krys pri immobilizatsionnom stresse na fone alloksanovogo diabeta.

Content of free hydroxyproline, total collagen and neutral salt-soluble, citrate-soluble, nonsoluble fractions of collagen and also collagenolytic activity on combined immobilization stress days 3, 10, 15 and 30 in alloxan diabetes were studied in homogenates of the cortical zone of rats' kidneys. Changes in the fractional collagen composition were found phasic. The additional stress load on its days 1-10 attenuates but in the following days aggravates the catabolic action of alloxan diabetes on collagen metabolism in the kidneys.

[The biopolymer metabolism of the connective tissue in the aorta under intraventricular injections of neuropeptides]. / Obmen biopolimerov soedinitel'noi tkani v aorte pri intraventrikuliarnykh vvedeniiakh neiropeptidov.

The metabolism of connective tissue biopolymers in the blood serum and in the aorta under repeated intraventricular injections of P-substance, L-enkephalin and B-endorphine was studied in chronic experiments on rabbits. The alternations of the central neurochemical processes, caused by prolonged intraventricular injections of neuropeptides were proved to lead to intensification of metabolic processes in the connective tissue characterized by the accumulation of its biopolymers in the aorta wall. The injection of P-substance, in contrast to opioid peptides, is accompanied by more marked alternations.

[Change in indicators of biopolymer metabolism in connective tissue upon central administration of angiotensin II]. / Izmenenie pokazatelei obmena biopolimerov soedinitel'noi tkani pri tsentral'nom vvedenii angiotenzina II.

Some patterns of connective tissue metabolism were studied in rabbit blood and aorta after local administration of angiotensin II into lateral ventricle of brain and ventromedian nucleus of hypothalamus. Within the first 10 days of the chronic experiments catabolism of connective tissue predominated, while anabolic processes, accompanied by accumulation of collagen in aorta, were elevated within 30 days. The alterations observed were most distinct after microinjection of angiotensin II into hypothalamus. Both modulating effect of angiotensin II on the adrenohypophysial system and the peptide immediate action were apparently responsible for alterations in metabolism of connective tissue-related biopolymers.

[Hormonal homeostasis and intraocular pressure in chronic emotional stress caused by influences acting on the amygdala]. / Gormonal'nyi gomeostaz i vnutriglaznoe davlenie pri khronicheskom émotsional'nom stresse, vyzvannom vozdeìstviiami na mindalevidnyi kompleks.

Changes in intraocular pressure, eye hydrodynamics and the amount of hypophyseal, thyroid, adrenal and pancreatic hormones were studied during continuous stimulation of amygdaloid complex or after administration of angiotensin II into the structure in rabbits. The effects involved changes in hormonal homeostasis and elevation of intraocular pressure due to a hypersecretion of intraocular fluid. The administration of angiotensin II during the amygdala stimulation enhanced the changes.

[Changes in the hormone content of the blood during chronic electrical stimulation of the midbrain]. / Izmenenie soderzhaniia gormonov v krovi pri khronicheskom élektricheskom razdrazhenii srednego mozga.

The levels of hormones of the hypophysis (ACTH, TTH, CTH), thyroid gland (T3, T4), adrenal glands (epinephrine, norepinephrine, cortisol) and pancreas (insulin, glucagon) increased during a prolonged electrostimulation of the reticular nucleus of mesencephalon in rabbits. Administration of the substance P returned the hormonal levels to normal.

[Indices of biopolymer metabolism in connective tissue during repeated stress]. / Pokazateli obmena biopolimerov soedinitel'noi tkani pri mnogokratnom stresse.

Experiments on rats have shown that daily strong stress actions (immobilization) brought about the marked increase in the 11-oxycorticosteroid level and indices of the biopolymer exchange in the connective tissue (free oxyproline, glycosaminoglycanes, sialic acids). Under the acupuncture action (weak stresses) all the above indices were changed mainly after the first influence. Preliminary acupuncture stimulations prevent deep changes in the exchange of biopolymers in the connective tissue, developing under strong stresses.

[Changes in the concentration of various collagen fractions after electric stimulation and electrocoagulation of the rabbit amygdaloid body]. / Izemenenie soderzhaniia razlichnykh fraktsii kollagena pri élektricheskoi stimuliatsii i élektrokoaguliatsii mindalevidnogo kompleksa mozga krolikov.

Content of catecholamines, 11-hydroxycorticosteroids, free and bound hydroxyproline in blood as well as metabolism of collagen in rabbit aorta wall were studied after electrostimulation and bilateral electrocoagulation of brain amygdaloid complex. The stimulation was shown to alter the content of adrenal gland hormones and activated the collagen metabolism in aorta wall. After electrocoagulation within the first month content of noradrenaline, 11-hydroxycorticosteroids and accumulation of collagen in aorta tissue were decreased.

[Adrenal hormone level and collagen metabolism in the aortic wall under the effect of changes in the amygdaloid complex]. / Uroven' gormonov nadpochechnikov i obmen kollagena v stenke aorty pri vozdeistviiakh na mindalevidnyi kompleks.

The blood catecholamine, 11-hydroxycorticosteroid and free hydroxyproline content and collagen metabolism in the rabbit aortic wall were studied under conditions of chronic electrostimulation and bilateral amygdaloid electrocoagulation. It was found that electrostimulation of the amygdaloid lateral nucleus causes changes in the adrenocorticotropin content, activating collagen metabolism and accumulation in the aortic wall. A fall of the noradrenaline, 11-hydroxycorticosteroid concentration and activation of collagen metabolism, accompanied by its accumulation in the aortic wall, are seen during the 1st month after electrocoagulation.

[Collagen metabolism in chronic electrical stimulation of the amygdaloid complex]. / Obmen kollagena pri khronicheskoi élektricheskoi stimuliatsii mindalevidnogo kompleksa.

The content of adrenaline, noradrenaline, 11-hydroxycorticosteroids, free and bound hydroxyproline in the peripheral blood of rabbits and collagen metabolism in the aortal wall were studied under chronic electrostimulation of the amygdaloid complex. Electrostimulation of the lateral nucleus of the amygdaloid was shown to induce definite shifts in the content of adrenocortical hormones and leads to collagen metabolism activation that results in collagen accumulation by the aortal wall.