摘要:

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 pHiand lactic acid were measured by31P and1H NMR. The results showed that insulin‐induced hypoglycemia markedly inhibits production of lactic acid, but has no effect on brain pHiduring ischemia. These findings suggest that, at least under some conditions, the acidosis produced by cerebral ischemia is not due to accumulation of lacti

ISSN:0952-3480    

DOI:10.1002/nbm.1940060102

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractFrequency shift/concentration calibration curves applicable to the use of shift reagents (SRs) forin vivo23Na MRS studies can be obtained from experiments with whole blood. Here, they are reported for titrations of rat blood with the SRs DyTTHA3−and TmDOTP5−. There are a number of considerations that must be made in order to derive accurate calibration curves from the experimental data. These include the effects of bulk magnetic susceptibility (BMS, since the SRs are paramagnetic), the effects of water flux (since addition of the SR stock solution to blood renders the plasma hyperosmotic), and the consequences of restricted distribution of the SR anion in the erythrocyte suspension. We give in some detail the BMS shift theory that obtains in this case and show also how it applies to excised perfused organ as well asin vivostudies. Also, we report significant effects of adjuvant Ca2+additions in the TmDOTP5−titrations. These are very important to the successful use of this SRin vivo. Finally, our considerations of BMS lead naturally to an understanding of its manifestations in the shifts of the1H2O resonance frequencies of cell suspensions and tissues induced by SRs. Since these are being increasingly reported, and often misinterpreted, we devote an experiment and some discussion to this subject. We show that this phenomenoncannotbe used to quantitatively discriminate intra‐ and extracellular1H2O

ISSN:0952-3480    

DOI:10.1002/nbm.1940060103

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractRats were given intravenous15NH4+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 studiedin vivoby15N NMR spectroscopy at 20.27 MHz for15N. 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 decreased15NH 4+removal in the liver led to increased15NH3diffusion 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 vivoactivity of glutamine synthetase in rat brain was estimated to be 3.5 μmol/h/g. Comparison with reported optimumin vitroactivity suggests thatin situconcentrations of some substrates and cofactors limit the activity of g

ISSN:0952-3480    

DOI:10.1002/nbm.1940060104

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractIn vivo19F NMR measurements of the fluorinated neuroleptic melperone [4′‐fluoro‐4‐(4‐methylpiperidino)‐butyrophenone hydrochloride] in the rat brain were performed using a geometrically optimized surface coil at 4.7 T. It was possible for the first time to detect a signal of a monofluorinated neuroleptic drug with a time resolution of 30 min after i.p. application. The kinetic time course of the investigated neuroleptic melperone was recorded over 6 h and showed that the half‐life in the rat brain is 4.3 h. The total amount of drug and its metabolites in the brain was estimated to be 50 μM. the chemical shift of the19F NMR signal shows the same upfield shift relative to that in aqueous solution as has been reported for trifluorinated neu

ISSN:0952-3480    

DOI:10.1002/nbm.1940060105

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe phosphagen cost of maximal isometric twitch and tetanic contractions in rat gastrocnemius muscle was measuredin situby31P NMR with acquisitions gated to precise time points after a brief (<10 s) burst of contractions. Alteration of twitch stimulation frequency did not affect the energy cost per contraction. Pooled results of four twitch rates from 1 to 8 Hz produced an average cost of 0.257±0.012 μmol ATP/g/twitch. This value was compared with the initial twitch cost estimated from the time zero derivative of an exponential fit of averaged scan phosphocreatine (PCr) data from a previous study of 8 min of contractionin situat 0.75 Hz. Agreement of the two estimates validates the use of the fitting/derivative method to assess energy cost and confirms the monoexponential character of the PCr time course. Evaluation of muscle pH changes demonstrated that all ATP use during the brief twitch contraction bouts could be accounted for by PCr hydrolysis. Results also showed a brief delay in onset of PCr recovery, consistent with the response time of oxidative systems. Tetanic contractions of 100 ms duration at 100 Hz required 2.17±0.07 μmol ATP/g muscle/contraction, in general agreement with estimates reported using a variety of other meth

ISSN:0952-3480    

DOI:10.1002/nbm.1940060106

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe present study describes a protocol for the determination ofin vivoabsolute molar concentrations of Li+in the human brain using a double tuned1H/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 of7Li and1H in the brain is compared to the same ratio in a phantom containing known concentrations of Li+. The7LiT1values in the brains of five patients receiving lithium therapy were measured. The average result wasT1= 3.5±0.25s. The phantom solution was adjusted to have thisT1value. 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

ISSN:0952-3480    

DOI:10.1002/nbm.1940060107

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractUA hepatomas, GH3 prolactinomas andN‐methyl‐N‐nitrosourea‐induced mammary tumours, which were subcutaneously grown in rats, have been studied by31P MRS using non‐localized pulse‐acquire, image selectedin vivospectroscopy (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 accu

ISSN:0952-3480    

DOI:10.1002/nbm.1940060108

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe characteristics of the31P MR spectra from a large central volume in the brain of 47 healthy adults (aged 25–85 years) were assessed. Spectral parameters were estimated by means of a time‐domain fitting technique. Statistical uncertainties of the estimates were determined by means of the Cramer‐Rao theory and minimized by introducinga prioriknowledge into the fitting procedure. Age‐dependency of the spectral parameters was assessed by means of linear regression. Significant differences between individuals were established for some parameters. A significant age‐dependency (p⩽0.001) of ca 20% over the age range considered was found for the intensity of the phosphocreatine res

ISSN:0952-3480    

DOI:10.1002/nbm.1940060109

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractProton high‐resolution MRS of human plasma allows the rapid detection, on the same spectrum, of many compounds originating from different metabolic pathways. In this paper, we illustrate the modifications of the plasma metabolic profiles recorded by proton NMR spectroscopy in different classes of cancers. These modifications can be easily monitored with graphic aids such as ‘star plots’ which define for each type of cancer a particular pattern describing the most altered metabolic pathways. By using ‘star plots’ three types of metabolic patterns have been distinguished: (i) the ‘inflammatory’ pattern characterized by an increase of glycosylated moieties of glycoproteins; (ii) a ‘lipid modified’ pattern, characterized by various modifications occurring mainly in the lipid moieties detected by MRS; and (iii) a pattern which is often observed in sarcomas and mainly characterized by an alteration in theN‐acetyl glucosamine/N‐acetyl neuraminic acid ratio. This study demonstrates the ability of proton MRS of plasma to rapidly detect the occurrence of metabolic modifications brought about by cancer

ISSN:0952-3480    

DOI:10.1002/nbm.1940060110

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractInformation about the control of mitochondrial function in skeletal musclein vivocan be obtained from the relationship between the rate of mitochondrial oxidation and the intracellular concentrations of phosphorus metabolites, although the analysis is complicated by the constraints imposed by the creatine kinase equilibrium. The rate of phosphocreatine (PCr) recovery after exercise measured by31P MRS is an estimate of net oxidative ATP synthesis. Analysing such data from normal and abnormal human muscle, we show that the approximately exponential recovery kinetics of ADP and PCr imply that the rate of PCr resynthesis has a hyperbolic dependence on [ADP] but remains approximately linear with respect to the concentration of orthophosphate (Pi) and therefore also [PCr] and [creatine]. Both kinds of relationship are consistent with experimental data from exercising animal muscle and also with data from isolated mitochondria which suggest kinetic control of mitochondrial ATP synthesis of [ADP]. These relationships are altered in proven mitochondrial disease. This analysis offers a way to quantify mitochondrial function and its abnormalitiesin vivo.

ISSN:0952-3480    

DOI:10.1002/nbm.1940060111

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY