[Structural and functional changes in rat liver mitochondria under calcium ion loading in the absence and presence of flavonoids]. / Strukturnye i funktsional'nye izmeneniia mitokhondrii pecheni krys pri nagruzke ionami kal'tsiia v otsutstvie i v prisutstvii flavonoidov.

The aim of the present work was to elucidate the mechanisms of calcium ion-induced impairments of the ultrastructure and functional activity of isolated rat liver mitochondria in the absence and presence of a number of flavonoids in vitro. In the presence of exogenous Ca²âº (20-60 µM), mitochondrial heterogeneity in size and electron density markedly increased: most organelles demonstrated a swollen electron-light matrix, bigger size, elongated cristae and a reduced their number, a damaged native structure of the inner membrane up to its detachment, and some mitochondria showed a more electron-dense matrix (condensed mitochondria). The calcium-induced opening of the mitochondrial permeability transition pores (MPTP) resulted in the ultrastructural disturbances and in the effective inhibition of the respiratory activity of rat liver mitochondria. The flavonoids (10-25 µM) naringenin and catechin, dose-dependently inhibited the respiratory activity of mitochondria and stimulated the MPTP opening in the presence of Ca²âº ions. Since Ruthenium red, an inhibitor of the mitochondrial Ca²âº uniporter, effectively prevented Ca²âº-induced MPTP opening both in the absence and presence of flavonoids, we hypothesized that the effect of flavonoids on the MPTP opening could be mediated by stimulation of the Ca²âº uniporter.

[Morpho-functional changes in the liver and the possibility of their correction in the offspring of rats with cholestasis].

The study aims to clarify the influence of experimental cholestasis mother on the structure of the liver of young rats in early postnatal development (Day 2) and to explore the possibility of the correction of these disturbances with Ursofalk drug. Material was obtained from 30 outbred albino rat pups and studied using histological, histochemical, morphometric and electron microscopic methods. It was found that under the influence of maternal cholestasis, the liver of the offspring demonstrated the dilation of sinusoidal capillaries, the decreased activity of succinate dehydrogenase and increased activity of NADH dehydrogenase in hepatocyte cytoplasm, the development of significant ultrastructural abnormalities (disappearance of lipid droplets, accentuated heterogeneity of mitochondrial size and shape, increased number of lysosomes). The application of Ursofalk partially restored hepatocyte structure and metabolism.

[Mesenchymal stem cells as perspective method of fibrosis/cirrhosis treatment].

UNLABELLED: THE PURPOSE OF THE REVIEW: Discuss the background and available results of transplantation of bone marrow stem cells as a promising treatment of hepatic fibrosis. KEY PROVISIONS: Actuality of the problem of chronic hepatitis is present due to their progressive course with the formation of liver cirrhosis and a high level of mortality. Conservative treatment of patients with decompensated process requires a liver transplantation that is compounded by the high percentage of graft reinfection in infectious hepatology. It is necessary to study the use of bone marrow-derived stem cells transplantation, because MSCs have certain therapeutic potential, low immunogenicity and the capacity for directional migration. In experimental models MSCs mechanisms of action are shown to limit the progression of liver fibrosis and stimulation of regeneration processes. In clinical studies good tolerability and relative safety of administration of autologous MSCs have reported as well as the positive effects on liver synthetic function, a decrease in the severity of cirrhosis on class Child-Pugh and MELD, reduction in overall mortality are shown. The results of our own prospective pilot study using autologous MSCs from bone marrow in patients with HCV-associated liver cirrhosis are described. CONCLUSION: MSCs can exert multiple synergistic effects on the hepatic stellate cells, reduce inflammation in the liver tissue remodeling processes and fibrogenesis. For objective evidence of the clinical benefits of the method, evaluation of long-term efficacy and safety of MSCs, as well as developing rational strategies, further clinical studies are required.

Morphological changes in the liver, thymus, spleen, and small intestine of animals after leucine treatment.

Leucine treatment (100 mg/kg daily for 5 days) leads to activation of the hepatocyte nuclear system and granular endoplasmic reticulum and to a drastic increase in the number of mitochondria, characterized by polymorphism. In the spleen, Malpighian bodies and periarterial lymphoid sheaths are enlarged, lymphocytes infiltrate the periarterial zone, and the mantle zone is enlarged. In the thymus, the width of the cortical matter shrinks, while that of the medulla increases. The content of lymphocytes in the medulla decreases, while that of Hassal's bodies increases. Unambiguous effects of leucine on the small intestinal morphology (mainly on the villous epithelium) were shown. Goblet cells in the villous epithelium were sharply stenosed because of decreased secretory granules in them.

[Using leucine and zinc sulfate for the correction of metabolic disturbances induced by paracetamol].

A mixture of leucine and zinc sulfate (4 : 1; 100 mg/kg body weight) produces a hepatoprotective effect, preventing the ultrastructural injury of hepatic tissue and the disturbance of free amino acid metabolism caused by a toxic dose of paracetamol.

[The effect of one-time external low- and high-dose gamma-irradiation on rat thyroid structure at the acute and remote periods].

A study of the morphological structure of the thyroid was made at the acute (1, 3, 6 hours) and remote periods (1, 4, 24, 48 weeks) following the external gamma-irradiation at doses of 0.25-5.0 Gy using histologic and electron microscopic methods. At the acute period, morphological changes prevailed, which reflect the functional alterations (changes of the nucleic and of the follicular diameters and of the colloid density). Frequently they hare a non-synchronous character. At more remote periods, destructive (colloidorrhage, desquamation, hemorrhage) and reparative changes reveal in thyroid, which and by the development of the sclerotic processes and of the morphological signs of decreased functional activity of the gland (increased follicular size and colloidal density, flatness of follicular epithelium and pronounced decreasing of the thyrocytes ultra structure number). The presence of such morphological changes after high and low-dose irradiation (<1.0 Gy) shows high sensitivity of the thyroid to single external radiation.

Protective effects of melatonin against carbon tetrachloride hepatotoxicity in rats.

Melatonin is an indolamine, mainly secreted by the pineal gland into the blood of mammalian species. The potential for protective effects of melatonin on carbon tetrachloride (CCl(4))-induced acute liver injury in rats was investigated in this work. CCl(4) exerts its toxic effects by generation of free radicals; it was intragastrically administered to male Wistar rats (4 g kg(-1) body weight) at 20 h before the animals were decapitated. Melatonin (15 mg kg(-1) body weight) was administered intraperitoneally three times: 30 min before and at 2 and 4 h after CCl(4) injection. Rats injected with CCl(4) alone showed significant lipid and hydropic dystrophy of the liver, massive necrosis of hepatocytes, marked increases in free and conjugated bilirubin levels, elevation of hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in plasma, as well as NO accumulation in liver and in blood. Melatonin administered at a pharmacological dose diminished the toxic effects of CCl(4). Thus it decreased both the structural and functional injury of hepatocytes and clearly exerted hepatoprotective effects. Melatonin administration also reduced CCl(4)-induced NO generation. These findings suggest that the effect of melatonin on CCl(4)-induced acute liver injury depends on the antioxidant action of melatonin.

[Functional and morphological characterization of rat thyroid gland at remote periods following single high and low dose radiation exposure]. / Funktional'no-morfologicheskaia kharakteristika shchitovidnoi zhelezy krys v otdalennye sroki posle odnokratnogo vozdeistviia radiatsionnogo izlucheniia v bol'shikh i malykh dozakh.

A study of the morphological structure and functional activity of the rat thyroid gland was carried out after 22 months following a single exposure to external radiation. The 3-month-old animals were irradiated with doses of 0.25, 0.5, 1.0, 2.0 and 5.0 Gy. Blood was assayed for thyroxin (T4) and triiodothyronine (T3) levels, while liver tissue--for NADP-MDH activity and thyroid tissue--for thyroperoxidase activity. The thyroid was studied histologically, morphometrically and by electron microscope. The decreased T4 concentrations 2.59-fold in the 5.0 Gy group, the increased T3/T4 in the 2.0 and 0.25 Gy groups, the reduced diameter of cellular nuclei and follicles, the flat follicular epithelium and diminished number of thyrocyte ultrastructures indicate thyroid hypofunction in the irradiated animals. The morphological changes are characterized by enhanced diffuse and focal sclerotic changes in thyroid, most pronounced at high irradiation doses (1.0-5.0 Gy), whereas the hemosiderosis foci suggest that the structural changes are consequences of radiation-induced destructive injuries in the gland parenchyma. Two of the thyroids (0.5 Gy) demonstrate foci with pronounced lymphoid infiltration, while follicular carcinomas were detected in 4 thyroids (2.0 Gy), and in one thyroid (0.5 Gy) in one thyroid (5.0 Gy). The remote effects of radiation were dose-dependent destructive, sclerotic and atrophic processes, decreased functional activity, stimulation of development of autoimmune aggression and carcinogenesis in thyroid.

[Dynamics of structural changes in rat liver after single dose of gamma-irradiation]. / Dinamika strukturnykh izmenenii v pecheni krys posle odnokratnogo vozdeistviia gamma-izlucheniia.

Histological changes and alterations in biophysical and biochemical parameters in liver of gamma-irradiate rats have been investigated. The gamma-irradiation of the whole body of rats with a single dose of 1 Gy did not cause any impairments of beam structure of rat liver, but resulted in the lymphocytic infiltrations of portal tracts which were not accompanied by formation of spotty areas of necrosis in adjacent areas of lever parenchyma. gamma-Irradiation stimulated proliferation of the hepatocytes and induced time-dependent mitochondrial structure lesions. Post-irradiation changes in cell cytoplasm appeared as disordering in reticulum-endothelial system, among them enlarging and fragmentation of its cisterns, cytoplasmic vacuolization, enhancement of the number of lysosomes and of the lipid inclusion contents. These facts revealed the mobilization of the additional energy resources for recovery of metabolic processes in rat liver. Post-irradiation increase of the level of the hepatocyte membrane lipid peroxidation products preceded liver morphological alterations. The membrane lipid microviscosity decreased in 1 and 3 days after irradiation. As a result of damages of hepatocyte membrane, the activity of the alanin- and asparagin-aminotransferases in blood serum increased 6 hours after. We can conclude that the whole body single gamma-irradiation with a dose of 1 Gy leads to the reversible but significant damages to the rat liver cell membrane structures. These damages might be the reason of radiation-induced liver morphological alterations.

Influence of Ukrain on patients with surgically treated breast cancer. Part IV. Electromicroscopic and cytochemical evaluation.

The present studies were undertaken to evaluate by light and by electron microscopy the influence of Ukrain on the morphology of breast cancer. The studies were carried out on material obtained from ten patients with breast cancer, treated preoperatively with Ukrain. Control material for the studies was obtained from patients of similar age and advancement of the disease, who did not receive Ukrain. The data obtained in the present studies indicate that Ukrain is responsible for severe changes in morphology of tumour cells. Histological examination by both light and electron microscopy revealed cells characteristic of those undergoing apoptosis. The stromal changes of the tumour were characterized by intensive proliferation of the connective tissue accompanied by an immune reaction expressed by mononuclear infiltrates.

[The effect of phosphorylation on oxidative and CoA- and NAD+-independent turnover of pyruvate by pyruvate dehydrogenase complex in the brain]. / Vliianie fosforilirovaniia na okislitel'noe i CoA- i NAD+- nezavisimoe prevrashchenie piruvata piruvatdegidrogenzanym kompleksom mozga.

It was shown that in the presence of ATP and Mg2+ the phosphorylation of the partially purified pyruvate dehydrogenase complex and the enzyme in isolated brain mitochondria inhibited the oxidative activity of the pyruvate dehydrogenase complex. The phosphorylation did no affect essentially the nonoxidative decarboxylation of pyruvate to form CO2 and acetaldehyde. In native mitochondria from the bovine brain the nonoxidative activity of the pyruvate dehydrogenase complex reached about 10% as compared to the oxidative activity of enzyme.

[Effect of thiamine and its antimetabolite oxythiamine on the proliferative activity of carcinosarcoma Walker 256 cells]. / Vliianie tiamina i ego antimetabolita oksitiamina na proliferatsiiu kletok kartsinosarkomy Uoker 256.

The microscopic studies of tumours from rats injected with thiamine at a dose of 20 mg/kg for 5 days have shown that sites of hemorrhages and necrosis are considerably more extensive than in tumours of control animals. Injections of the same doses of oxythiamine increase the rate of pathologic mitoses in tumour cells and decrease the tumour weight by 45%, limit the synthesis of thiamine diphosphate and inhibit the transketolase activity in tissues.

[Thiamine pyrophosphate-dependent enzymes in the regenerating liver of albino rats under different regimens of oxythiamine administration]. / Aktivnost' tiaminpirofosfatsoderzhashchikh fermentov v regeneriruiushchei pecheni belykh krys pri razlichnykh rezhimakh vvedeniia oksitiamina.

Activities of the thiamine pyrophosphate-dependent enzymes (pyruvate dehydrogenase, oxoglutarate dehydrogenase, transketolase) were increased in regenerating rat liver tissue as compared with their activities in the intact tissue. After administration of oxythiamine (20 mg/kg, within 10 days, subcutaneously) into the animals the enzymatic activity studied was decreased.