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DW Bonhaus KK Weinhardt M Taylor A DeSouza PM McNeeley K Szczepanski DJ Fontana J Trinh CL Rocha MW Dawson LA Flippin RM Eglen 《Canadian Metallurgical Quarterly》1997,36(4-5):621-629
The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described. 相似文献
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MW Byrne 《Canadian Metallurgical Quarterly》1997,2(4):27-34
Preventive services to assist parents to understand their children's developmental needs and to devise positive, culturally appropriate strategies for managing them are not recognized as important by most third party health service payers, especially managed care programs. Room-To-Grow is an intervention designed to meet identified community needs in a culturally appropriate and sensitive way. This article discusses the evolution of this intervention and the problems encountered in finding appropriate reimbursement streams. 相似文献
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HC Kwaan M Levin S Sakurai O Kucuk MW Rooney LJ Lis JW Kauffman 《Canadian Metallurgical Quarterly》1997,26(6):1061-1068
Digital gangrene was observed in a patient who had angiographic findings of digital arterial occlusion. The patient's blood showed a marked red blood cell aggregation with rouleaux formation in long chains, which could not be dispersed at shear rates up to 200 sec-1. Studies of the patient's blood revealed the presence of an abnormal fibrinogen capable of aggregating normal red blood cells. This fibrinogen was found by Raman spectroscopy to have an increased alpha-helical content, whereas the beta-sheet content was decreased. Defibrinogenation therapy with ancrod resulted in a dramatic symptomatic relief. The disappearance of the abnormal fibrinogen 6 months later and an absence of a family history indicate that this dysfibrinogenemia was acquired. 相似文献
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Dawn M. Scates John K. Hartwell John B. Walter Mark W. Drigert Jason M. Harp 《Nuclear Engineering and Design》2010,240(10):2493-2499
The US Department of Energy has embarked on a series of tests of TRISO coated particle reactor fuel intended for use in the Very High Temperature Reactor (VHTR) as part of the Advanced Gas Reactor (AGR) program. The AGR-1 TRISO fuel experiment, currently underway, is the first in a series of eight fuel tests planned for irradiation in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). The AGR-1 experiment reached a peak compact averaged burnup of 9% FIMA with no known TRISO fuel particle failures in March 2008. The burnup goal for the majority of the fuel compacts is to have a compact averaged burnup greater than 18% FIMA and a minimum compact averaged burnup of 14% FIMA. At the INL the TRISO fuel in the AGR-1 experiment is closely monitored while it is being irradiated in the ATR. The effluent monitoring system used for the AGR-1 fuel is the Fission Product Monitoring System (FPMS). The FPMS is a valuable tool that provides near real-time data indicative of the AGR-1 test fuel performance and incorporates both high-purity germanium (HPGe) gamma-ray spectrometers and sodium iodide [NaI(Tl)] scintillation detector-based gross radiation monitors. To quantify the fuel performance, release-to-birth ratios (R/B's) of radioactive fission gases are computed. The gamma-ray spectra acquired by the AGR-1 FPMS are analyzed and used to determine the released activities of specific fission gases, while a dedicated detector provides near-real time count rate information. Isotopic build up and depletion calculations provide the associated isotopic birth rates. This paper highlights the features of the FPMS, encompassing the equipment, methods and measures that enable the calculation of the release-to-birth ratios. Some preliminary results from the AGR-1 experiment are also presented. 相似文献