[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.

[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.

[Change in inorganic polyphosphate chain length depending on the stage of Saccharomyces cerevisiae growth]. / Izmenenie dliny tsepi neorganicheskikh polifosfatov v zavisimosti ot stadii rosta Saccharomyces cerevisiae.

The dynamics of the content and the degree of polymerization of polyphosphates (PPs) during the growth of Saccharomyces cerevisiae VKM Y-1176 was studied by chemical methods and P NMR spectroscopy. The overall PP content of Saccharomyces cerevisiae cells growing in orthophosphate-sufficient medium was found to increase until glucose was exhausted in the medium. In the early logarithimic phase, the degree of polymerization of PPs (high-polymeric PPs in particular) fell drastically. Further cultivation of yeast in the glucose-depleted medium led to a decrease in the cellular content of all PP fractions without any considerable shortening of their chain length; by the 24th h, high-polymeric PPs accumulated in the cells. Shortening of PPs against a background of their intense synthesis in yeast cells growing in glucose-and orthophosphate-sufficient medium can be explained by the involvement of so far unknown mechanisms of activation of polyphosphate-depolymerizing enzymes.

[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.

[Stability of a new product of oxidative stress in bacterial cells]. / Stabil'nost' novogo produkta okislitel'nogo stress v kletkakh bakterii.

Data on 32P-label incorporation with subsequent addition of non-radiolabelled o-phosphate suggest that the new phosphorus compound, 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC), accumulated in the cells of some bacterial species in response to oxidative stress does not rapidly exchange phosphorus with external o-phosphate 3 hours after the introduction of its synthesis inducers into the Corynebacterium ammoniagenes culture. The accumulated MEC is retained in the cells despite the action of the cell wall synthesis inhibitor, chloramphenicol, or the energetic poisons, KCN and iodoacetate and also under anaerobic conditions. It has been shown that incubation of the cell-free lysate of a non-induced culture, Micrococcus luteus, with MEC does not result in MEC hydrolysis; therefore, MEC accumulation after the redox-mediator addition is hardly due to the hydrolase inactivation but, rather, is due to the activation of the MEC-synthesizing enzyme. The cells of C. ammoniagenes incorporate 32P from [32P]MEC but not 14C from [14C]MEC. This points to MEC hydrolysis prior to the uptake of its phosphoryl fragment by the cells. In this case 32P is found in the fractions differing by their position from MEC fractions. Experiments with sheep erythrocytes and mouse splenocytes revealed that MEC (10-100 micrograms per 1,000,000 splenocytes) does not influence the antibody production by these cells, whereas used at concentrations of 200-550 micrograms per 1,000,000 cells, MEC enhances the antibody production. However, while doing so, MEC causes the destruction of a considerable portion of splenocytes and sheep erythrocytes.

[Effect of antiseptics and redox-cycling agents on Corynebacterium ammoniagenes and related microorganisms in relation to synthesis of a new macroergic compound]. / Deistvie antisepticheskikh sredstv i redokstsikliruiushchikh agentov na Corynebacterium ammoniagenes i rodstvennye mikroorganizmy v sviazi s sintezom novogo makroérga.

Sublethal concentration of the antiseptic composition Desoxon-1 was shown to provoke in cells of Corinebacterium ammoniagenes in a liquid medium the biosynthesis and accumulation of a novel macroergic 2-methylbutane-1,2,3,4-tetraol-2,4-cyclopyrophosphate. This substance is also synthesized when C. ammoniagenes is cultivated in a solid agar medium supplemented with benzylviologen. Cells preloaded with the new cyclopyrophosphate maintain its content when treated with 4% phenol, DP-2, Desoxon-1 or boiled and heated in an autoclave. Experiments with Mycobacterium tuberculosis and BCG revealed the ability of these bacteria to grow in a medium supplemented with BV++ possibly due to ability of synthesis of a new cyclopyrophosphate which was shown to correlate with resistance toward redox-cycling drugs. Accumulation of polyphosphates in the control cells of M. tuberculosis was illustrated by 31P-NMR spectroscopy and disappearance of the polyphosphates during cultivation in a BV(++)-supplemented medium. No signal of the new cyclopyrophosphate was yet registered in cells of M. tuberculosis by 31P-NMR.

[Changes in the replication apparatus and phosphorus-containing metabolite pool in experimental tumors in animals during development]. / Izmeneniia v apparate replikatsii i sostoianii pula fosforsoderzhashchikh metabolitov éksperimental'nykh opukholei zhivotnykh v protsesse razvitiia.

Activity of replicase complex enzymes involving thymidine kinase (TK), ribonucleotide reductase (RR), DNA-polymerases alpha and beta as well as DNA synthesis and single breaks in DNA were studied during growth of P388 ascites tumor. Under these conditions the rate of DNA synthesis was distinctly decreased via salvage pathway and de novo. Single breaks were not detected in the preexistent DNA within various periods after transplantation of P338 leukemic cells. Retardation of DNA synthesis during tumor growth correlated with a decrease in TK, RR and DNA-polymerase alpha activities, while DNA-polymerase beta activity was markedly increased. Growth of melanoma B16 was accompanied by a decrease in content of ATP, ADP, NAD, phosphocreatine and phosphosaccharides as well as by an increase in the level of inorganic phosphates.

[A high-resolution 31P-NMR study of the disorders in the energy metabolic system of Ehrlich ascites cancer cells exposed to antitumor preparations]. / Issledovanie metodom 31P-IaMR vysokogo razresheniia narusheii v sisteme énergeticheskogo metabolizma kletok astsitnogo raka Erlikha pri vozdeistvii protivoopukholevykh preparatov.

The disturbance in energetic metabolism of Ehrlich ascite carcinoma cells during antitumor drug treatment was examined using high-resolution 31P-NMR. The value of antitumor drug effect was shown to be characterized by the kinetics of ATP and KF level alteration in tumor cells. The results correlated with the indexes of therapeutical activity of studied drugs.

[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 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.

[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.

[Possibilities of using proton nuclear magnetic resonance spectroscopy in multicomponent analysis of the urine in glomerulonephritis]. / Vozmozhnost' ispol'zovaniia spektroskopii iadernogo magnitnogo rezonansa na protonakh dlia mnogokomponentnogo analiza mochi pri glomerulonefrite.

Methodological approaches to investigation of low-molecular urine metabolites in health and glomerulonephritis (GN) by means of proton nuclear magnetic resonance spectroscopy (1H NMR) have been analysed. The ways to preserve and concentrate the urine samples by freezing and lyophilization for further storage and spectra quality improvement are substantiated. The method of the spectra treatment with calculation of relative levels of urine substances is detailed. The differences in the ratios of excreted low-molecular metabolites revealed in healthy subjects and GN patients in relation to the severity of chronic renal insufficiency confirm the feasibility of using the 1H NMR data of urine as diagnostic and predictive criteria in GN.

[The status of lymphocytes from immunocompetent organs in the development of experimental tumors from 1H-NMR data]. / Sostoianie limfotsitov immunokompetentnykh organov pri razvitii éksperimental'nykh opukholei po dannym 1H-IaMR.

Thymus and lymph node lymphocytes in L-1210 ascite lymphoma, Lewis tumor, 22a hepatoma have been studied by NMR. Lymphocyte 1H-NMR spectra can to a certain extent reflect the state of immune system of an organism, in particular, they can sense both transformation of lymphocytes, and development of several tumors which are not accompanied by transformation of lymphocytes. In the latter case, changes in lymphocyte spectra takes place at terminal stages of carcinogenesis and are less pronounced than at transformation of lymphocytes. NMR spectra parameters can also distinguish between reaction of males and females to tumor formation.

[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.

[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.

[Rat liver energetics according to data of 31P-NMR in extreme states of the processes of biosynthesis of proteins and nucleic acids]. / Energetika pecheni krysy po dannym 31P-IaMR pri ékstremal'nykh sostoianiiakh protsessov biosinteza belkov i nukleinovykh kislot.

The dynamics of phosphomonoesters, phosphodiesters, Pi, ATP, ADP, NAD(H+) and uridine diphosphoglucose (UDPG) levels in rat liver upon sharp oscillations in the rates of protein and nucleic acid biosynthesis induced by a sublethal++ dose of cycloheximide was studied, using the 31P-NMR method. The results obtained with preparations of native liver are unaffected by fractionation, homogenization and chemical extraction procedures. It was demonstrated that oscillations of Pi, ATP and UDPG levels in liver cells reflect the changes in the energy consumption and intracellular energy-linked processes (e.g., glycolysis, oxidative phosphorylation, glycogen synthesis and consumption) under conditions of variable macromolecular synthesis rates. The oscillations in phosphomonoesters and phosphodiesters levels are mainly due to cycloheximide-induced lipid metabolism disturbances.

[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.