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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/G wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i)(MRS) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pHi. For each tumour type, pHMRS was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An assessment of 31P MRS as a method of measuring pH in rat tumours. 148 71

The changes in hepatic energy state were assessed by 31P-nuclear magnetic resonance spectroscopy (31P-MRS) and arterial ketone body ratio (AKBR) in brain dead dogs. 31P-MRS and AKBR were measured before and at 3 hours after brain death. Wiggers' shock model was employed to compare the energy metabolism during hypotension. 1) The brain death model: Systemic blood pressure changed from 178.3/115.0 mmHg (mean) in the control period, to 259.5/162.5 mmHg during Cushing phenomenon (CU period) and to 63.3/51.7 mmHg after completion of brain death (BD period). beta-ATP/Pi increased from 1.27 +/- 0.14 (mean +/- SEM) to 1.46 +/- 0.16 in the early CU period, and then decreased to 1.11 +/- 0.15 at 60 minutes after BD, followed by a gradual increase to 1.33 +/- 0.13 at 3 hours after BD. Intracellular pH (pHi) increased alkaline to the control value. AKBR decreased from 1.10 +/- 0.26 to 0.46 +/- 0.15 in the CU period (p less than 0.05) and then increased to 1.48 +/- 0.25 after BD. 2) Wiggers' shock model: Systemic blood pressure was 190.0/112.5 mmHg in the control period, 83.8/51.3 mmHg during exsanguination (EX period) and 185.0/117.0 mmHg after retransfusion (RT period). beta-ATP/Pi decreased from 1.17 +/- 0.13 to 0.61 +/- 0.10 in the EX period (p less than 0.05) and increased to 1.37 +/- 0.08 in the RT period. The pHi deviated from 7.33 +/- 0.07 to 6.82 +/- 0.14 in the EX period (p less than 0.01) and to 7.51 +/- 0.21 in the RT period. AKBR decreased from 1.00 +/- 0.11 to 0.21 +/- 0.04 in the EX period and increased to 1.08 +/- 0.12 in the RT period. The energy metabolism of the liver was well maintained in the state of brain death in spite of remarkable hypotension, although that was not the case with Wiggers' shock model. It was suggested that the combination of 31P-MRS and AKBR was useful for the evaluation of graft liver viability.
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PMID:Energy metabolism of the liver in brain dead dogs assessed by 31P-NMR spectroscopy and arterial ketone body ratio. 186 70

The relationship between regional oxidative and total rCMRglc in five healthy volunteers in activated and non-activated areas of the brain has been investigated with positron emission tomography (PET). The tracers [1-11C]-D-glucose and [2-18F]2-fluoro-2-deoxy-D-glucose were used. A previous study has shown that the former may be used to measure the rate of glucose oxidation while the latter tracer is used to measure the total rate of glucose consumption. Regional activation was performed (voluntary finger movements). Use of a computerized brain atlas enabled comparison between the regional oxidative and total rCMRglc in each volume element of the brain for the group of subjects. The values of total and oxidative rCMRglc, when calculated for each volume element of the brain and displayed in a scatter plot, were found to be symmetrically grouped around a straight line which passes close to the origin. The slope of this line varied between the subjects. This indicates that, on the average, the fraction of non-oxidative glucose utilization is constant within each subject, regardless of the value of rCMRglc and, further, that the fraction of non-oxidative glucose utilization varies between subjects. The total and oxidative CMRglc in the activated left hand area were 23.4 +/- 0.9% (mean +/- SEM) and 11.7 +/- 0.3%, respectively, higher than in the contralateral homologous non-activated area. Our interpretation of the difference is that regional activation increases the fraction of non-oxidative glucose consumption. This interpretation is supported by a previous PET study using [15O]O2, and by studies using MRS technique.
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PMID:Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography. 804 34

We evaluated the use of hyperglycaemia to reduce tumour pH in dog with spontaneous tumours. Dogs were randomized to two groups: control and glucose. Intravenous administration of 20% glucose was used to induce and maintain hyperglycaemia. Extra- and intracellular tumour pH were measured using interstitial pH microelectrodes and 31P-MRS, respectively. During the administration of glucose, the mean (+/- SEM) blood glucose concentration was 419.8 (+/- 32.8) and 121.1 (+/- 8.0) mg/dl for the glucose and control groups, respectively. The mean extracellular tumour pH before and following 90 min of hyperglycaemia was 7.15 (+/- 0.08) and 7.15 (+/- 0.09). During consecutive measurements, intracellular tumour pH did not change significantly for the control group or the group subjected to hyperglycaemic manipulation. In contradistinction to previous rodent studies, our results demonstrate that hyperglycaemia alone is not sufficient to manipulate either intra- (pHi) or extracellular (pHe) hydrogen ion concentration in spontaneous canine soft tissue tumours.
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PMID:Manipulation of intra- and extracellular pH in spontaneous canine tumours by use of hyperglycaemia. 824 84

1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd-DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n = 17), mammary carcinoma (n = 24), melanoma (n = 12) and those originating from other tumors (n = 13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE = 135 ms. Apart from trends toward reduced signals of choline-containing compounds (Cho) and reduced post-Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post-Gd MRI enhancement (33 +/- 5%, means +/- SEM; n = 24) and elevated Cho signals compared with normal contralateral brain tissue (70 +/- 5% of contralateral N-acetyl aspartate signal; p < 0.001). The other metastases showed either unambiguous lipid signals (n = 30) or MRS detectable Lact (n = 12) and were heterogeneous on MRI with divergent signals of Gd-enhancement (49 +/- 5% vs 14 +/- 8%, p < 0.001) and Cho (88 +/- 10 vs 47 +/- 8% of contralateral NAA; p = 0.02). Those with Lact were significantly larger compared with both other groups (p < 0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).
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PMID:1H MR spectroscopy detection of lipids and lactate in metastatic brain tumors. 888 70

We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x 20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients with both upper and lower motor neuron signs had a significantly decreased concentration of NAA (9.13 +/- 0.28 mM, mean +/- SEM) in the primary motor cortex when compared with healthy controls (10.03 +/- 0.22 mM). In conclusion, the slightly decreased concentration of NAA in the primary motor cortex from ALS patients may represent a loss of neurons in this region.
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PMID:Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. 948 13

19F-MRS (magnetic resonance spectroscopy) was used to study the pharmacokinetics of 5-fluorouracil (5-FU) in human (HT29) tumour xenografts, with and without pretreatment of the mice using either thymidine (40 min) or interferon-alpha (2 and 24 h). A 200 mg/kg i.p. bolus dose of 5-FU was eliminated from control tumours with a t1/2 of 25.4 +/- 2 min (mean +/- SEM, n = 11), while both thymidine (500 mg/kg) and interferon (50,000 IU/mouse) significantly increased t1/2 to 36.5 +/- 6.1 (n = 5) and 48.1 +/- 13.6 min (n = 4), respectively (P = 0.04, Gabriel's ANOVA). Thymidine increased 5-FU anabolism to cytotoxic 5-fluoronucleotides, and decreased the amount of tumour catabolites; the latter probably recirculated from liver since isolated HT29 cells did not catabolize 5-FU. These in vivo observations were confirmed by 19F-MRS quantification of tumour extracts. Interferon did not significantly affect 5-FU metabolism in the tumour or liver, nor the 5-FU t1/2 in liver. Treatment of tumours with 5-FU or interferon had no effect on tumour growth, whereas the combination strongly inhibited growth. 31P-MRS of HT29 tumours showed that 2 and 24 h after i.p. injections of interferon there was a significant increase in the pHint of 0.3 +/- 0.04 units (P = 0.002), while pHext and the tumour NTP/Pi ratio were unchanged. The large increase in the negative pH gradient (-delta pH) across the tumour plasma membrane caused by interferon suggest the delta pH may be a factor in tumour retention of 5-FU, as recently shown in isolated tumour cells.
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PMID:A pharmacokinetic and pharmacodynamic study in vivo of human HT29 tumours using 19F and 31P magnetic resonance spectroscopy. 961 92

We developed a two-compartment pharmacokinetic model to systematically characterize 19F magnetic resonance spectroscopy (19F MRS) data on the concentration time course of psychotropic compounds measured in human brain. Using this model, brain volume of distribution and clearance were calculated for fluvoxamine as an index compound. Our interest in formalizing a multicompartment model was motivated by recent advances in the field of brain spectroscopy that allow the noninvasive characterization of brain uptake and elimination half-lives of fluorinated psychotropic compounds. Differences between central compartment single-dose and steady-state half-lives and the peripheral elimination half-life at steady state were used to formulate the model. Application of the model is illustrated using previously published data on the elimination half-lives of fluvoxamine from plasma and brain at steady state, along with the literature values for single-dose plasma elimination half-life. Applying the model, brain volume of distribution (1.12 L/kg +/- 0.2 SEM) and clearance (1.01 L/hour +/- 0.12 SEM) were calculated for fluvoxamine. The bioavailability of fluvoxamine to the brain from plasma was 1.85 +/- 0.23 SEM. The underlying multicompartment pharmacokinetics of fluvoxamine were reflected by the difference between brain and plasma elimination half-lives from steady state. This method to derive pharmacokinetic parameters using 19F MRS measurements of drug concentration in brain can be applied to characterize the pharmacokinetics of other fluorinated psychotropic compounds.
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PMID:Characterization of human brain pharmacokinetics using a two-compartment model. 1034 45

Time-resolved 31-phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) of the biceps femoris muscles was performed during exercise and recovery in six healthy sedentary male subjects (maximal oxygen uptake; 46.6 +/- 1.7 (SEM) ml.kg-1.min-1), 5 male sprinters (56.2 +/- 2.5), and 5 male long-distance runners (73.6 +/- 2.2). Each performed 4 min of knee flexion exercises at absolute values of 1.63 W and 4.90 W, followed by 5 min of recovery in a prone position in a 2.1 T superconducting magnet with a 67 cm bore. 31P-MRS spectra were recorded every 12.8 s during the rest-exercise-recovery sequence. Computer-aided contour analysis and pixel imaging of phosphocreatine peaks (PCr) and inorganic phosphate (Pi) were performed. The work loads in the present study were selected as mild exercise (1.63 W) and heavy exercise (4.90 W), corresponding to 18-23% and 54-70% of maximal exercise intensity. Long-distance runners showed a significantly smaller decrement in PCr and less acidification at a given exercise intensity compared to those shown by sedentary subjects. The transient responses of PCr and Pi during recovery were characterized by first-order kinetics. After exercise, the recovery rates of PCr and Pi were significantly faster in long-distance runners than in sedentary subjects (P < 0.05). Since it is postulated that PCr resynthesis is controlled by aerobic metabolism and mitochondrial creatine kinase, it is suggested that the faster PCr and Pi recovery rates and decreased acidification seen in long-distance runners during and after exercise might be attributed to their greater capacity for aerobic metabolism.
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PMID:The rate of phosphocreatine hydrolysis and resynthesis in exercising muscle in humans using 31P-MRS. 1249 22

Previously, magnetic resonance spectroscopy studies of alterations in cerebral metabolite concentration during functional activation have been focused on phosphocreatine using 31P MRS and lactate using 1H MRS with controversial results. Recently, significant improvements on the spectral resolution and sensitivity of in vivo spectroscopy have been made at ultrahigh magnetic field strength. Using highly resolved localized short-TE 1H MRS at 11.7 T, we report metabolic responses of rat somatosensory cortex to forepaw stimulation in alpha-chloralose-anesthetized rats. The phosphocreatine/creatine ratio was found to be significantly decreased by 15.1 +/- 4.6% (mean +/- SEM, P < 0.01). Lactate remained very low (approximately <0.3 micromol/g w/w) with no statistically significant changes observed during forepaw stimulation at a temporal resolution of 10.7 min. An increase in glutamine and a decrease in glutamate and myo-inositol were also detected in the stimulated state. Our results suggest that, under the experimental conditions used in this study, increased energy consumption due to focal activation causes a shift in the creatine kinase reaction towards the direction of adenosine triphosphate production. At the same time, metabolic matching prevails during increased energy consumption with no significant increase in the glycolytic product lactate in the focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats.
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PMID:Metabolic alterations in focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats measured by 1H MRS at 11.7 T. 1618 71


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