Chemicals and Drugs Commons^™

Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas

Bioelectrics Publications

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate …

"It’S Just Another Thing”: Perceptions Of Well Water Quality And Barriers In An Arsenic Hot Spot, Linzy Rosen

Honors Theses

Privately owned water is the primary source of drinking water for 43 million Americans. Although residential or private wells are susceptible to a variety of contaminants, the Safe Drinking Water Act of 1974 positions individuals as responsible for the testing, remediation, and management of this water. Despite the elevated presence of arsenic in Maine, which is linked to various cancers, cardiovascular disease, and neurological damage, little is known about how private well owners perceive the safety and quality of their own water.

This study takes a qualitative approach to understanding concerns and opinions by conducting semi - structured interviews with …

Personalised Antimicrobial Dosing In Paediatric Cystic Fibrosis, Sahand Imani

Theses

Children with cystic fibrosis (CF) are predisposed to recurrent pulmonary exacerbations throughout their lifetime. This is characterised by an acute worsening of respiratory symptoms in the setting of bacterial infection and results in significant morbidity and mortality. Appropriate antimicrobial therapy is fundamental to management, in particular aminoglycoside antibiotics. Tobramycin is the preferred aminoglycoside of choice, usually administered intravenously for 7 to 14 days.

Tobramycin dosing can be challenging in patients with CF. This is due to the underlying pharmacokinetic derangements (e.g., volume of distribution, organ function) frequently observed in this population. Accordingly, the use of standard dosing (based on age …

Botanicals As Prospective Agents Against Sars-Cov-2 Virus, Vyacheslav Dushenkov, Anna Dushenkov

Publications and Research

The COVID-19 high morbidity and mortality resulted in a worldwide healthcare emergency that triggered accelerated and amplified efforts in the relevant areas of health sciences research and practice. Purpose: To assess the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus. Methods: This narrative review examined the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus based on the references limited to the English language and published up to February 2022 and retrieved from common academic search engines using multiple keywords and their combinations. The scientific names of plant species were confirmed using World Flora Online …

Physician Assisted Dying (Pad): An Investigation Into The Mechanistic Action Of Opioid, Benzodiazepine, And Barbiturate Administration As An Alternative Measure To Forgoing Life Sustaining Treatment And Aggressive Palliation., Jordana Chanel Deighton

CMC Senior Theses

Whilst modern medicine has increased longevity, the rise in life expectancy has brought about new struggles, namely that of aging and age related disease. Thus, humanity has been presented with a new problem: at what point is death preferable to aggressive life-prolonging treatment in the face of inevitable death? And if so, what right do individuals have to control the circumstances of their death? In the West, traditionally, individuals who seek to end their own lives in the face of terminal illness opt for forgoing artificial hydration and nutrition. Driven by an increase in desire for autonomous dignified death, a …

Marijuana And Patents: The Complicated Relationship Between Patent Rights And The Federal Criminalization Of Marijuana, Reza Roghani Esfahani, Howard Bromberg

Articles

Difficult questions arise in the context of marijuana-related inventions, patent procurement, and patent enforcement. These questions are a subset of the contradictions in the law of marijuana, where the federal government prohibits marijuana use and yet many of the states legalize, regulate, and tax it. This federal prohibition could discourage research into the health effects of marijuana and makes it difficult for marijuana-related innovations to satisfy statutory patentability requirements. It also renders enforcement of marijuana patents questionable, making marijuana businesses and patent owners vulnerable to nonpracticing patent entities, sometimes called "patent trolls."

Bone Morphogenetic Proteins Shape TReg Cells, Piotr Kraj

Biological Sciences Faculty Publications

The transforming growth factor-β (TGF-β) family includes cytokines controlling cell behavior, differentiation and homeostasis of various tissues including components of the immune system. Despite well recognized importance of TGF-β in controlling T cell functions, the immunomodulatory roles of many other members of the TGF-β cytokine family, especially bone morphogenetic proteins (BMPs), start to emerge. Bone Morphogenic Protein Receptor 1α (BMPR1α) is upregulated by activated effector and Foxp3+ regulatory CD4+ T cells (Treg cells) and modulates functions of both of these cell types. BMPR1α inhibits generation of proinflammatory Th17 cells and sustains peripheral Treg cells. This finding underscores the importance of …

Mechanism For Selective Binding Of Aromatic Compounds On Oxygen-Rich Graphene Nanosheets Based On Molecule Size/Polarity Matching, Heyun Fu, Bingyu Wang, Dongqiang Zhu, Zhicheng Zhou, Shidong Bao, Xiaolei Qu, Yong Guo, Lan Ling, Shourong Zheng, Pu Duan, Jingdong Mao, Klaus Schmidt-Rohr, Shu Tao, Pedro J.J. Alvarez

Chemistry & Biochemistry Faculty Publications

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding …

Investigating The Physical Stability Of Amorphous Pharmaceutical Formulations, Travis W. Jarrells

Theses and Dissertations--Pharmacy

Amorphous formulations, including amorphous solid dispersions (ASDs), consisting of the active pharmaceutical ingredient (API) intimately mixed in a polymeric matrix, are an attractive formulation approach to improve drug delivery, dissolution, and solubility. However, an amorphous API in an ASD is in a higher energy state compared to the crystalline drug and results in most ASDs being inherently unstable. The polymer helps to stabilize the amorphous drug against crystallization such that the resulting homogenous mixture maintains its solubility advantage relative to the crystalline form. One challenge of ASDs is that the presence of impurities including crystals or residual solvent, variations in …

The Relative Contribution Of Liver And Intestine In Reverse Cholesterol Transport, Rupinder Kaur

Theses and Dissertations--Pharmacy

Despite decades of advances in research, death due to cardiometabolic disease remains the largest contributor to mortality in the US. While present therapies oppose “forward cholesterol transport,” and atherosclerotic plaque progression, they do not remove cholesterol from established atherosclerotic plaques. Reverse cholesterol transport (RCT) is the active process of mobilizing peripheral cholesterol for excretion through the hepatobiliary (transhepatic cholesterol elimination, THCE) or intestinal (transintestinal cholesterol elimination, TICE) pathways. Currently, there are no clinically approved therapeutics that target RCT. Elucidation of the mechanisms that govern RCT and TICE, and the subsequent identification of novel targets is of importance. The present work …

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

Graduate Theses/Dissertations

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y₂ receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y₂ R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …

The Benefit Of Bdnf Modification In The Treatment Of Post-Stroke Depression, Christine Gordynskiy-Ageyev

Capstone Showcase

Neuroplasticity has been a rapidly expanding area of research, and its findings have elucidated the potential of taking advantage of some of its components for the treatment of various neural pathologies. Stroke is the most common cause of long-term disability, and it is a disease process that affects many people. There are many rehabilitation programs that seek to restore a patient’s motor and cognitive functions after stroke; if not fully, then at least partially. Unfortunately, mental health changes contribute in large part to the overall disability of a patient, but these changes are not always targeted in these programs. In …

Safety, Efficacy, And Reversibility Of Novel Male Contraceptives For Improved Pregnancy Prevention, Danielle Anton

Capstone Showcase

Unintended pregnancy is a global issue that can result from contraceptive failure or from a lack of contraceptive use. A literature search was conducted to explore novel methods of male contraceptives being developed for improved pregnancy prevention. Seven articles were selected, reporting on either oral contraceptive pills, transdermal gel, injectable hormonal, or bilateral intravas deferens polymer injection. The most common adverse events reported across all studies include changes in libido, mood, weight gain, acne, and headache. After reaching hormone and sperm concentration levels sufficient for pregnancy prevention, authors reported complete reversibility of contraceptive effects. Four studies described changes in various …

Management Of Adult Growth Hormone Deficiency Related To Hypopituitarism, Kellie Jamin

Capstone Showcase

The treatment of growth hormone deficiency (GHD) is well-established in childhood but less understood in adults, given the more complex role that growth hormone (GH) assumes in this population. Decreased functionality of the pituitary gland, otherwise known as hypopituitarism, can present with an isolated GHD in adulthood, which may result from a number of factors including neoplasm, ischemia, infection, traumatic injury, or systemic disease. Adult GHD may be definitively diagnosed with a stimulation test, the insulin tolerance test (ITT) being the study of choice. With a positive ITT, the disorder can be treated with growth hormone replacement therapy (GHRT), which …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability, Bethany Eaton

All Master's Theses

Mitochondria are cellular organelles that are becoming more recently studied. One of their main functions is the production of energy through cellular respiration, which is crucial to cell life. However, they are also associated with numerous disease states. It is hypothesized that reactive oxygen species (ROS), largely produced in mitochondria, induce oxidative stress and affect mitochondrial morphology along with cell viability. This study compares chemical exposure of menadione, an ROS producer, and phthalates (plasticizers) on two mouse hepatocyte cell lines to determine the effects they have on mitochondrial morphology and cell viability. Three experiments were performed to analyze the effects …

Remdesivir Analog As Sars-Cov-2 Polymerase Inhibitor: Virtual Screening Of A Database Generated By Scaffold Replacement, Amgad Albohy, Mohamed A. Said, Mohamed A. Abdelrahman, Hany Said

Pharmacy

By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2. In this study, we used the interactions of the co-crystallized metabolite of remdesivir with SARS-CoV-2 RdRp isozyme (PDB 7BV2) to design an analog with potential …

Evaluation Of A Modified Redon Fit Test Protocol For Half-Mask Respirators, Riley Duncan, Olivia Dawson, Leshan J. Kimbrough

Scholar's Day

The purpose of this study was to investigate whether a modified REDON method is as effective and accurate compared to the reference method when measuring respirator fit for elastomeric half-mask respirators using the Quantifit® CNP instrument.

Synthesis And Evaluation Of Novel Tyrosinase Inhibitors, Virginia Bailey

Honors Program Theses

Melanin is responsible for the protection against ultraviolet light and the pigmentation of mammalian skin, hair, and eyes.1–3 This indolic polymer is located in the epidermis of mammals and is produced through melanogenesis in specialized cells called melanocytes. Over production of melanin in humans can produce unwanted aesthetic products such as dark spots, freckles, solar lentigo (age spots), melasma, and even cancer.2,4,5 The overproduction of melanin during post-harvest handling causes enzymatic browning of produce resulting in a loss of nutritional value, a decrease in shelf life, and a decline flavor.2,6–8 Tyrosinase is an oxidoreductase, type-3, copper-containing glycoprotein located in the …

Why Glucagon Matters For Hypoglycemia And Physical Activity In Individuals With Type 1 Diabetes, Sheri R. Colberg

Human Movement Studies & Special Education Faculty Publications

No abstract provided.