Stages of acquisition and cessation for adolescent smoking: an empirical integration

Adolescent cigarette smoking acquisition and cessation were integrated into a single nine-stages-of-change continuum using the transtheoretical model of change framework. Findings in a high school student sample (n > 700) showed that a few of the never smokers were planning to try smoking, and half of the current smokers were contemplating quitting. More than half of former smokers were long-term quitters. The high pros of smoking scores assessing coping benefits of cigarettes were related to smoking acquisition and the high con (disadvantages) scores to long-term abstinence. Never smokers were most tempted to try smoking when they anticipated that smoking would help reduce negative and increase positive mood. Current and former smokers were tempted due to peer cigarette offers and negative mood. These temptations were significantly reduced among ex-smokers.     

Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies

Comparison of the high-resolution X-ray structures of the native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible. The movement at the tip of the flaps could be as large as 7 A. On the basis of this observation, cyclic cyanoguanidines have been designed, synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The choice of cyclic cyanoguanidines over cyclic guanidines was based on the reduced basicity of the former. X-ray structure studies of the HIV PR complex with cyclic cyanoguanidine demonstrated that in analogy to cyclic urea, cyclic cyanoguanidines also displace the unique structural water molecule. The structure-activity relationship of the cyclic cyanoguanidines is compared with that of the corresponding cyclic urea analogues. The differences in binding constants of the two series of compounds have been rationalized using high-resolution X-ray structure information.     

Bioactivation and irreversible binding of the cognition activator tacrine using human and rat liver microsomal preparations. Species difference

Tacrine's [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate, (THA)] metabolic fate was examined using human and rat liver microsomal preparations. Following 1-hr incubations with human microsomes, [14C]THA (0.4 microM) was extensively metabolized to 1-hydroxyTHA with trace amounts of 2-, 4-, and 7-hydroxyTHA also produced. Poor recovery of radioactivity in the postreaction incubates suggested association of THA-derived radioactivity with precipitated microsomal protein. After exhaustive extraction, 0.034, 0.145, 0.126, and 0.012 nmol eq bound/mg protein/60 min of THA-derived radioactivity was bound to human liver preparations H109, H111, H116, and H118, respectively. Preparations H109 and H118 were lower in P4501A2 content and catalytic activity as compared with preparations H111 and H116. Incubations of equimolar [14C]1-hydroxyTHA with human liver microsomes also resulted in binding to protein, although to a lesser extent than observed with THA. [14C]THA (0.4 microM) was incubated for 1 hr with rat liver microsomes (1 microM P-450) prepared from noninduced (N), phenobarbital (PB), isoniazid (I), and 3-methylcholanthrene (3-MC)-pretreated animals. In all incubations, 1-hydroxyTHA was the major biotransformation product detected. After exhaustive extraction, 0.048, 0.054, 0.049, and 0.153 nmol eq/mg protein/60 min of THA-derived radioactivity was bound to microsomal protein from N, PB, I, and 3-MC pretreated rats. Increased binding with 3-MC induced rat liver preparations suggests the involvement of the P-450 1A subfamily in THA bioactivation. Glutathione (5 mM) coincubation inhibited the irreversible binding of THA-derived radioactivity in both human and 3-MC-induced rat liver preparations, whereas human epoxide hydrase (100 micrograms/incubate) had a relative minor effect. A mechanism is proposed involving a putative quinone methide(s) intermediate in the bioactivation and irreversible binding of THA. A species difference in THA-derived irreversible binding exists between human and noninduced rat liver microsomes, suggesting that the rat is a poor model for studying the underlying mechanism(s) of THA-induced elevations in liver marker enzymes found in clinical investigations.     

Cysteine contributions to metal binding preference for Zn/Cd in the beta-domain of metallothionein

Previous studies showed that metals in the beta-domain of metallothionein(MT) are more readily exchangeable and the level of avidity is sitespecific. This is reflected by energy differences computed with a series ofsimulated structures derived from X-ray crystallography. In this study, weexamined further the contribution of each of the nine cysteines in thebeta-domain. By semi-empirical MNDO calculations, we observed that therelative average binding strength is the strongest for Cys21 to Cd[M4] andfor Cys26 to Zn[M3], except for the bridging cysteines. These resultssuggest that binding site preference for Zn/Cd is determined by bindingstrength between specific cysteines and metal ion species.     

Influence of product species selection on thermochemical equilibrium calculations. Part I: Energetic materials

Chemical equilibrium calculations are made for a number of Carbon C, Hydrogen H, Nitrogen N, and Oxygen O, explosive compositions. A methodology is established to systematically limit the number of product species available in thermochemical equilibrium calculations. The calculations are then compared with “baseline” results obtained using an extensive product species library consisting of 900 gas-phase and 600 condensed-phase product species. Errors in bulk thermodynamic properties (detonation velocity and pressure) and in product chemical composition are quantified in terms of the number of species considered as products of reaction. The properties at states along an expansion isentrope are also presented.