Medical Toxicology Commons^™

In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Tanvi Desai, Pavan K. Cherukui, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess distinctive physicochemical properties (e.g., small sizes and high surface area-to-volume ratios) and promise a wide variety of applications, ranging from the design of high quality consumer products to effective disease diagnosis and therapy. These properties can lead to toxic effects, potentially hindering advances in nanotechnology. In this study, we have synthesized and characterized purified and stable (nonaggregation) silver nanoparticles (Ag NPs, 41.6 ± 9.1 nm in average diameter) and utilized early developing (cleavage-stage) zebrafish embryos (critical aquatic and eco- species) as in vivo model organisms to probe the diffusion and toxicity of Ag NPs. We found that single …

Severe Lamotrigine Neurotoxicity Treated With Intralipid Emulsion Therapy, Philip W. Moore Do, Megan C. Urquhart Do, Dale L. Mcmillion Do, Keith K. Burkhart Md, Louis R. Cantilena Jr, Md, J Ward Donovan Md

Department of Emergency Medicine

No abstract provided.

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

Arsenic Represses Myogenesis And Neurogenesis Through Epigenetic Mechanisms, Repressed Transcription Factors, And Altered Wnt Signaling Pathway, Gia-Ming Hong

All Dissertations

Arsenic is a toxicant commonly found in water systems around the world. Evidence from epidemiological studies indicates that chronic arsenic exposure can result in cancer, central nervous system and sensory deficits, effects on development, and neuromuscular deficits. However, the molecular mechanism of arsenic's toxicity remains largely unclear. In this study, both C2C12 mouse myoblast cells and mouse embryonic stem cells (mESCs) were used as models of arsenic mediated developmental toxicity in humans to investigate the effects of sodium arsenite on cellular differentiation.
Results from our first and second studies indicate that exposure of 20nM sodium arsenite to C2C12 mouse myocyte …

Impacts Of Psychotropic Pharmaceuticals On Hybrid Striped Bass: Altered Predation Behavior As A Function Of Changes In Brain Chemistry, Joseph Bisesi

All Dissertations

Advances in Analytical Chemistry have led to the detection of low concentrations of pharmaceuticals and personal care products (PPCPs) in wastewater treatment plant effluents as well as their receiving waters. Antidepressants are routinely found among these contaminants, but have been shown to be relatively non-toxic at environmentally measured concentrations using traditional toxicity testing techniques. The neurochemical mode of action of antidepressants warrants investigation of the effects these chemicals may have on fish behavior due to the highly conserved nature of neurotransmitter transporter targets. Using a predator prey bioassay designed in our laboratory, previous studies has shown that the antidepressant fluoxetine …

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese …

Lentiviral-Mediated Rnai Knockdown Yields A Novel Mouse Model For Studying Cyp2b Function, Basma Damiri

All Dissertations

The Cyp2b subfamily contains five members (Cyp2b9, Cyp2b10, Cyp2b13, Cyp2b19, and Cyp2b23) of which three (Cyp2b9, Cyp2b10, Cyp2b13) are hepatic enzymes involved in xenobiotic detoxification. In this study, we made a Cyp2b-knockdown mouse using lentiviral-promoted shRNA homologous to all five Cyp2b subfamily members in FVB/NJ mouse to characterize Cyp2b's role in xenobiotic detoxification. We assessed the in vivo function of Cyp2bs in the toxicity from pesticides (i.e. parathion) and drugs (i.e. zoxazolamine). We demonstrated that Cyp2b isoforms play a key role in parathion and Zoxazolamine metabolism and toxicity. In addition, we in partially phenotyped and characterized Cyp2b-KD model and assessed …

Identifying And Reducing Lead Exposure Associated With The Use Of Cultural Practices In Southern Nevada Hispanic Communities, Maria Castillo-Couch

UNLV Theses, Dissertations, Professional Papers, and Capstones

Despite large amounts of national data on lead and childhood lead poisoning, the status of childhood lead exposure in Nevada as a result of the use of cultural practices in the Hispanic population is unknown. The influx of immigrant Hispanic populations to Nevada, their low education level, the high number of them who are living in poverty present an increased risk for children to be exposed to lead through the use of imported consumables, home remedies and alternative medicine (i.e., healers/ sobadores).

A 61-question survey collected data from Hispanics over 18 years of age who have or take care …

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …

P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress …

The Role Of Xpg In Processing (Cag)N/(Ctg)N Dna Hairpins, Caixia Hou, Tianyi Zhang, Lei Tian, Jian Huang, Liya Gu, Guo-Min Li

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: During DNA replication or repair, disease-associated (CAG)n/(CTG)n expansion can result from formation of hairpin structures in the repeat tract of the newly synthesized or nicked DNA strand. Recent studies identified a nick-directed (CAG)n/(CTG)n hairpin repair (HPR) system that removes (CAG)n/(CTG)n hairpins from human cells via endonucleolytic incisions. Because the process is highly similar to the mechanism by which XPG and XPF endonucleases remove bulky DNA lesions during nucleotide excision repair, we assessed the potential role of XPG in conducting (CAG)n/(CTG)n HPR.

RESULTS: To determine if the XPG endonuclease is involved in (CAG)n/(CTG)n hairpin removal, two XPG-deficient cell lines (GM16024 …

Differential Subcellular Distribution Of Rat Brain Dopamine Receptors And Subtype-Specific Redistribution Induced By Cocaine., Pamela J Voulalas, John Schetz, Ashiwel S Undieh

College of Pharmacy Faculty Papers

We investigated the subcellular distribution of dopamine D(1), D(2) and D(5) receptor subtypes in rat frontal cortex, and examined whether psychostimulant-induced elevation of synaptic dopamine could alter the receptor distribution. Differential detergent solubilization and density gradient centrifugation were used to separate various subcellular fractions, followed by semi-quantitative determination of the relative abundance of specific receptor proteins in each fraction. D(1) receptors were predominantly localized to detergent-resistant membranes, and a portion of these receptors also floated on sucrose gradients. These properties are characteristic of proteins found in lipid rafts and caveolae. D(2) receptors exhibited variable distribution between cytoplasmic, detergent-soluble and detergent-resistant …

Δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 And Peptide Transporter 2*2 Haplotype May Differentially Mediate Lead Exposure In Male Children, Christina Sobin, Natali Parisi, Tanner Schaub, Marisela Gutierrez, Alma Ortega

Selected Works Temporary Series

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, d-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and/or peptide transporter 2*2 haplotype (hPEPT2*2) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects …

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Does Treatment Of Premature Labor With Terbutaline Increase The Risk Of Autism Spectrum Disorders?, Robert L. Brent Dr.

The Selected Works of Robert Brent

none

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract

The Role Of The Pediatrican In The Effort To Prevent Congenital Malformations, Robert L. Brent Dr.

The Selected Works of Robert Brent

No

Evaluation Of Reproductive And Developmental Risks Of Caffeine, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract provided.

The Professonal Responsibility Model Of Obstetrical Ethics: Avoiding The Perils Of Clashing Rights, Robert L. Brent, Frank A. Chervenak, Md, Laurence B. Mccullough, Phd

The Selected Works of Robert Brent

Obstetric ethics is sometimes represented by polarized views. One extreme asserts the rights of the fetus as the overwhelming ethical consideration. Both assertions are overly simplistic. Such oversimplification is called reductionism. This article explains the fallacy of rights-based reductionism and 2 models of obstetric ethics based on it and explains why the fetal rights reductionism model and the pregnant woman's rights reductionism model result in conceptual and clinical failure and therefore should be abandoned. The article argues for the professional responsibility model of obstetric ethics, which emphasizes the importance of medical science and compassionate clinical care of both the pregnant …

An Evidence-Based Review Of Fat Modifying Supplemental Weight Loss Products., Amy M Egras, William R Hamilton, Thomas L Lenz, Michael S Monaghan

College of Pharmacy Faculty Papers

Objective. To review the literature on fat modifying dietary supplements commonly used for weight loss. Methods. Recently published randomized, placebo-controlled trials were identified in PubMed, MEDLINE, International Pharmaceutical Abstracts, Cochrane Database, and Google Scholar using the search terms dietary supplement, herbal, weight loss, obesity, and individual supplement names. Discussion. Data for conjugated linoleic acid (CLA), Garcinia cambogia, chitosan, pyruvate, Irvingia gabonensis, and chia seed for weight loss were identified. CLA, chitosan, pyruvate, and Irvingia gabonensis appeared to be effective in weight loss via fat modifying mechanisms. However, the data on the use of these products is limited. Conclusion. Many obese …

Androgen Increases Angiotensin Receptor Type 1a On Smooth Muscle Cells To Promote Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Xuan Zhang

University of Kentucky Doctoral Dissertations

The purpose of this study was to determine whether androgen promotes AT1aR expression on smooth muscle to confer high prevalence of AngII-induced AAAs in hyperlipidemic mice. In addition, we also investigate the role of androgen in the progression of established AngII-induced AAAs.

First, we sought to examine the role of endogenous androgen in the growth of established AngII-induced AAAs. By castrating male mice, we demonstrated that removal of endogenous androgen significantly decreased the progressive lumen dilation of established AngII-induced AAAs in male ApoE-/- mice, but had no effect on external AAA diameters. These results suggest that androgen contributes to the …

Identification Of Activities Involved In Cag/Ctg Repeat Instability, Nelson Lap Shun Chan

University of Kentucky Doctoral Dissertations

CAG/CTG repeat instability is associated with at least 14 neurological disorders, including Huntington’s disease and Myotonic dystrophy type 1. In vitro and in vivo studies have showed that CAG/CTG repeats form a stable hairpin that is believed to be the intermediate for repeat expansion and contraction.

Addition of extra DNA is essential for repeat expansion, so DNA synthesis is one of the keys for repeat expansion. In vivo studies reveal that 3’ CTG slippage with subsequent hairpin formation (henceforth called the 3’ CTG slippage hairpin) occurs during DNA synthesis. It is proposed that hairpin tolerance machinery is activated because prolonged …

Mir-17* Suppresses Tumorigenicity Of Prostate Cancer By Inhibiting Mitochondrial Antioxidant Enzymes, Yong Xu, Fang Fang, Jiayou Zhang, Sajni Josson, William H. St. Clair, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Aberrant micro RNA (miRNA) expression has been implicated in the pathogenesis of cancer. Recent studies have shown that the miR-17-92 cluster is overexpressed in many types of cancer. The oncogenic function of mature miRNAs encoded by the miR-17-92 cluster has been identified from the 5' arm of six precursors. However, the function of the miRNAs produced from the 3' arm of these precursors remains unknown. The present study demonstrates that miR-17* is able to suppress critical primary mitochondrial antioxidant enzymes, such as manganese superoxide dismutase (MnSOD), glutathione peroxidase-2 (GPX2) and thioredoxin reductase-2 (TrxR2). Transfection of miR-17* into prostate cancer PC-3 …

Mycotoxins In Grains – Causes, Prevention And Control, Hester F. Vismer

INTSORMIL Presentations

Discusses mycotoxins, their effect on grain, mitigation considerations, and resulting human toxicology.

The Catalytic Function Of The Rev1 Dcmp Transferase Is Required In A Lesion-Specific Manner For Translesion Synthesis And Base Damage-Induced Mutagenesis, Ying Zhou, Jillian Wang, Yanbin Zhang, Zhigang Wang

Toxicology and Cancer Biology Faculty Publications

The Rev1-Polζ pathway is believed to be the major mechanism of translesion DNA synthesis and base damage-induced mutagenesis in eukaryotes. While it is widely believed that Rev1 plays a non-catalytic function in translesion synthesis, the role of its dCMP transferase activity remains uncertain. To determine the relevance of its catalytic function in translesion synthesis, we separated the Rev1 dCMP transferase activity from its non-catalytic function in yeast. This was achieved by mutating two conserved amino acid residues in the catalytic domain of Rev1, i.e. D467A/E468A, where its catalytic function was abolished but its non-catalytic function remained intact. In this mutant …

Troglitazone Stimulates Beta-Arrestin-Dependent Cardiomyocyte Contractility Via The Angiotensin Ii Type 1a Receptor., Douglas G G. Tilley, Anny D. Nguyen, Howard A. Rockman

College of Pharmacy Faculty Papers

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR gamma-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR gamma activity, thus we hypothesized that a PPAR gamma agonist may exert physiologic effects via the angiotensin II type 1(A) receptor (AT1(A)R). In AT1(A)R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR gamma agonist troglitazone (Trog) enhanced AT1(A)R internalization and recruitment of endogenous beta-arrestin 1/2 (beta arr1/2) to the AT1(A)R. A fluorescence assay to …

Acetylation Of Wrn Protein Regulates Its Stability By Inhibiting Ubiquitination, Kai Li, Rui Wang, Enerlyn Lozada, Wei Fan, David K. Orren, Jianyuan Luo

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: WRN is a multi-functional protein involving DNA replication, recombination and repair. WRN acetylation has been demonstrated playing an important role in response to DNA damage. We previously found that WRN acetylation can regulate its enzymatic activities and nuclear distribution.

METHODOLOGY/PRINCIPAL FINDING: Here, we investigated the factors involved in WRN acetylation and found that CBP and p300 are the only major acetyltransferases for WRN acetylation. We further identified 6 lysine residues in WRN that are subject to acetylation. Interestingly, WRN acetylation can increase its protein stability. SIRT1-mediated deacetylation of WRN reverses this effect. CBP dramatically increases the half-life of wild …

Antidepressant Stimulation Of Cdp-Diacylglycerol Synthesis Does Not Require Monoamine Reuptake Inhibition, Marwa A. Aboukhatwa, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

Background: Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of …

A Bland–Altman Comparison Of The Lead Care® System And Inductively Coupled Plasma Mass Spectrometry For Detecting Low-Level Lead In Child Whole Blood Samples, Christina Sobin, Tanner Schaub, Natali Parisi, Eva De La Riva

Selected Works Temporary Series

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 μg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 μg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2–12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests …

Letter To The Editor: Reproductive Toxicology, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.