Pharmacology, Toxicology and Environmental Health Commons^™

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The …

The Impact Of Urbanization On Mosquito-Borne Viruses, Nikhita Puthuveetil

UROP Posters

Mosquito-borne diseases such as yellow fever, dengue, and West Nile are rapidly emerging across the globe. Their emergence is often aided by the growth of their vector population, or the organisms that transmit the virus to the host. Urbanization and land use often destroys the habitat of the virus and its vector. However, the virus and its vector often survive despite the changes to its environment. The goal of this paper is to find out exactly how urbanization and changes in land use affect mosquito-borne viruses and how these viruses survive despite the destruction of their habitats. To understand how …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

Nickel And Copper Mixture Toxicity To Daphnia In Soft Water, Prachi Deshpande

Theses and Dissertations (Comprehensive)

Industrially important metals, such as Cu and Ni, sometimes are present at elevated concentrations in lakes, including those in the Sudbury, ON region. Although they are essential metals, their divalent-cation state (Cu²⁺ and Ni²⁺) can be toxic at high concentrations in the water. The free-ion toxicity of each of these metals has been studied in isolation, but rarely as a mixture. The economic importance of Cu²⁺ and Ni²⁺ makes them essential to study in the context of mixture toxicity. The objectives were to: (1) determine Cu and Ni mixture toxicity to Daphnia through acute LC50 …

Do Toxicity Modifying Factors Influence Acute Or Chronic Toxicity Of Thulium To Hyalella Azteca?, Alexandria H. Loveridge

Theses and Dissertations (Comprehensive)

The industrial demand for rare earth elements (REEs) is growing and as a result, environmental exposure is a concern. Very little is understood about the toxicity of REEs in aquatic environments. The objective of this research is to evaluate the acute and chronic toxicity of Tm and to also understand the toxicity modifying influence of dissolved organic matter (DOM) and cationic competition (Ca2+, Mg2+ and Na+). Furthermore, the aim of this study was to determine linkages between Tm bioaccumulation, growth and survival during chronic exposures. Standard methods (Environment Canada) were followed for both 96h acute and 14d chronic tests, in …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Lifetime And Effectiveness Evaluation Of Ceramic Pot Filters, Carlo Salvinelli

Doctoral Dissertations

"Poor water quality is a major contributing factor to disease in developing countries. Ceramic pot filters (CPFs) represent an effective and sustainable technology for poor communities, but the characterization of CPF lifetimes is on-going, and the water production seems to be the limiting factor. This dissertation describes laboratory and field investigations conducted to characterize the parameters that impact CPF effectiveness and lifetime in terms of water production and treatment efficacy, both under controlled and real use conditions.

CPF initial flow rate is the most common quality control parameter, but it may not be representative of the long-term effectiveness of the …

Validation Of Type 2 Diabetes Risk Variants Identified By Genome-Wide Association Studies In Northern Han Chinese, Ping Rao, Yong Zhou, Siqi Ge, Anxin Wang, Xinwei Yu, Mohamed Ali Alzain, Andrea K. Veronica, Jing Qiu, Manshu Song, Jie Zhang, Hao Wang, Honghong Fang, Qing Gao, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background:

More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population.

Method:

In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January …

Mechanisms Of Pancreatic Beta Cell Dysfunction In Diabetes, Vaibhav Sidarala

Wayne State University Dissertations

Diabetes is a serious medical condition characterized by decreased insulin secretion from pancreatic β-cells and decreased insulin sensitivity in the peripheral tissues, resulting in elevated levels of blood glucose. According to the International Diabetes Federation, about 387 million cases have been reported worldwide in the year 2013 and it is estimated that about 500 million people would be affected by 2050. Type 2 diabetes, which accounts for about 90% of the total number of cases, is caused by decreased insulin sensitivity in the peripheral tissues and decreased glucose-stimulated insulin secretion from the pancreatic β-cells. The underlying mechanisms involved in β-cell …

Neuronal Insult Either By Exposure To Lead Or By Direct Neuronal Damage Cause Genome-Wide Changes In Dna Methylation And Histone 3 Lysine 36 Trimethylation, Arko Sen

Wayne State University Dissertations

Prenatal and postnatal exposure to pervasive neuro-toxicants such as Lead (Pb) has been reported to causes extensive and diverse changes in the epigenetic profile. Among epigenetic modification, DNA methylation (5mC) is perhaps the most widely studied and has been proposed to be potential early biomarkers for Pb toxicity. Several studies have demonstrated the association between Pb-exposure and 5mC. However most of these studies are restricted to looking at a specific set of target genes or repetitive elements. Therefore, one of the main objectives of our study was to use an unbiased genome-wide approach to look at Pb-exposure associated changes in …

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

The Role Of The State, Multinational Oil Companies, International Law & The International Community: Intersection Of Human Rights & Environmental Degradation Climate Change In The 21st Century Caused By Traditional Extractive Practices, The Amazon Rainforest, Indigenous People And Universal Jurisdiction To Resolve The Accountability Issue, Marcela Cabrera Luna

Master's Theses

Local, national and international conventions that protect indigenous sovereignty and their territories, where many of the resources are extracted from by multinational corporations (MNCs) particularly oil, the number one commodity of the world and cause of climate change, continue to be jeopardized because of the lack of a clear international legal framework that can protect them and potentially hold multinationals accountable for their actions. These practices are causing not only environmental issues to the indigenous and surrounding communities, but climate change is in fact, the real human rights issue of the 21^st century and it affects everyone. By using …

The Smell Of Hopelessness, Juline Cariba Rachel Party

Capstones

Rafts of sargassum seaweed kilometers wide have been invading the Caribbean for more than five years, but 2015 was the worst. Tons of seaweed stretch from Texas south to Trinidad and Tobago, with the Lesser Antilles suffering the most damage. Residents near beaches are exposed to an insidious and pernicious danger, scientists say, from fumes that smell like rotten eggs, emitted by the decaying algae. The odor also drives tourists away from beaches and restaurants, and the tourism economy is collapsing.Amid the algae crisis, an elderly woman, Virginie Mark, is trying to survive. She struggles with her health, finances and …

Impact Of Executive Order 13211 On Environmental Regulation: An Empirical Study, Elizabeth Ann Glass Geltman

Publications and Research

A great deal has been written about the Energy Policy Act of 2005 exempting oil and gas operations using hydraulic fracturing from the purview of certain federal environmental laws. Far less attention has been paid to George W. Bush’s Executive Order 13211 (EO 13211), entitled “Actions Concerning Regulations that Significantly Affect Energy Supply, Distribution or Use.” The executive order requires federal agencies to evaluate the impact of federal regulations on “supply, distribution and use of energy.” This study examined the impact of EO 13211 on United States environmental and conservation regulations proposed and promulgated by federal agencies. The study found …

Is Dexamethasone 4mg A More Effective Anti-Emetic Than Dexamethasone 8mg For The Prevention Of Early Post-Operative Nausea And Vomiting In Women Undergoing Laparoscopic Gynecological Surgery?, Steven B. Doyle

Doctoral Projects

Postoperative nausea and vomiting (PONV) is a common problem in the surgical setting. It affects as much as 20 to 80 percent of patients undergoing surgery (D'souza, Swami, & Bhagwat, 2011). PONV can lead to increased patient costs and recovery time by causing the patient to stay in the healthcare facility for a longer period of time. A retrospective cohort study was completed to examine whether or not there was a significant difference between patients who received 4mg and 8mg of dexamethasone in the incidence of PONV. All patients studied received ondansetron intraoperatively as their primary anti-emetic. English speaking patients …

The Effectiveness Of A Preoperative Multimodal Antiemetic Regimen On Reducing Early Postoperative Nausea And Vomiting In Total Joint Arthroplasty Patients, Jerry Mosley

Doctoral Projects

Postoperative nausea and vomiting (PONV) occurs frequently in all types of surgeries including after total joint orthopedic procedures. The resulting PONV can lead to many unwanted occurrences including immobilization, distress, and many serious adverse health complications. These unwanted occurrences may then lead to increased cost to the patient and healthcare facility. Administration of a preoperative multimodal regimen known to reduce PONV has the potential to reduce such unwanted anesthetic side effects influencing a reduction in overall healthcare cost. The purpose of this study is to determine the effectiveness of the preoperative kit which includes the administration of metoclopramide, famotidine, ondansetron, …

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Street Drug Markets Beyond Favelas In Belo Horizonte, Brazil, Elenice De Souza Oliveira, Braulio Figueiredo Alves Silva, Marcos Oliveira Prates

Department of Justice Studies Faculty Scholarship and Creative Works

This study examines whether social disorganization mechanisms that explain clusters of street drug markets in socially disorganized neighborhoods in developed countries can also help explain geographical patterns of drug dealing across neighborhoods in Belo Horizonte, Brazil. Data for this study includes drug arrests from 2007 to 2011 and socio demographic data from the 2010 Census. To examine the influence of exploratory variables on drug market locations, the Negative Binominal regression model was used at two levels of analysis—the Belo Horizonte city center and other neighborhoods including favelas. The findings show that a high hot spot of street drug markets located …

Lead Exposure In Children Through Water And Soil, Sravya Maru

Environmental Management & Risk Assessment (PH 560)

Lead is a metal which has the ability to spread in the earth’s crust and has corrosive property. It is a naturally occurring metal which is soft in nature. Lead exposure in children is through various pathways and the major concentrated sources are the soil and drinking water. Children are most susceptible to lead exposure is due to their growing/developing bodies which are very sensitive to lead. Lead poisoning in children is a preventable environmental disease affecting many children around the world. This paper discusses how soil and water plays a major role in lead exposure to children’s routine life. …