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Biomedical subjects

D Leibfritz

Publications and source records attributed to D Leibfritz.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations.

The working rat heart model was used for 31P nuclear magnetic resonance (NMR) studies during normoxia, hypoxia and reoxygenation. Aortic flows of about 35 ml/min could be achieved which equals 65% of the values obtained outside the NMR magnet. Addition of dihydrolipoic acid (DHL) at a concentration of 0.3 mumol/l during hypoxia accelerated the recovery of aortic flow and stabilized it during reoxygenation. During hypoxia, inorganic phosphate contents (Pi) were significantly higher in controls. The phosphate shift indicated a pH decrease in control to 6.98, in DHL treated hearts the calculated pH was 7.15. During both hypoxia and reoxygenation, the phosphocreatinine (PCr) contents were higher in the DHL treated hearts than in controls. In the controls, saturation transfer measurements revealed a decrease of the flux PCr-->ATP during initial reoxygenation, whereas after addition of 0.3 mumol/l of DHL during hypoxia creatine kinase flux remained constant or increased. In isolated rat heart mitochondria, creatine kinase activities were measured under saturating and non-saturating concentrations of PCr. An increase in activity was observed under low PCr (non-saturating) conditions in the presence of 0.7 nmol DHL per mg of protein. At higher concentrations of DHL, creatine kinase activity was increased under all conditions. An increase in ATP synthesis in the working rat heart under influence of DHL is corroborated by NMR spectroscopy.

Adenosine Triphosphate↗
PubMed1993

Correlation of function and energy metabolism in rat ischemic skeletal muscle by 31P-NMR spectroscopy: effects of torbafylline.

The aim of this study was to correlate function of rat ischemic skeletal muscle directly with energy metabolism, to investigate the effects of torbafylline, a novel xanthine derivative potentially useful for the treatment of peripheral vascular occlusive disease and other ailments of skeletal muscle, and to get insight into its mechanism of action. Phosphocreatine (PCr), inorganic phosphate (Pi) and pH were estimated at rest, during induced contractions and during the recovery phase after cessation of electrical stimulation in rat hind limb muscles with two weeks unilateral chronic ligation of the femoral artery. Concomitantly, contraction force was measured in terms of tension developed during the stimulation interval. The effects of torbafylline [7-ethoxymethyl-1-(5-hydroxy-5-methylhexyl)3-methylxanthine] on the above parameters were studied after chronic oral gavage (25 mg/kg body weight per day); treatment started the day after surgery and the last drug application was performed the day of the final experiments. Control animals received physiological saline under the same conditions. During rest no major differences could be detected either in PCr and Pi levels or in pH between the different muscles, ischemic or not and treated or not. During compelled contractions, PCr and pH decreased and Pi increased in all muscles. Differences between muscles and treatments emerged as the PCr drop was more pronounced in ischemic saline treated muscles and the Pi increase in drug treated muscles (normal and ischemic) were clearly less marked than in saline treated ones. Contraction force decreased rapidly during the 12 min electrical direct stimulation and fatigability increased from 67% in normal muscle to 88% in ischemic muscle. Drug treatment induced strikingly less fatigability as it was 44.5% in normal and only 62% in ischemic muscle. However, most marked differences in metabolite levels and pH were measured during the recovery period. As an indication of disturbed energy balance, the recovery of PCr, Pi and pH was seriously hampered in ischemic saline treated muscles; especially pH being still significantly decreased during the entire chosen recovery period of 15 min. Torbafylline not only restored function, but also helped the muscle recover faster and better from exhaustion, as all the parameters returned gradually to normal levels.

Animals↗
PubMed1992

On the application of ultra-fast RARE experiments.

The ultra-fast application of the RARE experiment is described in detail, with special emphasis on its multifarious applications with preparation experiments that produce transverse magnetization. The factors affecting the temporal evolution of the magnetization during the experiment are described, and the implications for the slice profile when using a Gaussian refocusing pulse are experimentally examined. The choice of phase-encoding scheme for use with preparation experiments is discussed, as is the use of various phase-encoding schemes to reduce line broadening in the phase-encoding direction if a number of averages are acquired. An explanation for the decomposition of the echo are into two components if the read gradient is imbalanced is given, and the experimental conditions necessary for the coherent addition of these two echo groups are described. An alternative sequence that removes one of these groups from the acquisition window is proposed. The sensitivity of the sequence to flow and motion is investigated, and the drastic loss of signal in this situation explained. The in vivo and in vitro application of preparation experiments leading to the accurate measurement of T1, T2, diffusion constant, and magnetization transfer characteristics is presented. The implementation of zoom-imaging using spin- and stimulated-echo preparation is described, and 3D in vivo spin-echo zoom images are presented. Simple phantom experiments demonstrating the feasibility of chemical-shift selective and spectroscopic imaging are also given.

Animals↗
PubMed1992

T1 snapshot FLASH measurement of rat brain glioma: kinetics of the tumor-enhancing contrast agent manganese (III) tetraphenylporphine sulfonate.

The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema.

Animals↗
PubMed1992

In situ nuclear magnetic resonance of N pulse labels monitors different routes for nitrogen assimilation.

Nuclear magnetic resonance offers the possibility of noninvasive in situ observation of (15)N pulse labeling in the presence of light. In vivo, exclusively the delta-nitrogen of Gln is labeled in the cyanobacterium Microcystis firma when glutamate synthase is inhibited by azaserine. In contrast, the green alga Chlorella fusca is additionally capable of incorporating nitrogen into Glu, thus providing evidence for an anabolic function of glutamate dehydrogenase in this organism.

Journal Article↗
PubMed1992

Conformational regions of Boc-Ala-Aib-Ala-OMe. Sampling with molecular dynamics simulations using time averaging of distance restraints.

The method of time averaging of distance restraints in molecular dynamics simulations is applied to Boc-Ala-Aib-Ala-OMe in order to demonstrate the improved sampling properties of this method compared to conventional distance restraining. Two conformational regions, beta-turn type II and gamma-turn, are seen during MD runs at a simulation temperature of 500 K, while in simulations with conventional distance restraining, no conformational transitions could be observed for temperatures up to 1000 K.

Amino Acid Sequence↗
PubMed1990

The energy requirements of pH homoeostasis define the limits of pH regulation--a model.

The regulation of intracellular pH of Platymonas subcordiformis cells is investigated with 31P-NMR spectroscopy at various external pH values. The limits of pH homeostasis differ between respiring cells and cells solely glycolyzing. The former retain their normal cytoplasmic pH for external pH values from 5 to more than 12, while in the latter intracellular pH is less stable below external pH 6, and external pH of more than 11 causes hydrolysis of intracellular polyP. The power necessary to maintain a stable intracellular pH is calculated from the electrochemical potential and H+/OH- flux rates across the cell membrane. H+/OH- transport across the membrane by diffusion as well as through hydrogen-bonded chains is considered. Comparison of the minimal power necessary to keep intracellular pH stable at various external pH values by ATP consuming processes with the estimated power available to aerobic and anaerobic cells in the dark shows that different energy turnover may explain the different behaviour of the cells when exposed to extreme pH values.

Adenosine Diphosphate↗
PubMed1990

Biotransformation of mafosfamide in P388 mice leukemia cells: intracellular 31P-NMR studies.

The intracellular transformation of cis-mafosfamide has been studied in P388 mice leukemia cells using 31P-NMR spectroscopy. For this purpose the cells were entrapped in low-gelling-temperature agarose threads. Internal pH of the cells, determined from the position of the intracellular inorganic phosphate, was 7.2. The cell membrane was permeable to 4-hydroxycyclophosphamide and aldophosphamide and less permeable to phosphoramide mustard. 4-Ketocyclophosphamide and carboxyphosphamide signals were not detectable in cells either sensitive or resistant to oxazaphosphorine treatment.

Animals↗
PubMed1990

Improved metabolite editing by the 1D soft COSY technique with 270 degrees Gaussian-shaped pulses.

Recently we proposed Gaussian-shaped pulses to overcome the dynamic range problem within a 1D Soft COSY pulse sequence for the editing of metabolites in their natural environment. Similar to the development of the application of a COSY technique, the ECZOTIC sequence was introduced for the same purpose. A brief comparison of the abilities of both sequences is given in the first part of this communication, and the second part deals with the improvement of phase behavior within 1D Soft COSY by use of 270 degrees pulses.

Filtration↗
PubMed1990

A simple method of generating variable T1 contrast images using temporally reordered phase encoding.

A rapid method of generating T1 images by means of an inversion pulse followed by a fast low-angle imaging experiment is presented. The T1 contrast is manipulated by a temporal reordering of the phase-encoding gradient, resulting in an almost completely free choice of T1 contrast, without any extra restriction on the size of the data acquisition matrix. The intrinsic rapidity of the sequence renders it insensitive to motion artifacts and lends itself to multipoint T1 calculations. The method is particularly well suited to high-field imaging.

Animals↗
PubMed1989

A 13C NMR study on fluxes into the Krebs cycle of rabbit renal proximal tubular cells.

Suspensions of rabbit renal proximal tubular (PCT) cells were incubated with [2-13C] and [3-13C]pyruvate. The perchloric acid extracts of the cell pellets were examined by 13C NMR. All experiments showed that enriched lactate, alanine, glutamate, and glutamine were the main metabolic intermediates, and that enrichment to a minor extent was found in the glutamate residue of glutathione (GSH). From these experiments, it could be deduced that PCT cells show a highly glycolytic activity, whereas enrichment of glucose exhibits gluconeogenesis. The estimation by 13C NMR of the ratio of the flux into the Krebs cycle via pyruvate carboxylase to the flux via pyruvate dehydrogenase is discussed. From incubations with 10 mM 13C-labelled pyruvate, we calculated from the relative enrichments of the glutamate carbon atoms that the ratio of pyruvate carboxylase to pyruvate dehydrogenase is 1.44 +/- 0.04 in rabbit renal proximal tubules.

Animals↗
PubMed1988

A 13C-NMR study on the influxes into the tricarboxylic acid cycle of a renal epithelial cell line, LLC-PK1/Cl4: the metabolism of [2-13C]glycine, L-[3-13C]alanine and L-[3-13C]aspartic acid in renal epithelial cells.

Perchloric acid extracts of LLC-PK1/Cl4 cells, a renal epithelial cell line, incubated with either [2-13C]glycine L-[3-13C]alanine, or D,L-[3-13C]aspartic acid were investigated by 13C-NMR spectroscopy. All amino acids, except labelled glycine, gave rise to glycolytic products and tricarboxylic acid cycle (TCA) intermediates. For the first time we also observed activity of gamma-glutamyltransferase activity and glutathione synthetase activity in LLC-PK1 cells, as is evident from enrichment of reduced glutathione. Time courses showed that only 6% of the labelled glycine was utilized in 30 min, whereas 31% of L-alanine and 60% of L-aspartic acid was utilized during the same period. 13C-NMR was also shown to be a useful tool for the determination of amino acid uptake in LLC-PK1 cells. These uptake experiments indicated that glycine, alanine and aspartic acid are transported into Cl4 cells via a sodium-dependent process. From the relative enrichment of the glutamate carbons, we calculated the activity of pyruvate dehydrogenase to be about 61% when labelled L-alanine was the only carbon source for LLC-PK1/Cl4 cells. Experiments with labelled D,L-aspartic, however, showed that about 40% of C-3-enriched oxaloacetate (arising from a de-amination of aspartic acid) reached the pyruvate pool.

Alanine↗
PubMed1988

31P FLASH NMR imaging.

A method of 31P FLASH NMR imaging is described using a low flip angle excitation pulse and three-dimensional Fourier transform spectroscopic imaging (3DFT). In vivo high-resolution 31P NMR spectra are obtained for each of 32 x 32 image elements using a minimum measuring time of 1.5 min. 31P FLASH images of a rat showing the spatial distribution of phosphocreatine, alpha-, beta-, and gamma-ATP have been measured in a 4.7-T magnet with a spatial resolution of 6 mm.

Adenosine Triphosphate↗
PubMed1988

Cerebrospinal fluid: detection of tumors and disk herniations with MR spectroscopy.

Cerebrospinal fluid (CSF) samples from 84 patients with confirmed or suspected diseases of the central nervous system were studied with hydrogen-1 magnetic resonance (MR) spectroscopy. In 19 of the patients, clinical chemical tests of the CSF indicated normal protein contents and normal quantities of cells; these samples were used as controls. Preliminary results indicate that tumors may be reflected in the MR spectra of CSF; disk herniations could not be distinguished on the basis of the MR spectral characteristics.

Brain Neoplasms↗
PubMed1987

Sodium binding to and protonation of ATP: a multinuclear magnetic double resonance study at 8.46 tesla.

We show that the interaction of ATP with Na+ and H+, whether binding or dissociation, gives rise to exchange broadened 31P-NMR spectra at 8.4 T, pH 6.7 and 310 K. We interpret the effect as being due to a two-step conversion between two NMR-differentiated ATP pools. A quantitative analysis yields all involved equilibrium constants and some of the dynamic parameters. Our results help to understand previous studies of magnesium binding to ATP and the appearance of high-field in vivo 31P-NMR spectra.

Adenosine Triphosphate↗