Cisatracurium, (1R, 1'R, 2R, 2'R)-2,2-1,5-pentanediylbis-oxy(3-oxo- 3,1-propanediylbis1-(3,4-dimethoxyphenyl)-methyl-1,2,3,4- tetrahydro-6,7-dimethoxy-2-methylisoquinolinium dibenzenesulphonate ...(51W89), is an intermediate-acting neuromuscular blocking agent. 51W89 is one of ten isomers contained in Tracrium (atracurium besylate) and represents approximately 15 percent of the atracurium mixture. Clinical studies have indicated that 51W89 is more potent and is significantly weaker as a histamine releaser than atracurium. In vitro studies in human plasma have shown that, like atracurium, 51W89 spontaneously degrades at physiological pH by Hoffmann elimination to form laudanosine and the quaternary monoacrylate. Subsequent ester hydrolysis of the monoacrylate generates the monoquaternary alcohol. In rat plasma, 51W89 is also metabolized by non-specific carboxylesterases to the monoquaternary alcohol and the monoquaternary acid, the former being rapidly hydrolysed further to the more stable acid. It has been reported that laudanosine can be further metabolized via N-dimethylation to yield tetrahydropapaverine. The rate-limiting step in the degradation of 51W89 in human plasma is Hofmann elimination, whilst in rat plasma, the action of non-specific carboxylesterases is rate limiting. As part of the development of 51W89, the disposition of 14C-51W89 following a single intravenous bolus dose was studied in various animal species and humans. In the present work, we describe the identification of 51W89 metabolites in urine and bile from these studies by high performance liquid chromatography/mass spectrometry using pneumatically-assisted electrospray ionization coupled to an on-line radioactivity monitor.
This randomised prospective clinical study compared the use of an absorbable suture (subcuticular 4:0 polyglactin 910) and a non-absorbable suture (5:0 monofilament polypropylene) for elective carpal ...tunnel decompression wound closure. An increased perception of pain was reported by the patients in the polypropylene (Prolene®) group. At the 6-week assessment, there was a higher level of residual wound inflammation in the polyglactin 910 (Vicryl®) group.
Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. ...The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the compounds--N, O-didemethylated metabolite (21), O-demethylated metabolite (22), and diltiazem N-oxide (27)--have been recently reported and have not previously been synthesized. The identities of all eight synthetic metabolites have been verified with samples obtained from human urine using combined LC-MS/MS. The Ca2+ antagonistic activities of diltiazem and its metabolites (except 27) were studied on hamster aorta preparations depolarized with KCl. The order of potencies (IC50 +/- SE, microM) is as follows: diltiazem (0.98 +/- 0.47) greater than 17 (2.46 +/- 0.38) greater than or equal to 23 (3.27 +/- 1.02) greater than 26 (20.2 +/- 10.5) greater than 22 (40.4 +/- 15.4) greater than or equal to 25 (45.5 +/- 18.1) greater than 21 (112.2 +/- 33.2) greater than or equal to 24 (126.7 +/- 24.2). Structure-activity relationships are also discussed.
Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat ...from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.
A sensitive, robust and high throughput mass spectrometry based method is described for the determination of the glucocorticoid fluticasone propionate in plasma. The method employs solid-phase ...extraction in 96 well microtitre plate format which has been automated by means of a custom built Zymark robotic system. The extracts are analysed by liquid chromatography–tandem mass spectrometry using thermally and pneumatically assisted electrospray ionisation and selected reaction monitoring. The method is both accurate and precise with both intra- and inter-assay precision (C.V.) of less than <6%. The method provides a lower limit of quantification of 20 pg/ml from 0.5 ml of human plasma, sufficient to monitor systemic concentrations of inhaled fluticasone propionate at therapeutic doses.
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