bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hypoglycemia on changes of brain lactic acid and intracellular pH produced by ischemia
Authors: Nagai Y. , Naruse S. , Weiner M. W. 
Published: March 2007

AbstractPrevious investigators have attributed the fall of brain intracellular pH (pHi) produced by ischemia to accumulation of lactic acid. The goal of the present experiments was to examine the hypothesis that the acidosis produced by cerebral ischemia is due to accumulation of lactic acid. The present experiments inhibited lactic acid production by lowering glucose availability using insulin‐induced hypoglycemia. The adverse effects of hypoglycemia were prevented by the prior elevation of β‐hydroxybutyric acid and acetoacetic acid induced by a high lipid diet. Brain pHi and lactic acid were measured by 31P and 1H NMR. The results showed that insulin‐induced hypoglycemia markedly inhibits production of lactic acid, but has no effect on brain pHi during ischemia. These findings suggest that, at least under some conditions, the acidosis produced by cerebral ischemia is not due to accumulation of lactic acid.
A 15N NMR study of in vivo cerebral glutamine synthesis in hyperammonemic rats
Authors: Kanamori Keiko , Parivar Farhad , Ross Brian D. 
Published: March 2007

AbstractRats were given intravenous 15NH4+ infusion at a rate of 2.2 or 5.5 mmol/h/kg body wt to induce hyperammonemia, as animal models of hepatic encephalopathy. Its effect on cerebral amino acid metabolism was studied in vivo by 15N NMR spectroscopy at 20.27 MHz for 15N. Cerebral [γ‐15N]glutamine (present at a tissue concentration of 4–9 μmol/g) and [α‐15N]glutamate/glutamine (6 μmol/g) were clearly observed in living rats within 9‐18 min. In portacaval‐shunted rats, final cerebral [γ‐15N]glutamine concentrations were higher than those in controls after the same infusion period, presumably because decreased 15NH removal in the liver led to increased 15NH3 diffusion into the astrocytes. In control rats, cerebral [γ‐15N]glutamine pool increased at a rate of 1.7 μmol/h/g when blood ammonia concentration was 0.8 mM. 15N enrichment in γ‐15N was 71%. From these observations, in vivo activity of glutamine synthetase in rat brain was estimated to be 3.5 μmol/h/g. Comparison with reported optimum in vitro activity suggests that in situ concentrations of some substrates and cofactors limit the activity of glutamine synthetase in vivo.
Relaxation times and concentrations of 7Li in the brain of patients receiving Lithium therapy
Authors: Kushnir T. , Itzchak Y. , Valevski A. , Lask M. , Modai I. , Navon G. 
Published: March 2007

AbstractThe present study describes a protocol for the determination of in vivo absolute molar concentrations of Li+ in the human brain using a double tuned 1H/7Li surface coil. The protocol follows the method of Thulborn and Ackerman [J. Mag. Reson. 55, 357–371 (1983)] where the ratio of the signal intensities of 7Li and 1H in the brain is compared to the same ratio in a phantom containing known concentrations of Li+. The 7Li T1 values in the brains of five patients receiving lithium therapy were measured. The average result was T1 = 3.5±0.25s. The phantom solution was adjusted to have this T1 value. The protocol was applied for eight bipolar patients receiving lithium therapy. The average ratio of brain to serum lithium molar concentration was found to be 0.59±0.12.
An assessment of artefacts in localized and non‐localized 31P MRS studies of phosphate metabolites and pH in rat tumours
Authors: Howe F. A. , Stubbs M. , Rodrigues L. M. , Griffiths J. R. 
Published: March 2007

AbstractUA hepatomas, GH3 prolactinomas and N‐methyl‐N‐nitrosourea‐induced mammary tumours, which were subcutaneously grown in rats, have been studied by 31P MRS using non‐localized pulse‐acquire, image selected in vivo spectroscopy (ISIS) and one‐dimensional chemical shift imaging (1‐D CSI) techniques. Comparisons have been made with measurements from acid extracts of these tumour types and surrounding tissues (i.e., muscle and skin). Since muscle containing high concentrations of phosphocreatine (PCr) is often found adjacent to the tumour, we have compared the ratio of the PCr to γ‐NTP peaks in the spectra with the same ratio calculated from the acid extract data, and have used deviations between the two sets of data to assess the discrimination of the MRS localization technique to signals from the tissue surrounding the tumour. Extract data showed an average NTP content of 1.25 μmol/g wet wt for all three tumour types. PCr (at 0.42 μmol/g wet wt), was significant only in the GH3 prolactinoma whereas it was negligible in the other tumour types (<0.1 μmol/g wet wt). There was good agreement between the ISIS PCr/γ‐NTP ratio and the extract data for all tumours. However, the 1‐D CSI data showed an unexpectedly large contamination of the tumour spectrum with PCr signals from the skin which was shown by subsequent phantom experiments to be due to the curved geometry of tumour and skin rather than Fourier bleed. In pH measurements by MRS it was found that biological variability was greater than the effects of artefacts (due to either the chemical shift artefact in the ISIS technique or partial volume effects) in the localization technique. An average pH of 7.2 was observed for all tumours. By initially comparing data from different localization schemes with that from chemical extracts potential sources of error have been highlighted and show that phantom studies alone are not sufficient to fully assess the accuracy of localized MRS data.
1H NMR spectroscopy of colon tumors and normal mucosal biopsies; elevated taurine levels and reduced polyethyleneglycol absorption in tumors may have diagnostic significance
Authors: Moreno Angel , Rey Mercé , Montane Josep M. , Alonso Juli , Arús Carles 
Published: March 2007

AbstractTwenty‐three pairs of normal mucosa and colonic adenocarcinoma biopsy specimens have been examined in this pilot study by 1H NMR spectroscopy at 9.4 T to determine whether it was possible to find spectral malignancy markers. The 3.2 ppm (trimethylamine‐containing compounds)/0.9 ppm (methyl of fatty acids) resonance intensity ratio in water suppressed spectra, proposed by other authors as a malignancy marker, results in our hands, using resonance areas, in partial overlap between tumor and mucosa values, which reduces its diagnostic value. Furthermore, we have found that submucosa contamination could mask the normal mucosa pattern and artifactually decrease the 3.2/0.9 ppm, ratio value by increasing the 0.9 ppm resonance due to the known triglyceride content of normal submucosa. On the other hand, we have observed in the Hahn spin‐echo spectra of intact biopsies resonances arising from taurine and exogenous polyethyleneglycol (PEG). Their assignment and quantification has been carried out in perchloric acid extracts of the tissue biopsies. The taurine (3.4 ppm)/creatine (3.0 ppm) area ratio produced an excellent discrimination between normal mucosa and tumour groups while the PEG (3.7 ppm)/creatine (3.0 ppm) area ratio presented a large overlap, although it was clearly higher in the mucosae than in the tumors for paired samples. These two NMR observable parameters are in our hands highly discriminating and are accordingly proposed as malignancy markers in tissue biopsies although their possible utility for in vivo studies remains to be demonstrated.
Effect of acute and chronic hyponatremia on blood‐brain barrier function in the rat
Authors: Adler Sheldon , Williams Donald , Verbalis Joseph G. 
Published: March 2007

AbstractTo study whether acute or chronic hyponatremia alters blood‐brain barrier (BBB) permeability, rats made hyponatremic by constant desmopressin acetate infusion were studied by NMR spectroscopy and imaging. On constant volume ventilation and nitrous oxide, acute (1‐ and 2‐day) and chronic (7‐ and 14‐day) hyponatremic and normonatremic controls were infused with 0.25 M HCI. Despite reducing blood pH by at least 0.35 in <50min, brain pH, measured by 31P NMR, was unaffected in any group. As a second test of BBB function, gadolinium‐DTPA (Gd‐DTPA) was injected intravenously in these five groups. Coronal slice 1H NMR images obtained before and after Gd‐DTPA showed image intensity changes in multiple areas outside brain, but neither control nor hyponatremic rats showed any differences in cortex, white matter or cerebellum. To ascertain whether the threshold for BBB disruption was altered, hypertonic mannitol (1.5, 2.0 or 3.0 mL) was injected rapidly into one internal carotid artery and pre‐ and post‐Gd‐DTPA images obtained. In both control and hyponatremic rats only the largest dose caused detectable Gd‐DTPA leakage into brain. Thus, BBB function appears intact in both acute and chronic hyponatremia since neither H+ nor GD‐DTPA penetrated the barrier and resistance to mannitol disruption was unaffected by hyponatremia.
Non‐linear regression and variance ratio analysis of time based NMR data
Authors: Endre Zoltan H. , Duggleby Ronald G. 
Published: March 2007

AbstractBiomedical NMR experiments rely frequently on data obtained sequentially over time. A method is presented for analysis of time based NMR data, which allows modelling of continuous and discontinuous functions to observed intensity changes by non‐linear regression and which uses variance ratio analysis to compare these models statistically. The method eliminates many of the usual problems in the parametric analysis of experimental values obtained at discrete time points and of comparison of the coefficients of model functions which require unsubstantiated assumptions about the distribution of parameters and ignore internal correlations which may exist between such parameters. The variance ratio method is illustrated for multiple time courses obtained with 23Na NMR of perfused rat kidney undergoing hypoxic perturbation in the presence of different treatments.
Simultaneous 31P NMR spectroscopy and laser doppler flowmetry of rat brain during global ischemia and reperfusion
Authors: Kloiber O. , Miyazawa T. , Hoehn‐Berlage M. , Hossmann K.‐A. 
Published: March 2007

AbstractThe relationship between blood flow and metabolism was studied in halothane‐anaesthetized, normothermic rats submitted to 30 min global ischemia by four‐vessel occlusion. Phosphocreatine (PCr), ATP, intracellular pH and intracellular magnesium (pMg) were measured by 31P NMR spectroscopy, and blood flow by laser Doppler flowmetry. Prior to ischemia the PCr/ATP ratio of fully relaxed spectra was 2.4±0.3, intracellular pH was 7.26±0.15 and pMg was 3.26±0.13. Vascular occlusion led to complete cessation of blood flow in four out of eight rats, and to incomplete ischaemia (< 10% of control) in the other four animals. During vascular occlusion EEG flattened and energy metabolism broke down in all but one animal with a residual blood flow of 8% of control. pH declined to 6.70±0.08. The speed of electrophysiological and metabolic recovery after 30 min ischemia varied considerably from animal to animal. Variability depended mainly on the recirculation delay (i.e., the interval from vascular release to normalization of blood flow) but was independent of residual blood flow during ischemia, pre‐ischemic glucose, ischemic or post‐ischemic acidosis, or the degree of post‐ischemic hypoperfusion. After 3 h recirculation PCr and intracellular pH returned to normal but pMg was slightly increased, and ATP was reduced by up to 50% in all animals except the rat with incomplete breakdown of energy metabolism during ischemia. The dissociation between PCr and ATP is attributed to a loss of total adenylate, the severity of which depends on the quality of post‐ischemic recirculation. The data refute the hypothesis that the quality of post‐ischemic metabolic recovery depends mainly on the severity of tissue acidosis but stress the importance of post‐ischemic haemodynamic factors for the speed and quality of brain resuscitation.
An in vivo31P MRS study of patients with liver cirrhosis: Progress towards a non‐invasive assessment of disease severity
Authors: Munakata T. , Griffiths R. D. , Martin P. A. , Jenkins S. A. , Shields R. , Edwards R. H. T. 
Published: March 2007

AbstractFourteen patients with liver cirrhosis of differing severity participated in a one‐dimensional chemical shift imaging 31P MRS study of the liver. Patients were divided into two groups according to the severity of their liver disease using Child's classification and the aminopyrine breath test (AB test). Seven normal volunteers without liver disease acted as controls. The phosphomonester (PME) peak in normal subjects was 4.77% (95% confidence interval, CI: 4.11–5.42) of total phosphorus. The PME peak was significantly elevated in both mild cirrhosis [5.80% (95% CI: 5.46–6.14), p=0.0051, vs normal subjects] and severe cirrhosis [9.64% (95% CI: 8.71–10.57), p=0.0002, vs normal subjects and p=0.001, vs mild cirrhosis]. There was a significant negative linear correlation (r=0.88, p<0.01) of PME with the percentage dose of 14CO2 excreted over 2 h in the AB test. pH values in patients with mild cirrhosis [7.45 (95% CI: 7.35–7.55)] but not severe cirrhosis [7.36 (95% CI: 7.25–7.47)] were significantly elevated (p=0.04) compared to normal subjects [7.29 (95% CI: 7.17–7.41)]. Comparison of the peak area of PME at TR = 0.5 s against that using TR = 5.0 s in cirrhotic liver suggested no reduction in T1 of phosphorus metabolites in cirrhosis. A relationship between the severity of liver cirrhosis and a relative increase in PME was demonstrated and this was not due to a reduction of T1. This study highlights the clinical potential of 31P MRS as a non‐invasive means of assessing the severity of liver cirrhosis.
Proton‐decoupled 31P chemical shift imaging of the human brain in normal volunteers
Authors: Murphy‐Boesch Joseph , Stoyanova Radka , Srinivasan Ravi , Willard Tamela , Vigneron Daniel , Nelson Sarah , Taylor June S. , Brown Truman R. 
Published: March 2007

AbstractProton‐decoupled, 31P three‐dimensional (3‐D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity, and reduced power deposition at both frequencies. Proton‐decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz‐4 proton decoupling with continuous wave bi‐level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from non‐localized FIDs and spectra localized with 3‐D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the Pi resonance show no significant variations (6.9±0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.
Esophageal cancer phospholipid characterization by 31P NMR
Authors: Merchant Thomas E. , de Graaf Peter W. , Minsky Bruce D. , Obertop Huug , Glonek Thomas 
Published: March 2007

AbstractPhospholipid extracts of surgical tissue specimens from 18 patients, consisting of normal esophagus, distal esophageal tumor and normal stomach, were analyzed using 31P NMR. The prominent phospholipids detected in these tissues included cardiolipin (CL), phosphatidylethanolamine plasmalogen, phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylcholine plasmalogen and phosphatidylcholine (PC). Very small quantities of the phospholipids lysophosphatidylcholine, phosphatidic acid, phosphatidylglycerol, and an uncharacterized phospholipid at −0.13 δ also were detected in some of the 54 tissue specimens analyzed. The mean relative concentrations of these phospholipids, in mole percentages of total detected phosphorus, were determined from the acquired spectra and used to differentiate among the three tissue groups. The relative concentrations of the following phospholipids differed significantly (p<0.001) among the respective tissue groups: normal esophagus vs esophageal tumor, PS, SPH, PI, PC; normal esophagus vs normal stomach, CL, PE, PS, SPH; esophageal tumor vs normal stomach, CL, PE. Membrane phospholipids implicated in modulating the growth and metastases of tumors of epithelial origin can be profiled to discriminate among normal esophagus, distal esophageal tumor and normal stomach using 31P NMR.
A selective inversion recovery method for the improvement of 23Na NMR spectral resolution in isolated perfused rat hearts
Authors: Simor Tamás , Kim Sung K. , Chu Wen‐Jang , Pohost Gerald M. , Elgavish Gabriel A. 
Published: March 2007

AbstractShift‐reagent‐aided 23Na NMR spectroscopy allows differentiation of the intracellular (Nai) and extracellular sodium (Na0) signals. The goal of the present study has been to develop a 23Na NMR spectroscopic method to minimize the intensity of the shift‐reagent‐shifted Na0 signal and thus increase Nai resolution. This is achieved by a selective inversion recovery (SIR) method which enhances the resolution between the Nai and Na0 peaks in shift‐reagent‐aided 23Na NMR spectroscopy. The application of SIR with Dy(TTHA), Tm(DOTP), or with low concentrations of Dy(PPP)2 results in both good spectral resolution and physiologically acceptable contractile function in the isolated, perfused rat heart model.
The effect of oestrogen ablation on the phospholipid metabolite content of primary and transplanted rat mammary tumours
Authors: Smith T. A. D. , Baluch S. , Titley J. C. , Ormerod M. G. , Eccles S. , Tombs A. J. , Leach M. O. , Griffiths J. R. , McCready V. R. 
Published: March 2007

AbstractThe concentration of phospholipid metabolites was determined in chemical extracts from two types of rat mammary tumours and compared with proliferation data (S‐phase fraction). One of the tumours was an oestrogen‐sensitive transplanted tumour. In this tumour the concentration of phosphocholine (PC) and glycerophosphorylcholine (GPC) correlated strongly with the S‐phase fraction but not with the number of cells actively synthesizing DNA. Oestrogen ablation resulted in tumour regression. Regressing tumours contained less PC and more GPC than those actively growing. The other tumour was induced in rats by intravenous administration of N‐methyl N‐nitrosourea. Phosphoethanolamine (PE), PC and GPC levels were not associated with the S‐phase fraction in this tumour. Oestrogen ablation resulted in tumour regression. There was no significant difference between the regressing and growing tumours in PE, PC or GPC content.
Use of computer simulations for quantitation of 31P ISIS MRS results
Authors: Matson Gerald B. , Meyerhoff Dieter J. , Lawry Theodore J. , Lara Rosemarie S. , Duijn Jeff , Deicken Raymond F. , Weiner Michael W. 
Published: March 2007

AbstractThe difficulties in quantitation of in vivo 31P spectra are exacerbated by the fact that, in general, coils with inhomogeneous B1 fields are used with in vivo samples. A general method for quantitation of in vivo 31P MRS results obtained with the ISIS localization method was developed using computer simulations. The simulation calculates the preparation of the sample magnetization throughout the sample by the ISIS pulse sequence, as well as the sensitivity of signal reception. The calculation accounts for both the B1 field and the B0 gradients applied to the sample. The sensitivity of the experiment is expressed by integration of the simulated signal over the sample, assuming a homogeneous sample. The primary advantage of this approach is that a separate localization experiment on a phantom of known concentration is not required each time parameters of the localization experiment, such as dimensions or location of the localized volume, are altered. In addition, the simulations indicate the degree of contamination (signal from outside of the localized volume) that occurs, and provide a means of comparing different executions of the ISIS experiment. Experiments were performed on phantoms to verify the simulations, and experimental results on human brain and liver are reproduced to show that this approach provides reasonable estimates of metabolite levels in terms of molar concentrations.
Cerebral metabolism of [1,2‐13C2]glucose and [U‐13C4]3‐hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy
Authors: Künnecke Basil , Cerdan Sebastian , Seelig Joachim 
Published: March 2007

AbstractThe metabolism of [1,2‐13C2]glucose and [U‐13C4]3‐hydroxybutyrate was studied in rat brain with in vivo and in vitro 13C NMR spectroscopy, taking advantage, in particular, of homonuclear 13C‐13C spin coupling patterns. After infusion of [1,2‐13C2]glucose or [U‐13C4]3‐hydroxybutyrate into rats, the uptake of the substrates in brain and their metabolism to [1‐13C]bicarbonate could be detected with in vivo 13C NMR spectroscopy. At the end of the infusion experiment, methanol/HCI/HCIO4 extracts of the brain tissue were further analysed by high resolution 13C NMR spectroscopy. The 13C spin coupling patterns revealed entirely different isotopomer distributions for the closely related cerebral metabolites glutamate, glutamine and 4‐aminobutyric acid. A quantitative analysis of the 13C spectra demonstrated (i) the existence of two kinetically distinct pools of glutamate, (ii) a pronounced CO2 fixation via pyruvate carboxylase in the glial cells accounting for as much as 38% of the oxaloacetate synthesis in the glial tricarboxylic acid cycle, (iii) a cerebral pyruvate recycling system contributing maximally 17% of the pyruvate metabolism through the pyruvate dehydrogenase in neurons, and (iv) a predominant production of 4‐aminobutyric acid from glutamate synthesized in the neurons. In addition, the labelling pattern of N‐acetyl aspartate upon infusion of labelled glucose or 3‐hydroxybutyrate provided insight into the synthesis of this compound in mammalian brain. While the acetyl moiety originates from the metabolic equivalent of the C‐1–C‐2 part of cerebral glutamate, the aspartyl moiety is not in direct contact with the intermediates of glycolysis or of the tricarboxylic acid cycles.
Extracellular volume and transsarcolemmal proton movement during ischemia and reperfusion: A 31P NMR spectroscopic study of the isovolumic rat heart
Authors: Clarke Kieran , Stewart Laura C. , Neubauer Stefan , Balschi James A. , Smith Thomas W. , Ingwall Joanne S. , Nédélec Jean‐François , Humphrey Stuart M. , Kléber André G. , Springer Charles S. 
Published: March 2007

AbstractWe have measured, directly and simultaneously, changes in extracellular volume and intra‐ and extracellular pH during ischemia in the isolated rat heart using 31P NMR spectroscopy. Hearts were perfused with buffer containing 15 mM sodium phenylphosphonate at pH7.4. Wash in and wash out experiments showed that phenylphosphonate entered only the extracellular (interstitial, vascular and chamber) space of the heart and had no adverse effects on myocardial energetics, contractile function or coronary flow rate. Hearts were subjected to 28 min of total, global ischemia, during which the phenylphosphonate resonance area in the 31P NMR spectra decreased by 83%, indicating that extracellular fluid had moved rapidly from the heart to the bath surrounding the heart, partly as a result of vascular collapse. A separate, morphological study confirmed that 95% of the vasculature had collapsed by 28 min ischemia. Intra‐ and extracellular pH were determined from the chemical shifts of the Pi and the phenylphosphonate resonances, respectively. In the pre‐ischemic rat heart, intracellular pH was 7.15±0.03 and extracellular pH was 7.39±0.03. By 4 min of ischemia, intra‐ and extracellular pH were the same and decreased concomitantly throughout the remainder of ischemia to final values of 6.09±0.19 and 6.16±0.23, respectively. On reperfusion, the extracellular volume and pH returned to pre‐ischemic levels within 1 min, but restoration of intracellular pH took >2.5 min. Thus, a large volume of extracellular fluid moves out of the rat heart to the surrounding bath and the intra‐ and extracellular pH become the same during total, global ischemia.