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131.
132.
Effects of SP500263, a Novel Selective Estrogen Receptor Modulator, on Bone, Uterus, and Serum Cholesterol in the Ovariectomized Rat 总被引:1,自引:0,他引:1
Sutherland MK Brady H Gayo-Fung LM Leisten J Lipps SG McKie JA O'Leary E Patnaik N Anderson DW Bhagwat SS Stein B 《Calcified tissue international》2003,72(6):710-716
We describe here the activity of a novel selective estrogen receptor modulator, SP500263. When given to adult ovariectomized (OVX) rats for 28 days at doses of 0.3, 1, or 3 mg/kg/day, we found that SP500263 partially protected against OVX-induced loss of bone mineral content in the distal ends of femurs and in the whole bone. SP500263 also antagonized the OVX-induced increase in body weight. However, unlike 17-estradiol, SP500263 at efficacious doses did not prevent the OVX-induced loss in uterine wet weight. A small but significant effect on uterine wet weight was noted with raloxifene dosed at 1 mg/kg. As expected, SP500263 but not raloxifene acted as an estrogen antagonist on the uterus in adult rats when administered for 7 days at 30 mg/kg/day. Finally, SP500263 had no statistically significant effects on total serum cholesterol and serum triglycerides in OVX rats treated for 28 days. Raloxifene had no significant effects on body weight, bone mineral content, and serum cholesterol or triglycerides in the OVX-rat model. In summary, SP500263 is a new orally active SERM that acts in rats as an estrogen agonist on bone without causing uterine stimulatory effects.
Present addresses: M. Kung Sutherland, Celltech R&D, Inc., Bothell, WA 98021, USA. L. M. Gayo-Fung, Structural Genomix Inc., San Diego, CA 92121, USA. E. OLeary, Chugai Pharma,USA, San Diego, CA 92121, USA, D. W. Anderson, Graceland University, Lamoni, IA 50140, USA. 相似文献
133.
134.
Zhu YF Gross TD Guo Z Connors PJ Gao Y Tucci FC Struthers RS Reinhart GJ Saunders J Chen TK Killam Bonneville AL Chen C 《Journal of medicinal chemistry》2003,46(11):2023-2026
Based on SAR from bicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported. 相似文献
135.
Several novel series of iodinated compounds based on the thioflavin backbone structure have been developed and characterized. These iodinated compounds showed high specific binding to amyloid beta (Abeta) aggregates with subnanomolar to nanomolar affinities. Probes like IMPY and MIPA display high brain uptakes and fast washout in normal mice, resulting in low background signals (presumably no amyloid plaques present in normal mouse brain), whereas TZDM shows long brain retention in normal mice suggesting high nonspecific in vivo binding. It is likely that tracers, that is, IMPY or MIPA, with desirable in vivo properties, will provide the highest target to non-target ratio; therefore, they are most likely to be successful as imaging agents targeting Abeta plaques in the brain. 相似文献
136.
Although perforation of the appendix is considered a risk factor for female tubal infertility, the epidemiologic evidence supporting this relation is inconsistent. Risk factors for tubal infertility were compared for 121 women with documented primary tubal infertility attending in vitro fertilization clinics in Toronto, Canada, from July to December 1998 and 490 controls who were pregnant during the same time period. Self-administered questionnaires and review of medical records were used to assess exposures. The authors found that neither history of acute appendicitis nor perforation of the appendix was a statistically significant risk factor for tubal infertility. The crude odds ratio for perforated appendicitis was 3.4 (95% confidence interval (CI): 0.9, 12.9), and the adjusted odds ratio was 1.4 (95% CI: 0.3, 6.2). In addition to increased age and annual income, cigarette smoking (odds ratio (OR) = 2.0, 95% CI: 1.2, 3.2), history of endometriosis (OR = 6.0, 95% CI: 2.8,12.8), and history of pelvic inflammatory disease (OR = 6.0, 95% CI: 2.8, 12.8) were significantly associated with tubal infertility in multivariate analysis. These data do not provide substantial evidence that perforation of the appendix is an important risk factor for female tubal infertility. 相似文献
137.
Wong BC Wang WH Wong WM Lau GK Fung FM Kung NN Chu KM Lai KC Hu WH Hu FL Liu XG Chan CK Yuen MF Hui WM Lam SK 《Alimentary pharmacology & therapeutics》2001,15(6):843-849
AIM: To compare the efficacy and tolerability of a 3-day quadruple therapy with a standard 7-day triple therapy in eradicating Helicobacter pylori infection and healing duodenal ulcers. METHODS: Patients with H. pylori-positive duodenal ulcers were randomized to receive either lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 400 mg twice daily for 7 days (LCM-7) or lansoprazole 30 mg, clarithromycin 500 mg, metronidazole 400 mg, and bismuth subcitrate 240 mg twice daily for 3 days (LCMB-3). No pre- or post-treatment acid suppression was used. Follow-up endoscopy was performed at week 6. RESULTS: A total of 118 patients were recruited. Sixty patients in the LCM-7 group and 53 patients in the LCMB-3 group returned for endoscopy. Intention-to-treat eradication rates were 87% and 86% (P=0.94) and per protocol eradication rates were 87% and 94% (P=0.29) in the LCM-7 and LCMB-3 groups, respectively. Per protocol and intention-to-treat ulcer healing rates were 98% and 98% in LCM-7 and 100% and 91% in LCMB-3, respectively. There were no significant differences in efficacy in relation to the initial metronidazole and clarithromycin susceptibility. Significant reduction in the duration of side-effects was found in the LCMB-3 group. CONCLUSION: The 3-day quadruple therapy is highly effective, better tolerated and can be considered as a first-line therapy in duodenal ulcer management. 相似文献
138.
Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak 总被引:18,自引:0,他引:18
Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer. 相似文献
139.
A 74-year-old woman suffered from lower legs weakness after a motor vehicle accident. Magnetic resonance imaging (MRI) on the seventh posttraumatic day, revealed a lumbar spinal subdural hematoma at the level of L4-5. After surgical intervention to remove the subdural hematoma, the patient made a complete recovery. 相似文献
140.
OBJECTIVE: The delivery of appropriate treatment to persons who have mental and substance use disorders is of increasing concern to clinicians, administrators, and policy makers. This study sought to describe use of appropriate mental health and comprehensive substance abuse care among adults in the United States with probable co-occurring disorders. METHODS: Data from the Healthcare for Communities survey, which is based on a national household sample studied in 1997 and 1998, were used to identify individuals who had probable co-occurring mental and substance use disorders. The sociodemographic and clinical characteristics of these individuals and their use of services were recorded. Logistic regression analysis was used to identify variables associated with receipt of mental health and substance abuse treatment and with receipt of appropriate treatment. RESULTS: Estimates for the U.S. adult population based on the weighted survey data indicated that 3 percent of the population had co-occurring disorders. Seventy-two percent did not receive any specialty mental health or substance abuse treatment in the previous 12 months; only 8 percent received both specialty mental health care and specialty substance abuse treatment. Only 23 percent received appropriate mental health care, and 9 percent received supplemental substance abuse treatment. Perceived need for treatment was strongly associated with receipt of any mental health care and with receipt of appropriate care. CONCLUSIONS: Despite the availability of effective treatments, most individuals who had co-occurring mental health and substance use problems were not receiving effective treatment. Efforts to improve the care provided to persons who have co-occurring disorders should focus on strategies that increase the delivery of effective treatment. 相似文献