Thesis--Ohio State University. / Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 1995. / Includes bibliographical references (leaf 77-98).

Thesis (M.P.H.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 42-45).

Inaug.-Diss.--Friedrich-Wilhelms-Universitat, Bonn. / Vita. Includes bibliographical references.

Inaug.-Diss.--Friedrich-Wilhelms-Universitat, Bonn. / Vita. Includes bibliographical references.

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references (leaves 222-233). Also available via World Wide Web.

Thesis (Ph. D.)--Lehigh University, 2006. / Includes vita. Includes bibliographical references (leaves 121-156).

>Magister Scientiae - MSc / The pathology of neurodegenerative disorders involves multiple steps, and it is probably for this reason that targeting one particular step in a multi-step process has only yielded limited results. Nitric oxide (NO) is synthesised from L-Arginine by an enzyme known as nitric oxide synthase (NOS). Three isoforms of NOS exist, including endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). In the central nervous system (CNS), nNOS is involved in the synthesis of NO, which is involved in various neurological functions. NO is a free radical and this probably explains why an excess amount of it has been implicated in the development of neurodegenerative disorders. In the CNS, the Nmethyl- D-aspartate (NMDA) receptor in its active state allows the influx of calcium ions which activate nNOS thus increasing the amount of NO and other detrimental reactive nitrogen species within neuronal cells. Calcium entry through voltage-gated calcium channels (VGCC) may also contribute to this. Although calcium ions are important for physiological functioning, an excess is responsible for excitotoxicity, which can ultimately lead to neurodegeneration. Our aim was to synthesise a series of adamantane-derived compounds that act at multiple target sites in the neurodegenerative pathway. By conjugating benzyl and phenylethyl moieties with different functional groups (-H, -NO2, -NH2, -NHC(NH)NH2, -OCH3) to the amantadine structure, we aimed to synthesise compounds that display calcium channel and NMDA receptor (NMDAR) channel inhibition, as well as selective inhibition of nNOS. A series of compounds (-H, -NO2, -NH2, -OCH3) were obtained in yields that varied between 16.5 % and 90.25 %. These novel compounds were tested for calcium influx through VGCC and NMDAR inhibition using synaptoneurosomes isolated from rat brain homogenate against the reference compounds MK-801, NGP1-01, amantadine, memantine and nimodipine. A lack of success with the synthesis of the guanidine compounds prevented the use of the oxyhemoglobin capture assay for the determination of nNOS inhibitory activity of these compounds. The novel synthesised compounds display inhibitory activity towards VGCC and the NMDAR in the micromolar range. Further tests are recommended on compounds SE-1, SE-4, SE-11 and SE-12 as they displayed good inhibitory activity against both NMDAR- as well as ii KCl-mediated calcium influx. These novel compounds may be better therapeutic options than amantadine and memantine as they inhibit both NMDAR and VGCC-mediated calcium influx, whereas amantadine and memantine only inhibit NMDA-mediated calcium influx. These novel adamantane derived compounds may possibly serve as novel leads or potential therapeutic agents for the treatment of neurodegenerative disorders.

Clinical neuropsychologists are often called upon to make decisions on the genuineness of cognitive deficits following a head injury. This is a difficult task, particularly when deficits are subtle, as there are few reliable tools to aid the clinician in his or her decision making process. In the present study, normal participants instructed to feign brain injury (M) , traumatically brain-injured individuals (BI) , and normal controls (C), completed a series of computer-administered implicit memory (IM) tasks. Results were compared to those for the Victoria Symptom Validity Test (VSVT; Slick, Hopp, Strauss, & Pinch, 1994; Slick, Hopp, Strauss, & Thompson, 1997), a commercially available forced-choice recognition task. All IM tasks included items which had been previously presented once, twice or four times, as well as foils (items not previously presented). Previous exposure to test items was expected to be associated with increased accuracy (Hits) and decreased Response Latency. Participants in the BI and C groups were expected to perform equally well and better than the M group participants with respect to Hits. Response Latency on incorrect items (Misses) was also expected to discriminate M participants from BI and C participants because the conscious decision to provide an incorrect response was expected to increase decision making time. Results with respect to overall Hits were confirmed (M=127.87, M=129.72, and M=107.10 for the BI, C, and M groups, respectively) . Increased accuracy with repetition of items in the priming phase was not confirmed, likely because both BI and C participants performed close to ceiling levels. Discriminant function analysis based on total Hit rates, resulted in correct classification of 85 percent (46 out of 54) of the participants. This was comparable to the results for Hard items combined on the VSVT. Response Latency measures did not effectively discriminate among groups, while results did indicate a main effect of Presentation Level (priming) on Response Latency with participants, independent of Group Membership, tending to respond most quickly (Hits only) to items presented 4 times during the priming phase and least quickly to items presented only once. Overall, results suggest that further investigation of IM tasks for the detection of conscious malingering is warranted as these tasks appear to tap the dimensions on which the general population hold misconceptions about the effects of brain injury, i.e., overall ability/performance and response latency. / Graduate

No description available.