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71.
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
72.
OBJECTIVE: To examine the relationship between pregnancy incidence and the level of serum E2 during danazol therapy. DESIGN: Danazol was given by 200 mg four times daily for 3 months. Serum E2 level was checked after completing the therapy, but before stopping medication. Patients then were advised to conceive at the appropriate time over a 6-month period. SETTING: Reproductive and Endocrine Laboratory of the Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. PATIENTS: Infertile women with invasive endometriosis receiving conservative surgery and danazol treatment. INTERVENTIONS: Serum E2 is checked before medication and at the end of danazol therapy, but before stopping medication. MAIN OUTCOME MEASURES: Whether pregnancy is related to the change of serum E2 caused by danazol therapy. RESULTS: There were 24 pregnancies in 38 patients with invasive endometriosis after treatment. Pregnant patients had significantly lower serum E2 levels as compared with the nonpregnant patients. CONCLUSIONS: After conservative surgery for invasive endometriosis associated with infertility, the therapeutic period of danazol treatment could be shortened to 3 months. Because there is significant correlation of fecundability and serum E2 after danazol medication, serum E2 could be a guideline for predicting pregnancy or for prolonging or changing of treatment after danazol therapy. 相似文献
73.
The recent demonstration that myocardial Ca(2+)-independent phospholipase A2 exists as a complex of catalytic and regulatory polypeptides that is modulated by ATP has suggested a novel mechanisms through which alterations in glycolytic flux can be coupled to the generation of eicosanoids which facilitate insulin secretion. To determine the potential relevance of this mechanism, we examined the kinetic characteristics, substrate specificities, and cellular locus of phospholipase A2 activity in pancreatic islets. Rat pancreatic islets contain a Ca(2+)-independent phospholipase A2 activity which is optimal at physiologic pH, preferentially hydrolyzes phospholipid substrates containing a vinyl ether linkage at the sn-1 position, and prefers arachidonic acid compared to oleic acid in the sn-2 position. Rat islet Ca(2+)-independent phospholipase A2 activity is inhibited by the mechanism-based inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one and is stimulated by ATP. Purification of beta-cells from dispersed pancreatic islet cells by fluorescence-activated cell sorting demonstrated that beta-cells (but not non-beta-cells) contain Ca(2+)-independent, ATP-stimulated phospholipase A2 activity. Remarkably, clonal RIN-m5f insulinoma cells, which possess a defect in glucose-induced insulin secretion, contain a Ca(2+)-independent phospholipase A2 which is not modulated by alterations in ATP concentration. Collectively, these results and those of an accompanying paper [Ramanadham et al. (1993) Biochemistry (following paper in this issue)] implicate Ca(2+)-independent phospholipase A2 as a putative glucose sensor which can couple alterations in glycolytic metabolism to the generation of biologically active eicosanoids and thereby facilitate glucose-induced insulin secretion. 相似文献
74.
75.
Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus. 相似文献
76.
Nintu Mandal S. C. Datta K. M. Manjaiah B. S. Dwivedi R. Kumar P. Aggarwal 《Polymer-Plastics Technology and Engineering》2018,57(17):1760-1770
Novel zincated nanoclay polymer composites (ZNCPCs) with variable percentage of commercial bentonite and nanobentonite (8%, 10% and 12% of monomer for each case) were synthesized. Polyacrylic acid-Polyacrylamide copolymer was synthesized using N, N-Methylene bisacrylamide as crosslinker and ammonium persulfate as initiator. Clays as well as ZNCPCs were characterized by XRD, SEM, TEM and FTIR. 12% nanoclay containing formulation showed slowest release rate. ZNCPCs containing 8% clay recorded highest Zn content as well as highest equilibrium water absorbency. Biodegradation study revealed that Aspergillus spp was more effective as compared with Trichoderma spp in degradation of ZNCPCs. 相似文献
77.
Amino acid sequence of a four-iron-four-sulphur ferredoxin isolated from Bacillus stearothermophilus
T Hase N Ohmiya H Matsubara RN Mullinger KK Rao DO Hall 《Canadian Metallurgical Quarterly》1976,159(1):55-63
A novel method of RNA fractionation based on a gradual release of the RNA molecules from ribonucleoprotein complexes has been used for the analysis of ribosomal and non-ribosomal complexes of rat liver cytoplasm. Adsorption of native ribonucleoproteins on a Celite column (occuring through only the protein moiety) followed by a consequent dissociation of RNP complexes brought about by various agents results in RNA fractionation in accordance with the tightness of the RNA-protein bonds. The cytoplasmic ribosomal and rapidly labelled non-ribosomal RNA species are separated into several fractions identified as 18S and 28S rRNA's, mRNA and messenger-like RNA. A relatively small fraction (about 10% of the total) of rRNA tenaciously bound to protein has been also revealed. 相似文献
78.
PJ Colletier AS Garden WH Morrison H Goepfert F Geara KK Ang 《Canadian Metallurgical Quarterly》1998,20(8):674-681
BACKGROUND: This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy. METHODS: One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years. RESULTS: Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues. CONCLUSIONS: Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site. 相似文献
79.
This paper describes the various technological aspects related to adhesive wear of cast aluminium–silicon (Al–Si) alloys. Number of hypothesis and theories proposed in the last two decades in order to explain the different phenomenon related with wear and friction, and influence of test parameters (such as load, sliding speed, counter-surface) and work material properties (like mechanical and metallurgical) on tribological behaviour of aluminium–silicon alloys have been presented and discussed. 相似文献
80.