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Articles 61 - 89 of 89
Full-Text Articles in Chemicals and Drugs
Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy
Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy
Theses, Dissertations and Capstones
Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …
The [E]Motionless Body No Longer: Tracing The Historical Intersections Of Mental Illness And Movement In The American Asylum, Holly Adele Herzfeld
The [E]Motionless Body No Longer: Tracing The Historical Intersections Of Mental Illness And Movement In The American Asylum, Holly Adele Herzfeld
Senior Projects Spring 2017
Senior Project submitted to The Division of Multidisciplinary Studies of Bard College.
Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd
Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd
Biomedical Sciences ETDs
The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.
The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …
Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo
Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo
Forensic Science Theses
Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley
Theses and Dissertations--Pharmacology and Nutritional Sciences
Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …
The Effectiveness Of A Preoperative Multimodal Antiemetic Regimen On Reducing Early Postoperative Nausea And Vomiting In Total Joint Arthroplasty Patients, Jerry Mosley
Doctoral Projects
Postoperative nausea and vomiting (PONV) occurs frequently in all types of surgeries including after total joint orthopedic procedures. The resulting PONV can lead to many unwanted occurrences including immobilization, distress, and many serious adverse health complications. These unwanted occurrences may then lead to increased cost to the patient and healthcare facility. Administration of a preoperative multimodal regimen known to reduce PONV has the potential to reduce such unwanted anesthetic side effects influencing a reduction in overall healthcare cost. The purpose of this study is to determine the effectiveness of the preoperative kit which includes the administration of metoclopramide, famotidine, ondansetron, …
Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd
Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd
Dissertations & Theses (Open Access)
Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth
By Geoffrey Grandjean
Advisory Professor: Garth Powis, D. Phil
Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand [1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …
Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen
Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen
Theses and Dissertations--Pharmacy
Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.
Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …
Ten Weeks With Green Beans...And Then Some: Determination Of Bisphenol-A (Bpa) In Canned Goods From Arkansas Markets Using Fluorescence Spectrophotometry, Rachel Pruett
Honors Theses
Bisphenol A (BPA) is a chemical widely used in production of consumer goods. It has come under scrutiny recently after being labeled as an endocrine disruptor (ED), mostly causing adverse effects in infants and young children. It has been associated with diabetes, cardiovascular disease, and abnormal maturation. Because it is so commonly used in product development, humans are exposed to BPA through various means, such as ingestion or dermal absorption. It is a concern that the combined exposure could cause serious effects even in small doses.
In canned foods, the chemical is made into an epoxy resin to provide a …
Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee
Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee
Theses and Dissertations
Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds
By Daniel E. Lee, Ph.D.
A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.
Virginia Commonwealth University, 2015
Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry
Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …
Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini
Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini
Theses and Dissertations
DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol (Tg) at the first (Tg1) , second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3’ terminus was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate …
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Theses and Dissertations--Neuroscience
The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …
Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal
Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal
Doctoral Dissertations
Dried Whole plant Artemisia annua as a novel antimalarial therapy September 2014 Mostafa Ahmed Elfawal Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Stephen M. Rich Malaria is one of the worst vector-borne parasitic diseases in the developing world. The World Health Organization (WHO) estimated that 215 million cases of malaria occurred, with >655,000 deaths; half the world’s population is at risk of contracting the disease. Drugs are primary weapons for reducing malaria in human populations. Successful drugs are highly efficacious and inexpensive to manufacture synthetically. However, emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that …
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Doctoral Dissertations
Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …
Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian
Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian
Seton Hall University Dissertations and Theses (ETDs)
Azapeptides are a class of peptide mimics (peptidomimetics), which have served as valuable tools for the development of peptide based therapeutic agents. The therapeutic promise of azapeptides has been correlated to its primary sequence modification which translates into bio-active secondary structures that improves the pharmacological properties of the native peptide sequence. More specifically, azapeptides contain a semicarbazide within the peptide backbone which restricts the peptide bond torsion angles (φ, ψ) into pre-organized b-turn secondary structures. Thus, azapeptides have been shown to stabilize bio-active b-turn secondary structures responsible for high affinity and selective binding to a target …
Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao
Dissertations & Theses (Open Access)
The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies …
Arsenic Contamination In Groundwater In Vietnam: An Overview And Analysis Of The Historical, Cultural, Economic, And Political Parameters In The Success Of Various Mitigation Options, Thuy M. Ly
Pomona Senior Theses
Although arsenic is naturally present in the environment, 99% of human exposure to arsenic is through ingestion. Throughout history, arsenic is known as “the king of poisons”; it is mutagenic, carcinogenic, and teratogenic. Even in smaller concentrations, it accumulates in the body and takes decades before any physical symptoms of arsenic poisoning shows. According to the World Health Organization (WHO), the safe concentration of arsenic in drinking water is 10 µg/L. However, this limit is often times ignored until it is decades too late and people begin showing symptoms of having been poisoned.
This is the current situation for Vietnam, …
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Dissertations & Theses (Open Access)
The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …
Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof
Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof
Dissertations & Theses (Open Access)
Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …
Modelling Β2ar Regulation, Sharat J. Vayttaden
Modelling Β2ar Regulation, Sharat J. Vayttaden
Dissertations & Theses (Open Access)
The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …
Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon
CMC Senior Theses
The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.
Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …
Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff
Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff
Chancellor’s Honors Program Projects
No abstract provided.
Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull
Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull
Dissertations & Theses (Open Access)
Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.
We have examined the response …
Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson
Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson
Theses, Dissertations and Capstones
Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …
Studies On The Regulation Of Mu Opioid Receptor Mrna Expression In Shsy-5y Human Neuroblastoma Cells, Xin Yu
Studies On The Regulation Of Mu Opioid Receptor Mrna Expression In Shsy-5y Human Neuroblastoma Cells, Xin Yu
Seton Hall University Dissertations and Theses (ETDs)
Prolonged exposure to morphine down-regulates mu opioid receptors (MOR) on both undifferentiated and differentiated (retinoic acid or phorbol ester treated) SHSY-5Y cells. However, morphine pretreatment does not alter MOR receptor affinity for morphine. To investigate the molecular basis for MOR regulation after exposure to its selective agonists, we have developed a quantitative competitive reverse transcriptase-polymerase chain reaction (QC-RT PCR) to quantify the expression of MOR in SHSY-SY cells. Differentiation of SHSY-5Y cells with retinoic acid or phorbol ester up regulated MOR mRNA expression by 30 % and 78%, respectively. A 24 hours treatment with morphine (10 µM) down regulated MOR …
Modulatory Effects Of Citrus Flavonoids Towards The Metabolism And Mutagenicity Of Environmental Carcinogens, Wayne L. Bear
Modulatory Effects Of Citrus Flavonoids Towards The Metabolism And Mutagenicity Of Environmental Carcinogens, Wayne L. Bear
Loma Linda University Electronic Theses, Dissertations & Projects
The environmental carcinogens classified as heterocyclic amines (HCA’s) and the tobacco-specific nitrosamine NNK generally require internal enzymatic activation. This activation occurs via cytochrome P450 (CYP) enzymes and leads to metabolites that bind to human DNA which may in turn cause mutations which may then in turn lead to carcinogenesis. Certain nonnutritive plant compounds termed phytochemicals may protect against HCA and NNK-induced mutagenesis and carcinogenesis. We investigated the potential protective effects of five different phytochemicals of the flavonoid class which naturally occur in citrus. These flavonoids were diosmin, naringin. naringenin, rutin, and quercetin. Our results suggest that naringenin and quercetin were …
Effect Of Cocaine On Rabbit Renin Angiotensin System: Cocaine Detection In Adult And Fetal Tissue And Adult Plasma Using Ion Mobility Spectrometry, Barbara Belinda Guinn
Effect Of Cocaine On Rabbit Renin Angiotensin System: Cocaine Detection In Adult And Fetal Tissue And Adult Plasma Using Ion Mobility Spectrometry, Barbara Belinda Guinn
Biological Sciences Theses & Dissertations
Ion mobility spectrometry (IMS) was used to detect cocaine and/or the metabolite ecgonine methyl ester (EME) in tissue and plasma samples from male, maternal, and fetal New Zealand White (NZW) rabbits. EME was consistently detected in all adult plasma samples 5 minutes after the injection of cocaine hydrochloride (cocaine•HCI, 2 mg/kg). EME was also in the liver, kidneys, testicles, and ovaries. Five minutes after the injection of cocaine•HCI, the male arterial pressure (MAP) increased from a mean control value of 79 ± 3.2 mmHg to 88 ± 4.1 mmHg, and the pCO2 increased from a control value of28 ± …
Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott
Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott
Loma Linda University Electronic Theses, Dissertations & Projects
The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD2 rose significantly in 2B segments, but did not change …
Sulfatides As Opiate Receptors: An Evaluation Of The Opiate Binding Potential Of Sulfogalactosylgylcerolipid, Darby Geoghegan Hand
Sulfatides As Opiate Receptors: An Evaluation Of The Opiate Binding Potential Of Sulfogalactosylgylcerolipid, Darby Geoghegan Hand
Chemistry & Biochemistry Theses & Dissertations
Cerebroside sulfate (CS) has recently been shown to bind opiate drugs in a pharmacologically relevent manner and therefore satisfy the structural requirements of an opiate receptor. Seminolipid (SGG), a novel sulfated galactosyl. glycerolipid that has been isolated from the testes of a variety of mammals, may be viewed as a structural analog of CS. In view of this structural similarity, it is reasonable to presume that SGG may also bind opiate drugs. The isolation of SGG from boar testes was accomplished using silica gel dry column chromotography with a chloroform: methanol water solvent system. The structure and purity of the …