Chemicals and Drugs Commons^™

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 …

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 …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

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.

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 …

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 …

Addressing Antibiotic Resistance From Farm-Raised Fish Imported To The United States, Nicholas Ali

Bard Center for Environmental Policy

Misuse of medically important antibiotics in animal production threatens the effectiveness of drugs that are vital in combating disease and infections. Recently, the FDA implemented regulations to limit the use of and access to veterinary drugs. However, these regulations only affect domestic production operations. Because over 90% of seafood consumed in the U.S. is imported from countries with different regulatory standards and because the U.S. has an import inspection rate of less than 1%, antibiotic resistance stemming from imported aquaculture is still a risk that is not sufficiently accounted for. This research investigates how the U.S. has reacted to 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 …

A Rational Design Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves That Improves Their Impaired Axonal Conduction, Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K. Kinsella, Charles Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran Nolan, J. Oliver Dolly

Articles

K+ channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2′-((5,5′(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2′carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ current activation, and slowed its kinetics. It …

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 …

Metformin And Vitamin B12 Deficiency: Consequences And Patient Monitoring, Kathryn Dietz

Physician Assistant Scholarly Project Posters

• The incidence of type 2 diabetes has been increasing at a rapid rate in the United States.

• Metformin is recommended as the first line treatment to be started at the time of diagnosis in all patients without contraindications and has been associated with vitamin B12 deficiency.

• There are currently no clinical guidelines for the routine monitoring of B12 levels in this population.

• The purpose of this scholarly project is to determine if there are consequences of this deficiency and to make recommendations for screening patients.

• It includes current research that focuses on the pathophysiology of …