Pharmacology, Toxicology and Environmental Health Commons^™

Sinusoidal Endothelial Cell-Derived Extracellular Matrix Regulates Basal And Stimulated Macrophage Activation., Lauren G. Poole

College of Arts & Sciences Senior Theses

Fatty liver disease, be it from alcohol (ALD), obesity (NAFLD) or other sources (e.g. viral infection), share similar mechanisms of disease progression. One potential mechanism is that altered sinusoidal endothelial cell (SEC) extracellular matrix (ECM) favors a more inflammatory phenotype in resident macrophages (i.e., Kupffer cells). Here, the hypothesis was tested that SEC-derived matrices directly affect the inflammatory response of macrophages. Methods. Transformed sinusoidal endothelial cells (TSECs) were cultured for 24 or 72 hours. Culture plates were then washed with a solution that selectively removed the cells, but preserved the ECM. Cultured macrophages (RAW 264.7 cells) were then seeded on …

Evaluation Of Colloidal Stability And Ecotoxicity Of Metal-Based Nanoparticles In The Aquatic And Terrestrial Systems, Lok R. Pokhrel

Electronic Theses and Dissertations

Intrinsic to the many nano-enabled products are atomic-size multifunctional engineered nanomaterials, which upon release contaminate the environments, raising considerable health and safety concerns. This Ph.D. dissertation is designed to investigate (i) whether metals or oxide nanoparticles are more toxic than ions, and if MetPLATE^TM bioassay is applicable as a rapid nanotoxicity screening tool; (ii) how variable water chemistry (dissolved organic carbon (DOC), pH, and hardness) and organic compounds (cysteine, humic acid, and trolox) modulate colloidal stability, ion release, and aquatic toxicity of silver nanoparticles (AgNP); and (iii) the developmental responses of crop plants exposed to Ag- or ZnO- (zinc …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

A Need For Green: An Approach For Motivating Environmentally Sustainable Practices At The University Of Rhode Island, Alyssa Mason, Mary Vidal

Senior Honors Projects

“Never underestimate the power of a few committed people to change the world. Indeed, it is the only thing that ever has." -Margaret Meade

Colin Beavan’s No Impact Man details his yearlong experiment to live without creating any environmental impact. As sophomores we were inspired by Beavan’s journey but also skeptical of living a completely no-impact lifestyle as college-students. Although we were motivated to try to live sustainably, our efforts were dormant until our junior year. That year we decided that we would attempt to live up to the standards set forth by Beavan--understanding that some practices would be harder …

Liposomal Fasudil, A Rho-Kinase Inhibitor, For Prolonged Pulmonary Preferential Vasodilation In Pulmonary Arterial Hypertension, Vivek Gupta, Nilesh Gupta, Imam H. Shaik, Reza Mehvar, Ivan F. Mcmurty, Masahiko Osa, Eva Nozik-Grayck, Fakhrul Ahsan

Pharmacy Faculty Articles and Research

Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were …

The Effects Of Selected Drugs On The Memory Recall Of Sleep Deprived Mice, Jenn Pauldurai

Capstone Research Projects

Humans often make use of the neurotransmission altering effects of drugs such as caffeine, ephedrine, and ethanol. These drugs induce changes in memory and learning ability, specifically when used for sleep deprivation. English white mice (Mus musculus) have been shown to exhibit similar cognitive changes when administered drugs while sleep deprived. A sample of 20 mice was divided into three experimental groups (each group receiving a different drug) and one control group. Maze-testing demonstrated that mice performance decreased with sleep deprivation (Treatment-1) but all groups returned to baseline performance when injected (IP) with selected drugs (Treatment-2), regardless of …

Pd123319 Augments Angiotensin Ii-Induced Abdominal Aortic Aneurysms Through An At2 Receptor-Independent Mechanism, Alan Daugherty, Debra L. Rateri, Deborah A. Howatt, Richard Charnigo, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: AT2 receptors have an unclear function on development of abdominal aortic aneurysms (AAAs), although a pharmacological approach using the AT2 receptor antagonist PD123319 has implicated a role. The purpose of the present study was to determine the role of AT2 receptors in AngII-induced AAAs using a combination of genetic and pharmacological approaches. We also defined effects of AT2 receptors in AngII-induced atherosclerosis and thoracic aortic aneurysms.

METHODS AND RESULTS: Male AT2 receptor wild type (AT2 +/y) and deficient (AT2 -/y) mice in an LDL receptor -/- background were fed a saturated-fat enriched diet, and infused with either saline or …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.

Accessible Medical Equipment For Patients With Disabilities In Primary Care Clinics: Why Is It Lacking?, Jennifer Renee Pharr

Environmental & Global Health Faculty Research

Background: Previous research has identified inaccessible medical equipment as a barrier to health care services encountered by people with disabilities. However, no research has been conducted to understand why medical practices lack accessible equipment.

Objectives/Hypothesis: The purpose of this study was to examine practice administrators’ knowledge of accessible medical equipment and cost of accessible medical equipment to understand why medical practices lack such equipment. Hypotheses were: 1) Practice administrators lacked knowledge about accessible medical equipment and 2) The cost of accessible medical equipment was too great compared to standard equipment for the clinic.

Methods: This study was a mixed methods …

Partners In Spread Prevention, Nancy C. Balcom

Wrack Lines

Working together to stop the spread of aquatic invasive species.

Cultivating Resistance: Food Justice In The Criminal Justice System, Caitlin M. Watkins

Pitzer Senior Theses

This Senior Thesis in Environmental Analysis seeks to explore the ways in which certain food-oriented programs for incarcerated women and women on parole critically resist the Prison Industrial Complex and the Industrial Food System by securing social and ecological equity through the acquisition of food justice. It focuses on three case studies: the Crossroads’ Meatless Mondays program, Fallen Fruit from Rising Women: A Crossroads Social Enterprise, and Cultivating Dreams Prison Garden Project: An Organic Garden for Women in Prison. Each project utilizes food as a tool to build community, provide valuable skill sets of cooking and gardening, and educate women …

Immunological And Reproductive Health Assessment In Herring Gulls And Black-Crowned Night Herons In The Hudson-Raritan Estuary, Keith A. Grasman, Kathy R. Echols, Thomas M. May, Paul H. Peterman

University Faculty Publications and Creative Works

Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs. The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003. In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively). The phytohemagglutinin (PHA) skin response assessed T cell function in …

Release Of Avian Neurotensin In Response To Intraluminal Contents In The Duodenum Of Chickens, Teresa F. Degolier, Robert E. Carraway

Biological Sciences Faculty Publications

Peripheral and hepatic-portal plasma levels of neurotensin (NT) in fed and fasted chickens were determined using RIA. Portal levels of NT1-13 (fed = 61.3 ± 3.9 fmol/mL; fasted = 44.5 ± 3.9 fmol/mL) were significantly higher than peripheral levels (fed = 8.2 ± 3.3 fmol/mL; fasted = 7.8 ± 3.0 fmol/mL) collected from the wing vein, indicating that some NT is metabolized in the liver. Portal plasma levels of NT collected from fed birds were also significantly higher than portal plasma levels of NT collected from fasted birds. Neurotensin, as identified by HPLC, exhibited a 2-fold increase in plasma extracts …

Imatinib Reverses Doxorubicin Resistance By Affecting Activation Of Stat3-Dependent Nf-Κb And Hsp27/P38/Akt Pathways And By Inhibiting Abcb1, Jonathan T. Sims, Sourik S. Ganguly, Holly Bennett, J. Woodrow Friend, Jessica Tepe, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, …

Overcoming Tumor Drug Resistance By Activating Amp-Activated Protein Kinase And Destabilizing Oncoproteins, Min Shen

Wayne State University Dissertations

Although considerable progress has been achieved in the field of cancer therapeutics, primary or acquired drug resistance remains a fundamental cause of therapeutic failure in cancer therapy. Among different mechanisms characterized that are responsible for tumor drug resistance, there is increasing evidence suggesting that dysregulation of gene expression, especially oncogene or tumor suppressor gene expression, at either gene transcription or protein synthesis level, can contribute to the drug-resistant phenotype. AMP-activated protein kinase (AMPK) is a well-known major cellular energy sensor, which negatively regulates metabolic pathways such as protein synthesis, fatty acid oxidation and glucose consumption. Activation of AMPK may suppress …

Mechanisms Of Cytokine-Induced Metabolic Dysfunction Of The Pancreatic Beta-Cell, Abiy Mussa Mohammed

Wayne State University Dissertations

MECHANISMS OF CYTOKINE-INDUCED METABOLIC DYSFUNCTION OF THE PANCREATIC BETA-CELL

by

ABIY MUSSA MOHAMMED

August 2013

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Type I diabetes is characterized by an absolute insulin deficiency due to loss of pancreatic â-cell mass by autoimmune aggression. During the progression of the disease proinflammatory cytokines such as IL-1â, TNFá and INFã are secreted by infiltrated and activated T-cells and macrophages which ultimately damage the pancreatic â-cell. However, the signaling mechanisms involved in cytokine-induced damage are only partially understood. Phagocyte-like NADPH oxidase [NOX2] has been shown to play regulatory roles in the …

Atrazine And Nitrate In Public Drinking Water Supplies And Non-Hodgkin Lymphoma In Nebraska, Usa, Martha G. Rhoades, Jane L. Meza, Cheryl L. Beseler, Patrick J. Shea, Andy Kahle, Julie M. Vose, Kent M. Eskridge, Roy F. Spalding

School of Natural Resources: Faculty Publications

A secondary analysis of 1999–2002 Nebraska case-control data was conducted to assess the risk of non-Hodgkin lymphoma (NHL) associated with exposure to nitrate- and atrazine-contaminated drinking water. Water chemistry data were collected and weighted by well contribution and proximity of residence to water supply, followed by logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). We found no association between NHL risk and exposure to drinking water containing atrazine or nitrate alone. Risk associated with the interaction of nitrate and atrazine in drinking water was elevated (OR, 2.5; CI, 1.0–6.2). Risk of indolent B-cell lymphoma was higher …

Flavonoids And 3-Arylcoumarin From Pterocarpus Soyauxii (Abstract), Zushang Su, Ping Wang, Wei Yuan, Shiyou Li

NCPC Publications and Patents

No abstract provided.

Chemical Constituents From The Fruit Body Of Chlorophyllum Molybdites, Zushang Su, Ping Wang, Wei Yuan, Shiyou Li

NCPC Publications and Patents

A new glycoxyuracil and 15 known compounds were isolated from the fruit body of Chlorophyllum molybdites. The structures were determined from their NMR and MS data and by comparison with literature data. Compounds 2–5, 10–11, 13, and 15–16 were isolated from the genus Chlorophyllum for the first time. Compounds (1–9) did not show cytotoxicity against two human cancer cell lines, A549 and Panc-28 (GI50 > 50 μM).

Toxicological Effects Of Cerium Oxide Nanoparticle Aggregates On Caenorhabditis Elegans, Steven N. Rogers

Theses, Dissertations and Capstones

Assessing the toxicity and unique reactivity of nanoparticles in biological systems has become an relevant and quickly growing area of environmental toxicology research. The broad use of nanoparticles in industrial and commercial commodities results in exposure of these nano-compounds to the environment, the ecosystems, and humans. While previous data has suggested that cerium oxide (CeO₂) nanoparticles are relatively safe to cultured cells much less is known about the potential toxicity of these materials at the organismal level. In this study we employed transgenic Caenorhabditis elegans (C. elegans) strains to assess the toxicity of CeO₂ nanoparticles under “real-world” …

Nucleic Acid Oxidation In Human Health And Disease, Mu-Rong Chao, Pavel Rossner Jr., Siamak Haghdoost, Hueiwang Anna Jeng, Chiung-Wen Hu

Community & Environmental Health Faculty Publications

No abstract provided.

[6]-Gingerol: A Novel At1 Antagonist For The Treatment Of Cardiovascular Disease (Abstract), Qing Liu, Jinjin Liu, Haili Guo, Shengnan Sun, Shifeng Wang, Yanling Zhang, Shiyou Li, Yanjiang Qiao

Faculty Publications

No abstract provided.

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Psychologists And Medications In The Era Of Interprofessional Care: Collaboration Is Less Problematic And Costly Than Prescribing, William N. Robiner, Tim R. Tumlin, Tanya Tompkins

Faculty Publications

Increasing emphasis on interprofessionalism and teamwork in healthcare renders psychologists’ collaborations critical and invites reexamination of psychologists’ roles related to medications. The Collaboration Level outlined by the APA’s Ad Hoc Task Force is more achievable and in synch with health reform than prescription privileges (RxP). RxP remains controversial due to training and safety concerns, lacking support from health professionals, psychologists, and consumers. Differences in educational preparation of psychologists relative to prescribing professionals are discussed. Enactment of only three of 170 RxP initiatives reveals RxP to be a costly, ineffectual agenda. Alternatives (e.g., integrated care, collaboration, telehealth) increase access without risks …

Determinación Del Efecto Teratogénico En El Desarrollo Del Tejido Óseo En Rattus Norvegicus Cepa Wistar, Inducido Por La Presencia De Arsénico A Concentraciones Encontradas En Aguas De Zimapán, Hidalgo, México, Mireya Quiterio-Pérez, Juan Carlos Gaytán-Oyarzún, Scott Monks, Alberto José Gordillo-Martínez, Francisco Prieto-García

Estudios científicos en el estado de Hidalgo y zonas aledañas

En el presente trabajo se evaluaron los posibles efectos teratogénicos del Arsénico (As) de las mismas concentraciones registradas en aguas de Zimapán, Hidalgo, empleando ejemplares de Rattus norvegicus de la cepa Wistar, preñadas. Las cuales se sometieron a diferentes concentraciones de Arsenato de Sodio (1887.91 mg/l, 943.95 mg/l y 0.5 mg/l), la concentración 0.5 mg/l corresponde a la registrada en agua de Zimapán, Hidalgo, así como Trióxido de Cromo (166.0 mg/l) utilizado como control positivo y Sacarosa al 5% como un control negativo. Los ejemplares se expusieron del día 7º al 15º de gestación, y se sacrificaron el día 19º …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

The Analgesic And Anticonvulsant Effects Of Piperine In Mice, I A. Bukhari, M S. Alhumayyd, A L. Mahesar, A H. Gilani

Department of Biological & Biomedical Sciences

Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy

Polymeric Nanocarriers And Their Oral Inhalation Formulations For The Regional Delivery Of Nucleic Acids To The Lungs, Denise Santos Conti

Wayne State University Dissertations

Gene therapy has attracted attention in the fields of medicine, pharmacy, and bionanotechnology due to the potential for treating a large number of medically relevant diseases. Oral inhalation (OI) is a promising route for the administration of therapeutics, including small molecules and biomacromolecules, such as nucleotides, peptides, and proteins, to (locally) and through (systemically) the lungs. The use of OI is especially attractive for the delivery of nucleic acids as it provides a direct and non-invasive route for targeting the lungs. Pressurized metered-dose inhalers (pMDIs), are the most commonly used OI in treatment of lung diseases and are thus promising …

El Uso De Helmintos Parásitos Como Bioindicadores En La Evaluación De La Calidad Del Agua: Lago De Tecocomulco Vs. Laguna De Metztitlán, Hidalgo, México, Scott Monks, Griselda Pulido-Flores, Christian E. Bautista-Hernández, Berenice Alemán-García, Jorge Falcón-Ordaz, Juan Carlos Gaytán-Oyarzún

Estudios científicos en el estado de Hidalgo y zonas aledañas

Como parte integral de la evaluación de la calidad ambiental del estado de Hidalgo, este estudio tiene énfasis en los helmintos parásitos de los peces y su uso como bioindicadores de la calidad de agua en Lago de Tecocomulco y Laguna de Metztitlán. Como parte del estudio, se obtuvieron los parámetros ecológicos de la infección para cada especie. En Lago Tecocomulco se registraron dos especies de digéneos (larvas), Posthodiplostomum sp. y Diplostomum sp. en el cerebro, los ojos y el mesenterio de dos especies de peces nativos de la zona (Chirostoma jordani y Girardinicthys viviparus); un céstodo (larva), …

The Effects Of Acute Nicotine Administration On Memory Formation And Neural Activity In The Hippocampus, Perirhinal Cortex, And Medial Septum: Implications For Neurodegenerative Disorders, Matthew Wishnoff

Behavioral Neuroscience Honors Papers

Within the general public, nicotine is commonly thought of as a harmful molecule due to its role in tobacco addiction. However, nicotinic stimulation of the cholinergic system has also been shown to enhance cognitive functioning. This enhancement is thought to be caused by an increase in the release of the neurotransmitter, acetylcholine (ACh), which is responsible for mediating a variety of cognitive processes, such as REM sleep and memory formation. Recent research by Melichercik and colleagues shows that systemic nicotine administration enhances memory acquisition for both object location and object recognition memory in rats, as assessed by a modified version …