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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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We investigated the follow-up methods used by counseling centers to evaluate the individual counseling services that they provide. A sample of 80 centers was selected for study; these were centers that indicated that the primary form of evaluation was a locally developed instrument used to assess clients' post counseling status and satisfaction with their counseling. We used a questionnaire to assess data-gathering procedures, follow-up practices, rates of return, and uses made of the data as well as resulting problems and trends. Major issues addressed include the low percentage of return rates of satisfaction questionnaires and the effect of these rates on possible response bias. The use of center survey results to evaluate client status and counselors' work is discussed. The issue of the timing of satisfaction surveys of clients is raised, particularly in light of procedures that combine clients who have previously terminated counseling and clients still in the process of counseling. The issues of self-report and the need for more rigorous methodologies are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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