Medicine and Health Sciences Commons^™

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Investigation Of The Association Of Exposures To Fire-Related Hazards With Pulmonary Function Of Firefighters, David G. Goldfarb

Dissertations and Theses

Background. Firefighters are habitually exposed to hazardous toxicants which place them at an elevated risk for numerous adverse health outcomes. An example of this is the associations observed in other works between inhalation of combustion byproducts from urban structural fires and both acute and chronic pulmonary dysfunction. To-date, the characterization of firefighters’ exposures to dangerous chemicals in smoke from non-wildfire incidents, both directly through personal monitoring and indirectly from work-related records is scarce. Prior works investigating the association between routine firefighting and pulmonary function have relied on crude metrics such as years of service and numbers of responses to …

Elisa Validation Method For The Detection Of Ketamine In Hair, Daria A. Centonza

Student Theses

An ELISA method was developed and validated to detect ketamine in human hair samples. Ketamine is an anesthetic drug that causes memory loss, dissociative sensations, and hallucinations. Due to these adverse effects, ketamine is a common drug used in drug facilitated sexual assaults (DFSAs). It is very important to be able to detect the substances used in DFSAs over a longer period of time due to the delayed reporting of these crimes. Victims, often out of fear and from the sedative/memory loss effects of the drugs, tend to report these crimes when it is too late to use urine and …

Results Of A Phase 1, Randomized, Placebocontrolled First-In-Human Trial Of Griffithsin Formulated In A Carrageenan Vaginal Gel, Natalia Teleshova, Maria J. Keller, José A. Fernández Romero, Barbara A. Friedland, George W. Creasy, Marlena G. Plagianos, Laurie Ray, Patrick Barnable, Larisa Kizima, Aixa Rodriguez, Nadjet Cornejal, Claudia Melo, Gearoff Cruz Rodriguez, Sampurna Mukhopadhyay, Giulia Calenda, Shweta U. Sinkar, Thierry Bonnaire, Asa Wesenberg, Shimin Zhang, Kyle Kleinbeck, Kenneth Palmer, Mohcine Alami, Barry R. O'Keefe, Patrick Gillevet, Hong Hur, Yupu Liang, Gabriela Santone, Raina N. Fichorova, Tamara Kalir, Thomas M. Zydowsky

Publications and Research

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

Allergy And Anaphylaxis From The Prehospital Perspective, Anthony E. Conrardy

Dissertations and Theses

Anaphylaxis is considered a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy causing substance. It is estimated that up to 5% of the population has experienced anaphylaxis, with 1% of hospitalizations and 0.1% of emergency department patients having fatal outcomes. We characterized the population of patients encountered by the EMS agency (786 patients) that had a provider impression of “allergic reaction” and then utilized logistic regression models to estimate associations with the administration of epinephrine in the prehospital setting. Additionally, we used incident location data for all patient encounters of the EMS agency …

Exposure Characterization And Assessment Of Airborne Chemicals And Sars-Cov-2 Transmission In New York City Nail Salons, Amelia P. H. Watkins

Dissertations and Theses

Background: Currently, there are 156,000 people employed as manicurists or pedicurists in the United States. Employment in this sector is expected to grow by 10% over the next decade. Exposure assessments have revealed that salon workers are chronically exposed to a variety of substances that cause respiratory sensitization, developmental problems, contact dermatitis, blood, liver, and kidney issues, as well as nervous system impacts. Most recently, the SARS-Cov-2 pandemic has raised the issue of the vulnerability of nail salon workers to airborne infectious diseases as well. This dissertation aims to characterize and assess the chemical exposures that nail salon workers …

Chemical Exposure From Manufactured Gas Plants: Public Health Risks?, Aneeza Hussain

Publications and Research

This project aims at identifying the chemicals and their risk factors to public health, which were found underneath Public Place, a brownfield next to the Gowanus Canal. The site is heavily contaminated with coal tar — a toxic chemical by-product of gas manufacturing, which happened at the site for 100 years until the gas plant closed down in the 1960s and the land was seized by the city. Recently, the city has planned to develop Public Place into “Gowanus Green” and which will be comprised of a school and low-income housing units on this site. The aim of this research …

Understanding Of Aerosol Transmission Of Covid 19 In Indoor Environments, Adama Barro, Cathal O'Toole, Jacob S. Lopez, Matthew Quinones, Sherene Moore

Publications and Research

Our reason for discussing severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) or 2019 novel corona virus (Covid-19), is to understand its aerosol transmission characteristics in indoor spaces and to mitigate further spread of this disease by designing a new HVAC system. The problem that we are tackling is the spread of covid-19 droplets through aerosol transmission by looking at potential engineering solutions to the existing HVAC systems. The purpose is to eradicate the spread of the COVID-19 by testing indoor spaces in an effort to understand the effectiveness of ventilation controls. We believe that scientists and engineers have not …

Using Short Chain Fatty Acids To Inactivate Pseudomonas Aeruginosa Biofilms, Stephen Lee

Dissertations and Theses

Abstract

Using Short Chain Fatty Acids to Disinfect Pseudomonas Aeruginosa Biofilms

by

Stephen Lee

Background

The study of bacteria typically focuses on the planktonic or free-living single-cell state that is purely cultured in a laboratory for subsequent growth with appropriate media. Although this traditional way of growing bacteria has been paramount to the understanding of bacterial behavior, physiology, and pathogenesis, bacteria rarely exist as pure cultures of planktonic growth forms in the natural habitat. Bacterial contamination of environmental surfaces, in the form of biofilms, is a prime public health problem and causes numerous infections within the general public. Biofilms are …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Parp1-Targeted Radiotherapies, Stephen Jannetti

Dissertations, Theses, and Capstone Projects

Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Simultaneous Determination Of Fourteen Antipsychotic Drugs In Whole Blood By Solid Phase Extraction And Liquid Chromatography Tandem Mass Spectrometry, Theresa M. Dawe

Student Theses

Anti-psychotic drugs are commonly prescribed to patients to treat several mental conditions, such as bipolar, schizophrenia, and manic-depressive disorder. The analysis of anti-psychotic drugs in blood is a common practice in clinical and forensic toxicology, to monitor drug treatment (therapeutic drug monitoring) or to explain the cause of the impairment or intoxication in human performance and in postmortem cases. However, most of the current studies have been performed in plasma, and a limited number in blood. We developed and validated a method to confirm and quantify a panel of commonly prescribed anti-psychotic drugs in whole blood using solid phase extraction …

Zolpidem Facilitated Sexual Assaults: A Hair Method Validation, Danielle N. Chasworth

Student Theses

A liquid chromatography tandem mass spectrometry (LC-MSMS) method was developed and validated to detect for the presence of zolpidem in human hair samples. Zolpidem is a sedative hypnotic whose adverse effects make it a common drug found in drug facilitated crimes (DFC). It is important to be able to detect and quantitate the drug after a long period of time due to the victim’s delayed reporting of the crime. Hair’s long window of detection makes it a useful matrix for DFC investigations. The linear range of the assay was targeted at 2 pg/mg to 1,000 pg/mg and experiments designed to …

Regulation Of Radioactive Fracking Waste, Elizabeth Ann Glass Geltman, Nichole Leclair

Publications and Research

Natural gas extracted form shale reached record production totals in 2015 in the United States and the US Energy Information Administration (EIA) forecasts natural gas production will continue to increase. Wastes from shale gas extraction can contain the radioactive isotopes radium-226 (Ra-226) and radium-228 (Ra-228), which decay further into radon (Rn). Exposure to radon, a form of naturally occurring radioactive materials (NORM), is the leading cause of lung cancer in the United States, after smoking. This article explores how states handle the disposal of technologically enhanced naturally occurring radioactive materials (TENORM) and/or NORM waste from oil and gas operations to …

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Quantitative Analysis Of Opioids And Cannabinoids In Wastewater Samples, Alethea Jacox

Student Theses

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups. We developed and validated an analytical method for the detection and quantification of opioids (morphine, oxycodone, hydrocodone, oxymorphone and hydromorphone), and cannabinoids (9-tetrahydrocannabinol, 11-nor 9-carboxy- tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide) in raw influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Method validation included linearity (5–1 000 ng/L for opioids, 10–1 000 ng/L for cannabinoids), imprecision (<21.2%), accuracy (83%–131%), matrix effect (from –35.1% to –14.7%) and extraction efficiency (25%–84%), limit of detection (1–5 ng/L) and quantification (5–10 ng/L) and auto-sampler stability (no loss detected). River, sewage overflow and wastewater samples were collected in triplicate from different locations in New York City and stored at -20 C until analysis. River water samples were negative for all the compounds. Water from sewage overflow location tested positive for morphine (10.7 ng/L), oxycodone (4.2–23.5 ng/L), oxymorphone (4.8 ng/L) and hydromorphone (4.2 ng/L). Wastewater samples tested positive for morphine (133.0– 258.3 ng/L), oxycodone (31.1– 63.6 ng/L), oxymorphone (16.0–56.8 ng/L), hydromorphone (6.8–18.0 ng/L), hydrocodone (4.0– 12.8 ng/L) and THCCOOH (168.2– 772.0 ng/L). This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Airborne Infectious Agents And Other Pollutants In Automobiles For Domestic Use: Potential Health Impacts And Approaches To Risk Mitigation, Syed A. Sattar, Kathryn E. Wright, Bahram Zargar, Joseph R. Rubino, M. Khalid Ijaz

Publications and Research

Theworld total of passenger cars is expected to go fromthe current one billion to >2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Inquiry Into The Implementation Of Bush’S Executive Order 13211 And The Impact On Environmental And Public Health Regulation, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

Executive Order 13211, promulgated in 2001, requires the federal government to consider the impact of federal action on energy independence as part of the George W. Bush’s National Energy Policy. This law review examines whether EO 13211 was used to curtail environmental protection and natural resource conservation. The article begins with a review of the procedure required of federal agencies under EO 13211 and its associated documents. The paper then examines case law and published federal rulemaking proceedings and examines how federal agencies apply tests to evaluate the potential energy effect. The study concludes that EO 13211 strikes a reasonable …

Impact Of Executive Order 13211 On Environmental Regulation: An Empirical Study, Elizabeth Ann Glass Geltman

Publications and Research

A great deal has been written about the Energy Policy Act of 2005 exempting oil and gas operations using hydraulic fracturing from the purview of certain federal environmental laws. Far less attention has been paid to George W. Bush’s Executive Order 13211 (EO 13211), entitled “Actions Concerning Regulations that Significantly Affect Energy Supply, Distribution or Use.” The executive order requires federal agencies to evaluate the impact of federal regulations on “supply, distribution and use of energy.” This study examined the impact of EO 13211 on United States environmental and conservation regulations proposed and promulgated by federal agencies. The study found …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson

Publications and Research

The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …