[Case of Recklinghausen's disease presenting as acute porphyria in the terminal stage].
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Biomedical subjects
Publications and source records attributed to H Masumoto.
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Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, rapidly reacts with peroxynitrite, the rate constant being of the order of 10(6) M-1 s-1; the reaction yields the selenoxide of the parent molecule, 2-phenyl-1,2-benzisoselenazol-3(2H)-one 1-oxide, as the sole selenium-containing product; a stoichiometry of 1 mol of ebselen reacted and of the selenoxide formed per mole of peroxynitrite was observed. The reaction was studied in detail at neutral and alkaline pH (pH 10-11). It also proceeds at acidic pH where peroxynitrous acid (ONOOH) is predominant, the yield of the selenoxide being lower because peroxynitrous acid (pKa = 6.8) decays rapidly. Reduction of the selenoxide in cells to regenerate ebselen would allow for a sustained defense against peroxynitrite. This novel reaction constitutes a potential cellular defense line against peroxynitrite, one of the important reactive species in inflammatory processes.
2-(Methylseleno)benzanilide (MeSe), a main metabolite of ebselen in vivo, rapidly reacts with peroxynitrite, yielding 2-(methylseleninyl)benzanilide (MeSe = O) as the sole selenium-containing product. The reaction proceeds efficiently at acidic pH where peroxynitrous acid (ONOOH) is predominant, suggesting that MeSe reacts faster with ONOOH than with the peroxynitrite anion (ONOO-). MeSe is much less reactive with hydrogen peroxide. The second-order rate constant for the reaction at 22 degrees C was estimated from the relationship between substrate consumption and peroxynitrite concentration as 2.2 x 10(4) M-1 s-1 and 2.7 x 10(3) M-1 s-1 at pH 3.9 and 7.0, respectively, and from intermolecular competition with ascorbic acid as 3.4 x 10(3) M-1 s-1 at pH 7.1. The rate constant is about 2 orders of magnitude lower than that for the reaction of ebselen with peroxynitrite, but about 1-2 orders of magnitude higher than that reported in the literature for methionine or ascorbate. The selenoxide can be reduced back to MeSe by thiols. MeSe has previously been considered to be an inert metabolite of ebselen, but may show antioxidant activity against peroxynitrite.
The maze procedure may be performed in combination with valve operations to treat chronic atrial fibrillation associated with valve dysfunction. Although we initially used the modified Cox maze III procedure, a more limited partial maze procedure is now preferred because the left atrium might be considered as the electrical impetues for atrial fibrillation. In this study we compared the results of 30 patients (group I) who underwent the full biatrial modified Cox maze III and 20 (group II) patients the partial maze procedure. While the rates of restored sinus rhythm were the same in both groups at 6-month follow-up (I: 83.3%, vs II: 80%), the following advantages were noted in the patients undergoing the partial maze procedure: shorter operative times, lesser elevations of creatine phosphokinase, lower rate of blood transfusion, lower rate of junctional rhythm soon after the operation, and a higher P wave in those patients with restored sinus rhythm. The effectiveness of the partial maze procedure seems equal to that of the biatrial modified Cox maze III procedure for atrial fibrillation associated with valve disease. The partial maze procedure is simple and less invasive, and thus might be applied more frequently as an additional procedure to valve operations without additional risk.
An application of encapsulated lipase to the hydrolysis of triacetin (triglyceride of acetic acid) was carried out with a continuous stirred tank reactor, in which the encapsulated enzyme was dispersed. An automatic control device to control pH of the reaction mixture at a desired level was designed and installed in the reactor system. Conversion of triacetin at the steady state operation with pH controlled became significantly higher than that without pH control. A particular kinetic model proposed by the authors, which regarded the mass-transfer through the wall of microcapsules as a dominant resistance to the overall reaction rate, was also applicable to simulate the behaviour of CSTR system as in the case of packed-bed reactor.
Oxidations of the piperidine ring by chemical model and liver microsomal systems were investigated with a simple piperidine derivative, N-benzylpiperidine (BP) (3), as the substrate in order to probe the generality and the mechanism of the biotransformation of the piperidine ring. The piperidine ring of BP (3) as well as that of phencyclidine (1) was suggested to be oxidized to a ketone at the beta-position in the meso-tetraphenylporphinatoiron(III) chloride system, and the reaction was expected to occur in the liver microsomal system. The beta-oxo formation was observed directly in the liver microsomal system, and found to be dependent on cytochrome P-450. Then it was suggested that the piperidine-beta-oxo formation was a general oxidation pathway of the piperidine biotransformation. Hydrogen abstraction in the reaction was not a rate-determining step. Therefore, we presumed a possible mechanism of beta-oxo formation via BP-iminium (21). From the comparative study on the reactivities of dipropylbenzylamine (DPB) (18) and BP (3), and the stabilities of iminium (Im+) species of BP (3) and DPB (18), it was suggested that BP-Im+ (21) was relatively stable and was the most likely precursor of BP-beta-oxo (6). BP-Im+ (21) and its free base, enamine (29), afforded large amounts of BP-beta-oxo as well as BP-alpha-oxo (9) in the chemical model and the microsomal systems. This evidence supported the iminium-enamine mechanism expressed as scheme III.
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