Advanced Molecular Biologic Techniques In Toxicologic Disease, 2012 University of Massachusetts Medical School
Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer
Gyongyi Szabo
The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of …
Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, 2012 University of Massachusetts Medical School
Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo
Gyongyi Szabo
AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, have …
Nadph Oxidase 4 Mediates Insulin-Stimulated Hif-1Α And Vegf Expression, And Angiogenesis In Vitro, 2012 Fudan University, China
Nadph Oxidase 4 Mediates Insulin-Stimulated Hif-1Α And Vegf Expression, And Angiogenesis In Vitro, Dan Meng, Aihong Mei, Junxu Liu, Xueling Kang, Xianglin Shi, Ruizhe Qian, Sifeng Chen
Toxicology and Cancer Biology Faculty Publications
Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs). Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, …
Nevirapine Hepatotoxicity: Case Report And Discussion, 2012 Thomas Jefferson University
Nevirapine Hepatotoxicity: Case Report And Discussion, Matt Baichi
The Medicine Forum
Nevirapine (viramune) is a nonnucleoside reverse transcriptase inhibitor commonly used in combination with other antiretroviral medicines in the treatment of HIV/AIDS. The safety profile of nevirapine, as determined by review of prospective clinical trials, reports rash with an incidence of 16% as the most common side effect. Clinical hepatitis is reported to occur with an incidence of 1%. A review of the literature shows many case reports of nevirapine-induced hepatotoxicity in patients receiving both treatment and prophylaxis for HIV. The purpose of this case report is to stress the importance of early recognition and withdrawal of the offending drug.
Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth By Targeting Vegfr- 2 Regulated Akt/Mtor/P70s6k Signaling Pathways, 2012 University of Kentucky
Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth By Targeting Vegfr- 2 Regulated Akt/Mtor/P70s6k Signaling Pathways, Poyil Pratheeshkumar, Amit Budhraja, Young-Ok Son, Xin Wang, Zhuo Zhang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Mei Xu, Gang Chen, Jia Luo, Xianglin Shi
Toxicology and Cancer Biology Faculty Publications
Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Cancer prevention using natural products has become an integral part of cancer control. We studied the antiangiogenic activity of quercetin using ex vivo, in vivo and in vitro models. Rat aortic ring assay showed that quercetin at non-toxic concentrations significantly inhibited microvessel sprouting and exhibited a significant inhibition in the proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Most importantly, quercetin treatment inhibited ex vivo angiogenesis …
Interprofessional Education In Didactic And Experiential Settings At The Jefferson School Of Pharmacy, 2012 Thomas Jefferson University
Interprofessional Education In Didactic And Experiential Settings At The Jefferson School Of Pharmacy, Elena M. Umland, Cynthia A. Sanoski, Emily R. Hajjar, Bhavik Shah
College of Pharmacy Faculty Papers
Presented at: 2012 Annual Meeting of the American Association of Colleges of Pharmacy in Kissimmee, Florida.
Objective:
To evaluate the various IPE offerings at a new school of pharmacy at a large academic medical center.
Human Endometrial Stromal Stem Cells Differentiate Into Megakaryocytes With The Ability To Produce Functional Platelets, 2012 Wright State University - Main Campus
Human Endometrial Stromal Stem Cells Differentiate Into Megakaryocytes With The Ability To Produce Functional Platelets, Jinju Wang, Shuzhen Chen, Cheng Zhang, Samantha Stegeman, Teresa Pfaff-Amesse, Ying Zhang, Wenfeng Zhang, Lawrence Amesse, Yanfang Chen
Pharmacology and Toxicology Faculty Publications
Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin …
Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., 2012 Physicians for Human Rights
Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson
Publications and Research
The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …
Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, 2012 Dartmouth College
Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham
Dartmouth Scholarship
Background: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.
Methods: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We …
Uptake And Toxic Effects Of Surface Modified Nanomaterials In Freshwater Aquatic Organisms, 2012 Clemson University
Uptake And Toxic Effects Of Surface Modified Nanomaterials In Freshwater Aquatic Organisms, Brandon Seda
All Dissertations
Nanomaterials are a class of materials with unique properties due to their size, and the association of these properties with the toxicity of nanomaterials is poorly understood. The present study assessed the toxic effects of stable aqueous colloidal suspensions of three distinctly different classes of nanomaterials in aquatic organisms. The fullerene, C70, was stabilized through non-covalent surface modification with gallic acid. Toxicity of C70-gallic acid was confirmed to exhibit similar toxic effects as C60-fullerene, including changes in antioxidative processes in Daphnia magna. Daphnia magna fecundity was significantly reduced in 21d bioassays at C70-gallic concentrations below quantifiable limits (0.03 mg/L C70). …
Effects Of Restricted Fructose Access On Body Weight And Blood Pressure Circadian Rhythms, 2012 Wright State University
Effects Of Restricted Fructose Access On Body Weight And Blood Pressure Circadian Rhythms, Danielle Senador, Swapnil Vijay Shewale, Maria Claudia Irigoyen, Khalid M. Elased, Mariana Morris
Pharmacology and Toxicology Faculty Publications
High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution) intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1) 24 h water (control); (2) 24 h fructose (F24); (3) 12 h fructose during the light phase (F12L); (4) 12 h fructose during the dark phase (F12D). All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with …
Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, 2012 University of Kentucky
Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, Yong Xu, Daret K. St. Clair, Fang Fang, William H. St. Clair
Toxicology and Cancer Biology Faculty Publications
Background: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy.
Methodology/Principal Findings: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa …
Identifying And Reducing Potential Risks Of Contamination In Food Packaging, 2012 California Polytechnic State University - San Luis Obispo
Identifying And Reducing Potential Risks Of Contamination In Food Packaging, Jeffrey Daniel Stollenwerk
Graphic Communication
The purpose of this study was to identify the possible health hazards in food packaging and evaluate each component of food packaging for risks and potential improvements. There have been recent cases in which contaminants have been identified in various food packaging products that pose potential harm to consumers. National authorities, like the Food and Drug Administration and the European Food Standards Agency, regulate these contaminants and create regulations for industry standards.
Contaminants travel from food packaging to the food-surface through a process called migration. Migration varies depending on the usage of different substrates, inks, varnishes, and printing technologies. Each …
Ex Vivo And In Vivo Methods And Related Compositions For Generating Hematopoietic Stem Cell Populations, 2012 University of Kentucky
Ex Vivo And In Vivo Methods And Related Compositions For Generating Hematopoietic Stem Cell Populations, Gary Van Zant, Ying Liang
Toxicology and Cancer Biology Faculty Patents
Various embodiments provide methods and related compositions for increasing the population size of hematopoietic stem cells (HSCs) in patients that may benefit from reconstitution of stem cells and/or differentiated cells of the blood lineage. The present methods enable the production of HSCs ex vivo and in vivo by reducing latexin expression and/or latexin activity within HSC exposed to various antagonists. Inhibition of latexin expression and/or latexin activity by various antagonists can promote HSC proliferation and/or inhibit HSC apoptosis. Antagonists that can reduce latexin expression and/or latexin activity can be utilized to regenerate endogenous HSCs within patients affected with disorders, diseases, …
The Use Of Cerium Oxide And Curcumin Nanoparticles As Therapeutic Agents For The Treatment Of Ventricular Hypertrophy Following Pulmonary Arterial Hypertension, 2012 Marshall University
The Use Of Cerium Oxide And Curcumin Nanoparticles As Therapeutic Agents For The Treatment Of Ventricular Hypertrophy Following Pulmonary Arterial Hypertension, Madhukar Babu Kolli
Theses, Dissertations and Capstones
Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by inflammation, increased pulmonary vascular resistance, right ventricular failure and premature death. Monocrotaline (MCT) has been used to induce PAH in laboratory rats. Previous in vitro and in vivo work suggested that cerium oxide (CeO2)-and curcumin nanoparticles exhibit anti-inflammatory activity; however, it is unknown if these materials are effective for the treatment of PAH induced cardiac hypertrophy. To determine the efficacy of CeO2 nanoparticle treatment in preventing MCT-induced RV hypertrophy, male Sprague Dawley rats were divided into one of three groups (control, MCT, or MCT + CeO2 nanoparticle, n=6/group). …
Physiological And Toxicological Roles Of Abc Transporters In Cellular Efflux Of Substrates, 2012 University of Kentucky
Physiological And Toxicological Roles Of Abc Transporters In Cellular Efflux Of Substrates, Donna J. Coy
Theses and Dissertations--Toxicology and Cancer Biology
ATP-binding cassette (ABC) transporters are transmembrane proteins that transport a wide variety of substrates across intra and extra-cellular membranes. A few examples of endo and xenobiotic substrates are metabolic products, lipids, sterols, and drugs. An important function of ABC transporters involved in export is to prevent intracellular the buildup of toxic products. Several ABC transporters have also been associated with drug resistance upon treatment with chemotherapeutic agents. P-glycoprotein (P-GP) and the multidrug resistant (MRP) transporters of the ABC C family are examples of transporters that confer chemo-resistance.
We have studied two unique roles of ABC transporters in the liver and …
Novel Mechanism Leading To Mismatch Repair Deficiency And Mutator Phenotype, 2012 University of Kentucky
Novel Mechanism Leading To Mismatch Repair Deficiency And Mutator Phenotype, Janice Ortega Rodríguez
Theses and Dissertations--Toxicology and Cancer Biology
DNA mismatch repair (MMR) is a critical genome-maintenance system. It ensures genome stability by correcting mismatches generated during DNA replication, suppressing homologous recombination, and inducing apoptosis in response to severe DNA damage. As a result, defects in MMR lead to genome-wide mutations and susceptibility to both hereditary and sporadic cancer syndromes. The hallmark of cancer cells defective in MMR is their ability to display frequent instability in simple repetitive DNA sequences, a phenomenon called microsatellite instability (MSI). However, only ~70% of the MSI-positive tumors have identifiable MMR gene mutations, indicating that additional factor(s) are responsible for the MSI phenotype in …
Mnsod And Autophagy In Prevention Of Oxidative Mitochondrial Injuries Induced By Uvb In Murine Skin, 2012 University of Kentucky
Mnsod And Autophagy In Prevention Of Oxidative Mitochondrial Injuries Induced By Uvb In Murine Skin, Vasudevan Bakthavatchalu
Theses and Dissertations--Toxicology and Cancer Biology
UVB radiation is a known environmental carcinogen that causes DNA damage and increase ROS generation in mitochondria. Accumulating evidence suggests that mtDNA damage and increased ROS generation trigger mitochondrial translocation of p53. Within mitochondria, p53 interacts with nucleoid macromolecular complexes such as mitochondrial antioxidant MnSOD, mitochondrial DNA polymerase Polγ, and mtDNA. Mitochondria are considered to be a potential source for damage-associated molecular patterns (DAMPs) such as mtDNA, cytochrome C, ATP, and formyl peptides. Intracytoplasmic release of DAMPs can trigger inflammasome formation and programmed cell death processes. Autophagic clearance of mitochondria with compromised integrity can inhibit inflammatory and cell death processes. …
Severe Lamotrigine Neurotoxicity Treated With Intralipid Emulsion Therapy, 2012 Lehigh Valley Health Network
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.
In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, 2012 Old Dominion University
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 …