No abstract

Abstract— γ‐Vinyl GABA (4‐amino‐hex‐5‐enoic acid, RMI 71754) is a catalytic inhibitor of GABA‐T in vitro. When given by a peripheral route to mice, it crosses the blood‐brain barrier and induces a long‐lasting, dose‐dependent, irreversible inhibition of brain GABA transaminase (GABA‐T). Glutamate decarboxylase (GAD) is only slightly affected even at the highest doses used. γ ‐Vinyl GABA has little or no effect on brain succinate semialdehyde dehydrogenase, aspartate transaminase and alanine transaminase activities. GABA‐T inhibition is accompanied by a sustained dose‐dependent increase of brain GABA concentration. From the rate of accumulation of GABA it was estimated that GABA turnover in brain was at least 6.5 μmol/g/h. Based on recovery of enzyme activity the half‐life of GABA‐T was found to be 3.4 days, that of GAD was estimated to be about 2.4 days. γ ‐Vinyl GABA should be valuable for manipulations of brain GABA metabolism.

We examine whether firms use social media to strategically disseminate financial information. Analyzing S&P 1500 firms' use of Twitter to disseminate quarterly earnings announcements, we find that firms are less likely to disseminate when the news is bad and when the magnitude of the bad news is worse, consistent with strategic behavior. Furthermore, firms tend to send fewer earnings announcement tweets and “rehash” tweets when the news is bad. Cross-sectional analyses suggest that incentives for strategic dissemination are higher for firms with a lower level of investor sophistication and firms with a larger social media audience. We also find that strategic dissemination behavior is detectable in high litigation risk firms, but not low litigation risk firms. Finally, we find that the tweeting of bad news and the subsequent retweeting of that news by a firm's followers are associated with more negative news articles written about the firm by the traditional media, highlighting a potential downside to Twitter dissemination. JEL Classifications: G14; G38; M10; M21; M41.

Incubation of rat brain 4-aminobutyrate aminotransferase with 4-amino-hex-5-enoic acid, a substrate analog of 4-aminobutyric acid, results in a time-dependent irreversible loss of enzymatic activity. In the presence of 0.1 mM inhibitor the half-life of the inactivation process is approximately 6 min. Low concentrations of L-glutamic acid or 4-aminobutyric acid protect against this inactivation, while 2-oxoglutarate prevents this protection, suggesting that only the pyridoxal form of the enzyme is susceptible to inhibition by 4-amino-hex-5-enoic acid.The irreversible inhibition of mammalian 4-aminobutyrate aminotransferase by 4-amino-hex-5-enoic acid is selective. There is no inhibition of this enzyme from Pseudomonas.fZuorescens with the inhibitor at mM concentrations. Even at 10 mM there is no irreversible inhibition of mammalian glutamate decarboxylase or of aspartate aminotransferase, while alanine aminotransferase is inhibited over 500 times more slowly than rat brain 4-aminobutyrate transaminase.4-Aminobutyric acid is believed to be an important inhibitory neurotransmitter in mammalian brain [l]. The major pathway for its degradation is via transamination with 2-oxoglutarate. Fowler and John [2] have described the specific irreversible inhibition of brain aminobutyrate transaminase by ethanolamine-0-sulphate, a substrate analog of 4-aminobutyric acid, which was effective in vivo when given intracisternally. Recently, 4-amino-hex-5-enoic acid (4-acetylene derivative of aminobutyric acid) was shown to be a potent catalytic inhibitor of aminobutyrate transaminase from Pseudomonas fluovescens [3,4]. In addition, it is effective against mammalian brain aminobutyrate transaminase in vitvo [5] and in vivo [5,6] when administered peripherally (P.o., i.p., i.v.).The concept of catalytic inhibition of enzymes as an approach toward the rational design of specific, irreversible, active-site-directed inhibitors of enzymes has attracted much attention, and has recently been Ahhrevintiom. Pyridoxal-P, pyridoxal phosphate. Ei7:yrnes.

Propofol proves to be an excellent sedative for ERCP and shows a shorter recovery time than midazolam. Because of the narrow therapeutic window, we recommend close patient monitoring.