Pharmacology, Toxicology and Environmental Health Commons^™

Chemical, Microbial And Safety Profiling Of A Standardized Withania Somnifera (Ashwagandha) Extract And Withaferin A, A Potent Novel Phytotherapeutic Of The Millennium, Pawan Kumar, Samudra P. Banik, Apurva Goe, Sanjoy Chakraborty, Manashi Bagchi, Debasis Bagchi

Publications and Research

Background:Withania somnifera (L.) Dunal, popularly known as Ashwagandha, is an ethnomedicinal plant with multiple pharmacotherapeutic applications. The diverse medicinal properties of the plant are largely due to the presence of withanolides, a group of C28 ergostane based steroidal lactones, with several sites of unsaturation and oxygenation. Withaferin A, a major with anolide present in Ashwagandha plant accounts for its emerging new roles to treat cancer, arthritis, inflammatory responses, immunomodulatory properties, and neuronal disorders. The root and leaf extracts are specifically important constituent materials for the development of phytotherapeutics, mostly intended for oral consumption. Several studies have been carried out …

Effects Of Combined Ethanol And Nicotine Administration On Delay Discounting In Male And Female Sprague-Dawley Rats, Rebecca Lillian Chalme

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ethanol (EtOH) and nicotine (NIC) are among the most commonly used and co-used drugs in the world. Co-use occurs in people who use one or both drugs chronically, but also in people who only consume one or both drugs acutely, often in a “bingeing and chipping” pattern. Given that each drug on its own has previously been shown to affect impulsive choice in delay-discounting procedures, with some indication that drug effects could vary by sex, the purpose of the present experiments was to investigate effects of combined EtOH and NIC at a range of dose combinations on delay discounting in …

Detection And Observed Correlations Of Statin And Beta-Blocking Pharmaceuticals In West Virginia Surface Waters And Ichthyofauna, Joseph W. Kingsbury

Graduate Theses, Dissertations, and Problem Reports (ETD)

Within this thesis the source, presence, and the estimated ecotoxicological effects of cardiovascular medicines, specifically statins and beta-blockers are described within the Buckhannon, Tygart Valley, and West Fork Rivers of West Virginia. Included within this thesis is a general introduction providing key background information and relevant research related to the source, presence, and known toxicity of statins and beta-blockers. Following the general introduction there are 3 distinct chapters. Chapter 1 focuses on the estimated demographic based source loadings and the surface water concentration characteristics of statins and beta-blockers within the three rivers. Chapter 2 investigates the effects of statins and …

The Role Of Platelet-Activating Factor And Microvesicle Particles In Intoxicated Thermal Burn Injury-Induced Multiple Organ Failure, Rushabh Pawan Lohade

Browse all Theses and Dissertations

Intoxicated thermal burn injury (ITBI) is more severe than thermal burn injury (TBI) alone and causes significant morbidity and mortality. Evidence from mouse models that replicate the human condition of multiple organ dysfunction has been informative. ITBI results in enhanced bacterial translocation from the gut, increased levels of proinflammatory mediators, and immune cell infiltration in various organs, resulting in inflammation in multiple organs with subsequent dysfunction. In addition, ITBI induces delayed systemic immunosuppression. To understand the mechanism(s) underlying ITBI-induced inflammation and damage in multiple organs, we investigate the role of Platelet-activating factor (PAF) and subcellular microvesicle particles (MVPs) in this …

Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad

Browse all Theses and Dissertations

Cathepsin L is a lysosomal cysteine protease that is encoded by the CTSL gene in humans. Previous results have shown that CTSL expression and activity towards the DNA repair protein XPA are elevated in lysates of confluent/quiescent HaCaT keratinocytes. Because other nuclear proteins, including 53BP1 and histone H3, have also been reported to be CTSL substrates under conditions of cell differentiation, senescence, or quiescence, CTSL expression and activity (cleavage) of multiple nuclear proteins was examined in lysates from HaCaT cells and other cell lines at various days after plating and cell confluency. Our study found that adding CTSL inhibitors to …

Characterization Of Atr Kinase Function In Quiescent Human Keratinocytes When Exposed To Solar Simulating Uv Radiation, Hrishikesh Tryambak Kadam

Browse all Theses and Dissertations

Cell cycle control, DNA repair, and cell survival have all been linked to the ataxia-telangiectasia and Rad3-related (ATR) kinase, a vital part of the DNA damage response system. In this work, we looked at the role of ATR kinase in human keratinocytes that were dormant and exposed to solar simulating light (SSL). Our findings demonstrated that SSL activates the ATR kinase, phosphorylating downstream substrates such as KAP1, Chk2, and H2AX. In addition, we noticed that quiescent keratinocytes exposed to SSL experienced a decrease in viability when ATR kinase activity was inhibited. Our research indicates that in quiescent keratinocytes exposed to …

Validation Of A Cell Line Model For Studying Xpd Protein Function In Nucleotide Excision Repair, Naga Swathi Sree Kavuri

Browse all Theses and Dissertations

The various environmental factors like toxic chemicals, chemotherapeutic agents and UV radiation impact human health by altering physiological functions of the normal living cells. One of the main consequences of exposure to these factors is DNA damage. Although, living system have inherent DNA repair mechanisms such as Nucleotide Excision Repair (NER), which removes DNA lesions from the genome in the form of small, approximately 30-nt-long DNA oligonucleotides. The accumulation of unrepaired DNA adducts as a result of this NER deficiency causes a variety of syndromes, including Xeroderma Pigmentosum (XP), Cockayne Syndrome, Neurological syndrome, and carcinoma of skin. To understand more …

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

Browse all Theses and Dissertations

Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …

Differences In Drifting Invertebrate Communities Across Arctic Ecozones And The Influence On Potential Growth Of Grayling (Thymallus Arcticus), Charles Chanyi

Theses and Dissertations (Comprehensive)

Invertebrate drift is a key process that potentially affects multiple levels of food web organization within stream environments. However, our understanding of the mechanistic drivers of drift in high latitude streams and subsequent bottom-up control that drift may have on fish predators in these environments remains understudied. This project aimed to gain the baseline knowledge of how drift functions across two major high latitude ecozones, the boreal forest and tundra, and how those possible differences in drifting community characteristics may impact drift-feeding Arctic grayling (Thymallus arcticus). These objectives were accomplished by characterizing stream environments across both ecozones, sampling …

Co-Occurrence Of Marine And Freshwater Phycotoxins In Oysters, And Analysis Of Possible Predictors For Management, Sarah K. D. Pease, Todd A. Egerton, Kimberly S. Reece, Marta P. Sanderson, Michelle D. Onofrio, Evan Yeargan, Adam Wood, Amanda Roach, I-Shuo Wade Huang, Gail P. Scott, Allen R. Place, Amy M. Hayes, Juliette L. Smith

Biological Sciences Faculty Publications

Oysters (Crassostrea virginica) were screened for 12 phycotoxins over two years in nearshore waters to collect baseline phycotoxin data and to determine prevalence of phycotoxin co-occurrence in the commercially and ecologically-relevant species. Trace to low concentrations of azaspiracid-1 and -2 (AZA1, AZA2), domoic acid (DA), okadaic acid (OA), and dinophysistoxin-1 (DTX1) were detected, orders of magnitude below seafood safety action levels. Microcystins (MCs), MC-RR and MC-YR, were also found in oysters (maximum: 7.12 μg MC-RR/kg shellfish meat wet weight), warranting consideration of developing action levels for freshwater phycotoxins in marine shellfish. Oysters contained phycotoxins that impair shellfish health: karlotoxin1-1 and …

The Path To U.S. National Registration Of A Toxic Bait For The Control Of The Small Indian Mongoose, Carmen C. Antaky, Steven C. Hess, Emily W. Ruell, Israel L. Leinbach, Shane R. Siers, Robert T. Sugihara

Human–Wildlife Interactions

The small Indian mongoose (Urva auropunctata [syn. Herpestes auropunctatus]; mongoose) is a highly invasive species in its introduced range that negatively impacts ecosystems. Mongooses depredate native species, serve as a vector of disease posing a risk to human health, and cause sanitation issues in food processing facilities and public areas. Introduced for biocontrol in the late 1800s in Hawaiʻi and the Caribbean, mongooses currently have well-established populations across multiple islands in both island archipelagos and have invaded numerous other locations throughout the world. The concern of accidental introduction to mongoose-free islands, the difficulty in species detection, and the …

An Exploration Of The Causes And Effects Of Interpersonal Conflict Related Stress Among A Self-Selected Cohort Of Second Level Teachers In Ireland, Patrick Bruce

Theses

Teaching has been classified by researchers as a high stress profession. Stress in teaching has been reported to have many negative health outcomes and also affects productivity. The literature also reports that stress in teaching is a difficult matter to resolve satisfactorily, with mixed outcomes from interventions. An emergent cause of work-related stress in education is IPC and this study sets out to investigate the prevalence of this underreported phenomena.

A sample of 25 teachers working in Irish second level schools were recruited. Semi structured interviews were conducted to report on the experiences of stress, it’s causes and effects both …

Mitigation Of Nicotine Reward And Withdrawal By The N-Acyl Amino Acids: N-Oleoyl Glycine And N-Oleoyl Alanine, Kimberly Karin

Theses and Dissertations

A growing body of research is exploring the efficacy of N-acyl amino acids (N-oleoyl glycine; OlGly and N-oleoyl alanine; OlAla) in rodent models of drug reward and dependence. In particular, OlGly attenuated the reinforcing effects of nicotine in the mouse nicotine-induced conditioned place preference (CPP) paradigm and reduced somatic and affective signs of mecamylamine-precipitated withdrawal in nicotine-dependent mice. Based on the addition of a methyl group on the head group, OlAla was proposed to have increased metabolic stability compared to OlGly. While OlAla has been assessed in assays of reward and withdrawal of opioids, cocaine, and …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Effect Of Spinach Enriched With Zinc And Ω-3/Vitamin E Treatment Against Fluoride-Induced Nephrotoxicity And Bone Calcification Disturbance In Rats, Anfal Djouadi, Samir Derouiche

The Thai Journal of Pharmaceutical Sciences

Objective: The goal of this study was to evaluate the alone or associated spinach, zinc, and ω-3/Vitamin E capacity to improve the renal function and bone calcification altered by fluoride in Wistar rats. Methods: In this study, 36 female Wistar albino rats were used; divided into six groups (n = 6); all groups except the control rats received orally 400 ppm of fluoride as sodium fluoride (NaF) in drinking water during 70 days and then four groups treated in the past 15 days by: Spinach powder, zinc, ω-3/Vitamin E, and spinach+ zinc + ω-3/Vitamin E. Some biochemical and histological markers …

The Efficacy Of Vitamin B6 And Alpha-Lipoic Acid In Preventing Levetiracetam Depressant-Like Behavior In Mice, Azadeh Mesripour, Nasime S. Musavie

The Thai Journal of Pharmaceutical Sciences

Background: Some antiepileptic drugs for instance levetiracetam cause depression in patients. Vitamin B6 is a cofactor involved in the neurotransmitter synthesis. α-Lipoic acid (ALA) is a mitochondrial cofactor that can prevent neuronal damage. The aim of this study was to evaluate the effectiveness of B6 and ALA for preventing levetiracetam depression in mice. Methods: Male NMRI mice (weighing 25 ± 3 g) were used. Levetiracetam (20 mg/kg), and pretreatments with ALA (20, 40 mg/kg), Vitamin B6 (100 mg/kg), or imipramine (10 mg/kg) as the control positive were all administered intraperitonealy for 14 consecutive days. The locomotor test and forced swimming …

Barriers And Facilitators Of Wound Care Services Provided By Community Pharmacists In Selangor, Malaysia: An Exploratory Qualitative Study, Hamidi Drahman, Mohd Shahezwan Abd Wahab, Mohd Faiz Mustaffa, Azyyati Mohd Suhaimi

The Thai Journal of Pharmaceutical Sciences

Introduction: Community pharmacists (CPs) are often the first point of contact for patients to obtain health-related advice, including on wound management. Wound care services have been proposed as a community pharmacy practice area to be promoted in Malaysia. Objectives: This study aims to explore the types of wound care services provided by Malaysian CPs, and the factors associated with its provision. Methods: This study utilized the qualitative method to collect in-depth information about the barriers and facilitators associated with the provision of wound care services among a sample of CPs. Interview transcripts were analyzed using thematic content analysis. Results: Twenty-three …

Comparing The Microbiomes Of Dental Plaques In 19th Century Ancestral Remains, Ananya Udyaver

UROP Posters

During the construction of VCU’s Hermes A. Kontos Medical Sciences Building in April 1994, nineteenth century ancestral remains were found in an abandoned well on the Medical College of Virginia (MCV) campus. This well, now known as the East Marshall Street Well (EMSW), is thought to have been used as a disposal location for cadaver dissection for surgical and other medical waste in the past. VCU is now seeking to use DNA sequencing technology to match and assemble bones from each individual for a proper burial, uncover the cultural and historical context in which these people lived, and bring a …

Promoting Healthier Treatment Outcomes In Obese Cancer Patients Taking High Dose Methotrexate, Carly Dell'ova

Walden Dissertations and Doctoral Studies

Cancer and obesity rates continue to rise, creating enormous public heath burdens to the individual and at the national and global levels, reducing quality of life, and increasing spending. Moreover, the relationships between cancer and obesity are not well understood. A commonly used chemotherapy for several types of cancer is high dose methotrexate (HDMTX). Along with chemotherapy, especially at high doses, comes toxicity to specific organs and the entire body. However, limited research has been conducted on obese cancer patients as they are often excluded from clinical studies. Practitioners need to better understand how to dose these patients to provide …