METAPHYSEAL CORTICAL DEFECT AND TUMOR-LIKE PROCESSES OF LONG BONES (A LITERATURE REVIEW AND OWN OBSERVATIONS).

Metaphyseal cortical defect (metaphyseal fibrous defect, cortical fibrous defect) of the long bones is a quite common variant of the bone structure's pathologic changes. The cortical defects and similar to their tumor-like processes (non-ossifying fibroma, benign fibrous histiocytoma etc.) are characterized by particular qualities of the clinical symptoms and radiologic signs. The aim of this article is to analyze a known literature data about cortical fibrous defects of long bones and similar to their tumor-like processes and present results of our own observations. We have observed 52 patients with different variants of bone lesions (metaphyseal cortical defect as the variant of pathological bone restructuring, local form of fibrous dysplasia, giant cell tumor, solitary done cyst, benign fibrous histiocytoma, non-ossifying fibroma). Complex clinical and radiologic differential diagnosis is based on a thorough study of the history findings, the degree of pain intensity and radiologic signs of pathological processes (location, sizes, number of destruction nodes as well as dynamics of changing). Revealed features along with histological verification undoubtedly influence on choice of medical tactics.

[Gender differences in emotion regulation in response to texts with violent content].

We investigated gender differences in emotion regulation depending on the cognitive disclosure of negative emotive content of 3 different texts after their presentations. For the purposes of the study we varied order between (i) completing of special checklists, created for specification of emotive and arousing attributes of the text contents and (ii) readings of autonomic activity. Results suggested that completing of the checklists increased engagement in processing of the most arousing text's content in men, while no effect was found in women, who were proposed to be engaged in content processing already during the text presentation. Results of the present study are discussed in the context of the recent findings on the emotional regulation.

[Cardiovascular reactivity to emotional texts in subjects with low and high level of psychoticism].

The article presents the results of comparative study of groups of subjects with low and high level of psychoticism. Heart rate, heart rate responses to inspiratory and expiratory Valsalva maneuvers, and blood pressure were measured before and after presentation of the texts with validated negative content in groups of subjects with low and high psychoticism scores. It was hypothesized that subjects with high level of psychoticism would be less engaged in the processing of negative contents of the texts and their physiological reactivity (physiological resources submitted for support of cognitive processing) would be less pronounced compared to subjects with low level of psychoticism. Significant main effect of psychoticism was obtained for changes in heart rate to expiratory Valsalva maneuver after presentations of the texts. Significant interaction effects of gender and psychoticism were obtained for systolic blood pressure. Other cardiovascular variables were not sensitive to the level of psychoticism. These effects of psychoticism were independent of other individual traits, such as neuroticism, extraversion, lie (social desirability), anger, trait anxiety and depression.

Role of nitric oxide in the regulation of mechanosensitive ionic channels in cardiomyocytes: contribution of NO-synthases.

The role of NO in the regulation of currents passing through ion channels activated by cell stretching (mechanically gated channels, MGC), particularly through cation-selective K(+)-channels TRPC6, TREK1 (K(2P)2.1), and TREK2 (K(2P)10.1), was studied on isolated mouse, rat, and guinea pig cardiomyocytes using whole-cell patch-clamp technique. In non-deformed cells, binding of endogenous NO with PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxy-3-oxide) irreversibly shifted the diastolic membrane potential towards negative values, modulates K(ir)-channels by reducing I(K1), and blocks MGC. Perfusion of stretched cells with PTIO solution completely blocked MG-currents. NO-synthase inhibitors L-NAME and L-NMMA completely blocked MGC. Stretching of cardiomyocytes isolated from wild type mice and from NOS1(-/-)- and NOS2(-/-)- knockout mice led to the appearance in MG-currents typical for the specified magnitude of stretching, while stretching of cardiomyocytes from NOS3(-/-)- knockout mice did not produce in MG-current. These findings suggest that NO plays a role in the regulation of MGC activity and that endothelial NO-synthase predominates as NO source in cardiomyocyte response to stretching.

Role of nitric oxide in activity control of mechanically gated ionic channels in cardiomyocytes: NO-donor study.

Whole-cell ionic currents through mechanically gated channels (MGC) were recorded in isolated cardiomyocytes under voltage clamp conditions. In unstrained cells, NO donors SNAP and DEA-NO activated MGC and induced MG-like currents. In contrast, in stretched cells with activated MGC, these NO-donors inactivated and inhibited MGC.

Sex differences in long chain fatty acid utilization and fatty acid binding protein concentration in rat liver.

Female sex and estrogen administration are associated with increased hepatic production of triglyceride-rich lipoproteins; the basis for this has not been fully elucidated. Inasmuch as hepatic lipoprotein production is also influenced by FFA availability and triglyceride biosynthesis, we investigated sex differences in FFA utilization in rat hepatocyte suspensions and in the components of the triglyceride biosynthetic pathway. Isolated adult rat hepatocyte suspensions were incubated with albumin-bound [(14)C]oleate for up to 15 min. At physiological and low oleate concentrations, cells from females incorporated significantly more (14)C into glycerolipids, especially triglycerides, and into oxidation products than did male cells, per milligram cell protein. At 0.44 mM oleate, incorporation into triglycerides in female cells was approximately twice that in male cells. Comparable sex differences were observed in cells from fasted animals and when [(14)C]-glycerol incorporation was measured. At higher oleate concentrations, i.e., fatty acid:albumin mole ratios in excess of 2:1, these sex differences were no longer demonstrable, suggesting that maximal rates of fatty acid esterification and oxidation were similar in female and male cells. In female and male hepatic microsomes, specific activities of long chain acyl coenzyme A synthetase, phosphatidate phosphohydrolase, and diglyceride acyltransferase were similar, but glycerol-3-phosphate acyltransferase activity was slightly greater in females at certain substrate concentrations. Microsomal incorporation of [(14)C]oleate into total glycerolipids was not significantly greater in females. In further contrast to intact cells, microsomal incorporation of [(14)C]oleate into triglycerides, although significantly greater in female microsomes, accounted for only a small fraction of the fatty acid esterified.The binding affinity and stoichiometry of partially purified female hepatic fatty acid binding protein (FABP) were similar to those of male FABP. In contrast, the concentration of FABP, per milligram cytosolic protein, was 44% greater in female liver than in male, as indicated by measurement of [(14)C]oleate binding and of 280 nm OD in the FABP fraction of 105,000 g supernate after gel filtration chromatography. These experiments demonstrate profound sex differences in hepatocyte utilization of long chain fatty acids at concentrations within and below the physiological range, and suggest that these are attributable at least in part to corresponding differences in cytosolic FABP concentration. At higher FFA concentrations, sex differences in hepatocyte FFA utilization are virtually eliminated, suggesting that under these conditions, differences in FABP concentration are not rate determining. Sex differences in hepatic lipoprotein production may largely reflect these important differences in the initial stages of hepatocyte FFA utilization.

Sex steroid modulation of fatty acid utilization and fatty acid binding protein concentration in rat liver.

The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [(14)C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [(14)C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [(14)C]oleate utilization. With maturation, total [(14)C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [(14)C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [(14)C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [(14)C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [(14)C]oleate utilization were greater, relative to FABP concentrations, than in 60-d-old animals. The sex differences that characterize fatty acid utilization in adult rat hepatocytes are not present in cells from immature animals, and reflect in part the influence of sex steroids. It remains to be determined whether the observed relationship of hepatic FABP concentration to [(14)C]oleate utilization in adult cells is causal or secondary to changes in cellular fatty acid uptake effected through another mechanism. In either case, modulation of triglyceride-rich lipoprotein production by six steroids appears to be mediated to a significant extent by their effects on hepatic fatty acid utilization.

Evidence for multiple enzymes in the dolichol utilizing pathway of glycoprotein biosynthesis.

A comparison has been made of the enzymes catalyzing the transfer of mannose, glucose and N-acetylglucosamine from, respectively, GDPmannose, UDP-glucose and UDP-N-acetylglucosamine to endogenous dolichol phosphate (Dol-P) in liver Golgi membranes. Evidence is presented with suggests that all three reactions utilize the same pool of Dol-P. The transfer of mannose from GDP-Man to Dol-P is not inhibited by 0.1 mM UDP or UMP; 0.1 mM GDP did block the accumulation of mannose in Dol-P-Man. The net transfer of glucose and N-acetylglucosamine to Dol-P is prevented by 0.1 mM UDP but not 0.1 mM GDP. UDPglucose inhibits the reverse of the glucose transfer reaction but not the reverse of the N-acetylglucosamine or mannose trasfer reaction. On the basis of this, and other data, it is concluded that the three sugar transfer reactions utilize separate enzymes.

Induction of fatty acid binding protein by peroxisome proliferators in primary hepatocyte cultures and its relationship to the induction of peroxisomal beta-oxidation.

The induction of liver fatty acid binding protein (L-FABP) by the peroxisome proliferators bezafibrate and clofibrate was compared with the induction of peroxisomal (cyanide-insensitive) palmitoyl-CoA oxidation in cultured rat hepatocytes maintained on a substratum of laminin-rich (EHS) gel. This substratum was chosen because marked induction of both L-FABP and peroxisomal palmitoyl-CoA oxidation was effected by bezafibrate in hepatocytes supported on EHS gel, whereas only peroxisomal palmitoyl-CoA oxidation was induced in hepatocytes maintained on collagen-coated plates. In control cells on EHS, activity of peroxisomal palmitoyl-CoA oxidation remained stable, while L-FABP abundance declined with time, and L-FABP mRNA was undetectable after 5 days. In cultures exposed to bezafibrate or clofibrate, peroxisomal palmitoyl-CoA oxidation activity was induced earlier and more rapidly than L-FABP. When fibrates were withdrawn, peroxisomal palmitoyl-CoA oxidation declined rapidly, whereas L-FABP continued to increase. L-FABP induction was accompanied by a striking increase in mRNA specifying this protein. Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I, effectively doubled peroxisomal palmitoyl-CoA oxidation activity. However, tetradecylglycidic acid markedly inhibited fibrate induction of L-FABP and peroxisomal palmitoyl-CoA oxidation but, unexpectedly, did not prevent the fibrate-induced proliferation of peroxisomes. Maximal induction of both L-FABP and peroxisomal palmitoyl-CoA oxidation was produced at a bezafibrate concentration in the culture medium (0.05 mM) much lower than that of clofibrate (0.3 mM). Also, bezafibrate, but not clofibrate, inhibited [1-14C]oleic acid binding to L-FABP with a Ki = 9.5 microM. We conclude that hepatocytes maintained on EHS gel provide an important tool for investigating the regulation of L-FABP. These studies show that the induction of peroxisomal beta-oxidation and L-FABP by peroxisome proliferators are temporally consecutive but closely related processes which may be dependent on a mechanism distinct from that which leads to peroxisome proliferation. Furthermore, the mechanism of action of the more potent peroxisome proliferator, bezafibrate, may be mediated, in part, by interaction of this agent with L-FABP.

[Contents of general, bound and free cortisol in sheep blood during different periods of acute radiation sickness]. / Soderzhanie obshchego, sviazannogo i svobodnogo kortizola v syvorotke krovi baranov v razlichnye periody ostroi luchevoi bolezni.

The hypothalamic-hypophyseal-cortical multifetal sheep system reaction was examined to respond the sharp single action X-rays dosed 0.96 and 3.84 Gr. The primary irradiation answer was accompanied by expressed hypercorticoidism, which essentially increased with irradiation dose rising and followed the induction of CRF-hypothalamic activity. The secondary sheep hypercorticoidism preceded the clinico-hematomancy and depended on irradiation dose. Hypercorticoidism-2 resulted in blood free bioactive cortisol content increasing. The compensative decrease of named system activity favoured to beam illness outcome. It the prognosis was poor the free and reached its peek before animal death. These data can be used as a test for beam illness outcome prognosis.

[Evaluation of biological sequelae for cattle in the zone of the Chernobyl accident]. / Otsenka biologicheskikh posledstvii dlia krupnogo rogatogo skota v zone Chernobyl'skoi katastrofy.

The influence of Chernobyl NPP outburst on cattle from farms in Russia and Belorussia was examined since 1988 to 1996. Changes in the level of thyroid hormones and imbalance in cAMP/cGMP ratio with increased cAMP concentration in blood were found. The content of cAMP and E, F2a prostaglandins was varied because of the disturbances in the rate of their metabolism. Two critical periods of pregnancy in cows were revealed. In the first half of pregnancy (the 4th-5th month) disorders in thyroid prevailed. In the second half (7th-9th month) changes in testosterone, progesterone, estradiol and estriol concentration were the most actual.

[Temperature-sensitive mutant of bacteriophage D3 and its use for the purpose of demonstrating the location of prophage in Pseudomonas aeruginosa cells]. / Temperaturochuvstvitel'nyi mutant bakteriofaga D3 i ispol'zovanie ego s tsel'iu vyiasneniia lokalizatsii profaga v kletkakh Pseudomonas aeruginosa.

For the first time a thermoinducible mutant, known as D3ct, has been obtained from Pseudomonas aeruginosa phage and used for lysogenizing culture PAO2604 Met--Ilv--. After a temperature shock phage D3ctwas induced from lysogenic strain PAO2604 (D3ct), and its development went along the lytic line. From the population of PAO2604 (D3ct) cells only 0.07% survived; in these cells the faulty excision of the prophage probably occurred at a high temperature. After thermoinduction 2.8% of the colonies formed by the survivors were auxotrophic in leucine. Such frequency of the appearance of the additional nutritional requirement for leucine suggests that the prophage was incorporated into the chromosome adjacent to some gene responsible for biosynthesis of leucine. In the process of faulty excision phage D3 retained a part of the host chromosome.

[Novel hybrid inhibitors of the phage T7 RNA polymerase: synthesis, docking and screening in vitro].

A number of new hybrid heteroaromatic compounds, consisting of tricyclic fragments (acridone, thioxanthone and phenazine) and bicyclic fragments (benzimidazole, benzothiazole and benzoxazole) were synthesized using the method, developed by the authors. As a result of screening against the transcription model system of the phage T7 DNA-dependent RNA polymerase three effective inhibitors of the RNA syntheses with the IC50 value of 8.9, 5.7 and 19.8 microM were detected. To cast light on the mode of interaction between the synthesized compounds and the target, the molecular docking was applied to the model pocket of the phage T7 RNA polymerase transcription complex. It was established that these ligands form networks of H-bonds with residues of the pocket conservative amino acids and pi-interaction with the Mg2+ ion. A planar geometry of the hybrid molecules, realized due to the intramolecular H-bonds, proved to be an important structural feature, which correlates with an efficacious inhibitory activity.

[Design of transcription inhibitors on the basis of n-arylamides of 9-methyl- and 9-methoxyphenazine-1-carboxylic acids].

A convenient method of synthesis was developed and two series of N-arylamides of 9-methyl- and 9-methoxyphenazine-1-carboxylic acids were obtained. By the molecular docking method the mode of the synthesized compounds interaction with catalytic pocket of the RNA polymerase T7 transcription complex was simulated. Key ligand-receptor intermolecular contacts were identified. They are realized by various types of non-covalent interactions with line of conservative amino acid residues involved in recognition of incoming nucleotide, catalytic act of RNA synthesis as well as in stabilizing the RNA-DNA hybrid at early steps of transcription. In silico data indicate sufficient affinity of ligands for the receptor and allow to predict their ability to inhibit the functioning of RNA polymerase T7 transcription complex that is consistent with preliminary experimental results. Initial testing in a model RNA polymerase T7 transcription system demonstrates significant inhibition of in vitro RNA synthesis by investigated compounds at a concentration of 25 microg/ml (approximately 80 microM).