Pharmacy and Pharmaceutical Sciences Commons^™

Chronic Voluntary Alcohol Drinking Causes Anxiety-Like Behavior, Thiamine Deficiency, And Brain Damage Of Female Crossed High Alcohol Preferring Mice, Hong Xu, Hui Li, Dexiang Liu, Wen Wen, Mei Xu, Jacqueline A. Frank, Jing Chen, Haining Zhu, Nicholas J. Grahame, Jia Luo

Molecular and Cellular Biochemistry Faculty Publications

The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water …

Protecting P-Glycoprotein At The Blood-Brain Barrier From Degradation In An Alzheimer's Disease Mouse Model, Yujie Ding, Yu Zhong, Andrea Baldeshwiler, Erin L. Abner, Björn Bauer, Anika M. S. Hartz

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Failure to clear Aβ from the brain is partly responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood-brain barrier is the efflux transporter P-glycoprotein (P-gp). In AD, P-gp levels are reduced, which contributes to impaired Aβ brain clearance. However, the mechanism responsible for decreased P-gp levels is poorly understood and there are no strategies available to protect P-gp. We previously demonstrated in isolated brain capillaries ex vivo that human Aβ40 (hAβ40) triggers P-gp degradation by activating the ubiquitin-proteasome pathway. In this pathway, hAβ40 initiates P-gp ubiquitination, leading to internalization and …

Apolipoprotein E Genotype-Dependent Nutrigenetic Effects To Prebiotic Inulin For Modulating Systemic Metabolism And Neuroprotection In Mice Via Gut-Brain Axis, Lucille M. Yanckello, Jared D. Hoffman, Ya-Hsuan Chang, Penghui Lin, Geetika Nehra, George Chlipala, Scott D. Mcculloch, Tyler C. Hammond, Andrew T. Yackzan, Andrew N. Lane, Stefan J. Green, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: The goal of the study was to identify the potential nutrigenetic effects to inulin, a prebiotic fiber, in mice with different human apolipoprotein E (APOE) genetic variants. Specifically, we compared responses to inulin for the potential modulation of the systemic metabolism and neuroprotection via gut-brain axis in mice with human APOE ϵ3 and ϵ4 alleles.

METHOD: We performed experiments with young mice expressing the human APOE3 (E3FAD mice and APOE4 gene (E4FAD mice). We fed mice with either inulin or control diet for 16 weeks starting from 3 months of age. We determined gut microbiome …

Evaluating Opioid Dispensing Rates Among Pediatrics And Young Adults Based On Cures Data Reporting In California From 2015–2019, Michael T. Phan, Courtney Wong, Daniel M. Tomaszewski, Zeev N. Kain, Brooke Jenkins, Candice D. Donaldson, Michelle Fortier, Sun Yang

Pharmacy Faculty Articles and Research

Background

Receipt of opioid prescriptions in pediatric and young adult patients may be a risk factor for future opioid misuse. Data from prescription drug monitoring programs provide insight on outpatient opioid use. In our study, we analyzed the opioid dispensing rates for pediatrics and young adults in California. Methods

A secondary analysis was performed from 2015–2019 using Controlled Utilization Review and Evaluation System data. This database provides dispensing data of controlled substances in California. Patients younger than 25 years who were prescribed opiates were analyzed by county. We further divided them into two groups (children: ≤14 years; adolescents and young …

Guideline-Directed Heart Failure Therapy In Patients After Left Ventricular Assist Device Implantation, Bailey M. Colvin, James C. Coons, Craig J. Beavers

The VAD Journal

Background: Left ventricular assist devices (LVADs) are used as an advanced therapy option for patients with stage D heart failure. These devices provide mechanical unloading of the heart as either a bridge to transplant or recovery, or as destination therapy. In patients with LVADs, there are emerging data on the use of heart failure guideline-directed medical therapy (GDMT) to improve outcomes. This review describes the current evidence available for the use of neurohormonal blocking agents in patients with LVADs.

Methods: Articles were found using PubMed and web searches for heart failure therapies/neurohormonal blockade and LVADs. Studies were included if they …

Clinical Pharmacology And Dosing Regimen Optimization Of Neonatal Opioid Withdrawal Syndrome Treatments, Fei Tang, Chee M. Ng, Henrietta S. Bada, Markos Leggas

Pharmaceutical Sciences Faculty Publications

In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well-defined and knowledge of patient-specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level. Although there …

Preclinical Evaluation Of Artesunate As An Antineoplastic Agent In Ovarian Cancer Treatment, Anthony Mcdowell Jr., Kristen S. Hill, Joseph Robert Mccorkle, Justin W. Gorski, Yilin Zhang, Ameen A. Salahudeen, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

BACKGROUND: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment.

METHODS: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

Interactions Of Neuroimmune Signaling And Glutamate Plasticity In Addiction, Cassandra D. Gipson, Scott Rawls, Michael D. Scofield, Benjamin M. Siemsen, Emma O. Bondy, Erin E. Maher

Family and Community Medicine Faculty Publications

Chronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe …

Dna Repair Pathways In Cancer Therapy And Resistance, Lan-Ya Li, Yi-Di Guan, Xi-Sha Chen, Jin-Ming Yang, Yan Cheng

Toxicology and Cancer Biology Faculty Publications

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Meropenem-Induced Pancytopenia In A Preterm Neonate: A Case Report, Kashif Hussain, Muhammad Sohail Salat, Naureen Mohammad, Ambreen Mughal, Sidra Idrees, Javaid Iqbal, Gul Ambreen

Department of Biological & Biomedical Sciences

Background: A post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate.
Case presentation: A preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 10³ cells/mm³, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm³ on days …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …

Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian …

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …

Ketamine Infusions For Post-Cesarean Pain In Patients With Opioid Use Disorder, Talitha Budi, Johanna Cobb, Wendy Craig, Heather Turcotte, Janelle Richard, Aurora Quaye

Costas T. Lambrew Research Retreat 2021

Discussion:

• Opioid consumption may be reduced during ketamine infusion without significant side effects

• Further investigation planned with a prospective, randomized, double-blind, placebo-controlled trial.

Preventive Healthcare Services Receipt And Primary Care Provider Utilization Among People Who Inject Drugs, E K. Nenninger, Kinna Thakarar

Costas T. Lambrew Research Retreat 2021

Introduction:

People who inject drugs (PWID) face barriers to accessing primary care providers (PCPs) and preventive services, but are at increased risk for preventable infections

Preventive services can be accessed through PCPs, or while hospitalized or at community organizations like syringe service programs (SSPs)

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 …

The Time Trial® Network Facilitates Rapid Clinical Trial Activation, Patient Screening, And Enrollment In Molecularly Targeted Trials, Stephanie O'Leary, Megan Shulman, Kevin Ritt, Meghan Degele, Ewelina Protomastro, Jennifer Clauson, Amy Franzen, Ian Churchill Anderson, Minal A. Barve, David N. Oubre, Victor Priego, Angela Saverimuthu, Francis Mark Senecal, Raju Kumar Vaddepally, Kimberly L. Blackwell, Matthew M. Cooney

Articles, Abstracts, and Reports

No abstract provided.

New Evidence For P-Gp-Mediated Export Of Amyloid-Β Peptides In Molecular, Blood-Brain Barrier And Neuronal Models, Amanda B. Chai, Anika M. S. Hartz, Xuexin Gao, Alryel Yang, Richard Callaghan, Ingrid C. Gelissen

Sanders-Brown Center on Aging Faculty Publications

Defective clearance mechanisms lead to the accumulation of amyloid-beta (Aβ) peptides in the Alzheimer’s brain. Though predominantly generated in neurons, little is known about how these hydrophobic, aggregation-prone, and tightly membrane-associated peptides exit into the extracellular space where they deposit and propagate neurotoxicity. The ability for P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, to export Aβ across the blood-brain barrier (BBB) has previously been reported. However, controversies surrounding the P-gp–Aβ interaction persist. Here, molecular data affirm that both Aβ₄₀ and Aβ₄₂ peptide isoforms directly interact with and are substrates of P-gp. This was reinforced ex vivo by the …

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

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 …

Impact Of 17-Beta Estradiol And Moderate-Intensity Exercise On Mesenteric Arterial Function Of Uc Davis Type-2 Diabetes Mellitus Rats, Md Rahatullah Razan

University of the Pacific Theses and Dissertations

The studies in this dissertation were designed to investigate the impacts of estrogen (17-β estradiol/E2) and moderate-intensity exercise (MIE) on the mesenteric arterial (MA) function of the University of California Davis type-2 diabetes mellitus (UCD-T2DM) Rat model. Our recent report suggests that diabetes impairs MA vasorelaxation in both sexes of the UCD-T2DM model. Particularly, we reported that MA from prediabetic male rats showed a greater impairment compared to that in prediabetic females. However, when females become diabetic, they exhibit a greater vascular dysfunction than males. Therefore, the aim of the first study was to investigate whether female sex hormone, specifically …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Association Of Incident Cancer To Low-Value Care And Healthcare Cost Burden Among Elderly Medicare Beneficiaries, Chibuzo Iloabuchi

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States (US), 25% of healthcare spending is considered wasteful because it is spent reimbursing low-value care. Low-value care is the utilization of healthcare services, medical tests, and procedures that have unclear or no clinical benefit to patients but still exposes them to risk. World-wide, low-value care imposes a significant economic burden on patients, payers, governments, and society. Cancer care among older adults > 65 years is one of the biggest drivers of healthcare expenditure in the US and accounts for nearly 40% of all spending, and low-value care among cancer patients is prevalent and contributes to the financial …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Re: "Psychiatric Medication Users By Age And Sex"., Kelsey Sicker

Ambulatory and Primary Care Articles

No abstract provided.

Apixaban Discontinuation For Invasive Or Major Surgical Procedures (Adios): A Prospective Cohort Study., Geno J. Merli, Walter K. Kraft, Luis H. Eraso, Taki Galanis, Lynda J. Thomson, Geoffrey O. Ouma, Eugene Viscusi, Jerald Z. Gong, Edwin Lam

Department of Medicine Faculty Papers

Background

Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care peri-operative management.

Methods

This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician.

Results

One hundred and …