Biomedical subjects

K Nicolay

Publications and source records attributed to K Nicolay.

At least 55 records · Page 3Linked to original sources

PubMed2000

In vivo (31)P-NMR diffusion spectroscopy of ATP and phosphocreatine in rat skeletal muscle.

The aim of this study was to measure the diffusion of ATP and phosphocreatine (PCr) in intact rat skeletal muscle, using (31)P-NMR. The acquisition of the diffusion-sensitized spectra was optimized in terms of the signal-to-noise ratio for ATP by using a frequency-selective stimulated echo sequence in combination with adiabatic radio-frequency pulses and surface coil signal excitation and reception. Diffusion restriction was studied by measuring the apparent diffusion coefficients of ATP and PCr as a function of the diffusion time. Orientation effects were eliminated by determining the trace of the diffusion tensor. The data were fitted to a cylindrical restriction model to estimate the unbounded diffusion coefficient and the radial dimensions of the restricting compartment. The unbounded diffusion coefficients of ATP and PCr were approximately 90% of their in vitro values at 37 degrees C. The diameters of the cylindrical restriction compartment were approximately 16 and approximately 22 microm for ATP and PCr, respectively. The diameters of rat skeletal muscle fibers are known to range from 60 to 80 microm. The modelling therefore suggests that the in vivo restriction of ATP and PCr diffusion is not imposed by the sarcolemma but by other, intracellular structures with an overall cylindrical orientation.

Adenosine Triphosphate↗

PubMed2000

NMR spectroscopic evaluation of cerebral metabolism in hydrocephalus: a review.

Cerebral ischemia contributes to cerebral damage in hydrocephalus. Many studies have reported changes in cerebral blood flow and metabolism, supporting this hypothesis. Magnetic resonance spectroscopy (MRS) enables us to investigate cerebral metabolism in a non-invasive and longitudinal manner, thereby providing a promising way of evaluating pathophysiological changes in experimental and clinical hydrocephalus. In this review, the potential of 1H (proton) and 31P (phosphorus) MRS in the assessment of cerebral metabolism will be summarized, and a synopsis of in vitro and in vivo MRS studies in experimental and human hydrocephalus will be presented. Changes in high-energy phosphate metabolism, intracellular pH and lactate production in several MRS studies are presumed to reflect cerebral ischemia. In vivo information on neuronal damage, maturational delay and membrane phospholipid metabolism may also be derived from 1H and 31P MRS data. Technical, methodological and pathophysiological considerations, which are important for a correct interpretation and comparison of different MRS studies, will be discussed. Finally, we will draw some conclusions on the significance of these MRS findings and the applicability of MRS in the diagnosis and evaluation of clinical hydrocephalus.

Animals↗

PubMed1999

Correlation between tissue depolarizations and damage in focal ischemic rat brain.

Ischemia-induced depolarizations may play a key role in the development of cerebral ischemic injury. Our goal was to assess the relationship between tissue depolarizations and tissue damage in focal ischemia. We performed multi-electrode cortical direct current (DC) potential recording and, subsequently, diffusion-weighted and T(2)-weighted magnetic resonance imaging (MRI) in rats after i) cortical application of KCl, and ii) permanent and transient middle cerebral artery (MCA)-occlusion in rats. Cortical KCl application induced 10.0+/-2.2 transient negative DC potential shifts per h on the ipsilateral hemisphere (i.e. cortical spreading depressions) (n=4). During 6 h of permanent MCA-occlusion (n=9) 1-10 DC potential shifts were observed, dependent on the brain location. Anoxic depolarization developed in the ischemic core. Outside ischemic areas DC potential shifts resembled cortical spreading depressions. Depolarizations in cortical ischemic borderzones were also transient, but generally long-lasting. Reperfusion induced 1 (n=5) or 3 h (n=6) after MCA-occlusion resulted in repolarization in 2.9+/-1.5 min. Ischemic lesion volumes after 7 h, calculated from diffusion-weighted and T(2)-weighted MR images, correlated significantly with total depolarization time in cortical perifocal zones (R=0.741, p<0.05), but not with the number of depolarizations. The extent of ischemic damage, as measured from alterations in the water diffusion coefficient and T(2), was also significantly related to the total time of depolarization (R=0.762 and 0.738, respectively, p<0.01). We conclude that early ischemic tissue injury is related to the total duration of tissue depolarization and not to the frequency of depolarizations.

Animals↗

PubMed1999

Off-resonance metabolite magnetization transfer measurements on rat brain in situ.

Off-resonance metabolite magnetization transfer (MT) experiments were performed on rat brain in vivo and post mortem, with short (18 msec) and long (144 msec) echo-time 1H nuclear magnetic resonance (NMR) spectroscopy. In vivo and post mortem, the methyl protons of total creatine and all protons from glutamate/glutamine showed a strong MT effect on off-resonance saturation, as well as the methyl protons from lactate post mortem. Other resonances, like that of A-acetyl aspartate, showed a much smaller, but detectable, MT effect. The results obtained were confirmed by combining off-resonance saturation with two-dimensional correlation spectroscopy. Three water suppression techniques, i.e., presaturation, chemical shift-selective (CHESS), and selective water eliminated Fourier transform (WEFT) were evaluated for their ability to generate an MT effect, to assess their possible influence on metabolite quantification. Presaturation and selective WEFT led to alterations of the total creatine, lactate, and N-acetyl aspartate resonance intensities, while CHESS had no effect. Finally, it was shown that water protons play an important role in the generation of the observed metabolite MT effects.

Animals↗

PubMed1999

Global HDO uptake in human glioma xenografts is related to the perfused capillary distribution.

The aim of this study is to evaluate the existence of a possible relationship between global deuterium-labeled water (HDO) uptake rates and the diffusion geometry of human glioma xenografts in nude mice. HDO diffusion times in the whole extravascular tumor volume were estimated by combining quantitative (1)H-MR diffusion imaging and morphometric analysis of intercapillary distances in two tumor lines with a different perfused vascular architecture. HDO uptake was measured independently using (2)H-magnetic resonance spectroscopy. Time constants of HDO-uptake curves (tau) were compared to estimations of maximum HDO diffusion times (t(difmax)). Tumors with a homogeneously perfused capillary distribution showed a mono-exponential HDO uptake. The t(difmax) was comparable to tau values of HDO uptake curves: t(difmax) varied between 74 and 368 sec and the range of tau values was 115-370 sec. Heterogeneously perfused tumors had a bi-exponential HDO uptake with t(difmax) in between the tau values of the fast and slow uptake phase. These findings indicate that the global HDO uptake is related to the perfused capillary distribution in human glioma xenografts. That HDO uptake rates indeed can depend on the perfused capillary distribution was substantiated in experiments with two-dimensional (2D) models. In these models with a diffusion-limited HDO uptake, HDO uptake curves could be approximated by curves derived from 2D HDO diffusion simulations. Magn Reson Med 42:479-489, 1999.

Animals↗

PubMed1999

Effect of carbogen breathing on the physiological profile of human glioma xenografts.

The aim of this study was to evaluate the effect of carbogen breathing on the physiological profile of human glioma xenografts. Near infrared spectroscopy was used to investigate changes in oxy- and deoxyhemoglobin concentrations in tumor blood. Oxygen tension changes in tumor tissue were evaluated by (19)F-MR relaxometry, using perfluoro-15-crown-5-ether, and modifications of tumor blood perfusion (TBP) were analyzed by fast dynamic (1)H-MR imaging of Gd-DTPA uptake. Finally, changes of the bioenergetic status and pH of tumor cells were analyzed by (31)P-MRS. After 5 to 8 min of carbogen breathing, the average oxygen tension increase in tumor tissue was 4.6 +/- 1.3 mm Hg, which is in agreement with an increase of the oxyhemoglobin concentration in tumor blood (Delta[O(2)Hb] = 9. 2 +/- 3 microM). However, simultaneously the TBP was reduced, the bioenergetic status was diminished, and pH was decreased. As 100% O(2) breathing alone did not result in a detectable increase of oxyhemoglobin in tumor blood, the increase of the tumor oxygenation by carbogen appears to be mediated by its CO(2) content. This component may cause a nutrient-limited decrease of oxidative energy metabolism, indirectly via a steal-effect and/or by inhibition of the glycolytic rate resulting from tissue acidification. Magn Reson Med 42:490-499, 1999.

Animals↗

PubMed1999

Magnetic coupling of creatine/phosphocreatine protons in rat skeletal muscle, as studied by (1)H-magnetization transfer MRS.

Off-resonance saturation caused a reduction of the 3.04 ppm NMR signal from the methyl protons of creatine in rat hindleg skeletal muscle. (1)H-NMR spectra were recorded over a 200 kHz range of off-resonance saturation frequencies. The span of frequencies over which the creatine signal was reduced greatly exceeded that expected for direct saturation by the off-resonance RF-field. This suggests that there is a motionally restricted proton pool which exchanges magnetization with the free creatine pool. The experimental data were fitted to characterize the immobilized proton pool and the exchange kinetics, using a two-pool exchange model. The immobile pool was estimated to amount to ca. 2.5% of the mobile pool of free creatine, while the rate of exchange between the mobile and immobile configurations is ca. 2.3 sec(-1). After depletion of phosphocreatine by termination of the animal, the MT effect on the creatine methyl protons remained unchanged. This indicates that phosphocreatine and creatine both contribute to the MT phenomenon. Selective saturation of the mobile water pool also led to a reduction in the intensity of the total creatine methyl signal, suggesting that water and creatine are magnetically coupled via a macromolecular interface. The precise mechanism responsible for and the biological significance of the pronounced creatine magnetization transfer effect in rat skeletal muscle remains to be established. Magn Reson Med 42:665-672, 1999.

Animals↗

PubMed1999

MRI-based quantification of cerebral edema in individual SHRSP rats using averaged criteria determined before the occurrence of edema.

This study evaluated whether it is possible with T2-weighted MRI to quantitatively relate image-outcome in a single, individual case with that of a standardized control group that did not show these pathologies. An animal model of hypertension-related cerebral damage, the salt-loaded, stroke-prone spontaneously hypertensive rat (SHRSP), was applied. Very similar values for cerebral edema were found when using either the individual or the averaged threshold. The values were positively correlated with each, as edema(averaged threshold) = 0.12 + 0.99 x edema(individual threshold) (Pearsons coefficient = 0.99, p < 0.0001). This line was virtually congruent with the line of identity. Thus, by determination of the averaged threshold in the healthy salt-loaded SHRSP, a parameter was obtained to calculate cerebral edema with the specifically used T2-weighted MRI protocol, in any rat.

Animals↗

PubMed1999

Diffusion tensor imaging in biomechanical studies of skeletal muscle function.

In numerical simulations of skeletal muscle contractions, geometric information is of major importance. The aim of the present study was to determine whether the diffusion tensor imaging (DTI) technique is suitable to obtain valid input with regard to skeletal muscle fibre direction. The accuracy of the DTI method was therefore studied by comparison of DTI fibre directions in the rat tibialis anterior muscle with fascicle striation patterns visible on high-resolution magnetic resonance imaging (MRI) and with fibre directions in an actual longitudinal section (ALS) through the same muscle. The results showed an excellent qualitative agreement between high-resolution MRI and DTI. Despite less accurate quantitative comparison with ALS, it was concluded that DTI does indeed measure skeletal muscle fibre direction. After the experiment, it was possible to determine an appropriate voxel size (0.9 mm3) that provided enough resolution and acceptable accuracy (5 degrees) to use DTI fibre directions in biomechanical analyses. Muscle deformation during contraction, resulting from a finite element simulation with a mesh that was directly generated from the experimental data, has been presented.

Animals↗

PubMed1999

Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain.

The reduction of the apparent diffusion coefficient (ADC) of brain tissue water in acute cerebral ischemia, as measured by diffusion-weighted magnetic resonance imaging, is generally associated with the development of cytotoxic edema. However, the underlying mechanism is still unknown. Our aim was to elucidate diffusion changes in the intracellular environment in cytotoxic edematous tissue. The ADC of intracellular metabolites was measured by use of diffusion-weighted 1H-magnetic resonance spectroscopy after (1) unilateral N-methyl-D-aspartate (NMDA) injection and (2) cardiac arrest-induced global ischemia in neonatal rat brain. The distinct water ADC drop early after global ischemia was accompanied by a significant reduction of the ADC of all measured metabolites (P < 0.01, n = 8). In the first hours after excitotoxic injury, the ADC of water and the metabolites taurine and N-acetylaspartate dropped significantly (P < 0.05, n = 8). At 24 and 72 hours after NMDA injection brain metabolite levels were diminished and metabolite ADC approached contralateral values. Administration of the NMDA-antagonist MK-801 1.5 hours after NMDA injection completely normalized the water ADC but not the metabolite ADC after 1 to 2 hours (n = 8). No damage was detected 72 hours later and, water and metabolite ADC had normal values (n = 8). The contribution of brain temperature changes (calculated from the chemical shift between the water and N-acetylaspartate signals) and tissue deoxygenation to ischemia-induced intracellular ADC changes was minor. These data lend support to previous suggestions that the ischemia-induced brain water ADC drop may partly be caused by reduced diffusional displacement of intracellular water, possibly involving early alterations in intracellular tortuosity, cytoplasmic streaming, or intracellular molecular interactions.

Animals↗

PubMed1999

Spatial assessment of the dynamics of lactate formation in focal ischemic rat brain.

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

Animals↗

PubMed1999

Phosphorylation state of red and white muscle in tilapia during graded hypoxia: an in vivo (31)P-NMR study.

The aim of this study was to measure the energetic consequences of hypoxia in different types of skeletal muscle within a single tilapia species (n = 5). To that aim, 81.0 MHz (31)P-nuclear magnetic resonance (NMR) spectra were collected, alternately, from three surface coils placed adjacent to the tissues of interest (dorsal white muscle, ventral white muscle, and lateral red muscle) during a graded hypoxia load over 6 h followed by a 5-h recovery period. The fish were contained in a flow cell, enabling us full control of the oxygen content of the bathing medium. The intracellular pH and the concentrations of ATP, phosphocreatine (PCr), and P(i) were determined from the NMR spectra. For normoxia, biochemical differences for [gamma-ATP], [PCr], and [sugar phosphates] (SP) were observed between all three locations, especially between the red and white muscle. During hypoxia stress, loss of phosphorylated compounds (PCr+P(i)+SP) was observed at all locations but was the most severe in red muscle. When the aerobic (respirometry) and anaerobic ((31)P-NMR) ATP production via an energy balance are compared, flexible metabolic depression is demonstrated during anaerobioses. It is concluded that control of the aerobic and anaerobic component of metabolism during metabolic depression is independent of each other.

Adenosine Triphosphate↗

PubMed1999

Early-onset but not late-onset endothelin-A-receptor blockade can modulate hypertension, cerebral edema, and proteinuria in stroke-prone hypertensive rats.

-The ability of endothelin receptor blockade to prevent and to treat established cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist A127722. SHRSP were subjected to 1% NaCl intake. The start of treatment with A127722 (35 and 70 mg. kg-1. d-1, respectively) was either synchronized with salt loading or initiated after the first observation of cerebral edema with T2-weighted magnetic resonance imaging. In untreated control animals median survival was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset A127722 treatment increased median survival to 233 days (range, 92 to 407 days; P<0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days; P<0.05 versus control) with 70 mg/kg. The development of cerebral edema was prevented, and systolic blood pressure and proteinuria were dose-dependently reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages in the basal ganglia shortly before death. Late-onset A127722 treatment failed to affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral edema was reduced but not as well as in early-onset treatment. Development of hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722 treatment was initiated at the start of salt-loading. However, A127722 treatment did not prolong survival in SHRSP with cerebral edema. This suggests that in SHRSP the endothelin A receptor participates actively in the development of increased blood pressure and initiation of organ damage but participates minimally in established malignant hypertension and progression of target-organ damage.

Animals↗

PubMed1999

Effects of hypoxia-ischemia and inhibition of nitric oxide synthase on cerebral energy metabolism in newborn piglets.

The present study was designed to examine the effects of inhibition of nitric oxide synthase on cerebral energy metabolism after hypoxia-ischemia in newborn piglets. Ten 1- to 3-d-old piglets received N(omega)-nitro-L-arginine (NNLA), an inhibitor of nitric oxide synthase (NNLA-hypoxia, n = 5), or normal saline (hypoxia, n = 5) 1 h before cerebral hypoxia-ischemia. After the infusion, hypoxia-ischemia was induced by bilateral occlusion of the carotid arteries and decreasing FiO2 to 0.07 and maintained for 60 min. Thereafter, animals were resuscitated and ventilated for another 3 h. Using 1H- and 31P-magnetic resonance spectroscopy, cerebral energy metabolism was measured in vivo at 15-min intervals throughout the experiment. Phosphocreatine to inorganic phosphate ratios decreased from 2.74 +/- 0.14 to 0.74 +/- 0.36 (hypoxia group) and 2.32 +/- 0.17 to 0.18 +/- 0.10 (NNLA-hypoxia group) during hypoxia-ischemia. Thereafter, phosphocreatine to inorganic phosphate ratios returned rapidly to baseline values in the hypoxia group, but remained below baseline values in the NNLA-hypoxia group. Intracellular pH decreased during hypoxia-ischemia and returned to baseline values on reperfusion in both groups. Intracellular pH values were lower in the NNLA-hypoxia group (p < 0.001, ANOVA). Lactate was not present during the baseline period. After hypoxia-ischemia, lactate to N-acetylaspartate ratios increased to 1.34 +/- 0.28 (hypoxia group) and 2.22 +/- 0.46 (NNLA-hypoxia group). Lactate had disappeared after 3 h of reperfusion in the hypoxia group, whereas lactate to N-acetylaspartate ratios were 1.37 +/- 1.37 in the NNLA-hypoxia group. ANOVA demonstrated a significant effect of NNLA on lactate to N-acetylaspartate ratios (p < 0.001). Inhibition of nitric oxide synthase by NNLA tended to compromise cerebral energy status during and after cerebral hypoxia-ischemia in newborn piglets.

Animals↗

PubMed1999

Cerebral metabolism in experimental hydrocephalus: an in vivo 1H and 31P magnetic resonance spectroscopy study.

OBJECT: Brain damage in patients with hydrocephalus is caused by mechanical forces and cerebral ischemia. The severity and localization of impaired cerebral blood flow and metabolism are still largely unknown. Magnetic resonance (MR) spectroscopy offers the opportunity to investigate cerebral energy metabolism and neuronal damage noninvasively and longitudinally. Previous 1H MR spectroscopy studies have shown an increased lactate resonance that is suggestive of anaerobic glycolysis. The aim of this study was to assess cerebral damage and energy metabolism in kaolin-induced hydrocephalus in adult rats by using in vivo 1H and 31P MR spectroscopy. The presence of lactate was correlated with high-energy phosphate metabolism and intracellular pH. The measurement of relative concentrations of N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) served to assess neuronal damage. METHODS: Hydrocephalus was induced in adult rats by surgical injection of kaolin into the cisterna magna. Magnetic resonance studies, using a 4.7-tesla magnet, were performed longitudinally in hydrocephalic animals at 1 (10 rats), 8 (six rats), and 16 weeks (six rats) thereafter, as well as in eight control animals. To evaluate ventricular size and white matter edema T2-weighted MR imaging was performed. The 1H MR spectra were acquired from a 240-microl voxel, positioned centrally in the brain, followed by localized 31P MR spectroscopy on a two-dimensional column that contained the entire brain but virtually no extracranial muscles. The 1H and 31P MR spectroscopy peak ratios were calculated after fitting the spectra in the time domain, intracellular pH was estimated from the inorganic phosphate (Pi) chemical shift, and T2 relaxation times of 1H metabolites were determined from the signal decay at increasing echo times. CONCLUSIONS: In hydrocephalic rats, ventricular expansion stabilized after 8 weeks. White matter edema was most pronounced during acute hydrocephalus. Lactate peaks were increased at all time points, without a decrease in phosphocreatine (PCr)/Pi and PCr/adenosine triphosphate (ATP) peak ratios, or pH. Possibly lactate production is restricted to periventricular brain tissue, followed by its accumulation in cerebrospinal fluid, which is supported by the long lactate T2 relaxation time. Alternatively, lactate production may precede impairment of ATP homeostasis. The NAA/Cho and tCr/Cho ratios significantly decreased during the acute and chronic stages of hydrocephalus. These changes were not caused by alterations in metabolite T2 relaxation time. The decreases in the NAA/Cho and tCr/Cho ratios implicate neuronal loss/dysfunction or changes in membrane phospholipid metabolism, as in myelin damage or gliosis. It is suggested that 1H MR spectroscopy can be of additional value in the assessment of energy metabolism and cerebral damage in clinical hydrocephalus.

Animals↗

PubMed1998

Suppression of cortical spreading depressions after magnesium treatment in the rat.

The aim of this study was to investigate whether the neuroprotective properties of magnesium in cerebral ischaemia involve suppression of repetitive tissue depolarizations. Cortical spreading depressions (CSDs), evoked by cortical KCl application, and cardiac arrest-induced anoxic depolarization (AD) were measured by extracellular DC recording on intact rat brain. At 90 min after onset of CSDs saline, MK-801 (3 mg/kg) or MgSO4 (90 mg/kg) was given i.v. Latency time to AD was measured after 4 h. The frequency of CSDs was significantly reduced in animals treated with MgSO4 or MK-801. AD was significantly delayed by MgSO4 but not by MK-801. Our results suggest that suppression of depolarization by magnesium may play a role in its neuroprotective properties in cerebral ischaemia.

Animals↗

PubMed1998

Dextran strongly increases the Michaelis constants of oxidative phosphorylation and of mitochondrial creatine kinase in heart mitochondria.

Macromolecules restore the morphological changes which occur upon isolation of mitochondria in normally used isolation media. It was shown that in the presence of dextrans the permeability of mitochondrial outer membrane for adenine nucleotides decreases which may have considerable implications for the transport of ADP into the mitochondria. In this study the effect of dextran on the apparent Michaelis constants of oxidative phosphorylation and mitochondrial creatine kinase (mi-CK) of rat heart mitochondria was investigated. Mitochondria were isolated either in normally used isolation media or in the additional presence of 15% dextran 20 in order to avoid changes in the oncotic conditions on the mitochondria during preparation and investigation. Except for an increased contamination with extramitochondrial ATPases the basic functional properties of these mitochondria were normal. With oxygraphic measurements it was found that Km(ADP) of oxidative phosphorylation increased from 16 +/- 4 microM ADP (without dextran) to 50 +/- 15 microM (15% dextran 20) and to 122 +/- 62 microM (25% dextran 20) irrespective of the mode of preparation of the mitochondria. Using spectrophotometric measurements the effect of dextran on the Km(ATP) of mi-CK was investigated in three systems (a) as soluble enzyme, (b) bound to mitoplasts, (c) and in intact rat heart mitochondria. The addition of 10% dextran had no effect on kinetic properties of solubilized mi-CK. In intact heart mitochondria, however, the addition of dextran caused an augmentation of Km(ATP) from 332 +/- 91 microM (control) to 525 +/- 150 microM ATP (10% dextran) and 641 +/- 160 microM ATP (30% dextran). In mitoplasts the effect of dextran disappeared (control, 230 +/- 19 microM ATP; 10% dextran, 238 +/- 28 microM ATP) indicating that the outer mitochondrial membrane is a prerequisite for the modulation of the transport of adenine nucleotides into the intermembrane space by macromolecules. To investigate the effects of viscosity of dextran solutions on the diffusion of adenine nucleotides across the outer membrane, dextrans with different molecular size (20, 40 70 and 500 kDa) were used. The viscosity of the 10% solutions drastically increased with the molecular size of the dextrans used, but the effects of different dextran solutions on the kinetic constants were the same. From these results it was concluded that neither the viscosity nor the molar concentration but the content of macromolecules (mass/vol.) correlates with restrictions of diffusion into the intermembrane space of mitochondria with intact outer membranes. Assuming that a dextran concentration of 15% mimicks the intracellular oncotic pressure on mitochondria in vivo, the apparent Km(ATP) of oxidative phosphorylation within the intact cell seems to be about 50 microM ADP which is somewhat higher than the cytoplasmic free ADP concentration as reported for the intact heart.

Adenine Nucleotides↗

PubMed1998

Adiabatic water suppression using frequency selective excitation.

A new method for B1-insensitive water suppression using adiabatic RF pulses is described. The transition zone of the inversion profile of adiabatic full passage (AFP) pulses is used for frequency-selective excitation followed by dephasing of the excited water with magnetic field gradients. Several improvements of AFP pulses, which also have implications for other applications, are described. The technique was evaluated by simulations based on the Bloch equations (including relaxation), in vitro experiments and an in vivo verification on neonatal and adult rat brain.

Animals↗