Chemicals and Drugs Commons^™

The Mechanism Of Cirp In Inhibition Of Keratinocytes Growth Arrest And Apoptosis Following Low Dose Uvb Radiation, Yi Liao, Jianguo Feng, Yi Zhang, Liling Tang, Shiyong Wu

United States Food and Drug Administration: Publications

UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm²), but not high dose (50 mJ/cm²), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and …

Monitoring Harm Perceptions Of Smokeless Tobacco Products Among U.S. Adults: Health Information National Trends Survey 2012, 2014, 2015, Shari P. Feirman, Elisabeth A. Donaldson, Mark Parascandola, Kimberly Snyder, Cindy Tworek

United States Food and Drug Administration: Publications

Introduction: Changes to the U.S. smokeless tobacco landscape in recent years include a change to health warnings on packages, the implementation of bans in some stadiums, and the launch of a federal youth pre- vention campaign. It is unclear whether such changes have impacted consumer beliefs about smokeless tobacco. This study examines relative harm perceptions of smokeless tobacco compared to cigarettes among adults and assesses changes in smokeless tobacco harm perceptions over time.

Methods: We analyzed data from three cycles (2012, 2014, 2015) of the Health Information National Trends Survey (HINTS). Using 2015 data, we assessed bivariate associations between smokeless …

Garlic Inhibits Inflammation During Dengue Infection, Alex R. Hall

Theses and Dissertations

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. There has been a recent global trend of increased epidemic activity, and DENV infection is considered a serious emerging health problem worldwide. A relatively unexplored approach to develop new treatments for dengue virus infection and the prevention of severe disease development is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during the host response to dengue virus infection. Several studies have proposed that it is the oxidative stress response induced by dengue virus infection that is responsible …

Functional Role Of The Homeobox Transcription Factor Six1 In Neoplastic Transformation Of Human Keratinocytes, Maria Hosseinipour

Theses and Dissertations

The homeobox transcription factor SIX1 contributes to both tumor development and progression. Numerous studies have determined that the inappropriate expression of embryonic genes, in particular transcription factors, contributes to carcinogenesis. SIX1 is essential for the development of numerous organs including the auditory and olfactory system as well as the kidney, by promoting proliferation, survival and migration of progenitor cells during embryogenesis. SIX1 has also been shown to increase cancer cell proliferation, survival and invasion. The aberrant expression of SIX1 occurs in numerous adult and pediatric cancers. We have previously determined that our in-vitro model system for HPV16-mediated tumorigenesis shares many …

Individual Differences In Markers Of Cholinergic Signaling Correlating To Fear And Extinction Learning, Grace C. Jones

Theses and Dissertations

Posttraumatic stress disorder (PTSD) results when individuals are exposed to a life threatening event, assault, serious injury, or other traumatic incident. Individuals with PTSD are impaired in their ability to extinguish fear memories, resulting in intrusive symptoms that impair their ability to live otherwise healthy lives. It remains unclear why some individuals exposed to traumatic events develop PTSD while others do not. Acetylcholine has been shown to play a critical role in fear learning, but its role in fear extinction is not well understood. This study utilized a rat model of fear learning and extinction to determine if individual differences …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Molecular Modeling Of Novel Tryptamine Analogs With Antibiotic Potential Through Their Inhibition Of Tryptophan Synthase, Jared Schattenkerk

CMC Senior Theses

The growing prevalence of antibiotic-resistant bacteria is a global health crisis that threatens the effectiveness of antibiotics in medical treatment. Increases in the number of antibiotic-resistant bacteria and a drop in the pharmaceutical development of novel antibiotics have combined to form a situation that is rapidly increasing the likelihood of a post-antibiotic era. The development of antibiotics with novel enzymatic targets is critical to stall this growing crisis. In silico methods of molecular modeling and drug design were utilized in the development of novel tryptamine analogs as potential antibiotics through their inhibition of the bacterial enzyme tryptophan synthase. Following the …

Vitamin D Deficiency And Suicide, Miriam Salamon

The Science Journal of the Lander College of Arts and Sciences

Vitamin D deficiency, in an increasingly modernized world, is a major global health issue and so is major depressive disorder (MDD) and its high fatality risk. Studies suggest that there may be a connection between the two. Several studies have found a connection between low levels of vitamin D and higher rates of major depressive disorder, depressive symptoms and suicidal ideation. Specifically, lower concentrations of vitamin D was seen in the subgroup of patients with suicidal thoughts when comparing with non-suicidal depressed patients. A likely reason for this may be the well- researched role vitamin D plays in regulation of …

Luteinizing Hormone And Alzheimer’S Disease: Impact And Possibilities Of Treatment, Rachel Walkin

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a common neurodegenerative disease that is the 6th leading cause of death in the United States. An estimated 5 million Americans are afflicted nationwide and the cost to the economy is valued at 259 billion dollars. Additionally, unlike other major causes of death in the United States, there is no treatment for Alzheimer’s Disease. Alzheimer’s is a progressive disease and it is strongly tied to aging. In most cases symptoms make their first appearance in the late 60’s and gradually worsen, eventually leading to a loss of cognitive function and death. The two outstanding changes in the …

Toward Biochemical Conversion Of Lignocellulose On-Farm: Pretreatment And Hydrolysis Of Corn Stover In Situ, Alicia A. Modenbach, Sue E. Nokes, Michael D. Montross, Barbara L. Knutson

Biosystems and Agricultural Engineering Faculty Publications

High-solids lignocellulosic pretreatment using NaOH followed by high-solids enzymatic hydrolysis was evaluated for an on-farm biochemical conversion process. Increasing the solids loadings for these processes has the potential for increasing glucose concentrations and downstream ethanol production; however, sequential processing at high-solids loading similar to an on-farm cellulose conversion system has not been studied. This research quantified the effects of high-solids pretreatment with NaOH and subsequent high-solids enzymatic hydrolysis on cellulose conversion. As expected, conversion efficiency was reduced; however, the highest glucose concentration (40.2 g L^-1), and therefore the highest potential ethanol concentration, resulted from the high-solids combined pretreatment …

Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.

Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.

Results: Our analyses included 698 …

A Comparison Of Sex Differences In Psychotropic Medication Use In Older People With Alzheimer's Disease In The Us And Finland, Daniela C. Moga, Heidi Taipale, Anna-Maija Tolppanen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, Qishan Wu, Gregory A. Jicha, Danijela Gnjidic

Pharmacy Practice and Science Faculty Publications

Aims—Given the high prevalence of psychotropic medication use in people with dementia and the potential for different prescribing practices in men and women, our study aimed to investigate sex differences in psychotropic medication use in older adults with Alzheimer’s disease (AD) living in the US and Finland.

Methods—We used data collected between 2005 and 2011 as part of the National Alzheimer’s Coordinating Center (NACC) in the US, and Medication use and Alzheimer’s disease (MEDALZ) cohorts in Finland. We evaluated psychotropic medication use (antidepressant, antipsychotic, anxiolytic, sedative, or hypnotic) in participants aged 65 years or older. We employed multivariable …

Localization Of Fam171b Mrna Expression In Mouse Brain Using In-Situ Hybridization, Ashani Kumudika Sudasinghe

All Graduate Theses, Dissertations, and Other Capstone Projects

Proteins containing polyglutamine (polyQ) tracts within their primary amino acid sequence are particularly interesting because expansion mutation within them has been shown to underlie a growing list of severe neurodegenerative disorders including Huntington's Disease and several types of Spinocerebellar Ataxias. FAM171B is a novel polyQ protein that was originally identified via large scale sequencing efforts. However, to date, very little is known regarding its normal cellular function and expression pattern. In this study, in situ hybridization was utilized to assess whether FAM171B is expressed in developing (postnatal days 7, 21, 42) and adult mouse brains. The results of the experiments …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

Expression Of Fam171b Protein In Mouse Brain Tissue, Quan Tran

All Graduate Theses, Dissertations, and Other Capstone Projects

Polyglutamine (polyQ) diseases are inherited fatal neurodegenerative disorders caused by expansion of trinucleotide cytosine-adenine-guanine (CAG) repeats, encoding abnormally long glutamine tracts in respective disease proteins. Currently, there are nine polyQ diseases- including Huntington’s disease and a number of Spinocerebellar ataxias. Interestingly, expanded polyQ proteins are prone to aggregate, and this aggregation may underlie neurodegeneration. In this study, we investigate the expression and localization of FAM171B (a novel polyQ protein) in the brain. Western blotting reveals that FAM171B protein is indeed expressed in the developing and adult mouse brain. Furthermore, immunohistochemical analyses suggests widespread localization of FAM171B to many brain regions …

All-Cause Mortality In Hiv-Positive Adults Starting Combination Antiretroviral Therapy: Correcting For Loss To Follow-Up, Nanina Anderegg, Leigh F. Johnson, Elizabeth Zaniewski, Keri N. Althoff, Eric Balestre, Matthew Law, Denis Nash, Bryan E. Shepherd, Constantin T. Yiannoutsos, Matthias Egger

Publications and Research

Objective: To estimate mortality in HIV-positive patients starting combination antiretroviral therapy (ART) and to discuss different approaches to calculating correction factors to account for loss to follow-up.

Methods: A total of 222 096 adult HIV-positive patients who started ART 2009–2014 in clinics participating in the International epidemiology Databases to Evaluate AIDS collaboration in 43 countries in sub-Saharan Africa, Asia Pacific, Latin America, and North America were included. To allow for underascertainment of deaths due to loss to follow-up, two correction factors (one for the period 0–6 months on ART and one for later periods) or 168 correction factors (combinations of …

Anti-Inflammatory And Immune-Modulating Effects Of Rice Callus Suspension Culture And Blueberry Extract On An In-Vitro Inflammatory Bowel Disease Model, Kyle Michael Driscoll

Dissertations, Master's Theses and Master's Reports

Rice Callus Suspension Culture (RCSC) has been shown to exhibit potent anticancer activity in vitro. In this study we aimed to investigate the anti-inflammatory and immune-modulating properties of RCSC on three inflamed normal colon epithelial cell lines, InEpC, NCM 356, and CCD 841 CoN. As a comparative, we additionally analyzed the anti-inflammatory effects of Highbush blueberries on two inflamed colon cell cultures, NCM 356 and CCD 841 CoN. Furthermore, we sought to characterize the bioactive compounds in RCSC responsible for anti-cancer, anti-inflammatory, and immune-modulating effects. This work will be an essential starting point for understanding and identifying possible bioactive …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Multiple Targets For Novel Therapy Of Fsgs Associated With Circulating Permeability Factor., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Genochi, Ram Sharma, Tarak Srivastava, Amna Ilahe, Pooja Budhiraja, Aditi Gupta, Ellen T. Mccarthy

Manuscripts, Articles, Book Chapters and Other Papers

A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A …

Anti-Inflammatory And Neuroprotective Role Of Natural Product Securinine In Activated Glial Cells: Implications For Parkinson’S Disease, Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J. Lithgow, Julie K. Andersen, Shankar J. Chinta

Faculty Publications & Research of the TUC College of Pharmacy

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects …

Piwi Is Required To Limit Exhaustion Of Aging Somatic Stem Cells, Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T. Madden, Victoria V. Lunyak, Heinrich Jasper

Faculty Publications & Research of the TUC College of Pharmacy

Please see the graphical abstract in the supplemental files.

Steroid Hormone Receptors As Prognostic Markers In Breast Cancer, Maggie C. Louie, Mary B. Sevigny

Faculty Publications & Research of the TUC College of Pharmacy

Despite the existence of many promising anti-cancer therapies, not all breast cancers are equally treatable, due partly to the fact that focus has been primarily on a few select breast cancer biomarkers- notably ERα, PR and HER2. In cases like triple negative breast cancer (ERα-, PR-, and HER2-), there is a complete lack of available biomarkers for prognosis and therapeutic purposes. The goal of this review is to determine if other steroid receptors, like ERβ and AR, could play a prognostic and/or therapeutic role. Data from various in vitro, in vivo, and clinical breast cancer studies were examined …

Succination Impairs Protein Folding And Promotes Chop Stability In The Adipocyte During Diabetes, Allison Manuel

Theses and Dissertations

Type 2 diabetes mellitus has been diagnosed in ~21 million people in the United States and is closely correlated with obesity, prompting the need for a detailed understanding of adipocyte metabolism in the development of diabetes. The intake of excess nutrients surpasses the energy requirements of the cell and leads to increased mitochondrial stress in the adipocyte. We have shown that this is associated with increased levels of the mitochondrial metabolite fumarate. Fumarate can react with cysteine thiol groups to form the chemical modification S-(2-succino)cysteine (2SC), also termed protein succination. Succination is significantly increased in the adipose tissue of type …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Assessment Of The Use Of Overdose Education And Naloxone Distribution By Maine Buprenorphine/Naloxone Prescribers, Stephen Kirsch

Muskie School Capstones and Dissertations

Background: Overdose deaths, specifically related to opioids, have been identified as a public health problem both nationally and in the state of Maine. Overdose Education and Naloxone Distribution (OEND) is an innovative model of patient education that has been shown to be effective in increasing knowledge of overdose risk and has the potential to help reduce opiate related overdose deaths.

Methods: A 28-item web-based survey examining clinician attitudes, OEND practices and characteristics was distributed to 196 Maine based physicians with a Drug Enforcement Agency waiver to prescribe burprenorphine/naloxone. Facilitators and barriers to the provision of OEND were also assessed. Surveys …

The Relationship Between Alcohol Use And Familial And Social Influence In College Nursing Students, Darren C. Crooks, Kathleen A. Gillota

Williams Honors College, Honors Research Projects

College students are a population with a high prevalence of risky consumption of alcohol and nursing students, specifically, are no exception. Yet few studies have been done on the use of alcohol in the student-nurse population. Since nursing education and practice are highly stressful, unhealthy coping strategies, such as risky alcohol consumption, are sadly common and seriously detrimental.

This paper explores the self-reported consumption of alcohol in undergraduate nursing students as related to peer, familial, and social influences. Based on the Biopsychosocial Model, many different factors contribute to alcohol use. Using anonymous online survey methodology and convenience sampling, data about …

Lead Content Of Lip Balms: A Cross Sectional Convenience Sample With Exposure Assessment Estimating An Average Daily Intake For Young Children, Julie Grunklee

Dissertations and Theses @ UNI

Lead remains one of the largest environmental toxins affecting children today (Costa, et al., 2004). It is associated with lower IQ, learning difficulties, decreased economic potential and other negative health effects and social behaviors (Kordas et al., 2006). In the United States (U.S.), high amounts of lead remain in and immediately around housing built before 1978 (Tarragó, 2015) as well as a variety of other sources, including cosmetics such as lip balms, that are marketed to the most lead-vulnerable population: young children. Lip balm was found to be the source a lead poisoned child in Minnesota (Minnesota resident, 28 years …

Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott

Theses and Dissertations--Molecular and Cellular Biochemistry

The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation …

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression, Karen Hodgson, Laura Almasy, Emma E. M. Knowles, Jack W. Kent Jr., Joanne E. Curran, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Mary D. Woolsey, Ravindranath Duggirala, Peter T. Fox, John Blangero, David C. Glahn

School of Medicine Publications

Background and aims—While the prevalence of major depression is elevated amongst cannabis users, the role of genetics in this pattern of comorbidity is not clear. This study aimed to estimate the heritability of cannabis use and major depression, quantify the genetic overlap between these two traits, and localize regions of the genome that segregate in families with cannabis use and major depression.

Design—Family-based univariate and bivariate genetic analysis.

Setting—San Antonio, Texas, USA

Participants—Genetics of Brain Structure and Function study (GOBS) participants: 1,284 Mexican-Americans from 75 large multi-generation families and an additional 57 genetically unrelated spouses.

Measurements …

Structure-Function Investigation Of Proteins Involved In Cellulose Biosynthesis By Escherichia Coli, Thomas Brenner

Theses and Dissertations (Comprehensive)

Bacteria thrive within multicellular communities called biofilms consisting of a self-produced matrix. Biofilm matrices improve bacterial adherence to surfaces while creating a barrier from host immune responses, disinfectants, antibiotics and other environmental factors. Persistent colonization by the widely distributed pathogens, Escherichia coli and Salmonella spp., has been linked to production of biofilms composed of the exopolysaccharide cellulose. Cellulose-containing biofilms are also important to Acetobacter, Sarcina, Rhizobium and Agrobacterium species to form symbiotic and pathogenic interactions. In Enterobacteriaceae, two operons (bcsABZC and bcsEFG) are proposed to encode for proteins that form a cellulose biosynthetic complex that spans the …