Society for Research on Nicotine and Tobacco

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.     

Curative factors in alcohol and drug treatment: behavioral and disease model perspectives

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.     

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咖啡因是促进糖代谢和脂肪代谢最好的元素,但有一个前提,要喝不加糖和不加咖啡伴侣的黑咖啡,这一点要切记     

Lack of Effect of Exogenous or Endogenous Gastric Inhibitory Polypeptide on the Elimination Rate of Intralipid® in Man

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.     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

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.     

Didemnin B Conformation and dynamics of an antitumour and antiviral depsipeptide studied in solution by 1H and 13C. n.m.r. spectroscopy

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.     

Alcohol and Expectancy: subjective, psychophysiological and behavioral responses to alcohol stimuli in severely, moderately and non-dependent drinkers

Thirty male subjects, 10 severely and 10 moderately alcohol dependent, along with 10 non-dependent controls, were studied in four experimental drinking conditions. Each subject participated in each condition. All subjects received a priming dose of 2 ml 40% vodka/kg or placebo, and a drinking test of 1 ml 40% vodka/kg 45 minutes later. Subjects were told that the priming dose contained ‘alcohol’ in two conditions and ‘soft drinks’ in the two other conditions of the Balanced placebo design. Self-reported desire for a drink and experienced effects from alcohol were more influenced by instructions than by the actual presence of alcohol, although a peak BAG of 0.11% were reached if all available alcohol were consumed (not all subjects did so). Severely dependent subjects demonstrated more craning than the other groups, this difference was observed in the presence of information about alcohol, regardless of whether alcohol was present or not. No differences in speed of drinking were found. The severely dependent subjects showed a higher general arousal than moderately and non-dependent subjects in this experimental setting, as measured by skin conductance level, and they displayed a higher skin conductance response to the instruction that alcohol was to be given. Severely dependent subjects showed a hypothermic response to alcohol. The results confirm our previous findings that expectations of alcohol exerts greater influence on craving than pharmacological effects of alcohol, but the severely dependent subjects are reacting more strongly to alcohol cues than less dependent alcoholics. In addition, the experiment demonstrates that psychophysiological responses are elicited by alcohol cues, and supports a classical conditioning model of alcohol dependence.     

Effect of the Peroxisome Proliferator, Ammonium Perfluorooctanoate (C8), on Hepatic Aromatase Activity in Adult Male CrI:CD BR (CD) Rats

The incidence of Leydig cell adenomas increases in CD rats fedfor 2 years with the hepatic peroxisome proliferator, ammoniumperfluorooctanoate (C8). Treatment with C8 increased the serumconcentration of estradiol in 2-week gavage studies, and feedingstudies at various time points up to 2 years, and was also accompaniedby increases in liver weight and hepatic ß-oxidationactivity. Since peroxisome proliferators induce both hepaticß-oxidation and specific cytochrome P450 enzymes,C8 may also induce aromatase (cytochrome P450-19A1), the cytochromeP450 mono oxygenase which converts androgens to estrogens. Thishypothesis was investigated in the present study. Adult maleCD rats were dosed daily by gavage for 14 days with 0, 0.2,2, 20, or 40 mg C8/kg body wt. An additional group, the pair-fedcontrol, was fed at a rate matched to the daily consumptionby the 40 mg C8/kg group. Treatment with C8 produced a dose-dependentdecrease in body weight, and increases in absolute and relativeliver weights, and in the protein yield of hepatic microsomes.These C8-induced changes were associated with a 2-fold increasein the serum concentration of estradiol and up to a 16-foldincrease in total hepatic aromatase activity. A significantlinear correlation was established between serum estradiol andtotal hepatic aromatase activity. The absolute weights and thearomatase activity of the testes were not affected by C8. Hepaticperoxisomal ß-oxidation activity and the microsomalconcentration of total cytochrome P450 were also increased byC8. A comparison of estimated EC50 values suggested that theseparameters may be less sensitive to induction by C8 than hepaticaromatase activity. Co-incubation of control liver microsomeswith C8 in the aromatase assay for 2 hr dose dependently reducedthe apparent aromatase activity. This inhibition of aromatasein vitro but increase in vivo was further investigated usingcultured rat hepatocytes. Decreases in aromatase activity werefound after up to 42 hr of treatment with C8, but the enzymeactivity was increased almost 2-fold after 66 hr. The resultsof this study suggest that the increased serum concentrationof estradiol produced by C8 in rats is at least partly due toa direct effect on the liver to increase synthesis of estradiolthrough induction of aromatase cytochrome P450 in the endoplasmicreticulum.