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A simple ternary complex model of drug-receptor interaction has been used to extend the procedure of pharmacological resultant analysis, enabling the quantitation of interactions between allosteric modulators and orthosteric antagonists. Equations derived in the theoretical treatment were used to analyse functional data for the interaction between the allosteric modulator gallamine and the orthosteric antagonist scopolamine, with oxotremorine as the agonist, at rat tracheal muscarinic acetylcholine receptors. Quantitative estimates of the affinity of gallamine for the allosteric site (pKZ = 4.7) and the extent of negative, heterotropic co-operativity between gallamine and scopolamine (α′ = 13.1) were obtained. Furthermore, an alternative direct, model-fitting approach, that does not rely on the determination of concentration ratios, was also developed, and yielded similar results. It is suggested that the approach presented in this paper is useful for quantifying interactions between orthosteric antagonists and allosteric modulators, particularly when the extent of co-operativity is low or the modulators possess multiple pharmacological properties, or both. 相似文献
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The ASI as a still developing instrument: response to Mäkelä 总被引:1,自引:1,他引:0
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Latent transition analysis for longitudinal data 总被引:1,自引:0,他引:1
WAYNE F. VELICER ROSEMARIE A. MARTIN LINDA M. COLLINS 《Addiction (Abingdon, England)》1996,91(S12):S197-S209
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Iron overload and liver fibrosis 总被引:1,自引:0,他引:1
MJP ARTHUR 《Journal of gastroenterology and hepatology》1996,11(10):1124-1129
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ARTHUR J. FARKAS JOHN P. PIERCE SHU-HONG ZHU BRADLEY ROSBROOK ELIZABETH A. GILPIN CHARLES BERRY ROBERT M. KAPLAN 《Addiction (Abingdon, England)》1996,91(9):1271-1280
Prospective data from the California Tobacco Surveys (n=2066) were used to perform a critical test of the Prochaska et al. (1991) stages of change model. When the stages of change model was used as a stand alone predictor, smokers in preparation at baseline were more likely to be in cessation at follow-up than smokers in pre-contemplation at baseline (OR adj="1.9)" When stage membership was combined with baseline measures of addiction including smoking behaviors and quitting history, it was not a significant predictor of future cessation. A prediction equation that combined daily vs. occasional smoking, cigarettes per day smoked, life-time quits of at least a year, and quits of more than 5 days in the previous year discriminated smokers in cessation at follow-up of 1 to 2 years better than did the stages of change model. The area under the ROC curve for the equation based on addiction measures was 69.3% vs. 55.1% for the stages of change. Cessation rates ranged from 7.7% to 35.7% for the four-category addiction equation compared with 15.1% to 24.9% for stages of change model. 相似文献
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NEWTON PAUL E.; BOLTE HENRY F.; DALY IRA W.; PILLSBURY BRIAN D.; TERRJLL JAMES B.; DREW ROBERT T.; BEN-DYKE ROGER; SHELDON ARTHUR W.; RUBIN LIONEL F. 《Toxicological sciences》1994,22(4):561-576
Fischer 344 rats were exposed by inhalation to Sb2O3 (antimonytrioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and23.46 mg/m3 for 6 hr/day, 5 days/week for 13 weeks followedby a 27-week observation period. Subsequently, an inhalationon-cogenicity study was conducted at exposure levels of 0, 0.06,0.51, and 4.50 mg/m3 for 12 months followed by a 12-month observationperiod. The Sb2O3 in the subchronic study had a mass medianaerodynamic diameter (MMAD) of 3.05 ± 0.21 microns (mean± SD) with a geometric standard deviation (GSD) of 1.57± 0.06. In the chronic study, the MMAD was 3.76 ±0.84 and the GSD was 1.79 ± 0.32. Except for the eyes,no adverse clinical observations were attributed to Sb2O3 ineither study. In the subchronic study, corneal irregularitieswere seen after about 2 weeks of exposure and did not abateduring the observation period. In the chronic study, ophthalmoscopicevaluation at 24 months revealed a dose-related increase incataracts of 11, 24, 28, and 32% (both sexes combined) for eachgroup, respectively. Body weights were significantly lower (6%)than the control group's weights in the 23.46 mg/m3 males inthe subchronic study. These rats did not recover this weightduring the 27-week observation period. Body weights of the femalesin both studies and males in the chronic study were unaffected.There were no Sb2O3 effects on clinical chemistry or he-matologyin either study. Mean absolute and relative lung weights weresignificantly increased in the 4.92 and 23.46 mg/m3 groups inthe subchronic study. The 23.46 mg/m3 group's lung weights didnot recover to control levels during the 27-week observationperiod. Lung weights for rats in the chronic study were unaffected.Microscopic changes in the lungs in the subchronic and chronicstudy were limited to subacute-chronic interstitial inflammation,increased numbers of alveolar-in-traalveolar macrophages, foreignmaterial in the alveolar-in-traalveolar macrophages in the peribronchialand perivascular (chronic study only) lymphoid aggregates andin the peribronchial lymph nodes, granulomatous inflammation/granulomas,and fibrosis. In the chronic study, any observed neoplasms occurredwith comparable incidence among all groups and were within thehistorical range for controls. Clearance of Sb2O3 from the lungwas burden dependent and was reduced by 80/ in the 4.50 mg/m3group in the chronic study. The previously reported studies,which found Sb2O3 to be a carcinogen, were run at higher lungburdens. Under the exposure conditions of the current study,Sb2O3 was not a carcinogen. 相似文献
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