Chemicals and Drugs Commons^™

Discovery Of Selective Probes Targeting Rna Polymerase I, Xiao Tan

Theses and Dissertations--Chemistry

RNR Polymerase I (RNA Pol I) is a “factory” that orchestrate the transcription of ribosomal rRNA for constructing ribosomes as a primary workshop for protein translation to sustain cell growth. Misregulation of RNA Pol I can cause uncontrolled cell proliferation, which leads to the development of cancer. Yeast (Saccharomyces cerevisiae) is a valuable model system to study RNA Pol I. Recently, the X-ray crystal structure of the yeast homologue of RNA Pol I was elucidated, offering the structural basis to selectively target this transcriptional machinery. The approach to selective RNA Pol I targeting was to disrupt the interaction …

Vibrational Characterization Of Granulosa Cells From Patients Affected By Unilaterial Ovarian Endometriosis: New Insights From Infrared And Raman Microspectroscopy, Valentina Notarstefano, Giorgia Gioacchini, Hugh Byrne, Carlotta Zaca, Eleni Sereni, Lisa Vaccari, Andrea Borini, Oliana Carnevali

Articles

Endometriosis is a chronic gynaecological disease characterised by the presence of endometrial cells in extra-uterine regions. One of the main factors impacting on the fertility of women affected by endometriosis is the poor oocyte quality. Granulosa Cells (GCs) regulate oocyte development and maintain the appropriate microenvironment for the acquisition of its competence; hence, the dysregulation of these functions in GCs can lead to severe cellular damages also in oocytes. In this study, luteinized GCs samples were separately collected from both ovaries of women affected by Unilateral Ovarian Endometriosis and analysed by infrared and Raman microspectroscopy. The spectral data were compared …

Regenerative Potential Of Mesenchymal Stem Cell Derived Exosomes, Andrew P. Wong

Theses and Dissertations

Bone defects are a pervasive complication arising from many clinical conditions, both mechanical and pathological. Current treatments for large bony defects focus on applying bone grafts or synthetic materials to the defect area. Cell-based—and especially stem-cell—therapies have advanced greatly thanks to increasing attention focused on their ability to generate new tissues in situ with biomechanical properties approaching that of native tissue, but they suffer from their own shortcomings as well. Exosomes have been shown to play critical roles in cell-signaling and tissue regeneration and are therefore potentially ideal therapeutic vehicles for treating bone defects. Exosomes are small microvesicles counted amongst …

Pharmacodynamics Of Monoamine Transporter Releasing Agents And Reuptake Inhibitors, Alexa Holloway

Theses and Dissertations

Ligands of the human monoamine transporters encompass a wide range of both illicit and therapeutic drugs that act upon neural circuitry related to reward, motivation, and the processing of salient stimuli. The present study utilizes two methods for analyzing transporter substrates and inhibitors in order to characterize activity and assess potency. The first measures transient changes in intracellular calcium as a surrogate for transporter activity by harnessing the electrical coupling of monoamine transporters and L-type calcium channels. This is used to analyze novel chimera of the strong hDAT inhibitors methylphenidate and ��-PPP in order to assess the contribution of specific …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

In Vitro Metabolism Of The Synthetic Cannabinoids Px-1, Px-2, Px-3 And A Comparison Of Their Clearance Rates In Human Liver Microsomes, Travon Cooman

Graduate Theses, Dissertations, and Problem Reports (ETD)

Detection of SCs in body fluids continue to be a challenge because of limited metabolism data, lack of standards and reference mass spectrometry data. In vivo and in vitro experiments help elucidate metabolite markers for novel psychoactive substances and can prompt synthesis of standards to verify proposed metabolites. In this study, metabolism of three SCs N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamine (PX-1), N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluropentyl)-1H-indazole-3-carboxamide (PX-2), and N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (PX-3) were investigated using human liver microsomes. Previous studies showed PX-3 as the most potent CB1 and CB2 receptor agonist.

Half-life and clearance data were acquired using liquid chromatography- tandem mass spectrometry. Metabolite elucidation was performed using liquid chromatography …

Discrimination Of Breast Cancer From Benign Tumours Using Raman Spectroscopy, Fiona Lyng, Damien Traynor, Thi Nguyet Que Nguyen, Aidan Meade, Fazle Rakib, Rafif Al-Saady, Erik Goormaghtigh, Khalid Al-Saad, Mohamed H. Ali

Articles

Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million cases and 522,000 deaths in 2012. Breast cancer is diagnosed by histopathological examination of breast biopsy material but this is subjective and relies on morphological changes in the tissue. Raman spectroscopy uses incident radiation to induce vibrations in the molecules of a sample and the scattered radiation can be used to characterise the sample. This technique is rapid and non-destructive and is sensitive to subtle biochemical changes occurring at the molecular level. This allows spectral variations corresponding to disease onset to be detected. The aim …

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao

Scripps Senior Theses

In response to the growing rates of antibiotic resistance in human bacterial pathogens, this study explores the natural products involved in the defensive symbiosis between actinobacteria and fungus-growing ants to uncover new potential antibiotics. This study also seeks to understand the function of natural antibiotics in their ecological contexts, especially those involved in defensive symbioses. Defensive symbiosis can be a beneficial platform for discovering useful antibiotics, because antibiotics in these relationships must be able to selectively inhibit enemies without harming hosts, and are therefore likely more specific and less toxic. Pseudonocardia sp. associated with Trachymyrmex septentrionalis ants demonstrated antibiotic activity …

Improving Dopamine Monitoring With Ncam And The Effects Of Intranasal Oxytocin On Dopamine Signaling In The Rat Brain, Darren Earl Ginder

EWU Masters Thesis Collection

Dopamine (DA) is a neurohormone highly involved in learning and memory. Oxytocin (OXT), another neurohormone, has also been implicated in learning and memory. Fast-scan cyclic voltammetry (FSCV) is a method used for the real-time examination of DA neurotransmission in the brain. Implanting FSCV electrodes is an invasive technique that likely results in an inflammatory response (i.e. gliosis) that can restrict FSCV recording of DA signals. Neural cell adhesion molecule (NCAM) may reduce gliosis and potentially improve the ability of FSCV electrodes to monitor DA signaling. Chapter 1 Methods: FSCV electrodes were coated with NCAM and implanted in the rat brain. …