[Morphologic and molecular-genetic characteristics of carcinoma, adenoma and surrounding tissue of the thyroid gland]. / Morfologicheskaia i molekuliarno-geneticheskaia kharakteristika raka, adenom i okruzhaiushchei tkani shchitovidnoi zhelezy.

The majority of thyroid tumors are not homogeneous histologically, this creating difficulties in interpretation of different carcinoma variants. The aim of the study was a complex comparative study of morphogenetic changes in carcinoma, adenoma and surrounding thyroid tissue. Surgical material from 48 patients operated because of nodular (multinodular) euthyroid goiter in Moscow Medical Academy in 1990-1997 was used. It was established that all the observations of early thyroid carcinoma diagnosed clinically as a nodular (multinodular) euthyroid goiter were represented by differentiated forms of thyroid carcinoma. Thyroid carcinoma was characterized by higher values of biomolecular markers as compared to adenomas and surrounding tissue. High values of c-myc expression in adenomas and surrounding tissue may indicate possible genetic rearrangements. A peculiar feature of carcinomas was the fact that deletions and replication errors in malignant tumors in this study were found simultaneously in the three genes investigated. As to different histological types of carcinoma, the most frequent deletions of the genes studied were observed in medullary and papillary-follicular carcinoma. High values of heterozygosity loss were found already in adenomas and surrounding tissues, this indicating the presence of the genetic changes already in the benign tumors and surrounding tissue.

[The effect of the quaternary ammonium salt of conidine oligomer-25 (QAS CO-25) on the activity of prothrombin complex factors]. / Vliianie chetvertichnoi ammoniinoi soli oligomera-25 konidina (ChAS O-25K) na aktivnost' faktorov protrombinovogo kompleksa.

Quaternary ammonium salt of oligomer-25 conidine (QAS O-25C) was used for regulation of hypocoagulation effect of Syncumar--anticoagulant of indirect type of action. The experiments were carried out on male rats. Experimental methods included thromboelastography, determination of thromboplastin time (after Quick) and determination of activity of single coagulation factors. It was shown that injection of QAS O-25C reliably do not affect blood coagulation. The combined action of QAS O-25C and Syncumar resulted in a twofold increase in the activity of factors IX and X within 24 h after the injection and in complete recovery after 48 h. After Syncumar injection per os we observed deep-hypercoagulation which was maintained even within 48 after the injection. The effect of QAS O-25C modulating the Syncular anticoagulant activity is probably connected with intensification of protein synthesis in the liver and, specifically, with an increase in the yield of active precursors of the factors of prothrombin complex.

[Carnosine as a stimulator of cytotoxic and phagocytic function of peritoneal macrophages]. / Karnozin kak stimuliator tsitostaticheskoi i fagotsitarnoi funktsii peritoneal'nykh makrofagov.

Biochemical changes in peritoneal macrophages and their relatedness to the cytostatic and phagocytotic function in C3HA mice injected with a single intraperitoneal dose of 0.45 mM carnosine and 4-methyluracil or stimulated with peptone have been studied. During the first 24 hours after injection both carnosine and 4-methyluracil increase the activity of adenosine deaminase and purine nucleoside phosphorylase, the key enzymes of purine catabolism which is the main source of O2-. radicals in macrophages. In carnosine-stimulated macrophages the activity of membrane 5'-AMP nucleotidase decreases on days 1-3 after injection which points to alleviation of adenosine-induced inhibition as well as to macrophage activation. Carnosine increases the cytostatic and phagocytotic activities of macrophage coupled to O2-. production. The mechanism of the stimulating effect of carnosine on macrophages seems to consist in the dipeptide interaction with specific receptors localized on the plasma membrane of macrophagal cells.

[Effect of carnosine and 4-methyluracil on the development of experimental hepatitis in rats]. / Vliianie karnozina i 4-metiluratsila na razvitie éksperimental'nogo gepatita u krys.

A comparative study of the hepatoprotective effect of carnosine and 4-methyluracil under CCl4-induced acute toxic hepatitis has been carried out. The extent of liver injury and its regeneration were established from morphological data as well as from changes in the activities of alanine aminotransferase (ALT) and histidase and the bilirubin content in blood serum. Hyperlipoperoxidation in the liver and serum was assessed by the amount of TBA-active products. It was found that by day 10 of experimental hepatitis ALT and histidase levels in blood sera of untreated animals exceeded the normal values 1.3- and 3.9-fold, whereas those in the carnosine-treated group approximated the values characteristic of intact animals. The activity of serum ALT in animals treated with vitamin B12 or 4-methyluracil exceeded normal values 1.5 and 1.6 times, whereas that of histidase was 2.5 and 2.7 times as high. Carnosine and 4-methyluracil inhibited (in approximately the same degree) the formation of TBA-active products in the liver. According to morphological dta, cessation of CCl4 injections was accompanied by rapid regeneration of liver tissues in all animal groups. Carnosine enhanced regenerative processes in parenchymatous and connective tissues in a far greater degree in comparison with other drugs. The mitotic index in the carnosine-treated group exceeded more than twofold the corresponding parameters in untreated animals. Possible mechanisms of carnosine action on liver repair are discussed.

[Nucleic acid synthesis and spatial organization of DNA in the presence of heparin and the quaternary ammonium salt of the conidin oligomer-25]. / Sintez nukleinovykh kislot i prostranstvennaia organizatsiiaDNK v prisutstvii geparina i chetvertichnoi ammoniinoi soli oligomera-25 konidina.

A comparative study of polyconidin effects in the replicative and transcription activity of hepatocyte DNA in intact animals, and on peculiarities of spatial organization DNA in the DNA complex with oligomer-25 conidin was carried out. It was shown that polyconidin binding to DNA results in "cross-linking". This process is accompanied by formation of liquid-crystalline dispersion without abnormal optical activity. Liquid crystals possess high density packing of DNA molecules complexed with quaternary ammonium salt of oligomer-25 conidin. The addition of heparin to liquid-crystalline dispersions or phases, destroys the structure of the DNA complex with quaternary ammonium salt of oligomer-25 conidin. As a result "free" DNA molecules appear, they form the cholesteric liquid-crystalline phase. An increase in transcription activity and synchronization of DNA synthesis in hepatocyte was demonstrated. A correlation between chromatin modification and biological activity of chromatin after formation of the DNA--oligomer-25 conidin complex is proposed.

[Effects of 4-methyluracil and carnosine on healing of skin wounds in rats]. / Vliianie 4-metiluratsila i karnozina na zazhivlenie kozhnykh ran u krys.

In experiments in vivo and in vitro the authors studied antioxidative properties of 4-methyluracil and carnosine, their capacity to inhibit sex and accelerate healing of skin wounds. 4-methyluracil and carnosine discover almost the same capacity to decrease in the tissues of the wound and the blood serum in the formation of various intermediate products of free radical oxidation. Data are given on the study of the dynamics of wound healing after a 5-day treatment with equimolar quantities.

[Synthesis of nucleic acids and dynamics of morphological indices of the granulation tissue of skin wounds in rats treated with 4-methyluracil]. / Sintez nukleinovykh kislot i dinamika morfologicheskikh pokazatelei granuliatsionnoi tkani kozhnykh ran u krys, lechennykh 4-metiluratsilom.

Effect of 4-methyl uracil on dynamics of morphological patterns and the rate of nucleic acids synthesis was studied in granulation tissue developed during healing of full-layer skin wounds. Application of ointment containing 4-methyl uracil onto the wounds exhibited an antiinflammatory efficiency and decreased accumulation of leukocytes in the wound. The drug shortened the mitotic cycle in dividing fibroblasts, as a result of which periods of DNA synthesis became more frequent exhibiting two days duration. The rate of RNA synthesis was increased 1.5-2-fold. Content of acid glycosaminoglycans and collagen was increased in intercellular space surrounding fibroblasts.

[Heparin and its antagonist--a quaternary ammonium salt of oligomer-25-conidine: distribution in subcellular organelles, effect on DNA synthesis in the regenerating rat liver]. / Geparin i ego antagonist--chetvertichnaia ammoniinaia sol' oligomera-25-konidina: raspredelenie po subkletochnym organellam, vliianie na sintez DNK v regeneriruiushchei pecheni krys.

Dynamics of distribution in subcellular organelles as well as effects on DNA synthesis of heparin, polycanidine (ChAS oligomer of 25 canidine) and their complexes were studied in regenerating rat liver tissue after partial hepatectomy. Polycanidine and heparin penetrated from circulation into hepatocyte cells, nuclei and mitochondria. After consecutive administration of polyelectrolytes polycanidine increased 2-2.5-fold the amount of heparin entering into cells. Polycanidine formed stable complexes with DNP in nuclei. Heparin and its complexes with polycanidine decreased the DNA synthesis within first day. Heparin appears to be responsible for the inhibitory effect, whereas administration of polycanidine only into animals caused a slight increase in 3H-thymidine incorporation into DNA as compared with controls.

[Dynamics of nucleic acid synthesis in the granulation tissue of skin wounds in the rat]. / Dinamika sinteza nukleinovykh kislot v granuliatsionnoi tkani kozhnykh ran krys.

Dynamics of nucleic acid synthesis was studied in granulation tissue, harvested within 2-11 days after an injury of rats with full-layer skin wounds, simultaneously with evaluation of the morphometric patterns of the tissue. Synthesis of nuclear DNA exhibited a wave-shaped dynamics. The intervals between the maximal values of the DNA synthesis constituted 3 days. Within the early steps of wound healing the intensive incorporation of 3H-thymidine into mitochondrial DNA was found, which appears to occur due to active mitochondriogenesis. In dynamics of total and nuclear RNA contents two peaks were observed, which did not coincide in time, thus suggesting the wave-shaped increase in biosynthetic processes in cells.

[Effect of the synthetic heparin antagonist, conidine oligomer 25, on the synthesis of nucleic acids in regenerating liver cells]. / Vliianie sinteticheskogo antagonista geparina oligomera-25 konidina na sintez nukleinovykh kislot v kletkakh regeneriruiushchei pecheni.

Localization of 14C-conidine oligomer (the synthetic antagonist of heparin) and of polyelectrolyte complex heparin-conidine oligomer 25 was studied in cells of regenerating liver tissue within 20 hrs after partial hepatectomy in rats. Effects of heparin, conidine oligomer 25 and of their polyelectrolyte complex on synthesis of nucleic acids were studied. Conidine oligomer 25 penetrated from circulation into hepatocytes and subcellular organelles of regenerating liver cells and was localized mainly in cytosol (75-88%). In nuclei and mitochondria of the hepatocytes 14C-conidine oligomer 25 was mostly found in the fraction of low density of the organelles. Polyanion heparin, polycation conidine oligomer 25 and their polymeric complex impaired replication and transcription processes.

[Interrelationship between activity of nuclear ribonucleotide reductase and DNA synthesis of hepatocyte nuclei during liver tissue regeneration]. / Vzaimosviaz' aktivnosti iadernoi ribonukleotidreduktazy s sintezom DNK v iadrakh gepatotsitov pri regeneratsii pecheni.

Dynamics of 3H-thymidine incorporation into nuclear DNA and activity of nuclear ribonucleotide reductase were studied within 2 days after partial hepatectomy. The curves describing dynamics of DNA synthesis and the activity of ribonucleotide reductase were of wave-shaped pattern. Maximal enzymatic activity was reached 2 hrs before the nuclear DNA synthesis maximum. An inhibitor of ribonucleotide reductase was found in the globulin fraction of intact liver nuclei; after addition of the inhibitor the activity of the enzyme was decreased 4-5-fold, if the ratio of protein in preparations inhibitor/enzyme was as high as 1:40.

[Thymidine kinase and nucleoside phosphotransferase in blood of animals after partial hepatectomy and in patients with inflammatory diseases]. / Timidinkinaza i nukleozidfosfotransferaza v syvorotke krovi zhivotnykh posle chastichnoi gepatéktomii i u liudei s vospalitel'nymi zabolevaniiami.

Distinct activation of thymidine kinase (exceeding 2-3-fold the control values) as well as of nucleoside phosphotransferase (about 50% higher as compared with controls) was observed in blood serum of rats within 24 hrs after partial hepatectomy. Within 48 hrs after beginning of the tissue regeneration the activities of both these enzymes were decreased 1.5-fold; the values normalized within 72 hrs. These enzymatic activities were detected in blood of the patients with impairments of liver, kidney and some other tissues.

[Structure and biosynthetic functions of rat liver mitochondrial fractions]. / Struktura i biosinteticheskie funktsii mitokhondrial'nykh fraktsii pecheni krys.

Two mitochondrial fractions, dissimilar in their sedimentation characteristics, were isolated from rat liver homogenates using differential centrifugation. Morphological peculiarities of mitochondria of both these fractions, their capacity to protein and DNA synthesis as well as activities of several key enzymes of DNA biosynthesis were studied. The differences observed are discussed in terms of age dissimilarities of the mitochondria in the population.

[Effect of sturines A and B on DNA synthesis and ribonucleotide reductase and thymidine kinase activity in regenerating rat liver]. / Vliianie sturinov A i B na sintez DNK i aktivnost' ribonukleotidreduktazy i timidinkinazy v regeneriruiushchei pecheni krys.

After a single intravenous administration of sturines A and B into rats subjected to partial hepatectomy, during the periods, corresponding to maximal synthesis of DNA, incorporation of 3H-thymidine into nuclear DNA was decreased by 20-30% and incorporation into mitochondrial DNA--by 40-50%, as compared with control. The treatment with sturines led to distinct decrease in activity of nuclear thymidine kinase and ribonucleotide reductase but did not affect the enzymatic activity in mitochondria. The sturine preparations (at concentrations 10(-6)--10(-3) M) inhibited the activity of these enzymes (of both nuclear and mitochondrial origin) in vitro.

[Mitochondrial thymidine kinase isoenzymes from normal and proliferating rat liver tissues]. / Izofermenty mitokhondrial'noi timidinkinazy iz normal'noi i proliferiruiushchikh tkanei pecheni krys.

Isoenzyme composition of thymidine kinase was studied in submitochondrial fractions of liver tissue with various proliferative activity (intact, regenerating livers and Zhaidel ascites hepatoma) using polyacrylamide gel disc electrophoresis. Three zones, corresponding to proteins with Rf 0.1-0.2 (I), Rf 0.5-0.55 (II) and Rf 0.85-0.87 (III) and exhibiting thymidine kinase activity, were found in fractions of cytoplasmic and mitochondrial matrix proteins from resting and proliferating rat liver tissues. In fractions of outer and inner mitochondrial membranes three zones of the enzymatic activity were also observed but two of them did not coincide in the Rf value with the thymidine kinase isoenzymes from cytoplasmic fraction and mitochondrial matrix: I Rf 0.1-0.16, II Rf 0.35-0.4 and III Rf 0.62-0.68. Redistribution of the enzymatic activity between thymidine kinase isozymes occurred in conversion of liver tissue from the resting state to increased proliferation. In these cases slowly migrating enzymatic fraction (Rf 0.1-0.2) was activated in mitochondrial matrix and membranes; formation of TMP, catalyzed by isozymes with fast mobility (Rf 0.5-0.55 in matrix and Rf 0.62-0.68 in membrane fractions of mitochondria), which are typical for intact liver tissue, was decreased, respectively.

[Correlation of mitochondrial ribonucleotide reductase and thymidine kinase activities with the synthesis of mitochondrial DNA in rat liver during regeneration]. / Vzaimosviaz' aktivnosti mitokhondrial'noi ribonukleotidreduktazy i timidinkinazy s sintezom mitokhondril'noi DNK v lecheni krys v protsesse regeneratsii.

3H-thymidine incorporation into DNA of heavy mitochondria from regenerating rat liver and the change of mitochondrial thymidine kinase and ribonucleotide reductase activities are studied in vivo in regenerating rat liver within 6--48 hours after hepatectomy. Synthesis of mitochondrial DNA and changes in the activity of the enzymes studied are found to be undulate. Thymidine kinase activity maxima coincide with those of 3H-thymidine incorporation. Maximal activity of ribonucleotide reductase pre-exists maxima of mitochondrial DNA synthesis.

[Some properties of cytoplasmic thymidine kinase and nucleoside phosphotransferase from rat liver]. / Nekotorye svoistva tsitoplazmaticheskikh timidinkinazy i nukleozidfosfotoransferazy iz pecheni krys.

The activities of two deoxythymidine-phosphorylating enzymes--thymidine kinase and nucleoside phosphotransferase--were found in the cytoplasmic fraction of normal and regenerating rat liver. The specific activity of nucleoside phosphotransferase appeared to be by 50% higher than that of thymidine kinase. Nucleoside phosphotransferase has a broad specificity for the phosphate donor. This enzyme is more stable to heating and prolonged dialysis as compared to thymidine kinase. The enzymes respond differently to the addition of d-TTP, d-CTP and sturins A and B: thymidine kinase is strongly inhibited by these agents whereas nucleoside phosphotransferase is insensitive to d-TTP and d-CTP and is only slightly inhibited by sturins. On the other hand the activity of nucleoside phosphotransferase is considerably decreased after addition of ATP. Changes in the activities of both enzymes during 50 hrs following partial hepatectomy were studied. Two activity maxima were observed at 20-22 and 40-46 hrs of regeneration. Using polyacrylamide gel electrophoresis, three isoforms of both enzymes were found. The ratio between the isoenzyme content of the two enzymes from the cytoplasmic fraction of regenerating liver varied as compared to normal.

[Mitochondrial thymidine kinase and ribonucleotide reductase from rat liver and rat hepatoma 27]. / Mitokhondrial'nye timidinkinaza i ribonukleotidreduktaza iz kletok pecheni i gepatomy 27 krys

Fractions of heavy and light mitochondria are isolated from homogenates of homologous rat tissues (intact liver, regenerating liver within 24 hours after hepatectomy and 27 hepatoma) by means of differential centrifugation. It is found that tumour mitochondria have higher heterogeneity and lower buyoant density than mitochondria from normal hepatocytes. The activity of two enzymes of DNA precursors synthesis (ribonucleotide reductase and thymidine kinase) in subcellular fractions is demonstrated to correlate with the tissue growth rate. A single injection of cyclic AMP into hepatectomised rats resulted in the retardation of the regeneration process, and the activity of both enzymes reached its normal level in all the fractions studied after 24 hours after the operation. Thymidine kinase and ribonucleotide reductase are located mainly in the mitochondrial matrix, however, pronounced enzyme activity is observed also in membrane fractions. The activity of the enzymes in the fraction of external mitochondria membranes in rapidly growing tissues is 2--3 times as high as in the same fraction from normal rat liver.