Selective and non-selective trophic actions on central cholinergic and dopaminergic neurons in vitro.
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beta-Adrenoceptor blockers with disparate properties may have differential influences on arterial pulse wave velocity (PWV). Therefore, influences of single medium doses of bisoprolol, propranolol and celiprolol on PWV were compared in healthy subjects. Arterial PWV was obtained from the time delay between flow pulses measured from the root of the aorta and the popliteal artery. Bisoprolol and propranolol decreased arterial PWV more than placebo (P less-than-or-equal to .002) and celiprolol (P<.0001). In conclusion, the acute effects of bisoprolol and propranolol on arterial PWV in normotensive subjects seem to differ from that of celiprolol.
1. D-myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an isomer of the second messenger substance, D-myo inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes anti-inflammatory and analgesic effects and antagonism of neuropeptide Y (NPY)-mediated cellular responses. 2. However, not all responses elicited by this neuropeptide are sensitive to antagonism by pp56. Evidence is emerging, at least in certain tissues, that other receptor populations, in addition to those for NPY, are also sensitive to inhibition by pp56. 3. A direct or allosteric interaction of pp56 at receptors for NPY is now considered unlikely and it is more probable that pp56 might interfere at some point in the phosphatidylinositol signaling pathway, possibly at the level of the plasmalemmal inositol 1,3,4,5, tetrakisphosphate receptor. 4. Full realization of the therapeutic potential of this novel compound, however, must await a thorough characterization of the cellular mechanism(s) associated with the various pharmacological effects of pp56.
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On the basis of nucleic acid relationships, the family Neisseriaceae consists of the genera Neisseria, Kingella, Simonsiella and of Alysiella filiformis, Eikenella corrodens, and the CDC groups EF-4 and M-5. Differentiation, especially of the new members of the family, by conventional phenotypic characteristics is difficult and in some cases leads to doubtful results. On the other hand, cellular components proved to be suitable for the characterization of bacterial taxa. We investigated the cellular carbohydrates derived from whole cell hydrolysates of the above mentioned taxa with the exception of Neisseria by gas chromatography/mass-spectrometry. The analysis revealed characteristic patterns for all taxa considered, although with some species of which only few strains were investigated so far only preliminary results could be established. With the method used, the carbohydrate analysis could be completed within six hours starting from a pure culture. All strains investigated exhibited a common pattern with ribose, arabinose, glucose, and galactose. Qualitative and quantitative differences in contents of fucose, sorbose, rhamnose, threose, heptose, galactosamine and an amino sugar similar to glucosamine discriminated members of the taxa investigated. To achieve a taxonomically precise differentiation of the species investigated by conventional phenotypic features as available in commercial rapid test kits, these tests should be completed by the carbohydrate analysis technique presented.
Synthetic chemosensors hold great potential in many diagnostic applications. In this study, we describe the design and preparation of the first encoded combinatorial library of chemosensors for tripeptides. Subsequent screening of the library resulted in the discovery of novel chemosensors able to distinguish between random tripeptides.
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Heme oxygenases from the bacterial pathogens Neisseriae meningitidis (nm-HO) and Pseudomonas aeruginosa (pa-HO) share significant sequence identity (37%). In nm-HO, biliverdin IXalpha is the sole product of the reaction, whereas pa-HO yields predominantly biliverdin IXdelta. We have previously shown by NMR that the in-plane conformation of the heme in pa-HO is significantly different from that of nm-HO as a result of distinct interactions of the heme propionates with the protein scaffold [Caignan, G. A., Deshmukh, R., Wilks, A., Zeng, Y., Huang, H. W., Moenne-Loccoz, P., Bunce, R. A., Eastman, M. A., and Rivera, M. (2002) J. Am. Chem. Soc. 124, 14879-14892]. In the report presented here, we have extended these studies to investigate the role of the distal helix by preparing a chimera of nm-HO (nm-HOch), in which distal helix residues 107-142 of nm-HO have been replaced with the corresponding residues of the delta-regioselective pa-HO (112-147). Electronic absorption spectra, resonance Raman and FTIR spectroscopic studies confirm that the orientation and hydrogen bonding properties of the proximal His ligand are not significantly altered in the chimera relative those of the wild-type proteins. The catalytic turnover of the nm-HOch-heme complex yields almost exclusively alpha-biliverdin and a small but reproducible amount of delta-biliverdin. NMR spectroscopic studies reveal that the altered regioselectivity in the chimeric protein likely stems from a dynamic equilibrium between two alternate in-plane conformations of the heme (in-plane heme disorder). Replacement of K16 with Ala and Met31 with Lys in the chimeric protein in an effort to tune key polypeptide-heme propionate contacts largely stabilizes the in-plane conformer conducive to delta-meso hydroxylation.
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The endo:exo ratio of 0.35:1 for the reaction of cyclopentadiene with methyl methacrylate observed in organic solvents can be converted to 3:1 in chloroaluminate ionic liquids with their effective reuse in Diels-Alder reactions.
[reaction: see text] We have found a new synthetic method for the preparation of the alpha-bromoketones that are brominated in the less activated terminal position of unsymmetrical ketones. Brominations in short reaction times (kinetically controlled) provided internally brominated compounds as a major product. However, brominations in longer reaction times (thermodynamically controlled) gave more of the terminally brominated compound through the reversible reaction by Br(2) and produced hydrogen bromide. Several brominated compounds at the terminal position were successfully prepared through the new synthetic route.
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