In addition to the rhodopsin crystal structure, high-resolution crystal structures of ligand-mediated G-protein-coupled receptors (GPCRs) have recently become available, and these have become attractive templates for developing homology models of several GPCRs of therapeutic interest. These crystal structures and the homology models derived from them have provided significant insights into ligand–receptor interactions. Moreover, several studies have demonstrated that the structural models are indeed suitable for virtual screening of compound databases to identify new ligands for various GPCRs. Recent examples of such virtual screening against GPCRs are discussed in this review. 相似文献
The goals of this report are: 1) to review the number needed to treat (NNT) concept, which, although well established in many sectors of medicine, is still relatively new to the radiotherapy community; 2) to discuss several clinical radiotherapy examples illustrating the inherent advantages of the NNT approach; and 3) to discuss potential future roles of the NNT concept within radiotherapy. 相似文献
It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield. 相似文献
Purpose. The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined.
Material and Methods. Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes).
Results. The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008).
Conclusion. Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch. 相似文献