[Biomarkers of angiogenesis and endothelial dysfunction in children and adolescents with chronic viral hepatitis.]

At some works, it has been shown there are signs of damage and endothelium dysfunction in patients with chronic viral hepatitis (CVH) and liver cirrhosis of viral etiology the severity of these conditions depends on the severity of the pathological process. Evaluation of the role of angiogenic factors and endothelial dysfunction in persistent of CVH in children and adolescents. 35 patients were examined: of which 11 with chronic hepatitis B (CHB) and 24 with chronic hepatitis C (CHC). The reference group consisted of 120 practically healthy persons of the corresponding age and sex. VEGF-A, angiotensin (ANG), soluble receptors of VEGF-A (sVEGF-R1 и sVEGF-R2) and trombomodulin (TM) have been investigated in serum by enzyme immunoassay using special kits (BCM Diagnostics, USA). Other endothelial dysfunction markers as von Willebrand factor (vWf) was determined in blood plasma by immunoturbidimetry (Siemens, Germany), plasminogen (PLG) was investigated due to extended coagulation. In children with CVH, regardless of etiology, the concentration of VEGF-A was significantly lower, and sVEGF-R2, sVEGF-R1 and TM was higher than in children without liver disease (p <0.001, p <0.05, p <0.01, p <0.001, respectively). The concentration of TM and the level of PLG activity in patients with CHC were slightly higher than in CHB. Decreased level of VEGF-A and increased expression of its soluble receptors indicate enhanced inhibition of angiogenesis in CVH, which may indicate the pathogenetic role of this phenomenon in the development of liver damage in CHC.

[Changes in serum levels of the key factors of angiogenesis in different outcomes of combined injuries in children]. / Izmeneniia kontsentratsii v syvorotke krovi kliuchevykh faktorov angiogeneza pri razlichnykh iskhodakh sochetannoi travmy u detei.

AIM: To study the changes in the key angiogenic factors VEGF-A and angiogenin (ANG) in children with different outcomes of combined injuries. MATERIAL AND METHODS: Contents of VEGF-A and ANG in blood serum were determined by enzyme immunoassay. The study included 40 patients, 21 boys and 19 girls. Patients were divided into 4 groups according to the outcome of injury: 1 - the recovery or mild residual symptoms; 2 - disabled; 3 - vegetable state; 4 - death. Patients were examined at different times after injury: 1-6 days, 7-11 days, 12-19 and 20-33 days. RESULTS AND CONCLUSION: In the first days after injury, the content of VEGF-A in patients of 1-3 groups was at the level of the reference group, moreover, in patients of the 3rd group it was close to the top edge. In group 4, the content of VEGF-A was maximal in the first days after injury and then gradually decreased to the point of death. In groups 1 and 3, the level of VEGF-A increased significantly starting from the 2nd week while in group 2 this indicator was slightly increased approaching later (up to 33 days of observation) to the upper values in the reference group. In the 3rd group, the content of VEGF-A reached the plateau on the 19th day after injury and was higher than the reference data, but lower than in patients of the 1st group. No correlation between the changes in ANG content at different times after combined injuries and outcome was found. There was a trend towards decreased levels of ANG, especially after 3-4 weeks after injury. The data obtained are important for the control over processes of vascular and tissue reparation after injury and for searching for effective ways of treatment of altered angiogenesis in such patients.

[Current status of vascular remodeling and angiogenesis in chronic liver diseases].

The review focuses on the analysis of researches on the pathophysiology of liver vascular bed, mesenteric vessels, as well as the characteristics of angiogenesis in CLD. The results of this review shows that one of the most important areas of research is soluble vascular endothelial growth factor receptors, disclosing their importance for prognosis and treatment of diseases that occur with severe disorders of angiogenesis, including in CLD.

[THE MODERN CONCEPTS OF HEMOSTASIS SYSTEM UNDER CHRONIC DISEASES OF LIVER: THE PUBLICATIONS REVIEW].

The disorder of system of hemostasis under chronic diseases of liver results in coagulation imbalance affecting both primary and secondary hemostasis. The shifting of hemostasis balance beyond the limits of physiological standards in such patients can result either in bleeding or thrombosis. For a long time already it is considered that in patients with chronic diseases of liver alterations in hemostasis system and occurrence of bleeding are very often interrelated. However results of such screening coagulation tests as prothrombin time and activated partial thromboplastin time poorly correlate with onset and duration of bleeding, for example after liver biopsy and also with occurrence of gastro-intestinal bleeding in patients with terminal stage of diseases of liver The foreign publications of last decade contest concept of cause and effect relationship between changes of indicators of screening coagulation tests and risk of development of bleeding in patients with chronic diseases of liver The publications also dispute both usefulness of the given tests in evaluation of hemorrhages and expediency of therapeutic strategies in the case of correction of anomalous results of mentioned tests. This issue in patients with rare diseases is factually unexplored. For example, there are single publications concerning patients with glycogenous disease type. The bleeding in such patients begin in early childhood They are related to dysfunction of thrombocytes and decreasing of particular oligomers of von Willebrand factor Hence, disorders in various chains of hemostasis system in patients with chronic diseases of liver are characterized by many unresolved issues that hinder furthering of development of diagnostic biomarkers. At that, diagnostic of coagulopathies and correction of pathological conditions in such patients the new tests are to be developed to monitor states of hemostasis system in patients with chronic diseases of liver, rare nosologic forms included.

[Molecular mechanisms of genetic damages of the myocardium in cardiomyopathy].

The review highlighted problems of reorganization of myocardical contractile and cytoskeletal proteins in cardiomyopathy (CM). The role of the genetic factors coding contractile proteins, proteins of thin and thick filaments, and also extracellular matrix proteins in processes of formation and development of hypertrophic (HCM) and dilated (DCM) cardiomyopathy are analyzed. The mechanisms responsible for the changes in cardiac proteins on regulation involved into force generation, its transfer, recycling ATP, impairments in transmembranal signals, that finally lead to cardiac cell dysfunction determining various manifestations of CM are considered.

[Zinc and copper blood plasma and erythrocyte value in adolescent with the different types of pathology].

Comparative analysis the value of the cation of zinc and copper in the blood plasma and erythrocytes were performed in the different diseases in children and adolescent. The patients with bronchopulmonary diseases, liver diseases, low cardiovascular malformation and growth inhibition were examined. Increase the value of the intracellular zinc and copper was detected in patients with the definite bronchopulmonary diseases, which can on the one hand, reflected the activation of the antioxidant protection system and by another hand, reflected destructive metalloproteinase. Decrease the value of the intracellular copper in bronchopulmonary patients with the lung emphysema and Kartagnera syndrome indicate about the falure of the compensatory reactions and needs the additional investigation. It was detected that copper content in the blood plasma and the copper accumulation in erythrocyte were decrease in patients with liver diseases in comparison with the health children. The increase of copper value in erythrocyte in children with low cardiovascular malformation was detected and need the additional investigation. In children with the growth inhibition was detected appreciable decrease the value of the free zinc and copper ions in erythrocytes and copper in the blood plasma, which can explained the physical developmental lagging.

[Biochemical and immunological markers of insufficiency of blood circulation at children with cardiomiopathies].

Complex clinical-laboratory investigation of children with congestive heart failure (CHF) developed on the basis of dilated cardiomyopathy and hypertrophic cardiomyopathy has been carried out. The development of CHF in children with cardiomyopathy was accompanied by changes of blood serum lactate, MB isoform of creatine phosphokinase, TNF-6, interleukin-6 (IL-6) (but not IL-2), and soluble receptors for IL-2 and IL-6.

[The influence of sodium nitroprusside, the possible donor of nitric oxide on activity ATPases and lipid peroxidation of erythrocytes of sick children].

The effect of sodium nitroprusside, possible nitric oxide donor, on the activities of Ca2+, Mg(2+)- and Na+, K(+)-ATPases and lipid peroxidation was investigated in erythrocytes in vitro. Sodium nitroprusside caused 3-fold increase of mechanical and peroxidative erythrocyte hemolysis and also increase of bound malonic dialdehyde. Sodium nitroprusside-treated erythrocytes were also characterized by increased Na+, K(+)-ATPase activity.

[Biochemical changes of red blood cells in children with cerebral palsy and other organic brain disorders].

One hundred and twenty-five children with cerebral palsy (n = 108) and organic CNS lesions (n = 17) have been studied. A control group included 30 children without any neurological lesions. Lipids and phospholipids spectra, Ca, Mg- and Na, K-ATPases, intensity of red blood cells lipid peroxidation and erythrocyte free magnesium content have been determined. Children with cerebral palsy had a higher percentage of cholesterol ethers and final products of lipid peroxidation in red blood cells--Shiff bases and a decrease of intraerythrocytic free magnesium. Patients with atonic-astatic syndrome were characterized by a sharp increase of Na, K-ATPase activity accompanied by increased content of such phospholipids as cardiolipin and phosphatide acid as well as Shiff bases. In patients with organic CNS lesions, Shiff bases content was similar to that in the control group, intracellular magnesium also did not differ significantly from the controls, but cardiolipin, phosphatide acid, cholesterol ethers and triglycerol concentrations were reduced. All the patients with neurological disorders had an increased percentage of phosphatidilcholin in red blood cells.

[Lipid peroxidation in neurological pathology in children].

The intensity of lipid peroxidation (LPO) was studied by the content of the listed below in erythrocytes of children with neurological pathology: diene conjugates, trienketones and LPO products. Intensified LPO processes were registered in children with neurology and primarily in those with cerebral spastic infantile paralysis (CSIP). The detected changes in the LPO products of erythrocyte membranes depended on a disease variation on an intellectual development of sick child. The LPO activation affects possibly the development (lesion) of craniocerebral innervation in patients. Changed LPO parameters were found in examined sick children to be most closely related with the development of their motor skills and with the formation of the bone-muscle system, thus, an essentially higher content of LPO products was registered in erythrocytes of children with a reduced muscular activity (in those not capable of sitting, standing or walking). Considering the above stated and with respect to the deficit of Vitamin E registered in such patients, children with CSIP or with impending CSIP need, obviously a prolonged membrane-stabilizing therapy by antioxidants and essential phospholipids including traps of radicals, which should cut the number of children with severe CSIP and with residual perinatal lesions of the central nervous system.

[Biochemical changes in neurological pathology].

Literature data on biochemical changes of structural and functional state of biological membranes seen at neurological pathology have been reviewed.

[Red cell phospholipid composition in children with neurological pathology]. / Fosfolipidnyi sostav érotrotsitov pri nevrologicheskoi patologii u detei.

Changes of red cell membrane phospholipid composition were studied in children with different neurological disorders--cerebral palsy, organic CNS damages and perinatal encephalopathy. The percentages of phosphatidylcholin and, in some cases, of phosphoglycerides increase depending on the disease type. The above changes were determined by craniocerebral innervation disturbances and concerned mainly the content of phosphatidylcholin, phosphatidylserine and phosphatidylethanolamin. The determination analysis established that the changes of erythrocytes phospholipid content correlated with clinical state severity and intellectual development of children, and to depend on the disease type and may affect directly development/disturbance of craniocerebral innervation and intellectual development. The age changes were shown to influence phosphatid acid percentage in the patients.

[Age-specific features of the cyclic nucleotide system in children]. / Vozrastnye osobennosti sistemy tsiklicheskikh nukleotidov u detei.

The content of cyclic nucleotides (cAMP and cGMP) in the plasma and peripheral blood leukocytes, levels of their daily urinary excretion, and the activities of adenylate cyclase and cAMP-dependent phosphodiesterase responsible for the synthesis and degradation of cAMP in the leukocytes were studied in 114 healthy children aged 0 to 15 years. The levels of cyclic nucleotides in the blood plasma and leukocytes were found to gradually increase with age, as well as urinary excretion of cAMP. Both cAMP synthesis and degradation were found intensified with age. The detected age-specific features of cyclic nucleotides are important criteria for the assessment of the development of children and their health status. The findings may be used as reference values in assessment of the status of cyclic nucleotides in children with various diseases.

[Cellular mechanisms of calcium regulation of cardiac rhythm in children with ectopic arrhythmias]. / Kletochnye mekhanizmy kal'tsievoi reguliatsii serdechnogo ritma u detei s éktopicheskimi aritmiiami.

Regulation of intracellular calcium homeostasis by means of secondary mediators calmodulin and 4,5-inositol phosphates (products of phosphatidyl inositol hydrolysis) was studied in children with ectopic forms of arrhythmias. Alterations in the system calmodulin-Ca2+ and the activity of phosphoinosite metabolism correlated highly with clinical manifestations of the arrhythmias. The data obtained suggest that a number of molecular mechanisms and responsible for arrhythmias were realized in cell membranes and depended on a complex of intracellular messengers affected within various steps of the hormonal signal transmission.