Morphometric characterization of the neuromuscular junction of rodents intoxicated with 2,4-dithiobiuret: evidence that nerve terminal recycling processes contribute to muscle weakness.
ABSTRACT 2,4-Dithiobiuret (DTB) causes ascending motor weakness when given chronically to rodents. In muscles of animals with DTB-induced weakness, quantal release of acetylcholine (ACh) is impaired. We examined in detail the structural changes that occurred at neuromuscular junctions and their associated Schwann cells of extensor digitorum longus (EDL) muscles of male rats treated with DTB to the onset of muscle weakness, 5-8 days. Our objective was to assess the involvement of the Schwann cells and to determine the most likely primary targets of DTB. At the onset of muscle weakness, nerve terminals exhibited some enlarged regions, but did not sprout. Terminal Schwann cells became flatter and expanded to cover most of the endplate. The extent of invasion of the synaptic cleft by Schwann cell processes was not significantly different from controls; extension of Schwann cell sprouts away from the junction was not seen. Thus, the morphology of the Schwann cells, although clearly affected by DTB, does not suggest that they contribute directly to the physiological defects of DTB-treated terminals. Abnormal tubulovesicular structures or tangles of neurofilaments were clustered in the centers of about 25% of treated terminals. Fewer synaptic vesicles occupied the region opposite the postsynaptic folds. Vesicle volumes were variable and included some very large vesicles, corresponding with the variable MEPP amplitudes reported previously for terminals of DTB-treated rodents. The postsynaptic area stained by rhodamine-labeled alpha-bungarotoxin expanded with terminal swelling, apparently by unpleating of the postsynaptic folds. No loss of ACh receptors or spread of ACh receptors beyond terminal boundaries was detected. Morphometric data are consistent with the conclusion that DTB affects, either directly or indirectly, vesicular release of ACh and the subsequent vesicular recycling process.
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ABSTRACT: Carbon with the C(0) state has been reported recently, examples of which were known for the past decades. Silicon in the Si(0) state and phosphorus in the P(I) state are also known experimentally. This prompted us to search for divalent N(I) compounds, which resulted in the identification of ::N(←L)(2)(⊕) systems with bicoordinated nitrogen in the N(I) formal oxidation state. It was found that several biguanide derivatives (especially in their protonated state) belong to this class. Quantum chemical analysis provided the structural details, molecular orbitals, charge localization (vs delocalization) trends, etc. This class of compounds has been found to be characterized by two lone pairs on the central nitrogen, very similar to the central carbon in divalent C(0) compounds (::C(←L)(2)). The new bonding environment for nitrogen reported in this article, divalent nitrogen N(I), is clearly different from the nitrenium ions NR(2)(⊕). The electronic structure and reactivity of representative examples of this novel class of divalent nitrogen N(I) systems (::N(←L)(2)(⊕)) have been analyzed in detail, in terms of molecular orbitals, atomic charges, protonation energies, complexation energies with Lewis acids like BH(3), AlCl(3), and AuCl and compared with those of divalent C(0) systems.The Journal of Physical Chemistry A 06/2011; 115(26):7645-55. DOI:10.1021/jp111017u · 2.78 Impact Factor
Biochemistry and Cell Biology 01/1961; 39(4):787-827. DOI:10.1139/o61-081 · 2.35 Impact Factor
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ABSTRACT: In several literature reports biuret and its sulfur analogs are reported to exist in their diketo form with general formula H2NCXNHCYNH2 (X = O, Y = O, biuret; X = Y = S, dithiobiuret; and X = O, Y = S, thiobiuret). On the other hand, recently reported results on the electronic structure of biguanide analogs (X = Y = NH)demonstrated that a form equivalent to diketo is not the preferred structure. Thus, a systematic ab initio study on the tautomeric preferences of biuret and its sulfur analogs (dithiobiuret and thiobiuret) has been carried out. The results indicate that an interplay of conjugative stabilization and intramolecular hydrogen bonding to play a role in tautomeric preferences. Energy and geometric parameters, natural bond orbital analyses have been employed to understand the chemistry of the title compounds. The results indicate that unlike biguanides, these compounds prefer diketo forms containing hydrogen on the bridging nitrogen (N4) and in a trans-arrangement (1a–4a). However, tautomerization of these keto forms to the corresponding enol isomers was also found to be highly probable. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008International Journal of Quantum Chemistry 01/2008; 108(7):1277 - 1286. DOI:10.1002/qua.21629 · 1.17 Impact Factor