Pharmacology, Toxicology and Environmental Health Commons^™

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 …}

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 …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

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.

Role Of Na+K+2cl- Co-Transporters In Insulin Secretion, Saeed Alshahrani

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The objective of this study is to investigate the role of intracellular chloride concentration ([Cl^-]i) in insulin secretion in vivo and in vitro.

The maintenance of high [Cl^-]i in insulin-secreting pancreatic β-cells plays an important role in glucose-induced depolarization and insulin secretion. Insulinotropic glucose concentrations i.e., >6 mM induces electrical activity in β-cells which results in insulin secretion. This electrical activity is mainly due to electrogenic efflux of Cl^- from β-cells through volume-regulated anion channels (VRAC). The solute carrier family 12 group A member 1 (Slc12a1) and 2 (Slc12a2) encode several splice variants of the …

Investigation Of The Absorptive Potential Of Polymeric Nanoparticles Across The Lungs And Their Development For Efficient Systemic Delivery Following Pulmonary Administration, Abdul Khader Mohammad

Wayne State University Dissertations

The lungs are an attractive route for drug delivery due to their high epithelial surface area available for absorption, a thin epithelium and extensive vasculature to name a few. Accordingly, a vast number of small molecule drugs, peptides, and proteins have been used to investigate their translocation across the lungs with many of the tested candidates showing excellent pharmacokinetics following pulmonary administration. Findings from all these studies over the years have strongly established the lungs as a route for drug delivery of small molecules and proteins. Nanoparticles on the other hand have gained increasing interest in drug delivery due to …

Multifunctional Bioreducible Nanoparticles For Gene Therapy, Jing Li

Wayne State University Dissertations

Gene therapy is a promising therapeutic strategy to treat diseases caused by single or multiple gene mutations. Non-viral gene delivery vectors exhibit many advantages over viral vectors, including enhanced safety, versatility in choosing different types of therapeutic nucleic acids, and ease of formulation. However, low transgene efficiency and lack of targeting ability remain major challenges. Bioreducible polyplexes (polyelectrolyte complexes of disulfide-containing polycations and nucleic acids) utilize the redox potential gradient existing between extracellular space and intracellular environment as a physiological stimulus to enhance delivery of therapeutic nucleic acids to the subcellular space. Bioreducible containing polyplexes undergo intracellular reduction mediated GSH, …

Valproic Acid-Induced Teratogenesis In Japanese Rice Fish (Oryzias Latipes) Embryogenesis, Mengmeng Wu

Electronic Theses and Dissertations

Valproic acid (VPA) was introduced as an antiepileptic in 1967 in France and it has become the most prescribed anticonvulsive drug therapy worldwide since then. In the clinic, valproic acid is selected to treat absence seizures, myoclonic seizures, generalized tonic-clonic seizures, atonic attacks and partial seizures. Epilepsy is the second most comneurologic disorder that affects pregnant women (0.5%–1%). Approximately 1 out of 250 pregnant women are taking antiepileptic drugs. Valproic acid is designated as a human teratogen, which induces major congenital anomalies, facial dysmorphic features, and autistic-like behaviors, which affect verbal, cognitive, communicative, and social abilities of affected children. We …

Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs

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Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …

Evaluation Of Cm-2,525 As A Neuroprotectant Against Sarin: A Comparison With 8-Oh-Dpat, Amanda R. Furman

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Exposure to the chemical warfare agent sarin produces long term neurological deficits. The long term medical consequences could be averted with the development of neuroprotectants to preserve brain function. In our mouse model, the combination of the carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) with the organophosphorus (OP) nerve agent sarin was used to render mice more sensitive to poisoning and reduce the amount of hydrogen fluoride cleaved from sarin during binding to esterases. Since carboxylesterase acts as a scavenger, reducing the levels causes sarin to have a greater inhibition effect on acetylcholinesterase. These smaller doses permitted the use of doses similar to …

Use Of Phage Display Libraries To Select For B-Cell Receptor-Specific Peptides Of Chronic Lymphocytic Leukemia Cells, Richard M. Chou

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Peptides with high affinity to the B-cell receptor (BCR) fused to a toxin could be an effective therapy for Chronic Lymphocytic Leukemia (CLL) patients. We screened captured BCR of a CLL patient with peptides from 7 and 12-mer phage display libraries, using two strategies. Lymphocytes from two patients diagnosed with CLL expressing two different unmutated VH genes (VH 1-3 and VH4-34, respectively) were used. Membrane BCRs were obtained from patient CLL cells by lysis, identified by western blot, semi-quantified and screened with phage libraries. The first strategy involved using patient VH4-34 BCRs which were captured using goat anti-human IgM to …

Light-Limited Access To Fructose Alters Metabolic Function And Adipose Tissue Catecholaminergic Activity In Mice, Naima Salem Rodwan

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Consumption of high levels of fructose produces glucose intolerance, sympathetic nervous system activation, and renal dysfunction. A diet high in fructose may play a role in the worldwide epidemic of obesity and diabetes. The aim of this study was to test the hypothesis that time (light/dark) limited access to fructose influences body fat, metabolic function, and adipose tissue catecholaminergic activity in mice. Male C57BL/6 mice were given standard chow and assigned to one of three groups: Control (n=10, water 24h); FL (n=11, 10% fructose solution during 12h light period); and FD (n=10, 10% fructose solution during 12h dark period). Metabolic …

Enhanced Angiotensin Ii-Induced Cardiac And Aortic Remodeling In Ace2 Knockout Mice, Mahmoud Alghamri

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Activation of the renin angiotensin system (RAS) is a well-known driving force, governing the aggravation and progression of CVD and associated target organ damage. Angiotensin (Ang) converting enzyme 2 (ACE2), a new member within the RAS family, was first cloned from the ventricle of patient with heart failure. ACE2 was shown to be upregulated under pathological conditions. We hypothesize that loss of ACE2 negatively affects cardiac function and exacerbates hypertrophic cardiomyopathy and aortic remodeling in response to Ang II. Eight weeks old ACE2 knock out (KO) and wild type (WT) mice were infused with Ang II s.c. (1000 ng/kg/min for …