Chemicals and Drugs Commons^™

A Semiparametric Modeling Approach For Analyzing Clinical Biomarkers Restricted To Limits Of Detection, Sandipan Dutta, Susan Halabi

Mathematics & Statistics Faculty Publications

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Synthesis, Characterization And Photophysical Properties Of Ytterbium Complexes Of Functionalized Porphyrins And Porpholactone, Beibei Liu

Masters Theses

The unique structure and superior properties of lanthanide porphyrins enable them to be used in a broad variety of applications, especially in medical diagnosis fields. This research focuses on modifying the porphyrin ligands in various places, resulting in broader absorption in the red region and strong emission in the near-infrared region for these ytterbium(III) porphyrin complexes. The design, synthesis and characterization for DMPH₂-BDP, DMPH₂-COOH, TPLH₂ ligands and YbDMP-BDP, YbDMP-COOH complexes are described. The photophysical properties of these ligands and complexes including their absorbance, fluorescence and quantum yields are also presented. Both the synthesized ligands and …

Overcoming Mechanisms Of Acquired And Innate Doxorubicin Resistance Using Nanomedicine And Tumor-Associated Macrophage Immunotherapy, Rashed M. Almuqbil

Theses and Dissertations

ABSTRACT

Overcoming Mechanisms of Acquired and Innate Doxorubicin Resistance Using Nanomedicine and Tumor-Associated Macrophage Immunotherapy

By Rashed M. Almuqbil, Pharm.D.

Director: Sandro R.P. da Rocha, PhD

Cancer is a leading cause of death worldwide. The available treatment for solid tumors may include surgery, radiotherapy, immunotherapy, and chemotherapy or a combination of all those regimens. Chemotherapy is widely used in the treatment of both lung cancers and breast cancer, including metastases, irrespective of type and stage. The poor rates of survival can be attributed to late diagnosis, and due to the development of acquired and innate chemoresistance. Lung tumors are intrinsically …

Standardization Of E-Cigarette Research: Addressing The Analysis Of Total Nicotine And Free Base Nicotine In E-Cigarettes, Vinit Gholap

Theses and Dissertations

Electronic cigarettes (e-cigarettes) are one of the major sources of exposure to nicotine, an addictive chemical. Since 2016, the Food and Drug Administration (FDA) has started regulating these products under the Tobacco Control Act yet, specifications about the nicotine content in these products have not been established. In e-cigarettes, nicotine concentration ranges from 0 to >50mg/mL. Additionally, several e-cigarette related parameters have been identified which can affect nicotine delivery to users. Of these factors, nicotine forms (protonated and free base) have been found to play a significant role in nicotine absorption profiles yet, a limited and contradictory research is available …

A Determination Of The Aerosolization Efficiency Of Drugs Of Abuse In A Eutectic Mixture With Nicotine In Electronic Cigarettes, Laerissa Reveil

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigarettes) were originally advertised as an alternative nicotine delivery system to facilitate smoking cessation. However, their popularity for recreational use has increased due to focuses on their trendiness, convenience, and discreteness along with concerns for its use to consume drugs other than nicotine (DOTN). With the adulteration of e-liquids, usually containing nicotine, with other substances, a greater understanding on how DOTN interact with the e-liquid constituents and how they are delivered to the user is necessary. E-liquids were prepared with 50:50 propylene glycol:vegetable glycerin, pure nicotine, pure methadone hydrochloride, and 1:1 methadone hydrochloride:nicotine and aerosolized via an automated …

Drug Loaded Mesoporous Nanocarriers For The Treatment Of Aspergilliosis, Madeline Brooks, Emily Hunt

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

A Tool For Segmentation Of Secondary Structures In 3d Cryo-Em Density Map Components Using Deep Convolutional Neural Networks, Yongcheng Mu, Salim Sazzed, Maytha Alshammari, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Although cryo-electron microscopy (cryo-EM) has been successfully used to derive atomic structures for many proteins, it is still challenging to derive atomic structures when the resolution of cryo-EM density maps is in the medium resolution range, such as 5–10 Å. Detection of protein secondary structures, such as helices and β-sheets, from cryo-EM density maps provides constraints for deriving atomic structures from such maps. As more deep learning methodologies are being developed for solving various molecular problems, effective tools are needed for users to access them. We have developed an effective software bundle, DeepSSETracer, for the detection of protein secondary structure …

Causal Inference Multiple Imputation Investigation Of The Impact Of Cannabinoids And Other Substances On Ethnic Differentials In Us Testicular Cancer Incidence, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

Background: Ethnic differences in testicular cancer rates (TCRs) are recognized internationally. Cannabis is a known risk factor for testicular cancer (TC) in multiple studies with dose-response effects demonstrated, however the interaction between ancestral and environmental mutagenic effects has not been characterized. We examined the effects of this presumed gene-environment interaction across US states. Methods: State based TCR was downloaded from the Surveillance Epidemiology and End Results (SEER) website via SEERStat. Drug use data for cigarettes, alcohol use disorder, analgesics, cannabis and cocaine was taken from the National Survey of Drug Use and Health a nationally representative study conducted annually by …

Mechanism For The Unfolding Of The Top7 Protein In Steered Molecular Dynamics Simulations As Revealed By Mutual Information Analysis, Ognjen Perišić, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

We employed mutual information (MI) analysis to detect motions affecting the mechanical resistance of the human-engineered protein Top7. The results are based on the MI analysis of pair contact correlations measured in steered molecular dynamics (SMD) trajectories and their statistical dependence on global unfolding. This study is the first application of the MI analysis to SMD forced unfolding, and we furnish specific SMD recommendations for the utility of parameters and options in the TimeScapes package. The MI analysis provided a global overview of the effect of perturbation on the stability of the protein. We also employed a more conventional trajectory …

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …

Understanding The Impact Of Solvents In Oral Solid Dosage Formulation And Process Development, Matthew Kyle Defrese

Theses and Dissertations--Pharmacy

The successful delivery of chemical compounds for the purpose of therapeutic treatments and prophylactics is a substantial undertaking in modern drug development. Notably, the adoption of high throughput screening techniques has led to the proliferation of poorly water soluble and/or highly potent molecules which further complicate development activities. Spray dried amorphous solid dispersions are an increasingly important formulation strategy to overcome solubility issues while wet granulation approaches are the method of choice for the preparation of highly potent APIs in oral solid dosage forms.

A common connection between these critical techniques is their reliance on solvent-based processing that can often …

Investigation Of The Biosynthesis Of The Nucleoside Antibiotic Sphaerimicin, Jonathan Overbay

Theses and Dissertations--Pharmacy

Antibiotic-resistance has become a widespread problem in the United States and across the globe. Meanwhile, new antibiotics are entering the clinic at an alarmingly low rate. Highly-modified nucleosides, a class of natural products often produced by actinobacteria, target MraY bacterial translocase I. MraY is a clinically unexploited enzyme target that is ubiquitous and essential to peptidoglycan cell wall biosynthesis. The nucleoside antibiotics known vary in efficacy and the functionalities contributing to improved activity is poorly understood. Sphaerimicin, a newly discovered modified nucleoside, has potent inhibitory activity with an IC50 of 13.65 nM against MraY. In general, sphaerimicin is primarily effective …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

Base-Labile Protecting Groups For Stepwise Peg Synthesis, Logan D. Mikesell

Dissertations, Master's Theses and Master's Reports

Stepwise synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling two PEG moieties together under the basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps – deprotection, deprotonation, and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in only two steps – deprotection and coupling – in one pot. The …

The Role Of Cannabidiol In The Treatment Of Pediatric Patients With Refractory Epilepsy, Evan Chidley

Capstone Showcase

THE ROLE OF CANNABIDIOL IN THE TREATMENT OF PEDIATRIC PATIENTS WITH REFRACTORY EPILEPSY

Author(s) and affiliations: Evan Chidley¹, MMS (c), MPH (c)

¹Arcadia University; [email protected]; (515) 201-6901

Introduction: Intractable epilepsy in children can significantly impair quality of life and anti-epileptic drugs (AEDs) do not adequately reduce seizures for all pediatric patients. Recently, cannabidiol (CBD), one of the main compounds of marijuana, has shown promise as a potential treatment for uncontrolled seizure activity. This paper poses the following question: In pediatric patients with drug-resistant epilepsy, is cannabidiol (CBD) more effective in reducing seizure activity than traditional anti-epileptic drugs …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …