Pharmacology, Toxicology and Environmental Health Commons^™

Functionalized Carbon Nanotubes In Hydrophobic Drug Delivery, Kun Chen

Dissertations

The direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation is presented. The approach is tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that have very different aqueous solubility. It is observed that the f-CNTs dispersed in the water serve as nucleating sites for crystallization and are readily incorporated into the drug particles without altering crystal structure or other properties. The results show that the hydrophilic f-CNTs dramatically enhance dissolution rate for both drugs. The increased degree of functionalization leads to higher hydrophilicity and therefore faster dissolution …

Pyrrolo[2,3-D]Pyrimidine Classical Antifolates For Targeted Cancer Chemotherapy- Applications Of Bioisosteric And Regioisomeric Substitutions For Improved Tumor-Selectivity And Potency, Manasa Punaha Ravindra

Electronic Theses and Dissertations

In 2018, it is estimated that 1,735,350 new cases of cancer and 609,640 deaths from the disease will be diagnosed in the United States alone. Conventional chemotherapy is by far the most successful category of clinical oncology, having cured (complete remission (CR), without return) or provided clinical benefit to millions of people. However, since its earliest discovery, the major causes of failure of conventional cancer chemotherapy have been dose-limiting toxicities and development of resistance. There is a desperate ongoing search for new cancer therapies as tumor-targeted agents (without harming normal cells or tissues) with low propensity for the development of …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Engineering Eden: The World's Attempt To Outsmart Water Scarcity, Kaitlin A. Sullivan

Capstones

Countries around the world are running out of fresh water, 43 already live with water scarcity, requiring more water than they have. In 2015 the global water crisis took first place in The World Economic Forum’s assessment of the risks that will have the most significant impact on economies, environments and people. Water beat out 27 other long-term risks including infectious diseases and weapons of mass destruction. What happened to Crowley County on the plains of Southeastern Colorado is a cautionary tale of borrowed water. It's been called the Detroit of Colorado, decimated by the reliance of a single industry. …

Examining Environmental Hazards In Rental Homes And Habitability Laws In Clark County, Nevada, Jorge Luis Bertran

UNLV Theses, Dissertations, Professional Papers, and Capstones

It is well established that home conditions are linked to the health outcomes of occupants. There are over 880,000 housing units in Clark County, Nevada; nearly half of those are renter-occupied units (ROUs). Currently, there is limited research on the characteristics of environmental hazards found in Clark County ROUs and the strength of habitability statutes created to protect tenants from substandard housing. Understanding how renters in Clark County are affected by environmental hazards in ROUs and the processes by which landlords and tenants resolve grievances related to those hazards would benefit public health. It would enhance the ability to quickly …

Effects Of Ambient Air Pollution On Asthma-Related Emergency Department Visits Within The Las Vegas Metropolitan Area, Loiren E. Monardes

UNLV Theses, Dissertations, Professional Papers, and Capstones

The objective of this research was to evaluate the risk for asthma-related Emergency Department visits and their association with ambient air pollution within the Las Vegas metropolitan area. All data were aggregated by date and ZIP Code. The association was analyzed by applying the distributed lag non-linear model in an attempt to identify elevated concentrations of specific air pollutants

as triggers and their delayed effects (lag days). Relative Risk (RR) and 95% confidence intervals were produced, while adjusting for socioeconomic status. This ecological population-based study analyzed daily asthma counts of Emergency Department visits from January 1st, 2009 to December 31st, …

Development Of Chloroquine-Containing Hpma Copolymers For Drug Delivery, Fei Yu

Theses & Dissertations

Abstract

Development of Chloroquine-containing HPMA Copolymers for Drug Delivery

Fei Yu, Ph.D.

University of Nebraska Medical Center, 2018

Supervisor: David Oupický, Ph.D.

Synthetic polymers have been extensively explored for improved delivery of anticancer agents. Polymers can be designed as either carriers of existing drugs or as polymeric drugs with intrinsic pharmacological activity. Advantages of such polymeric drugs include common positive features of polymer-drug conjugates, such as targeted delivery of drugs, altered pharmacokinetic and biodistribution, improved drug safety, but also favorable pharmacological activities due to multivalent receptor-ligand interactions.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are safe drugs that have been in clinical …

The Opposing Roles Of Glun2c And Glun2d Nmda Receptor Subunits In Modulating Neuronal Oscillations, Zhihao Mao

Theses & Dissertations

N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels consisting of two GluN1 subunits and two other subunits from among GluN2A-2D and GluN3A-3B subunits. NMDARs play critical roles in synaptic plasticity, learning and memory, and higher brain function such as cognition and perception. Dysfunction of NMDARs (hyper-function and hypo-function of NMDARs) are related to various diseases, including stroke, schizophrenia, Alzheimer’s disease, and others. However, to date, NMDARs antagonists have mostly failed in clinical trials due to adverse effects.

NMDARs antagonists replicate the core symptoms of schizophrenia which may underlie its ability to alter neuronal oscillations in the neural circuitry of different brain …

Network Pharmacology-Guided Development Of A Novel Integrative Regimen To Prevent Acute Graft-Vs.-Host Disease, Ming Lyu, Zhengcan Zhou, Xiaoming Wang, Hong Lv, Mei Wang, Guixiang Pan, Yuefei Wang, Guanwei Fan, Xiumei Gao, Benjamin Feng, Yan Zhu

Peer Reviewed Articles

Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing …

Macromolecular-Clustered Facial Amphiphilic Antimicrobials, Md Anisur Rahman, Marpe Bam, Edgar Luat, Moumita Sharmin Jui, Mitra S. Ganewatta, Tinom Shokfai, Mitzi Nagarkatti, Alan W. Decho

Faculty Publications

Bacterial infections and antibiotic resistance, particularly by Gram-negative pathogens, have become a global healthcare crisis. We report the design of a class of cationic antimicrobial polymers that cluster local facial amphiphilicity from repeating units to enhance interactions with bacterial membranes without requiring a globally conformational arrangement associated with highly unfavorable entropic loss. This concept of macromolecular architectures is demonstrated with a series of multicyclic natural product-based cationic polymers. We have shown that cholic acid derivatives with three charged head groups are more potent and selective than lithocholic and deoxycholic counterparts, particularly against Gram-negative bacteria. This is ascribed to the formation …

Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz

Graduate Theses and Dissertations

Biofiltration without pre-ozonation has the capability to remove natural organic matter (NOM) fractions that serve as precursors of disinfection byproducts (DBPs), which include the four regulated trihalomethanes (THMs) and dichloroacetonitrile (DCAN). Rapid small-scale column tests (RSSCTs) and Pilot Plant filters operated at empty-bed contact times (EBCTs) of 4, 8, and 16 minutes were used to evaluate the performance of nutrient-amended (free ammonia and phosphorus) biofiltration for THM and DCAN precursor removal, as measured using formation potential (FP) tests. NOM surrogates – which include dissolved organic carbon (DOC), specific ultraviolet absorbance (SUVA254) and fluorescence-PARAFAC components – were measured weekly throughout the …

Toxicity Of Formulated Insecticide Mixtures To Apis And Non-Apis Bees, Joseph Edward Belsky

Graduate Theses and Dissertations

This work investigates ecotoxicology of new insecticide mixtures to Apis and non-Apis bees. Previous studies have demonstrated the acute and sub-lethal toxicity of individual active ingredient insecticides to honey bees and to a lesser extent non-Apis bees. However, the contact toxicity of formulated premix insecticides containing multiple active ingredients to bees has not been thoroughly assessed. To address this void, laboratory studies simulating exposure to four premix insecticides under different field-realistic scenarios were conducted for two bee species.

Honey bee, Apis mellifera (Linnaeus) contact exposure was examined by simulating three scenarios: (1) when bees continuously forage in a field and …

Watersheds In Planetary Health Research And Action, Aaron Jenkins, Anthony Capon, Joel Negin, Ben Marais, Tania Sorrell, Margot Parkes, Pierre Horwitz

Research outputs 2014 to 2021

Watersheds (also known as water catchments and river basins) are recognised in contemporary science as important natural systems in which to investigate the complex socioecological foundations of health. A watershed is the spatially bound geophysical unit within which surface and shallow groundwater drain to a single collecting stream or river (see appendix). Watersheds are physical and abstract systems: they are open and hydrologically permeable, yet can be represented as functionally distinct. Collectively, watersheds comprise a complex hierarchical network, and thus exemplify the upstream and downstream nature of ecosystems. Watersheds include the social actors, relationships, and institutions located within their boundaries. …

Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush

Electronic Theses and Dissertations

There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than …

Particulate Hexavalent Chromium Does Not Induce Centrosome Amplification In Sperm Whale And Bowhead Whale Cells., Jennifer Haruka Toyoda

Electronic Theses and Dissertations

Hexavalent chromium [Cr(VI)] is a widespread environmental and occupational carcinogen. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the dominant theory. How numerical CIN arises is unclear, but it correlates with centrosome amplification. Both phenotypes are hallmarks of cancers, early events in carcinogenesis, and have been shown to occur after Cr(VI) exposure to human skin and lung fibroblasts. In this study, we investigate numerical CIN and centrosome amplification in whale cells. Whales are our closest marine relatives, have long lifespans, and are exposed to environmental Cr(VI). Importantly, they have low cancer rates and cell culture studies …

The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat

Electronic Theses and Dissertations

Cadmium is present in food and groundwater. Tobacco smoking and occupational exposure are also major sources for cadmium. Cadmium is primarily accumulated in liver, a major organ metabolizing exogenous chemicals. Chemical metabolism may cause detoxification, but it can also cause bio-activation resulting in liver damage. Cytochrome P450s (CYP) are major liver metabolism enzymes, and cadmium chloride (CdCl2) can induce CYP2A5 in mice. We examined the effect of CYP2A5 on CdCl2-induced liver injury using CYP2A5-knockout (cyp2a5-/-) mice. The cyp2a5-/- mice and their control WT mice were injected CdCl2 intraperitoneally at 5 mg/kg body weight, respectively, to induce liver injury. …

The Role Of Cathelicidin In The Regulation Of Gut Microbiota And Inflammasome Activation In Alcoholic Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Alcoholic liver disease (ALD) is characterized by gut dysbiosis and hepatic and intestinal inflammation. Gut microbiota is critically maintained by antimicrobial peptides (AMPs) expressed in the epithelial and immune cells. AMPs are also identified as immune-regulators in various diseases. Previous studies demonstrated that deficiency of AMPs REG3 lectins exacerbated alcoholic steatohepatitis. LL-37 is the sole member of human cathelicidin AMP family, named CRAMP in mouse. Despite of the extensive studies in infectious diseases and in gut-microbiota-related inflammatory bowel disease, the role of LL-37/CRAMP in ALD is yet unknown. Our previous studies showed a decreased intestinal CRAMP in a mouse model …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

Analysis Of Synthetic Opioids In Postmortem Blood, Vitreous Humor, And Brain Tissue, Rachel K. Chesser

Student Theses

In the United States, the use of new synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data is limited and provides challenges to toxicologists. The focus of this project was to examine the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. New methods were developed and validated to quantify 13 synthetic opioids …

Profile Interview With Norman E. Fenn, Shannon L. Castek

Purdue Journal of Service-Learning and International Engagement

Shannon L. Castek is a fourth-generation Boilermaker and fourth-professional-year student in the Purdue University College of Pharmacy. Throughout her time in pharmacy school, Shannon has enjoyed supplementing her curricular work with service-learning activities, participating in health screenings and immunization events with the Purdue chapter of the American Pharmacists Association–Academy of Student Pharmacists. She plans to pursue a pharmacy residency following graduation to achieve her dream of becoming an ambulatory care pharmacist. In this article, Shannon highlights the service-learning endeavors of Dr. Norman Fenn in the College of Pharmacy.

The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh

Purdue Journal of Service-Learning and International Engagement

Christian Egly is a fourth-year (P4) pharmacy student in the Purdue University College of Pharmacy. During his years at Purdue, he worked in labs performing bench research in clinical pharmacology and biochemistry. He plans to work in the pharmaceutical industry after graduation. During his fourth year, he completed rotations in business development at Kashiv Pharma, LLC, and was hired there for an internship in 2017. In the article, Christian describes his personal experiences at Kashiv Pharma, LLC, and how industry can positively affect patient communities.

Consumption Profiles Of Illicit And Neuropsychiatric Drugs In Urban And Rural Communities In Kentucky Using Sewage Epidemiology, Tara Croft, Katelyn Foppe, Rhiannon Huffines, Bikram Subedi

Posters-at-the-Capitol

The drug overdose deaths in the USA increased by ~20% from 2015 to 2016 to the total >63,600 drug overdose deaths in 2016. Kentucky is among the highest rate of drug overdose death states in the USA. The current estimates of the prevalence of substance abuse are based on the self-reported surveys, overdose/toxicological reports, and drug-related crime statistics. Survey-based conventional approaches are not only cost and time-intensive but also underestimate the actual consumption of drugs. As “wastewater never lie,” the drug residues in raw wastewater collected from the centralized wastewater treatment plants were utilized to determine the consumption rate of …

The United States And Canadian System Of Healthcare: A Comparative Study, Mopelola O. Mopelola

University Honors Program

There is a lot to be said about the world of healthcare. The significance of the role our health plays in our lives cannot be overemphasized. The idea of this paper is to explore two of the largest and functional healthcare systems in the world. The purpose of this is because of some key differences between the systems of healthcare that are very important as they relate to the accessibility and availability of healthcare and also the quality of care that is received. The two countries being compared in this paper are the United States and Canada. These countries utilize …

Impact Of Precision Medicine On Drug Repositioning And Pricing: A Too Small To Thrive Crisis, Venkataswarup Tiriveedhi

Biology Faculty Research

The pricing of targeted medicines continues to be a major area of contention in healthcare economics. This issue is further complicated by redefining the role of molecular testing in precision medicine. Currently, whilst pricing of clinical laboratory diagnostics is cost-based, drug pricing is value-based. The pricing for molecular testing is under pressure to change the traditional business model, for it has a critical subsidiary role in determining the final value of targeted medicines. The market size for drugs is reduced by molecular testing when patients with the same disease are stratified based on their genetics, it is critical to determine …

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of …

Assesing Port Reception Facilities For Ship Generated Solid Waste : The Case Of The Port Of Walvis Bay, Namibia., Shapua Randy Mandela Kalomo

World Maritime University Dissertations

No abstract provided.

Resilience Of The Nigerian Coastal Socio-Ecological System : Case Study Of The Niger Delta Region, Chinenye Joy Ijiomah

World Maritime University Dissertations

No abstract provided.

A Qualitative Assessment Of Disability Friendly Water And Sanitation Facilities In Primary Schools, Rumphi, Malawi., Harlod Zaunda, Rochelle H. Holm, Ambumulire Itimu-Phiri, Mphatso Malota, Sian White

Faculty and Staff Scholarship

Students with disabilities commonly face barriers when accessing water and using sanitation and hygiene facilities at school. International frameworks have prompted governments to enact local policies that enshrine these rights, guarantee equitable access to education and mandate inclusive infrastructure. This research was designed to explore whether Malawi has translated good policies into practice. Data were gathered in Rumphi district, Malawi, through structured field observations in ten schools and interviews with students with a disability (n = 23), teachers (n = 11) and government stakeholders (n = 2). No school had facilities that fully meet the needs of students with disabilities, …

Addressing Environmental Gentrification: Improving Environmental Health For Children And Youth Without Displacement, Tania Schusler, Amy Krings

Social Work: School of Social Work Faculty Publications and Other Works

Historically, low income communities and communities of color have borne the brunt of environmental pollution with limited access to environmental amenities. This has arisen, in part, due to marginalized communities’ lack of access and influence in environmental decision making, as well as legacies of racial and ethnic housing segregation (Cole & Foster, 2001). Environmental justice concerns include the disproportionate placement and inequitable regulation of polluting facilities in areas populated by people who are poor and/or racial minorities (Bryant, 1995: Bullard, 1993; Mohai & Bryant, 1992; Lavelle & Coyle, 1992). The inequitable distribution of environmental pollution is especially problematic for children’s …

Isobavachalcone Sensitizes Cells To E2-Induced Paclitaxel Resistance By Down-Regulating Cd44 Expression In Er+ Breast Cancer Cells, Junfeng Shi, Yi Chen, Wenxing Chen, Cuiju Tang, Honghong Zhang, Yuetong Chen, Xiuwei H. Yang, Zhi Xu, Jingsun Wei, Jinfei Chen

Pharmacology and Nutritional Sciences Faculty Publications

Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E₂)‐induced paclitaxel resistance and that E₂ could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E₂ could …