Pharmacology Commons^™

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Integrated Nanoscale Imaging And Spatial Recognition Of Biomolecules On Surfaces, Congzhou Wang

Theses and Dissertations

Biomolecules on cell surfaces play critical roles in diverse biological and physiological processes. However, conventional bulk scale techniques are unable to clarify the density and distribution of specific biomolecules in situ on single, living cell surfaces at the micro or nanoscale. In this work, a single cell analysis technique based on Atomic Force Microscopy (AFM) is developed to spatially identify biomolecules and characterize nanomechanical properties on single cell surfaces. The unique advantage of these AFM-based techniques lies in the ability to operate in situ (in a non-destructive fashion) and in real time, under physiological conditions or controlled micro-environments.

First, AFM-based …

Structural Determinants Of Abuse-Related Neurochemical And Behavioral Effects Of Para-Substituted Methcathinone Analogs In Rats, Julie S. Bonano

Theses and Dissertations

Methcathinone (MCAT) is the β-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like “bath salts” in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse …

An Evaluation Of The Central Neurotoxic Effects Of Aroclor 1254, A Commercial Mixture Of Polychlorinated Biphenyls, In Mice, Diane L. Rosin

Theses and Dissertations

Polychlorinated biphenyls (PCBs) are industrial compounds whose ubiquitous environmental contamination has been known since the late 1960's. Incidents of human intoxication have been reported, most notably, the "Yusho" incident that affected over 1600 people in Japan in 1968. A broad spectrum of adverse effects are produced by PCBs, including some neurological symptoms. While examination of the toxic effects of PCBs has received much attention, there has been little work on the neurotoxicity of PCBs. The intent of the experiments presented in this thesis is to provide further information on the central neurotoxicity of PCBs in mice.

A commercial mixture of …

The Effects Of Streptozotocin-Induced Diabetes On Responses To Opiates And Other Centrally-Acting Pharmacologic Agents, Glenn Stuart Simon

Theses and Dissertations

Diabetes mellitus affects millions of people. Although diabetics can lead relatively normal lives, all treatments for the disease are symptomatic and not curative. The purpose of this investigation was to determine whether the sensitivity to opiates and other selected centrally-acting drugs in animals is altered by streptozotocin (STZ)-induced diabetes. A second objective was to determine which aspect of the diabetic syndrome primarily was responsible for the altered sensitivity. Other experiments were performed in an attempt to elucidate the mechanism whereby this altered sensitivity occurred.

STZ-induced diabetes or dextrose-induced transient hyperglycemia did not have a significant effect on the duration of …

The Responsiveness Of Murine Tumors To Maleic Vinyl Ether, Paal Christian Klykken

Theses and Dissertations

Studies were undertaken to characterize the immune status of mice bearing the Lewis lung carcinoma (LLC) and to maximize the cure rate of LLC and Madison l09 carcinoma (Ml09) bearing mice by employing the immunomodulator maleic vinyl ether (MVE) in combination with surgery or radiotherapy.

The pattern of immunodeficiency in mice bearing the LLC appeared to be in contrast to most studies. LLC mice with a minimal tumor burden were found to have a diminished ability to phagocytize sheep erythorcytes (SRBC) or elicit an antibody response to the same antigen. Vascular clearance and phagocytic uptake of ⁵¹Cr-labeled SRBC into …