Chemicals and Drugs Commons^™

The Involvement Of Estrogen Receptors In Astrocyte Survival, Lauren M. Johnson

Theses and Dissertations

Estrogens are a class of hormones that are demonstrated to be neuroprotective. The levels of estrogen in the body decline during menopause which can cause a variety of symptoms. Hormone replacement therapy (HRT) is a treatment option for menopause, however, it has been demonstrated to have adverse side effects. Of the treatment options for adverse side effects of HRT, Selective estrogen Down-regulators do not appear to have an agonist effects on estrogen receptors while Selective estrogen receptor Modulators do. The aim of this study was to determine the role that estrogen receptors play in the survival of astrocytes when placed …

Human Anatomy And Physiology Preparatory Course: Part 1 Of 4 (Interactive), Carlos Liachovitzky

Open Educational Resources

The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).

The entire course has four parts:

• Part 1
• Part 2
• Part 3
• Part 4

Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.

The organization and …

Contraceptive Provision To Adolescent Females Prescribed Teratogenic Medications., Stephani L. Stancil, Melissa K. Miller, Holley Briggs, Daryl Lynch, Kathy Goggin, Gregory Kearns

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population.

METHODS: A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic …

Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle

Articles

Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …

Understanding Dna Condensation By Low Generation (G0/G1) And Zwitterionic G4 Pamam Dendrimers, Min An

Theses and Dissertations--Chemistry

Cationic polymers have shown potential as gene delivery vectors due to their ability to condense DNA and protect it from cellular and restriction nucleases. Dendrimers are hyperbranched macromolecules with precisely defined molecular weights and highly symmetric branches stemming from a central core. The nanosize, tunable surface chemistries and ease of surface functionalization has made dendrimers an attractive alternative to conventional linear polymers for DNA delivery applications. The commercially available, cationic dendrimer poly(amidoamine) or PAMAM is the most widely studied dendrimer for use as a gene delivery vector. The aim of this dissertation is to provide an increased understanding of the …

Artemisinin Production By Plant Hairy Root Cultures In Gas- And Liquid-Phase Bioreactors, Nivedita Patra, Ashok K. Srivastava

Articles

Key message

Alternative biotechnological protocol for large-scale artemisinin production was established. It featured enhanced growth and artemisinin production by cultivation of hairy roots in nutrient mist bioreactor (NMB) coupled with novel cultivation strategies.

Artemisinin is used for the treatment of cerebral malaria. Presently, its main source is from seasonal plant Artemisia annua. This study featured investigation of growth and artemisinin production by A. annua hairy roots (induced by Agrobacterium rhizogenes-mediated genetic transformation of explants) in three bioreactor configurations—bubble column reactor, NMB and modified NMB particularly to establish their suitability for commercial production. It was observed that cultivation of …

Design And Testing Of An Ehr-Integrated, Busulfan Pharmacokinetic Decision Support Tool For The Point-Of-Care Clinician., Susan M. Abdel-Rahman, Matthew L. Breitkreutz, Charlie Bi, Brett J. Matzuka, Jignesh Dalal, K Leigh Casey, Uttam Garg, Sara Winkle, J Steven Leeder, Jeanann Breedlove, Brian Rivera

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Busulfan demonstrates a narrow therapeutic index for which clinicians routinely employ therapeutic drug monitoring (TDM). However, operationalizing TDM can be fraught with inefficiency. We developed and tested software encoding a clinical decision support tool (DST) that is embedded into our electronic health record (EHR) and designed to streamline the TDM process for our oncology partners.

METHODS: Our development strategy was modeled based on the features associated with successful DSTs. An initial Requirements Analysis was performed to characterize tasks, information flow, user needs, and system requirements to enable push/pull from the EHR. Back-end development was coded based on the algorithm …

Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky

Manuscripts, Articles, Book Chapters and Other Papers

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by …

Novel Spoxazomicins Derived From Streptomyces Sp. Rm-14−6 Attenuate Ethanol Induced Cytotoxicity In Vitro, Meredith A. Saunders

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol use disorder. Ultimately, chronic alcohol use may result in neurological deficits, with up to 85% of alcoholics exhibiting signs of cognitive decline. However, biochemical and behavioral factors contributing to this decline have remained elusive. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about mechanisms underlying these deficits and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for alcohol use disorders in a rodent organotypic hippocampal slice culture mode. Experiment 1 sought …

The Identification Of The Direct And Indirect Pathways Through Which Leptin Facilitates Synaptic Plasticity In The Hippocampus, Catherine Van Doorn

Theses and Dissertations

Leptin, a peptide synthesized by adipocytes in the periphery, has been shown to play significant roles in feeding and energy expenditure mediated by the hypothalamus. Growing evidence supports the role of leptin in influencing synaptic plasticity in the hippocampus in that leptin dose-dependently enhances LTP, alters morphology and neurogenesis, facilitates spatial learning and memory, as well as memory retention. Models of leptin deficiency and resistance have further supported the importance of leptin in synaptic plasticity by exhibiting deficits in electrophysiological, morphological and behavioral tests that are improved after leptin restoration. The effects of leptin when applied directly into the hippocampus …

Morphogenic Effects Of Dopamine In Cultured Rat Hippocampal Astrocytes, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and addictive behaviors brought about by drugs of abuse. Scientific investigation of drugs of abuse and their effects on CNS function has traditionally been directed at understanding the role of neurons. However, astrocytes, which constitute approximately half of all human brain cells, play a dynamic role in many essential nervous system functions, including neurotransmission, ion homeostasis, and immune defense. Dopamine effects on astrocytes have been historically understudied, yet research indicates that astrocytes express dopamine receptors and are sensitive to dopaminergic activity. Importantly, astrocytes, comprise a morphologically heterogeneous population of cells, and a distinction …

The Role Of Epidermal Stem/Progenitor-Like Cells In Hpv-Mediated Pre-Neoplastic Transformation, Yvon L. Woappi

Theses and Dissertations

The role of epidermal basal stem cells in dysplasia is a matter of great interest in the human papillomavirus (HPV)-driven cancers. To assess the relationship between “stemness” and HPV-mediated transformation, we made use of 3-D suspension culture and fluorescence activated cell sorting (FACS) to purify stem/progenitor-like cells from primary normal human keratinocyte (NHKc) cultures. We found that NHKc cells derived from multicellular keratinocyte spheroids were enriched for a basal subpopulation of epidermal stem-like cells, that could be maintained for prolonged time in culture and used to conduct transfection experiments with full-length HPV16 DNA. Thus, by using these stem cell enrichment …

Deciphering The Interacting Regions And Functions Of The Rad51d-Nono Protein Complex During Dna Damage Response, Latarsha Porcher

Theses and Dissertations

Genomic instability is one of the major components represented in the “Hallmarks of Cancer.” DNA interstrand crosslinks and double-stranded breaks are two of the most severe causes of genomic instability. Homologous recombination (HR) plays a major role in resolving both types of DNA lesions, requiring a homologous template and the RAD51 paralog complex of proteins. One member of this complex is the RAD51D ovarian cancer susceptibility gene product. To better elucidate RAD51D modifications and functions, several protein interaction screens were performed, and one of the novel proteins identified was NONO (a.k.a. p54nrb). Decreased expression of either RAD51D or NONO conferred …

Differences In Resting-State Functional Connectivity Of Chronic Migraine, With And Without Medication Overuse Headache, And The Effectiveness Of Sphenopalatine Ganglion Block As A Treatment For Repairing Dysfunctional Connectivity., Kaitlin Krebs

Theses and Dissertations

Chronic Migraine (CM) is a debilitating neurological condition that occurs when the migraine frequency progresses to a chronic state of more than 15 headache days per month. The overuse of analgesic medication (MOH) is one of the most prominent risk factor of this chronification and little is known about why it is a cause. The repetitive inhibition of the Sphenopalatine Ganglion is one promising treatment that is used to treat chronic migraine. The purpose of this study is to determine if a specific pattern of disruption is present for chronic migraine, both with and without medication overuse headache, and if …

Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma., Bridgette Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Methcathinone Analogue Activity At The Human Serotonin Transporter, William Drake Varn

Theses and Dissertations

In the last few years, there has been continued concern about synthetic drug abuse in both the United States and worldwide. Small adjustments in drug compound structure often allow synthetic drug makers to manufacture a legal product that can produce the same highs as illegal counterparts. Unfortunately, this is happening faster than the government can outlaw the drug compounds, and a wide variety of synthetics are now appearing on the street. This study evaluated the effects on the human serotonin transporter of six different 4-para substituted methcathinone compounds. Using a Xenopus oocyte model, the efficacy of each MCAT analogue …

The Effects Of Testosterone Supplementation On Cognitive Functioning In Older Men, Eka Wahjoepramono, Prita Asih, Vilia Aniwiyanti, Kevin Taddei, Satvinder Dhaliwal, Stephanie Fuller, Jonathan Foster, Malcolm Carruthers, Giuseppe Verdile, Hamid R. Sohrabi, Ralph Martins

Research outputs 2014 to 2021

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer’s disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Can A Metallated Cyclen Species Be Used To Prepare New Odorants?, Jalynn Taylor-Farmer

Undergraduate Research Posters

Scientists in the fragrance industry are constantly searching for new odors to create as well as new, more efficient processes to create them. Scientists mainly look for new ways to synthesize fragrances that will reduce the impact on the environment, produce them at lower costs, produce higher yields, and sometimes to produce a more potent odor [4]. In this research, we investigated the use of metallic macrocycles and/or metal-dioxygen chemistry to prepare new fragrances.

Cyclen (1,4,7,10-tetraazacyclododecane) has significant uses in many pharmaceutical and medicinal research developments such as advances in targeted cancer and Alzheimer’s agents. Macrocyclic amines like cyclen are …