Organophosphorus (OP) compounds are found in household pest control products, plastics, and petroleum. Due to the neurotoxic nature of OP compounds, exposure can cause both acute and delayed symptoms, including organophosphate-induced delayed neuropathy (OPIDN). This syndrome is characterized by Wallerian-like degeneration of nerves in the central and peripheral nervous system after exposure to neuropathic OP compounds. There are many questions surrounding the mechanisms of the onset of OPIDN, including possible alterations in proteins associated with neuronal maintenance and repair. This dissertation investigated the changes in levels of neurotrophins in vivo and how in vitro levels of neurotrophin receptors and their downstream signaling cascades are affected after exposure to OP compounds. We also characterized the molecular weight of a soluble factor responsible for inducing neurite outgrowth in vitro after in vivo exposure to a neuropathic OP compound. We evaluated in vivo endpoints using enzyme-linked immunosorbant assays. Results indicated that nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are found in chicken spinal cord but do not increase as a result of exposure to neuropathic OP compounds. This study also noted that NGF, BDNF, and NT-3 concentrations were not altered after exposure to a non-neuropathic OP compound. We evaluated in vitro endpoints using Western blots, ultrafiltration, and digital morphometry. These studies revealed that activated forms of high-affinity and low-affinity neurotrophin receptors are present after OP compound exposure, that the ratio of these two receptors to each other is stable after OP compound exposure, and that the activated form of the low-affinity receptor, which can lead to apoptosis, was present in greater levels than the activated form of the high-affinity receptor. Furthermore, OP compound exposure resulted in time-dependent changes of protein levels central to the mitogen-activated kinase and phosopholipase C-gamma intracellular pathways. Changes in a third pathway, the protein kinase C pathway, were dependent on the concentration and type of OP compound. Finally, in vitro neurite length was not affected by the type of OP compound administered in vivo or when a whole protein fraction was separated by molecular weight. This research has revealed in vivo consequences and early effects on intracellular protein and activated neurotrophin receptor levels after OP compound exposure. These early effects may contribute to the delayed development of neurotoxic effects associated with OP compound exposure. / Ph. D.

The hydrolysis of 4-Nitrophenylphosphate (NPP) as model substrate in the presence of several cobalt (III) amine [N4Co(OH)(H2O)]2+ and copper bipyridyl [Cu(bpy)(H2O)2]2+ complexes in oil in water microemulsion media was investigated. The reaction was monitored by measuring the absorbance of the nitrophenolate ion produced in the reaction aliquots with time under the experimental conditions. The order of effectiveness of the microemulsion systems towards the hydrolysis of NPP in the presence of these metal ions were found to be cationic > anionic > aqueous at neutral pH. The results of the present investigation exhibits stoichiometric turnovers for the 1:1, 2:1 and 3:1 cobalt to NPP ratio and catalytic turnovers for the [Cu(bpy)2+ to NPP ratio of 1:20. Catalysis in the microemulsion mediated reaction solutions was evident even in low concentrations of the metal ions in 1:2000 metal to NPP ratio. An explanation for the enhanced catalytic activity of the [Cu(bpy)(OH)(H2O)]2+ complex for the hydrolysis of NPP is afforded and the application of the above model systems for possible environmental decontamination of toxic organophosphates is anticipated. / Chemistry / M.Sc. (Chemistry)

The light stability of 0,0-diethyl-0-(4-ethylthiophenyl)phosphorothioate, a parent structure of a new class of fibre-reactive organophosphorus insectproofing agents for use on wool textiles was extensively examined. The rate of degradation of 0,0-diethyl-0-(4-ethylthiophenyl)phosphoro-thioate in polar and non-polar solution and on wool upon irradiation by simulated sunlight was investigated using high performance liquid chromatography.. The major photodegradation products in each case were correlated with the HPLC retention times of synthetically prepared compounds. The main product formed was the sulphoxide, 0,0-diethyl-O-(4-ethylsulphinylphenyl)phosphorothioate, whose insecticidal activity against the major textile pests was shown to be similar to that of the parent compound. In polar solution a polar product which could not be identified was formed. Both 4-ethylsulphinylphenol and 4-ethyIsulphony1-phenol were found on wool but not in solution. The effect of various ultraviolet stabilizers on the rate of photodegradation of 0,0-diethyl-0-(4-ethylthiophenyl)phosphorothioate was also examined. Ultraviolet absorbers of the 2-hydroxybenzophenone and 2-hydroxybenzotriazole classes conferred the best protection in each case. However, on wool typical wool dyes applied at conventional levels were also effective.

xv, 130 leaves : ill. ; 26 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1971) from the Dept. of Agricultural Biochemistry and Soil Science, Waite Agricultural Research Institute, University of Adelaide

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 32-46).

In 1981, illegal processing of rapeseed oil by a Spanish oil refinery resulted in the mass foodborne illness epidemic known as Toxic Oil Syndrome (TOS). The toxic oil associated with this epidemic was sold in neighborhood markets and by itinerant salesmen as inexpensive olive oil. Ingestion of the toxic oil resulted in more than 20,000 illnesses and over 1,500 deaths in Spain. The etiologic agent of TOS remains unknown. In addition, animal studies have provided little insight into the mechanisms of toxicity because no animal model exhibits the symptoms of TOS. Researchers of Eosinophilia- Myalgia Syndrome (EMS) are in a similar quandary. EMS occurred in the United States in 1989, and the symptoms of this illness parallel TOS quite closely. The MRL/lpr mouse model has been suggested as a possible model for immunotoxicity caused by environmental exposure. Since the symptoms of most chronic phase patients appeared to be immunologically mediated, the MRL/lpr mouse was chosen as the animal model for the present experiment. Sixty two mice were used. Groups often mice were gavaged with three different dose levels of 2% aniline denatured low-erucic acid rapeseed oil (Canola oil) and mercuric chloride as a positive control. Ten mice were untreated as a naive control. Two mice were sacrificed upon arrival as a negative control. All mice treated with toxic oil displayed a decreased rate of weight gain relative to the naive control. Serum antinuclear antibodies (ANA) were detected using indirect immunofluorescence, and anti-type IV collagen antibodies (ACA) were detected using an ELISA technique. The mice receiving toxic oil displayed increased serum ANA titers relative to the naive control. However, there did not appear to be a relationship between toxic oil dose and ANA titer. All animals receiving oil displayed decreased serum ACA titers relative to the naive control. In this case, a direct relationship existed between ACA [p.2 of abstract missing]. / Graduation date: 1999

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 114-121). Also available via the Internet.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1994. / Vita. Abstract. Includes bibliographical references (leaves 167-187). Also available via the Internet.

Thesis (Ph. D.)--Washington State University, August 2010. / Title from PDF title page (viewed on July 21, 2010). "Department of Chemistry." Includes bibliographical references (p. 217-218).

Thesis (Ph.D.) - University of St Andrews, May 2009. / Restricted until 11th May 2011.