Pharmacology, Toxicology and Environmental Health Commons^™

Towards Gene Therapy Of Parkinson’S Disease: Implantation Of Ruc-Gdnf Secreting Mammalian Cell Lines Into Rat Brain, Hua Liu

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study is to develop a new approach for monitoring the function of implanted cells by a Renilla luciferase -glial cell line derived neurotrophic factor (RUC-GDNF) fusion protein in CSF. The RUC-GDNF protein is expected to report GDNF secreted from the cell by bioluminescence through luciferase activity.

Current ex vivo gene therapy using GDNF is limited by lack of a monitoring mechanism to determine the expression of GDNF once transformed cells or vector DNA are injected into animal models. Since the therapeutic concentration of GDNF secreted into cerebrospinal fluid (CSF) by implanted cells is too low for …

Mechanisms Of Calcium Buffering And Aging In Neurons: Testing The Limits Of Homeostasis, William James Pottorf Ii

Loma Linda University Electronic Theses, Dissertations & Projects

Intracellular calcium ([Ca²⁺]i) is an ubiquitous second messenger that integrates multiple and diverse neuronal pathways that include development and maturation, gene expression, synaptic plasticity, transmitter release, excitability, and even cell death. Upon neuronal excitation the [Ca²⁺]i increases rapidly and the calcium buffering system reacts quickly to restore [Ca²⁺]i to basal levels in order to reset the cell for the next stimulus and avoid prolonged exposure to cytotoxic levels of high [Ca²⁺]i. The aging process appears to causes multiple changes in the ability of neurons to regulate [Ca²⁺]i homeostasis and an …

Investigations On The Use Of Ion Mobility Spectrometry For Clinical Chemistry Applications, Henri Parson Patten

Theses and Dissertations in Biomedical Sciences

The major objective of this research is to examine ion mobility spectrometry as a rapid screening tool for specific application to clinical chemistry research and laboratory use. Methodology was developed for target analytes representing several classes of physiologically active substances, including anesthetics, illicit drugs, and their metabolites. The IMS characteristics of animal tissues and other compounds such as amino acids and proteins were determined. Quality assurance and control procedures were developed for specific quality data objectives. Criteria were established relating to use of IMS for assessing the precision and accuracy of data, qualitative screening, and semi-quantitative analyses.

It was found …

Validation Of Passive Air Sampling Monitors Onboard United States Navy Submarines, Larry A. Mcfarland

Community & Environmental Health Theses & Dissertations

An operating submarine creates a unique air quality mixture of compounds that result from a combination of human metabolism, construction materials, materials brought onboard and compounds created through the interaction of ship systems. A comprehensive study of submarine atmospheres is ongoing during deployments of U.S. Navy nuclear submarines. As part of the overall effort, a paired air sampling comparison field validation was conducted to compare the air sampling effectiveness of passive diffusive monitors compared to more traditional active air sampling methods when sampling for acrolein, formaldehyde and ozone in the enclosed submarine atmosphere. Acrolein monitors containing 2-hydroxymethylpiperidine (HMP) impregnated glass …

Toxicity Of Tolyltriazole To Bacillus Microorganisms, Christopher J. Leonard

Theses and Dissertations

The safety of air travel in cold weather depends upon the use of aircraft deicing fluids (ADAF). The environmental and toxic effects of the ADAF component tolyltriazole are not well understood. Tolyltriazole is a potential human carcinogen and has exhibited microbial toxicity in Microtox test. This research used two methods to investigate the toxicity of tolyltriazole on bacillus shaped microorganisms. The first method compared the dissolved oxygen uptake of microcosms exposed to varying concentrations of tolyltriazole. When exposed to 1000 ppm tolyltriazole, all isolated species showed inhibition in respiration. There was no evidence that tolyltriazole at

Chromate Dissociation From Primer Paint In Simulated Lung Fluid, Tiffany J. R. Morgan

Theses and Dissertations

OSHA has proposed a new strontium chromate exposure standard that would potentially cause Air Force paint facilities to be in violation of the proposed standard if adopted. This proposed reduction make the continued use of chromate containing primer paints very difficult. There is currently no acceptable replacements for chromate containing primer paints on AF aircraft. This study suggests that paint particles with chromate bound in primer paint may be unavailable for bodily absorption if inhaled and a reduced standard for painting applications may be unnecessary. Primer paint overspray was collected into simulated lung fluid (SLF) and allowed 6 hr, 24 …

A Pharmacokinetic Study Of The Effects Of Stress On Chemical Exposure, Sierra H. Suhajda

Theses and Dissertations

Following the Gulf War there were many concerns raised about human exposure to the combination of chemicals and stress. Stress causes several changes in basic functions of a human body, from breathing and blood flow changes to hormonal and enzyme changes, and increased permeability of the blood-brain barrier. Each of these changes can strongly influence chemical uptake, distribution, and accumulation in the body. The purpose of this thesis was to model and predict the changes that will occur when stress is combined with chemical exposure. Physiologically-based pharmacokinetic (PBPK) modeling is one tool that can be used to visualize, predict, and …

Effects Of Polychlorinated Biphenyl Exposure On Development And Sexual Differentiation In Ranid Tadpoles, Mary J. Rybitski

Dissertations, Theses, and Masters Projects

The effects of AroclorRTM1242 exposure on developing amphibians were examined by exposing southern leopard frogs, Rana sphenocephala, to a contaminated diet throughout the larval period. Treatment groups consisted of an untreated control, a solvent control, 17beta-estradiol, and three PCB doses (10, 100, and 1000 mug/g). PCB accumulation and biotransformation were examined. Effects of PCB exposure on metamorphosis and sexual differentiation were assessed. PCB accumulation was not statistically different between the egg masses. Levels of PCBs in the tissues differed in a dose related manner. Within treatments, body weight appeared to be the major factor correlated with PCB concentration. Congener patterns …