Pharmacology, Toxicology and Environmental Health Commons^™

Northern Gateway Pipeline: Why American Environmental Groups Are Funding Canadian Ones In The Fight Against It., Richard Philp

Data and Test Instruments

The Canadian federal government, supported by the right wing press, has being trying to paint as a conspiracy the financial support of Canadian aboriginal groups and environmental ones by offshore environmental interests. This brief article points out why such action is entirely legitimate and discusses the recent history of oil leaks and the risks associated with the Northern Gateway pipeline.

The Cyclin-Like Protein Spy1/Ringo Promotes Mammary Transformation And Is Elevated In Human Breast Cancer, Mohammad Al Sorkhy, Rosa-Maria Ferraiuolo, Espanta Jalili, Agnes Malysa, Andreea R. Fratiloiu, Bonnie F. Sloane, Lisa A. Porter

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. …

Toxicological Assessment Of Intra‐Tracheal Instilled Nanoceria On Kidneys Of Sprague‐Dawley Rats, Geeta Nandyala

Theses, Dissertations and Capstones

Recent studies suggest that use of nanoceria in industry is associated with increased risk of human and environmental exposure. How inhaled nanoceria might affect the kidneys is not yet known. To investigate this possibility, Sprague Dawley rats were exposed to a single dose of 7mg/kg body weight cerium oxide nanoparticles by intratracheal instillation. Animals were sacrificed at day 1, 3, 14, or 28 days after exposure and the kidneys collected for histological and biochemical analysis. No significant difference was observed in kidney to body weight ratio between the different groups. Hematoxylin and eosin staining did not reveal any significant changes …

Reduce, Reuse, Recycle? An Examination Of Factors Influencing Environmental Behavior In Denver, Colorado, Dan J. Kasper

Electronic Theses and Dissertations

Non-recycling and non-composting of municipal solid waste have important natural resource management implications, in that they both reduce energy, water, and raw natural resource use. Responsible waste management also likely has positive climate impacts by virtue of reducing greenhouse gas emissions. Recycling and composting are pro-environmental behaviors that have been shown to be influenced by numerous socio-demographic and psychological factors. This study analyzes the correlation of a number of variables with frequency of recycling and composting in select census tracts in Denver, CO, USA, with the goals of informing waste management policy and contributing to the overall pro-environmental behavior literature. …

Toxic Effects Of Copper, Cadmium, And Methoxychlor Shown By Neutral Red Retention Assay In Two Species Of Freshwater Molluscs, Nikolett Molnar, Peter Fong

Biology Faculty Publications

We used neutral red retention assay in lysosomes of digestive gland cells as an indicator for stress effects by the environmental contaminants Cu, Cd, and the pesticide methoxychlor in two freshwater molluscs, the unionid mussel, Elliptio complanata (Lightfoot) and the ramshorn snail Helisoma trivolvis (Say). Mussels and snails were exposed for 7 and 14 days to Cu and Cd each at nominal concentrations of 2.5 μg/L, 5.0 μg/L, and 10.0 μg/L, and to methoxychlor concentrations of 1.0 μg/L, 10.0μg/L, and 100.0 μg/L. Both mussels and snails exposed to Cu showed a significant increase in the percent of destabilized lysosomes compared …

The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.

In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …

Vascular Kv7 (Kcnq) Potassium Channels As Therapeutic Targets In Cerebral Vasospasm, Bharath Kumar Mani

Dissertations (6 month embargo)

Cerebral vasospasm, a grave sequel to subarachnoid hemorrhage (SAH), is characterized by prolonged severe constriction of arteries in the base of the brain, including the basilar artery. Spasmogens (serotonin, endothelin and vasopressin), elevated in response to SAH, induce persistent depolarization of the myocytes in the artery wall, leading to continuous influx of calcium (Ca2+) through voltage-sensitive Ca2+ channels (VSCC) resulting in hyperconstriction (spasm). The spasm of the arteries restricts blood flow to the brain, inducing ischemic neurological deficits and consequential high morbidity and mortality. The cellular pathogenesis of cerebral vasospasm is poorly understood and the therapeutic options are limited.

Kv7 …

Analysis Of Gene Expression Alterations In Premalignant Progression From Normal Mammary Epithelium To Ductal Carcinoma In Situ By Multiple Orthogonal Tools, Hitchintan Kaur

Wayne State University Dissertations

Mammary ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. The molecular and genetic changes underlying the progression from normal breast tissue to DCIS are not clearly understood. The goal of the present study was to determine gene expression changes in different DCIS models (MCF10.DCIS, SUM102 and SUM225) in comparison to normal breast epithelial cells (MCF10A) that may enable us to identify novel markers of disease progression and potential therapeutic targets. We cultured the cells in three dimensional reconstituted basement membrane (3D rBM) for RNA extraction and used the …

Extinction Risk And Bottlenecks In The Conservation Of Charismatic Marine Species, Loren Mcclenachan, Andrew B. Cooper, Kent E. Carpenter, Nicholas K. Dulvy

Biological Sciences Faculty Publications

The oceans face a biodiversity crisis, but the degree and scale of extinction risk remains poorly characterized. Charismatic species are most likely to gar- ner greatest support for conservation and thus provide a best-case scenario of the status of marine biodiversity. We summarize extinction risk and diagnose impediments to successful conservation for 1,568 species in 16 families of marine animals in the movie Finding Nemo. Sixteen percent (12–34%) of those that have been evaluated are threatened, ranging from 9% (7–28%) of bony fishes to 100% (83–100%) of marine turtles. A lack of scientific knowledge impedes analysis of threat status …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

The Role Of Ecological Models In Linking Ecological Risk Assessment To Ecosystem Services In Agroecosystems, Nika Galic, Amelie Schmolke, Valery E. Forbes, Hans Baveco, Paul Van Den Brink

Valery Forbes Publications

Agricultural practices are essential for sustaining the human population, but at the same time they can directly disrupt ecosystem functioning. Ecological risk assessment (ERA) aims to estimate possible adverse effects of human activities on ecosystems and their parts. Current ERA practices, however, incorporate very little ecology and base the risk estimates on the results of standard tests with several standard species. The main obstacles for a more ecologically relevant ERA are the lack of clear protection goals and the inherent complexity of ecosystems that is hard to approach empirically. In this paper, we argue that the ecosystem services framework offers …

Development Of A Framework Based On An Ecosystem Services Approach For Deriving Specific Protection Goals For Environmental Risk Assessment Of Pesticides, Karin M. Nienstedt, Theo C. M. Brock, Joke Van Wensem, Mark Montforts, Andy Hart, Alf Aagaard, Anne Alix, Joes Boesten, Stephanie K. Bopp, Colin Brown, Ettore Capri, Valery E. Forbes, Herbert Köpp, Matthias Liess, Robert Luttik, Lorraine Maltby, José P. Sousa, Franz Streissl, Anthony R. Hardy

Valery Forbes Publications

General protection goals for the environmental risk assessment (ERA) of plant protection products are stated in European legislation but specific protection goals (SPGs) are often not precisely defined. These are however crucial for designing appropriate risk assessment schemes. The process followed by the Panel on Plant Protection Products and their Residues (PPR) of the European Food Safety Authority (EFSA) as well as examples of resulting SPGs obtained so far for environmental risk assessment (ERA) of pesticides is presented. The ecosystem services approach was used as an overarching concept for the development of SPGs, which will likely facilitate communication with stakeholders …

Associations Between Serum Concentrations Of Polychlorinated Biphenyls, Serum Carotenoids, And The Probability Of Metabolic Syndrome In The National Health And Nutrition Examination Survey 2003-2004, Carolyn R. Hofe

Theses and Dissertations--Nutritional Sciences

Diabetes and cardiovascular disease are leading causes of death and disability in the United States. These chronic diseases are clinical sequelae of metabolic syndrome (MetS), a condition that affects approximately one-third (1/3) of American adults. Metabolic syndrome occurs in response to environmental and genetic influences, among them food intake, a sedentary lifestyle, BMI, advancing age, and exposure to persistent organic pollutants (POPs). POPs are known to cause endocrine disruption and PCBs cause oxidative stress, disrupt endothelial cell integrity, and promote atherosclerosis. Nutrition plays a significant role in the prevention and management of these chronic diseases and has been shown to …

Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman

Wayne State University Dissertations

Accumulations of autophagosomes and non-esterified cholesterol are

observed in several cell lines derived from lysosomal storage diseases,

including Niemann Pick Type C (NPC). The relationship between

autophagosome accumulation and lysosomal non-esterified cholesterol is

unclear. Exposure of murine hepatoma 1c1c7 cultures to the cationic

amphiphilic drugs (CADs) U18666A, imipramine and clozapine caused

lysosomal non-esterified cholesterol and autophagosome accumulation.

Measurement of LC3-II conversion in the presence of lysosomal inhibitors

bafilomycin A1 and NH4Cl, degradation of long-lived proteins, and

colocalization of GFP-LC3 and LAMP1 indicated an increase in

autophagosome synthesis without compensatory increase in clearance.

Autophagosome synthesis was blocked using 3-MA to monitor …

Short-Term Associations Between Pm2.5, Black Carbon, Delta-C, And Cardiovascular Diseases In A Large Developing Megacity, Daniel Malashock

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Association between ambient air pollution and cardiovascular disease (CVD) have been demonstrated by many epidemiological studies in developed countries, however few studies have been performed in developing countries of Asia.

Trace Element Analysis Of Environmental And Clinical Materials Using Novel Instrumentation Based On X-Ray Fluorescence Spectrometry : New Capabilities For Public Health Laboratories, Kathryn G. Mcintosh

Legacy Theses & Dissertations (2009 - 2024)

X-ray fluorescence (XRF) spectrometry is a well-established analytical technique for determining the elemental content of many different materials. XRF has long been used for public health applications, particularly for identifying lead-based paint hazards. The primary advantage of XRF over other atomic spectrometric techniques is that it is nondestructive. In addition, little sample preparation is required, so results are obtained rapidly and at low cost. The principal aim of this study was to characterize the utility and reliability of current XRF instrumentation for use in the environmental health sciences. Interest in the use of XRF for detecting lead in children's toys …

Occupational Exposure And Risk Of Skin Cancer In A Multinational European Study, Simona Surdu

Legacy Theses & Dissertations (2009 - 2024)

Non-melanoma skin cancers (NMSC) comprise more than one third of all cancers, and are increasing worldwide. The most common NMSC are Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC). Studies on humans and animals suggest that sunlight and arsenic play important roles in the pathogenesis of these skin malignancies. However, the number of epidemiological studies focusing on NMSC in workers exposed to ultraviolet (UV) radiation or airborne arsenic is limited, and the findings are contradictory.

Association Between Chemical Constituents Of Particulate Matter And Cardiovascular And Respiratory Morbidities In Nys, Rena Jones

Legacy Theses & Dissertations (2009 - 2024)

Improved understanding of health risks from short- and long-term exposure to fine particulate matter (PM_2.5) constituents may explain seasonal and geographic heterogeneity in PM_{2.5-health associations and inform control efforts targeting PM sources. Few studies have examined PM species health effects; most have been limited by their exposure assessments and modeling approaches. The goals of this project were to improve the PM exposure assessment and explore relationships between PM2.5 species and health in acute and chronic contexts.}

Evaluation Of The Short- And Long- Term Drinking Water Sustainability Programs For Point Water Sources And Public Water Supplies (Pws) In Developing Countries : Case Study Of Uganda, Shedrack R. Nayebare

Legacy Theses & Dissertations (2009 - 2024)

Providing quantity and quality potable water in Uganda and other developing countries is still significantly problematic. This project aimed at identifying and prioritizing possible actions on how sustainable and high quality potable water in Uganda's water supply systems could be improved. A review of both the current water supply systems and Ugandan government programs was completed in an effort to describe the existing state of Uganda's water supply. Aspects of quantity, quality, treatment methods, infrastructure, storage and distribution of water for the different water systems were assessed. These characteristics were compared to water supply systems and regulations in the U.S., …

Seafood Consumption And Use Of Asian Herbal Preparation As A Source Of Exposure To Multiple Trace Elements In The Study Of Metals And Assisted Reproductive Technologies (Smart), Dongsul Kim

Legacy Theses & Dissertations (2009 - 2024)

As, Cd, Cs, Hg, Pb, and Zn may be associated with in vitro fertilization (IVF) outcomes. Seafood and Asian herbal preparations are identified as sources of exposure to these essential and non-essential trace elements in humans. The goal of the study is to assess associations between seafood consumption and the use of Asian herbal preparations and levels of essential and non-essential trace elements in biologic specimens collected from couples undergoing IVF. Fifty-nine couples completing a first IVF cycle at the University of California, San Francisco (UCSF) Center for Reproductive Health were recruited to participate in the Study of Metals and …

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

IP Theory

No abstract provided.

Effects Of Partner Proteins On Bca2 Ring Ligase Activity, Stephanie Bacopulos, Yutaka Amemiya, Wenyi Yang, Judit Zubovits, Angelika Burger, Martin Yaffe, Arun K. Seth

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2.

Methods

Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays.

Results

Ten unique …

Novel Inhibitors Of The Bacterial De Novo Purine Biosynthesis Enzymes, N5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase, Maria V. Fawaz

Wayne State University Theses

Antibiotic resistance has seen a significant increase during the past decade. The increasing frequency of the drug-resistant bacterial infections has amplified the need for novel antimicrobial agents. De novo purine biosynthesis is one area that has great potential for antibacterial drug development because this pathway is different in microorganisms versus humans. The difference in the pathway is centered on the synthesis and utilization of the purine intermediate N⁵-carboxy-5-aminoimidazole ribonucleotide (N⁵-CAIR). Previous studies have shown that N⁵-CAIR is a key intermediate in purine biosynthesis in bacteria, yeast and fungi, but not in humans. N^{5 …}

Calcium Montmorillonite Clay Reduces Urinary Biomarkers Of Fumonisin B₁ Exposure In Rats And Humans, Abraham Robinson, Natalie M. Johnson, A. Strey, John F. Taylor, Alicia Marroquin-Cardona, N. J. Mitchell, Evans Afriyie-Gyawu, Nii-Ayi Ankrah, Jonathan H. Williams, Jia-Sheng Wang, Pauline E. Jolly, R. J. Nachman, Timothy D. Phillips

Environmental Health Sciences: Faculty Publications

Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in …

Full Issue: Volume 5, Issue 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Full Issue: Volume 6, Number 1

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Analogues Of The Epoxy Resin Monomer Diglycidyl Ether Of Bisphenol F: Effects On Contact Allergenic Potency And Cytotoxicity, Niamh O'Boyle, Tamara Delaine, Kristina Luthman, Andreas Natsch, Ann-Therese Karlberg

Articles

Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and non-occupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its …

Skin Irritation Study Of Two Patented Mix Extracts From Emblica, Ma-Khwaen And Khanun, Sareeya Reungpatthanaphong, Tuanta Sematong, Buppachart Potduang, Phanukit Kunhachan, Cholticha Niwaspragrit

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Moisturizing Gel Formulation Containing Pueraria Mirifica Extracts As An Anti-Wrinkle Agent, Thanachod Thammachat, Sompoch Tubcharoen, Sitthiphong Soradech, Somnuk Promdang

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …