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Dissertations / Theses on the topic 'Pharmacology|Pharmaceutical sciences'

Author: Grafiati

Published: 9 July 2021

Last updated: 2 February 2022

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1

Peterson, Amity. "Characterization and Pharmacogenetics of Hepatic Phase I Exemestane Metabolism." Thesis, Washington State University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10266284.

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<p> Exemestane (EXE) is an endocrine therapy used to combat postmenopausal breast cancer. Several studies have reported substantial differences in clinical outcomes between EXE-treated patients, as well as inexplicable variability in serum concentrations of EXE and its major metabolite, 17β-dihydroexemestane (17β-DHE). For many pharmaceuticals, drug response is influenced by patient-specific genetic factors related to xenobiotic metabolism. Thus, it is possible that allelic variation in genes involved in EXE metabolism contributes to inter-individual differences in patient outcomes,

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2

Fraser, Graeme L. "Characterization of [delta] opioid receptor function in rat brain by pharmacological and antisense techniques." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38454.

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The opioid family of G-protein coupled receptors comprises four known receptor subtype genes (delta, mu, kappa, ORL1) and further receptor heterogeneity within each opioid receptor subfamily has been proposed. All four genes are expressed throughout the central nervous system and are believed to modulate a variety of behavioural responses including analgesia. Opiate drugs such as morphine that are selective for the mu receptor subtype are effective analgesics, but their chronic use is limited by the appearance of side effects such as respiratory depression, constipation and dependence. Consequ

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3

Li, Bing. "Drug solubility studies by using combined solubilization techniques." Diss., The University of Arizona, 2000. http://hdl.handle.net/10150/284037.

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This study focuses on the development of mathematical models that explain and predict the combined effects of pH control and complexants (cyclodextrin), pH control and surfactants, as well as pH control and cosolvents on the total solubility of the drug. The total solubility of the drug is expressed as the sum of the concentrations of individual species. In complexant-water and surfactant-water systems free unionized drug [Dᵤ] and free ionized drug [Dᵢ] are present along with either complexed unionized drug [DᵤL] and complexed ionized drug [DᵢL], or micellar unionized drug [DᵤM] and micellar i

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4

Gezginci, Mikail Hakan. "Synthesis and in vitro antimycobacterial activity of some pyridine and pyrazinecarboxylic acid isosteres." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284057.

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Tuberculosis has been one of the most commonly encountered infectious diseases of humans throughout history. The discovery and introduction of effective treatments in the 1940s resulted in a decline of the incidence of the disease until the 1980s, which marked a sharp turn in this trend with an increase in the number of reported cases in the world. The prevalence of mycobacterial infections in poorer nations and centers of urban decay, and especially in immunologically compromised patients indicates the need for new and better treatments. In this study, to contribute to the worldwide effort to

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5

Cai, Yuli 1961. "Disposition kinetics of Amphotericin-B in rats." Thesis, The University of Arizona, 1991. http://hdl.handle.net/10150/291689.

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The disposition kinetics of Amphotericin-B (Am-B) were investigated in rats in three different dose groups. Each group contained four rats. The serum and urine Am-B concentrations were analyzed by reversed-phase HPLC. There were no significant differences for total body clearance and half-lives as a function of dose. Those observations suggested systemic dose-independent behavior of Am-B. However, renal clearance of Am-B decreased significantly as Am-B dose increased; whereas, no renal damage was observed during the experiment. The present studies suggested that renal clearance was dose-depend

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6

Custodio, Joseph M. "Predicting intestinal transporter effects in food-drug interactions and the role of food on drug absorption." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3324590.

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7

Kim, Shinja Rhea. "Pharmacokinectic and pharmacodynamic aspects of cocaine and its interaction with ethanol." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/289511.

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The main purpose of the research described in this dissertation was to evaluate various aspects of cocaine in pharmacokinetics and pharmacodynamics including: physiologically based-pharmacokinetics modeling; the influence of ethanol on cocaine disposition. Further, cocaine and cocaethylene (CE) were compared using pharmacokinetic-pharmacodynamic (PK-PD) models. Lastly, PK-PD models after cocaine and a combination of cocaine and ethanol dose were developed. Cocaine was administered by iv with or without ethanol in rats. CE was formed only in the group of rats given cocaine in the presence of et

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8

Keiser, Michael James. "Relating protein pharmacology by ligand chemistry." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3378494.

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9

Riviere, Kareen. "Investigation of the enhancement of drug synergy by co-delivery in targeted liposomes." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3390075.

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10

Furbacher, Todd Raymond. "Bioassay-guided isolation of potential antineoplastic natural products from Southwestern plants." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/279927.

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This dissertation details the investigation of numerous plants for potential antineoplastic compounds. 144 plants (391 extracts) were prescreened with an assortment of assays. The pre-screens included an Agrobacterium tumefaciens/potato disk gall tumor inhibition assay, a Saccharomyces cerevisiae mutant topoisomerase assay, and an Escherichia coli plasmid scission assay. Bioassay-guided fractionation was conducted on three plants, Phoradendron juniperinum, Psorothamnus thompsoniae , and Acourtia thurberi, using a different assay for each. Phoradendron juniperinum (Viscaceae) was screened with

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11

Chance, Jeffrey John. "Liquid-phase sensing strategies for the thickness shear mode acoustic wave sensor." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0009/NQ36964.pdf.

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12

Adams, James Corey. "Mapping drug chemistry from the viewpoint of small molecule metabolism." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3359572.

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Thesis (Ph. D.)--University of California, San Francisco, 2009.<br>Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3519. Adviser: Patricia C. Babbitt. Includes supplementary digital materials.

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13

Akther, Farjana. "Sexual Dimorphism in Aortic Function of UC Davis Type 2 Diabetes Mellitus Rat Model: Estrogen Specific Responses." Scholarly Commons, 2019. https://scholarlycommons.pacific.edu/uop_etds/3600.

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Little is known about the interaction between diabetes and sex in vasculature. This study was designed to investigate the effects of estrogen as well as type 2 diabetes (T2D) on aortic function in rats with respect to sex. To test the effects of T2D and sex, UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model was used. To study the effects of estrogen, ovariectomized Sprague- Dawley female rats and UCD-T2DM rats at pre-diabetic stage were used and the rats were implanted subcutaneously either with placebo or 17 β-estradiol pellets (60 days release, 1.5mg/pellets). The plasma analytes for me

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14

Cao, Jieyun. "The role of sex hormones on monocarboxylate transporter expression in tissues related to drug disposition." Scholarly Commons, 2019. https://scholarlycommons.pacific.edu/uop_etds/3599.

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Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport monocarboxylates such as ketone bodies, lactate and pyruvate, as well as drugs such as gamma-hydroxybutyric acid. CD147 acts as an ancillary protein for MCT1 and MCT4, and is involved in membrane trafficking. Previously, it has been shown that MCT expression changes under different sex hormone conditions in skeletal muscle and Sertoli cells. However, it is unknown if MCTs, SMCTs or CD147 demonstrate sex differences in tissues where they play an important role in drug disposition. Monocarboxyla

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15

Rice, Peter J. "Understanding Drug Action: An Introduction to Pharmacology." Digital Commons @ East Tennessee State University, 2014. http://amzn.com/1582121125.

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This highly readable introduction to the science of pharmacology assumes only a modest understanding of biology, chemistry, and human physiology. Author Peter J. Rice provides readers with a survey of the scientific understanding of drug action. He discusses pharmacology at a basic scientific level to build a framework of how drugs work, and he supplements this discussion with information on some representative drugs that are used clinically. KEY FEATURES: Concise and systematic introduction to the science of pharmacology; Knowledge objectives in each chapter; Glossary of key terms in each cha

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16

Pappas, Beverly. "Mechanistic Study of p23-Mediated Aryl Hydrocarbon Receptor Expression." Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3131.

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The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which is involved in diverse biological functions ranging from cancer metastasis to immune regulation. This receptor forms a cytoplasmic complex with Hsp90, p23, and XAP2. We have previously reported that down-regulation of p23 triggers degradation of the AHR protein, uncovering a potentially dynamic event which controls the cellular AHR levels without ligand treatment. Here we investigate the underlying mechanisms for this p23 effect using wild-type HeLa and the p23 knockdown HeLa cells. Reduction of the Hsp90 and XA

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17

Sheng, Wanhui. "AN EXTENSION OF PLANARIAN BEHAVIORAL MODEL: CANNABINOID PHYSICAL DEPENDENCE AND WITHDRAWAL." Master's thesis, Temple University Libraries, 2016. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/402376.

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Pharmaceutical Sciences<br>M.S.<br>Background: Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 (10 μmol/L) for 1 h displayed a significant (p < 0.05) decrease in spontaneous locomotor velocity (pLMV) when subsequently tested in drug-free, but not in drug-containing, water. This demonstrated abstinence-induced withdrawal from a CB-R agonist as a manifestation of the development of physical dependence. Purpose: The purp

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18

Guillemard, Véronique. "Design and chemical synthesis of selective cancer therapeutics." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85073.

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The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is the lack of selectivity which leads to severe side effects and limited efficacy, and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted.<br>Growth factor receptors are one of the most extensively studied groups of tumor markers. The implicatio

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19

McReynolds, Kathrine Dawn. "1. Development of a novel ELISA for the testing of glycobioconjugates as anti-HIV agents 2. Synthesis of potential inhibitors of the HIV entry mechanism 3. Probing the secondary structural characteristics of oligosaccharides utilizing circular dichroism." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/283988.

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AIDS, or acquired immunodeficiency syndrome, is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus that is capable of rapid genetic mutation, which makes the virus and the disease difficult to treat. Several drug therapies are currently available, in the form of viral enzyme inhibitors. Other inhibitors of the viral entry and replication process are being investigated to enhance the drug therapy arsenal. Our research has focused on the development of HIV entry inhibitors. We are working towards the development of novel carbohydrate-based agents that are capable of binding th

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20

Sun, Jingjing. "Exploring the effect of alpha2 receptor on brain 5-HT via a mechanism-based pharmacodynamic model." Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/154.

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Purpose: 5-hydroxytryptamine (5-HT) is an important neurotransmitter in depression. It is believed that α 1 and α 2 adrenoceptors mediate the 5-HT level in the brain. The mechanism is complex and not well explored. Especially in different combination treatments, the receptor systems may show varied modulation capability. Additionally, some research has suggested that α 2 heteroceptors may contribute to the time delay problem in dual depression treatment which is thought as the time needed for certain inhibition receptor to get desensitized. We hypothesized that the α 2 adrenoceptors had inhibi

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21

Vyas, Piyush Manhur. "Sulfonamide-induced cutaneous drug reactions: role of bioactivation, oxidative stress and folate deficiency." Diss., University of Iowa, 2006. https://ir.uiowa.edu/etd/81.

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Sulfonamide- and sulfone-induced hypersensitivity reactions are thought to be mediated through bioactivation of parent drug molecule(s) to their respective reactive metabolite(s). In order to explain the cutaneous drug reactions caused by sulfonamides and sulfone, a mechanism can be proposed by which the bioactivation of these drugs in keratinocytes of the skin forms reactive hydroxylamine metabolites that can covalently bind to cellular proteins, which in turn act as antigens leading to the cascade of immune reactions resulting in a cutaneous drug reaction.

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22

Hui, Tina Hsiao-Tin. "Design and test of a pharmacologic screen for the adaptogenic properties of plant drugs : a master's thesis." Scholarly Commons, 1992. https://scholarlycommons.pacific.edu/uop_etds/2231.

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Panax ginseng C.A. Mey. (Araliaceae), which has been known in China for more than 4000 years, occupies a particular place among tonic remedies. Pharmacological investigations of the roots have shown that the basic effect of ginseng's action is its capacity to increase the nonspecific resistance of the organism to various untoward influences. In addition to ginseng, another plant of the Araliaceae family is used in a similar manner and is known as Siberian ginseng, Eleutherococcus senticosus (Rupr. et Maxim.) Maxim.). Its roots have been very extensively investigated by Russian scientists. Gins

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23

Akbar, Shahid. "Hypothermic activity of repin, a sesquiterpene lactone from Centaurea solstitialis." Scholarly Commons, 1993. https://scholarlycommons.pacific.edu/uop_etds/2757.

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Powdered aerial parts of the weed yellow starthistle (Centaurea solstitialis, Compositae) and the methanol extract, alkaloidal and fatty fractions of the methanol extract of the aerial parts, injected intraperitoneally, produced a highly significant hypothermia in conscious normal rats. Other significant symptomatology included sedation, decreases in spontaneous motor activity, depressed respiration, mydriasis, ear blanching, enophthalmos and anuria. Four sesquiterpene lactones of the guaianolide type (repin, solstitialin-A, janerin and cynaropicrin), constituents of yellow starthistle, showed

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24

Zhang, Tianmin. "Effects of Ainp2 and beta-tubulin on the Arnt-dependent signaling pathways." Scholarly Commons, 2010. https://scholarlycommons.pacific.edu/uop_etds/2645.

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Aryl hydrocarbon receptor nuclear translocator (Arnt) belongs to the basic helix-loop-helix/Per-Arnt-Sim protein family. Our lab is interested in identifying the protein factors that modulate the Arnt-dependent pathway. We identified a novel Arnt-interacting peptide Ainp2 with an estimated size of 9 kDa. The endogenous Ainp2 protein is not found in MCF-7 cells. Another protein that is of interest to us is β-tubulin. Beta-tubulin is the monomeric subunit of microtubules. I have presented my thesis in two parts: the first part is focused on Ainp2 and the second part is on β-tubulin. The purpose

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25

Matos, Francisca Fatima. "Opioid Receptor Effects Of Two Aminotetralin Derivatives In Guinea Pig Ileum Longitudinal Muscle And Mouse Vas Deferens Preparations." Scholarly Commons, 1987. https://scholarlycommons.pacific.edu/uop_etds/3394.

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Two substituted analogs of 3-amino-2,2-dimethyltetralin, namely 3-dimethylamino-7-hydroxy-2,2-dimethyl-1-tetralone HBr (J) and 3-dimethylamino-7-hydroxy-2,2-dimethyl-1-tetralol (MRSAL) were evaluated for opioid agonist and antagonist activity using the electrically-stimulated guinea pig ileum longitudinal muscle and mouse vas deferens preparations. The effects of these compounds in these tissues were compared to those induced by several opioid prototype agonists at mu, kappa and delta sites (normorphine, dihydromorphine, ethylketocyclazocine, U-50,488H, beta -endorphin, dynorphin 1-13, leu-enk

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26

ARORA, DEEPIKA. "IN VITRO MODELS FOR INHALED CORTICOSTEROID (ICS) AEROSOLS: A STUDY OF THEIR BIOPHARMACEUTICS AND PHARMACOLOGY." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1650.

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Lung cellular disposition and anti-inflammatory pharmacology of inhaled corticosteroids (ICSs) is complex, comprised of a cascade of aerosol deposition and dissolution, followed by cellular uptake for local pharmacological action. This project hypothesized that the kinetics of dissolution for certain ICS aerosols generated from inhaler products were kinetically rate-determined for their cellular uptake and local pharmacological action. A novel dissolution testing system was developed to determine the dissolution kinetics for the ICS aerosols. A total of 5 ICSs aerosols generated from 6 inhale

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27

Zheng, Yujuan. "The role of aryl hydrocarbon receptor (AHR) in drug-drug interaction and the expression of AHR in Pichia Pastoris." Scholarly Commons, 2019. https://scholarlycommons.pacific.edu/uop_etds/3580.

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The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear tra

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28

Malla, Ritu. "Role of PRAS40 in mammalian target of rapamycin (mTOR) modulation in cancer and insulin resistance." Scholarly Commons, 2016. https://scholarlycommons.pacific.edu/uop_etds/129.

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Dysregulation of PI3K-AKT-mTOR pathway has been reported in various pathologies, such as cancer and insulin resistance. The proline-rich AKT substrate of 40-kDa (PRAS40), also known as AKT substrate 1 (AKT1S1), lies at the crossroads of these cascades and inhibits the activity of the mTOR complex 1 (mTORC1) kinase. Firstly, our findings showed that disruption of PRAS40, a substrate of AKT and component of mTORC1, alters glucose homeostasis and prevent hyperglycemia in the streptozotocin (STZ)-induced diabetes mouse model. PRAS40 ablation resulted in a mild lowering of blood glucose levels and

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29

Shah, Khyati Niral. "Mechanism of tamoxifen resistance in breast cancer." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/138.

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Acquired tamoxifen resistance develops in the majority of hormone responsive breast cancers and frequently involves overexpression of the PI3K/AKT axis. Here, breast cancer cells, with elevated endogenous AKT or overexpression of activated AKT exhibited tamoxifen-stimulated cell proliferation and enhanced cell motility. To gain mechanistic insight on AKT-induced endocrine resistance, gene expression profiling was performed to determine the transcripts that are differentially expressed post-tamoxifen therapy under conditions of AKT overexpression. Consistent with the biological outcome, many of

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30

Chen, Jinyun. "REGULATION OF INTRACELLULAR ARYL HYDROCARBON RECEPTOR PROTEIN LEVELS." Scholarly Commons, 2020. https://scholarlycommons.pacific.edu/uop_etds/3675.

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The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which controls tumor growth and metastasis, T cell differentiation, and liver development. Expression levels of this receptor protein are sensitive to the cellular p23 protein levels in immortalized cancer cell lines. As little as 30% reduction of the p23 cellular content can suppress the AHR function. Here we reported that down-regulation of the p23 protein content in normal, untransformed human bronchial/tracheal epithelial cells to 48% of its content also suppresses the AHR protein levels to 54% of its content. Thi

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31

Penchala, Sravan C. "Characterization of AG10, a potent stabilizer of transthyretin, and its application in enhancing in vivo half-life of therapeutic peptides." Scholarly Commons, 2016. https://scholarlycommons.pacific.edu/uop_etds/130.

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The misassembly of soluble proteins into toxic aggregates, including amyloid fibrils, underlies a large number of human degenerative diseases. Cardiac amyloidoses, which are most commonly caused by aggregation of Immunoglobulin (Ig) light chains or transthyretin (TTR) in the cardiac interstitium and conducting system, represent an important and often underdiagnosed cause of heart failure. Two types of TTR-associated amyloid cardiomyopathies are clinically important. The Val122Ile (V122I) mutation, which alters the kinetic stability of TTR and affects 3% to 4% of African Americans, can lead to

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32

Treki, Mahmud Sighayer. "Formulation and evaluation of propylene glycol monostearate microspheres for sustained release of nitrofurantoin." Scholarly Commons, 1988. https://scholarlycommons.pacific.edu/uop_etds/3366.

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Sustained release of nitrofurantoin (NFT) from microspheres of propylene glycol monostearate (PGM) and of PGM and ethoxylated stearyl alcohol (ESA) prepared by the meltable dispersion and cooling process was investigated. The microspheres (30-850 mu) were nonsticky, discrete and free flowing. Both the rate and extent of in vitro release of NFT (from NFT-PGM microspheres in distilled water at 37 degrees C under constant agitation at 50 rpm) declined with decreasing NFT/PGM ratio. The effect of incorporating ESA over the range of 0.01 to 0.05% w/w of PGM in formulations with NFT/PGM ratios of 1:

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Han, Xiaoyuan. "Sex differences in aortic endothelial function of diabetic rats: Possible involvement of superoxide and nitric oxide production." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/136.

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Little is known about the interaction between diabetes and sex in vasculature. This study was designed to investigate whether there were sex differences in rat aortic endothelial function in diabetes, and to examine the potential roles of superoxide and nitric oxide (NO) in this sex-specific effect. Two diabetic animal models were used: streptozotocin (STZ)-induced type 1 diabetic rats (at early and intermediate stages of disease) and Zucker type 2 diabetic fatty (ZDF) rats. Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in aortic rings pre-contracted with phenyle

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Huang, Wei Hua. "Chemical investigation on root barks of Oplopanax horridus." Thesis, University of Macau, 2012. http://umaclib3.umac.mo/record=b2590373.

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Berry, Elicia Bee Ean. "Intracellular signalling by arachidonic acid metabolites." Thesis, University of Auckland, 2006. http://hdl.handle.net/2292/3111.

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In intrauterine tissues, pro-inflammatory cytokines and prostaglandins (PGs) have been identified as key mediators in the maintenance of pregnancy and parturition. The rise in PGD2 detected in the amniotic fluid before labour prompted the research presented in this thesis which describes the effects of 15-deoxy Δ12,14 -prostaglandin J2 (15d-PGJ2), a non-enzymatic metabolite of PGD2, on amnion-derived WISH and JEG3 choriocarcinoma cells as models of the amnion and chorion trophoblasts, respectively.15d-PGJ2 induced apoptosis in both cell lines in a concentration-dependent fashion (2.5-10 µM). A

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Collier, Abby Cherise. "Expression and activity of enzymes in the human placenta: pharmacological & toxicological consequences in AZT therapy." Thesis, University of Auckland, 2002. http://hdl.handle.net/2292/3138.

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The aim of this thesis was to study xenobiotic metabolising enzymes (XME) in the human placenta, in particular the uridine diphosphate glucuronosyltransferases' (UGTs) role in the metabolism, transfer and disposition of the drug AZT, and to develop the human placental perfusion model into the first trimester. UGT, β-glucuronidase, Cytochrome p4501A (CYPIA) and CYP reductase were present and active in the human placenta. CYP2E1 protein was expressed but not active. CYPIA, CYP2EI and the UGT2B subfamily were expressed across gestation, but the UGTIA subfamily was only expressed in first trimeste

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Patlolla, Karthik Reddy. "Predicting aqueous solubility of pharmaceutical agents by solid dispersion prepared by solvent evaporation method." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/268.

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Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research o

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Samoshin, Andrey V. "Diastereoselective acylation of trans-2-substituted-cyclohexanols and glycosidase inhibition studies." Scholarly Commons, 2011. https://scholarlycommons.pacific.edu/uop_etds/275.

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Part I. The reaction between chiral acyl chlorides and trans -2-substituted-cyclohexanols proceeds diastereoselectively, i.e. produces mixtures of unequal amounts of diastereomers. We found for the first time that addition of pyridine or diisopropylethylamine accelerates the acylation, and unexpectedly for some substituents (RX) may completely invert its diastereoselectivity. These observations have been rationalized in terms of a stereoselective intramolecular assistance by the RX group to the acylation of the neighboring hydroxyl ("bait-and-hook" mechanism). A series of trans -2-substituted-

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Nannapaneni, Vijaysri. "Preparation of amorphous forms to increase the solubility of poorly soluble drugs using spray drying." Scholarly Commons, 2011. https://scholarlycommons.pacific.edu/uop_etds/274.

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Spray drying is widely used in enhancing the aqueous solubility of poorly soluble compounds. In this study, the mechanism of solubility enhancement was characterized using three model drugs-naproxen, ketoprofen and furosemide. Physical mixtures of the model drug with polyvinylpyrrolidine and spray dried composites were subjected to Fourier Transform Infrared Sprectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (XRPD). The data showed that the crystalline model drugs were converted to amorphous form upon spray drying, whereas the physical mixtures did not c

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Yang, Dazhou. "Synthesis and biophysical evaluation of thiazole orange derivatives as DNA binding ligands." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/141.

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Guanine-rich telomeric DNA at the end of chromosomes can form a unique DNA tertiary structure - G-quadruplex, which is known to inhibit the binding of telomerase to telomeric regions in cancer cells and thus regulate unrestricted cancer cell growth. Hence, G-quadruplex DNA has recently become a promising target in oncology. The formation of G-quadruplex structures is greatly facilitated by G-quadruplex binding ligands such as Thiazole orange (TO). Compared with other G-quadruplex binding ligands, TO has an intriguing tunable fluorescence property. Upon binding to DNA, the fluorescence of TO ca

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Tejomurthula, Sravanthi. "Overexpression of Human Aryl Hydrocarbon Receptor in E.coli Using Two Different Solubility Enhancing Tags." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/261.

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Dioxins such as TCDD are environment pollutants whose toxic effects are mediated via aryl hydrocarbon receptor (AhR) signaling pathway. AhR is a ligand sensitive transcription factor. The unbound AhR resides in cytoplasm as a complex containing p23, Hsp90 and XAP2. Upon ligand binding, AhR undergoes conformational change and translocates into the nucleus. Once the AhR dimerizes with AhR nuclear translocator (Arnt), the chaperone proteins in the complex get dissociated followed by the activation of transcription of various genes such as CYP1A1 and CYP1A2 by AhR-ARNT heterodimer. Various cancers

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Vutukuru, Naresh Kumar Reddy. "Apparent dissolution rate enhancement of poorly-water soluble drugs by adsorption technique." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/269.

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Nearly 70% of the new chemical entities (NCE’s) discovered are poorly-water soluble drugs and the number of poorly-water soluble drugs are increasing rapidly in the drug discovery. Most of the NCE’s are lipophilic and have dissolution rate issues. Low dissolution rate of the drugs result in poor bioavailability. To overcome poor bioavailability, an adsorption technique is developed to enhance the apparent dissolution rate of poorly-water soluble drugs. In this study, two poor-water soluble model drugs, ibuprofen and carvedilol were used. Methanol, DMF, DMSO and PEG400 were used as solvents and

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Naidu, Prathyusha. "Catalase-loaded liposomal magnesium phosphate nanoparticles for intracellular protein delivery." Scholarly Commons, 2016. https://scholarlycommons.pacific.edu/uop_etds/266.

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Proteins are large biomolecules that have great therapeutic potential in treating many human diseases. Proteins exert higher specificity and more complicated functions; they are well endured and less inclined to evoke immune responses when compared to small molecule drugs. However, exogenous proteins when administered intravenously are prone to immune reactions. Chemical and enzymatic denaturation, and poor penetration into cells are some other challenges for clinical use of intracellular proteins. Proteins that enter cells through endocytosis will be eventually degraded in lysosomes if they d

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Kondepudi, Karthik Chalam. "Computational prediction of enhanced solubility of poorly aqueous soluble drugs prepared by hot melt method." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/267.

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Solubility is the concentration of a solute in a saturated solution at a given temperature and pressure. Solubility of a drug in aqueous media is a pre-requisite to achieve desired concentration of a drug in the systemic circulation. Low aqueous solubility is a major problem encountered with formulation development of recently designed new chemical entities. Solubility of poorly soluble drugs is enhanced by physical and chemical modifications of drug. Shake flask method is the most commonly used experimental method to determine solubility. However, this method has several limitations. A single

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Vangala, Swathi. "Human Cytochrome P450 3A4 Over-Expressing IEC-18 and MDCK Cell Lines as an In-Vitro Model to Assess Gut Permeability and the Enzyme Metabolism." Scholarly Commons, 2013. https://scholarlycommons.pacific.edu/uop_etds/273.

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Purpose. The fate of an orally administered drug is dependent on many parameters before it can reach the systemic circulation, including drug absorption and first-pass metabolism in the gut and the liver. Mammalian cells lines such as MDCK and Caco-2 are commonly employed to assess drug permeability but they lack or have low expression level of drug metabolism enzyme expression such as CYP3A4, which contributes to significant first-pass gut and liver metabolism for many drugs. Consequently, these cell lines are not sufficient to integrate metabolism when assessing drug absorption. Here, we tes

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Arikatla, Swetha. "Effect of Tumor Microenvironmental Conditions on Non Small Cell Lung Cancer." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/126.

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Tumor microenvironmental conditions play a vital role in promoting metastasis and tumor recurrence. Due to inefficient vasculature, cancer cells experience hypoxia, glucose deprivation and low pH even during the early stages of tumor growth. Tumor cells are proposed to adapt to these microenvironmental conditions by acquiring increased migratory and invasion potential and tumor initiating ability. Our research addresses the effect of these biochemical factors of the tumor microenvironment (TME) on motility, epithelial to mesenchymal transition (EMT) and stemness of non-small cell lung cancer (

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Ponnakanti, Himaja. "Soluble and Functional Overexpression of the Ligand Binding Domain of Mouse Aryl Hydrocarbon Receptor in E.Coli." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/260.

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The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor whose toxicity and carcinogenesis is mediated through various polyaromatic hydrocarbons and other environmental pollutants. The role of AhR in carcinogenesis is an area of concern due its altered levels in various tumors. AhR binds structurally diverse ligands and may elicit different responses upon ligand binding. The crystal structure of mouse AhR PAS-A domain was already obtained due to the robustness of mouse AhR in comparison to human. There is a possibility of overexpressing mouse AhR ligand binding

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Zhang, Changfeng. "Investigation of the endoplsmic reticulum calcium stores for their potential roles in neuroprotection using the NG115-401L neuronal cell line model." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/142.

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There is significant interest in the field of neuroscience to gain a better understanding of how neurons die in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We have used the neuronal cell line NG115-401L with unique calcium signaling characteristics to test the hypothesis that improving calcium loading into the endoplasmic reticulum (ER) to increase ER calcium levels acts as a possible neuroprotective response. We approached this problem using both pharmacological and genetic approaches targeting the central mediator of calcium uptake in the ER localized sarco/endop

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Shaker, Nuha. "Examining the Influence and Role of Pharmacogenetics among Children with Autism Spectrum Disorder." TopSCHOLAR®, 2017. https://digitalcommons.wku.edu/theses/2037.

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Pharmacogenetics is the study of genomic-guided individualized drug prescription that plays an important role in preventing the severe adverse effects of drugs, decreasing the time and cost of therapeutic choices, and directing healthcare professionals to choose medications that are effective and safe. It is noteworthy that this approach becomes highly beneficial in patients suffering from chronic diseases or disorders, since these conditions may require multiple and long term pharmacological therapies, as in children with autism spectrum disorder (ASD). However, public acceptance is a major c

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Cao, William Sam. "Characterization and application of human pluripotent stem cell-derived neurons to evaluate the risk of developmental neurotoxicity with antiepileptic drugs in vitro." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/131.

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The risks of damage to the developing nervous system of many chemicals are not known because these studies often require costly and time-consuming multi-generational animal experiments. Pluripotent stem cell-based systems can facilitate developmental neurotoxicity studies because disturbances in nervous system development can be modeled in vitro. In this study, neurons derived from embryonal carcinoma (EC) and induced pluripotent stem (iPS) cells, were first characterized to establish their suitability for developmental neurotoxicity studies. The EC stem cell line, TERA2.cl.SP-12, was differen

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