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 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)
NMR Biomed
PMID:An assessment of 31P MRS as a method of measuring pH in rat tumours. 148 71

Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies.
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PMID:Perfusion imaging. 173 82

The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half-maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase. 188 22

Significant water vapor sorption at room temperature by the crystalline and lyophilized forms of L-660,711, a potent, selective leukotriene D4 receptor antagonist, has been measured and shown to produce increasingly more nonflowing, semisolid masses with increasing relative humidity. Thermal analysis, SEM, powder X-ray diffraction, solid-state NMR, and thermomicroscopic measurements reveal that water vapor sorbed at room temperature converts the crystalline form to a noncrystalline form resembling the lyophilized sample. Evidence is presented to indicate that L-660,711 has surface active properties with a critical micellization concentration of approximately 1 x 10(-4) M and an ability to form thermotropic and lyotropic mesomorphic phases when the crystal is heated above 80 degrees C in the anhydrous state; it is lyophilized from aqueous solution, and it is exposed to relative humidities at and above 12%, at room temperature.
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PMID:Solid-state phase transitions initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist. 202 61

Trimethylamines are required as substrates in the biosynthesis of a number of important molecules in the cell. Herein, we describe the use of choline, deuterated in its 9 methyl positions, as an NMR label for following the distribution and metabolism of methyl groups after intravenous choline infusion. Deuterium (2H) NMR spectroscopy of the rabbit kidney in vivo revealed a linear uptake of infused choline that was directly proportional to the rate of infusion. The sensitivity limit for the spectroscopic studies in vivo was in the order of 100 microM for a 2 min data collection. After the infusion, 2H NMR imaging of the kidney in vivo demonstrated high trimethylamine concentrations in both the cortex and inner medulla but not in the outer medulla. The inner medullary fraction, however, was more labile to diuresis induced by furosemide. Companion high resolution 2H NMR studies of extracts revealed a cortex betaine/choline concentration ratio of 0.69 +/- 0.05 (mean +/- SEM, n = 3) before furosemide administration. Following furosemide infusion, the cortex betaine/choline concentration ratio was 3 +/- 1 (n = 6). Thus, 2H renal images following furosemide treatment can be interpreted as metabolic maps of betaine distribution. In addition, extraction studies revealed high concentrations of labelled choline and betaine in the liver. These data demonstrate that 2H-labelled choline is an effective marker of choline methyl metabolism in vivo and should provide a unique tool for the investigation of this important substrate.
NMR Biomed 1990 Aug
PMID:Renal distribution and metabolism of [2H9]choline. A 2H NMR and MRI study. 220 49

The ability to measure ATP synthesis rates using 31P-NMR spectroscopy is demonstrated in the normal, ischemic, and postischemic myocardium in vivo. Cardiopulmonary bypass (CBP) was employed to induce 20 min of global myocardial ischemia, and to conduct magnetization transfer measurements during the ischemic episode and following reperfusion and return to normal circulation. For the first few minutes of ischemia, transfer of magnetization from ATP gamma to Pi was extensive and the resultant fractional reduction (delta M/M0) in the Pi resonance intensity reached approximately 100%. Subsequent to reperfusion and stabilization off CPB and on normal circulation, both the fractional reduction and the spin-lattice relaxation time, T1*, of the Pi resonance were determined when ATP gamma spins were saturated. Under these conditions, the unidirectional ATP synthesis rate was 0.41 +/- 0.09 (SEM, N = 4) mumol/s/g wet wt. The data suggest that in the canine myocardium in vivo, glycolytic enzymes mediate a very rapid exchange between Pi and ATP gamma-phosphates during early phases of ischemia; in the postischemic reperfused myocardium, however, the glycolytic contribution to the unidirectional Pi----ATP rate measured by NMR in vivo is relatively small compared to that observed in glucose-perfused, postischemic rat hearts.
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PMID:Measurement of ATP synthesis rates by 31P-NMR spectroscopy in the intact myocardium in vivo. 237 2

The response of tumours to treatment with the cytostatic drugs cisplatin (CDDP) or doxorubicin (DXR) was followed in vivo by 31P NMR spectroscopy. A CDDP-sensitive parent line (IgM-I) and a CDDP-resistant subline (IgM/CDDP) of the IgM-immunocytoma grown s.c. on LOU/M WsL rats were used. Animals from both tumour groups (n = 33) were divided into 3 subgroups: CDDP-treated (1 mg/kg), DXR-treated (10 mg/kg) and control. In 3 out of the 4 treated subgroups where the tumours regressed to less than one half of the initial size, 31P NMR spectroscopy revealed alkaline shifts of 0.31-0.41 pH units at day 4, while the ratio of nucleoside triphosphate to Pi in the tumours, increased continuously to 250-435%. Following CDDP treatment, the 31P NMR spectra of the non-responding IgM/CDDP tumours showed a similar pH increase (0.37 units). The ratio of NTP/Pi showed a temporary decrease to 63 +/- 14% SEM at day 1, which was followed by a recovery to 130 +/- 12% at day 2 and 119 +/- 15% at day 4. The control tumours showed no change in pH and a gradual decrease in the ratio of NTP/Pi. In DXR-treated rats the concentrations of DXR in the immunocytoma tumour and its subline were similar, but in the CDDP-treated rats the IgM-I tumours contained significantly higher levels of platinum than the IgM/CDDP tumours, both measured at 3 and 4 days after administration. The continuous increase in NTP/Pi ratio observed in the responding tumours, is a phenomenon characteristic of tumour regression, while the early temporary decrease in tumour NTP/Pi ratio could be associated with resistance to CDDP. Whether the reported response-specific spectral change applies to other tumour types and other treatment regimens remains to be established.
NMR Biomed 1990 Jun
PMID:31P NMR study of cisplatin- and doxorubicin-induced changes in tumour metabolism in rats with a cisplatin-sensitive or -resistant immunocytoma. 238 59

The build-up and clearance of halothane in rat brain have been measured non-invasively by 19F NMR spectroscopy using a surface coil placed on the intact scalp. When the halothane supply (3% in O2/N2O, 33/66%) was turned off, the 19F signal decreased exponentially to approximately 50% of the initial value, with a time constant, in normal rats, of 8.6 +/- 0.7 min (mean +/- SEM, n = 16), followed by a decay slower by at least one order of magnitude. The time constant of the rapid decay (tau), which was found to be specific for brain, was reduced in hypoxic/hypercapnic (5% O2/5% CO2) rats to 2.9 +/- 0.2 min (p = 0.001, n = 4), in rats infused with physostigmine (20 micrograms/kg/min i.v.) to 5.7 +/- 0.3 min (p = 0.005, n = 6) and increased in rats injected with pentothal (40 mg/kg i.p.) to 10.7 +/- 1.6 min (p = 0.2, n = 5). Based on the theory of exchange of inert gas at the lungs and tissues developed by Kety, the rapid exponential decay of the 19F signal was used to calculate relative cerebral blood flow (CBF). Assuming the cortical CBF in a normal rat to be about 130 mL min-1 100 g-1, the following CBF values (means +/- SEM) were obtained: controls 130 +/- 10, hypoxia/hypercapnia 390 +/- 59, hypercapnia 220 +/- 25, physostigmine 195 +/- 26, pentothal 105 +/- 23 mL min-1 100 g-1. These values are in good agreement with published values obtained with established methods.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR Biomed 1989 Sep
PMID:Non-invasive determination of cerebral blood flow changes by 19F NMR spectroscopy. 251 56

The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty-four hours after nutritional replenishment the PD rats and continuously well-fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as 'ATP/Pi ratio') in PD rats in contrast to an unchanged ATP/Pi ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 +/- 0.03 [SEM] vs 6.95 +/- 0.04; p less than 0.02). Tumor response in the PD group was significantly (p less than 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/Pi ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.
NMR Biomed 1989 Jun
PMID:31P NMR study of the impact of dietary manipulation on tumor metabolism and response to methotrexate. 264 Dec 88

We systematically evaluated three different methods of preparing canine myocardium for NMR relaxometry: using whole specimens, specimens sliced into approximately 2-mm3 pieces, and specimens minced into pieces less than 2 mm3. NMR relaxation times were determined at 20 MHz. T1 relaxation time and water content were not different among the three methods. However, T2 values differed significantly between whole and sliced samples (mean +/- SEM = 51.2 +/- 2.2 ms (whole) vs 54.3 +/- 2.7 ms (sliced): P less than 0.05). Minced myocardium showed a similar increase that was not statistically significant. We conclude that tissue preparation methods must be controlled when performing NMR relaxometry studies.
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PMID:In vitro NMR characterization of mammalian myocardium: effect of specimen integrity on relaxation times. 267 1


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