Pharmacology, Toxicology and Environmental Health Commons^™

The Status Of Childhood Lead Poisoning And Prevention In Nevada, Usa, Anne Rothweiler, Elena E. Cabb, Shawn Gerstenberger

Environmental & Global Health Faculty Research

One of the first steps in addressing the problem of childhood lead poisoning is to identify the possible sources of exposure in specific communities and target high-risk populations with appropriate interventions. Due to several factors, such as lack of funding and lack of blood lead reporting, little information exists regarding the occurrence of childhood lead poisoning and the prevalence of potential exposure sources in the state of Nevada. Following the recent establishment of a Nevada-based Lead Poisoning Program, we compiled the most current information available on Nevadans, and use this knowledge to suggest future research objectives and outreach activities for …

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe

Biological Sciences Faculty Publications

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

Biodosepr-2006 Consensus Committee Report On Biodosimetric Methods To Evaluate Radiation Doses At Long Times After Exposure, Steven L. Simon, Ian Bailiff, André Bouville, Paola Fattibene, Ruth A. Kleinerman, David C. Lloyd, Stephen W.S. Mckeever, Alexander Romanyukha, Alexander V, Sevan’Kaev, James D. Tucker, Albrecht Wieser

Uniformed Services University of the Health Sciences

The requirements for biodosimetric techniques used at long times after exposure, i.e., 6 months to more than 50 years, are unique compared to the requirements for methods used for immediate dose estimation. In addition to the fundamental requirement that the assay measures a physical or biologic change that is proportional to the energy absorbed, the signal must be highly stable over time to enable reasonably precise determinations of the absorbed dose decades later. The primary uses of these biodosimetric methods have been to support long-term health risk (epidemiologic) studies or to support compensation (damage) claims. For these reasons, the methods …

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …

Immunogenicity Of Terephthalate, A Constituent Of Synthetic Polymers, And Its Modulation By Adjuvants, Youssef Aachoui

All-Inclusive List of Electronic Theses and Dissertations

Objective: In this study we have focused on the potential immunotoxicity resulting from exposure to phthalate compounds which are widely present as basic constituents of many synthetic polymers.

Arsenic Exposure Is Associated With Decreased Dna Repair In Vitro And In Individuals Exposed To Drinking Water Arsenic, Angeline S. Andrew, Jefferey L. Burgess, Maria M. Meza, Eugene Demidenko, Mary G. Waugh, Joshua W. Hamilton, Margaret R. Karagas

Dartmouth Scholarship

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora …

Accumulation Of Phycotoxins In The Mussel Mytilus Galloprovincialis From The Central Adriatic Sea, Maja Pavela-Vrančić, Ivana Ujević, Živana Ninčević Gladan, Ambrose Furey

Physical Sciences Publications

Surveys of DSP (Diarrheic Shellfish Poisoning) toxin profiles in the mussel Mytilus galloprovincialis from coastal waters of the central Adriatic Sea, over the years 1995 to 2001, demonstrate that incidents of shellfish toxicity in this area are dominated by the occurrence of okadaic acid (OA) and a PTX derivative, 7-epi-pectenotoxin-2-seco acid (7-epi-PTX-2SA). Toxin composition and the relative ratio of toxic components in shellfish is in correlation with the occurrence of DSP producing organisms from the Dinophysis species along with Prorocentrum micans and Lingulodinium polyedrum. The occurrence of D. sacculus shortly before the appearance of OA in shellfish implicates its possible …

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Antibiotic Resistant And Coliform Bacteria In The Ohio River; 2002 To 2004, Lisa Marie Smith

Theses, Dissertations and Capstones

During 2002 and 2003 samples, collected every five miles along the Ohio River, were analyzed for total cultivable bacteria, ciprofloxacin resistant bacteria, erythromycin resistant bacteria, tetracycline resistant bacteria, and fecal coliforms. During 2004 samples were analyzed for total cultivable bacteria, ciprofloxacin resistant bacteria, sulfamethizole resistant bacteria, tetracycline resistant bacteria, Virginiamycin resistant bacteria, total coliforms, and Escherichia coli. The objectives of this study were to systematically collect data on fecal coliforms, E. coli, and antibiotic resistant bacteria in the Ohio River and its major tributaries; to determine if antibiotic resistance populations are correlated to each other or to coliforms; and …

Science-Based Organic Farming 2006: Toward Local And Secure Food Systems, Charles A. Francis, Katja Koehler-Cole, Twyla Hansen, Peter Skelton

Publications from the Center for Applied Rural Innovation (CARI)

Organic farming includes growing food and fiber—animals, agronomic crops, horticultural fruits and vegetables, related products—as one dynamic and rapidly evolving component of our complex U.S. food system. Even as more farmers are moving toward organic certification and participation in an environmentally sound and economically lucrative market, questions arise about the long-term social impacts and sustainability of a set of practices that has gone from a movement to an industry. Consolidations in the organic trade have brought multinational corporations to the table, as they have observed a grassroots activity that has grown by 20% per year for the past two decades, …

Critical Evaluation Of The Claims Made By Pharmaceutical Companies In Drug Promotional Material In Pakistan, Dileep Kumar Rohra, Anwarul Hassan Gilani, Ismail Kamal Memon, Ghazala Perven, Muhammad Talha Khan, Hina Zafar, Rakesh Kumar

Department of Biological & Biomedical Sciences

Background: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan.
Methods: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceuticalrepresentatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of …

The Speciation Of Metals In Mammals Influences Their Toxicokinetics And Toxicodynamics And Therefore Human Health Risk Assessment, Robert A. Yokel, Stephen M. Lasley, David C. Dorman

Pharmaceutical Sciences Faculty Publications

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal …

The Effects Of An Analgesic (Biofreeze®) On The Motoneuron Pool Excitability Of The Soleus Muscle, Desiree R. Barth

All-Inclusive List of Electronic Theses and Dissertations

Objective: The purpose of this study was to determine the effects on the Hoffman reflex and motor response with an analgesic (Biofreeze®). Design: The study was a 2X6 design. The independent variables in this study were treatment and time. The dependent variables were the H-reflex (volts) and the M response (volts). Treatment was randomly assigned to control for the effects of order. Setting: This study took place in the Exercise Physiology Laboratory located in the Health and Human Performance Building at Indiana State University. Subjects: 14 volunteers who were physically active and had no known neurological problems. Measurements: Skin and …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Environmental Factors In Autoimmunity: Assessment Of Immunotoxicity Of Phthalates In The Induction Of Lupus-Type Anti-Dna Antibodies, So-Yon Lim

All-Inclusive List of Electronic Theses and Dissertations

Objectives: Little is known of the role of specific environmental factors in promoting autoimmune disorders such as systemic lupus erythematosus (SLE). The broad objective of this study was to address how exposure to phthalates, common environmental factors m foods, and biomedical devices could affect the immune functions of resistant and autoimmune-prone mice. Methods: The environmental chemical model used in this study is phthalates, which are widely used in various forms and readily occur during day-to-day human contacts. Groups of nonautoimmune-prone (BALB/c, DBA/2 and C57BL/6) and susceptible (NZB, NZB/W Fl) mice were immunized with phthalates ( ortho, meta and para) conjugated …

Takagi–Sugeno Fuzzy Modeling Of Skin Permeability, Deepak R. Keshwani, David D. Jones, Rhonda M. Brand

Department of Agricultural and Biological Systems Engineering: Faculty Publications

The skin is a major exposure route for many potentially toxic chemicals. It is, therefore, important to be able to predict the permeability of compounds through skin under a variety of conditions. Available skin permeability databases are often limited in scope and not conducive to developing effective models. This sparseness and ambiguity of available data prompted the use of fuzzy set theory to model and predict skin permeability. Using a previously published database containing 140 compounds, a rule-based Takagi–Sugeno fuzzy model is shown to predict skin permeability of compounds using octanol-water partition coefficient, molecular weight, and temperature as inputs. Model …

Respiratory Symptoms In Relation To Residential Coal Burning And Environmental Tobacco Smoke Among Early Adolescents In Wuhan, China: A Cross-Sectional Study, C. Anderson Johnson, Jiang Xia, Päivi M. Salo, Yan Li, Grace E. Kissling, Edward L. Avol, Chunhong Liu, Stephanie J. London

CGU Faculty Publications and Research

Background

Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children's respiratory health are not well characterized.

Methods

Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment.

Results

Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07–2.29] and without colds (OR = 1.44, 95% CI: 1.05–1.97). For smoking in the home, …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

Do Recent Data From The Seychelles Islands Alter The Conclusions Of The Nrc Report On The Toxicological Effects Of Methylmercury?, Alan H. Stern, Joseph L. Jacobson, Louise Ryan, Thomas A. Burke

Wayne State University Associated BioMed Central Scholarship

Abstract

In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to …

Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku

Loma Linda University Electronic Theses, Dissertations & Projects

Of all body tissues, the brain is the least tolerant of ischemia so much that interruption of cerebral blood flow by 5 sec can cause syncope, with irreversible tissue damage if the ischemia last a few minutes. In this respect, the body has an imperative duty of ensuring constant and adequate blood supply to the brain. It does so through a series of intrinsic and extrinsic control factors of which adrenergic and nitric oxide-releasing nerves are components. My research examined the interaction between these two nerve-types with emphasis on the mechanisms involved as well as on changes in their functions …

Studies On The Regulation Of Mu Opioid Receptor Mrna Expression In Shsy-5y Human Neuroblastoma Cells, Xin Yu

Seton Hall University Dissertations and Theses (ETDs)

Prolonged exposure to morphine down-regulates mu opioid receptors (MOR) on both undifferentiated and differentiated (retinoic acid or phorbol ester treated) SHSY-5Y cells. However, morphine pretreatment does not alter MOR receptor affinity for morphine. To investigate the molecular basis for MOR regulation after exposure to its selective agonists, we have developed a quantitative competitive reverse transcriptase-polymerase chain reaction (QC-RT PCR) to quantify the expression of MOR in SHSY-SY cells. Differentiation of SHSY-5Y cells with retinoic acid or phorbol ester up regulated MOR mRNA expression by 30 % and 78%, respectively. A 24 hours treatment with morphine (10 µM) down regulated MOR …

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …

Enhancement Of Disease And Pathology By Synergy Of Trichuris Suis And Campylobacter Jejuni In The Colon Of Immunologically Naive Swine, Linda S. Mansfield, David T. Gauthier, Sheila R. Abner, Kathryn M. Jones, Stacey R. Wilder, Joseph F. Urban

Biological Sciences Faculty Publications

Campylobacter jejuni, a leading cause of bacterial gastroenteritis, has different age distribution and disease expression in developing and developed countries, which may be due to the endemnicity of infection and the age of acquisition of immunity. Differences in disease expression are not solely dependent on the C jejuni strain or virulence attributes. Another modulating factor in developing countries may be endemic nematode infections such as Trichuris, which drive type 2 cytokine responses and down-regulate type I immune responses. In this study, three-day-old germfree pigs given dual infections with Trichuris suis and C jejuni had more frequent, more severe …

Embryo And Gamete Development Upon Exposure To Cca Components: Cro3, Cuo, And As2o5, Nerbana Talaat-Elsebaei Mahmoud

Theses and Dissertations in Biomedical Sciences

Production of functional gametes and healthy embryos is essential for proliferation of all vertebrates, especially humans. Many compounds have toxic effects on developing gametes and embryos among which are chromium trioxide (CrO₃), cupric oxide (CuO) and arsenic pentaoxide (As₂O₅) as a mixture (CCA) or individually. Controversy surrounding the safety of CCA-treated wood centers primarily on the toxicity of its components and the potential for these metals to be released from the wood.

The aim of this research is to test the hypothesis that CCA components have deleterious effects on embryo development, oocyte maturation and …

Historical Development Of The Linear Nonthreshold Dose-Response Model As Applied To Radiation, Ronald L. Kathren

The University of New Hampshire Law Review

[Excerpt] "Despite the nearly universal adoption of the linear nonthreshold dose response model (LNT) as the primary basis for radiation protection standards for the past half century, the LNT remains highly controversial and a contentious topic of discussion among health physicists, radiation biologists, and other radiological scientists. Indeed, it has been pointed out that the LNT has assumed the status of a paradigm, synonymous with an ideal, standard, or paragon or perhaps to some, a sacred cow. Reduced to its very basics, the LNT postulates that every increment of ionizing radiation dose, however small, carries with it a commensurate increase …

Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths Via Rhog-Mediated Mechanisms, Victor May, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during evelopment. In mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio, broadly expressed throughout the body, is expressed at a lower level in the nervous system. To evaluate the role of Kalirin in fiber initiation and outgrowth, we microinjected cultured sympathetic neurons with vectors encoding Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense oligonucleotides blocked the …

Modulatory Effects Of Citrus Flavonoids Towards The Metabolism And Mutagenicity Of Environmental Carcinogens, Wayne L. Bear

Loma Linda University Electronic Theses, Dissertations & Projects

The environmental carcinogens classified as heterocyclic amines (HCA’s) and the tobacco-specific nitrosamine NNK generally require internal enzymatic activation. This activation occurs via cytochrome P450 (CYP) enzymes and leads to metabolites that bind to human DNA which may in turn cause mutations which may then in turn lead to carcinogenesis. Certain nonnutritive plant compounds termed phytochemicals may protect against HCA and NNK-induced mutagenesis and carcinogenesis. We investigated the potential protective effects of five different phytochemicals of the flavonoid class which naturally occur in citrus. These flavonoids were diosmin, naringin. naringenin, rutin, and quercetin. Our results suggest that naringenin and quercetin were …

The Standardized Fish Bioassay Procedure For Detecting And Culturing Actively Toxic Pfiesteria, Used By Two Reference Laboratories For Atlantic And Gulf Coast States, Joann M. Burkholder, Harold G. Marshall, David W. Seaborn, Nora J. Deamer-Melia

Biological Sciences Faculty Publications

In the absence of purified standards of toxins from Pfiesteria species, appropriately conducted fish bioassays are the "gold standard" that must be used to detect toxic strains of Pfiesteria slop. from natural estuarine water or sediment samples and to culture actively toxic Pfiesteria. In this article, we describe the standardized steps of our fish bioassay as an abbreviated term for a procedure that includes two sets of trials with fish, following the Henle-Koch postulates modified for toxic rather than infectious agents. This procedure was developed in 1991, and has been refined over more than 12 years of experience in …

Workplace Pollution: Nuclear Safety, Ethics, And The Exploitation--Avoidance Argument, Kristin Shrader-Frechette

RISK: Health, Safety & Environment (1990-2002)

The author reviews evidence of poor worker health and safety practices in United States Department of Energy nuclear facilities in contending that less protective standards for workplace hazards constitute an environmental injustice not rectified by a hazard pay premium.

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …