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1.
STEPHEN J. HEISHMAN DAVID J. K. BALFOUR NEAL L. BENOWITZ DOROTHY K. HATSUKAMI JON M. LINDSTROM JUDITH K. OCKENE 《Addiction (Abingdon, England)》1997,92(5):615-634
The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetylcholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine-containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among youth in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually not successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers. 相似文献
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Unlike the general psychotherapy field which has been subjected to extensive process analysis, there are no systematic studies of treatment processes in the alcohol and drug treatment literature. As a necessary first step to study treatment process, the alcohol and drug literature was culled for references to treatment processes. Thirty-five separate processes were identified and were broadly categorized as either disease model, behavioral or general psychotherapy processes. A national survey of treatment expert's views on treatment processes was conducted to determine whether certain processes would be considered as most important in the treatment of alcohol or drug problems. Results of this survey indicate that experts tend to rate certain processes as most important in the resolution of alcohol and drug problems. Results suggest that it is possible to identify core disease model and behavioral treatment processes. These processes might be used to assess the relative effectiveness of each therapeutic approach. Finally, results indicated that while disease model and behavioral experts tended to differ strongly on their ratings of the importance of some processes, there seems to be a trend toward integrating behavioral processes into a traditional disease model framework. The use of these results in constructing an instrument to measure processes used in alcohol and drug treatment is discussed. 相似文献
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Abstract Six healthy subjects were studied by means of an intravenous fat tolerance test on three occasions, in the fasting state, in the postprandial state, and during an intravenous infusion of gastric inhibitory polypeptide (GIP). No effects on the elimination rate of Intralipid® were seen either by endogenous or exogenous GIP. 相似文献
9.
The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data. 相似文献
10.
MARK S. SEARLE JON G. HALL ILIAS KYRATZIS LAURENCE P.G. WAKELIN 《Chemical biology & drug design》1989,34(6):445-454
The solution conformation of didemnin B, the most potent member of a family of depsipeptides that shows antitumour, antiviral, and immunosuppressive activity, has been studied in chloroform solution using n.m.r. spectroscopy. 1H and 13C spectra have been assigned from analysis of a number of two-dimensional homonuclear and heteronuclear chemical shift correlation experiments which confirm the recently corrected primary structure of the molecule. The conformation of the peptide has been deduced from measurements of the temperature dependence of the NH chemical shifts, analysis of coupling constant data and primarily through NOE effects observed in the rotating frame. Interproton distance bounds determined from a quantitative analysis of the ROE data provide 41 constraints from which a family of closely related structures were calculated using distance geometry algorithms. A type II β-turn involving residues Thr6, Leu7, and Pro8 is well represented in the computed conformers as is a hydrogen bonding interaction between the NH of Leu3 and the carbonyl oxygen of Thr6. This latter interaction causes the linear portion of the structure to fold back over the depsipeptide ring, imparting to it a degree of structural stability as well as giving the molecule a somewhat globular character. Only one transannular hydrogen bond, between 1st1 NH and Leu3 carbonyl, stabilizes the conformation of the depsipeptide, which has an irregular non-planar configuration. The small temperature coefficients (< 2.0 × 10?3ppm/°C) for the NHs of 1st1 and Leu3 are consistent with their involvement in these hydrogen bonding interactions. We find that many of the structural features observed in the crystalline form of didemnin B are conserved in solution. Analysis of the 13C spin-lattice relaxation rates of the protonated carbons reveals small variations in effective correlation times at specific sites in the molecule. The data suggests that the peptide segment encompassing residues Leu3through to Thr6 is in a more motionally restricted part of the structure. 相似文献