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Pharmacology

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Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Identifying Rna Splicing Changes During Alcohol Withdrawal Using An Optimized Rna-Seq Analysis Pipeline, Yasaswi Veera, Luana Martins De Carvalho, Amy Lasek Jan 2026

Identifying Rna Splicing Changes During Alcohol Withdrawal Using An Optimized Rna-Seq Analysis Pipeline, Yasaswi Veera, Luana Martins De Carvalho, Amy Lasek

UROP Posters

Alcohol use disorder (AUD) causes long-lasting changes in brain gene expression and RNA splicing, particularly in the ventral hippocampus. This study analyzes RNA-Seq data from rats exposed to chronic alcohol and withdrawal to identify transcript-level and splicing alterations. An optimized RNA-Seq pipeline using STAR, FeatureCounts, edgeR, and WGCNA improved efficiency by 25-40% while maintaining consistency across 25 datasets. Results reveal changes in neural signaling and stress-response pathways associated with withdrawal. This work provides both biological insight into AUD and a reproducible computational framework for transcriptomic analysis.

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Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin May 2025

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

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Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin Apr 2025

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

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Synthetic Nucleoside Labels For Studying Cell-Free Dna, Dibya Guragai Jan 2025

Synthetic Nucleoside Labels For Studying Cell-Free Dna, Dibya Guragai

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Cell-free DNA (cfDNA) can arise from dying cells or be actively secreted by living cells, and is found either unbound, within extracellular vesicles, or in other macromolecular complexes. cfDNA plays roles in intercellular communication and immune responses and is clinically used for diagnostics through PCR and DNA sequencing. Interestingly, our lab has detected lesions in cfDNA after treatment with DNA-damaging agents including UVB and cisplatin. These findings prompted further investigation into which DNA lesions and labels can be found in the cell-free space. Importantly, we sought a mechanism of labeling DNA with a synthetic nucleoside to enable robust tracing using …

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Systemic Effects Of Varying Degrees Of Thermal Burn Injuries In Young Mice: Role Of Microvesicle Particles And Platelet-Activating Factor, Prince Wilfred Jan 2025

Systemic Effects Of Varying Degrees Of Thermal Burn Injuries In Young Mice: Role Of Microvesicle Particles And Platelet-Activating Factor, Prince Wilfred

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Thermal burn injuries (TBI) result in local and systemic effects, particularly when a large body surface area is exposed to TBI. This study investigates the systemic effects of varying degrees of TBI in the murine model, focusing on the role of microvesicle particles (MVP) and Platelet-activating Factor (PAF) in mediating bacterial translocation and systemic inflammation. Utilizing the murine model, we analyzed MVP levels in the skin and blood, bacterial translocation in the gut, and the expression of pro-inflammatory mediators in the major organs at the 2-hour post-burn time point. Our studies revealed that after the two hours’ time point TBI …

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The Circadian Modulating Drug Sr8278 Slows Cell Proliferation Independent Of Rev-Erbs, Ushaswini Atluri Jan 2025

The Circadian Modulating Drug Sr8278 Slows Cell Proliferation Independent Of Rev-Erbs, Ushaswini Atluri

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The small molecule compound SR8278 was initially identified as an antagonist of the REV-ERB proteins, which play an important role in regulating circadian rhythms. Furthermore, the use of SR8278 in preclinical models has been demonstrated to ameliorate a variety of different pathologies. Using RNA-seq analysis of HaCaT keratinocytes treated with SR8278, our laboratory found that SR8278 induces a down regulation of genes involved in the G1/S phase transition of the cell cycle and an up regulation of genes involved in cholesterol biosynthesis. RT-qPCR and western blot analyses confirmed that SR8278 treatment led to lower expression of several factors involved in …

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The Role Of Rad51 And Its Paralogs In Dna Damage Response In Quiescent Cells Exposed To Solar Simulating Uv Radiation, Angitha Radhakrishnan Nair Jan 2025

The Role Of Rad51 And Its Paralogs In Dna Damage Response In Quiescent Cells Exposed To Solar Simulating Uv Radiation, Angitha Radhakrishnan Nair

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Rad51, and its five paralog proteins Rad51B, Rad51C, Rad51D, XRCC2, and XRCC3, are crucial in homologous recombination (HR) repair of DNA double-strand breaks. Prior studies have extensively shown the roles of Rad51 in the S/G2 phase, but its role in the G0/G1 phase is still unclear. Our lab focuses on studying the role of Rad51 and its paralogs in quiescent cells. RT-qPCR and western blots helped us understand the expression of Rad51 paralogs in proliferating and quiescent keratinocyte cells. Using a pharmacological inhibitor of Rad51, we found that Rad51 promotes quiescent cell survival after exposure to UV radiation. Like Rad51, …

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The Role Of Base Excision Repair In Dna Damage Responses In Human Keratinocytes Exposed To Solar Simulating Uv Radiation, Mobolaji Eniola Alabi Jan 2025

The Role Of Base Excision Repair In Dna Damage Responses In Human Keratinocytes Exposed To Solar Simulating Uv Radiation, Mobolaji Eniola Alabi

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Ultraviolet (UV) radiation from the sun is the most prominent source of exogenous UV damage to DNA. UV directly causes damage by forming UV photoproducts, including pyrimidine-pyrimidone (6-4) photoproducts ((6-4) PPs), which significantly distort the helical structure of DNA and interfere with transcription and replication processes. The only known repair process of these photoproducts in human cells is nucleotide excision repair (NER). However, a recent study reported an APE1-dependent base excision repair (BER) of a subset of UV photoproducts. The study showed that deletion or inhibition of APE1, PARP1, NTH1, XRCC1, and FEN1 led to a 2-fold increase in sensitivity …

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Characterization Of Atr Kinase Function In Quiescent Keratinocytes Exposed To Solar Simulating Uv Radiation, Mohamed Sameer Cholakkathody Jan 2025

Characterization Of Atr Kinase Function In Quiescent Keratinocytes Exposed To Solar Simulating Uv Radiation, Mohamed Sameer Cholakkathody

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This study examines the role of Ataxia Telangiectasia and Rad3-related kinase in quiescent human keratinocytes exposed to solar-simulated UV radiation (SSL). The ATR inhibitor VE-822 did not significantly affect cell viability in the absence of UV exposure, showing that ATR kinase activity is not essential for quiescent cell survival in the absence of additional genotoxic stress. After SSL exposure, ATR inhibition did not impact acute cell viability but reduced the cells’ long-term ability to proliferate. Western blot analysis demonstrated that VE-822 potently suppressed phosphorylation of ATR target proteins KAP1 and CHK2 in a dose-dependent manner after SSL exposure, confirming strong …

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Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran Jan 2025

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

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Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel Dec 2024

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

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Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli Jan 2024

Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli

Theses and Dissertations

Managing pain requires a delicate balance between the advantages of opioid analgesia and the possible adverse effects. This balance becomes even more difficult in hospice and palliative care environments where dosage regimens are frequently ambiguous. Some hospice patients experience opioid resistance, in which opioids no longer produce an analgesic effect on a patient. Evidence-based analyses frequently omit this vulnerable population, resulting in a need for concrete procedures. The emergence of pharmacogenomic analysis and personalized treatment presents a solution to this problem by using each patient's genomic data to interpret opiate dosing. This pharmacogenomic study aimed to single nucleotide polymorphisms (SNPs) …

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Characterization Of The Hydroxyurea-Induced Cell Elongation Phenotype In Fission Yeast Ssb1-20 Mutant, Yeseswi Archana Guduri Jan 2024

Characterization Of The Hydroxyurea-Induced Cell Elongation Phenotype In Fission Yeast Ssb1-20 Mutant, Yeseswi Archana Guduri

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Eukaryotic SSB, also known as replication protein A (RPA), is a single-stranded DNA binding protein that is highly conserved in eukaryotes. It is essential in multiple cellular functions such as DNA replication, repair, recombination, and cell cycle checkpoint signaling. Studying SSB’s or RPA’s checkpoint functions in cells is challenging due to its crucial role in cell survival. Exploring this possibility, we performed an extensive genetic screening of ssb1, which encodes the largest subunit of RPA, looking for nonlethal mutants that lack the checkpoint function. This screen has identified 25 primary mutants that are sensitive to genotoxins namely HU and MMS. …

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Characterization Of Cisplatin-Dna Adduct Release From Cancerous And Non-Cancerous Cell Lines, Aleena Alex Jan 2024

Characterization Of Cisplatin-Dna Adduct Release From Cancerous And Non-Cancerous Cell Lines, Aleena Alex

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Cisplatin is an effective chemotherapeutic agent that is used to treat lung, breast, esophageal, ovarian, and pancreatic cancers. Despite being effective in treating a wide variety of cancer types, its cytotoxicity to off-target healthy tissues restricts its therapeutic application. The platinum atom of cisplatin interacts with DNA and results in the formation of inter-and intra-strand crosslinks, which are often referred to as DNA adducts. These adducts are mutagenic and potentially lethal to cells. The sole pathway for cells to excise intra-strand cisplatin-DNA adducts from the genome is through nucleotide excision repair. The fate of unrepaired DNA adducts is not understood …

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Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy For Alcohol-Associated Liver Disease., Jeffrey Warner May 2023

Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy For Alcohol-Associated Liver Disease., Jeffrey Warner

Electronic Theses and Dissertations

Introduction Alcohol-associated liver disease (ALD) is a common chronic liver disease and healthcare burden, and a spectrum of pathologies ranging from steatosis to steatohepatitis, fibrosis, and alcohol-associated hepatitis (AH). Despite its prevalence, there are limited effective therapeutic options for the treatment of ALD/AH. Previous evidence suggested that inhibition of soluble epoxide hydrolase (sEH), a lipid metabolism enzyme which degrades beneficial metabolites of dietary polyunsaturated fatty acids, may be a beneficial strategy. The central hypothesis of the current dissertation is that sEH inhibition will ameliorate alcohol-associated liver injury and inflammation in mouse models of ALD. Methods To determine the efficacy of …

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Pharmacokinetics Of Single Feeding Of Cannabidiol In Cattle: A Pilot Study, Haley Cornette Apr 2023

Pharmacokinetics Of Single Feeding Of Cannabidiol In Cattle: A Pilot Study, Haley Cornette

Honors College Theses

Cannabidiol (CBD) is a substance that has been used in complementary medicine for many years. However, modern medicine has little knowledge of how this substance is utilized and metabolized in ruminant animals. Regulations on quality assurance and use in animals are lacking, and CBD supplementation in livestock is not approved. If CBD supplements can be shown to be safe and effective, detection in the animal will be important for determining regulation of use. A withdrawal period can then be established to allow time for deterioration of product to safe levels before livestock products enter human markets. This study sought to …

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Xeroderma Pigmentosum Type A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation And Solar Simulated Light Via Platelet-Activating Factor Receptor Signaling Pathway, Pranali Sushil Manjrekar Jan 2023

Xeroderma Pigmentosum Type A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation And Solar Simulated Light Via Platelet-Activating Factor Receptor Signaling Pathway, Pranali Sushil Manjrekar

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Increased vulnerability to the DNA-damaging effects of ultraviolet (UV) radiation is a hallmark of the uncommon genetic disorder Xeroderma Pigmentosum (XP). The Nucleotide Excision Repair (NER) route uses the DNA Damage Recognition and Repair component XPA to identify and get rid of damaged DNA segments. Although the solar UVB (290-320 nm) radiation is necessary for humans to produce vitamin D, it may also induce erythema and inflammatory reactions, and in some pathological situations, such as XPA deficiency, results in increased UV responses (photosensitivity). Our group has previously shown, using cell lines and mice, that increased synthesis of the lipid mediator …

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To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi Jan 2023

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

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Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …

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The Role Of Platelet-Activating Factor And Microvesicle Particles In Intoxicated Thermal Burn Injury-Induced Multiple Organ Failure, Rushabh Pawan Lohade Jan 2023

The Role Of Platelet-Activating Factor And Microvesicle Particles In Intoxicated Thermal Burn Injury-Induced Multiple Organ Failure, Rushabh Pawan Lohade

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Intoxicated thermal burn injury (ITBI) is more severe than thermal burn injury (TBI) alone and causes significant morbidity and mortality. Evidence from mouse models that replicate the human condition of multiple organ dysfunction has been informative. ITBI results in enhanced bacterial translocation from the gut, increased levels of proinflammatory mediators, and immune cell infiltration in various organs, resulting in inflammation in multiple organs with subsequent dysfunction. In addition, ITBI induces delayed systemic immunosuppression. To understand the mechanism(s) underlying ITBI-induced inflammation and damage in multiple organs, we investigate the role of Platelet-activating factor (PAF) and subcellular microvesicle particles (MVPs) in this …

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Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad Jan 2023

Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad

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Cathepsin L is a lysosomal cysteine protease that is encoded by the CTSL gene in humans. Previous results have shown that CTSL expression and activity towards the DNA repair protein XPA are elevated in lysates of confluent/quiescent HaCaT keratinocytes. Because other nuclear proteins, including 53BP1 and histone H3, have also been reported to be CTSL substrates under conditions of cell differentiation, senescence, or quiescence, CTSL expression and activity (cleavage) of multiple nuclear proteins was examined in lysates from HaCaT cells and other cell lines at various days after plating and cell confluency. Our study found that adding CTSL inhibitors to …

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Characterization Of Atr Kinase Function In Quiescent Human Keratinocytes When Exposed To Solar Simulating Uv Radiation, Hrishikesh Tryambak Kadam Jan 2023

Characterization Of Atr Kinase Function In Quiescent Human Keratinocytes When Exposed To Solar Simulating Uv Radiation, Hrishikesh Tryambak Kadam

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Cell cycle control, DNA repair, and cell survival have all been linked to the ataxia-telangiectasia and Rad3-related (ATR) kinase, a vital part of the DNA damage response system. In this work, we looked at the role of ATR kinase in human keratinocytes that were dormant and exposed to solar simulating light (SSL). Our findings demonstrated that SSL activates the ATR kinase, phosphorylating downstream substrates such as KAP1, Chk2, and H2AX. In addition, we noticed that quiescent keratinocytes exposed to SSL experienced a decrease in viability when ATR kinase activity was inhibited. Our research indicates that in quiescent keratinocytes exposed to …

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Validation Of A Cell Line Model For Studying Xpd Protein Function In Nucleotide Excision Repair, Naga Swathi Sree Kavuri Jan 2023

Validation Of A Cell Line Model For Studying Xpd Protein Function In Nucleotide Excision Repair, Naga Swathi Sree Kavuri

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The various environmental factors like toxic chemicals, chemotherapeutic agents and UV radiation impact human health by altering physiological functions of the normal living cells. One of the main consequences of exposure to these factors is DNA damage. Although, living system have inherent DNA repair mechanisms such as Nucleotide Excision Repair (NER), which removes DNA lesions from the genome in the form of small, approximately 30-nt-long DNA oligonucleotides. The accumulation of unrepaired DNA adducts as a result of this NER deficiency causes a variety of syndromes, including Xeroderma Pigmentosum (XP), Cockayne Syndrome, Neurological syndrome, and carcinoma of skin. To understand more …

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To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi Jan 2023

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

Browse all Theses and Dissertations

Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …

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Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos Jan 2023

Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos

Theses and Dissertations

Pain is a major public health concern that is commonly associated with behavioral depression, and a major goal in pain treatment is alleviation of pain-related behavioral depression. High-efficacy mu opioid receptor (MOR) agonists (e.g. fentanyl, morphine, oxycodone) are effective to treat pain, but their use is limited by side effects that not only endanger the patient but may also obscure analgesic rescue of pain-depressed behavior. The ongoing epidemic of opioid abuse and overdose deaths has stimulated research to discover non-opioid alternative analgesics; however, this search neglects the clinical potential of safer intermediate-efficacy MOR agonists (e.g. buprenorphine). The objective of the …

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Vapourized Cannabis Extract Administration Impairs Memory And Alters Neural Activity In Laboratory Rats, Megan Chladny Jan 2023

Vapourized Cannabis Extract Administration Impairs Memory And Alters Neural Activity In Laboratory Rats, Megan Chladny

Theses and Dissertations (Comprehensive)

Although people have smoked cannabis for millennia, administration of cannabis by heating the dried plant material or distilled extracts to a temperature just below the combustion point (i.e., vapourization or "vaping") has rapidly increased over the past few years (Javadi-Payder, Cole, and Taffe, 2018; Manwell, Charchoglyan, Brewer, Matthews, Heipel, and Mallet, 2014). Conversely, most of the cannabinoid research using rodent models has used parenteral routes of administration to examine the effects of purified cannabis extracts such as ∆9-tetrahydrocannabinol (THC), making it difficult to directly compare laboratory research to human drug use. Building on previous studies showing that THC …

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A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing Sep 2022

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., …

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Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun Aug 2022

Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun

Electronic Theses and Dissertations

Cannabidiol (CBD) is the most abundant non-psychotropic cannabinoid constituent of Cannabis sativa. CBD is potentially therapeutic for the eye through antioxidant, anti-inflammatory, and neuroprotective effects. However, the effect of CBD on intraocular pressure (IOP)- the major risk factor for glaucoma- is controversial and large variability exists in the literature. IOP is regulated through aqueous humor (AH) dynamics in trabecular meshwork (TM) tissues. Measurement of CBD in AH and correlation with effects on IOP would clarify what concentrations mediate changes to IOP. Therefore, the overall goal of this dissertation is to measure CBD in ocular tissues and correlate concentrations with …

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Pharmacometabolomics Profiling Of Preterm Infants Validates Patterns Of Metabolism Associated With Response To Dexamethasone Treatment For Bronchopulmonary Dysplasia., Bradley Stockard, Cheri Gauldin, William E. Truog, Tamorah Lewis Jun 2022

Pharmacometabolomics Profiling Of Preterm Infants Validates Patterns Of Metabolism Associated With Response To Dexamethasone Treatment For Bronchopulmonary Dysplasia., Bradley Stockard, Cheri Gauldin, William E. Truog, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response. Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort. A total of 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed …

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A Psychopharmacology Review Of Brexpiprazole, Nicole A. Marion Apr 2022

A Psychopharmacology Review Of Brexpiprazole, Nicole A. Marion

Conspectus Borealis

Brexpiprazole is an antipsychotic drug often used to help treat schizophrenia and major depressive disorder. This review paper breaks down the drugs history including what it is used for, how it is used, and how it was developed. Pharmacokinetics including administration routes, steady states, and metabolism. This review also describes pharmacodynamics, focusing on drug affinity. It will also discuss pharmacological effects pulling evidence from clinical trials. Last this review will describe the toxicology and safety of brexpiprazole.

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Replication Stress Induced By The Ribonucleotide Reductase Inhibitors Guanazole, Triapine, And Gemcitabine In Fission Yeast, Mashael Yahya A Alyahya Jan 2022

Replication Stress Induced By The Ribonucleotide Reductase Inhibitors Guanazole, Triapine, And Gemcitabine In Fission Yeast, Mashael Yahya A Alyahya

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Replication stress can be produced by various exogenous or endogenous factors that perturb the movement of replication forks. To overcome the stress, the cells provoke the DNA replication checkpoint to mobilize several pathways to protect the forks, maintain genome integrity, and promote cell survival. Defects in the replication checkpoint cause forks collapse, leading to chromosomal DNA damage or cell death. Although the replication checkpoint is crucial for genome integrity in all eukaryotes, the underlying mechanisms remains to be fully understood. To investigate the mechanisms of DRC, hydroxyurea (HU), an established inhibitor of ribonucleotide reductase (RNR), has been widely used in …

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