Pharmacology, Toxicology and Environmental Health Commons^™

The Role Of Diet In Inflammatory Bowel Diseases, Aviva Smilow

The Science Journal of the Lander College of Arts and Sciences

Inflammatory Bowel Disease encompasses two diseases, Crohn’s Disease and Ulcerative Colitis. During the last 70 years the evolving of diet in the industrialized countries has led to the utilization of foods that have been processed rather than those in their more natural original state. This increase in the processing of foods has been correlated with the more recent occurrence of metabolic diseases such as Inflammatory Bowel Disease. Patients suffering from this problem exhibit lesser amounts of anti-inflammatory bacteria such as Roseburia and Faecalibacterium and increased amounts of pro-inflammatory bacteria Escheria and Fusobacterium. Since diet directly alters the composition of the …

Ground Ingredients: Analysis Of Lead Exposure In The California Condor’S (Gymnogyps Californianus) Ground Foraging Habitat, Evan Michael Mcwreath

Graduate Theses, Dissertations, and Problem Reports (ETD)

The California Condor (Gymnogyps californianus) is a critically endangered species that reached its nadir in 1987 with a population of 27 birds in the wild. Intensive management efforts have been implemented to aid the condors’ recovery, however, anthropogenic factors, like use of lead ammunition, continue to cause fatalities in this vulnerable population. Lead toxicosis, which is responsible for approximately 40% of all condor deaths since 1992, is one of the most significant threats to condors. In birds lead poisoning leads to neurological dysfunction, reproductive impairment, immune suppression, gastrointestinal disturbance, anemia, and ultimately increased vulnerability to predation, starvation, and infection. For …

Effects Of E-Cigarette Flavoring Chemicals On Human Macrophages And Bronchial Epithelial Cells, Anna Manzi Morris

Graduate Theses, Dissertations, and Problem Reports (ETD)

E-cigarettes and vapes are relatively new devices which are popular among young adults and teens. These devices vaporize an “e-liquid” for the user to inhale, which typically contains a mixture of propylene glycol (PG), vegetable glycerin (VG), varying concentrations of nicotine, and flavoring chemicals. Due to these flavoring chemicals being intended for ingestion as a food additive, their respiratory health effects are not well understood. Thousands of e-cigarette flavors are available on the market, many of which have the potential for toxicity. The majority of e-liquid flavoring chemicals (ELFCs) have not been tested for inhalation safety. In this study, we …

Metal Nanomaterials: Immune Effects And Implications Of Physicochemical Properties On Sensitization, Elicitation, And Augmentation Of Allergic Disease, Katherine Adair Roach

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many allergenic metals are being manufactured in nanoparticulate forms. Although the decreased size profile of metal nanomaterials has been consistently associated with more pronounced lung toxicity compared to larger materials, it is unclear if metal-induced immunotoxic effects exhibit a similar size-dependency.

The central hypothesis of these studies was that metal nanoparticles cause more pronounced immunomodulatory effects on allergic processes than larger forms of respective metals. Moreover, it was anticipated that, similar to their inflammatory potential in airways, the magnitude of these responses would correlate best with the dose metric of surface area.

The first set of studies utilized fine and …

Behavioral Impairment Following Gestational Exposure To Titanium Dioxide Nanomaterial Aerosols In Male And Female Rats, Matthew Leland Eckard

Graduate Theses, Dissertations, and Problem Reports (ETD)

Engineered nanomaterials (ENMs) are beginning to be recognized as hazardous to human and animal health. Titanium dioxide (TiO2) is primarily used as a whitening agent in paints, plastics, and sunscreens. While relatively inert in its bulk form, nano-TiO2 (diameter) can produce prolonged inflammation and oxidative stress in target tissue. Recently, the potential for nano-TiO2 to cause neuroinflammation and damage has heightened concerns about its continued use. One important concern is that nano-TiO2, and other metal oxide ENMs, may affect fetal neurodevelopment. Accordingly, it is imperative to screen ENMs, like TiO2, for possible neurotoxicity following developmental exposures. The current set of …

The Acute Effect Of Propanil On Reproductive Hormones, Ovarian Gene Expression And Splenic Cells In C57bl/6 Female Mice, Malia Danielle Berg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Earlier evidence indicates exposure to propanil, a post-emergent herbicide used on rice and wheat fields, increases the number of antibody-secreting cells (ASC) in the spleen of mice after immunization with heat-killed Streptococcus pneumoniae (HKSP, 2x10⁸ CFU). Interestingly, an intact hypothalamic-pituitary-gonadal (HPG) axis is required for this immune response assessed on day 7-10 after immunization in female mice. Hence, an overarching premise is that propanil arbitrates the connection between the reproductive and immune system by altering the concentration of hormones involved in the HPG axis, which may then affect the populations of splenic cells. Hypotheses were tested with C57Bl/6 female …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Negative Effects Of Common Herbicides On Non-Target Invertebrates, Debbi Albanese

College of Graduate Studies: Theses & Dissertations

Three herbicide formulations, Roundup® Ready to Use Weed and Grass Killer, Bayer Advanced Southern Weed Killer for Lawns and Pure 20% Vinegar Solution were directly applied to eggs of four species of butterflies, Danaus plexippus, Papilio cresphontes, Papilio polyxenes and Papilio troilus. Roundup and Bayer Advanced containing 2,4-D, mecoprop-p and dicamba significantly reduced hatch success in all four species. Lethal and sublethal effects of these herbicides on the earthworm, Eisenia andrei, was also examined. Direct contact by E. andrei with a heavy dose of the herbicides applied to tops of soil 24 hours prior was lethal to earthworms. …

Synthesis Of N-Heterocyclic Molecules And Their Applicability Towards Ion Sensing: Polymeric Chemosensors, Aikohi M. Ugboya

College of Graduate Studies: Theses & Dissertations

Critical to biological and environmental processes are anions because often times their relative concentration in our body can be an indicator of one’s well-being. Therefore, highly sensitive and cost-efficient methods for ions recognition is necessary for human health. In recent times, polymeric chemosensors have become a vital tool for sensing ions because of its higher sensitivity and good mechanical properties compared to their monomeric counterparts. These sensors are designed to produce a measurable response in the presence of a targeted ion such as an electrochemical or optical signal. The unique structure and the photophysical properties of the 1,2,3-triazole core coupled …

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 …