Surfactant-assisted organic reactions in water. Effect of ultrasound on condensation reactions between active methylene compounds and arylaldehydes.

A series of quaternary ammonium salts has been tested as phase transfer agents to promote condensation reactions in an aqueous solution of sodium hydroxide in the absence of any organic solvent. Methyltrioctylammonium chloride (Aliquat 336) emerges as the most efficient catalyst. Sonication of the reaction media has a poor but positive kinetic effect.

Characterization of ionized heterocyclic carbenes by ion-molecule reactions.

1,2-Hydrogen shift isomers of ionized pyridine, thiazole and imidazole are readily characterized by the study of their associative ion-molecule reactions with dimethyl disulfide in the quadrupole collision cell of a new hybrid sector-quadrupole-sector mass spectrometer. Efficient trapping reactions of CH(3)S(.) radicals are indeed observed and the actual structure of the adduct [M + CH(3)S](+) ions is clearly indicated by their high-energy collisional activation mass spectra. These trapping reactions are not observed for the 'conventional' pyridine, thiazole and imidazole molecular ions, which only react by charge exchange producing m/z 94, [CH(3)SSCH(3)](*+), ions.

31P NMR kinetics study of cardiac metabolism under mild hypoxia.

The effects of mild hypoxia on the metabolic and mechanical functions of isovolumic perfused rat hearts have been studied. 31P NMR has been used to follow the metabolite concentrations as well as the intracellular pH. Additionally, the energy transfer through the creatine kinase reaction was estimated by the magnetization-transfer technique. The needs of myofibrillar energy and of mitochondrial ATP production have been assessed through mechanical activity and oxygen-consumption rate. It has been observed that mild hypoxia simultaneously impairs contractile and metabolic functions. The aerobic ATP production is maintained under these conditions while anaerobic energy metabolism seems accelerated. The accumulation of some metabolites (ADP and P(i)) and the decrease of creatine kinase forward flux (Vfor) tend, however, to prove that ATP availability for myofibrils is lowered. The large aerobic energy production observed must therefore be explained by an energy wastage in the mitochondria. In spite of normal ATP concentration, a contractile dysfunction is observed and can be explained by the P(i) accumulation, which is known to impair the use of the myofibrillar ATP. Another hypothesis supported by the magnetization-transfer experiments is the poor ATP availability resulting from the ATP wastage in the mitochondria and from the inefficient energy transport by the PCr-Cr shuttle.

Mechanical and biochemical cardiac disturbances induced by bolus administration of iodinated contrast media and noniodinated solutions.

RATIONALE AND OBJECTIVES: Bolus injection of iodinated contrast media has been observed to alter myocardial mechanical function, but the consequences on cellular metabolism are poorly documented. Modifications of metabolic parameters (intracellular pH as well as adenosine triphosphate [ATP], phosphocreatine, and inorganic phosphate contents) and of mechanical function (coronary flow, heart rate, and left ventricular developed pressure) were simultaneously recorded on isolated rat hearts perfused over 2 minutes with a high osmolality contrast medium (HOCM) and two low osmolality contrast media (LOCM). In addition, the effects of test solutions mimicking the ionicity and the osmolality of LOCM were evaluated. METHODS: Isovolumic rat hearts were submitted to a 2-minute perfusion with oxygenated Radioselectan, Hexabrix, and Omnipaque (320 mgI/mL) at 37 degrees C. Metabolic parameters were obtained by P-31 nuclear magnetic resonance spectroscopy at 4.7 Tesla. Noniodinated ionic and nonionic solutions also were tested for comparison. RESULTS: HOCM irreversibly impairs the metabolic and mechanical functions, whereas ionic and nonionic LOCM and test solutions induce transient cardiac failure but no permanent alteration of the metabolic or mechanical parameters. CONCLUSION: In this protocol, HOCM causes irreversible degradation of the biochemical status and definitive heart failure, whereas ionic and nonionic LOCM only induce transient changes of myocardial function. Treatments with the LOCM do not induce any modification of the ATP and PCr content, and, at the end of the reperfusion period, the mechanical function is equivalent to that of control hearts. Depending on the ionic content of the solutions (iodinated or not), the evolution of the ventricular developed pressure after injection differs from one group of hearts to another. From these experiments, it is concluded that ionic imbalance and viscosity of the solutions, rather than iodine content or hyperosmolality, should be considered the causes of heart failure.

Relaxivity enhancement of low molecular weight nitroxide stable free radicals: importance of structure and medium.

The longitudinal relaxivities of seven water-soluble nitroxide derivatives of low-molecular weight have been measured at 5 degrees C and 37 degrees C in water and in serum between 0.01 and 200 MHz. The nuclear magnetic relaxation dispersion (NMRD) profiles show a clear relationship between the relaxivity observed in serum and the relative balance of the hydrophobic/hydrophilic character of the paramagnetic molecules. From the data analysis, contributions arising from a population of nitroxides characterized by reduced mobility can be extracted. The values of the correlation times are consistent with a system involving nitroxides adsorbed at the surface of albumin and magnetically interacting with the protons of hydrogen bonded water molecules.

pH and temperature effects on kinetics of creatine kinase in aqueous solution and in isovolumic perfused heart. A 31P nuclear magnetization transfer study.

Phosphorylated metabolites concentrations and creatine kinase kinetics are measured by 31P NMR in solution and in isovolumic perfused rat hearts submitted to hypo- and hyperthermia as well as to acidosis (37 degrees C). In the organ, temperature variation from 40 to 25 degrees C induces an increase of phosphocreatine (PCr) stores, a decrease of Pi and ADP concentrations, but does not affect the ATP pool. Creatine kinase forward flux (Vfor) is gradually reduced when the temperature is lowered both in vitro and in perfused heart. In normothermic and hypothermic conditions, a relationship is found between cardiac performance (rate pressure product, RPP), Vfor and ATP synthesis estimated through the myocardial oxygen consumption rate (MVO2). At 40 degrees C however, the RPP is reduced although both Vfor and MVO2 increase. In vitro experiments show an optimum pH of 7.7 for the forward creatine kinase reaction. In perfused heart submitted to acidosis, a decrease of PCr concentration is observed, whereas ATP and ADP contents remain unchanged. Heart creatine kinase flux increased as in hyperthermia. These high fluxes are attributed to the coupling of the creatine kinase reaction with energy consuming or producing reactions: the increase of energy demand related to non-contractile processes could explain the high MVO2 and Vfor observed in those conditions.

Stability assessment of gadolinium complexes by P-31 and H-1 relaxometry.

Longitudinal P-31 relaxation rate enhancements of phosphate groups have been measured at pH 7-7.2 and 310 degrees K on aqueous solutions containing adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and some lanthanide complexes (Gd-DOTA, Gd-HPDO3A, Gd-DO3A, Gd-DTPA, Gd-DTPA-BMA). The macrocyclic complexes induce linear enhancements of the relaxation rates of all phosphorus nuclei. For Gd-DOTA and Gd-HPDO3A, the mechanism of the interaction with the P-31 nuclei seems to be of the outer sphere type and a better efficiency is noted for the "neutral" Gd-HPDO3A. A short-lived ternary complex between Gd-DO3A and the phosphorylated metabolites appears to be formed enabling an inner sphere interaction. In solutions containing the open chain complexes, Gd-DTPA and Gd-DTPA-BMA, P-31 relaxation rates of ATP exhibit significant and nonlinear enhancements that are much larger than those observed for PCr and Pi. A ternary complex involving the lanthanide ion, its original chelator, and the ATP molecule is precluded by various experiments which confirm that the lanthanide ion shifts from the original complexes to the ATP phosphate groups.

31P nuclear magnetic resonance study of the effects of the calcium ion channel antagonist fantofarone on the rat heart.

The biochemical and mechanical effects of a new calcium ion channel antagonist, fantofarone ((2-isopropyl-1-((4-(3-(N-methyl-N-(3,4-dimethoxy-beta-phenethyl)-amino) propyloxy)benzenesulfonyl))-indolizine), on isovolumic perfused rat heart have been assessed by using 31P nuclear magnetic resonance (NMR) spectroscopy together with simultaneous monitoring of myocardial mechanical function. Cytosolic pH and phosphocreatine, adenosine triphosphate and inorganic phosphate contents were monitored by using 31P NMR. Heart rate, coronary flow and left ventricular developed pressure were measured routinely to assess mechanical function. Perfusion with 10 nM, 100 nM or 1 microM fantofarone for a period of 48 min did not cause any measurable metabolic changes. However, coronary vasodilatation and a partial positive inotropic effect were noted. A 15-min pretreatment with 100 nM did not protect against the deleterious effects of an 18-min period of normothermic, zero-flow ischemia. In contrast, a 20-min pretreatment period with 1 microM fantofarone significantly improved the recovery of mechanical performance, metabolic activity and pH after the same 18 min of ischemia. While only a slight protection of the ATP pool was noted during the ischemic period, major beneficial effects were observed during the reperfusion period, such that reflow was characterized by high recoveries of left ventricular pressure and rate pressure product (70-80%), low end diastolic pressure (< 10 mm Hg), significant recovery of ATP content (to 55%), a complete repletion of the phosphocreatine pool and a fast return of cytosolic pH to normal value.

Optimization schemes for selective excitations: application to the DIGGER pulses.

In this work, two distinct approaches to the tailoring of selective radiofrequency (RF) pulses were applied to a cos-sinc pulse of the DIGGER sequence used in localized spectroscopy. Ideally, three such pulses combined with a gradient in each direction destroy the Mz component of the magnetization everywhere but in the volume of interest. In the first approach, the optimal RF amplitude modulation is found by minimizing the difference between the ideal and the computed Mz profiles. In the second strategy, the RF pulse envelope is adjusted by optimization of the tip angle profile. Computed slice profiles optimized by each of these methods have been compared to experimental results. Simulations as well as experiments show that the second approach, which optimizes tip angles, is the most efficient.

Nuclear relaxation of human brain gray and white matter: analysis of field dependence and implications for MRI.

The dependence of 1/T1 on the magnetic field strength (the relaxation dispersion) has been measured at 37 degrees C on autopsy samples of human brain gray and white matter at field strengths corresponding to proton Larmor frequencies between 10 kHz and 50 MHz (0.0002-1.2 T). Additional measurements of 1/T1 and 1/T2 have been performed at 200 MHz (4.7 T) and 20 MHz (0.47 T), respectively. Absolute signal amplitudes are found to be proportional to the sample water content, not to the "proton density," and it is concluded that the myelin lipids do not contribute to the signal. Transverse magnetization decay data can be fitted with a triple exponential function, giving characteristic results for each tissue type, and are insensitive to variations of the pulse spacing interval. The longitudinal relaxation dispersion curves show characteristic shapes for each tissue type. The most striking difference is a large dispersion for white matter at very high fields. As a consequence, the relative difference in 1/T1 between gray and white matter shows a marked maximum around 10 MHz. Possible implications for MRI are discussed. A weighted least-squares fit of the dispersions has been performed using a four-parameter function of the form 1/T1 = 1/T1,w + D + A/(1 + (f/fc)beta'). The quality of the fit is superior to that of other functions proposed previously. The results of these fits are used to predict image contrast between gray and white matter at different field strengths.

Amiodarone pretreatment effects on ischemic isovolumic rat hearts: a P-31 nuclear magnetic resonance study of intracellular pH and high-energy phosphates contents evolutions.

Effects of amiodarone injected intravenously (i.v.) at two doses (10 and 20 mg/kg) on perfused isovolumic rat hearts were assessed by P-31 nuclear magnetic resonance (NMR). P-31 NMR is used to measure intracellular myocardial pH, phosphocreatine (PCr), and ATP contents time evolutions. Myocardial mechanical function is estimated by heart rate (HR), left ventricular developed pressure (LVP), and coronary flow (CF). In experimental procedure A (2-h retrograde perfusion), drug injection induced a dose-dependent bradycardia (10-20%) and a slight decrease in LVP but did not affect CF, pH, PCr, or ATP contents. Experimental procedure B consisted of 30-min stabilization, 18-min ischemia, and 72-min reperfusion. During ischemia, amiodarone did not preserve ATP and PCr pools and did not alleviate acidosis. ATP decreased to 30% of its control values, whereas the PCr peak was hardly detectable after 12 min of ischemia. After 24 min of reflow, HR, PCr, and pH of treated hearts recovered. LVP recovered after 36 min, whereas for control hearts, HR, PCr, and pH recovered after 42 min and LVP did not reach its control values at the end of reperfusion time. Faster pH recovery is explained by a preservation of Na+/K+ ATPase due to the influence of amiodarone on membrane lipid dynamics.

The effect of aging and storage conditions on excised tissues as monitored by longitudinal relaxation dispersion profiles.

Knowledge about the dependence of NMR parameters of excised tissues on time and storage conditions is important for correct interpretation of in vivo clinical results based upon in vitro measurements which in many cases are easier to perform. Literature data on this topic are scarce and sometimes contradictory. In this study, we investigated the change of the proton longitudinal relaxation rate (1/T1) of freshly excised rat tissues with storage conditions over a wide range of proton Larmor frequencies (0.01-50 MHz). Special interest was paid to long-term storage in the deep frozen state. After deep freezing of tissue samples on dry ice, no significant changes in 1/T1 over the whole frequency range could be observed for brain tissue, whereas for muscle and liver tissue characteristic alterations were detected. We conclude that for normal brain tissue this storage procedure is suitable for the prediction of in vivo 1/T1 results from in vitro studies.

The uncommon longitudinal relaxation dispersion of human brain white matter.

Human brain white matter exhibits an uncommonly strong dispersion of 1/T1 at high fields. An additional relaxation pathway via the myelin lipids, which are not directly visible to medical NMR due to their fast T2 decay, is proposed. Relaxation dispersion data are successfully analyzed on the basis of this model.

The importance of nuclear magnetic relaxation dispersion (NMRD) profiles in MRI contrast media development.

Observation of the relaxivity of MRI contrast media over a wide range of magnetic fields is not only necessary for predicting their efficiency at any field but also compulsory for understanding and improving their mechanisms of action. The best experimental approach to this problem is the field cycling method, which allows the exploration of nuclear relaxation over a broad interval of magnetic field intensity but requires a specially dedicated instrument called a relaxometer. Particularly relevant are the relaxivity profiles of the two chelates Gd-DOTA and Gd-DTPA. Both show an important decrease from low to high fields within the current imaging range (0.02 T to 1.5 T). Although high field relaxivities of these chelates are similar, Gd-DTPA becomes less efficient in facilitating water protons relaxation at fields lower than 0.15 T. This behavior has to be related to different electronic relaxation times due to a different chelate symmetry.

Field-cycling relaxometry: medical applications.

Relaxometry between 10 kHz and 200 MHz (0.2 mT and 4.7 T) with a field-cycling device and a high-field-strength magnetic resonance (MR) unit permitted the determination of longitudinal relaxation rates of tissues and chemical compounds at numerous field strengths. The resulting nuclear magnetic relaxation dispersion profiles allowed the prediction of tissue contrast and efficacy of contrast agents at any field strength. Pure T1 contrast of normal brain tissue and pathologic lesions (multiple sclerosis, astrocytoma) increased from low field strengths to a maximum between 10 and 20 MHz and decreased afterward. Quadripolar dips reflecting the interaction between water and nitrogen atoms of the protein backbone appeared at 2.15 and 2.8 MHz, reducing T1 and opening the possibility of shorter imaging times and better tissue discrimination at these field strengths. Furthermore, it was shown that zero T1 contrast between normal and pathologic tissue samples may exist at certain field strengths. Gadolinium diethylenetriaminepentaacetic acid and gadolinium tetraazacyclododecanetetraacetic acid provided different contrast enhancement depending on the field strength.

[Carbon 13 nuclear magnetic resonance conformation studies of peptides with analgesic activity]. / Etude conformationnelle par résonance magnétique nucléaire du carbone 13 de peptides à activité antalgique.

13C Nuclear magnetic resonance studies of proline peptides with central antalgic activity (Pro-Arg, Arg-Pro, Pro-Arg-Pro, Pro-Lys-Pro) indicate a predominance of trans conformation at all pH values; but their physiological activities appear to be related to the ability of the C-terminal proline peptides to assume the cis conformation.