DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,198.324 B2 Fortin (45) Date of Patent: Jun

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,198.324 B2 Fortin (45) Date of Patent: Jun USOO8198324B2 (12) United States Patent (10) Patent No.: US 8,198.324 B2 Fortin (45) Date of Patent: Jun. 12, 2012 (54) COMPOSITIONS COMPRISING Rubinstein, L.V., "Comparison of InVitro Anticancer-DrugScreen POLYUNSATURATED FATTY ACID ing Data Generated with a Tetrazolium Assay Versus a Protein Assay MONOGLYCERDES ORDERVATIVES Against a Diverse Panel of Human Tumor Cell Lines”. JNatl Cancer Inst, Jul. 4, 1990, 1113-1118, vol. 82, No. 13. THEREOF AND USES THEREOF Skehan, P. “New Colorimetric Cytotoxicity Assay for Anticancer DrugScreening”. JNatl Cancer Inst, Jul. 4, 1990, 1107-1112, vol.82. (75) Inventor: Samuel Fortin, Ste-Luce (CA) No. 13. Rose, D.P. “Omega-3 fatty acids as cancer chemopreventive agents'. (73) Assignee: Centre de Recherche sur les Phamarcology & Therapeutics, 1999, 217-244, 83. Biotechnologies Marines, Rimouski Ohta et al., “Action of a New Mammalian DNA Polymerase Inhibitor, (CA) Sulfoquinovosyldiacylglycerol'. Biol. Pharm. Bull., 1999, 111-116 22(2). (*) Notice: Subject to any disclaimer, the term of this Pacetti et al., “High performance liquid chromatography-tandem patent is extended or adjusted under 35 mass spectrometry of phospholipid molecular species in eggs from hens fed diets enriched in seal blubber oil'. Journal of Chromatog U.S.C. 154(b) by 387 days. raphy A, 2005, 66-73, 1097. Watanabe et al., “n-3 Polyunsaturated fatty acid (PUFA) deficiency (21) Appl. No.: 12/536,519 elevates and n-3 pufa enrichment reduces brain 2-arachidonoylglycerol level in mice'. Department of Clinical Appli (22) Filed: Aug. 6, 2009 cation. Institute of Natural Medicine, Toyama Medical and Pharma ceutical University, Prostaglandins, Leukotrienes and Essential Fatty (65) Prior Publication Data Acids 69 (2003) 51-59. US 2010/O196496 A1 Aug. 5, 2010 Schaafet al., “Polyunsaturated Monoglycerides and a Pregnadiene in Defensive Glands of the Water Beetle Agabus affinis”, University of Bayreuth, Department of Animal Ecology II, Lipids vol. 35. No. 5 Related U.S. Application Data (2000), pp. 543-550. (63) Continuation-in-part of application No. Schaafet al., “Polyunsaturated monoglycerides and a pregnadiene in PCT/CA2008/000530, filed on Mar. 19, 2008. defensive glands of the water beetle Agabus affinis”. Department of Aimal Ecology II, University of Bayreuth, Bayreuth, Germany. (60) Provisional application No. 60/895,795, filed on Mar. Lipids (2000), 35(5), 543-550. 20, 2007. Vandevoorde et al. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of (51) Int. Cl. 1-arachidonoylglycerol with monoacyglycerol lipase abd fatty acid A6 IK3I/22 (2006.01) amide hydrolase. Department of Pharmacology and Clinical A6 IK3I/20 (2006.01) Neuroscience, Umea University, Umea, Swed. Biochemical and Bio physical Research Communications (2005), 337(1), 104-109. Pub (52) U.S. Cl. ......... 514/549; 514/558: 514/559; 514/560 lisher: Elsevier. (58) Field of Classification Search .................. 514/549, Akoh, Casimir C. Lipase-catalyzed synthesis of partial glyceride. 514/558,559, 560 Dep. Food Sci. Technol. Univ. Georgia, Athens, GA, USA. See application file for complete search history. Biotechnoloy Letters (1993), 15(9), 949-954. An English abstract of JP2000044588. Yagi et al. Novel (56) References Cited monoacylglycosyl monoacylglycerols for Surfactants. (Agency of Industrial Sciences and Technology, Japan) Jpn. Kokai Tokkyo Koho U.S. PATENT DOCUMENTS (2000), 7 pp. CODEN. 6,180,671 B1 1/2001 Freedman et al. Rosu et al., “Enzymic synthesis of glycerides from DHA-enriched 6,552,081 B1 4/2003 Freedman et al. PUFAethyl ester by glycerolysis under vacuum”. Graduate school of 7,138.431 B1 1 1/2006 Chilton Bio- and Agro-Sciences, Laboratory of Molecular Biotechnology, 7,981,915 B2 7, 2011 Freedman Nagoya University, Nagoya Japan. Journal of Molecular Catalysis B. 2002fO188024 A1 12/2002 Chilton et al. Enzymatic (1988), 4(4), 191-198. 2004/0214799 A1 10, 2004 Mukai et al. 2009, 0291 102 A1 11/2009 Fortin (Continued) 2009,0292019 A1 11/2009 Fortin 2010, 0160261 A1 6, 2010 Fortin FOREIGN PATENT DOCUMENTS Primary Examiner — Kevin E Weddington WO O2O64166 8, 2002 (74) Attorney, Agent, or Firm — Bereskin & Parr WO O2O89787 11, 2002 LLP/S.E.N.C.R.L., s.r.l. WO 020964.08 12/2002 WO 2004O24136 3, 2004 WO 2004O64716 8, 2004 (57) ABSTRACT WO 2006, 117668 11, 2006 WO 2008O36353 3, 2008 There are provided various compounds and compositions comprising polyunsaturated fatty acid monoglycerides and OTHER PUBLICATIONS derivatives thereof. These compounds and compositions can Aggarwal et al., Chapter 10, Curcumin-Biologican and medicinal be useful as cancer chemopreventive agents. They can also be Properties, 2007, Medicinal and Aromatic Plants—Industrical Pro useful for enhancing solubility of various active agents and files, Turmeric, 45,297-368. enhancing their bioavailability. Monks, A., “Feasibility of a High-Flux Anticancer Drug Screen Using a Diverse Panel of Cultured Human Tumor Cell Lines”. JNatl Cancer Inst, Jun. 5, 1991, 757-766, vol. 83, No. 11. 29 Claims, 9 Drawing Sheets US 8,198.324 B2 Page 2 OTHER PUBLICATIONS An English Abstract of JP 02131418 of Okazaki et al., "Comparison of Enhanced and Routine Methods for Measuring Ambient Low Yamane et al. “Mutiple intensified performance of an enzyme-cata Level Sulfur Dioxide”. (Sansei Pharmaceutical Co., Ltd., Japan.) lyzed reaction in organic medium'. Laboratory of Molecular Jpn. Kokai Tokkyo Koho (1980), 7 pp. Biotechnology Graduates School of Bio- and Agro-Sciences, An abstract of Myrdal et al., “Solubilization of Drugs in Aqueous Nagoya University, Nagoya, Japan. Annals of the New York Acad Media' Department of pharmacy Practice and Science, College of emy of Sciences (1988), 864 (Enzyme Engineering XIV), 171-179. Pharmacy, The University of Arizona, Encyclopedia of pharmaceu Ando et al., “Reinvestigation of positional distribution of fatty acids tical technology, published on Oct. 2, 2006. in docosahexaenoic acid-rich fish oil triacyl-sn-glycerols'. Depar An abstract of Rohan et al., “Dietary factors and survival from breast ment of Marine Bioresources Chemnistry, Faculty of Fisheries, Hok cancer', National Cancer Institute of Canada (NCIC) Epidemiology kaido Universit, Hakodate, Japan. Lipids (2000), 35(5), 579-582. Unit, University of Toronto, Nutr Cancer 1993.20(2) 167-77. Kawashima et al., “Enzymatic synthesis of high-purity structured Kafrawy et al., “Docosahexaenoic acid in phosphatidylcholine medi lipids with caprylic acid at 1.3-positions and polyunsaturated fatty ates cytotoxacity more effectively than other (O-3 and (O-6 fatty acid at 2-positin”. Sonoda Wowen's Junior College, Hyogo, Japan. acids'. Department of Biology, Indiana University, Cancer Letters Journal of the American Oil Chemists' Society (2001) 78(6), 611 132(1998) 23-29. 616. Kawashima et al., “Inhibition of Rat Liver Microsomal Desaturases Watanabe et al. “n-3 Polyunsaturated fatty acid (PUFA) deficiency by Curcumin and Related Compounds'. Biosci. Biotech. Biochem. elevates and n-3 PUFA enrichment reduces brain 60(1), pp. 108-110, 1996. 2-arachidonoyglycerol level in mice' Institute of Natural Medicine, Shimizu et al., “Sesamin Is a Potent and Specific Inhibitor of A5 Department of Clinical Application, Toyama Medical and Pharma Desaturase in Polyunsaturated Fatty Acid Biosynthesis”. LIPIDS. ceutical University, Toyama, Japan. Prostaglandins Leukotrienes and vol. 26, No. 7, pp. 512-516, 1991. Essential Fatty Acids (2003), 69(1), 51-59. Nakano et al., “Inhibitory Effects of Capsaicinoids on Fatty Acid Watanabe et al., “Chemical signals involved in larval metamorphosis Desaturation in a Rat Liver Cell Line'. Biosci. Biotech. Biochem. in Hydroides Ezoensis(Serpulidae; Polychaeta). Part II: isolation and 65(8), pp. 1859-1863, 2001. identification of a new monoacyl Glycerol from adult tube clumps as Kawashima et al., “Nicardipine and Nifedipine Inhibit Fatty Acid a metamorphosis-including Substance'. Department of Applied Bio Desaturases in Rat Liver Microsomes’, Biosci. Biotech. Biochem. logical Chemistry, Faculty of Agricultur, Shizuoka University, 60(10), pp. 1672-1676, 1996. Shizuoka, Japan. Journal of Marine Biotechnology (1998), 61(1), Kawashima et al., “Inhibitory effects of alkyl gallate and its deriva 11-15. tives on fatty acid desaturation'. Biochimica et Biophysica Acta A partial English translation of Tanaka et al., Preparative separation 1299, pp. 34-38, 1996. of acylglycerol by cebtrifugal partition chromatography (CPC). Chau et al., “Monoglyceride and diglyceride lipases from human Tsukuba Res. Lab., Nippon Oil and Fats Co., Ltd., Tsukuba, Japan. platelet microsomes”. Biochimica et Biophysical Acta, 963, pp. 436 Yukagaku (1992), 41(1), 23-7. 444, 1998. Feng Li et al., "Biosynthesis of Docosahexaenoate-Containing Beharry et al., "Long-term docosahexaenoic acid therapy in a Glycerolipid Molecular Species in the Retina” Journal of Molecular congenic murine model of cystic fibrosis'. Am J Physiol Gastrointest Neuroscience (2001), vol. 16, 206-214. Liver Physiol 292:G839-G848, Nov. 9, 2006. An English abstract of JP7149786 of Yazama et al., C. R. Martin et al., “The safety and efficacy of oral docosahexaenoic “Glyceroglycolipid and Carcinogenic Promoter Inhibitor', pub acid Supplementation for the treatment of primary Sclerosing lished on Jun. 13, 1995. cholangitis—a pilot study”. Aliment Pharmacol Ther, Nov.30, 2011; Zerouga et al., “Synthesis of a Novel Phosphatidylcholine Conju 35:255-265. gated to Docosahexaenoic Acid and Methotrexate that Inhibits Cell Freedman et al.,
Load more

Recommended publications
  • Appendix E Papers That Were Accepted for ECOTOX
    Appendix E Papers that Were Accepted for ECOTOX E1. Acceptable for ECOTOX and OPP 1. Aitken, R. J., Ryan, A. L., Baker, M. A., and McLaughlin, E. A. (2004). Redox Activity Associated with the Maturation and Capacitation of Mammalian Spermatozoa. Free Rad.Biol.Med. 36: 994-1010. EcoReference No.: 100193 Chemical of Concern: RTN,CPS; Habitat: T; Effect Codes: BCM,CEL; Rejection Code: LITE EVAL CODED(RTN,CPS). 2. Akpinar, M. B., Erdogan, H., Sahin, S., Ucar, F., and Ilhan, A. (2005). Protective Effects of Caffeic Acid Phenethyl Ester on Rotenone-Induced Myocardial Oxidative Injury. Pestic.Biochem.Physiol. 82: 233- 239. EcoReference No.: 99975 Chemical of Concern: RTN; Habitat: T; Effect Codes: BCM,PHY; Rejection Code: LITE EVAL CODED(RTN). 3. Amer, S. M. and Aboul-Ela, E. I. (1985). Cytogenetic Effects of Pesticides. III. Induction of Micronuclei in Mouse Bone Marrow by the Insecticides Cypermethrin and Rotenone. Mutation Res. 155: 135-142. EcoReference No.: 99593 Chemical of Concern: CYP,RTN; Habitat: T; Effect Codes: CEL,PHY,MOR; Rejection Code: LITE EVAL CODED(RTN),OK(CYP). 4. Bartlett, B. R. (1966). Toxicity and Acceptance of Some Pesticides Fed to Parasitic Hymenoptera and Predatory Coccinellids. J.Econ.Entomol. 59: 1142-1149. EcoReference No.: 98221 Chemical of Concern: AND,ARM,AZ,DCTP,Captan,CBL,CHD,CYT,DDT,DEM,DZ,DCF,DLD,DMT,DINO,ES,EN,ETN,F NTH,FBM,HPT,HCCH,MLN,MXC,MVP,Naled,KER,PRN,RTN,SBDA,SFR,TXP,TCF,Zineb; Habitat: T; Effect Codes: MOR; Rejection Code: LITE EVAL CODED(RTN),OK(ARM,AZ,Captan,CBL,DZ,DCF,DMT,ES,MLN,MXC,MVP,Naled,SFR).
    [Show full text]
  • Cphi & P-MEC China Exhibition List展商名单version版本20180116
    CPhI & P-MEC China Exhibition List展商名单 Version版本 20180116 Booth/ Company Name/公司中英文名 Product/产品 展位号 Carbosynth Ltd E1A01 Toronto Research Chemicals Inc E1A08 SiliCycle Inc. E1A10 SA TOURNAIRE E1A11 Indena SpA E1A17 Trifarma E1A21 LLC Velpharma E1A25 Anuh Pharma E1A31 Chemclone Industries E1A51 Hetero Labs Limited E1B09 Concord Biotech Limited E1B10 ScinoPharm Taiwan Ltd E1B11 Dongkook Pharmaceutical Co., Ltd. E1B19 Shenzhen Salubris Pharmaceuticals Co., Ltd E1B22 GfM mbH E1B25 Leawell International Ltd E1B28 DCS Pharma AG E1B31 Agno Pharma E1B32 Newchem Spa E1B35 APEX HEALTHCARE LIMITED E1B51 AMRI E1C21 Aarti Drugs Limited E1C25 Espee Group Innovators E1C31 Ruland Chemical Co., Ltd. E1C32 Merck Chemicals (Shanghai) Co., Ltd. E1C51 Mediking Pharmaceutical Group Ltd E1C57 珠海联邦制药股份有限公司/The United E1D01 Laboratories International Holdings Ltd. FMC Corporation E1D02 Kingchem (Liaoning) Chemical Co., Ltd E1D10 Doosan Corporation E1D22 Sunasia Co., Ltd. E1D25 Bolon Pharmachem Co., Ltd. E1D26 Savior Lifetec Corporation E1D27 Alchem International Pvt Ltd E1D31 Polish Investment and Trade Agency E1D57 Fischer Chemicals AG E1E01 NGL Fine Chem Limited E1E24 常州艾柯轧辊有限公司/ECCO Roller E1E25 Linnea SA E1E26 Everlight Chemical Industrial Corporation E1E27 HARMAN FINOCHEM E1E28 Zhechem Co Ltd E1F01 Midas Pharma GmbH Shanghai Representativ E1F03 Supriya Lifescience Ltd E1F10 KOA Shoji Co Ltd E1F22 NOF Corporation E1F24 上海贺利氏工业技术材料有限公司/Heraeus E1F26 Materials Technology Shanghai Ltd. Novacyl Asia Pacific Ltd E1F28 PharmSol Europe Limited E1F32 Bachem AG E1F35 Louston International Inc. E1F51 High Science Co Ltd E1F55 Chemsphere Technology Inc. E1F57a PharmaCore Biotech Co., Ltd. E1F57b Rockwood Lithium GmbH E1G51 Sarv Bio Labs Pvt Ltd E1G57 抗病毒类、抗肿瘤类、抗感染类和甾体类中间体、原料药和药物制剂及医药合约研发和加工服务 上海创诺医药集团有限公司/Shanghai Desano APIs and Finished products of ARV, Oncology, Anti-infection and Hormone drugs and E1H01 Pharmaceuticals Co., Ltd.
    [Show full text]
  • S41598-020-68561-7.Pdf
    www.nature.com/scientificreports OPEN Prolongation of metallothionein induction combats Aß and α‑synuclein toxicity in aged transgenic Caenorhabditis elegans Dagmar Pretsch1*, Judith Maria Rollinger2, Axel Schmid3, Miroslav Genov 1, Teresa Wöhrer1, Liselotte Krenn2, Mark Moloney4, Ameya Kasture3, Thomas Hummel3 & Alexander Pretsch1 Neurodegenerative disorders (ND) like Alzheimer’s (AD), Parkinson’s (PD), Huntington’s or Prion diseases share similar pathological features. They are all age dependent and are often associated with disruptions in analogous metabolic processes such as protein aggregation and oxidative stress, both of which involve metal ions like copper, manganese and iron. Bush and Tanzi proposed 2008 in the ‘metal hypothesis of Alzheimer’s disease’ that a breakdown in metal homeostasis is the main cause of NDs, and drugs restoring metal homeostasis are promising novel therapeutic strategies. We report here that metallothionein (MT), an endogenous metal detoxifying protein, is increased in young amyloid ß (Aß) expressing Caenorhabditis elegans, whereas it is not in wild type strains. Further MT induction collapsed in 8 days old transgenic worms, indicating the age dependency of disease outbreak, and sharing intriguing parallels to diminished MT levels in human brains of AD. A medium throughput screening assay method was established to search for compounds increasing the MT level. Compounds known to induce MT release like progesterone, ZnSO­ 4, quercetin, dexamethasone and apomorphine were active in models of AD and PD. Thiofavin T, clioquinol and emodin are promising leads in AD and PD research, whose mode of action has not been fully established yet. In this study, we could show that the reduction of Aß and α‑synuclein toxicity in transgenic C.
    [Show full text]
  • Multiple Dietary Supplements Do Not Affect Metabolic and Cardio-Vascular Health Andreea Soare Washington University School of Medicine in St
    Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 Multiple dietary supplements do not affect metabolic and cardio-vascular health Andreea Soare Washington University School of Medicine in St. Louis Edward P. Weiss Washington University School of Medicine in St. Louis John O. Holloszy Washington University School of Medicine in St. Louis Luigi Fontana Washington University School of Medicine in St. Louis Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Soare, Andreea; Weiss, Edward P.; Holloszy, John O.; and Fontana, Luigi, ,"Multiple dietary supplements do not affect metabolic and cardio-vascular health." Aging.6,2. 149-157. (2014). https://digitalcommons.wustl.edu/open_access_pubs/2607 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. www.impactaging.com AGING, February 2014, Vol. 6, No 2 Research Paper Multiple dietary supplements do not affect metabolic and cardio‐ vascular health Andreea Soare1,2*, Edward P. Weiss1,3*, John O. Holloszy 1, and Luigi Fontana1,4,5 1 Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63130, USA 2 Department of Endocrinology and Diabetes, University Campus Bio‐Medico, Rome, Italy 3 Department of Nutrition and Dietetics, St. Louis University, St. Louis, MO 63130, USA 4 Department of Medicine, Salerno University School of Medicine, Salerno, Italy 5 CEINGE Biotecnologie Avanzate, Napoli, Italy * These authors contributed equally to this research Key words: supplements, endothelial function, arterial stiffness, inflammation, oxidative stress Received: 8/12/13; Accepted: 8/31/13; Published: 9/4/13 Correspondence to: Luigi Fontana, MD/PhD; E‐mail: [email protected] Copyright: © Soare et al.
    [Show full text]
  • Research Article Sesamin: a Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation
    Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 242810, 15 pages doi:10.1155/2012/242810 Research Article Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation Yun-Ping Lim,1, 2 Chia-Yun Ma,1 Cheng-Ling Liu,3 Yu-Hsien Lin,1 Miao-Lin Hu,3 Jih-Jung Chen,4 Dong-Zong Hung,1, 2 Wen-Tsong Hsieh,5 and Jin-Ding Huang6, 7 1 Department of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan 2 Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung 40447, Taiwan 3 Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan 4 Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 90741, Taiwan 5 School of Medicine and Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan 6 Institute of Biopharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan 70101, Taiwan 7 Department of Pharmacology, Medical College, National Cheng Kung University, Tainan 70101, Taiwan Correspondence should be addressed to Yun-Ping Lim, [email protected] Received 14 December 2011; Revised 30 January 2012; Accepted 6 February 2012 Academic Editor: Pradeep Visen Copyright © 2012 Yun-Ping Lim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI).
    [Show full text]
  • In Y1yq Studies of Suspected Mechanisms of Ddt-Resistance
    IN Y1YQ STUDIES OF SUSPECTED MECHANISMS OF DDT-RESISTANCE IN BLATTELLA GERM.ANICA (L.) by George Lawrence Rolof son Thesis submitted to the Graduate Faculty of the Virginia Polytechnic Institute in partial fulfillment for the degree of DOCTOR OF PHILOSOPHY in Entomology APPROVED: Donald G. Cochran James McD. Grayson Mary H. Ross Ryland E. Webb David A. West Blacksburg, Virginia May 1968 TABLE OF CONTENTS Page I. INTRODUCTION , . 1 II. LITERATURE REVIEW . 3 Early Insecticide Resistance •• . 3 Development of DDT • . 4 Development of DDT Resistance in Houseflies . 6 DDT-Resistance in Cockroaches and Other Insects 13 Inheritance of DDT Resistance . 18 Mode of Action of DDT . ~ . 23 DDT Synergism by Sesamex • • • • . .. 35 III. METIIODS AND MATERIALS . 42 Cockroach Strains • • • • • • 42 Treatment Procedure . 43 Sample Extraction and Cleanup it • • • • • • • • 44 Quantitation of DDT and Metabolites . 47 Thin Layer Chromatography . 48 IV. RESULTS AND DISCUSSION • • • . 50 Toxicological Date • . • • • if • • • 50 DDT Recovery , • • • • • • • • . 52 Penetration . 52 Detoxication • . • • 66 Excretion • • • • • • • • • • • • • • • • • • • 102 Combined Effects • • • ~ • • ~ j • • • • • ~ • ~ • • • • 122 ii iii Page v. STJMMARY 133 VI. REFERENCES CITED . .. 135 VII. VITA. 154 ACKNOWLEDGEMENTS The writer wishes to express his appreciation to Dr. Donald G. Cochran for his helpful criticisms and suggestions throughout the duration of this program. Appreciation is also extended to Dr. Jack L. Bishop for his helpful suggestions in the early part of this work and to Dr. James McD. Grayson for his continuous thoughtful encouragement. The writer is grateful to Drs. Cochran, Graysoni Ross, Webb and West for their critical reading of this manuscript and to Professor Rodney Young for the use of his laboratory and equipment.
    [Show full text]
  • Cns Active Principles from Selected Chinese Medicinal Plants
    THE FACULTY OF MEDICINE IN THE UNIVERSITY OF LONDON CNS ACTIVE PRINCIPLES FROM SELECTED CHINESE MEDICINAL PLANTS Thesis presented by MIN ZHU (BSc., MSc.) for the degree of Doctor of Philosophy Department of Pharmacognosy The School of Pharmacy University of London 1994 ProQuest Number: 10105154 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10105154 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT In order to identify potential central nervous system (CNS) active principles from plants, 10 Chinese herbs have been selected from literature reports, namely Schejflera hodinieri, Schejflera delavayi, Celastrus angulatus, Celastrus orbiculatus, Clerodendrum mandarinorum, Clerodendrum bungei, Periploca callophylla, Periploca forrestii, Alangium plantanifolium and Uncaria rhynchophylla. These plants were extracted by 70% ethanol and biologically screened by receptor ligand binding assays which included a 1-adrenoceptor, a2-adrenoceptor, p-adrenoceptor, 5HT1, 5HT1A, 5HT1C, 5HT2, opiate, benzodiazepine, Ca^-ion channel(DHP), K^-ion channel, dopamine 1, dopamine 2, adenosine 1, muscarinic, histamine 1, Na'^/K^ ATPase, GABA^ and GABAg receptors. The results of extract screening showed that all these plants were able to inhibit the specific binding of radioligands to at least one receptor at concentrations of 1 mg/ml.
    [Show full text]
  • Pregnane X Receptor (PXR) Polymorphisms and Cancer
    biomolecules Review PregnaneReview X Receptor (PXR) Polymorphisms andPregnane Cancer XTreatment Receptor (PXR) Polymorphisms and Cancer Treatment Aikaterini Skandalaki, Panagiotis Sarantis and Stamatios Theocharis * Aikaterini Skandalaki , Panagiotis Sarantis and Stamatios Theocharis * First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; [email protected] (A.S.); [email protected] (P.S.) * Correspondence:First Department [email protected]; of Pathology, Medical Tel.: School, +30-210-746-2116 National and Kapodistrian University of Athens, 11527 Athens, Greece; [email protected] (A.S.); [email protected] (P.S.) * Correspondence: [email protected]; Tel.: +30-210-746-2116 Abstract: Pregnane X Receptor (PXR) belongs to the nuclear receptors’ superfamily and mainly functions as a xenobiotic sensor activated by a variety of ligands. PXR is widely expressed in normal Abstract: Pregnane X Receptor (PXR) belongs to the nuclear receptors’ superfamily and mainly and malignant tissues. Drug metabolizing enzymes and transporters are also under PXR’s regula- functions as a xenobiotic sensor activated by a variety of ligands. PXR is widely expressed in normal tion. Antineoplastic agents are of particular interest since cancer patients are characterized by sig- and malignant tissues. Drug metabolizing enzymes and transporters are also under PXR’s regulation. nificant intra-variability to treatment response and severe toxicities. Various PXR polymorphisms Antineoplastic agents are of particular interest since cancer patients are characterized by significant may alter the function of the protein and are linked with significant effects on the pharmacokinetics intra-variability to treatment response and severe toxicities. Various PXR polymorphisms may of chemotherapeutic agents and clinical outcome variability.
    [Show full text]
  • Enzymatic Regulation of Vitamin E Status: Identification and Characterization of the Novel Tocopherol-Omega-Hydroxylase Pathway of Vitamin E Catabolism
    ENZYMATIC REGULATION OF VITAMIN E STATUS: IDENTIFICATION AND CHARACTERIZATION OF THE NOVEL TOCOPHEROL-OMEGA-HYDROXYLASE PATHWAY OF VITAMIN E CATABOLISM A Dissertation Presented to the Faculty of the Graduate School of Cornell University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Timothy Joseph Sontag January 2005 © 2005 Timothy Joseph Sontag ENZYMATIC REGULATION OF VITAMIN E STATUS: IDENTIFICATION AND CHARACTERIZATION OF THE NOVEL TOCOPHEROL-OMEGA-HYDROXYLASE PATHWAY OF VITAMIN E CATABOLISM Timothy Joseph Sontag, Ph.D. Cornell University 2005 Tocopherols and tocotrienols all possess to varying levels the vitamin E activity of α-tocopherol, the most bioactive form of the vitamin in vivo. α- Tocopherol is the most abundant vitamer in vivo, potentially explaining its higher bioactivity. This is despite higher dietary levels of other vitamers. The preferential retention of α-tocopherol appears to be at the level of elimination. Urinary metabolites of tocopherols, with the phytyl tail truncated to a three-carbon carboxylated moiety, were reported previously. The goal of this work was to elucidate the pathway(s) by which these metabolites are formed. Incubations of tocopherols in hepatocyte culture produced all expected intermediates in the predicted pathway of catabolism of vitamin E. This pathway involves ω-hydroxylation of a terminal methyl group of the phytyl tail, followed by step-wise removal of two or three carbon units by a β-oxidation mechanism. Analysis of microsomal enzyme activity led to the elucidation of CYP4F2 as the major P450 involved in the initial ω-hydroxylation reaction. Substrate-specificity of this enzyme was high, with activity toward γ- tocopherol being 10-fold greater than toward α-tocopherol.
    [Show full text]
  • Potential Intervention Targets in Utero and Early Life for Prevention of Hormone Related Cancers C
    Potential Intervention Targets in Utero and Early Life for Prevention of Hormone Related Cancers C. Mary Schooling, PhD,a, b Lauren C. Houghton, PhD,c Mary Beth Terry, PhDc abstract Hormone-related cancers have long been thought to be sensitive to exposures during key periods of sexual development, as shown by the vulnerability to such cancers of women exposed to diethylstilbestrol in utero. In addition to evidence from human studies, animal studies using new techniques, such as gene knockout models, suggest that an increasing number of cancers may be hormonally related, including liver, lung, and bladder cancer. Greater understanding of sexual development has also revealed the “mini-puberty” of early infancy as a key period when some sex hormones reach levels similar to those at puberty. Factors driving sex hormones in utero and early infancy have not been systematically identified as potential targets of intervention for cancer prevention. On the basis of sex hormone pathways, we identify common potentially modifiable drivers of sex hormones, including but not limited to factors such as obesity, alcohol, and possibly nitric oxide. We review the evidence for effects of modifiable drivers of sex hormones during the prenatal period and early infancy, including measured hormones as well as proxies, such as the second-to-fourth digit length ratio. We summarize the gaps in the evidence needed to identify new potential targets of early life intervention for lifelong cancer prevention. Strong associations between diethylstilbestrol exposure in utero and the subsequent risk of clear cell vaginal cancer offered the first epidemiologic evidence that a prenatal exposure, particularly a hormonal one, could lead to cancer later in life.
    [Show full text]
  • Bioavailability of Lignans in Human Subjects
    Nutrition Research Reviews (2006), 19, 187–196 DOI: 10.1017/NRR2006129 q The Authors 2006 Bioavailability of lignans in human subjects Thomas Clavel1,2, Joe¨l Dore´2 and Michael Blaut1* 1Department of Gastrointestinal Microbiology, Institute of Human Nutrition Potsdam-Rehbru¨cke, Arthur-Scheunert-Allee 155, 14558 Nuthetal, Germany 2Unit of Ecology and Physiology of the Digestive Tract, National Institute for Research in Agriculture, Jouy-en-Josas, France Dietary lignans are phyto-oestrogens that possibly influence human health. The present review deals with lignan bioavailability, the study of which is crucial to determine to what extent metabolism, absorption and excretion of lignans alter their biological properties. Since intestinal bacteria play a major role in lignan conversion, for instance by producing the enterolignans enterodiol and enterolactone, emphasis is put on data obtained in recent bacteriological studies. Phyto-oestrogens: Lignans: Enterolignans: Bioavailability: Human intestinal microbiota Introduction enterodiol (ED) and enterolactone (EL) (Borriello et al. 1985), the biological properties of which are proposed to be Phyto-oestrogens are dietary compounds of plant origin that more potent than those of plant lignans (Brooks & mainly include flavonoids and lignans. Since their chemical Thompson, 2005; Jacobs et al. 2005). Numerous data structure is similar to those of oestrogens, they have been presented in the present review deal primarily with SDG. studied for their involvement in hormone-related disorders, However, it must be emphasised that enterolignans are such as reproductive failure and breast cancer (Setchell & produced from plant lignans other than SDG and Adlercreutz, 1988). Meanwhile, it has become clear that it is MAT (Axelson et al.
    [Show full text]
  • House Memorial 42: Parkinson's Disease and Pesticide Exposure
    House Memorial 42: Parkinson’s Disease and Pesticide Exposure A Review of the Association between Pesticide Exposure and Parkinson’s Disease Respectfully Submitted by Retta Ward, Cabinet Secretary New Mexico Department of Health With contributions from the New Mexico Department of Agriculture November 7, 2013 1 Table of Contents Executive Summary ............................................................................................................................................... 3 Background ............................................................................................................................................................ 5 2013 Legislative Session ............................................................................................................................................ 5 Federal Regulation of Pesticides................................................................................................................................ 5 Pesticide Regulation in New Mexico ......................................................................................................................... 6 Methods ................................................................................................................................................................ 8 Literature Search ....................................................................................................................................................... 8 Inclusion and Exclusion Criteria ................................................................................................................................
    [Show full text]