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The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
provided by the
Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 221 to 222 of 222 (0.056 seconds)Spelling suggestions: "subject:"amedical pharmacology"" "subject:"amedical pharmacologyc""
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Exploring the molecular architecture of proteins: Method developments in structure prediction and designChavan, Archana G. 01 January 2014 (has links) (PDF)
Proteins are molecular machines of life in the truest sense. Being the expressors of genotype, proteins have been a focus in structural biology. Since the first characterization and structure determination of protein molecule more than half a century ago1, our understanding of protein structure is improving only incrementally. While computational analysis and experimental techniques have helped scientist view the structural features of proteins, our concepts about protein folding remain at the level of simple hydrophobic interactions packing side-chain at the core of the protein. Furthermore, because the rate of genome sequencing is far more rapid than protein structure characterization, much more needs to be achieved in the field of structural biology. As a step in this direction, my dissertation research uses computational analysis and experimental techniques to elucidate the fine structural features of the tertiary packing in proteins. With these set of studies, the knowledge of the field of structural biology extends to the fine details of higher order protein structure.
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Anti-Psychotic Drug Induced Tardive Dyskinesia: A Role for the Anti-Apoptotic Molecule CurcuminSookram, Christal D. 10 1900 (has links)
<p>Anti-psychotic drug (APD) administration can induce movement disorders including tardive dyskinesia (TD), characterized by abnormal movements of the oro-facial region and occasionally the trunk and limbs. The most widely accepted model of TD is the APD-induced vacuous chewing movement (VCM). While the mechanism of induction of TD remains unclear, there are two prevailing hypothesis: oxidative stress and dopamine supersensitivity. Currently available APDs antagonize dopamine D2 receptors (D2R) which can result in excessive dopamine accumulation and oxidation which was demonstrated to induce striatal neurodegeneration and increased oxidative stress. The dopamine supersensitivity hypothesis proposes that APD treatment causes an up-regulation of high affinity D2Rs to compensate for D2R antagonism. Curcumin, a derivative of turmeric, has been demonstrated to affect dopamine levels and hold significant anti-apoptotic potential. Thus, the goal of this study was to investigate curcumin’s potential to prevent haloperidol-induced behavioural and biochemical abnormalities. Four groups of rats were treated daily: control; haloperidol (at 2mg/kg intra-peritoneally); curcumin (at 200mg/kg orally in jello) and curcumin plus haloperidol. VCMs, catalepsy and locomotor activity were assessed. Animals were sacrificed and tissues removed for qPCR, immunoblot, receptor binding, and UPLC assessments. At day14 there was a significant increase in VCMs and catalepsy following haloperidol treatment, which was prevented by curcumin treatment. However, curcumin did not alter locomotor activity. Curcumin was demonstrated to increase the expression of the anti-apoptotic molecule BclXL and to increase striatal D2Rs. These investigations support the potential of curcumin in the prevention of TD and provide insight into the complex pathophysiology of this disorder.</p> / Doctor of Philosophy (Medical Science)
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