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31.
CS Walpole R Wrigglesworth S Bevan EA Campbell A Dray IF James KJ Masdin MN Perkins J Winter 《Canadian Metallurgical Quarterly》1993,36(16):2381-2389
Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency. 相似文献
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The design and operation principle of existing portable mechanization means and technological features of their application in assembling joints in plating are investigated; structural and technological features of tooling and assembly equipment are described, the physiology of labour in assembling plating joints is analysed, including static and dynamic loading of the hands when carrying over, holding and application of assembling means on different levels in relation to the height of the worker body, the maximum allowable weight and size parameters of portable mechanization means for assembling plating joints are determined and the results of development of new specialized equipment for mechanization of assembling of joints’ pneumohydraulic operating mode are described. 相似文献
33.
KB Alton T Kosoglou S Baker MB Affrime MN Cayen JE Patrick 《Canadian Metallurgical Quarterly》1998,20(2):307-323
Eptifibatide, a synthetic peptide inhibitor of the platelet glycoprotein IIb/IIIa receptor, has been studied as an antithrombotic agent in a variety of acute ischemic coronary syndromes. The purpose of the present study was to characterize the disposition of 14C-eptifibatide in man after a single intravenous (i.v.) bolus dose. 14C-Eptifibatide (approximately 50 microCi) was administered to eight healthy men as a single 135-microgram/kg i.v. bolus. Blood, breath carbon dioxide, urine, and fecal samples were collected for up to 72 hours postdose and analyzed for radioactivity by liquid scintillation spectrometry. Plasma and urine samples were also assayed by liquid chromatography with mass spectrometry for eptifibatide and deamidated eptifibatide (DE). Mean (+/- SD) peak plasma eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first sampling time (5 minutes), and concentrations then generally declined biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a mean terminal elimination half-life of 1.13 +/- 0.17 hours. Plasma eptifibatide concentrations and radioactivity declined in parallel, with most of the radioactivity (82.4%) attributed to eptifibatide. A total of approximately 73% of administered radioactivity was recovered in the 72-hour period following 14C-eptifibatide dosing. The primary route of elimination was urinary (98% of the total recovered radioactivity), whereas fecal (1.5%) and breath (0.8%) excretion was small. Eptifibatide is cleared by both renal and nonrenal mechanisms, with renal clearance accounting for approximately 40% of total body clearance. Within the first 24 hours, the drug is primarily excreted in the urine as unmodified eptifibatide (34%), DE (19%), and more polar metabolites (13%). 相似文献
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EM Manno DR Gress LH Schwamm MN Diringer CS Ogilvy 《Canadian Metallurgical Quarterly》1998,29(2):422-428
BACKGROUND AND PURPOSE: Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage. METHODS: Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of > 15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation. RESULTS: In 10 of 19 patients (53%), TCD velocities changed by > 15% and paralleled changes in mean arterial pressure. This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%). Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation. CONCLUSIONS: In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood flow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage. 相似文献
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MN Mévélec O Mercereau-Puijalon D Buzoni-Gatel I Bourguin T Chardès JF Dubremetz D Bout 《Canadian Metallurgical Quarterly》1998,20(4):183-195
GRA4, a dense granule protein of Toxoplasma gondii elicits both mucosal and systemic immune responses following oral infection of mice with cysts. We studied the antigenicity and immunogenicity of truncated and soluble forms of GRA4 expressed as glutathione S-transferase fusion proteins in Escherichia coli. Protein C (amino-acids 297-345) was particularly well recognized by serum IgG antibodies, milk IgA antibodies and intestinal IgA antibodies from T. gondii infected mice and by serum IgG antibodies from T. gondii infected humans and T. gondii infected sheep. One major B epitope was localized within the last 11 C-terminal residues of GRA4. A second epitope, recognized with lower frequency, was mapped within the region 318-334. In contrast, the N domain of GRA4 (amino acids 25-276) was poorly recognized. Oral immunization of C57BL/6 mice with N, C or NC (amino acids 25-276 fused to 297-345) in association with cholera toxin induced a significant production of serum anti-GRA4 IgG antibodies but a weak and inconsistent intestinal anti-GRA4 IgG antibody response and afforded partial resistance to oral infection with T. gondii. These results provide new molecular and immunological understanding of GRA4 and indicate that it is a potential candidate for oral vaccination against T. gondii. 相似文献
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