DOCSLIB.ORG

Information to Users

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Information to Users INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. HQgher quality 6 ” x 9” black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. UMI A Bell & Howell Infonnation Company 300 North Zeeb Road, Ann Arbor MI 48106-1346 USA 313/761-4700 800/521-0600 IN VITRO MECHANISTIC STUDIES OF PEROXISOME PROLIFERATION BY CHIRAL CLOFIBRATE ANALOGS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Shamina M. Rangwala, B. Pharm. ***** The Ohio State University 1997 Dissertation Committee: Dr. Dennis R. Feller, Adviser Approved by Dr. Norman J. Uretsky, Co-Adviser Dr. Lane J. Wallace Adviser ' Dr. Bethany J Holycross College of Pharmacy ÜMI Number: 9801766 UMI Microform 9801766 Copyright 1997, by UMI Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. UMI 300 North Zeeb Road Ann Arbor, MI 48103 ABSTRACT The mechanism by which clofibrate causes peroxisome proliferation is not known. A series of chiral clofibrate-related 2-(4-chlorophenoxy)acetic acid (CPAA) analogs were selected to examine the effects of stereoselectivity on activation of peroxisome proiiferator-activated receptor (PPAR) and stimulation of peroxisomal activity. The abilities of these compounds to activate the receptor were examined using transactivation assays using exogenously added PPARa in CV-1 and endogenous PPAR in H4IIEC3 cells. In both systems, the 2-n-propyl and 2-phenyl-substituted CPAA analogs were highly stereoselective activators of PPARa, suggesting that these compounds act via a receptor. The effects of these analogs on peroxisomal acyl-CoA oxidase aciidty was determined. There exists a strong correlation between the ability of a compound to activate PPAR and stimulate fatty acyl-CoA oxidase (AGO) activity, implicating a causal relationship between these events. Small modifications in structure around the 2 position of CPAA can result in dramatic alterations in stereoselectivity and potency, e.g., changing the n-propyl substituent to the isopropyl substituent results in the loss of stereoselectivity, while the substitution of the n-hexyl group with the phenyl group at the 2 -position results in a decrease in activity, however, the stereoselectivity increases strikingly. Enlargement of the chlorophenoxy group to the chlorobenzyloxy group leads to an increase in activity of the compound; however, addition of one more phenyl ring to this side-chain decreased activity, but increased stereoselectivity. We showed that the rank order o f stereoselectivity observed for activating PPAR and stimulating ACO activity is not conserved for displacing tritiated oleic acid from L-FABP. This indicates that binding to liver fatty acid binding protein (L-FABP) is not predictive of the peroxisome proliferative effects of these compounds. However, for non-metabolizable fatty acids tested, such as 2- bromopalmitic acid and perfluorinated octanoic acid, L-FABP may play an important role in the signaling pathways for these molecules as compared to xenobiotic peroxisome proliferators. Ciprofibrate and 2-n-propyl- and 2-phenyl-substituted CPAA analogs bind to the Xenopus PPARa ligand binding domain, displacing leukotriene B$ from this binding site. Thus, the peroxisome proliferative effects of the fibrates are probably mediated by the direct binding of these compounds to the PPARa. in To my parents, Mohsin and Sehra Rangwala, without your encouragement, faith and support, I would have never come this far. With my love and thanks. IV ACKNOWLEDGMENTS I would like to thank; Dr. Dennis Feller, for his advice, support and constant enthusiasm throughout my graduate career. Dr. Norman Uretsky, my co-adviser at OSU, for his advice and help, especially in the past two years. Other members of my dissertation committee, Drs. Wallace and Holycross, for their assistance during the preparation of this dissertation. Dr. Dan Noonan, Michelle O’Brien and George Yuan, at the University of Kentucky, for their friendship, help and support throughout this research. Dr. David Pasco, Chuan-Li Xu, Vincent Siu and all the other members of the Pasco lab at Ole Miss for their assistance and friendship and for tolerating my constant questions while setting up some of the experimental methods! Dr. JefiF Lawrence and Dr. Patrick Eacho, Eli Lilly and Company, for their assistance. Rose Smith and Kathy Brooks at OSU for their cheerful, eflBcient personalities, which helped making the move to Ole Miss less stressful. Becky Drewery for her friendship and help, especially while this dissertation was being written. My friends, both at OSU and Ole Miss; Suzette, Joya, Marina, Subbu, Ratna, Anish, Edwin, David, Reshma, Grace and Vivek, for their companionship which always made me feel like I belonged; thank you for making my graduate school experience an entirely enjoyable one. My family, whose love, encouragement and support has sustained me throughout my graduate study. VI VITA June 13, 1971 ............................................... Born-Bombay, India 1992 ..............................................................Bachelor of Pharmaceutical Sciences, University of Bombay. 1992 - 1993 .................................................. University Fellow, The Ohio State University. 1993 - present ...............................................Graduate Teaching and Research Associate The Ohio State University PUBLICATIONS O'Brien ML, Rangwala SM, Henry KW, Weinberger C, Crick DC, Waechter CJ, Feller DR and Noonan DJ. Convergence of three steroid receptor pathways in the mediation of nongenotoxic hepatocarcinogenesis. Carcinogenesis 17: 185-190, 1996. Feller DR, O'Brien M, Rangwala SM, Tortorella V, Loiodice F and Noonan DJ. Structural requirements of chiral clofibric acid analogs for activation of the rat peroxisome proiiferator-activated receptora (rPPARa). Ann. N. Y. Acad. Sci. 804: 713-715, 1996. Rangwala SM, O'Brien ML, Loiodice F, Longo A, Tortorella V, Noonan DJ and Feller DR. Stereoselective effects of chiral clofibric acid analogs on rat peroxisome proiiferator- activated receptor (PPARa) activation and peroxisomal fatty acid B-oxidation. Chirality 9: 37-47, 1997. vu Rangwala SM, O'Brien ML, Noonan DJ and Feller DR. Differential effects of statins on peroxisomal acyl CoA activity and the rat peroxisome proliferator activated receptor (rPPAR). FASEBJ. 9: A690, 1995. Rangwala SM, O'Brien M, Loiodice F, Tortorella V, Noonan DJ and Feller DR. Specificity of the effects of isomeric clofibric acid analogs on hepatic peroxisome proliferation. Toxicologist 3d'. 1\0, 1996 Rangwala SM, O’Brien M, Lawrence J, Eacho P, Tortorella V, Loiodice F, Longo A and Feller DR. Studies on the mechanism of peroxisome proliferation by clofibric acid analogs. Toxicologist 252, 1997. FIELD OF STUDY Major Field: Pharmacy Pharmacology vui TABLE OF CONTENTS Page Abstract................................................................................................................................ ii Dedication ............................................................................................................................ iv Acknowledgments ................................................................................................................ v Vita......................................................................................................................................vii List of Figures ....................................................................................................................xiii List of Tables .....................................................................................................................xvi Chapters: 1. Introduction ..............................................................................................................1 1.1 Peroxisomes ................................................................................................1 1.1.1 Morphology .......................................................................................1 1.1.2 Biogenesis ......................................................................................... 2 1.1.3 Biochemistry.....................................................................................2 1.2 Peroxisome
Load more

Recommended publications
  • Chemicals in the Fourth Report and Updated Tables Pdf Icon[PDF
    Chemicals in the Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 CDC’s Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 provides exposure data on the following chemicals or classes of chemicals. The Updated Tables contain cumulative data from national samples collected beginning in 1999–2000 and as recently as 2015-2016. Not all chemicals were measured in each national sample. The data tables are available at https://www.cdc.gov/exposurereport. An asterisk (*) indicates the chemical has been added since publication of the Fourth National Report on Human Exposure to Environmental Chemicals in 2009. Adducts of Hemoglobin Acrylamide Formaldehyde* Glycidamide Tobacco Alkaloids and Metabolites Anabasine* Anatabine* Cotinine Cotinine-n-oxide* Hydroxycotinine* Trans-3’-hydroxycotinine* 1-(3-Pyridyl)-1-butanol-4-carboxylic acid* Nicotine* Nicotine-N’-oxide* Nornicotine* Tobacco-Specific Nitrosamines (TSNAs) N’-Nitrosoanabasine (NAB)* N’-Nitrosoanatabine (NAT)* N’-Nitrosonornicotine (NNN)* Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)* Volatile N-nitrosamines (VNAs) N-Nitrosodiethylamine (NDEA)* N-Nitrosoethylmethylamine (NMEA)* N-Nitrosomorpholine (NMOR)* N-Nitrosopiperidine (NPIP)* N-Nitrosopyrrolidine (NPYR)* Disinfection By-Products Bromodichloromethane Dibromochloromethane Tribromomethane (Bromoform) Trichloromethane (Chloroform) Personal Care and Consumer Product Chemicals and Metabolites Benzophenone-3 Bisphenol A Bisphenol F* Bisphenol
    [Show full text]
  • Pfoa) Or Perfluorooctane Sulfonate (Pfos
    National Toxicology Program NTP U.S. Department of Health and Human Services NTP Monograph Immunotoxicity Associated with Exposure to Perfluorooctanoic Acid or Perfluorooctane Sulfonate September 2016 NTP MONOGRAPH ON IMMUNOTOXICITY ASSOCIATED WITH EXPOSURE TO PERFLUOROOCTANOIC ACID (PFOA) OR PERFLUOROOCTANE SULFONATE (PFOS) September, 2016 Office of Health Assessment and Translation Division of the National Toxicology Program National Institute of Environmental Health Sciences National Institutes of Health U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Systematic Review of Immunotoxicity Associated with Exposure to PFOA or PFOS TABLE OF CONTENTS Table of Contents ...............................................................................................................................II List of Table and Figures ................................................................................................................... IV Abstract ............................................................................................................................................. 1 Peer Review Of The Draft NTP Monograph ......................................................................................... 2 Peer-Review Panel .............................................................................................................................. 2 Introduction ...................................................................................................................................... 3 Objective and Specific Aims ...............................................................................................................
    [Show full text]
  • PFAS MCL Technical Support Document
    ATTACHMENT 1 New Hampshire Department of Environmental Services Technical Background Report for the June 2019 Proposed Maximum Contaminant Levels (MCLs) and Ambient Groundwater Quality Standards (AGQSs) for Perfluorooctane sulfonic Acid (PFOS), Perfluorooctanoic Acid (PFOA), Perfluorononanoic Acid (PFNA), and Perfluorohexane sulfonic Acid (PFHxS) And Letter from Dr. Stephen M. Roberts, Ph.D. dated 6/25/2019 – Findings of Peer Review Conducted on Technical Background Report June 28, 2019 New Hampshire Department of Environmental Services Technical Background Report for the June 2019 Proposed Maximum Contaminant Levels (MCLs) and Ambient Groundwater Quality Standards (AGQSs) for Perfluorooctane sulfonic Acid (PFOS), Perfluorooctanoic Acid (PFOA), Perfluorononanoic Acid (PFNA), and Perfluorohexane sulfonic Acid (PFHxS) June 28, 2019 Table of Contents Abbreviations ................................................................................................................................................. i Acknowledgements ...................................................................................................................................... iii Section I. Executive Summary ....................................................................................................................... 1 Section II. Introduction ................................................................................................................................. 2 Section III. Reference Dose Derivation ........................................................................................................
    [Show full text]
  • Health Effects Support Document for Perfluorooctanoic Acid (PFOA)
    United States Office of Water EPA 822-R-16-003 Environmental Protection Mail Code 4304T May 2016 Agency Health Effects Support Document for Perfluorooctanoic Acid (PFOA) Perfluorooctanoic Acid – May 2016 i Health Effects Support Document for Perfluorooctanoic Acid (PFOA) U.S. Environmental Protection Agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 822-R-16-003 May 2016 Perfluorooctanoic Acid – May 2016 ii BACKGROUND The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator of the U.S. Environmental Protection Agency (EPA) to periodically publish a list of unregulated chemical contaminants known or anticipated to occur in public water systems and that may require regulation under SDWA. The SDWA also requires the Agency to make regulatory determinations on at least five contaminants on the Contaminant Candidate List (CCL) every 5 years. For each contaminant on the CCL, before EPA makes a regulatory determination, the Agency needs to obtain sufficient data to conduct analyses on the extent to which the contaminant occurs and the risk it poses to populations via drinking water. Ultimately, this information will assist the Agency in determining the most appropriate course of action in relation to the contaminant (e.g., developing a regulation to control it in drinking water, developing guidance, or deciding not to regulate it). The PFOA health assessment was initiated by the Office of Water, Office of Science and Technology in 2009. The draft Health Effects Support Document for Perfluoroctanoic Acid (PFOA) was completed in 2013 and released for public comment in February 2014.
    [Show full text]
  • Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) November 2017 TECHNICAL FACT SHEET – PFOS and PFOA
    Technical Fact Sheet – Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) November 2017 TECHNICAL FACT SHEET – PFOS and PFOA Introduction At a Glance This fact sheet, developed by the U.S. Environmental Protection Agency Manmade chemicals not (EPA) Federal Facilities Restoration and Reuse Office (FFRRO), provides a naturally found in the summary of two contaminants of emerging concern, perfluorooctane environment. sulfonate (PFOS) and perfluorooctanoic acid (PFOA), including physical and Fluorinated compounds that chemical properties; environmental and health impacts; existing federal and repel oil and water. state guidelines; detection and treatment methods; and additional sources of information. This fact sheet is intended for use by site managers who may Used in a variety of industrial address these chemicals at cleanup sites or in drinking water supplies and and consumer products, such for those in a position to consider whether these chemicals should be added as carpet and clothing to the analytical suite for site investigations. treatments and firefighting foams. PFOS and PFOA are part of a larger group of chemicals called per- and Extremely persistent in the polyfluoroalkyl substances (PFASs). PFASs, which are highly fluorinated environment. aliphatic molecules, have been released to the environment through Known to bioaccumulate in industrial manufacturing and through use and disposal of PFAS-containing humans and wildlife. products (Liu and Mejia Avendano 2013). PFOS and PFOA are the most Readily absorbed after oral widely studied of the PFAS chemicals. PFOS and PFOA are persistent in the exposure. Accumulate environment and resistant to typical environmental degradation processes. primarily in the blood serum, As a result, they are widely distributed across all trophic levels and are found kidney and liver.
    [Show full text]
  • Cardiovascular Disease Dyslipidemia | Non-Pharmacologic Treatment |
    Cardiovascular Disease Dyslipidemia: Non-Pharmacologic Treatment Mark C. Houston, M.D., M.S. ABAARM, FACP, FACN, FAHA, FASH INTRODUCTION Cardiovascular disease (CVD) is the number one cause of morbidity and mortality in the United States,1 coronary heart disease (CHD) and myocardial infarction being the leading causes of death.1 The five major risk factors for CHD – hypertension, dyslipidemia, diabetes mellitus, smoking, and obesity – account for 80% of the risk for CHD.1,2 Interventions, both pharmacologic and nonpharmacologic, can improve all of these risk factors and decrease the incidence of CVD and its consequences, such as 3-6 myocardial infarction, angina, congestive heart failure and stroke. Recent guidelines by the National Cholesterol Education Program (NCEP) recommend more aggressive control of serum lipids to reduce the incidence of CHD.7 Nutritional and dietary therapy, weight loss, exercise, and scientifically-proven nutritional supplementation should be used initially in appropriately selected patients to manage dyslipidemia. Hypertriglyceridemia, which is frequently due to obesity, insulin resistance, metabolic syndrome and diabetes mellitus, deserves special attention.7 Pharmacologic therapy should be administered in those cases that are at high or very high-risk for CHD and those who do not respond to non-drug therapy. Many patients prefer non-drug therapies for many reasons including adverse effects of anti-lipid drugs, contraindications or allergic reactions to drugs, perceptions of adverse effects of drugs, or personal preference for natural or alternative therapies. A more aggressive integrative approach to the management of dyslipidemia is recommended to improve CHD outcomes, minimize adverse effects, and reduce health-care costs. NUTRITION AND EXERCISE Optimal nutrition and proper aerobic and resistance exercise form the cornerstone for the management of dyslipidemia.
    [Show full text]
  • Microbiota and Obesogens: Environmental Regulators of Fat Storage
    Microbiota and obesogens: environmental regulators of fat storage John F. Rawls, Ph.D. Department of Molecular Genetics & Microbiology Center for Genomics of Microbial Systems Duke University School of Medicine Seminar outline 1. Introduction to the microbiota 2. Microbiota as environmental factors in obesity 3. Obesogens as environmental factors in obesity Seeing and understanding the unseen Antonie van Leewenhoek 1620’s: Described differences between microbes associated with teeth & feces during health & disease. Louis Pasteur 1850’s: Helps establish the “germ theory” of disease. 1885: Predicts that germ-free animals can not survive without “common microorganisms”. Culture-independent analysis of bacterial communities using 16S rRNA gene sequencing 16S rRNA 16S SSU rRNA 16S rRNA gene V1 V2 V3 V4 V5 V6 V7 V8 V9 Culture-independent analysis of bacterial communities using 16S rRNA gene sequencing plantbiology.siu.edu Phylogenetic analysis of 16S rRNA genes revealed 3 domains and a vast unappreciated diversity of microbial life You are here Carl Woese Glossary • Microbiota / microflora: the microorganisms of a particular site, habitat, or period of time. • Microbiome: the collective genomes of the microorganisms within a microbiota. • Germ-free / axenic: of a culture that is free from living organisms other than the host species. • Gnotobiotic: of an environment for rearing organisms in which all the microorganisms are either excluded or known. Current techniques for microbiome profiling Microbial community Morgan et al. (2012) Trends in
    [Show full text]
  • Information to Users
    INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 0211150 The role of fatty acids and related analogs in mediating peroxisome proliferation in primary cultures of rat hepatocytes Intrasuksri, Urusa, Ph.D.
    [Show full text]
  • Perfluorooctanoic Acid (Pfoa) and Perfluorooctanesulfonic Acid (Pfos)
    WATER QUALITY FACT SHEET: PERFLUOROOCTANOIC ACID (PFOA) AND PERFLUOROOCTANESULFONIC ACID (PFOS) Chemical Properties: • PFOA and PFOS are fluorinated organic chemicals that are part of a larger man-made chemical group referred to as per- and polyfluoroalkyl substances (PFAS), which are resistant to heat, water, and oil. • The chemicals have been used in consumer products such as carpets, clothing, fabrics for furniture, paper packaging for food, and other materials (e.g., cookware) designed to be waterproof, stain- resistant or non-stick. • They also have been used in fire-retarding foam at airfields, military bases, and various industrial processes. • PFOA and PFOS have been the most extensively produced and studied PFAS. PFAS also includes GenX chemicals and perfluorobutane sulfonic acid (PFBS) which require further study. • PFAS tends to accumulate in groundwater with contamination typically localized and associated with facilities where the chemicals were produced or used to manufacture other products. Health Concerns: • In 2016, the United States Environmental Protection Agency (USEPA) issued a lifetime health advisory for PFOA and PFOS for drinking water. Municipalities were advised that they should notify their customers of the presence of levels over 70 ppt (0.07 µg/L) in community water supplies. • Studies indicate that PFOA and PFOS may result in adverse health effects including developmental effects to fetuses during pregnancy or breastfed infants, cancer, liver effects, immune effects, thyroid effects, and cholesterol changes. Regulatory Considerations: • The USEPA has not regulated PFOA and PFOS. There is no Federal MCL or MCLG. • In August 2019, the California State Water Resources Control Board Division of Drinking Water (DDW) updated notification levels for PFOA and PFOS from 14 ppt to 5.1 ppt for PFOA and from 13 ppt to 6.5 ppt for PFOS.
    [Show full text]
  • Perfluorooctanoic Acid Levels, Nuclear Receptor Gene Polymorphisms, And
    www.nature.com/scientificreports OPEN Associations among perfuorooctanesulfonic/ perfuorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study Sumitaka Kobayashi1, Fumihiro Sata1,2, Houman Goudarzi1,3, Atsuko Araki1, Chihiro Miyashita1, Seiko Sasaki4, Emiko Okada5, Yusuke Iwasaki6, Tamie Nakajima7 & Reiko Kishi1* The efect of interactions between perfuorooctanesulfonic (PFOS)/perfuorooctanoic acid (PFOA) levels and nuclear receptor genotypes on fatty acid (FA) levels, including those of triglycerides, is not clear understood. Therefore, in the present study, we aimed to analyse the association of PFOS/PFOA levels and single-nucleotide polymorphisms (SNPs) in nuclear receptors with FA levels in pregnant women. We analysed 504 mothers in a birth cohort between 2002 and 2005 in Japan. Serum PFOS/ PFOA and FA levels were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Maternal genotypes in PPARA (rs1800234; rs135561), PPARG (rs3856806), PPARGC1A (rs2970847; rs8192678), PPARD (rs1053049; rs2267668), CAR (rs2307424; rs2501873), LXRA (rs2279238) and LXRB (rs1405655; rs2303044; rs4802703) were analysed. When gene-environment interaction was considered, PFOS exposure (log10 scale) decreased palmitic, palmitoleic, and oleic acid levels (log10 scale), with the observed β in the range of − 0.452 to − 0.244; PPARGC1A (rs8192678) and PPARD (rs1053049; rs2267668) genotypes decreased triglyceride, palmitic, palmitoleic, and oleic acid levels, with the observed β in the range of − 0.266 to − 0.176. Interactions between PFOS exposure and SNPs were signifcant for palmitic acid (Pint = 0.004 to 0.017). In conclusion, the interactions between maternal PFOS levels and PPARGC1A or PPARD may modify maternal FA levels. Te genetic makeup of a person and the environmental factors might be responsible for regulating the levels of serum lipids, such as fatty acids (FA) and triglycerides (TG)1.
    [Show full text]
  • Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Reprod Manuscript Author Toxicol. Author Manuscript Author manuscript; available in PMC 2018 March 01. Published in final edited form as: Reprod Toxicol. 2017 March ; 68: 85–104. doi:10.1016/j.reprotox.2016.07.011. Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders Shuk-Mei Hoa,b,c,d,*, Ana Cheonga,b, Margaret A. Adgente, Jennifer Veeversa,c, Alisa A. Suenf,g, Neville N.C. Tama,b,c, Yuet-Kin Leunga,b,c, Wendy N. Jeffersonf, and Carmen J. Williamsf,* aDepartment of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America bCenter for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America cCincinnati Cancer Center, Cincinnati, Ohio, United States of America dCincinnati Veteran Affairs Hospital Medical Center, Cincinnati, Ohio, United States of America eDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America fReproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America gCurriculum in Toxicology, UNC Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure
    [Show full text]
  • Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark
    A Service of Leibniz-Informationszentrum econstor Wirtschaft Leibniz Information Centre Make Your Publications Visible. zbw for Economics Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas Working Paper Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark ZEW Discussion Papers, No. 10-062 Provided in Cooperation with: ZEW - Leibniz Centre for European Economic Research Suggested Citation: Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas (2010) : Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark, ZEW Discussion Papers, No. 10-062, Zentrum für Europäische Wirtschaftsforschung (ZEW), Mannheim This Version is available at: http://hdl.handle.net/10419/41440 Standard-Nutzungsbedingungen: Terms of use: Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Documents in EconStor may be saved and copied for your Zwecken und zum Privatgebrauch gespeichert und kopiert werden. personal and scholarly purposes. Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle You are not to copy documents for public or commercial Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich purposes, to exhibit the documents publicly, to make them machen, vertreiben oder anderweitig nutzen. publicly available on the internet, or to distribute or otherwise use the documents in public. Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, If the documents have been made available under an Open gelten abweichend von diesen Nutzungsbedingungen die in der dort Content Licence (especially Creative Commons Licences), you genannten Lizenz gewährten Nutzungsrechte. may exercise further usage rights as specified in the indicated licence. www.econstor.eu Dis cus si on Paper No. 10-062 Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark Ulrich Kaiser, Susan J.
    [Show full text]