Chemicals and Drugs Commons^™

Biological Reasons For The Neurotoxic Effects Of Mdma (‘Ecstasy’) On The Developing Fetus, Leah Schneeweiss

The Science Journal of the Lander College of Arts and Sciences

MDMA (3, 4-methylenedioxymethamphetamine) is an illicit, recreational drug known by many individuals as ‘Ecstasy.’ MDMA has gained popularity over the past decade and has become a drug of choice at dance parties and clubs because of the stimulating and hallucinogenic effects that it has on the central nervous system. Scientists have determined that MDMA causes neurotoxic damage to adults by harming the serotonergic system in the adult brain. Researchers discovered that embryos exposed to MDMA while in utero also suffer neurotoxic deficits, although not due to impairments in the embryos’ serotonergic systems. These deficits arise because of the cortisol increase …

Stability Of Lidocaine Tested By Forced Degradation And Its Interactions With Serum Albumin, Lindsay Nichols

STAR Program Research Presentations

A concern for future long-term manned space expeditions is the ability to treat illnesses with appropriate pharmaceuticals. However, pharmaceuticals degrade faster in space than on Earth presumably due to an abundance of space radiation. The stability of Lidocaine was investigated because it is a common pain reliever currently used on the International Space Station. One of the most common proteins in blood is serum albumin, which acts as a carrier to distribute drugs throughout the body. It is important to know how well the drug binds to serum albumin so that the rate of distribution of Lidocaine-bound protein in blood …

Detection Of Catecholamines Produced In Planktonic P. Aeruginosa And S. Aureus Treated With Adult Bovine Serum, Jorge A. Serrano, Anil Serrano, Shaleni Singh, Jaime Fuentes, Robert Crawford Dr., Rivkah Isseroff, Thomas Peavy

STAR Program Research Presentations

Bacterial biofilms play a critical role in inducing and sustaining chronic wounds that are serious health threats. Bacterial biofilms can also be found on medical prosthetics and implants that sustain infections in patients and cause life threatening situations. Bacteria self-produce these sticky extracellular substances termed a biofilm which help them to adhere to each other forming a community of microorganisms. One of the major issues is that biofilms have antimicrobial characteristics and provide protection from the immune system; biofilms are found in over 80% of human bacterial infections. Formation of a bacterial biofilm occurs when an individual (planktonic) bacterial cell …

Cancer Stem Cells In The Screening Of Anticancer Drugs For Central Nervous System Tumors, Sarah Elizabeth Daron-Mathis

Theses, Dissertations and Capstones

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments …

The Evolving Role Of Dendritic Spines And Memory: Interaction(S) With Estradiol, M. Frankfurt, V. Luine

Journal Articles

This article is part of a Special Issue "Estradiol and Cognition". Memory processing is presumed to depend on synaptic plasticity, which appears to have a role in mediating the acquisition, consolidation, and retention of memory. We have studied the relationship between estrogen, recognition memory, and dendritic spine density in the hippocampus and medial prefrontal cortex, areas critical for memory, across the lifespan in female rodents. The present paper reviews the literature on dendritic spine plasticity in mediating both short and long term memory, as well as the decreased memory that occurs with aging and Alzheimer's disease. It also addresses the …

A-803467, A Tetrodotoxin-Resistant Sodium Channel Blocker, Modulates Abcg2-Mediated Mdr In Vitro And In Vivo, Nagaraju Anreddy, Atish Patel, Yun-Kai Zhang, Yi-Jun Wang, Suneet Shukla, Rishil J. Kathawala, Priyank Kumar

Touro College of Pharmacy (New York) Publications and Research

ATP-binding cassette subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which has been implicated in the development of multidrug resistance (MDR) in cancer, apart from its physiological role to remove toxic substances out of the cells. The diverse range of substrates of ABCG2 includes many antineoplastic agents such as topotecan, doxorubicin and mitoxantrone. ABCG2 expression has been reported to be significantly increased in some solid tumors and hematologic malignancies, correlated to poor clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membrane transporter facilitates resistance to the …

Use Of Donepezil In Alzheimer's Disease: Suggested Practice Guidelines, Tamara Berg

Physician Assistant Scholarly Project Posters

Alzheimer’s disease (AD) is the cause of 60-80% of dementia (2014 Alzheimer’s disease, 2014). AD is estimated to affect over 5 million people over age 65 in the US (2014 Alzheimer’s disease, 2014). With the onset of baby boomers reaching the age of 65 and increased longevity it is estimated that 16 million persons will have Alzheimer’s by 2050. Eighty two percent of persons with AD are over age 85. In 2014 AD is the 6th leading cause of death and the highest cost disease in the US. (2014 Alzheimer’s disease, 2014)

The predicted increase in prevalence and incidence of …

Tolerability Of Induction Chemotherapy Dosing Practices In Acute Myeloid Leukemia Patients, Kaylene M. Peric, David J. Reeves

Scholarship and Professional Work – COPHS

For patients with high body surface areas (BSA), differing chemotherapy dosing strategies have been utilized in attempts to reduce toxicity. In a retrospective evaluation, we compared the effects of chemotherapy dosing in acute myeloid leukemia patients with high BSA (>2 m²) who received capped doses (n = 12) to those who received uncapped doses (n = 24), and to patients with BSA ≤ 2 m² (n = 42). There were no statistically significant differences among groups (BSA ≤ 2 m², BSA > 2 m² capped, and BSA > 2 m² uncapped) …

Levetiracetam-Induced Pancytopenia., Talal Alzahrani, Dana Kay, Saeed A. Alqahtani, Yamane Makke, Linda Lesky, Mohamad Z. Koubeissi

Neurology Faculty Publications

Pancytopenia is a rare side effect of levetiracetam (LEV) that is associated with severe morbidity that requires hospitalization. Here, we report a patient with a right temporoparietal tumor who underwent a temporal craniotomy with resection of the mass and was started on LEV for seizure prophylaxis per the neurosurgery local protocol. The patient developed LEV-induced pancytopenia, which was successfully managed by discontinuation of this medication. Our report aims to increase awareness of this rare cause of pancytopenia among clinicians.

Ghrelin, Timo D. Müller, Rubén Nogueiras, Mark L. Andermann, Zane B. Andrews, Stefan Anker, Jesús Argente, Allan Geliebter

Lander College of Arts and Sciences Publications and Research

Background: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.

Scope of review: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.

Major conclusions: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility …

Sex Differences In The Kinetic Profiles Of D- And L- Methylphenidate In The Brains Of Adult Rats, J. Bentley, F. Snyder, Stacy D. Brown, R. W. Brown, Brooks B. Pond

ETSU Faculty Works

OBJECTIVE: Methylphenidate is commonly used in the treatment of Attention Deficit Hyperactivity Disorder and narcolepsy. Methylphenidate is administered as a racemic mixture of the d- and l- threo enantiomers; however, the d-enantiomer is primarily responsible for the pharmacologic activity. Previous studies of the behavioral effects of methylphenidate have highlighted sex differences in the responsiveness to the drug, namely an increased sensitivity of females to its stimulatory effects. These differences may be due to differences in the uptake, distribution, and elimination of methylphenidate from male and female brains. Therefore, we compared the pharmacokinetics of d- and l- threo methylphenidate in the …

Synthesis And Evaluation Of Substituted Coumarin Derivatives As Inhibitors Of Monoamine Oxidase B, Ian A. Kieffer

Chemistry Theses

Monoamine oxidase B (MAO B) is of clinical importance due to its perceived role in neurodegenerative diseases such as Parkinson’s, making inhibitors of MAO B popular candidates for drug design. A series of coumarin derivatives have been prepared and assayed, revealing that the synthesized inhibitors act through a competitive mode of inhibition. In addition, these inhibitors are potent with Ki values in the nanomolar range. Overall, substitution at the 3- position of the coumarin was found to be important to inhibitor potency and further study of 3-aryl coumarin substitution computationally led to the prediction of 3-(3-aminophenyl)-6-hydroxycoumarin as a lead compound …

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

Transfer Rna Comes Of Age, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

"The year the journal RNA was founded was slated by some in scientific publishing to be the year that one particular type of RNA's run in the spotlight would end. In 1995 I had recently started as a post-doc with Dieter Söll at Yale when he came into the lab to solemnly inform us all that an editor at a certain (S)cience journal had just told him “we won't be publishing any more tRNA papers.” For a post-doc who had migrated across the Atlantic for the sole purpose of furthering his career by working on tRNA this was not great …

Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger

College of Graduate Studies: Theses & Dissertations

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.

Possible Effects Of Nanosecond Pulsed Electric Fields On Proteins, Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

The Effects Of Curcumin On The Expression Of P53 And Bcl-2 Oncoproteins On The Human Breast Carcinoma Cell Line Mda-Mb 468, Angelin S. Shajan

Theses and Dissertations

We studied the effects of curcumin on the proliferation and viability of MDA-MB-468 breast cancer cells and its effects on the expression ofBcl-2 and p53 proteins in these cells. Based on previous studies, we predicted a dose-dependent increase in p53 (tumor suppressor) expression, and a decrease in Bcl-2 (anti-apoptotic oncoprotein) expression. Briefly, MDA-MB468 cells were seeded into 12-well plates at 2.0 * 104 cells/well and allowed to grow for 72 hrs. Cells were treated with curcumin at 0, 25, 50 and 100 pM in triplicate at time zero and cultured for another 24 hours. All data were obtained using a …

Elucidation Of A Novel Pathway In Staphylococcus Aureus: The Essential Site-Specific Processing Of Ribosomal Protein L27, Erin A. Wall

Theses and Dissertations

Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N-terminus, which protrudes into the peptidyl transferase center where it interacts with both A-site and P-site tRNAs as well as with 23S rRNA. We observed that L27 in S. aureus and other Firmicutes is encoded with a short N-terminal extension that is not present in most Gram-negative organisms, and is absent from mature ribosomes. The extension contains a conserved cleavage motif; nine N-terminal amino acids are …

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 …

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …