Medicine and Health Sciences Commons^™

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 …

An Examination Of A Proposed Rule: Removal Of Sirva From The Vaccine Injury Table, Derrica N. Jackson

Honors Undergraduate Theses

Vaccines are one of the greatest modern medical inventions. Even though vaccines have saved lives, however, no medical product is proven to be completely safe. Vaccines can have rare and sometimes deadly reactions. To address such occurrences, the U.S. Department of Health and Human Services (HHS) hosts a program that reviews petitions for compensation of injuries caused by vaccination. The program is called the National Vaccine Injury Compensation Program (VICP). The VICP was established in 1986 to reduce the number of product liability lawsuits against vaccine manufacturers that threatened to increase the cost of vaccines and lower life-saving vaccine administration …

Effect Of Histone H4 Tail On Nucleosome Stability And Internucleosomal Interactions, Tommy Stormberg, Sridhar Vemulapalli, Shaun Filliaux, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Chromatin structure is dictated by nucleosome assembly and internucleosomal interactions. The tight wrapping of nucleosomes inhibits gene expression, but modifications to histone tails modulate chromatin structure, allowing for proper genetic function. The histone H4 tail is thought to play a large role in regulating chromatin structure. Here we investigated the structure of nucleosomes assembled with a tail-truncated H4 histone using Atomic Force Microscopy. We assembled tail-truncated H4 nucleosomes on DNA templates allowing for the assembly of mononucleosomes or dinucleosomes. Mononucleosomes assembled on nonspecific DNA led to decreased DNA wrapping efficiency. This effect is less pronounced for nucleosomes assembled on positioning …

Patient-Derived Induced Pluripotent Stem Cell Models For Phenotypic Screening In The Neuronal Ceroid Lipofuscinoses, Ahmed Morsy, Angelica V. Carmona, Paul C. Trippier

Journal Articles: Pharmaceutical Sciences

Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare, fatal, inherited neurodegenerative lysosomal storage disorders. Numerous genes (CLN1-CLN8, CLN10-CLN14) were identified in which mutations can lead to NCL; however, the underlying pathophysiology remains elusive. Despite this, the NCLs share some of the same features and symptoms but vary in respect to severity and onset of symptoms by age. Some common symptoms include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and in the rare adult-onset, dementia. Currently, all forms of NCL are fatal, and no curative treatments are available. Induced pluripotent stem …

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

Theses and Dissertations--Pharmacy

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

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

Pharmacist Provision Of Contraception Services In Kentucky: Opinions And Policy Interventions, Dustin K. Miracle

Theses and Dissertations--Pharmacy

Unintended pregnancy continues to be a prevalent issue across the United States, impacting millions of women annually. While several states have enacted policies expanding pharmacist services to allow for provision of hormonal contraception, Kentucky has yet to do so. Likewise, although provision of nonprescription hormonal contraception could be authorized under Kentucky regulation, prior to this study, this had yet to be done. The objectives of this study were to 1) understand the opinions of Kentucky pharmacists and student pharmacists regarding provision of hormonal contraception services through a board-authorized protocol, 2) understand the opinions of Kentucky pharmacists and student pharmacists regarding …

Examining Childhood Outcomes In Neonatal Abstinence Syndrome, Kailyn Conner

Theses and Dissertations--Pharmacy

Rates of neonatal abstinence syndrome have been rising over the past several years, alongside rising rates of opioid use disorder, propelled by the continuing Opioid Epidemic ravaging the country. Children born withdrawing from opioids they were exposed to in utero have known health complications through the first year of life that have been studied in the current literature. Less is known, however, about the outcomes these children face in childhood. As many of these children are progressing to childhood, there is an urgent need for healthcare system to prepare to handle the health needs of these children; outcomes related to …

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …

Towards A Holistic Risk Model For Safeguarding The Pharmaceutical Supply Chain: Capturing The Human-Induced Risk To Drug Quality, Heather R. Campbell

Theses and Dissertations--Pharmacy

Counterfeit, adulterated, and misbranded medicines in the pharmaceutical supply chain (PSC) are a critical problem. Regulators charged with safeguarding the supply chain are facing shrinking resources for inspections while concurrently facing increasing demands posed by new drug products being manufactured at more sites in the US and abroad. To mitigate risk, the University of Kentucky (UK) Central Pharmacy Drug Quality Study (DQS) tests injectable drugs dispensed within the UK hospital. Using FT-NIR spectrometry coupled with machine learning techniques the team identifies and flags potentially contaminated drugs for further testing and possible removal from the pharmacy. Teams like the DQS are …

Delineating The Biosynthesis Of Capuramycin-Type Antibiotics, Ashley L. Biecker

Theses and Dissertations--Pharmacy

New antibiotic scaffolds with novel drug targets are needed to combat the rise of drug-resistant, infectious microorganisms. The bacterial translocase I is a ubiquitous enzyme in the peptidoglycan biosynthetic pathway that has yet to be targeted by clinically used antibiotics. It catalyzes the transfer of N-acetylmuramoyl-pentapeptide to undecaprenylphosphate in order to generate lipid I during cell wall biosynthesis. A screening of bacterial translocase I inhibitors led to the discovery of the novel compound capuramycin and its analogues: A-500359s, A-503083s, and A-102395, produced by various species of actinomycetes. The capuramycins show potent activity against the bacterial translocase I with IC50s …

Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, Travis Murray

Dickinson Law Review (2017-Present)

Traditionally, state legislatures implemented Prescription Drug Monitoring Programs (“PDMPs”) to assist prescribers, pharmacists, and law enforcement in identifying patients likely to misuse, abuse, or divert controlled substances. PDMP databases contain a catalog of a patient’s recent controlled substances that pharmacies have filled, including the date, location, the quantity of medication filled, and the prescribing health care provider. Prescribers in Pennsylvania have a duty to query the PDMP before prescribing controlled substances in most clinical settings. Pharmacists have a similar duty in Pennsylvania to dispense safe and effective medication therapy to patients and to screen patients for potential signs of misuse, …

Impact Of A Primary Care Clinical Pharmacist On The Management Of Hepatitis C Viral Infection, Sierra Ferreiira, Adam Normandin, Linh Gagnon, Corinn Martineau

Costas T. Lambrew Research Retreat 2021

Interprofessional care including a pharmacist demonstrates a positive trend towards increasing access to care and improving adherence to Hepatitis C management in a primary care setting.

Metal-Organic Frameworks As Bacteria Mimicking Delivery Systems For Tuberculosis, Ailin Guo

Electronic Theses and Dissertations

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb), with an estimated 1.5 million deaths and 10 million infections each year. Although TB can be effectively treated with antibiotics, because of the complications and length of treatment, many people fail to complete the treatment which exacerbates the emergence of drug-resistant M. tb strains. The goal of this work is to develop biomimetic particles as host-directed therapy to target the infected macrophages. Two types of metal-organic frameworks (MOFs), MIL-100(Fe) and MIL-88A(Fe) were developed for bacteriamimicking particles. As a proof-of-concept, Mannose was selected as a ligand to target macrophages because …

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 …

Aplasia Cutis Congenital Of Scalp With Right Parietal Encephalocele- A Rare Association With Surgical Apropos, Dr. Anshika Tyagi, Dr. Col.T.S. Vasan

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Premature Ejaculation, Dr.Pogula Anusha, Dr.Pranahit Reddy, Dr. Kishor M

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Neonatal Varicella, Dr. Santosh Gunasekaran, Dr.Deepthi Thandaveshwara, Dr. Keerthana Srinivas

Digital Journal of Clinical Medicine

No abstract provided.

Fibroid Uterus, Adiyuga Sharath

Digital Journal of Clinical Medicine

No abstract provided.

Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor first discovered to be activated by exogenous ligands, such as dioxins, and helps promote downstream gene (e.g. CYP1A1) transcription to metabolize the toxicants. With the reports of various AHR targets genes, the expression levels and activities of AHR have been implicated in many physiological and pathological situations. Understanding how AHR protein level is regulated would provide more information to target AHR. AHR stays in the cytosol in the absence of ligand in a complex with HSP90, p23 and XAP2. After ligand activation, AHR translocates into the nucleus, fulfilling its transactivation function …

Immunostimulatory Membrane Proteins Potentiate H. Pylori-Induced Carcinogenesis By Enabling Caga Translocation, Matthew G. Varga, Cecily R. Wood, Julia Butt, Mackenzie E. Ryan, Wei-Cheng You, Kaifeng Pan, Tim Waterboer, Meira Epplein, Carrie L. Shaffer

Veterinary Science Faculty Publications

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, …

Rasburicase Utilization After Protocol Implementation Focused On Fixed Dosing By Limiting Use Of Weight-Based Dosing To Oncology Providers, Dakota Smith Bs, Jamie Gaul Pharmd, Bcps, Liam Dadey Pharmd, Bcps

Parkview Pharmacy Department

Dec 2021 ASHP Midyear Clinical Meeting / Poster

Objective: Evaluate the change in rasburicase use pre- and post-implementation of dosing restriction protocol.

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F) is known to induce inflammation, toxicity, or tumorigenesis, and is a concern in the occupational setting. U. S. facility employees are at risk of inhalation exposure of multi-walled carbon nanotubes and carbon nanofibers during primary and secondary manufacturing. To date, only one MWCNT, Mitsui-7 has been classified as possibly carcinogenic to humans (Group 2B), while all other materials were subsequently categorized as unclassifiable (Group 3). This class of material has recently been listed as a high priority to the International Agency for Research on Cancer due to this significant knowledge gap. Furthermore, …

Development, Optimization, And In Vitro Characterization Of Different Anesthetic Wound Products, Alia Alshammari

Electronic Theses and Dissertations

ABSTRACTAcute and chronic wounds can be a significant source of pain. In the past, pain associated with chronic wounds has been perceived as an inevitable complication of wound care. Fortunately, recent approaches in wound care have developed strategies to prevent and reduce pain when carrying out wound care. Local anesthetics have been used to that end. Lidocaine is the most widely used topical anesthetic in wound care. However, literature on topical Lidocaine has focused almost exclusively on the clinical application on intact skin. This dissertation aims to advance our understanding of anesthetic wound product formulation and development. Anesthetic wound ointments …

Sleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregiverssleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregivers, Sushmitha Inguva

Electronic Theses and Dissertations

This dissertation aimed at filling gaps in the body of Parkinson’s disease (PD) and sleep literature by synthesizing and appraising current knowledge on the influence of sleep on health-related quality of life (HRQoL) in persons with Parkinson’s (PWP) and their caregivers, conducting a psychometric evaluation of a HRQoL instrument among PWP, and applying a novel method to assess the dyadic relationship between sleep and HRQoL in PWP and their caregivers. First, the systematic literature review results showed that nocturnal and diurnal sleep problems among PWP are strong predictors of their HRQoL. Additionally, studies that focused on caregiver outcomes showed that …

Synthesis And Evaluation Of Hepatoprotective Effects Of A Tetrahydrocurcumin-Diglutaric Acid Prodrug, Nattapong Jongjitphisut

Chulalongkorn University Theses and Dissertations (Chula ETD)

Alcoholic liver disease (ALD) is a significant public health problem worldwide. Numerous natural molecules, including curcumin, have been extensively studied as potential treatment agents for ALD. Tetrahydrocurcumin (THC), the reductive metabolite of curcumin, was previously reported to exert the potent antioxidant activity against chemical-induced oxidative stress suggesting the potential of THC to be used as a protective agent for ALD. However, THC has poor water solubility limiting its pharmacological activity. In the present study, tetrahydrocurcumin-diglutaric acid (TDG) was synthesized. The solubility of TDG at pH 6.8 was higher than THC approximately 20 times with a logP value of 3.03. TDG …

Development Of Fenofibrate/Cyclodextrin Complex Loaded Eudragit Nanoparticles For Ocular Delivery, Soe Yadanar Khin

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purpose of this study was to develop Eudragit® -nanoparticles (NPs) eye drop formulations containing fenofibrate (FE) for diabetic retinopathy and age-related macular degeneration. Due to the limited aqueous solubility of FE, it may hamper the ocular bioavailability and results in low efficiency to treat such diseases. Hence, the increased solubility of FE was determined by complexation with cyclodextrins (CDs) and CD derivatives The solubility determination was evaluated by phase-solubility technique with heating method. Among CD tested, randomly methylated-b-CD (RMbCD) exhibited the best solubilizer with the highest complexation efficiency for FE. Moreover, the water-soluble polymer i.e., Soluplus® (SOL), poloxomer 407 …

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 …

The Characterization Of Purified Citrate-Coated Cerium Oxide Nanoparticles Prepared Via Hydrothermal Synthesis, Matthew L. Hancock, Robert A. Yokel, Matthew J. Beck, Julie L. Calahan, Travis W. Jarrells, Eric J. Munson, George A. Olaniyan, Eric A. Grulke

Chemical and Materials Engineering Faculty Publications

Hypothesis

Cerium oxide nanoparticles were synthesized using a hydrothermal approach with citric acid as a stabilizing agent. Citric acid adsorption onto the nanoceria particle surface can cease particle formation and create a stable dispersion for an extended shelf life. The product was dialyzed immediately following the synthesis to remove unreacted cerium that could contribute to biological effects. Nanoparticle characterization results are expected to help identify the surface citrate bonding structure.

Experiments

Many characterization techniques were utilized to determine size, morphology, surface properties, and citrate complexation on the nanoceria particle surface. These included transmission electron microscopy, electron energy loss spectroscopy, dynamic …

Research News, Publications, 2021, Volume 4, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period of October 1 through December 31, 2021