In vivo NMR in pharmaceutical research.

In vivo NMR techniques are currently well established in pharmaceutical research and will likely become increasingly important in the future, as they procure noninvasively morphological, physiological, and biochemical information. The status of magnetic resonance imaging (MRI) and spectroscopy (MRS) in drug development is discussed on the basis of the characterization and evaluation of a rat model of ischemic stroke and the development and profiling of drugs for cerebral ischemia in this model. It can be concluded that MRI is well suited for drug screening (quantitative determination of lesion size), while dynamic MRI and MRS techniques provide relevant information on the mechanism of drug actions. The possibility to follow changes, pathological and therapeutic, in the same individual is important from two points of view. First, variations due to interindividual differences may be eliminated, increasing the statistical power of the results. Second, dose and/or time dependence of a drug can be explored in the same individual. As a result, the number of animals required for a study will be reduced, which from both ethical and economic aspects is highly desirable.     

Manifolds with invariant semi-Riemannian almost product structure

A manifold M with semi-Riemannian almost product structure invariant relative to a transformation group G is considered. A connection with special G-invariance property is constructed in the corresponding bundle of frames.Translated from Ukrainskii Matematicheskii Zhurnal, Vol. 44, No. 7, pp. 926–931, July, 1992.     

Magnetic resonance findings in sarcoidosis of the thorax.

Fifteen patients with sarcoidosis underwent thoracic MRI examinations. The T2 signal intensity of lymphadenopathy varied, with no characteristic pattern noted. Three of four patients with bright lymph nodes on T2 images had stage I sarcoidosis, but low intensity nodes were also seen in stage I patients. Coronal images were complementary to axial images and better depicted subcarinal adenopathy. MRI does not distinguish the lymphadenopathy of sarcoidosis from other entities, but is useful for defining the anatomic extent of disease and differentiating pulmonary artery enlargement from adenopathy.     

Intramolecular hemiacetals. The acid-base-catalyzed ring-chain interconversion of 2-substituted 2-hydroxy-4,4-dimethylmorpholinium cations in aqueous solution.

The ring-chain tautomerism in aqueous solution of some aryl-substituted morpholinium salts (bromides), has been studied and equilibrium constants are reported. In the crystals the substrates exist entirely in their cyclic forms as hemiacetals, but in aqueous solution NMR measurements reveal that an equilibrium is established between the cyclic (hemiacetal) and the noncyclic (ketone) form, the degree of ring-opening being more pronounced with electron-donating aryl substituents at the carbonyl carbon. The kinetics of the ring-chain interconversion in water has been investigated spectrophotometrically by a 'pH jump' stopped-flow technique. General base catalysis is observed with a Br?nsted beta value apparently independent of substituent and equal to 0.60. The Hammett rho values for various base catalysts are close to those for very similar intermolecular reactions involving hemiacetal breakdown, leading to the suggestion of a 'normal' class n mechanism for base catalysis. For acid catalysis, however, a quite different situation is encountered, since no general acid but only (weak) catalysis by the hydronium ion can be detected. We believe this deviation from 'normal' general acid catalysis is caused by an electrostatic interaction, and we suggest that it might result from a change in the usual class e mechanism for general acid catalysis by a situation in which rate-limiting concerted proton transfer is replaced by rate-limiting preprotonation. This is supported by the observed drastic change in Hammett rho value for catalysis by the hydronium ion, compared with the 'normal' case. An interesting case is encountered for the 4-aminophenyl-substituted substrate, in which the amino group becomes protonated in acid solution, thus representing a new substituent. Despite this complication, the various equilibrium and rate constants may also be evaluated experimentally for this substrate.     

Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations in young women as determined using high performance liquid chromatography.

Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations of 21 young white women, 21-27 years, having radiomonitored pyridoxal 5'-phosphate and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate vitamin B-6 status were determined in an effort to establish normal ranges for plasma B-6 vitamers. B-6 vitamers and 4-pyridoxic acid were quantitated using reversed phase high performance liquid chromatography with fluorometric and ultraviolet detection. Pyridoxal phosphate values obtained by radioenzymatic and chromatographic, fluorometric and ultraviolet, assays were highly correlated as were pyridoxine phosphate values determined using both detectors. The B-6 vitamer and 4-pyridoxic acid values of these subjects should be of use in the establishment of normal ranges of these congeners in women.     

Certified reference materials for the quality control of analysis in the environment

Summary The Community Bureau of Reference (BCR) has undertaken the production of a wide range of certified reference materials (CRMs) for the improvement of accuracy and measurement harmony in various areas of concern at European Community level. This paper provides an overview of the sectors of the BCR-programme in the field of environment i.e. for water systems (water, sediment, biota), soil analysis (soil, fertiliser, waste), plant analysis (aquatic and terrestrial plants), analysis related to animals (e.g. muscle or liver) or man (e.g. industry and food).