Chemical Actions and Uses Commons^™

Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli

Masters Theses & Specialist Projects

Platinum compounds are widely used drugs in cancer treatments. Although DNA is the biological target, reaction of platinum compounds with proteins is also potentially significant. Our objective is to study the effects of leaving ligands on the relative reactivity between 5'-GMP (guanosine 5' phosphate), a key DNA target, and N-Acetyl - L-Methionine (N-AcMet), a key protein target. We have used NMR spectroscopy to monitor reactions with N-AcMet and 5'-GMP added to a platinum complex to see which products are formed preferentially. Previous research showed that both a non-bulky complex such as [Pt(en)(D₂O)₂]²⁺ [en=ethylenediamine], and a …

Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui

Chemistry Faculty Publications and Presentations

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …

Regulation Of Alpha Synuclein Following Chronic Methamphetamine Administration In Guinea Pigs: Correlation With Memory And Synaptic Plasticity, Adnouse Blanc

PCOM Biomedical Studies Student Scholarship

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were …

Biological Evaluation Of Cyclooxygenase-2 Inhibitor Nimesulide Derivatives As Anti-Agents, Amandeep Singh, Snigdha Chennamaneni

Undergraduate Research Posters 2012

Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. A series of new nimesulide analogs were evaluated with cell proliferation assay based on a non-small lung cancer cell line H292. The results showed that several derivatives were very active to against H292 cell growth with IC50s of sub nano mole. These results suggest the possibility of using these nimesulide derivatives as chemo preventive agents.

System Dynamics Modeling Of Medical Use, Nonmedical Use And Diversion Of Prescription Opioid Analgesics, Wayne Wakeland, Alexandra Nielsen, Teresa D. Schmidt

Complex Systems Faculty Publications and Presentations

The objective of the study was to develop a system dynamics model of the medical use of pharmaceutical opioids to treat pain, and the associated diversion and nonmedical use of these drugs. The model was used to test the impact of simulated interventions in this complex system. The study relied on secondary data obtained from the literature and from other public sources for the period 1995 to 2008. In addition, an expert panel provided recommendations regarding model parameters and model structure. The behavior of the resulting systems level model compared favorably with reference behavior data (R2=.95). After the base model …

Under The Gun: Ongoing Assaults On Bahrain’S Health System, Richard Sollom, Holly G. Atkinson

Publications and Research

In February 2011, the Government of Bahrain began targeting health professionals who treated protesters. In April 2012, PHR's Richard Sollom, Deputy Director, and Holly Atkinson, MD, FACP, past President of PHR's Board and volunteer expert, authored a report showing the devastation on Bahrain's health system that have resulted from the Government of Bahrain’s continued assault on doctors, patients, and the healthcare system.

The Effects Of Nicotine Administration On Behavior And Markers Of Brain Plasticity In A Rodent Model Of Psychosis, Marla K. Perna

Electronic Theses and Dissertations

Schizophrenia affects about 1% of the population. A hallmark of the disorder is increased dopamine D2 receptor sensitivity in the brain. Studies have shown that schizophrenics smoke cigarettes at approximately 4 times the rate of the general population. It has been suggested that nicotine use is a form of self-medication for symptoms in schizophrenia. Smoking behaviors typically begin in adolescence. We assessed effects of nicotine on behavior and brain plasticity in an adolescent rodent model of schizophrenia with the goal of identifying targets for smoking cessation. Methods: Rats were neonatally treated with quinpirole (a D2/D3 agonist) or saline and sensitized …

Environmental Friendly Synthesis, Characterization Of Surface Modifiable Starch Encapsulated Gold Nanoparticles With Bactericidal And Catalytic Activity, Dillon Pender

Mahurin Honors College Capstone Experience/Thesis Projects

In the present study, we report the green synthesis of gold nanoparticles (GNPs), using potato starch as a reducing as well as a stabilizing agent in an aqueous buffer medium. The resulting starch-GNPs (St-GNPs) were near spherical in shape with an average diameter of 15 ± 5 nm. In this approach, St-GNPs were characterized and investigated for their antibacterial properties against both gram negative (Escherichia coli) and gram positive (Staphylococcus epidermidis) bacteria. These St-GNPs were found to possess significant dose dependent antibacterial activity against bacteria. Also, St-GNPs showed a significant catalytic activity and can easily be …

Differential Effects Of Acute Amphetamine And Phencyclidine Treatment And Withdrawal From Repeated Amphetamine Or Phencyclidine Treatment On Social Interaction And Social Memory In Rats, Ming Li, Wei He, Rebecca Munro

Department of Psychology: Faculty Publications

Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals …

Analogues Of The Epoxy Resin Monomer Diglycidyl Ether Of Bisphenol F: Effects On Contact Allergenic Potency And Cytotoxicity, Niamh O'Boyle, Tamara Delaine, Kristina Luthman, Andreas Natsch, Ann-Therese Karlberg

Articles

Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and non-occupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its …

Life As A Swimmer, Danielle N. Coville

Chemistry and Biochemistry

No abstract provided.

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC₅₀ value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

Articles

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC₅₀ values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

Dissertations and 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 …

Key Data Gaps For Understanding Trends In Prescription Opioid Analgesic Abuse And Diversion Among Chronic Pain Patients And Nonmedical Users, Wayne W. Wakeland, John Fitzgerald, Aaron Gilson, J. David Haddox, Jack Homer, Lewis Lee, Louis Macovsky, Dennis Mccarty, Teresa D. Schmidt, Lynn Webster

Complex Systems Faculty Publications and Presentations

Population dynamics of medical and nonmedical prescription opioid usage and adverse outcomes were modeled. Critical parameter values were determined by their amount of influence on model behavior. Results suggest that closing these data gaps would help researchers to better identify ways to reduce the risk of adverse outcomes.

Characterization Of The Genes Involved In Biosynthesis And Transport Of Schizokinen, A Siderophore Produced By Rhizobium Leguminosarum Iari 917., David Jack Hammond

Electronic Theses and Dissertations

Iron is the 4th most abundant metal on the earth's crust and is required by most organisms as a cofactor for many enzymes; however, at physiological pH and aerobic conditions iron forms insoluble ferric oxyhydroxide polymers. Siderophores are low molecular weight compounds that scavenge ferric ions, bind with high affinity, and transport it into the cell via multicomponent transport systems. Rhizobia are soil dwelling organisms that form symbiotic relationships with host plants and fix atmospheric nitrogen, while the bacteria receive nutrients. R. leguminosarum IARI 917 produces a siderophore characterized as 'schizokinen'. In the present study, we have characterized the binding …

The Effects Of Nicotine Conditioned Place Preference In D2 Primed Adolescent Rats: Age-Related And Gender Effects., Yoko Emily Ogawa

Electronic Theses and Dissertations

This study investigated nicotine conditioned place preference (CPP) in two different ages of adolescence using a rodent model of schizophrenia. Both 2- and 3-chambered CPP apparatuses were used to test whether the CPP was due to an aversion to the white chamber. Animals were neontally treated with the dopamine D₂/D₃ agonist, quinpirole, or saline and raised to either early postweanling age (P 22) or adolescence (P 29). Rats were conditioned to prefer the white chamber using nicotine. Results showed that nicotine induced CPP and appeared to alleviate an increased stress response in D₂ primed animals, which …

An Analysis Of Nicotine Exacerbation Of Reductions In Ppi In A Rodent Model Of Schizophrenia., Amanda Marie Maple

Electronic Theses and Dissertations

Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is known to be reduced when the dopamine D² receptor is activated. We used a rodent model of psychosis in which increases in dopamine D_{2 receptor sensitivity are produced through neonatal quinpirole (a dopamine D2 / D3 agonist) treatment to rats. Rats were administered quinpirole (1mg/kg) or saline from postnatal day (P) 1-21. Rats were raised to adulthood and tested on PPI. Results showed that neonatal quinpirole treatment produced a significant reduction in PPI, and nicotine exacerbated this reduction. This reduction was partially blocked by …}

Nicotine Sensitization In A Rodent Model Of Schizophrenia: A Comparison Of Adolescents, Adults, And Neurotrophic Factors., Marla Kay Perna

Electronic Theses and Dissertations

The behavioral effects of nicotine on locomotor activity in a rodent model of psychosis were analyzed. This model is based on neonatal quinpriole treatment (a dopamine D2/D3 agonist) which causes increased D2 receptor sensitivity, a phenomenon known as D2 priming that is common in schizophrenia. D2-primed adolescent rats did not demonstrate nicotine-induced hypoactivity early in training, and males demonstrated more rapid sensitization to nicotine as compared to controls administered nicotine. D2-primed females administered nicotine demonstrated increased stereotypic behavior. D2-primed adult rats given nicotine demonstrated significantly more robust sensitization to nicotine than controls given nicotine. Brain-derived neurotrophic factor (BDNF) was analyzed …

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 …

Drug Of Choice As A Predictor Of Program Completion In A 12-Week Intensive Outpatient Program And Continuing Care Program, James R. Myers

Theses, Dissertations and Capstones

This study consisted of a one year examination of a twelve week Intensive Outpatient Program (IOP), followed by continuing care treatment, coupled with required attendance to a Twelve Step AA/NA Program. This study detailed the treatment plan available at a local Intensive Outpatient Program in Southern West Virginia. A sample, separating alcoholics from other substance abusers to obtain an estimated completion rate was used.

Tills thesis comprised a one-year history of subjects (6/30/98 -07/01/99). A total of 84 subjects entered into the Intensive Outpatient Program (IOP) within the above time frame. Determination of completion rates was based on a categorical …

Chemical Castration: Constitutional Issues Of Due Process, Equal Protection, And Cruel And Unusual Punishment, Linda Beckman

West Virginia Law Review

No abstract provided.

Effects Of Dextro-Methamphetamine On Subjective Fatigue, C. A. Dejohn, Scott Shappell, D. F. Neri

Publications

Declining aircrew performance during periods of sustained flight operations (SUSOPs) has underscored the need to develop effective countermeasures. This paper reports on the ability of the central nervous system (CNS) stimulant d-methamphetamine to alleviate the detrimental effects of a simulated SUSOPs on subjective fatigue. Subjective fatigue was repeatedly measured by three questionnaires. The simulated SUSOP started at 1800 and consisted of a 9-h planning session followed by 4 h of rest and a 14-h mission. After 6 h of sleep, the 9/4/14 work/rest/work pattern was repeated. At 4 1/2 h into the second mission, 13 subjects were administered 10 mg …

Effect Of Disulfiram On The Urinary Excretion Of The Serotonin Metabolites 5-Hydroxytryptophol And 5-Hydroxyindoleacetic Acid In Problem Drinkers, Mark D. Harding

Loma Linda University Electronic Theses, Dissertations & Projects

Problem drinkers (N=7) were given 500mg disulfiram daily for one week. Urine was collected before and after disulfiram intake. 5-Hydroxytryptophol (5-HTOL) was determined by a modification of the method of Davis et al. and adapted to high-performance liquid chromatography (HPLC) with an electrochemical detector setting of 0.75V. 5-Hydroxy-indoleacetic acid (5- HIAA) was determined using the HPLC method of Shihabi et al. (1980). Urinary excretion of 5-HTOL in ug/gm creatinine before and after disulfiram was 25.4± 3.3 and 110.5± 27.1 respectively, p < 0.02. 5-HIAA in mg/gm creatinine before and after disulfiram was 4.9±0.9 and 3.6±0.8 respectively, p > 0.16. The data shows that disulfiram administration alters serotonin metabolism resulting in increased 5-HTOL which is known to increase …

An Avoidance Response Bioassay For Aquatic Pollutants, Jeffrey A. Black, Wesley J. Birge

KWRRI Research Reports

Avoidance response bioassays were conducted with eight aquatic contaminants, including cadmium, copper, mercury, zinc, chloroform, dioctyl phthalate (DOP), trisodium nitrilotriacetic acid (NTA), and phenol. Tests were performed in a dual-channel fluviarium system, and the toxicant injection procedure used provided good regulation of exposure concentrations. Juvenile stages of largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus), and rainbow trout (Salmo gairdneri), and tadpoles of the American toad (Bufo americanus) proved to be suitable animals for evaluating avoidance or attraction responses. The trout was the most sensitive species tested.

Avoidance was significant in tests …

Buying Veterinary Products : Read The Label First, G A L Ward

Journal of the Department of Agriculture, Western Australia, Series 4

Chenicals for animal health, and processed feeds must be registered and labelled.

Registration is intended to insure that products are effective for the purpose they are sold, and safe when used according to instructions.

It is important to read the lable to understand the correct use of the product.

Radioprotection Of Oral Cavity Structures By S-2-(3-Aminopropylamino) Ethyl Phosphorothioate (Wr-2721), Ronald King

Masters Theses & Specialist Projects

Studies reporting a high concentration of WR-2721 in mouse salivary glands led to our studies of possible radioprotection of these glands by this drug from ionizing radiation. Oral effects of radiation in the presence of WR-2721 were studied in mice and dogs. Histological evaluation of mouse salivary glands irradiated with 1000 rads of ⁶⁰Co showed essentially no difference between control and experimental animals. Almost full regeneration of the serous salivary components occurred by 6 months in both groups and neither group had changes in the mucous glands. The use of higher doses of radiation in the mouse was prevented …

The Effect Of Insulin, Fluoride And Methyl Xanthines On The Hypothalamic-Parotid Gland Endocrine Axis, Reagan Ondler

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine the effect of insulin and fluoride on dentinal fluid movement (FM) in high-sucrose fed rats as mediated through the hypothalamic-parotid gland endocrine axis. In conjunction with the fluoride study, the possible involvement of cAMP was examined through the use of several methyl xanthines which are recognized as phosphodiesterase inhibitors.

Twenty-one day old, male Sprague Dawley rats were maintained on a high-sugar diet (62% sucrose) for 8-9 days at which time intravenous or arterial infusions of insulin, fluoride or the methyl xanthines were performed. Additional procedures included collecting plasma from rats which had …

Control Of Insects In Cotton, D G. Shedley, D. L. Hardy, P. J. Michael

Journal of the Department of Agriculture, Western Australia, Series 4

Results of two experiments at the Ord Irrigation area in 1968 indicate that farmers may be spending more than necessary to obtain economic control of cotton pests in some seasons.

One experiment clearly demonstrated the relationship between low insect numbers and improved cotton yields—the second indicated that a moderate but well timed spray schedule, especially during the early part of the season, can result in more economic insect control than an intensive spray schedule.