Is hypoxanthine a useful marker of perinatal hypoxia?
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Apgar Score↗
Biomedical subjects
T Grune
Publications and source records attributed to T Grune.
A study of anoxia in rat hepatocytes.
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Animals↗
Adenine nucleotide levels and lipid peroxidation at hypoxia and reoxygenation in different cell types.
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5'-Nucleotidase↗
Postischemic accumulation of the lipid peroxidation product 4-hydroxynonenal in rat small intestine.
4-Hydroxynonenal (HNE) as an indicator of lipid peroxidation was determined in rat jejunal mucosa. HNE was extracted as the dinitrophenylhydrazone derivative from the tissue, partially separated from other carbonyl compounds by thin-layer chromatography and measured by HPLC. During reperfusion of the small intestine following an ischemic period of 60 minutes a marked increase of the tissue concentration of HNE was observed. The mucosal HNE level passed a maximum value of 3.0 +/- 0.5 microM 10 min after the onset of reperfusion in comparison with 0.7 +/- 0.2 microM as initial value. The increased tissue level of the highly cytotoxic 4-hydroxyalkenal is suggested to be involved in the reperfusion induced morphological and biochemical changes of the small intestine.
Aldehydes↗
Transitions of hepatic purine metabolism of Ehrlich ascites tumor bearing mice in different phases of tumor growth.
The concentrations of purine nucleotides, nucleosides and nucleobases in hepatocytes taken from healthy control mice and from Ehrlich ascites tumor bearing mice have been measured. The level of adenine nucleotides in the hepatocytes was higher during the proliferating phase in comparison with the resting phase of tumor growth and with control mice hepatocytes. The tracerkinetic studies on purine catabolism have been carried out on liver cells at different periods of tumor growth. The dynamics of radioactive tracers was mathematically modelled by a system of differential equations for both the concentrations and the specific radioactivities of the metabolites. Large differences in metabolic flux rates between control hepatocytes and hepatocytes in different phases of tumor growth were observed. The final purine degradation of hepatocytes was found to be accelerated in the resting phase but not in the proliferating phase of tumor growth. This result is in accordance with increased ATP concentration of liver itself in the proliferating phase of tumor growth. A conclusion is possible that the liver does not supply nucleosides and nucleobases for the Ehrlich ascites tumor cells during the proliferating phase of tumor growth.
Adenosine Triphosphate↗
[Increased formation of free radicals in chronic lymphedema].
The erythrocytic glutathione concentration in patients with lymphatic edema was around 20% lower than that of healthy volunteers. In addition, there was a drastic increase in the plasma malondialdehyde concentration. These changes indicate vigorous generation and activity of free radicals in lymphatic edematous tissue.
Adult↗
Purine nucleotide levels in host tissues of Ehrlich ascites tumor-bearing mice in different growth phases of the tumor.
The pool sizes of purine nucleotides, nucleosides, and nucleobases were measured in the host tissues liver, skeletal muscle, and blood of Ehrlich ascites tumor-bearing mice during the different periods of tumor growth. There were large differences of tissue concentrations of these metabolites between control animals, animals in the logarithmic growth period of the Ehrlich ascites tumor, and animals in the resting phase of tumor growth. The ATP concentrations in liver, muscle, and erythrocytes were higher during the proliferating phase of the tumor compared with the ATP levels of these organs in healthy animals. In liver and skeletal muscle the ATP concentration decreased during the transition from proliferating into resting phase of tumor growth. The concentrations of nucleosides and nucleobases within the RBC and blood plasma deceased during the logarithmic growth phase but restored during the plateau period. As well as in the organs/cells investigated and in the body fluids (plasma, ascites fluid) a tremendous increase of adenosine concentration during the resting phase of tumor growth was observed. From changes of total purine ribonucleotide pattern an activation period in the nucleotide metabolic pathways of liver and skeletal muscle during the proliferating phase of tumor growth is postulated.
Adenine↗
Reversed-phase high-performance liquid chromatography of purine compounds for investigation of biomedical problems: application to different tissues and body fluids.
An overview of high-performance liquid chromatographic separation techniques (reversed-phase and ion-pair reversed-phase) used in the analysis of purine ribonucleotides, ribonucleosides and nucleobases, including procedures for sample preparation, is given. Coverage of the separation techniques is extended to the measurement of specific radioactivities of these compounds in tracer kinetic experiments for metabolic flux rate analyses. This article is focused on the development and adaptation of reversed-phase separation techniques for nucleotides, nucleosides and bases that are used to examine a variety of biomedical problems. The investigation of purine nucleotide metabolic disorders or physiological transitions in the pathomechanisms of different diseases and syndromes or in cell maturation processes, respectively, requires the application of chromatographic separation to a multitude of tissues and body fluids. These samples vary greatly in concentrations of purine compounds with low molecular mass, from ca. 5 mM to ca. 0.5 microM. The advantages and disadvantages of different techniques are critically discussed.
Animals↗
Optimized separation of purine bases and nucleosides in human cord plasma by capillary zone electrophoresis.
An optimized separation of the main purine compounds of human serum by capillary zone electrophoresis is presented. Separations were performed in an uncoated silica capillary (44 cm x 75 microns I.D., 37 cm to window) on a SpectraPhoresis 1000 system with UV detection. The separation of adenine (Ade), adenosine (Ado), guanine (Gua), guanosine (Guo), hypoxanthine (Hyp), inosine (Ino), xanthine (Xan) and uric acid (UA) was optimized with respect to pH, temperature, applied potential and hydrodynamic injection time. Optimum conditions were 20 mM borate buffer (pH 9.4), 37 degrees C, 20 kV and 9 s load and detection at 260 nm. Linearity extended from 1 to 125 microM. The sensitivity of the method was 0.5 microM, which is adequate for measuring Ade, Gua, Hyp and UA in plasma samples. Plasma samples from newborns were precipitated with an equal volume of perchloric acid (7%, v/v), the supernatant was adjusted to neutral pH with potassium carbonate and, before injection, the sample was alkalized with sodium hydroxide. The method presented here allows the determination of Ade, Guo, Hyp and UA. The levels of the determined purines were compared in samples from control newborns, preterm babies and newborns with asphyxia or acidic serum pH values.
Calibration↗
Accumulation of aldehydic lipid peroxidation products during postanoxic reoxygenation of isolated rat hepatocytes.
The accumulation of the aldehydic lipid peroxidation product 4-hydroxynonenal and thiobarbituric acid-reactive substances was demonstrated during anoxia/reoxygenation of isolated rat hepatocytes. 4-Hydroxynonenal was detected as dinitrophenylhydrazone derivative by means of an isocratic HPLC separation. The highest 4-hydroxynonenal level was found 15 min after the beginning of reoxygenation. The concentration of 4-hydroxynonenal was compared with the thiobarbituric acid-reactive substances formation, the glutathione status, and the cell viability. Addition of the xanthine oxidase inhibitor oxypurinol decreased the aldehyde formation during the reoxygenation phase. The same suppression of oxidative load by 20 microM oxypurinol (inhibition of xanthine oxidase) and by 1 mM oxypurinol (inhibition of xanthine oxidase plus radical scavenging) leads to two conclusions: First, the purine degradation is the primary radical source of postanoxic hepatocytes; second, the inhibition of radical generation by xanthine oxidase is the main component of cell protecting by oxypurinol. On the other hand, oxypurinol addition did not accelerate the adenosine 5'-triphosphate (ATP) restoration.
Adenosine Triphosphate↗
Estimation of steady-state flux rates in metabolic systems by computer simulations of radioactive tracer experiments.
The dynamics of radioactive tracers in metabolic systems can be mathematically modelled by coupled systems of differential equations for both the concentrations and the specific radioactivities of the metabolites involved. Computer simulations, i.e. direct fitting of numerical solutions of these equations to observed time-courses of metabolites and specific radioactivities, enables one to estimate unknown kinetic parameters of the system. The theoretical fundamentals of this approach and the main steps towards the quantitative assessment of flux rates in stationary metabolic systems are outlined. An application of the method to the purine nucleotide metabolism of Ehrlich ascites tumor cells is given based on a simplified model of this pathway. The obtained steady-state flux rates indicate a marked increase in the metabolism of the adenine nucleotides during the proliferating phase in comparison to the resting phase of tumor growth.
Adenine Nucleotides↗
Posttransfusional changes of 2,3-diphosphoglycerate and nucleotides in CPD-SAGM-preserved erythrocytes.
BACKGROUND: Posttransfusional changes of preserved red blood cells can influence the oxygen equilibrium curve which is mainly affected by the concentration of erythrocyte 2,3-diphosphoglycerate (DPG). MATERIAL AND METHODS: The regeneration kinetics of DPG and nucleotides (ATP, ADP, AMP, GTP, GDP) was determined over a period of 0-48 h in surgically treated patients following transfusion of DPG-depleted packed red cells stored for 14 days in CPD-SAGM. RESULTS: 3 h after transfusion the DPG levels raised up to 40% of the patients' prior DPG concentrations. Complete regeneration of the DPG concentrations occurred 36-48 h after transfusion. Changes in the nucleotide pattern indicate, after a temporary decrease of ATP and GTP levels (after 10-30 min) and an activation phase (after 3-12 h), the full regeneration of these parameters 24-48 h after transfusion. CONCLUSIONS: The regeneration kinetics of DPG should be taken into consideration for transfusions with blood units stored for more than 14 days, especially in patients with reduced compensatory mechanisms (coronary and cerebral scleroses, pacemaker, etc.) and large transfusion volumes.
2,3-Diphosphoglycerate↗
Trichlorobromomethane-induced changes of purine nucleotides in hepatocytes.
The changes in nucleotide content during CBrCl3 treatment were investigated. In the first 5-10 minutes a significant ATP decrease was detected. The GTP loss leading to 57% of the initial level after 10 min surpasses the ATP loss which leads to 70% of the initial value after 10 min. The increase in uric acid is not only the result of CBrCl3 induced reaction, because of no significant changes in adenine and hypoxanthine values. The uric acid pool reflected different influx and efflux processes. These changes were compared with nucleotide degradation and accumulation of nucleotide degradation products during anoxia.
Adenosine Triphosphate↗
Studies on lipoate effects on blood redox state in human immunodeficiency virus infected patients.
Several investigators have implicated that human immunodeficiency virus (HIV) infected patients have a compromised antioxidant defense system. Blood antioxidants are decreased and peroxidation products of lipids and proteins are increased in the patients. This may have pathophysiological implications, because antioxidants, such as glutathione, and reactive oxidants are involved in the regulation of the human immunodeficiency virus. Consequently it was suggested that HIV infected patients may benefit from antioxidant supplementation therapy. In a open and unblinded pilot study the short term effect of the natural antioxidant lipoate (Thioctacid) on blood antioxidants and peroxidation products was investigated in HIV positive patients (CDC IV). In the majority of the patients, lipoate increased plasma ascorbate (9 of 10 patients) total glutathione (7 of 7 patients), total plasma thiol groups (8 of 9 patients); T helper lymphocytes and T helper/suppressor cell ratio (6 of 10 patients), while the lipid peroxidation products malondialdehyde (8 of 9 patients) and 4-hydroxynonenal (7 of 9 patients) were decreased. The results of this pilot study indicate that lipoate supplementation changes the blood redox state of HIV infected patients. A prospective and longitudinal therapy study is warranted to investigate the long term effects of lipoate therapy on blood redox state, disease progression and incidence of opportunistic infections in HIV infected patients.
Adult↗
Release of 4-hydroxynonenal, an aldehydic mediator of inflammation, during postischaemic reperfusion of the myocardium.
For the first time it was demonstrated that 4-hydroxynonenal (HNE) is formed by the myocardium. 1 to 2 pmol HNE/min/mg protein were released from isolated perfused hearts of 18-month-old WKY rats during a normoxic period of perfusion. During the first minutes of reperfusion following 30 min of ischaemia, the mean value of HNE release increased in comparison to pre-ischaemic HNE release (pre-ischaemic control). However, the alterations were significant only in the second minute of reperfusion. HNE liberation significantly intensified during the early reperfusion period of hearts of 18-month-old spontaneously hypertensive rats (SHR, with cardiac hypertrophy and congestive heart failure) in comparison with the pre-ischaemic control period. Furthermore, HNE liberation from those hearts was higher than from hearts of normotensive control animals (WKY rats). Maximum quantities were observed 2 min after ischaemia, with 6 to 10 pmol HNE/min/mg protein. The results suggest that the formation of chemotactic products of radical-induced lipid peroxidation, such as HNE, is markedly increased in reperfused hypertrophic and failing myocardium, and emphasize the role of HNE as a possible chemotactic agent during postischaemic reoxygenation.
Aldehydes↗
Reoxygenation injury of rat hepatocytes: evaluation of nucleotide depletion and oxidative stress as causal components.
Isolated rat hepatocytes were used for the evaluation of nucleotide depletion and oxidative stress as two causal components of postischemic injury following oxygen deficiency. The ATP and GTP loss during anoxia was accompanied by temporary increases of nucleotide degradation products. The critical duration of anoxia for a complete ATP restoration during reoxygenation was between 30 and 60 min. The oxidative stress during reoxygenation was demonstrated by decrease of GSH concentration and increase of TBA-RS level. The tremendous GSH loss could not be balanced by the slight GSSG increase during reoxygenation. Prevention of GSH decrease and TBA-RS increase in parallel to prevention of viability loss in presence of oxipurinol in contrast to lacking improvement of ATP and GTP restoration by this drug speak in favor for the oxidative stress as major causal component for postischemic injury of hepatocytes in comparison with depletion of energy-rich purine nucleotides. The inhibition of formation of reactive oxygen species via xanthine oxidase reactions was found to be the dominant protective effect of oxipurinol against postischemic injury of hepatocytes in comparison with lacking influence on nucleotide salvage and ATP/GTP regeneration and with radical scavenging.
Adenosine Triphosphate↗
The metabolism of 4-hydroxynonenal, a lipid peroxidation product, is dependent on tumor age in Ehrlich mouse ascites cells.
4-Hydroxynonenal is a major product formed by lipid peroxidation from omega 6-polyunsaturated fatty acids as linoleic acid and arachidonic acid. This aldehyde is cytotoxic at high concentrations (in the range of 100 microM), disturbs cell proliferation at low concentrations and exhibits genotoxic effects. Furthermore, in the submicromolar range 4-hydroxynonenal is chemotactic and stimulates phospholipase C. 4-Hydroxynonenal is rapidly metabolized in eucaryotic cells. Here the metabolism of 4-hydroxynonenal was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The Ehrlich ascites tumor is a convenient biological model for the investigation of tumor cells in different age and proliferation phases of the tumor. The main products of 4-hydroxynonenal which were identified in the Ehrlich ascites cells were glutathione-HNE-conjugate, hydroxynonenoic acid and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of 4-hydroxynonenal was higher in cells of the early phase in comparison with cells of the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione during 4-hydroxynonenal utilization. The degradation of 4-hydroxynonenal and other aldehydic products of lipid peroxidation is postulated to be an important part of the intracellular antioxidative defense system.
Aldehydes↗
Changed purine nucleotide concentrations and enzyme activities in erythrocytes of haemodialysis patients undergoing erythropoietin therapy.
Therapy of renal anaemia in haemodialysis patients with chronic renal failure by application of recombinant human erythropoietin leads to an increase of the haematocrit. Rejuvenation of the erythrocyte population results in a decrease of the median density (D50), an increase of cell age-dependent enzyme activities, such as aspartate aminotransferase, and elevated concentrations of purine nucleotides in the erythrocytes. After density gradient separation of erythrocyte populations into cell age-dependent fractions, the concentrations of adenosine-5'-triphosphate, guanosine-5'-triphosphate and guanosine-5'-diphosphate were be found to be elevated by 25-100% in all cell fractions from haemodialysis patients, compared with a healthy control group. Therapy of haemodialysis patients with recombinant human erythropoietin leads to further increase (65%) of ATP in the younger (low density) cells, but not in the older (high density) cells. The elevated concentrations of ATP and total adenine nucleotides during recombinant human erythropoietin therapy possibly result in improved deformability of erythrocytes. The data point to an enhancement of the proportion of younger erythrocytes, but not to an improvement of the reduced life span of erythrocytes of haemodialysis patients during therapy with recombinant human erythropoietin.
Adenosine Diphosphate↗