Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
2 results
Search Results
Item Enhanced Solubility and Targeted Delivery of Drugs using Cucurbit[n]uril-Type Compounds(2013) Hettiarachchi, Gaya Kamelika; Briken, Volker; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)There is a significant decrease in the productivity of the drug development pipeline due to low drug solubility and high toxicity. Promising solutions to these issues are to use solubilizing excipients and targeted drug delivery systems (DDS). There is a constant demand for an increased diversity of excipients and DDSs because no one host molecule can encapsulate all drugs. Here we study the use of three novel cucurbit[n]uril (CB[n])-type compounds synthesized by Dr. Lyle Isaacs. Motor1 and Motor2 are highly soluble (105 mM and 14 mM) and unique in acyclic structure. The targeted delivery of drugs was explored using biotin functionalized CB[7]. Phase solubility experiments evaluated improvements to drug solubility. Host biocompatibility was assessed both in vitro and in vivo. In vitro bioactivity studies were conducted using Motor1 complexed with several anticancer drugs and biotin functionalized CB[7] complexed with oxaliplatin. Studies with Motor1 were repeated in vivo using NUDE mice baring human cervical cancer cell tumors. Motor1 and 2 significantly increased the solubility of drugs from many different therapeutic fields, such as paclitaxel (anticancer), cinnarizine (antihistamine), and 17a-ethynyl estradiol (hormone). CB[7] and Motor1 were non-toxicity up to 10 mM in human liver and kidney cell lines. Female Swiss Webster mice continued to gain weight and appeared healthy after three intravenous doses of Motor1 up to 1230 mg/kg. Bioactivity assays using anticancer drugs paclitaxel albendazole, camptothecin and PBS-1086 complexed in Motor1 resulted in significant cytotoxicity in HeLa cells. A pilot in vivo tumor treatment study showed tumor growth stabilization with these treatments. Biotin functionalized CB[7] showed cytotoxicity specifically in cells overexpressing the biotin receptor upon targeted delivery of oxaliplatin. The CB-type compounds significantly increased the solubility of a large variety of drugs across therapeutic fields. This coupled with host toxicity and drug bioactivity data indicate that these CB[n]-type compounds may be invaluable contributions to the toolbox of excipients and DDSs currently available.Item AN ECONOMIC ANALYSIS OF FACTORS IMPACTING HOSPITAL PATIENT OUTCOMES IN THE UNITED STATES(2006-08-07) Wei, Heng; Evans, William N; Economics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation is two essays that examine the impact of two distinct structural changes in hospitals. The first essay examines whether legislated changes in the minimum postpartum length of stay improve health outcomes for newborns. The second essay examines the consequences of nurse unions in hospitals. Much of the previous research about the relationship between postpartum length of stay and patient outcomes are potentially subject to an omitted variable bias because sicker newborns usually stay longer in the hospital. We overcome this problem by using passages of early discharge laws as a quasi experiment that generated exogenous increase in length of postpartum stays. The California Newborn's and Mother's Health Act of 1997 effective on August 26, 1997, mandated that private insurance carriers provide coverage for at least 48-hour hospital stays for normal deliveries and 96-hour hospital stays for cesarean deliveries. A similar federal law went into effect on January1, 1998. Using an interrupted time series design, we demonstrate that early discharge laws reduced considerably the fraction of newborns and mothers who were discharged early. In two-stage least square models using the state and Federal law as instruments for the length of hospital stay, we find that an additional day in the hospital reduces the probability of readmission by about one percentage point for complicated vaginal deliveries and c-sections of all types. For uncomplicated vaginal deliveries, we find there was no statistically significant change in 28-day newborn readmission rates. The second essay examines the impact of nurse unionization in hospitals on wages, hours, staffing ratio of nursing personnel. Using hospital-level panel data merged with data on union elections from the National Labor Relations Board, we compare the outcomes of nursing personnel in hospitals that became unionized during the sample period with hospitals that did not change union status. The results indicate that unions have a small negative impact on nurse wage rates and they encourage hospitals to use a larger fraction of contract employees. These difference-in-difference estimates also indicate that cross-sectional regressions tend to overstate the wage gains of union because unions are more likely to appear in higher-wage hospitals.