Imaging metabolite

Also the mirror image of the strueture I, eorreetly denoted as exo-3,10-dihydroxy-3,5,8,10-tetra-methyltrieyelo[6.2.2.0 ]dodeea-5,l 1-diene-4,9-dione, would be possible sinee enantiomers are not differentiated by NMR. A retro-Diels-Alder fragmentation of I to CsH/oO explains why the moleeular ion eorresponding to the moleeular formula C16//20O4 is not deteeted in the mass spee-trum. The metabolite I eould be formed by Diels-Alder dimerisation of 1,5-dimethyleyelohexa-l,3-dien-5-ol-6-one J as the primary metabolite which acts as diene and dienophile as well... 

Fehr, M., Ehrhardt, D. W., Lalonde, S. and Frommer, W. B. (2004a). Minimally invasive dynamic imaging of ions and metabolites in living cells. Curr. Opin. Plant Biol. 7, 345-51. 

Stoeckli M, Staab D, Schweitzer A. Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections. Int. J. Mass Spectrom. 2006 260 195-202. 

In a separate study, a protocol for Matrix-assisted laser desorption-ionization (MALDI) imaging mass spectrometry (IMS) has been proposed.18 This IMS technique provides a new approach to visualize spatial distribution of thousands of molecular species, including peptides, proteins, and their metabolites in two- or three-dimensional levels. This approach may also provide a straightforward method of determining the tissue distribution of multiple peptides or proteins in a quantitative manner.18 Chu et al.19 reported a nondestructive molecular extraction method to obtain proteins from a single FFPE or frozen tissue section, without destroying the tissue morphology, such... 

Durazzo TC, Gazdzinski S, Banys P, Meyerhoff DJ (2004) Cigarette smoking exacerbates chronic alcohol-induced brain damage a preliminary metabolite imaging study. Alcohol Clin Exp Res 28(12) 1849-1860... 

MR imaging provides determination of the MT-effect only for the water signal, whereas MR spectroscopy can enable determination of MT of metabolites. A detailed review on MT measurements by MR spectroscopy is given in Ref. 45. 

Fig. 29. Thirteen-year-old boy with Duchenne Dystrophy, (a) The fat selective image shows a fatty degeneration of all muscles in a cross-section of the lower limb. The fat tissue is orientated in the direction of the muscle fibres, and is present between the fibres and in the septa, (b, c) The spectra from both volume elements indicated in (a) reveal signals from EMCL. Muscle specific metabolites (TMA and creatine) are clearly reduced and not visible in the proton spectra due to the reduction of muscle tissue in favour of adipose tissue.

Besides the poor specificity of many of the assays used to determine plasma drug concentrations, another problem which has arisen from these studies has been the length of the "wash-out" period necessary before the patient is given the neuroleptic under investigation. As a result of the prolonged duration of blockade of dopamine receptors in the brain by conventional neuroleptics and their metabolites, it is necessary to allow a wash-out period of several weeks before the patients are subject to a pharmacokinetic study. This raises serious ethical questions. Perhaps with the advent of new imaging techniques it may be possible in the near future actually to determine the rate of disappearance of neuroleptics from the brain of the patient. This may enable the relationship between plasma concentration and clinical response to be accurately determined. 

In SUMMARY, it would appear that a detailed knowledge of the pharmacokinetics of the main groups of psychotropic drugs is only of very limited clinical use. This is due to limitations in the methods for the detection of some drugs (e.g. the neuroleptics), the presence of active metabolites which make an important contribution to the therapeutic effect, particularly after chronic administration (e.g. many antidepressants, neuroleptics and anxiolytics), and the lack of a direct correlation between the plasma concentration of the drug and its therapeutic effect. Perhaps the only real advances will be made in this area with the development of brain imaging techniques whereby the concentrations of the active drug in the... 

The potential of 4-p F]FMR for the imaging of sympathetic innervation is further confirmed by the development of analytical methods such as planar chromatographic analysis for the detection of its metabolites. This analytical method is well suited for microdialysis samples which have small volumes and low concentrations of compounds [177],... 

R.E. Hurd, D.M. Freeman, Metabolite specific proton magnetic-resonance imaging, Proc. Natl. Acad. Sci. USA 86 (1989) 4402-4406. 

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