Thesis (M.S.)--Naval Postgraduate School, 2002. / Thesis advisor(s):David R. Henderson, Douglas Moses. "AD-A405 877." Includes bibliographical references (p. 123-132). Also available online.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1974. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (J.C.L.)--Catholic University of America, 2003. / Includes bibliographical references (leaves 47-52).

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (M.A.)--Rowan University, 2007. / Typescript. Includes bibliographical references.

No description available.

Since 1963, the Narcotic Addiction Foundation of British Columbia has been administering Methadone, a synthetic drug, on a prolonged basis to a selected group of heroin addicts. For the purposes here, those addicts receiving Methadone on a continuous day to day basis for an indefinite period of time will be called prolongeds. Those addicts receiving Methadone in decreasing dosage over a twelve day withdrawal period will be referred to as regulars. Ingeborg Paulus, Research Associate at the Foundation, assessed the effectiveness of Methadone by comparing a group of addicts given the drug on a prolonged basis to a group of addicts undergoing regular twelve day withdrawal. The findings of her study showed that prolongeds committed fewer crimes than the regulars. The addicts in the prolonged group were significantly older than those in the regular group. Paulus found that age was the most important factor in the addicts' decreased use of narcotics. This tendency to use less drugs as the addict becomes older is known as the "maturing-out" process. Therefore, a decrease in crime by the prolonged group may not be solely attributable to Methadone, but to the age of the addict. The purpose of the present study is to test the causal relationship between the prolonged administration of Methadone to heroin addicts and their criminal behaviour. To carry out this study, the following two hypotheses were developed: (1) Heroin addicts commit fewer crimes when maintained on prolonged Methadone, and (2) Heroin addicts maintained on prolonged Methadone commit fewer crimes than heroin addicts who are given regular withdrawal. The research method used involved a retrospective, follow-up study utilizing all of the addicts in Paulus' sample who were between the ages of twenty-five and forty years. This was done in an effort to make the two groups more comparable in their age distribution. To test hypothesis one, a 'before and after' design was proposed that will allow investigation of the addict's criminal activity prior to and after his exposure to prolonged Methadone. To test the second hypothesis, the criminal behaviour of the prolongeds will be compared to the criminal behaviour of the regulars. Additional analysis are suggested to assist in assessing the comparability of the two groups. After considering the numerous and unexpected problems a researcher faces, it is concluded that, while it may be feasible to conduct this study using the sample available, one cannot depend on the reliability or validity of the findings to test the hypotheses conclusively. / Arts, Faculty of / Social Work, School of / Graduate

Yes / There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences.

Thesis (M.Soc.Sc. Psychology)--University of Waikato, 2006. / Includes bibliographical references (leaves 86-93) Also available via the World Wide Web.

Most known drug targets and metabolizing enzymes are located inside cells. Interactions with these proteins are determined by intracellular unbound drug concentrations. Assessing intracellular drug exposure is technically challenging, but essential for predicting pharmacokinetic, pharmacological, and toxicological profiles of new drugs. This thesis aims at establishing and applying a straightforward methodology to measure intracellular unbound drug concentrations. This was achieved by separately measuring cellular drug binding (fu,cell), and total intracellular drug accumulation (Kp). This allowed the calculation of intracellular drug bioavailability (Fic), which represents the fraction of the concentration added to the cells that is unbound in the cell interior. The methodology was initially developed in HEK293 cells, where the Fic of 189 drug-like compounds was measured. Binding to HEK293 cells was governed by compound lipophilicity and was correlated with binding to more complex systems, such as hepatocytes and brain. Due to negligible expression of drug transporters, Fic in this cell line was consistent with pH-dependent subcellular sequestration of lipophilic cations in low pH compartments. The methodology was then applied to study the effects of drug transporters on Fic. The uptake transporter OATP1B1 increased the Fic of its substrates in a concentration-dependent manner. In contrast, the Fic of P-gp substrates was decreased when P-gp was present. In human hepatocytes, the methodology allowed the determination of Fic without prior knowledge of transporter mechanisms or metabolic activity. Finally, the methodology was applied to measure the impact of Fic on target binding and cellular drug response. Intracellular concentrations of active metabolites of pro-drugs targeting the intracellular target thymidylate synthase were in agreement with the level of binding to this target. Further, high Fic was generally required for kinase and protease inhibitors to be active in cellular assays. In conclusion, the methodology can be used to predict if new drug candidates reach their intracellular targets in sufficient amounts. Furthermore, the methodology can improve in vitro predictions of drug clearance and drug-drug interactions, by measuring the drug available for intracellular enzymes. Finally, this work can be expanded to other xenobiotics, e.g., to predict their intracellular toxicity.