Neuropathic pain is defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system". In contrast to physiological pain that warns of noxious stimuli likely to result in tissue damage, neuropathic pain serves no protective function. Examples of neuropathic pain states include postherpetic neuralgia (shingles) and phantom limb / stump pain. This pain state also exists in the orofacial region, with the possibility of several variants including atypical odontalgia and burning mouth syndrome. There is a paucity of information on the prevalence of neuropathic pain in the orofacial region. One study assessed patients following endodontic treatment and found that approximately 3 to 6percent of patients reported persistent pain. Patients predisposed to the condition atypical odontalgia (phantom tooth pain) include those suffering from recurrent cluster or migraine headaches. Biochemical and neurobiological processes leading to a neuropathic pain state are complex and involve peripheral sensitisation, and neuronal plasticity of the central and peripheral nervous systems. Subsequent associated pathophysiology includes regional muscle spasm, sympathetic hyperfunction, and centralisation of pain. The relevant clinical features of neuropathic pain are: (i) precipitating factors such as trauma or disease (infection), (ii) pain that is frequently described as having burning, paroxysmal, and lancinating or sharp qualities, and (iii) physical examination may indicate hyperalgesia, allodynia and sympathetic hyperfunction. The typical patient complains of persistent, severe pain, yet there are no clearly identifiable clinical or radiographic abnormalities. Often, due to the chronicity of the problem, afflicted patients exhibit significant distress and are poor pain historians, thus complicating the clinician's task of obtaining a detailed and relevant clinical and psychosocial history. An appropriate analgetic blockade test for intraoral sites of neuropathic pain is mucosal application of topical anaesthetics. Other, more specific, tests include placebo controlled lignocaine infusions for assessing neuropathic pain, and placebo controlled phentolamine infusions for sympathetically maintained pain. The treatment and management of neuropathic pain is multidisciplinary. Medication rationalisation utilises first-line antineuropathic drugs including tricyclic antidepressants, and possibly an anticonvulsant. Topical applications of capsaicin to the gingivae and oral mucosa are a simple and effective treatment. Neuropathic pain responds poorly to opioid medication. Psychological assessment is often crucial in developing strategies for pain management. Psychological variables include distress, depression, expectations of treatment, motivation to improve, and background environmental factors. To enable a greater understanding of neuropathic pain, thereby leading to improved treatments, high-performance liquid chromatography-mass spectrometry is one analytical technique that has the potential to contribute to our knowledge base. This technique allows drugs and endogenous substances to be assayed from one sample in a relatively short time. The technique can identify, confirm, and measure the concentrations of multiple analytes from a single sample.

Thesis (Ph. D.)--Georgia State University, 2007. / Title from file title page. Gabor Patonay, committee chair; A.L. Baumstark, G. Davon Kennedy, Gregg Pratt, committee members. Electronic text (170 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Dec. 10, 2007. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

<p>The sequencing of genomes has caused a growing demand for functional analysis of gene products. This research field named proteomics is derived from the term proteome, which by analogy to genome is defined as all proteins expressed by a cell or a tissue. Proteomics is however methodologically restricted to the analysis of proteins with higher molecular weights. The development of a technology which includes peptides with low molecular weight and small proteins is needed, since peptides play a central role in many biological processes. </p><p>To study endogenous peptides and hormones, the peptidome, an improved method comprising rapid deactivation in combination with nano-flow liquid chromatography (LC) and mass spectrometry (MS) was developed. The method has been used to investigate endogenous peptides in brains of mouse and rat. Several novel peptides have been discovered together with known neuropeptides. </p><p>To elucidate the <i>post mortem</i> time influence on peptides and proteins, a time course study was performed using peptidomics and proteomics technologies. Already after three minutes a substantial amount of protein fragments emerged in the peptidomics study and some endogenous peptides were drastically reduced with increasing <i>post mortem</i> time. Of about 1500 proteins investigated, 53 were found to be significantly changed at 10 minutes <i>post mortem</i> as compared to control. Moreover, using western blot the level of MAPK phosphorylation was shown to decrease by 95% in the 10 minutes <i>post mortem </i>sample. </p><p>A database, SwePep (a repository of endogenous peptides, hormones and small proteins), was constructed to facilitate identification using MS. The database also contains additional information concerning the peptides such as physical properties. A method for analysis of LC-MS data, including scanning for, and further profiling of, biologically significant peptides was developed. We show that peptides present in different amounts in groups of samples can be automatically detected.</p><p>The peptidome approach was used to investigate levels of peptides in two animal models of Parkinson’s disease. PEP-19, was found to be significantly decreased in the striatum of MPTP lesioned parkinsonian mice. The localization and expression was further investigated by imaging MALDI MS and by <i>in situ</i> hybridization. The brain peptidome of reserpine treated mice was investigated and displayed a number of significantly altered peptides. This thesis demonstrates that the peptidomics approach allows for the study of complex biochemical processes.</p>

In this thesis, we investigated the surface composition and orientation of both pure room-temperature ionic liquids (Ils) and binary mixtures of the ILs of the type consisting of the 1-alkyl-3-methylimidazolium ([C[subscropt n]mim]���, n=4, 8, and 12) cation coupled with either [PF���]���, [BF���]���, [Cl]���, or [Br]���. The surfaces of the ILs were examined using both direct recoil spectrometry (DRS) and surface tension measurements. With DRS, a spectral signal produced by a recoiled surface atom indicates the existence of a particular molecular or ionic species at the interface. Derived from the signal are the atomic ratios, which are strongly dependent on the surface orientation of the surface species. The DRS findings are complimented with surface tension measurements, and the thermodynamics properties (surface enthalpy and entropy) derived from such measurements are related to the surface composition and orientation. From the experiments on the neat ILs, the surface compositions of the imidazolium-based ILs were determined. Furthermore, the effects of systematic variations of the cation size (the length of the 1-alkyl chain) and anion identity on the surface orientation of the organic cation were also examined. The surfaces of binary mixtures containing ~25 mol % of [C������mim][PF���] or [C������mim][BF���] in [C���mim}[BF���] were also investigated. The DRS and surface tension data of the mixtures were compared to those of the pure components to determine the composition and any changes in the orientations of the cations upon mixing. / Graduation date: 2004

Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007.

This thesis describes the application of mass spectrometry (MS) to glycoprotein and oligosaccharide analysis. Glycosylated proteins are involved in cell-cell and cell-matrix recognition. Applications of trypsin and proteinase K to hydrolyze glycoproteins into glycopeptides that are compatible with MS and MS/MS analysis are investigated. For successful site-specific analysis of glycans, glycopeptides with short peptide (3-8 residues) are needed. Although trypsin is an important enzyme for protein identification, proteinase K is superior for site-specific glycan analysis due to its potential to hydrolyze every glycoprotein to short glycopeptides. The gas-phase dissociation pathways, kinetics and energetics of protonated oligosaccharides are described. The oligosaccharides dissociate via cleavage at the glycosidic linkages during thermal activation. Using double resonance experiments, it was established that oligosaccharides undergo sequential and parallel fragmentation reactions. Furthermore, dissociation of product ions to secondary ions was confirmed. Arrhenius activation parameters, Ea and A for protonated alpha- and beta-linked D-glucopyranose oligosaccharides are reported.

Thesis (M. Sc.)(Chemistry)--University of Pretoria, 2005. / Includes summaries in English and Afrikaans. Includes bibliographical references. Available on the Internet via the World Wide Web.

This study focuses on the application of 193-nm excimer laser (ArF) photodissociation to tandem time-of-flight mass spectrometry. In particular, it focuses on identifying the optimal experimental conditions for peptide sequencing and applying the technology to interesting systems. The early focus is on optimizing the sample preparation conditions that define the initial internal energy state of MALDI-produced ions. Subsequent chapters investigate the effect of changing photodissociation laser conditions and define conditions under which the information content of the spectrum is maximized. Later chapters compare the photodissociation experiment to technologies that represent the current state of the art in tandem mass spectrometry, illustrating both the advantages and shortcoming of photodissociation TOF methodology. Finally, we apply photodissociation to the study of interesting systems of biological relevance, including (1) peptides derived from enzymatic digestion, (2) post-translationally modified peptides, and (3) peptide-transition metal ion complexes. In the final chapter we consider the analytical implications of the work as a whole and comment on the analytical viability of the methodology and look forward to new directions for the experiments.

The sequencing of genomes has caused a growing demand for functional analysis of gene products. This research field named proteomics is derived from the term proteome, which by analogy to genome is defined as all proteins expressed by a cell or a tissue. Proteomics is however methodologically restricted to the analysis of proteins with higher molecular weights. The development of a technology which includes peptides with low molecular weight and small proteins is needed, since peptides play a central role in many biological processes. To study endogenous peptides and hormones, the peptidome, an improved method comprising rapid deactivation in combination with nano-flow liquid chromatography (LC) and mass spectrometry (MS) was developed. The method has been used to investigate endogenous peptides in brains of mouse and rat. Several novel peptides have been discovered together with known neuropeptides. To elucidate the post mortem time influence on peptides and proteins, a time course study was performed using peptidomics and proteomics technologies. Already after three minutes a substantial amount of protein fragments emerged in the peptidomics study and some endogenous peptides were drastically reduced with increasing post mortem time. Of about 1500 proteins investigated, 53 were found to be significantly changed at 10 minutes post mortem as compared to control. Moreover, using western blot the level of MAPK phosphorylation was shown to decrease by 95% in the 10 minutes post mortem sample. A database, SwePep (a repository of endogenous peptides, hormones and small proteins), was constructed to facilitate identification using MS. The database also contains additional information concerning the peptides such as physical properties. A method for analysis of LC-MS data, including scanning for, and further profiling of, biologically significant peptides was developed. We show that peptides present in different amounts in groups of samples can be automatically detected. The peptidome approach was used to investigate levels of peptides in two animal models of Parkinson’s disease. PEP-19, was found to be significantly decreased in the striatum of MPTP lesioned parkinsonian mice. The localization and expression was further investigated by imaging MALDI MS and by in situ hybridization. The brain peptidome of reserpine treated mice was investigated and displayed a number of significantly altered peptides. This thesis demonstrates that the peptidomics approach allows for the study of complex biochemical processes.