Pharmacology, Toxicology and Environmental Health Commons^™

Anthropogenic Climate Change And Allergic Diseases, James Blando, Leonard Bielory, Viann Nguyen, Rafael Diaz, Hueiwang Anna Jeng

Community & Environmental Health Faculty Publications

Climate change is expected to have an impact on various aspects of health, including mucosal areas involved in allergic inflammatory disorders that include asthma, allergic rhinitis, allergic conjunctivitis and anaphylaxis. The evidence that links climate change to the exacerbation and the development of allergic disease is increasing and appears to be linked to changes in pollen seasons (duration, onset and intensity) and changes in allergen content of plants and their pollen as it relates to increased sensitization, allergenicity and exacerbations of allergic airway disease. This has significant implications for air quality and for the global food supply.

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 …

Effects Of Sediment-Associated Copper To The Deposit-Feeding Snail, Potamopyrgus Antipodarum: A Comparison Of Cu Added In Aqueous Form Or As Nano- And Micro-Cuo Particles, Chengfang Pang, Henriette Selck, Superb K. Misra, Deborah Berhanu, Agnieszka Dybowska, Eugenia Valsami-Jones, Valery E. Forbes

Valery Forbes Publications

Increasing use of engineered nanoparticles (NPs) is likely to result in release of these particles to the aquatic environment where the NPs may eventually accumulate in sediment. However, little is known about the potential ecotoxicity of sediment-associated engineered NPs. We here consider the case of metal oxide NPs using CuO to understand if the effects of NPs differ from micron-sized particles of CuO and aqueous Cu (CuCl₂). To address this issue, we compared effects of copper added to the sediment as aqueous Cu, nano- (6 nm) and micro- (μm) CuO particles on the deposit-feeding snail, Potamopyrgus antipodarum. …

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 …

Stability Study Of Broussonetia Papyrifera Leaf Extract, Suradwadee Thungmungmee, Komkanok Ingkaninan, Tasana Pitaksuteepong

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

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 …

Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons

USF Tampa Graduate Theses and Dissertations

In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …

Use And Development Of Computational Tools In Drug Discovery: From Small Molecules To Cyclic Peptides, Daniel Navarrete Santiago

USF Tampa Graduate Theses and Dissertations

The scope of this work focuses on computationally modeling compounds with protein structures. While the impetus of drug discovery is the innovation of new therapeutic molecules, it also involves distinguishing molecules that would not be an effective drug. This can be achieved by inventing new tools or by refining old tools. Virtual screening (VS, also called docking), the computational modeling of a molecule in a receptor structure, is a staple in predicting a molecule's affinity for an intended target. In our Virtual Target Screening system (also called inverse-docking), VS is used to find high-affinity targets, which can potentially explain absorption, …

Maternal Immune Dysregulation In The Pathogenesis Of Neurodevelopmental Disorders: Interleukin-6 As A Central Mechanism And Therapeutic Target Of Flavonoids, Ellisa Carla Parker-Athill

USF Tampa Graduate Theses and Dissertations

Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has …

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 …

Kv7 K+ Channels In Airway Smooth Muscle Cells As Target For Asthma Therapy, Priyanka Prakash Kakad

Master's Theses

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor …