摘要:

Abstract23Na NMR spectroscopy was used 1, to define the distribution of the shift reagent for cations, triethylenetetraminehexaacetatedysprosium(III), DyTTHA3−, in the living rat; 2, to define the characteristics of the Na resonances reporting intra‐ and extracellular Na+in skeletal musclein vivo; and 3, to calculate the Na+concentrations in the intra‐ and extracellular spaces of the gastrocnemius muscle during well‐perfused and ischemic conditions. The concentration of DyTTHA3−infused intravenously into the jugular vein of the living rat reached a maximum value of 8–9 mMin the extracellular space of the muscle after ca 40 min of infusion. This allowed excellent discrimination of extra‐ and intracellular Na signals (Naoand Nai, respectively) and did not spoil the resolution of concurrent31P NMR spectra. Infusion of shift reagent changed neither hemodynamic performance of the rat nor the high‐energy phosphate content of skeletal muscle. Shift reagent enters ca 15% (v/w) of the rat body weight; this corresponds to almost all of the “fast” or rapidly permeable extracellular space. It is excreted from the body with a pseudo‐first order rate constant of 0.0158 min−1. In resting muscle, we estimate that [Na+]iis 3–5 mMand, in muscle perfused with the sodium salt of the shift reagent, that [Na+]oin the fast exchangeable extracellular space is 166 mM. During 11 h of ischemia at 37°C, the area of the Nai+signal area monotonically increased sixfold. Based on estimates for maximum changes in fluid shifts reported by the decrease in the area of the Naosignal area, we calculate that the lower limit for [Na+]iafter 11 h of ischemia is 27 mM. The NMR‐visibility factors for the extracellular and intracellular Na+signals are essentially the same. This study demonstrates that the shift reagent DyTTHA3−is acutely non‐toxic and that the23Na NMR spectra obtained can be used to quantitate [Na+]oand [Na+]iin tissuesin vivo. Using this technique, we found that the transmembrane sodium gradient fell from ca 35 in well‐perfused skeletal mus

ISSN:0952-3480    

DOI:10.1002/nbm.1940030202

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

AbstractThe membrane transport kinetics of the disubstituted phosphorus oxyacid, hypophosphite, were studied in human red cells under equilibrium exchange conditions. Hypophosphite is an analogue of both the bicarbonate and phosphate ions and is known to be rapidly transported across the human red cell membrane via the anion transport protein, Band 3. The hypophosphite ion is a particularly useful probe of Band 3‐mediated membrane transport as the intracellular and extracellular species occur as distinct resonances in the31P NMR spectrum; as a result the membrane potential may also be readily inferred. We applied ‘overdetermined’ one‐dimensional exchange analysis to estimate the rates of exchange for influx and efflux. The apparent equilibrium exchange (ee) valuesK meefor the hypophosphite efflux and influx were different and while the efflux parameters were not able to be unambiguously defined, the measured apparent influx kinetic transport parameters wereV maxee= 1600 ± 190 amol cell−1s−1, an

ISSN:0952-3480    

DOI:10.1002/nbm.1940030203

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

AbstractPhotodynamic therapy utilizes the tumor localizing drug dihematoporphyrin ether and red laser light to produce both direct tumor cell destruction via damage to mitochondrial membranes, and also indirect cell kill via destruction of the tumor vasculature. As a first step towards examining the mechanistic relationship between metabolic and vascular effects of photodynamic therapy, murine RIF‐1 tumors were treated with a subcurative treatment (500J/cm2). Tumor metabolic status was monitored usingin vivo31P NMR before,duringand after the treatment. The tumor blood flow immediately before and after treatment was measured by direct intratumor injection of D2O saline and observation of the tracer signal clearance from the tumor via2H NMR. During the photodynamic therapy treatment, significant decreases were observed for the nucleoside triphosphate concentrations, tumor pH and tumor blood flow, while inorganic phosphate concentrations increased. Animals treated with laser light alone and those not given any treatment, demonstrated no significant changes in tumor metabolic status, tumor pH or tumor blood flow. Further studies are required to determine whether tumor blood flow or metabolic status is affected firs

ISSN:0952-3480    

DOI:10.1002/nbm.1940030204

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

AbstractThe dynamics of rat skeletal muscle energy metabolism in response to ischemia and reperfusion have been investigated byin vivo31P NMR spectroscopy. The time course of changes in the phosphocreatine, inorganic phosphate, ATP peaks and in intracellular pH during 2 and 4 h of tourniquet ischemia followed by up to 24 h of tissue reperfusion have been determined. Furthermore, the ATP and IMP concentrations in the soleus and tibialis muscles have been determined by high performance liquid chromatography analysis in response to ischemia and subsequent reperfusion. The results demonstrate an initial overshoot in the pH during the first minutes of ischemia. It is also shown that the muscles recover completely after 2 h of ischemia whereas the energy state of the muscle cell is not restored after 4 h of ischemia followed by up to 24 h of reperfusion. However, the soleus muscle recovers better than the tibialis. The results are discussed in terms of oxygen availability, reperfusion injury, IMP accumulation and different response between muscles with different fibre composition.

ISSN:0952-3480    

DOI:10.1002/nbm.1940030205

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

Abstract202 MHz31P NMR (11.7 T) was used to study the effects of culture medium pH on the levels of phosphate metabolites in three human tumor cell lines (XP29MAmal, a malignant xeroderma pigmentosum; CX‐1, a colon carcinoma; KB, a squamous cell carcinoma of the oral cavity). Cells were cultured in Roux flasks in HAM's F‐12 medium, and the pH was varied with the final medium change. After harvesting, 1–5 × 108cells were suspended in Ringer/HEPES buffer at pH 7.4 and 4°C for31P NMR studies. Cell adhesion and growth rate decreased with decreasing pH, but, down to ca pH 6.1, trypan blue exclusion and the observed levels of nucleoside di‐ and triphosphates (range: 22–37% of total phosphates detected), phosphocreatine (PCr, 2–5%) and Pi(5–11%) did not vary significantly with pH. For XP29MAmal cells in exponential growth phosphocholine levels decreased from 18–28% at pH 7.0 to ca 5% at pH 6.0, while phosphoethanolamine levels increased from 2–7% to 15%. Glycerophosphocholine (GPC) levels increased from ca 7% at pH 7.2 to 13% at pH 6.3. At pH<6.3 cytidine 5′‐diphosphate (CDP) choline became detectable (8–16%, δP: Pα= −8.13 ppm, Pβ= 8.93 ppm, for PCr = 0 ppm). However, confluent cells did not accumulate CDP‐choline when the pH was lowered. The cell lines CX‐1 and KB also show

ISSN:0952-3480    

DOI:10.1002/nbm.1940030206

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

AbstractLocalized31P NMR spectroscopy was used to study the developing human liver in three neonates and one infant, all with neonatal intracranial problems, but normal liver function. A prominent resonance was present in the phosphomonoester (PME) region of the spectrum of the neonates; the PME/ATP ratio was 1.0 ± 0.4 (repetition time 1 s), compared to the mean adult liver value of 0.2 ± 0.1. The saturation factor of PME in the neonates was large, indicating that the increase in PME/ATP reflected an increase in relative PME concentration. The chemical shift of the PME peak in the neonatal liver (6.8 ± 0.1) was similar to that found in neonatal brain, suggesting that phosphorylethanolamine may be a major constituent. The phosphodiester (PDE)/ATP ratio in these patients (0.4 ± 0.1) was decreased compared with the mean adult value (1.3 ± 0.2), and the saturation factor of PDE was small. The results from the infant were different from both the neonates and adults; PME/ATP was decreased compared to the neonates, but increased compared to adults. The saturation factor of PDE was increased compared to neonates. The biochemical implications of the observed changes in PME and PDE in paediatric liver are discussed in relation to membrane turn

ISSN:0952-3480    

DOI:10.1002/nbm.1940030207

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

ISSN:0952-3480    

DOI:10.1002/nbm.1940030208

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

摘要:

AbstractHigh resolution1H and13C NMR spectroscopic measurements including1H/13C 2D correlation and magnetic resonance imaging (MRI) studies, have been carried out on intact rabbit aortic tissuesex vivousing animals fed both normal and high cholesterol diets. The results show that1H and13C NMR spectroscopy can distinguish mobile lipids and can differentiate between normal triglyceride content and cholesterol‐enriched lipids, in intact tissue. There were considerable differences in the level of deposition of cholesteryl esters in animals all fed on the same diet. Confirmation is presented of temperature‐dependent differences in mobility and organization between the triglycerides found in control tissue and the cholesteryl esters found in aortas from high lipid diet animals. Water‐suppressed MRI showed evidence of lipid accumulation in the aortas of high cholesterol diet rabbits. It is concluded that the hypercholesterolaemic rabbit model of atherosclerosis, coupled with such NMR methods, may offer a noninvasive method of monitoring disease development, allowing the evaluation of the effect of therapeutic agents on the progress of atheroscle

ISSN:0952-3480    

DOI:10.1002/nbm.1940030209

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY

ISSN:0952-3480    

DOI:10.1002/nbm.1940030201

出版商:John Wiley&Sons, Ltd.    

年代:1990

数据来源: WILEY