Chemicals and Drugs Commons^™

Long-Term Lithium Use In The Younger Population: Do The Benefits Outweigh The Risks? - A Case Report, Seema Shekar, Alexander Garcia, Rachel Shmuts

Rowan-Virtua Research Day

For decades lithium has been the mainstay treatment for bipolar disorder. While its side effect profile is extensive and varied its most notable adverse effect, and one most feared by treating clinicians, is nephrotoxicity/ end-stage renal disease (ESRD). While the link between long-term lithium use and ESRD has been accepted by the medical community at large for many years, more recent scientific studies call the association into question. In fact, newer studies on the association between Li use and ESRD have shown a negative/inconclusive correlation. Despite this controversy the consensus still remains that ESRD secondary to long-term Li use is …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Development Of An Analytical Method For Determination Of Lead And Cadmium In Biological Materials By Gfaas Using Escherichia Coli As Model Substance, Michelle Catherine Gende, Martina Schmeling

Chemistry: Faculty Publications and Other Works

In this work, an analytical method was developed for the determination of lead and cadmium in biological samples using graphite furnace atomic absorption spectrometry. Escherichia coli (E. coli) was chosen as model substance for this purpose as it is readily available in most laboratories and can be quickly and easily prepared with a high turnaround rate. Four different sample preparation methods were initially evaluated with respect to percent recovery, limit of detection, and limit of quantification, and the most promising one was developed further. The final process involving microwave assisted digestion of the sample with nitric acid …

2-Deoxy-D-Glucose As India’S Response To Covid-19: A Commitment Or Conceit?, Ritwik Ghosh, Dipayan Roy, Subhankar Chatterjee, Julián Benito-León

Journal of Community Hospital Internal Medicine Perspectives

2-deoxy-D-glucose (2-DG) has recently been approved to treat moderate to severe COVID-19 patients in India. Here we discuss whether this is a well-thought-out step towards the long-term management of COVID-19 or a decision taken at the spur of the moment. 2-DG, an anticancer drug, also has immunomodulatory functions. Several studies have shown 2-DG to inhibit viral replication and cytokine storm. However, these findings are mostly on cells and animal models. The clinical trial that has become the basis of the approval of this drug in India is yet to be peer-reviewed and has not explicitly addressed several concerns, nor has …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) And Proteomic Evaluation Of Heparin-Binding Proteins From Ajwain (Trachyspermum Ammi) Seeds, Saud Alshammari

Pharmaceutical Sciences (PhD) Dissertations

Trachyspermum ammi, commonly known as ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered. The present study demonstrated the antiproliferative activity of ajwain nsLTP1 in MCF-7, AsPC-1, and MCF10A cell lines and its structural stability in human serum and high-temperature conditions. The antiproliferative activity of ajwain nsLTP1 was evaluated in MCF-7 and AsPC-1 cell lines using an MTT assay. Annexin V-FITC and PI staining were used to detect the …

Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales

Biomedical Engineering Undergraduate Honors Theses

Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

The Credible Empa-Reg Clinical Trials: Impacts Of Empagliflozin On Patients With Type 2 Diabetes Mellitus And At Risk Of Adverse Cardiovascular Events, Janai D. Minga

Honor’s College Freeman Research Journal

Background and Literature Review: There still exists limited evidence regarding the potential of effects of an inhibitor of sodium–glucose cotransporter 2 known as empagliflozin when it is added as part of the standard care when treating type 2 diabetes patients with a high risk of cardiovascular morbidity and mortality. A significant number of studies have investigated the potential impacts of empagliflozin in lowering the risk of death from heart failure related problems. Available literature reviews and meta-analysis are in consensus that the empagliflozin has positive effects when used to lower the glucose level in the blood of patients with …

Effects Of Increased Levels Of Relaxin Hormone In Women During Pregnancy In Relation To Spondylolisthesis: A Literature Review, Joselin R. Guerrero Rapalo

Honors Theses

No abstract provided.

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Honors Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …

Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov

Senior Honors Projects

The Heber W. Youngken Jr. Medicinal Garden is a one-of-a-kind resource that houses close to 300 medicinal plants and is filled to the brim with educational opportunities. For the College of Pharmacy, this garden has been the centerpiece of many classes taught here at the University of Rhode Island and has roots as a physical teaching space. While the garden contains a plethora of plant species, medicinal fungi have yet to have been included in the garden, despite their relevance as both sources of pharmaceutical drug discovery and as natural products with inherent physiological benefits themselves. The purpose of my …

Development And Implementation Of A Protocol For Denosumab Administration In An Outpatient Infusion Clinic, Erin Stavrakas

The Eleanor Mann School of Nursing DNP Capstone Projects

Denosumab, or Prolia, is a medication given to increase bone mineral density (BMD) and prevent fracture risk in patients with osteoporosis. Guidelines for monitoring of side effects, data on long-term effects, and appropriate precautions are still being researched and developed. Healthcare teams are often unaware of preventative care measures to guide informed clinical decision making and patient care management. The recognized gap in care also reduces the standardization of health care delivery in clinics administering Prolia; this gap can lead to errors and miscommunication between patients and healthcare teams an increased risk for side effects. The aim of this translation …

The Use Of Hallucinogens In The Treatment Of Mental Health Disorders, Brianna Gagen

Honors College Theses

The percent of people with mental health disorders in the United States have skyrocketed over the past decade. With stigma surrounding the discussion of mental health and the symptoms associated with it, often those that are suffering do not receive sufficient treatment, as they might with a physical illness. The current, common treatment options for common psychological disorders, like depression, anxiety, and post-traumatic stress disorder, are sometimes not effective in patients, due to resistance or poor response outcomes. Consequently, in order to research alternative therapeutic approaches for mental health disorders, scientists are researching the effects of several hallucinogenic drugs in …

Unveiling The Opioid Crisis: The Impact Of Opioids On Body Systems And Alternative Treatment Options To Reduce The Nationwide Opioid Epidemic, Krishna S. Patel, Elizabeth A. Manheim Ph.D.

Kean Quest

No abstract provided.

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

The opioid epidemic impacted over 12 million Americans in 2019. Although they are effective pain-relieving medications, they carry addictive and dangerous side effects. Opioids, like morphine, bind non-selectively in both central and peripheral tissues; however, dangerous side effects result from central activation. Inflamed conditions of injured tissues have a lower pH (pH=6-6.5) environment than healthy central tissue (pH=7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using computationally-based molecular extension and dissection techniques. Binding to the mu-opioid receptor (MOR) is dependent on protonation of the biochemically active amine group of morphine. Fluorination of a carbon …

Driving Under The Influence Of Drugs: Status In New York City And Development Of New Analytical Tools, Kayla Marschke

Student Theses

Driving under the influence of drugs (DUID) cases have increased in recent years. According to NHTSA, drug use among fatally injured drivers who were tested for drugs rose from 25% in 2007 to 61.4% in 2020. Knowing what drugs are used by the drivers and developing new analytical tools to detect them are essential to prevent this type of cases. The goals of this study were two-fold: 1) To investigate the prevalence of drugs and drug combinations in New York City based on data provided by the Office Chief Medical Examiner (2018-2019); 2) To develop and validate an analytical method …

Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio

Honors Scholar Theses

Tetrabenazine (TBZ), a vesicular monoamine transporter type 2 (VMAT-2) inhibitor, depletes dopamine and induces motivational deficits and other depressive symptoms in humans. Methylphenidate (MPH) is a dopamine transport blocker that is used to enhance motivational function. Previous studies have shown that in male rats, TBZ induces a shift in effort-related choice such that a low-effort bias is induced. In male rats this occurs at a dose range of 0.75-1.0 mg/kg TBZ, and this effect is reversible with co-administration of MPH. Recent studies have shown that females need a higher dose of TBZ (2.0 mg/kg) to show the low-effort bias. The …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Frequency Of Marijuana Use By California University Students Based On Gender And Ethnicity: A Quantitative Analysis, Evelyn Lorraine Anderson

Doctoral Dissertations and Projects

The purpose of this quantitative causal-comparative study was to determine the frequency of marijuana use by California university students based on gender and ethnicity. This study was important because marijuana is the most used illicit substance in the United States, and there is limited research regarding the demographic characteristics of California university students who use marijuana. The quantitative research design was used to describe the patterns of marijuana use by California university students. The setting was online. The participants included a random sample of 167 college students from five California state universities. The Daily Sessions, Frequency, Age of Onset, and …

Estimating The Analytical Performance Of Raman Spectroscopy For Quantification Of Active Ingredients In Human Stratum Corneum, Hichem Kichou, Emilie Munnier, Yuri Dancik, Kamilia Kemel, Hugh Byrne, Ali Tfayli, Dominique Bertrand, Martin Soucé, Igor Chourpa, Franck Bonnier

Articles

Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo) human stratum corneum (SC), using systematically varied doses of resorcinol, as model compound, and the performance is quantified according to key figures of merit defined by regulatory bodies (ICH, FDA, and EMA). A methodology is thus demonstrated to establish the limit of detection (LOD), precision, accuracy, sensitivity (SEN), and …

Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, Michael Mckeever

Dissertations

Amphiphiles play important roles in nature. These molecules contain both hydrophilic and hydrophobic regions, leading to some astonishing properties. The lipid bilayer of the cell membrane is a fascinating organization of amphiphilic phospholipids. Natural and synthetic amphiphiles, such as antimicrobial peptides, interact with the cell membrane. Such interactions can impact transport of molecules across the cell membrane, disrupting cell functions. In this work, a library of tryptophan-containing amphiphiles was synthesized and their antimicrobial properties were explored.

First, a library of bis(tryptophan) amphiphiles was synthesized. Preparation included a coupling reaction of a diamine with tryptophan residues, via their carboxy-termini, at …

Interactions Among Endothelial Nitric Oxide Synthase, Cardiovascular System, And Nociception During Physiological And Pathophysiological States, Niribili Sarmah, Andromeda M. Nauli, Ahmmed Ally, Surya M. Nauli

Pharmacy Faculty Articles and Research

Nitric oxide synthase (NOS) plays important roles within the cardiovascular system in physiological states as well as in pathophysiologic and specific cardiovascular (CV) disease states, such as hypertension (HTN), arteriosclerosis, and cerebrovascular accidents. This review discusses the roles of the endothelial NOS (eNOS) and its effect on cardiovascular responses that are induced by nociceptive stimuli. The roles of eNOS enzyme in modulating CV functions while experiencing pain will be discussed. Nociception, otherwise known as the subjective experience of pain through sensory receptors, termed “nociceptors”, can be stimulated by various external or internal stimuli. In turn, events of various cascade pathways …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas

Undergraduate Research Symposium Posters

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is associated with cirrhosis. Poor survival rate of HCC is due to diagnosis of HCC at late stage.

Fragment-Based Drug Discovery And Synthesis Of Sars-Cov-2 Therapeutics, Hannah Johnson '22

Student Publications & Research

Since the novel SARS-CoV-2 was first identified in late 2019, numerous waves of the virus have hit communities around the world, affecting public health, mental
health, economies, and more. While public health guidelines are in place and vaccines are available, an oral antiviral is still needed. Vaccines and guidelines help
to prevent the contraction of the virus, however these measures are not 100% effective. An oral antiviral would inhibit the replication of the virus after
contraction, therefore complementing the current measures against the coronavirus. Further, oral antivirals are easier to distribute than vaccines, making
effective COVID-19 treatments available to more …