MICROSCOPIC CHANGES OF THE KIDNEY IN EXPERIMENTAL HYPERHOMOCYSTEINEMIA ON THE BACKGROUND OF HYPER- AND HYPOTHYROIDISM.

Hyper- and hypothyroidism are two typical clinical conditions that can cause a variety of metabolic changes, including impaired sulfur-containing amino acids metabolism, increased risk of cardiovascular disease, renal dysfunction, and renal failure. Hypothyroidism has been shown to be associated with increased serum creatinine, decreased glomerular filtration rate, and an increased risk of chronic kidney disease. At the same time, the pathophysiological mechanisms of renal dysfunction induced by excessive iodothyronine secretion are poorly understood. The aim of the study was to establish the reorganization of the kidney structural components under the conditions of experimental hyperhomocysteinemia (HHCy), hyper- and hypothyroidism and their combined effects. Thiolactone HHCy was simulated by administering to animals exogenous homocysteine ​​(HC) in the form of thiolactone at a dose of 100 mg/kg body weight once a day for 28 days. Hyperthyroidism was simulated by daily administration of L-thyroxine at a dose of 200 µg/kg on 21st day, hypothyroidism - daily administration of mercazolyl at a dose of 10 mg/kg on 21st day. Separate groups of animals were administered L-thyroxine and mercazolyl in parallel with HC. A significant degree of dystrophic changes in the structural components of the kidneys under conditions of simulated hyperthyroidism and HHCy was established. Signs of vascular insufficiency in the kidneys were detected. Deformation of renal corpuscles, single focal thickenings and destruction of the outer layer of the renal corpuscle capsule were observed, there was a narrowing of the urinary space in the capsule. Microscopic study of the kidneys of animals under the combined effects of hypothyroidism and HHCy revealed the most significant destructive-degenerative changes in the filtration and reabsorption apparatus of the organ on the background of significant vascular disorders. An increase in number of glomeruli and a decrease of the urinary space of the Shumlyansky-Bowman's capsule were observed in the renal corpuscles. Podocytes underwent significant destructive changes. Damage to the epithelium in the system of tubules was manifested by cell hypertrophy. Under the conditions of simulated HHCy, hyper- and hypothyroidism, and especially with their combined effect, there are significant disorders of the vascular bed with remodeling of the vascular wall. On the background of hemodynamic disorders, there are significant destructive and dystrophic changes in the epitheliocytes of the renal corpuscles of the Shumlyansky-Bowman's capsule, the proximal and distal tubules of the nephron, the filtration and reabsorption apparatus of the nephrons of the organ.

INFLUENCE OF CHRONIC HYPERHOMOCYSTEINEMIA ON METABOLISM OF SULFUR CONTAINING AMINO ACIDS IN THE RATS' HEART AND BRAIN ON THE BACKGROUND OF HYPERTHYREOSIS AND HYPOTHYREOSIS.

The effect of experimental HHCy on the processes of transsulfuration of sulfur amino acids in the tissues of heart and brain, the levels of HCy, cysteine, H2S in blood serum of experimental animals with hyperthyroidism and hypothyroidism has been studied in the research. The experiment was performed on white male rats with simulated HHCy, hyper- and hypothyroidism, HHCy with different thyroid function. In the heart, the activity of cysteine aminotransferase (CAT), γ-glutamate cysteine ligase (γ-GCL), sulfite oxidase (SO) was determined. In the brain, the activity of cystathionine-ß-synthase (CBS), cysteine ​​dioxygenase (CDO), GCL and SO was determined. In serum the total level of HCy, cysteine ​​and H2S was evaluated. HHCy caused inhibition of transsulfuration pathway of cysteine in the brain that was evidenced by decreased activity of CBS and CAT in heart that caused increase in the level of HCy and cysteine ​​as well as decrease in the level of H2S in blood serum. Hyperthyroidism causes increased activity of CBS in brain and of CAT in heart. Hyperthyroidism leads to decrease in the level of HCy in blood serum compare to the control, as well as increase in the level of H2S compare to the group of animals with HHCy. Hypothyroidism causes inhibition of cysteine ​​metabolism, decrease in of HCy and cysteine levels. In cases of HHCy simulated by administration of thiolactone-HCy the activity of CBS and SO in the brain of rats, and CAT in the heart is increased. Hyperthyroidism causes increase of the activity of the CBS, CDO, and SO in the brain, as well as CAT in the heart. At the same time, the simultaneous administration of L-tyroxysin into the animals with HHCy leads to increase in the enzyme activity of CBS, CDO, γ-GCL and SO in the brain of the animals and increase of CAT and γ-GCL in the myocardium. Hypothyroidism in the brain of animals causes a decrease in the activity of the CBS, CAT and SO, and at the same time, the activity of SO only decreases in the myocardium of animals. An increase in the level of HCy and cysteine, a decrease in the level of H2S in the blood of experimental animals during hypothyroidism, as well as inhibition of the transsulfuration enzyme activity in the brain and heart are significant markers of the development of cardiovascular pathologies and mortality associated with hypothyroidism.

First occurrence and description of Aceria fraxiniflora (Felt, 1906) Acariformes: Eriophyoidea) from Europe.

Aceria fraxiniflora (Felt, 1906) is reported from Europe for the first time. This mite has never been described before and we therefore describe and illustrate the female and the nymph. The species was collected from the galled inflorescences and fruits of the introduced species Fraxinus pennsylvanica Marshall (Oleaceae) in Hungary, and from Fraxinus americana L. in Indiana, USA.

CORRELATION BETWEEN CONNECTIVE TISSUE METABOLISM AND THYROID DYSFUNCTION IN RATS WITH PERIODONTITIS.

The aim of the study was to clarify mechanisms of the periodontitis development in rats with thyroid dysfunction based on a comparative analysis of the correlations between the connective tissue metabolism indices and the concentration of thyroid stimulating hormone, free thyroxine and free triiodothyronine in blood serum. 12-14-week-old inbred white male rats (n=48) were included to the experiment. They were randomly divided into the following groups: control; animals with a model of periodontitis; animals with periodontitis in a setting of hyperthyroidism; animals with periodontitis in a setting of hypothyroidism. Concentrations of free thyroxine, free triiodothyronine and thyroid stimulating hormone were assayed with ELISA method. Collagenolytic activity, content of glycosaminoglycans, free hydroxyproline, fucose, unbound with proteins were determined by the spectrophotometric method. The linkages between the studied indices were established on the basis of the results of the correlation analysis using the Pearson correlation coefficient. Our research has found different interconnections between the indices of connective tissue metabolism and free triiodothyronine, free thyroxine and thyroid stimulating hormone concentrations in case of experimental periodontitis combined with thyroid dysfunction, indicating that thyroid gland has regulatory influence on connective tissue metabolism. In hypothyroid rats more correlations have been established compared to the hyperthyroid rats.

IMMUNOLOGICAL DISTRESS IN EXPERIMENTAL CRANIAL TRAUMA COMBINED WITH INSULIN DEPENDENT DIABETES (EXPERIMENTAL STUDY).

This article describes the immunological events and investigates important mediators of the inflammatory immune response after experimental cranial trauma combined with type I diabetes. It was shown that the rats with induced diabetes and traumatic brain injury suffered more profound damage to the immune system that was not restored back to the basal level within 14 days. Proinflammatory cytokine concentrations increased, while anti-inflammatory cytokine concentrations decreased by day 14, increasing risk for systemic inflammatory response syndrome and multi-organ failure. Factors responsible for humoral immunity and cell-mediated immunity were consistently lower by day 14, which might make diabetic rats more susceptible to infections compared to rats with brain injury alone.

[The dynamics of the immune status indices in conditions of cranio-cerebral trauma on background of a streptozotocin-induced diabetes mellitus in experiment].

Peculiarities of changes in the immune status in a cranio-cerebral trauma (CCT) on a background of a streptozotocin-induced diabetes mellitus (DM) were studied up. After CCT there are noted the inhibition of predominantly cellular link of immunity, accompanied by reduction of the CD3+ lymphocytes quantity, as well as lymphocytes of the main subpopulations CD4+ and CD8+, CD16+, reduction of the neutrophils phagocytic activity, a complement titer enhancement. Experimental CCT do not cause the essential changes in a CD19+ lymphocytes quantity. The CCT modelling on a background of a streptozotocin-induced DM causes the immune deficiency deepening, in a cellular and humoral links together, significant reduction of activity of a phagocytosis system and complement as well.

Monoclonal antibodies identify residues 199-216 of the integrin alpha2 vWFA domain as a functionally important region within alpha2beta1.

Integrin alpha2beta1 is the major receptor for collagens in the human body, and the collagen-binding site on the alpha2 subunit von Willebrand factor A-type domain (vWFA domain) is now well defined. However, the biologically important conformational changes that are associated with collagen binding, and the means by which the vWFA domain is integrated into the whole integrin are not completely understood. We have raised monoclonal antibodies against recombinant alpha2 vWFA domain for use as probes of function. Three antibodies, JA202, JA215 and JA218, inhibited binding to collagen, collagen I C-propeptide and E-cadherin, demonstrating that their function is important for structurally diverse alpha2beta1 ligands. Cross-blocking studies grouped the epitopes into two clusters: (I) JA202, the inhibitory antibody, Gi9, and a non-inhibitory antibody, JA208; (II) JA215 and JA218. Both clusters were sensitive to events at the collagen binding site, as binding of Gi9, JA202, JA215 and JA218 were inhibited by collagen peptide, JA208 binding was enhanced by collagen peptide, and binding of JA202 was decreased after mutagenesis of the cation-binding residue Thr(221) to alanine. Binding of cluster I antibodies was inhibited by the anti-functional anti-beta1 antibody Mab13, and binding of Gi9 and JA218 to alpha2beta1 was inhibited by substituting Mn(2+) for Mg(2+), demonstrating that these antibodies were sensitive to changes initiated outside the vWFA domain. Mapping of epitopes showed that JA202 and Gi9 bound between residues 212-216, while JA208 bound between residues 199-216. We have therefore identified two epitope clusters with novel properties; i.e. they are intimately associated with the collagen-binding site, responsive to conformational changes at the collagen-binding site and sensitive to events initiated outside the vWFA domain.

[Protective effect of cresacin in D-galactosamine-induced acute experimental hepatitis]. / Zakhysna diia krezatsynu za hostroho eksperimental'noho hepatytu, indukovanoho D-halaktozaminom.

Antioxidant properties of cresacin were studied on the model of galactosamine hepatitis and on the isolated liver cells of white male rats. It has been shown, that cresacin in a dose of 20 mg/kg effectively inhibits the processes of lipid peroxidation induced by hepatotoxin. Cresacin also normalized some components of fermentative and non-enzymatic antioxidant system. In particular the indexes of the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and the level of reduced glutathione, total phospholipids and ascorbic acid was increased for certain. In vitro, on the isolated hepatocytes, cresacin showed the dose-dependent antioxidant effect. This fact is confirmed by its property to inhibit the speed of formation of the malonic dialdehyde in the incubation medium.

[Tris(2-hydroxyethyl)ammonium ortho-cresyl acetate inhibits oxidative modification of the low density lipoproteins]. / Tris(2-oksiétil)ammonii ortokrezoksiatsetat ingibiruet okislitel'nuiu modifikatsiiu lipoproteinov nizkoi plotnosti.

Oxidative modification of low-density lipoproteins (LDLP) may play an important role in the pathogenesis of atherosclerosis. The work deals with the study of the inhibiting effect of tris(2-hydroxyethyl)ammonium orthocresoxyacetate (cresacin) on Cu+2-induced oxidation of human LDLP in vitro. The degree of LDLP oxidation was judged according to the accumulation of diene conjugates in the incubation medium. Inhibition of the degree of LDLP oxidation was found to be dependent on the dose of cresacin. The level of products forming during LDPL oxidation and reacting with thiobarbituric acid was also determined. Like in the previous case, the dose-dependent effect of inhibition of LDLP peroxidation by cresacin was also observed. It is concluded that cresacin is an effective inhibitor of LDLP oxidative modification in vitro.

[Role of the antioxidant system in the pathogenesis of toxic hepatitis]. / Rol' antioksidantnoi sistemy v patogeneze toksicheskogo gepatita.

Four subcutaneous administrations of 2 g/kg of tetrachloromethane to albino rats inhibited the hepatic activity of superoxide dismutase, catalase, glutathione peroxidase, reduced the concentrations of tocopherol, retinol, ascorbic acid, glutathiones, decreased the plasma level of ceruloplasmin and the total antioxidative activity of liver tissue. The magnitude of changes in antioxidative parameters depended on the severity of hepatocytic destruction.

[Status of the antioxidant, monooxygenase and humoral immune system of the body in d-galactosamine hepatitis]. / Stan antyoksydovoï, monooksihenaznoï ta humoral'noï system organizmu pri d-halactozaminovomu hepatyti.

Galactosamine model of toxic hepatitis in rats which, as to its morphobiochemical picture, is considered adequate to human hepatitis was used to study the role of disturbances of the functional state of antioxidant and monooxygenase systems as well as humoral area of the systems of immune protection in pathogenesis of the given disease. It is shown that most components of enzymatic and nonenzymatic antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, restored glutathione, phospholipids) are considerably inhibited by the toxin effect. At the same time content of ceruloplasmin is increased in the blood plasma. Considerable disturbances are also observed in the humoral chain of the immune system (content of immunoglobulins and circulating immune complexes varies) and in the processes of microsomal oxidation.

[The acetylcysteine correction of disorders of the oxidative processes in a toxic liver lesion]. / Korrektsiia atsetiltsisteinom narushenii okislitel'nykh protsessov pri toksicheskom porazhenii pecheni.

The damage of the liver in albino rats induces by CCl4 was followed by the disorders in the free radical, microsomal, and mitochondrial oxidation. The administration of acetylcysteine to the animals in a dose of 500 mg/kg 3 times a day resulted in normalization of chemiluminescence parameters of the liver tissue, the rate of oxygen consumption by microsomes and mitochondria of the hepatocytes, and in normalization of the succinatdehydrogenase, cytochromooxidase, H-ATP-ase activity and ATP concentration.

[Correction of disorders of oxidative processes in toxic liver injury using enterosorption]. / Korektsiia enterosorbtsiieiu porushen' okysniuval'nykh protsesiv pry toksychnomu urazhenni pechinky.

Liver injury with tetrachloromethane in white rats is accompanied by accumulation of hydroperoxides in the blood plasma and liver tissue and suppression of antioxidant system (the activity of superoxide dismutase, catalase, glutathione peroxidase, contents of SH-groups and total phospholipids drastically decreases). Ceruloplasmin level in plasma, on the contrary, increases. Enterosorbent SUGS-E in a dose of 19 g/kg partially normalizes violated balance between the activity of free radical processes and state of the antioxidant protection system.

[Antioxidant effect of dimethyl sulfoxide in acute liver injury by carbon tetrachloride]. / Antiokislitel'noe deistvie dimtilsul'foksida pri ostrom porazhenii pecheni tetrakhlormetanom.

After subcutaneous administration of dimethyl sulfoxide into rats with toxic, tetrachloromethane-produced impairment of liver tissue, lipid peroxidation was effectively inhibited in hepatocytes and the state of anti-oxidation system was improved. Antioxidative properties of dimethyl sulfoxide were shown also in vitro.

[Lipid peroxidation and impairement in erythrocytic properties in patients with ulcer disease before and after surgery]. / Perekysne okyslennia lipidiv i porushennia vlastyvostei erytrotsytiv u khvorykh na vyrazkovu khvorobu do i pislia operatsii.

The state of peroxide oxidation of lipids (POL) in the erythrocytes before and after the operation was studied. In patients with ulcer disease, the correlation between POL activity and changes in erythrocytic properties was noted. At the period of disease exacerbation, activation of POL processes in erythrocytes, suppression of the antioxidation protection (AOP), impairement in hemorheologic indices (increase in aggregation of erythrocytes, their resistance to acid hemolysis, reduction in their capacity for deformation) were revealed. Pronouncement of the pathologic changes after the operation depended on a background state of POL and AOP. In ulcer disease, the impairment in POL/AOP balance caused the development of postoperative complications. To prevent the development of complications, the administration of antioxidants is expedient.

[The effect of acetylcysteine on the antioxidant system in an experimental toxic lesion of the liver]. / Vliianie atsetiltsisteina na antioksidantnuiu sistemu pri éksperimental'nom toksicheskom porazhenii pecheni.

The liver damage by CCl4 in albino rats was followed by a drastic activation of lipid peroxidation processes and suppression of most components of the antioxidant system. The administration of acetylcysteine to the affected animals exerted the positive effect which manifested itself in a decrease of lipid peroxidation products content in the blood plasma and liver and in the partial normalization of the antioxidant protection system.

[Status of the free radical oxidation and antioxidant system in rats with toxic liver damage; effect of tocopherol and dimethylsulfoxide]. / Stan vil'noradykal'noho okislennia i antyoksydantovoï systemy u shchuriv z toksychnym urazheniiam pechinky; vplyv alpha-tokoferolu i dymetylsul'foksydu.

Carbon tetrachloride injected to white rats during four days in the dose of 2 g/kg drastically activates intensity of free radical lipid oxidation and induces impairment of the antioxidant system inhibition of the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, a decrease of SH-groups and general plasma ceruloplasmin level and total phospholipids in the liver. The greatest changes are observed by the 7th day. A complex use of tocopherol (30 mg/kg) and dimethyl-sulphoxide produce partial or complete normalization of all the above mentioned values. It is concluded that the optimization of the protective action of the antioxidant system requires a complex use of water and liposoluble antioxidants.