[Phosphorus-containing metabolites in the cells of anthracycline-resistant strains of leukemia P388]. / Issledovanie fosforsoderzhashchikh metabolitov v kletkakh antratsiklinustoichivykh shtammov leikoza P388.

The method of 31P nuclear magnetic resonance has been used to study in vivo the level of phosphorus-containing metabolites in cells of two strains of murine leukemia P388 with the phenotype of the multidrug resistance and in cells of the parent strain. Cells of both resistant strains showed a depressed level of phosphomonoesters in comparison with the parent one. The influence of rubomycin and emoksil on the level of phosphorus-containing metabolites of drug-resistant and -sensitive strains has been evaluated. The drugs were established not to affect practically the pool of these metabolites of the resistant strains. Both drugs significantly increased the pool of phosphomonoesters in the parent strain cells.

[The structure of products of modification of nucleotides and DNA by ethyleneimine and thio-TEPA]. / Stroenie produktov modifikatsii nukleotidov i DNK étileniminom i tiotéfom.

Previously undescribed products of dGMP, GMP, AMP, dCMP and TMP aminoethylation by ethylenimine and N,N',N"-triethylenethiophosphoamide (thio-TEPA) have been obtained and shown to be aminoethyl esters of nucleotides with the free or substituted amino group. In case of dGMP and GMP ethylenimine and tio-TEPA alkylate not only phosphate but also the base residue at the N7 position. The 7-aminoethyl derivatives of dGMP and GMP, which thio-TEPA afforded, were characterized whereas the corresponding ethylenimine derivatives are decomposed under alkaline conditions in the course of the isolation. Possible reasons of extreme instability of these compounds are given. For the first time the ability of thio-TEPA to alkylate DNA at position 7 of guanine residue is shown by means of the luninescence method.

[Directions of alkylation of deoxyguanosine and deoxyguanylic acid by thio-TEPA]. / Napravleniia alkilirovaniia dezoksiguanozina i dezoksiguanilovoi kisloty tiotéfom.

As exemplified with the reaction of well-known anticancer agent thio-TEPA with dGMP, the ability of ethylenimine derivatives to modify this DNA component under the conditions approaching the biological ones was demonstrated for the first time. Modification involves mainly the phosphate group alkylation. In addition, thio-TEPA alkylates the base in dGMP at position 7. The formation of dGMP 7-alkyl derivatives was confirmed by detecting the luminescent products generated in the course of this reaction.

[31P-NMR study of P-compounds metabolism in the liver of mice under stress]. / Izuchenie metodom IaMR P metabolizma fosforsoderzhashchikh soedinenii v pecheni myshi v usloviiakh stressa.

A method for quantitative calculation of 31P-NMR spectra of tissues is proposed. Change dynamics of concentrations of phosphor-containing metabolites in the mouse liver under starvation, physical load (swimming) and glucose load (intraperitoneally) was investigated. It has been shown that using starvation as a method for object standardization 12-24 hours starvation is the optimal one.

[Recording of high resolution 31P NMR spectra from the surface of a living object]. / Registratsiia spektrov IaMR P vysokogo razresheniia s poverkhnosti zhivogo ob"ekta.

A surface coil probehead was worked out for the superconducting 50 mm bore magnet of NMR a high resolution NMR spectrometer with the field strength 8,46 T (145.78 MHz for 31P nuclei) with a 50 mm slot. The requirements were analysed for the surface R.F. coil to obtain the greatest possible single/noise ratio at fixed space selectivity. Real penetration depth of the radio-frequency field into the specimen was estimated. Spectra of liver and abdominal muscle of anesthetized mouse were obtained. The probehead may be applied to obtain high resolution 31P spectra in vivo studies of animal organs.

[Possibility of the evaluation of the functional activity of human erythrocytes using the 31P-NMR method]. / O vozmozhnosti otsenki funktsional'noi aktivnosti éritrotsitov cheloveka metodom 31P-IaMR.

Intact human erythrocytes from venous blood were investigated. It has been found that the width and form of signals of 2.3 DFG vary strongly, but for the given person these characteristics of the signals are stable parameters. These variations were shown to correspond to the degree of inhomogeneity of erythrocytes population in venous blood as regards their relative concentrations of Hb and HbO2. The width of the signals of 2.3 DFG, so far reflects functional activity of the human red blood cells in oxygen transport.

[Proton magnetic resonance study of the changes in blood lipids in malignant and benign neoplasms]. / Issledovanie metodom protonnogo magnitnogo rezonansa izmeneniia soderzhaniia lipidov krovi pri zlokachestvennoi i dobrokachestvennoi opukholiakh.

High-resolution 1H-NMR spectrometry (360 MHz) was used in combination with thin layer chromatography to study changes in composition and molecular structure of inverted micelles of blood lipids from patients with breast and uterus cancer. Changes in relative intensity of NMR signals of lipids compared with norm were revealed. The changes in the lipid composition of blood components, in particular, in cholesterol content, determine the differences in structure and molecular mobility of these lipids, which probably explains the regularities observed in the NMR spectra.

[Letter: Study of the interaction of histones F1, F2b, F2a1, F3 with nucleotides by the method of high resolution nuclear magnetic resonance]. / Issledovanie vzaimodeistviia gistonov F1, F2b, F2a1, F3 s nukleotidami metodom iadernogo magnitnogo rezonansa vysokogo razresheniia

Interaction of nucleotides with histones F-1, F-2b, F-2a1, F-3 have been studied by NMP method. It has been found that the interaction of nucleotides with histones increase in the line F-1. F-2b, F-3, F-2a1. It is suggested that histone F-1 is bound with the nucleotides mainly by electrostatic forces. Bounding of histones F-2a1 and F-3 with nucleotides is due not only to electrostatic sinteractions but also to more specific bonds of the base ring with protein.

[High resolution NMR study of mitochondria and submitochondrial fragments]. / Issledovanie mitokhondrii i submitokhondrial'nykh fragmentov metodom IaMR vysokogo razresheniia

The PMR spectra of mitochondrias, inner and outer mitochondrial membranes and also, matrix and intermembrane material are presented. The essential effect of sonication on the structure of inner membranes of mitochondrias is demonstrated.

[Extraction of deuterated compounds from Chlorella sp. K. grown in D20]. / Poluchenie deiterirovannykh soedinenii iz Chlorella sp. K., vyrashchennoi v D20

A comparison of the three known methods made it possible to work out methods of complex extraction of deutero amino acids, deutero sugars and deutero vitamins from algae Chlorella sp. K., grown autotrophically in heavy water. An analysis of the isotopic composition of deutero amino acids by PMR indicates that treatment with HCl introduces 1H into side chains of some amino acids by chemical exchange (C2, 6H of tyrosine, C2H of histidine, rho-H of phenylalanin, beta-CH2-aspartate and gamma-CH2-glutamate. These exchanges made the amino acids convenient to be used as the substrates for the growth of heterotrophic selective deuterated organisms as a source of selective deuterated proteins.

[31P-NMR study of the levels of phosphorus-containing metabolites in the mouse liver during administration of highly dispersed zinc powder]. / Izuchenie metodom 31P-IaMR urovnia fosforsoderzhashchikh metabolitov v pecheni myshei pri vvedenii vysokodispersnogo poroshka tsinka.

The content of phosphor-containing metabolites as regards inorganic phosphate of tissues of the mouse liver after injection of zinc highly dispersed powder at the dose of 5 mg/kg has been established with quantitative calculation of 31P-NMR spectra. A decrease in the relative level of phosphor-containing metabolites in the liver regeneration on the first day after partial hepatectomy has been observed. It has been shown that the relative level of phosphor-containing metabolites after injection more decreased during the first two days after operation. The observed changes of P-compounds metabolites in the liver after injection of zinc highly dispersed powder are related to its stimulation effect on metabolism of sugar and phospholipids and on the cell respiratory process.

[Levels of labile phosphorus-containing metabolites]. / Soderzhanie labil'nykh fosforsoderzhashchikh metabolitov.

The work deals with the investigation of possible use of 31P-NMR for revealing metabolism changes in the mouse liver during the development of leukemia. This method was shown to permit observation of the extreme pattern of relative concentrations of sugar phosphate and bioorganic phosphate in the latent period. This observed increase in the metabolic activity of hepatocytes correlates with biophysical shifts found by other methods.

[Prognostically significant indices of the bioenergetic metabolism of the brain in experimental ischemia (a NMR spectroscopic study)]. / Nekotorye prognosticheski znachimye pokazateli bioénergeticheskogo metabolizma mozga pri ego ishemii v éksperimente (IaMR-spektroskopicheskoe issledovanie).

Initial levels of phosphate brain metabolites were measured using 31P NMR spectroscopy in rats which subsequently died or survived under bilateral ligation of common carotid arteries. A multidimensional analysis was applied. In the rats which died after the brain ischemia: (1), NAD and NADH+ concentrations were much higher than those of creatine phosphate or ATP (i.e. baseline dysbalance existed between the systems of hydrogen acceptors and major macroergic substances); (2), the force of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower than those of the surviving group. These regularities can be used in detection of special groups at high professional risk and in designing individual procedures of prevention and treatment of cerebral circulation disorders. The data are valuable in terms of development of drugs which would correct the dysbalance between hydrogen acceptors and macroergic systems thus providing a metabolic defense for the ischemic brain.

[Study of nucleotide biosynthesis by cultured Brevibacterium ammoniagenes using P31 nuclear magnetic resonance spectroscopy]. / Issledovanie biosinteza nukleotidov kul'turoi Brevibacterium ammoniagenes metodom spektroskopii IaMR na iadrakh P31.

Using P31 nuclear magnetic resonance, transformations of phosphorous compounds by the culture Brevibacterium ammoniagenes ATCC 6872 in the course of fermentation aimed at the synthesis of nicotinamide adenine dinucleotide were investigated. It was found that the NAD synthesis by the cells treated with surface active substances was markedly influenced by the presence of a small (initial) ATP quantity and was unaffected by an addition of the synthetic polyphosphate (n-40). It was demonstrated that the cells which were not treated with surface active substances contained orthophosphate, carbohydrate monophosphates, and minor quantities of nucleoside triphosphates, polyphosphates, mono- and dinucleotides. After treatment with surface active substances the cells lost these compounds. It is suggested that polyphosphates of the cell and adenosine monophosphate synthesized during its autolysis may enhance the recovery of the ATP level required to trigger glycolysis which serves as the major producer of ATP in the absence of oxidative phosphorylation.

[Evaluation of maximal Na K ATPase activity in the erythrocytes of patients with various types of arterial hypertension using the Na-23-NMR method]. / Otsenka maksimal'noi aktivnosti Na+, K+ ATFazy v éritrotsitakh u bol'nykh s razlichnymi formami arterial'noi gipertenzii metodom 23Na-IaMR.

The paper provides measurements of maximal Na+, K(+)-ATPase activity in 20 patients with hypertensive disease, 20 patients with secondary hypertension and 20 healthy donors. The investigation was made by high-resolution nuclear magnetic resonance using sodium nuclei. A significant decrease was found in Na+, K(+)-ATPase activity in the patients with hypertensive disease (9.0 +/- 0.3 mg-equiv. per lites cells an hour) as compared with those with secondary hypertension (10.3 +/- 0.3 mg-equiv. per liter cells an hour) and the controls (10.5 +/- 0.3 mg-equiv. per liter cells an hour), which supports the findings of impaired membrane morphology in hypertensive disease.

[Hypochromic effect of signal attenuation in 31P-NMR spectra of linear polyphosphates]. / Gipokhromnyi éffekt snizheniia intensivnosti signalov v 31P-IaMR spektrakh lineinykh polifosfatov.

Chemical shifts in 31P-NMR spectra of linear polyphosphates were studied. In each polyphosphate species tested, the sum of signal intensities of the internal (core) phosphate groups was proportional to the concentration of each polyphosphate, but the contribution of such groups to the total intensity of the signal decreased with increasing the length of the polyphosphate chain. An equation for estimating the polyphosphate chain length in biological objects taking into account a decrease in the 31P-NMR spectral intensity is proposed.

[The effect of gamma-hydroxybutyric acid on the reaction rate of phosphate-containing metabolites in the rat brain during ischemia estimated from (31)P-NMR spectroscopic data]. / Vliianie GOMK na tempy snizheniia makroérgicheskikh fosfatov mozga krys vo vremia ishemii po dannym prizhiznennoi (31)P-YaMR-spektroskopii.

Protective effects of gamma-hydroxybutyric acid on bioenergetic reactions were studied in brain of rats with ischemia using 31P-NMR spectroscopy in vivo. Intraperitoneal preadministration of gamma-hydroxybutyric acid at a dose of 400 mg/kg within 30-40 min before ischemia led to a decrease in the ATP pool in ischemic brain tissue, to alteration in the PCr/ATP ratio in the 31P-NMR spectrum, to prevention of Pi concentration increase and to increase in the intracellular acidosis development rate. Possible mechanisms of the gamma-hydroxybutyric acid effects on bioenergetic reactions in nervous tissue during ischemia are discussed.

[Free radical oxidation and tubular dysfunctions in patients with chronic kidney failure]. / Sobodnoradikal'noe okislenie i kanal'tsevye disfunktsii u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

Sixty patients with chronic renal failure (CRF) were studied for the rates of lipid peroxidation (LPO), the state of the antioxidative system (AOS) as well as for the morphofunctional state of biomembranes in renal tubules measured by excretion of low-molecular compounds tested in urine x by means of proton nuclear magnetic resonance spectroscopy. The control group numbered 35 patients with glomerulonephritis free of functional disturbances in the kidneys. The increased values of malonic dialdehyde levels in red blood cells and blood serum and those of diene conjugates in red blood cell membranes provide evidence for a significant increase of the LPO levels. Furthermore, depression of the AOS was revealed, manifested by the decreased levels of blood serum alpha-tocopherol as well as by unstable levels of superoxide dismutase in red blood cells. In the presence of the high LPO levels significant tubular dysfunctions were progressing, parallel with aggravation of renal function. Disturbances detected in excretion and reabsorption of amino acids (leucine, alanine, glycine, valine, histidine), thin organic acids and ketone bodies in CRF patients point to the existence of disturbances in tubular membranes. Tubular dysfunction appears to be caused by the disturbances of the biomembrane morphofunctional states induced by the high levels of free radical oxidation as well as by the AOS function failure.

[The effect of verapamil on the dynamics of decrease in the brain levels of phosphorus macroergs during ischemia studied by 31P-NMR in vivo]. / Vliianie verapamila na dinamiku snizheniia urovnei makroérgicheskikhfosfatov mozga pri ishemii po dannym 31P-IaMR spektroskopii in vivo.

Protective effects of verapamil on dynamics of phosphorus-containing metabolites were studied during 30 min complete ischemia by means of 31P NMR. Verapamil appears to decrease the ATP and creatine phosphate pools consumption in ischemic brain tissue. The efficiency of the drug depended on the administration procedure and was not similar in two different models of ischemia. Possible mechanisms of the verapamil effect on bioenergetics of nervous tissue are discussed.

[Effect of surface-active substances on the dynamics of intracellular pH in Fusidium coccineum]. / Vliianie poverkhnostno-aktivnykh veshchestv na dinamiku vnutrikletochnogo pH u Fusidium coccineum.

Correlation between the dynamics of intracellular pH and antibiotic synthesis in Fusidium coccineum strains with different biosynthetic capacity was studied. At the beginning of the intensive antibiotic synthesis the intracellular pH in the low-active and highly-active strains was minimum and maximum respectively. In the highly active strain an increase in the intracellular pH of the cytoplasm after the addition of Tween-80 and Factor-d2 analogs to the growth medium was observed.