[The alteration of the parameters of lipid peroxidation and the antioxidative system in the children presenting with pyo-inflammatory diseases of the middle ear].

The objective of the present study was to determine the amount of products of lipid peroxidation (dienic conjugates and malonic dialdehydes) together with antioxidative enzymes (catalase and superoxide dismutase) in 47 children presenting with acute pyo-inflammatory otitis media (APIOM) and 125 patients with chronic suppurative mesotympanitis (CSMT). In addition, 49 children presenting with chronic suppurative epitympanitis (CSET) and chronic suppurative epimesotympanitis (CSEMT) were included in the study. The data obtained were analysed and compared with the similar characteristics of 28 healthy children of the same age comprising the control group. The age of the children in different groups varied between 2 and 14 years. The study revealed the increase in the amount of lipid peroxidation products in all the groups with the simultaneous reduction of the activity of antioxidative enzymes; moreover, these values changed depending on the form and clinical course of the disease.

[The implementation of computer model in research of dynamics of proliferation of cells of thyroid gland follicle].

The article deals with the results of computational experiments in research of dynamics of proliferation of cells of thyroid gland follicle in normal condition and in the case of malignant neoplasm. The model studies demonstrated that the chronic increase of parameter of proliferation of cells of thyroid gland follicle results in abnormal behavior of numbers of cell cenosis of thyroid gland follicle. The stationary state interrupts, the auto-oscillations occur with transition to irregular oscillations with unpredictable cell proliferation and further to the "black hole" effect. It is demonstrated that the present medical biologic experimental data and theory propositions concerning the structural functional organization of thyroid gland on cell level permit to develop mathematical models for quantitative analysis of numbers of cell cenosis of thyroid gland follicle in normal conditions. The technique of modeling of regulative mechanisms of living systems and equations of cell cenosis regulations was used

[Computer simulation of thyroid regulatory mechanisms in health and malignancy].

The paper describes a computer model for regulation of the number of thyroid follicular cells in health and malignancy. The authors'computer program for mathematical simulation of the regulatory mechanisms of a thyroid follicular cellular community cannot be now referred to as good commercial products. For commercialization of this product, it is necessary to draw up a direct relation of the introduced corrected values from the actually existing normal values, such as the peripheral blood concentrations of thyroid hormones or the mean values of endocrine tissue mitotic activity. However, the described computer program has been also used in researches by our scientific group in the study of thyroid cancer. The available biological experimental data and theoretical provisions on thyroid structural and functional organization at the cellular level allow one to construct mathematical models for quantitative analysis of the regulation of the size of a cellular community of a thyroid follicle in health and abnormalities, by using the method for simulation of the regulatory mechanisms of living systems and the equations of cellular community regulatory communities.

[Biological effects of thyroxine in experimental carcinogenesis].

The study was undertaken to examine the in vitro and in vivo effects ofthyroxine Т4 at the concentrations of 10-4 M, 10-6 M, 10- M on the proliferative capacity and apoptosis of tumor cells of various pathogenesis. During the investigations, the authors used the unicellular suspension prepared from the surgical material obtained from 2 patients operated on for thyroid nodules (n = 1) and breast tumors in gynecomastia (n = 1) and evaluated the in vivo antitumor and antiproliferative activities of Т4, by using the melanoma B-16 inoculated in C57B1 mice. In the in vitro experiments, Т4 given in a dose of 10- М produced the highest cytotoxic activity against benign thyroid tumor cells (70±4.58%; p < 0.05). When used in this dose, T4 induced the greatest apoptotic death of the cells (9.0±0.90%; p < 0.05) as compared with the controls (1.0±0.30%). The in vitro effect of T4 in doses of 10-4 M, 10-6 M, 10- M on breast tumor cells in the presence of gynecomastia led to a decrease in levels of the oncogenic protein HER2/neu by an average of 27.25±1.14% (p < 0.001). In the in vivo experiments on a model of the tumor strain of melanoma B-16, T4 at the concentrations of 10-4 M, 10-6 M, 10- M showed a high antitumor activity (59.00±5.54%; p < 0.001 of tumor growth suppression by mass and 74.12±0.26%; p < 0.001 by volume). When given in a dose of 10- M, T4 displayed the highest antiproliferative activity (MI, 1.3±0.16%o, p < 0.001; AI, 10.65±1.39%, p < 0.001) as compared with the control group (MI, 4.96±0.43%o; AI, 4.43+0.40%).

[The membrane receptor binding of thyroid hormones in rat liver and brain cells in ontogeny]. / Membrannaia retseptsiia tireoidnykh gormonov v kletkakh pecheni i mozga krys v ontogeneze.

We studied changes of phospholipid and fatty acid composition of highly purified plasma membranes of liver and brain cells of rats over time during ontogenesis. Membranes were isolated from the organs of 2-day-old embryos, 6-day-old newborn rats, and adult rats. We examined the binding of thyroxine, a thyroid hormone, by preparations of plasma membranes from liver and brain at these times and have determined any tissue specificity in the development of membrane-mediated thyroxine reception during ontogenesis.

[Isolation and characteristics of the thyroxine membrane receptor]. / Vydelenie i kharakteristika membrannogo retseptora tiroksina.

A thyroxin receptor was isolated from rat liver plasma membranes by means of affinity chromatography. The receptor proved to be glycoprotein with a molecular mass of 40 kDa and contained 322 amino acid residues. Incorporation of the purified receptor into artificial phospholipid membrane was carried out.

[Effect of changes in erythrocyte lipid spectrum on erythrocyte functional parameters in patients with diabetes mellitus]. / Vliianie izmenenii lipidnogo spektra éritrotsitov na ikh funktsional'nye parametry u bol'nykh sakharnym diabetom.

Studies of the red cell lipid spectrum in diabetics and of the effects of bioactive substances and reconstruction of the red cell membrane lipid component on these cells aggregation have shown increased levels of lysophosphatidylcholine, cholesterol, cholesterol to phospholipid ratio, and saturated fatty acids in the presence of phosphatidylcholine reduction. Fluctuations in the levels of lipids of other classes were also revealed. Studies of red cell aggregation have revealed that incubation of donors' and diabetics' red cells with hormones did not lead to essential changes in the aggregation induced by alcian blue. Addition of an aliquot of plasma enriched for platelets, glycolipids and alpha-tocopherol resulted in a marked reduction of the aggregation degree and size of the aggregate. Phosphatidylcholine, phosphatidylinositol, and cholesterol-enriched liposome reconstruction of the red cell lipid composition also resulted in reduction of the aggregation degree and of the size of the red cell aggregate. This has brought the authors to a conclusion on a close relationship between the red cell lipid composition and the aggregation capacity in diabetics and on the possibility of regulating the red cell aggregation activity with bioactive substances.

[Membrane reception of thyroid hormones]. / Membrannaia retseptsiia tireoidnykh gormonov.

Comparative and competitive analyses of thyroxine (T4) and triiodothyronine (T3) binding to highly purified rat liver, brain and lung cell plasma membranes were carried out. The dependence of hormone binding on the time, temperature and concentration was studied. The effects of trypsin and partial delipidation on the binding parameters of thyroid hormones were investigated. Two thyroid hormone-binding sites were detected in cell plasma membranes of all tissues under study. The maximal binding of T4 to rat liver membranes and the maximal binding of T3 to rat brain membranes was observed in all experiments, the affinity for T3 being higher than that for T4. An important role of both protein and lipid components of plasma membranes in the membrane reception of thyroid hormones is proposed.

[Phospholipase A2 activity in human platelets. Isolation and purification of the enzyme]. / Aktivnost' fosfolipazy A2 v trombotsitakh cheloveka. Vydelenie i ochistka fermenta.

The activity of phospholipase A2 in blood platelets of healthy donors and IHD patients was examined. The enzyme activity was found to be increased 3-fold in platelets possessing a high level of functional activity (IHD) and by one order of magnitude in patients with myocardial infarction as compared with healthy donors. An enzyme preparation possessing a phospholipase activity was isolated from platelets by using salt extraction (KCl) and sonication. Purification of the enzyme by affinity chromatography resulted in two protein peaks both having a phospholipase A2 activity, the purification and molecular masses of these fractions being 768- and 2200-fold, and 13.5 and 15 kDa, respectively. It was supposed that these proteins are substrate-specific forms of phospholipase A2.

[The effect of changes in the lipid composition of membranes on the functional activity of platelets]. / Vliianie izmenenii lipidnogo sostava membran na funktsional'nuiu aktivnost' trombotsitov.

The phospholipid and fatty acid composition as well as the effect of platelet lipid composition modifications on the functional parameters of platelets were studied in blood sera from healthy donors and from patients with ischemic heart disease (IHD). It was found that the content of cholesterol and phospholipid hydrolysis products in IHD patients was increased. Reconstitution of the lipid composition of donor platelets by lysophosphatidylcholines, phosphatidic acid, fatty acids and cholesterol led to the increase of the platelet functional activity. It is suggested that the increased adsorption of Ca2+ on platelet surface is due to alterations in the platelet lipid composition in IHD and after modifications.

[The effect of calmodulin and chlorpromazine on the activity of phospholipases A2 from various sources]. / Vliianie kal'modulina i khlorpromazina na aktivnost' fosfolipaz A2 iz razlichnykh istochnikov.

The effects of calmodulin and chlorpromazine on purified phospholipase A2 preparations from snake venoms: cobra (Naja naja oxiana), echis (Ehis multisquamatus) and Agkistrodon halys halys, as well as on phospholipases A2 from rat liver mitochondria and human platelets were studied. It was shown that within the concentration range of 1-5 microM calmodulin stimulates the phospholipase activity. Chlorpromazine inhibits the activity of these enzymes, the degree of inhibition being different for various phospholipases. Calmodulin was shown to interact with the phospholipases in the absence of exogenous Ca2+. The results obtained indicate that all phospholipases tested are calmodulin-dependent enzymes.

[Autologous liposomes]. / Autologichnye liposomy.

A possibility to increase liposomal tropism to different organs by obtaining them from target lipid cells is considered. The interaction of liposomes of varying phospholipid and ganglioside composition with hepatic cells of rats was studied in vitro. It was found that this interaction was governed both by the phospholipid and ganglioside composition of the vesicles. Liposomes formed of phospholipids and gangliosides of target cells were captured better by the cells. Liposomes formed by summary hepatic phospholipids and gangliosides were shown to be eliminated more rapidly from the flow and to accumulate in the liver of the rats. This suggests that liposomal affinity for specific organs may be increased by changing the content and proportion of lipids in the liposomes to attain the maximal similarity to the composition of the target cell membranes.

[The lipid composition and aggregating capacity of thrombocytes in hyper- and hypothyroidism]. / Lipidnyi sostav i agregatsionnaia sposobnost' trombotsitov pri giper- i gipotireoze.

The aim of the work was to investigate the phospholipid composition and parameters of platelet aggregation in patients with hypo- and hyperthyroidism. The data obtained have shown that phospholipid liposomes added exogenously, changed the function of cell hemostasis and, in particular, decreased platelet aggregation. Unlike the other phospholipids, phosphatidylinositol, cardiolipin and phosphatidylserine produced the most significant effect on this index and corrected, to a certain extent, disturbed platelet functions in hypothyroidism.

[Effect of lipids on thrombocyte aggregation in patients with ischemic heart disease]. / Vliianie lipidov na agregatsiiu trombotsitov v krovi bo'lnykh ishemicheskoi bolez'niu serdtsa.

Platelet lipid composition was studied in healthy subjects and patients with coronary heart disease (CHD) and effects of various phospholipids (PL) were examined on aggregatory parameters. The patients with CHD was found to show higher levels of lysophosphatidylcholine (LPC), phosphatidic acid (PA), cholesterol (Chol), increased Chol/PL of saturated fatty acids, elevated malonic dialdehyde and lower phosphatidylinositol (PI) concentrations. Addition of liposomes from various PL classes to platelet-rich plasma indicated as follows. Phosphatidylserine (PS) liposomes caused a decrease in the platelet aggregation both in healthy subjects and CHD patients. Phosphatidylcholine- (PC), phosphatidylethanolamine- (PE), PI-, and LPC-liposomes increased the platelet aggregation in healthy subjects. Incubation of PE- and PI-liposomes with platelet-rich plasma from CHD patients resulted in lower platelet aggregation, whereas that of PC and LPC liposomes led to its increase. In CHD patients, the changes in the platelet lipid composition were likely to occur due to stimulation of lipid peroxidation and activation of platelet phospholipases, and diminished platelet aggregation caused by addition of PI- and PE-liposomes was likely to be associated with reconstruction of lipid composition and reduction of substrates of the phosphoinositide cycle.

[Protective action of liposome-incorporated surface antigens of the influenza virus by different methods of immunization]. / Protektivnoe deistvie vkliuchennykh v liposomy poverkhnostnykh antigenov virusa grippa pri razlichnykh sposobakh immunizatsii.

The influence of different routes of immunization on the protective effect of liposome-incorporated influenza A/PR/8/34 virus surface antigens was studied. Influenza virus surface antigens, neuraminidase and hemagglutinin, incorporated into liposomes, were shown to have a significant protective effect upon intraperitoneal and intranasal administration against a lethal dose of influenza virus as compared with immunization using a free antigen solution against the same infection. The protective effect is poor in intravenous immunization with influenza virus antigen-containing liposomes. It is concluded that combining of influenza virus antigens with liposomes may be used for preparation of new influenza vaccines.

[Phospholipase A2 and reacylation of phospholipids]. / Fosfolipaza A2 i reatsilirovanie fosfolipidov.

Transacetylation of labeled CoA-oleate and oleate into liposomes from dipalmitoyl phosphatidylcholine catalyzed by phospholipase A2 from rat liver mitochondria was studied. It was shown that the efficiency of CoA-oleate incorporation slightly exceeded that of oleic acid both in the phosphatidylcholine and lysophosphatidylcholine fractions. It was found also that some amount of the labeled substrate remains bound to the enzyme; the type of oleate and CoA-oleate binding differs, depending on their concentrations. The autonomy of lipid component formation in mitochondrial membranes is discussed.

[Effect of changes in the membrane lipid composition on the activity of respiratory chain enzymes in rat liver mitochondria]. / Vliianie izmenenii v lipidnom sostave membran na aktivnost' fermentov dykhatel'noi tsepi mitokhondrii pecheni krys.

The lipid composition and fatty acid spectrum of individual phospholipid fractions of internal and external membranes of mitochondria was studied in alloxan diabetes. It was found that the phosphatidylserine content is reduced under these conditions, while those of lysophosphatidylcholines, diphosphatidylglycerols and cholesterol are increased, and the fatty acids are saturated with phospholipids. The observed changes in the lipid composition of membranes cause a decrease in the rate of oxygen consumption in various metabolic states as well as in the activity of NAD X H+-, succinate and cytochrome oxidases in rat liver mitochondria.

[Quantitative composition and functional role of thyroid phospholipids in nodular hypothyroid goiter]. / Kolichestvennyi sostav i funktsional'naia rol' fosfolipidov shchitovidnoi zhelezy pri uzlovom gipotireoidnom zobe.

Correlations between change in the composition of thyroid nodal tissue individual phospholipids and intensity of oxidizing processes under the influence of various phospholipid liposomes were studied. The thyroid phospholipid fraction level was investigated in patients with nodular goiter. A decrease in the level of sphingomyelin and phosphatidylinositide by 54%, cardiolipin by 63%, phosphatidic acid by 70%, phosphatidylserine by 46%, phosphatidylcholine by 7% and a two-fold increase in the level of phosphatidylethanolamine as compared to the control one were shown. A study of a degree of reduction of oxidation metabolism by adding phospholipid liposomes to thyroid sections showed that the tissue of a node possessed weaker oxidizing activity as compared to the control one. O2 absorption and 14CO2 excretion up to 30% were lowered in a hyperthyroid node. An activating liposome effect was noted in thyroid nodal tissue, mostly in the presence of phosphatidylserine, cardiolipin and phosphatidylinositide; the weakest effect was produced by phosphatidylethanolamine and phosphatidylserine.

[Lipid composition of immunocompetent organs of tumor-bearing rats]. / Lipidnyi sostav immunokompetentnykh organov krys-opukholrnositelei.

A comparative study of phospholipid composition of thymus, spleen, bone marrow, liver and peritoneal exudate with sarcoma 45-bearing and normal rats was carried out. It was found that substantial changes in total phospholipid and cholesterol contents are observed only in peritoneal exudate of tumour-bearing animals. Some alterations were revealed in the content of individual fractions of investigated organs. The most pronounced changes in the contents of individual phospholipid fractions were found in peritoneal exudates of rats with sarcoma 45.