Pharmacology Commons^™

Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various ...

Mass Spectrometric Analysis Of Isotopic Abundance Ratio In Biofield Energy Treated Thymol, Mahendra Trivedi

Mahendra Kumar Trivedi

Determination Of Isotopic Abundance Ratio Of Biofield Energy Treated 1,4-Dichlorobenzene Using Gas Chromatography-Mass Spectrometry (Gc-Ms), Mahendra Trivedi

Mahendra Kumar Trivedi

Evaluation Of Isotopic Abundance Ratio In Biofield Energy Treated Nitrophenol Derivatives Using Gas Chromatography-Mass Spectrometry, Mahendra Trivedi

Mahendra Kumar Trivedi

Towards Pharmacovigilance Using Machine Learning To Identify Unknown Adverse Reactions Triggered By Drug-Drug Interaction, Tabassum Kakar, Xiao Qin, Susmitha Wunnava, Elke A. Rundensteiner

UMass Center for Clinical and Translational Science Research Retreat

Adverse Drug Reactions (ADRs) are a major cause of morbidity and mortality in world. There is thus a growing need of methods facilitating the automated detection of drugs-related ADR; especially ADRs that were not known from clinical trials but later arise due to drug-drug interactions. In this research our goal is to discover the severe unknown Adverse Drug Reactions caused by a combination of drugs, also known as Drug-Drug-Interaction. We propose to use Association Rule Mining to find the ADRs caused by using a combination of drugs yet not known to be caused if these drugs were taken individually. For ...

Bioavailability Of The Antimalarial Drug Artemisinin Delivered Orally As Dried Leaves Of Artemisia Annua: The Role Of Solubility And Protein., Matthew Desrosiers, Pamela Weathers

UMass Center for Clinical and Translational Science Research Retreat

Malaria treatment using orally consumed dried leaves of the artemisinin producing GRAS plant Artemisia annua has recently shown promise. Previously we showed, oral consumption of A. annua dried leaves (DLA) yielded >40 times more artemisinin in the blood of mice than treatment with pure artemisinin. Using the Caco-2 cell culture model of the human intestinal epithelium, we also showed that compared to pure artemisinin, digested DLA doubled the permeability (Papp). Here, using simulated human digestion, we show that artemisinin solubility is about seven times higher in digestates of DLA than in digestates of pure artemisinin, likely contributing to its enhanced ...

Evaluation Of The Isotopic Abundance Ratio In Biofield Energy Treated Resorcinol Using Gas Chromatography-Mass Spectrometry Technique, Mahendra Kumar Trivedi, Alice Branton, Dahryn Trivedi

Mahendra Kumar Trivedi

Leukemia Inhibitory Factor As A Neuroprotective Agent Against Focal Cerebral Ischemia, Stephanie Davis

Graduate Theses and Dissertations

Previous publications from this laboratory demonstrated that administration of leukemia inhibitory factor (LIF) (125 µg/kg) to young, male Sprague-Dawley rats at 6, 24, and 48 h after middle cerebral artery occlusion (MCAO) reduced infract volume, improved sensimotor skills, and alleviated damage to white matter at 72 h after the injury. In vitro studies using cultured oligodendrocytes (OLs) showed that LIF (200 ng/ml) also protects against 24 h of oxygen-glucose deprivation through activation of Akt signaling and upregulation of the antioxidant enzymes peroxiredoxin IV and metallothionein III. Other groups have demonstrated that LIF reduces neurodegeneration in animal models of ...

Inhibition Of Peroxide Removal Systems And Ascorbate-Induced Cytotoxicity In Pancreatic Cancer, Hannah Van Beek

Theses and Dissertations

Compared to normal cells, cancer cells tend to have higher concentrations of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂) due to an accelerated cellular metabolism. The high ROS content leaves cancer cells increasingly susceptible to oxidative stress-induced cell death. This susceptibility can be manipulated in selective cancer therapy by further increasing production of ROS or inhibiting peroxide removal systems or a combination of the two.

Pharmacological ascorbate (high-dose intravenous ascorbate) has been shown to sensitize pancreatic cancer to ionizing radiation (IR) by increasing production of ROS such as H₂O₂. Glutathione reductase (GR ...

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 ...

Cardiovascular Effects Evoked By Airway Nociceptive Reflexes In Healthy And Cardiovascular Diseased Rats, Justin Shane Hooper

Graduate Theses and Dissertations

Acute inhalation of airborne pollutants alters cardiovascular function and has been shown to have its greatest affects on individuals with pre-existing cardiovascular disease. Evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the cardiovascular responses evoked by inhalation of AITC (TRPA1 agonist) and capsaicin (TRPV1 agonist) in healthy Sprague Dawley (SD) and Wistar Kyoto (WKY) rats, and cardiovascular diseased Spontaneously Hypertensive (SH) rats. Inhalation of the agonists by healthy SD and WKY rats caused significant bradycardia, atrio-ventricular (AV) block and prolonged PR-Intervals. Inhalation of ...

Assessment Of The Role Of Poly (Adp-Ribose) Polymerase In Drug-Induced Cardiomyopathy, Alexis I. Brinkerhoff

Graduate Theses and Dissertations

Drug-induced cardiotoxicity has resulted in a thorough evaluation of patient doses, treatments, and rehabilitation. One of the most commonly prescribed chemotherapeutic agents is cyclophosphamide. The active metabolite, acrolein, is one of the most potent inducers of cardiomyopathy. In this study, research was conducted on the H9c2 (2-1) cardiomyocyte cell line derived from the embryonic myocardium of rattus norvegicus to assess its competency for evaluation of the change in poly (ADP-ribose) polymerase (PARP) activity. The application of this model to study the effects of acrolein on PARP activation was chosen as an ideal determinant of cell damage produced by nitrogen mustards ...

Thromboxane A2 And Tp Receptors: A Trail Of Research, Well Traveled, Perry V. Halushka Phd, Md

Journal of the South Carolina Academy of Science

This article was written is response to a request from the editor-in-chief as a result of my receiving the Governor’s Award in Scientific Awareness. My goal is to provide a glimpse into a 40 plus year research career that was predominately focused on the role of thromboxane A₂ and its receptor (TP) in physiologic and pathophysiologic processes in the cardiovascular system. It also enumerates the lessons learned along the way that may lead to a productive research career. Those lessons were; Perseverance, Think out of the box, Challenge the dogma, Take risks, Failure is not a bad thing ...

Phosphodiesterase Inhibition As A Mechanism Of Ion Channel Modulation By Celecoxib, Christina Jean Robakowski

Master's Theses

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which ...

Sensory Hypo-Excitability In A Rat Model Of Fetal Development In Fragile X Syndrome, Julia Berzhanskaya, Marnie Phillips, Jing Shen, Matthew Colonnese

Pharmacology and Physiology Faculty Publications

Fragile X syndrome (FXS) is characterized by sensory hyper-sensitivity, and animal models suggest that neuronal hyper-excitability contributes to this phenotype. To understand how sensory dysfunction develops in FXS, we used the rat model (FMR-KO) to quantify the maturation of cortical visual responses from the onset of responsiveness prior to eye-opening, through age equivalents of human juveniles. Rather than hyper-excitability, visual responses before eye-opening had reduced spike rates and an absence of early gamma oscillations, a marker for normal thalamic function at this age. Despite early hypo-excitability, the developmental trajectory of visual responses in FMR-KO rats was normal, and showed the ...

Discriminative Stimulus Properties Of Endogenous Cannabinoid Degradative Enzyme Inhibitors, Robert Owens Ii

Theses and Dissertations

Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the chief degradative enzymes of N-arachidonoyl ethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), respectively, elicits no or partial substitution for Δ⁹-tetrahydrocannabinol (THC) in drug discrimination procedures. However, combined inhibition of both enzymes fully substitutes for THC, as well as produces a full constellation of cannabimimetic effects. Because no published report to date have investigated whether an inhibitor of endocannabinoid hydrolysis will serve as a discriminative stimulus, the purpose of this doctoral dissertation was to investigate whether C57BL/6J mice would learn to discriminate SA-57 (4-[2-(4-Chlorophenyl)ethyl ...

Acute And Chronic Effects Of Inhalants In Intracranial Self-Stimulation, Matthew Tracy

Theses and Dissertations

Inhalants are a loosely defined diverse group of volatile substances which people abuse. Despite widespread misuse of inhalants, there are limited preclinical methods available to study the reinforcement-like properties of inhalants. One procedure which has demonstrated substantial promise as a tool to investigate inhalant pharmacology is the intracranial self-stimulation (ICSS) procedure. ICSS utilizes pulses of electrical stimulation to the mesolimbic reward pathway to serve as a temporally defined and controlled operant reinforcer with a highly adjustable efficacy. The first aim of the project was to characterize the effects of commonly abused inhalants: including toluene, trichloroethane, nitrous oxide, isoflurane and R134a ...

Physical, Spectroscopic And Thermal Characterization Of Biofield Treated Fish Peptone, Mahendra Trivedi

Mahendra Kumar Trivedi

Characterization Of Physicochemical And Spectroscopic Properties Of Biofield Energy Treated Bio Peptone, Mahendra Trivedi

Mahendra Kumar Trivedi

Characterization Of Physical, Thermal And Spectral Properties Of Biofield Treated 2-Aminopyridine, Mahendra Trivedi

Mahendra Kumar Trivedi