Pharmacology, Toxicology and Environmental Health Commons^™

Re: Pierce Et Al. Diacetyl And 2,3-Pentanedione Exposures Associated With Cigarette Smoking: Implications For Risk Assessment Of Food And Flavoring Workers Crit Rev Toxicol, 2014; 44(5): 420-435, Muge Akpinar-Elci, Omur Cinar Elci

Center for Global Health Publications

We were greatly dismayed by Pierce et al.’ s report on the associations between exposure to Diacetyl and 2,3-pentanedione and cigarette smoking (Pierce et al. 2014). It stated that “ Diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. ” Based on this finding, the authors suggested that “ previous claims of a significant exposure – response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all the cohorts evaluated had considerable smoking …

The Effects That Liquid And Solid Cattle Manure Have On The Water Quality Of Drainage Ditches In Putnam County, Ohio, Janelle Horstman

Honors Projects

Lake Erie has experienced harmful algal blooms with increased frequency since the mid-1990s due to excess nutrients from Rivers, such as the Maumee River, and largely agricultural watersheds. Nonpoint source pollution from agriculture contributes to eutrophication, algal blooms, and the degradation of water quality. This creates stress on aquatic fauna, reduced aesthetic quality, odor, and limits of the water for usage of drinking, recreation, and industry. This research paper asks what the contributions of having access to manure application records, soil records, and information about antibiotics have on what is known about manure management and antibiotic resistance, which has been …

Isolation And Characterization Of Natural Alpha-Glucosidase Inhibitors From Antioxidant Rich Red Wine Grapes (Vitis Vinifera), Hoda Chaouki Kadouh

Wayne State University Dissertations

Background: Diabetes is currently a global public health problem affecting people at all ages. Dietary antioxidants have been associated with a reduced risk of type 2 diabetes. Grape pomace contains considerable amounts of polyphenols and it has been reported to exhibit an inhibitory activity against alpha- glucosidases. Alpha-glucosidases, in turn, play a major role in controlling starch digestion and therefore postprandial blood glucose, a target for diabetes management.

Objective: This study aims to investigate the anti-diabetes potential of a selection of six grape pomaces and prepare and purify active components in the active variety that specifically inhibit intestinal alpha-glucosidases. The …

The Development Of Liquid Chromatography Mass Spectrometry Methods For The Analysis Of Cyanobacterial Toxins In Environmental Freshwaters, Brian Anthony Dineen

Theses

Cyanobacteria, also known as blue-green algae, are a common component of many freshwater and marine ecosystems and have a potential to produce several different classes of biotoxins. The most common class of cyanobacterial toxins are the microcystins (MCs) and cylindrospermopsins (CYLs). MCs are cyclic heptapeptides that display potent hepatotoxicity and are tumour promoters. CYLs are alkaloids that are cytotoxic and can cause illness and display hepatotoxic effects in animals and humans. Worldwide, these toxins have caused fatal poisonings to animals, birds and fish. Several incidents of human intoxications have been reported and the presence of these toxins in environmental waters …

Investigation Of Pyrrolizidine Alkaloids In Foods Using Liquid Chromatography Mass Spectrometry, Caroline Griffin

Theses

Pyrrolizidine Alkaloids (PAs) are known plant toxins which can cause hepatic veno-occlusive disease (HVOD) in both humans and livestock when ingested. Although PAs are primarily known for their hepatotoxicity they also induce genotoxicity, carcinogenicity and pneumotoxicity. PAs are consumed through plants as food, for medicinal purposes, or as contaminants of agricultural crops. Aside from ingesting the plants directly PA exposure may occur through the consumption of honey produced by bees that visit PA-containing plants or by drinking milk produced by animals that have consumed PA-containing plants. Possible PA contamination in our food chain is a potential health risk.

To assess …

Epigenetic Changes After Prenatal Environmental Tobacco Smoke Exposure And Asthma, Sonja Christensen

Graduate Student Theses, Dissertations, & Professional Papers

Allergic asthma affects over 300 million people worldwide. Multiple factors have been shown to alter an individuals' susceptibility to this allergic airway disease such as exposure to polycyclic aromatic hydrocarbons (PAHs), endotoxin, and environmental tobacco smoke (ETS). Prenatal exposure to these contaminants, especially ETS, has been shown to increase risk for an individuals’ asthma risk, however, the mechanism by which this happens is still unknown. Epigenetic alterations, particularly DNA methylation patterns, have been introduced as a proposed mechanism. The goals of this project were to use a house dust mite (HDM) murine model of asthma to determine the methylation alterations …

An Environmental Toxic Model Of Parkinson's Disease: The Fruit Fly, Jennene Lyda

Graduate Student Theses, Dissertations, & Professional Papers

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with no known specific cause; although genetic risk factors and/or environmental exposure are thought to be involved. The etiology of PD is currently unknown, although the combination of non-genetic components such as environmental exposures, the accumulation of exposure, and gene-environment interactions are thought to play a major role. However, despite this knowledge it is important to develop better models that parallel PD pathophysiology to further understand the mechanisms underlying dopaminergic neuron (DaN) damage. The use of mammalian models to study the degenerative processes in PD has been the most common …

Wastewater Influent And Effluent Concentrations Of 17 Beta-Estradiol: A Study Of The Influence Of A University Community And The Risk To Environmental Health, Kyle Heffron

Masters Theses

The concentration of 17β-estradiol (E2) was measured through stages of wastewater treatment at a central Illinois wastewater treatment plant (WWTP). E2 concentration was quantified using a competitive enzyme linked immunosorbent assay (ELISA). The concentration of E2 was compared with demographic effects of a university, physical parameters of the wastewater (dissolved oxygen, pH, and temperature) and daily influent and effluent flow rates. Effluent concentrations ranged from 0 to 25.3 ng L^-1 with an average discharge of 3.6 ng L^-1. E2 concentration was shown to increase at the start of each university semester, however, this trend was not observed …

The Effects Of 1, 3, & 7 Trisubstituted And 8-Cyclopentyl Alkylxanthines On Respiration In Newborn Rats, Nathan Creel Davidson

Masters Theses

Methylxanthines have been shown to be promising respiratory stimulants in newborns suffering from recurrent apnea. The respiratory stimulant effects of methylxanthines are most likely due to their antagonism of adenosine receptors. These drugs have been shown to stimulate respiration in newborn rats in doses in excess of 10 mg/kg body weight. Structure-activity studies have shown that methylxanthines not only differ in the antagonism of A₁ and A₂ adenosine receptors but also, as a consequence of their different chemical structures, differ in potency as respiratory stimulants. To assess this, two potent A₁ adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and …

Site-Directed Mutagenesis Of Conserved Amino Acids Residues In N5-Carboxyaminoimidazole Ribonucleotide Mutase: Converting N5-Cair Mutase Into Aminoimidazole Ribonnucleotide Carboxylase & Developing A High-Throughput Screening Assay For The Discovery Of N5-Carboxyaminoimidazole Ribonucleotide Mutase, Zhiwen Shi

Wayne State University Theses

The de novo purine biosynthesis pathway plays a critical role in providing new purines to the cell. Previous studies have shown differences between the human and bacterial pathways which suggests that pathway may be a potential target for antibiotic drug discovery. Three critical enzymes are involved in the pathway divergence. In the bacterial pathway, N5-CAIR synthetase (PurK) first converts AIR to N5-CAIR, which is then transformed into CAIR catalyzed by the enzyme N5-CAIR mutase (Class I PurE). In the human pathway, AIR carboxylase (Class II PurE) catalyzes the direct conversion of AIR to CAIR. Class I and Class II PurEs …

Design Of Functional Dendrimer Nanocarriers And Their Formulations In Propellant-Based Inhalers For Pulmonary Drug Delivery, Lin Yang

Wayne State University Dissertations

This Dissertation focuses on addressing two of the major challenges in developing pressurized metered dose inhalers for pulmonary drug / gene delivery to and through the lungs. First challenge is to design biocompatible moieties for the steric stabilization of suspension formulations in HFO-based propellants. Using a combination of tools including ab initio calculation, molecular dynamics simulation and high pressure tensiometry, potential fluorocarbon-philic moieties were systematically screened. Surfactants with those chemistries as tail fragments were studied at the HFO|H2O interface for their ability to lower the interfacial tension at HFO|H2O interface. Selected surfactants were further optimized for surfactant balance by altering …

The Association Of Cold Weather And All-Cause And Cause-Specific Mortality In The Island Of Ireland Between 1984 And 2007, Ariana Zeka, Stephen Browne, Helen Mcavoy, Patrick Goodman

Articles

Background: This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods: A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and an extended cold period (October-March), using distributed lag models. Model stratification by age and …

Species - Dependent Cardiac And Motor Responses To Cholinergic Stimulation In Daphnia Pulex And Daphnia Magna, Bryan James Hannan

Wayne State University Theses

The role of acetylcholine (ACh) in regulating the activity of the heart and `feeding current' driven by the beating thoracic appendages of Daphnia pulex and Daphnia magna was evaluated using acetylcholinesterase inhibitors (AChE-I) and muscarinic receptor agonists. Single animals, tethered to a stainless steel pin, were tested in a watertight aquatic chamber that allowed free movement of appendages and swimming antennae. Heart contraction rate and the rate of thoracic appendage beating were quantified optically by measuring fluctuating changes in light-intensity caused by movement. Physostigmine, neostigmine, oxotremorine, pilocarpine as well as nicotine were used to study ACh and AChE. Atropine was …

Military Contamination And Persistent Organochlorine Pesticide Exposure Among Alaska Natives, Samuel Byrne

Legacy Theses & Dissertations (2009 - 2024)

St. Lawrence Island Alaska is located in the Bering Sea, only 36 miles from Siberia. The island is home to approximately 1600 Siberian Yupik residents, who rely heavily on subsistence hunting and gathering. There are two formerly used defense (FUD) sites on the island, one of which has been the subject of an approximate $110 million cleanup effort. Environmental monitoring suggests localized soil and watershed contamination with PCBs, organochlorine pesticides and heavy metals. Previous research suggests the site may be a source of PCB exposure for local residents. The primary aim of the study was to determine whether subsistence activities …

Paternal Occupational Pesticide Exposure And Neural Tube Defects In The National Birth Defects Prevention Study, Stacy Marie Pettigrew

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT

Sleep Duration And Diabetes In An Adult Population Of Rural Upstate New York, Tarak Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Within the past five decades, there has been a rapid increase in the number of diabetic cases in the US. The number of diabetic cases increased from 1.5 million in 1959 to 25.8 million in 2011. Around the same time period, the average sleep duration per night decreased from 8 hours to 6.9 hours.

Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan

Legacy Theses & Dissertations (2009 - 2024)

Glucocorticoids (GCs) are potent regulatory factors for inflammation. The synthesis of GCs involves several cytochrome P450 enzymes, such as mitochondrial CYP11A1, CYP11B1, and microsomal CYP21. Previous studies have indicated that the GCs, including those released from adrenal glands, and those synthesized in extra-adrenal tissues, such as intestine, exert inhibitory effects on inflammatory bowel disease (IBD). In a previous study using an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, the results suggested that the intestinal P450s had a protective role in DSS-induced acute colitis. In this study, using a hypomorphic CPR mouse model (Cprlow), which presents a global …

Atrazine In Maternal Drinking Water Supply Below The Federal Maximum Contaminant Level And Risk Of Preterm Birth, Small For Gestational Age, Cryptorchidism And Hypospadias, Daniel Rice

Legacy Theses & Dissertations (2009 - 2024)

The prevalence of preterm birth, small for gestational age (SGA), and hypospadias has been increasing for several decades in the U.S resulting in significant morbidity and mortality and direct costs to society. Drinking water provides a mechanism for prolonged chronic exposure to environmental contaminants but is one of the least assessed environmental exposures in pregnancy and birth outcomes. To test the hypothesis that maternal exposure to atrazine through drinking water during pregnancy, or one or more trimesters of gestation, is associated with an increased risk of preterm birth, small for gestational age, cryptorchidism and hypospadias a retrospective cohort study was …

Improving The Microbial Source Tracking Toolbox : Evaluating The Use Of Selective Enrichments And Artificial Sweeteners In A Multi-Tiered Approach, Stacey A. Helming

Legacy Theses & Dissertations (2009 - 2024)

Microbial contamination of surface waters is a public health concern world-wide, with non-point source fecal input contributing to millions of cases of waterborne illness annually. Numerous techniques have been proposed to monitor for non-point source fecal contamination, but few studies have explored the correlation of multiple chemical and microbial fecal source tracking markers in ambient waters. Therefore, the purpose of these studies was to evaluate the use of multiple "ideal" markers of fecal contamination and improve upon any analytical techniques required to identify species-specific fecal contamination in surface waters. The use of selective enrichments to improve the sensitivity of end-point …

Symbiotic Associations Between Vibrio Cholerae And Copepods And Their Potential Public Health Impact, Gretchen Boria Pérez

Legacy Theses & Dissertations (2009 - 2024)

Vibrio cholerae O1 concentrate in copepods by attaching to their chitinous exoskeleton and gut, making these planktonic crustaceans participants in the spread of cholera in marine and estuarine environments. The role of the symbiosis in the spread of gastrointestinal disease caused by non-O1 serotypes has not been well-studied in fresh water systems. The goal of these studies was to determine whether symbiotic association of V. cholerae with copepods affects virulence of hemolysin/cytolysin toxin, suspected in V. cholerae non-O1 related morbidity. The reverse-transcription-polymerase chain reaction was used to evaluate the relative transcriptional response of hlyA, encoding hemolysin, by a non-O1 strain …

Perfluorinated Compounds, Thyroid Function, And Neuropsychological Status In Older Residents Of Upper Hudson River Communities, Srishti Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Perfluorinated compounds (PFCs) are widespread in the environment. Minimal data exist regarding the neurotoxicity and thyroid disruptive property of PFCs in aging populations and the possible mediating effects of thyroid hormones (THs). In this study, we assessed associations among PFCs, thyroid function, and neuropsychological status, and determined if the neurotoxic effects of PFCs are mediated by changes in THs in an aging population. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), thyroid stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), and total triiodothyronine (T3) in serum and performed neuropsychological tests in men and women aged 55-74 years and living …

Exposure Assessment And Risk Management Of Engineered Nanoparticles : Investigation In Semiconductor Wafer Processing, Michele Shepard

Legacy Theses & Dissertations (2009 - 2024)

Engineered nanomaterials (ENMs) are currently used in hundreds of commercial products and industrial processes, with more applications being investigated. Nanomaterials have unique properties that differ from bulk materials. While these properties may enable technological advancements, the potential risks of ENMs to people and the environment are not yet fully understood. Certain low solubility nanoparticles are more toxic than their bulk material, such that existing occupational exposure limits may not be sufficiently protective for workers. Risk assessments are currently challenging due to gaps in data on the numerous emerging materials and applications as well as method uncertainties and limitations.

Runner Identity And Sponsorship: Evaluating The Rock ‘N’ Roll Marathon, Nancy L. Lough, Jennifer Pharr, Jason O. Owen

Environmental & Global Health Faculty Research

The economic value of participation sport has been reported to eclipse spectator sport significantly. However, scholars have acknowledged the relative lack of research on this important segment of the sport market. The purpose of this study was to analyze the relationship between runner identity and race sponsor effectiveness. Surveys were sent to participants in the Las Vegas Rock ‘n’ Roll Marathon. The survey was constructed to measure runner identity, and sponsor effectiveness as interpreted through rates of recognition, recall and purchase intention. Runners were divided into three groups based on their runner identity score. Of the predictive variables, only runner …

Development And Evaluation Of Plga-S-S-Peg Micelles Coencapsulating Curcumin Difluorinated And Paclitaxel For Synergistic Therapeutic Efficacy, Lakshmi Deepika Cheemalakonda

Wayne State University Theses

ABSTRACT

DEVELOPMENT AND EVALUATION OF PLGA-S-S-PEG MICELLES COENCAPSULATING CURCUMIN DIFLUORINATED AND PACLITAXEL FOR SYNERGISTIC THERAPEUTIC EFFICACY

by

LAKSHMI DEEPIKA CHEEMALAKONDA

August 2014

Advisor: Dr. Joshua Reineke Major: Pharmaceutical Sciences Degree: Master of Science

Solid tumors like pancreatic tumor has unique property of forming a dense desmoplastic layer around the tumor cells making it difficult for the drug to transport across this layer. Multi drug resistance is also one of the major limitation of chemotherapy. Therefore the aim of this project was to make PLGA-SS-PEG micelles encapsulating CDF and paclitaxel for synergistic cancer therapy. CDF was found to have 16-fold better …

Functional Studies Of 5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase From Thermotoga Maritima, Mingyang Zhao

Wayne State University Theses

De novo purine biosynthesis is divergent depending upon the organism. In bacteria, yeasts and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxyaminoimidazole ribonucleotide (CAIR) by N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (Class I PurE). In animals, AIR is converted into CAIR by AIR carboxylase (Class II PurE). The distinction makes PurK and Class I PurE good targets in design of antimicrobial drugs. N5-CAIR is chemically unstable with t1/2 of about 0.9 minutes at pH 7.8 and 37 °C. If the production of N5-CAIR is not regulated relative to its conversion to CAIR, ATP utilization can rapidly become non-stoichiometric. …

Proteomic Discovery Of Protein Phosphatase 1 Catalytic Subunit Protein Interaction Partners In Human Skeletal Muscle, Zhao Yang

Wayne State University Theses

Protein Phosphatase 1 (PP1), a member of Serine/ Threonine Phosphatase family, targets its dephosphorylation activity on serine and threonine residues. As the catalytic subunit of PP1, PP1c can achieve its substrate specificity only by binding with PP1 regulatory subunits. Previous researches have shown that PP1c can involve in multiple functional regulation by associating with various interaction partners. Since serine/ threonine phosphorylation on the Insulin receptor substrate-1 (IRS1) may direct inactivation and degradation of IRS1, this phosphorylation activity is believed to be a source of Insulin Resistance. PP1 is hypothesized to dephosphorylate serine/ threonine site on IRS1, which may rescue the …

Comparative Study Of The Prevalence Of Psk41 In Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates Against Non- Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates And The Prevalence By Patient Severity, Poorva Mukund Divekar

Wayne State University Theses

COMPARATIVE STUDY OF THE PREVALENCE OF PSK41 IN HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AGAINST NON- HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AND THE PREVALENCE BY PATIENT SEVERITY

by

POORVA DIVEKAR

December 2014

Advisor: Dr. Emily T. Martin

Major: Pharmaceutical Sciences

Degree: Master of Science

Earlier studies have reported that pSK41 plays an important role in the transfer of vancomycin resistance from Vancomycin-resistant Enterococci (VRE) to S. aureus. This transfer leads to the development of Vancomycin-resistant S. aureus (VRSA). Thirteen VRSA cases have been reported in the United States since 2002. To determine and compare the prevalence of pSK41 in hVISA isolates …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …

Parent-Metabolite Pharmacokinetic Models For Tramadol – Tests Of Assumptions And Predictions, Sam Holford, Karel Allegaert, Brian J. Anderson, Butch Kukanich, Altamir B. Sousa, Amir Steinman, Bruno Pypendop, Reza Mehvar, Mario Giorgi, Nick Holford

Pharmacy Faculty Articles and Research

Allometric principles were used to discern cross-species differences in (±)-tramadol disposition and formation of its primary analgesic metabolite, (±)-O-desmethyl-tramadol (M1). Species differences in formation of M1 may help predict the analgesic effectiveness of tramadol. Tramadol was administered intravenously by a zero-order (constant infusion) process or rapid bolus dose and racemic concentrations of tramadol and M1 measured. Data were pooled to define differences between species (human, rat, cat, dog, goat, donkey and horse). A two-compartment linear disposition model with first-order elimination was used to describe tramadol and M1 disposition. Slow metabolizers were detected in 6% of the population and tramadol clearance …

Full Issue: Volume 8, Number 1

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.