DOCSLIB.ORG

Open Thesis__Cifelli .Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Open Thesis__Cifelli .Pdf The Pennsylvania State University The Graduate School The Department of Nutritional Sciences ALL-TRANS-RETINOIC ACID REGULATES VITAMIN A HOMEOSTASIS A Thesis in Nutrition by Christopher J. Cifelli 2006 Christopher Cifelli Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2006 The thesis of Christopher Cifelli has been reviewed and approved* by the following: A. Catharine Ross Professor and Dorothy Foehr Huck Chair in Nutrition Thesis Advisor Chair of Committee John L. Beard Professor of Nutrition Professor-in-charge, Graduate Program in Nutrition Michael H. Green Professor of Nutrition Head of the Department of Nutritional Sciences Ronald S. Kensinger Professor of Animal Nutrition * Signatures are on file in the Graduate School ABSTRACT All-trans-retinoic acid (RA) is the active metabolite of vitamin A (VA) that mediates the majority of VA-dependent functions, such as embryonic development, cellular proliferation and differentiation, testicular function, and immune function. RA and its isomers and metabolites have been extensively studied for their ability to treat or prevent numerous disease conditions. For instance, isomers of RA have been used pharmacologically to treat diseases of the skin and to treat certain cancers. Because of the clinical impact of RA on different disease conditions, it is important to delineate the affects of acute and chronic RA administration on both whole-body and tissue specific retinol and RA utilization and kinetics. Therefore, the overall research hypothesis in the present study is that RA regulates retinol and RA homeostasis in rats. This hypothesis was addressed in four separate studies First, the effects of chronic dietary RA administration on retinol utilization and kinetics were determined in rats with low VA stores using compartmental analysis. The results showed that RA supplementation lowered the disposal rate and system fractional catabolic rate of VA, resulting in a positive VA balance. Moreover, the model-predicted traced mass and residence times of the liver, lung, small intestine, and kidney were higher in the LA + RA rats. In contrast, there was no major difference in VA kinetics in the eyes, testes, adrenal glands, or remaining carcass between the groups. Thus, we conclude that chronic administration of RA to rats with low VA status affects the recycling, uptake, and mass of VA at both the whole-body level and in specific organs. Second, the effect of VA-status on the distribution and metabolism of a dose of [3H]RA was examined in VA-deficient (VAD), VA-marginal (VAM), VA-sufficient iii (VAS), and VA-repleted (VAD + retinyl palmitate) rats. The results of our study demonstrate that VA status affects both the organ distribution and metabolism of RA in rats. Specifically, VA-deficiency increased the total amount of radioactivity recovered from the liver, lung, and small intestine, while significantly reducing the amount of [3H]- metabolites of RA recovered in liver, lung, and small intestine. In contrast, the ratio of metabolized to unmetabolized RA was highest in the VAS rats. Additionally, the administration of retinyl palmitate to VAD rats, in a 20-h period resulted in increased hepatic stores of retinol, which allowed them to metabolize the [3H]RA in a manner similar to the VAS rats. Overall, our results indicate that the uptake, recycling, and utilization of RA are altered in a tissue-specific manner in response to decreasing stores of vitamin A. Third, the effects of exogenous RA on hepatic CYP26A1 expression was examined in naïve and RA-pretreated (RA-primed) rats. Our results showed that the acute administration of an intravenous dose (10 µg / 100 g body weight) significantly increased CYP26A1 mRNA expression in a time-dependent manner. In addition, the mRNA expression of CYP26A1 was higher in the RA-primed rats than in the naïve rats. Similarly, hepatic CYP26A1 protein levels were significantly increased within 30 minutes in both the naïve and RA-primed rats. However, CYP26A1 protein levels returned to (RA-primed) or near (naïve) levels within 90 minutes. Additionally, CYP26A1 mRNA and CYP26A1-related protein levels were directly correlated in both the naïve and RA-primed rats between 0 and 60 minutes. Finally, the average formation of RA-metabolites was greater in the RA-primed rats than in the naïve rats and the amount of metabolites of RA generated by rat liver microsomes increased over time. iv In conclusion, the results of our study demonstrate that CYP26A1 mRNA expression, CYP26A1-related protein expression, and hepatic RA-metabolizing activity all rapidly increased in response to i.v. RA in both naïve and RA-primed rats. Fourth, we investigated the effects of RA and lipopolysaccharide (LPS), a bacterial cell-wall component capable of stimulating an inflammatory response in rats, alone and in combination on the distribution and metabolism of a dose of [3H]RA in VA- marginal rats. The results showed that LPS significantly reduced the total amount of 3H recovered in the liver 10 and 30 minutes post-injection. Whereas LPS did not affect the total amount of [3H]-metabolites present in the liver, lung, or small intestine, RA pretreatment significantly increased the amount of [3H]-metabolites in each tissue at both 10 and 30 minutes. Moreover, this induction in RA metabolism occurred irrespective of LPS administration. Thus, the results of this study demonstrate that acute inflammation alters systemic RA homeostasis by disrupting the normal distribution of RA, while the conversion of [3H]RA to [3H]-labeled metabolites was significantly increased by RA alone indicating that LPS and RA independently affect RA metabolism in VA-marginal rats. Overall, the results presented here suggest that VA (retinol and retinoic acid) homeostasis is maintained through an autoregulatory process, with RA acting as the feedback messenger. In addition, we propose that tissue and plasma RA levels are homeostatically maintained within a narrow range despite nutritional and physiological stress, which allows the body to respond to minor alterations in whole-body VA status. v TABLE OF CONTENTS List of Figures……………………………………………………………………………ix List of Tables………………………………………………………………………….....x List of Abbreviations……………………………………………………………………xi Acknowledgements…………………………………………………………………….xiii Introduction and Hypotheses…………………………………………………………..1 Chapter 1: Review of the Literature…………………………………………………..4 Introduction……………………………………………………………………....5 Vitamin A Metabolism…………………………………………………………..5 1) Digestion and Absorption……………………………………………5 2) Cellular Retinoid-Binding Proteins………………………………….6 3) Retinol Esterification and Storage…………………………………...8 4) Retinol Mobilization and Retinol-Binding Protein………………….11 5) Retinoic Acid………………………………………………………...14 6) Retinoic Acid and Retinoid X Receptors……………………………16 7) Retinoic Acid Catabolism…………………………………………...18 Vitamin A and Immunity………………………………………………………..24 1) Overview of the Immune System…………………………………...24 2) Inflammation, Lipopolysaccharide, and the Toll-like Receptors…...26 3) Cytokines and the Hepatic Acute Phase Response…………………28 4) Vitamin A and Immune Function…………………………………..30 Conclusion……………………………………………………………………...33 vi Chapter 2: Retinoic Acid affects whole-body and organ-specific Vitamin A kinetics in Vitamin A-marginal rats……………………………………34 Introduction……………………………………………………………………35 Overview of Compartmental Analysis………………………………………...37 Research Design and Methods………………………………………………...42 Results and Discussion………………………………………………………...47 Chapter 3: Vitamin A status affects the distribution and catabolism of retinoic acid in rats…………………………………………………...62 Introduction……………………………………………………………………63 Research Design and Methods………………………………………………...65 Results…………………………………………………………………………70 Discussion……………………………………………………………………..79 Chapter 4: Exogenous retinoic acid can rapidly induce the transcription and translation of CYP26A1 in liver and increase hepatic retinoic acid metabolism in rat…………………………………………………………………….85 Introduction…………………………………………………………………...86 Research Design and Methods………………………………………………..88 Results………………………………………………………………………...93 Discussion…………………………………………………………………….100 Chapter 5: All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats…………………………………………………………….103 Introduction…………………………………………………………………...104 vii Research Design and Methods………………………………………………..107 Results………………………………………………………………………..111 Discussion……………………………………………………………………122 Chapter 6: Discussion and Conclusions…………………………………………...128 Introduction…………………………………………………………………..129 LRAT and CYP26 Regulate Retinoid Homeostasis…………………………130 Dietary Retinoic Acid Alters Vitamin A Kinetics in Rats with Low Vitamin A Status………………………………………………..131 Vitamin A Status Affects RA Distribution and Metabolism…………………133 Exogenous Retinoic Acid Rapidly Induces CYP26A1 mRNA and Protein Expression……………………………………………………134 Inflammation-Induced Changes in Retinoic Acid Metabolism………………137 Comparison of Retinoic Acid Doses…………………………………………139 Experimental Limitations and Future Directions…………………………….141 Conclusions…………………………………………………………………..142 Works Cited…………………………………………………………………………147 Appendix A: Supplemental Figures………………………………………………..173 viii LIST OF FIGURES Figure 1 Three-compartment model…………………………………………………….38 Figure 2 Mean observed and model-predicted fraction of injected dose in plasma………………………………………………………………………48 Figure 3 Mean observed and model-predicted fraction of injected dose in select organs………………………………………………………………..50 Figure 4
Load more

Recommended publications
  • Vitamin A: History, Current Uses, and Controversies M
    Vitamin A: History, Current Uses, and Controversies M. Shane Chapman, MD Vitamin A is required for the proper functioning of many important metabolic and physio- logic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it’s physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are contro- versial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail. Semin Cutan Med Surg 31:11-16 © 2012 Published by Elsevier Inc. KEYWORDS vitamin A, retinoids, carotenoids, sunscreens, bone metabolism, teratogenicity, depression, suicidal ideation, istotretinoin, inflammatory bowel disease. itamin A is a fat-soluble vitamin that is required for the molecules, retinal, for both low-light- and color vision. Ret- Vproper functioning of a diverse array of metabolic and inol is also converted to retinoic acid, which is a hormone- physiologic activities. Vision, hematopoiesis, embryonic de- like growth factor important for epithelial cell growth and velopment, skin cell differentiation, immune system func- differentiation. It is required for skin and bone health, but in tion, and gene transcription all require vitamin A.
    [Show full text]
  • Manual for Sugar Fortification with Vitamin a Part 3
    Manual for Sugar Fortification with Vitamin A Part 3 Analytical Methods for the Control and Evaluation of Sugar Fortification with Vitamin A Omar Dary, Ph.D. Guillermo Arroyave, Ph.D. with Hernando Flores, Ph.D., Florisbela A. C. S. Campos, and Maria Helena C. B. Lins Dr. Omar Dary is a research biochemist at the Institute of Nutrition of Central America and Panama (INCAP), Guatemala. Dr. Guillermo Arroyave is an international consultant in micronutrients residing in San Diego, California. Dr. Hernando Flores, Ms. Campos, and Ms. Lins are biochemists at the Universidad de Pernambuco, Brazil. MANUAL FOR SUGAR FORTIFICATION PART 3 TABLE OF CONTENTS ACKNOWLEDGMENTS ........................................................... v FOREWORD ...................................................................vii I. INTRODUCTION .......................................................... 1 II. PROPERTIES OF RETINOL AND RETINOL COMPOUNDS USED IN SUGAR FORTIFICATION .......................................................... 3 III. PRINCIPLES FOR DETERMINING RETINOL IN VITAMIN A PREMIX AND FORTIFIED SUGAR .................................................................. 5 A. Spectrophotometric method ............................................. 5 B. Colorimetric method .................................................. 6 IV. SPECTROPHOTOMETRIC DETERMINATION OF RETINOL IN PREMIX ........... 7 A. References .......................................................... 7 B. Principle ............................................................ 7 C. Critical
    [Show full text]
  • LC-MS-MS Quantitative Analysis of 12 Retinoids, Derivatives And
    LC-MS-MS quantitative analysis of 12 Retinoids, derivatives and metabolites in serum for clinical research use Rory M Doyle, Joshua Kline, Thermo Scientific Inc., 265 Davidson Avenue, Somerset, NJ 08873 ABSTRACT Reagents Table 1- Scan Parameters- SRM table Figure 1: Chromatograms and Retention time The following Fisher Scientific™ acids, reagents and solvents were used- Compound Rt Polarity Precursor Product Collision Rf Introduction: Liquid chromatography triple quadrupole mass spectrometry is suited for rapid analysis (min) (m/z) (m/z) Energies Lens F:\ASMS-STD\100ngml-STD 05/25/17 19:11:02 100ngml-STD of multiple analytes of similar and different structures and physicochemical properties. Retinoids are HPLC grade Water Formic Acid (V) (V) a diverse group of three different generations of biologically active compounds that physiologically RT: 0.00 - 5.29 RT: 0.00 - 5.29 Methanol Acetonitile RT: 0.86 RT: 3.16 impact the bodies’ functions and include- retinol, retinal, tretinoin, isotretinoin, etretinate, acitretin, Tazarotenic Acid 0.86 Positive 324.2 294/308 34.3/36.4 191 AA: 17396997 AA: 116868 Methyl-Tert-Butyl-Ether (MTBE) 100 Tazarotenic Acid 100 Bexarotene adapalene, bexarotene, tazarotene and metabolites. A sensitive and specific LC-MS/MS analytical Tazarotene 1.67 Positive 352.2 324.01294 26.4/40.1 206 research method was developed and optimized for the quantitation of retinoids and metabolites in 0 0 RT: 1.67 RT: 3.27 serum. Simple sample preparation techniques were used that included a protein crash and liquid- The standards and internal standards were made up in Methanol. Acitretin 2.51 Positive 327.2 176.9/159 10.3/17.4 101 AA: 88457528 AA: 527912 100 Tazarotene 100 Retinoic Acid liquid extraction.
    [Show full text]
  • Biological Activity and Metabolism of the Retinoid Axerophthene (Vitamin a Hydrocarbon)
    [CANCER RESEARCH 38, 1734-1738, June 1978] Biological Activity and Metabolism of the Retinoid Axerophthene (Vitamin A Hydrocarbon) Dianne L. Newton, Charles A. Frolik, Anita B. Roberts, Joseph M. Smith, Michael B. Sporn, Axel NUrrenbach, and Joachim Paust National Cancer Institute, Bethesda, Maryland 20014 [D. L. N., C. A. F., A. B. R., J. M. S., M. B. S.], and BASF Aktiengesellschaft, 6700 Ludwigshafen am Rhein, Germany ¡A.N., J. P] ABSTRACT ity and properties of this molecule. In this study we report a detailed investigation of the biological activity and metabo Biological properties of axerophthene, the hydrocarbon lism of axerophthene. Subsequent studies will deal with the analog of retino!, have been studied both in vitro and in possible effectiveness of this compound for prevention of vivo. In trachea! organ culture axerophthene reversed experimental breast cancer. keratinization caused by deficiency of retinoid in the culture medium; its potency was of the same order of magnitude as that of retinyl acetate. Axerophthene sup MATERIALS AND METHODS ported growth in hamsters fed vitamin A-deficient diets although less effectively than did retinyl acetate. Axer Axerophthene was synthesized as follows: 1100 g (1.75 ophthene was considerably less toxic than was retinyl mol) of crystalline all-E-retinyltriphenylphosphonium bisul acetate when administered repeatedly in high doses to fate (16) were dissolved in 1500 ml of dimethylformamide at rats. Administration of an equivalent p.o. dose of axer about 25°.A solution of 140 g (3.5 mol) of sodium hydroxide ophthene caused much less deposition of retinyl palmi- in 1100 ml of water was added while the temperature of the tate in the liver than did the same dose of retinyl acetate, mixture was kept at about 25°.After being stirred for 3 hr at while a greater level of total retinoid was found in the about 25°,the mixture was extracted with n-hexane (3 x mammary gland after administration of axerophthene.
    [Show full text]
  • Disturbed Vitamin a Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD)
    nutrients Review Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD) Ali Saeed 1,2, Robin P. F. Dullaart 3, Tim C. M. A. Schreuder 1, Hans Blokzijl 1 and Klaas Nico Faber 1,4,* 1 Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; a.saeed@umcg.nl (A.S.); t.c.m.a.schreuder@umcg.nl (T.C.M.A.S.); h.blokzijl@umcg.nl (H.B.) 2 Institute of Molecular Biology & Bio-Technology, Bahauddin Zakariya University, Multan 60800, Pakistan 3 Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; r.p.f.dullaart@umcg.nl 4 Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands * Correspondence: k.n.faber@umcg.nl; Tel.: +31-(0)5-0361-2364; Fax: +31-(0)5-0361-9306 Received: 7 November 2017; Accepted: 19 December 2017; Published: 29 December 2017 Abstract: Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs).
    [Show full text]
  • BUFF Safety Assessment of Retinol and Retinyl Palmitate As Used In
    BUFF Safety Assessment of Retinol and Retinyl Palmitate as Used in Cosmetics CIR EXPERT PANEL MEETING SEPTEMBER 10-11, 2012 August 16, 2012 Memorandum To: CIR Expert Panel From: Wilbur Johnson, Jr. Manager/Lead Specialist Subject: Re-review Document on Retinol and Retinyl Palmitate A final report on the safety assessment of retinol and retinyl palmitate with the following conclusion was published in 1987: On the basis of the available animal and clinical data presented in this report, the CIR Expert Panel concludes that retinyl palmitate and retinol are safe as cosmetic ingredients in the present practices of use and concentration. The Expert Panel confirmed this original conclusion in 2005, after reviewing published and unpublished data that became available since 1987. Since then, a National Toxicology Program (NTP) photocarcinogenicity study on retinyl palmitate and retinoic acid was completed and studies on the photogenotoxicity of retinyl palmitate and retinol have entered the published literature. With support from FDA, CIR staff determined that these new data warranted another re-review of the safety of retinol and retinyl palmitate in cosmetics. A copy of the re-review document on these two ingredients is included along with the CIR report history, Literature search strategy, Ingredient Data profile, Minutes from the June 13-14 2005 Expert Panel Meeting, 1987 published CIR final report on retinol and retinyl palmitate, and 2012 FDA VCRP data. The following memoranda from the Environmental Working Group (EWG) and Personal Care Products Council (PCPC) relating to the NTP photocarcinogenicity study on retinyl palmitate and retinoic acid are included as well: 1.
    [Show full text]
  • Review Article Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects
    Hindawi Publishing Corporation Journal of Lipids Volume 2013, Article ID 710290, 19 pages http://dx.doi.org/10.1155/2013/710290 Review Article Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects Angel Catalá1,2 1 Instituto de Investigaciones Fisicoqu´ımicas Teoricas´ y Aplicadas (INIFTA-CCT La Plata-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, 1900 La Plata, Argentina 2 Carrera del Investigador Cient´ıfico, Consejo Nacional de Investigaciones Cient´ıficas y Tecnicas´ (CONICET), 1900 La Plata, Argentina Correspondence should be addressed to Angel Catala;´ catala@inifta.unlp.edu.ar Received 6 September 2013; Accepted 7 October 2013 Academic Editor: Robert Salomon Copyright © 2013 Angel Catala.´ 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. I have been involved in research on polyunsaturated fatty acids since 1964 and this review is intended to cover some of the most important aspects of this work. Polyunsaturated fatty acids have followed me during my whole scientific career and I have published a number of studies concerned with different aspects of them such as chemical synthesis, enzymatic formation, metabolism, transport, physical, chemical, and catalytic properties of a reconstructed desaturase system in liposomes, lipid peroxidation, and 14 their effects. The first project I became involved in was the organic synthesis of[1- C] eicosa-11,14-dienoic acid, with the aim of demonstrating the participation of that compound as a possible intermediary in the biosynthesis of arachidonic acid “in vivo.” From 1966 to 1982, I was involved in several projects that study the metabolism of polyunsaturated fatty acids.
    [Show full text]
  • Risk Assessment of Vitamin a (Retinol and Retinyl Esters) in Cosmetics
    Risk assessment of vitamin A (retinol and retinyl esters) in cosmetics Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety Date: 22.08.12 Doc. no.: 10-405-3 final ISBN: 978-82-8259-059-4 VKM Report 2012: 25 VKM Report 2012: 25 Norwegian Scientific Committee for Food Safety (VKM) 10/405-3 final Risk assessment of vitamin A (retinol and retinyl esters) in cosmetics Ragna Bogen Hetland (Chair) Berit Granum Claus Lützow-Holm Jan Ludvig Lyche Jan Erik Paulsen Vibeke Thrane 2 Norwegian Scientific Committee for Food Safety (VKM) 10/405-3 final Contributors Persons working for VKM, either as appointed members of the Committee or as ad hoc experts, do this by virtue of their scientific expertise, not as representatives for their employers. The Civil Services Act instructions on legal competence apply for all work prepared by VKM. Acknowledgements The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has appointed a working group consisting of both VKM members and external experts to answer the request from the Norwegian Food Safety Authority. The members of the working group are acknowledged for their valuable work on this opinion. The members of the working group are: VKM members Ragna Bogen Hetland, Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics (Chair) Berit Granum, Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7459.288 B2 Bosley Et Al
    US007459288B2 (12) United States Patent (10) Patent No.: US 7459.288 B2 Bosley et al. (45) Date of Patent: Dec. 2, 2008 (54) METHOD OF PRODUCING RETINYL EP O O94771 5, 1983 ESTERS EP O 343 444 5, 1989 GB 2 0263.19 7, 1978 (75) Inventors: John Anthony Bosley, Kettering (GB); JP 56113760 9, 1981 Clive Roderick Harding, Trumbull, CT JP 612125.15 9, 1986 (US); Christopher Rawlins, Shambrook JP 622484.95 10, 1987 (GB); Julia Sarah Rogers, Shambrook JP 6032774 2, 1994 (GB); Ian Richard Scott, Stratford upon WO 99.32105 7, 1999 Avon (GB) WO O 1/78676 10, 2001 (73) Assignee: Unilever Home & Personal Care USA, division of Conopco, Inc., Greenwich, OTHER PUBLICATIONS CT (US) International Search Report, PCT/EP03/12206, mailed Mar. 1, 2004, (*) Notice: Subject to any disclaimer, the term of this 2 pp. patent is extended or adjusted under 35 GB Search Report, GB 0226270.7, dated Apr. 17, 2003, 1 p. U.S.C. 154(b) by 412 days. GB Search Report, GB0226270.7, dated May 21, 2003, 1 p. Maugard, et al., “Enzymatic Synthesis of Derivatives of Vitamin A in (21) Appl. No.: 10/534,520 Organic Media”, Journal of Molecular Catalysis B Enzymatic, vol. 8, No. 4-6, Feb. 18, 2000, pp. 275-280, XP002270 197. (22) PCT Filed: Oct. 27, 2003 O'Connor, et al., “Candida-Cylindracea Lipase-Catalysed Synthesis of Retinyl and Oleyl Palmitates Carbon Chain Length Dependence of (86). PCT No.: PCT/EPO3/12206 Esterase Activity”, Australian Journal of Chemistry, vol. 45, No. 4. 1992, pp. 641-649, XP0008027552.
    [Show full text]
  • A Study on the Latest Research Trends in Natural Products with Anti-Aging Effects
    Journal of Convergence for Information Technology e-ISSN 2586-4440 Vol. 9. No. 12, pp. 286-293, 2019 DOI : https://doi.org/10.22156/CS4SMB.2019.9.12.286 A Study on the Latest Research Trends in Natural products with Anti-Aging Effects Young-Hee Pyo1, Seon-Hee You2* 1Professor, Dept. of Beauty & Cosmetic, Osan University 2Adjunct professor, Dept. of Beauty Stylist-Major in Skin Care, Yeonsung University 항노화 효능을 가진 천연물에 대한 최신 연구 동향에 관한 연구 표영희1, 유선희2* 1오산대학교 뷰티&코스메틱계열 교수, 2연성대학교 뷰티스타일리스트과 겸임교수 Abstract In this study, four types of retinol, retinyl palmitate, adenocin, and polytoxylate-dretinamide, which are the ingredients of the Ministry of Food and Drug Safety Notice, included in the study. also we looked at trends in research on Sciadopitys verticillata, Prunella vulgaris, Celosia cristata L., Brazilin, Persicaria hydropiper, Astragalus membranaceus Bunge, Forsythiae Fructus, Lithospermum root, Rheum undulatum L. and Cistanche deserticola Y. C. Ma a natural material that has the efficacy of antioxidant aging. The anti-aging study so far has been found to be centered mainly on collagen production and elastase synthesis inhibition mechanisms. However, given that the aging process of the skin is caused by various ageing processes, it is believed that anti-aging studies using safe and effective natural materials that can help the skin age with various mechanisms should be conducted. Key Words : Anti-aging, Ministry of Food and Drug Safety, Elastase, Wrinkle Improvement, Natural Materials, Collagen 요 약 본 연구에서는 식약청 고시 원료인 레티놀, 레티닐팔미테이트, 아데노신, 폴리에톡실레이티드레틴아마이드 4종류와 항 노화의 효능을 가진 천연 원료인 금송, 하고초, 맨드라미, 브라질린, 여뀌, 황기, 연교, 자근, 대황, 육종 용에 대한 연구 동향을 살펴보았다.
    [Show full text]
  • Victoria Hiscock Discusses Vitamin a As a Skincare Ingredient
    SKIN/DERMATOLOGY VITAMIN A www.aestheticmed.co.uk “A” STA R Victoria Hiscock discusses vitamin A as a skincare ingredient ithout question, the greatest boon to anti- BIO-AVAILABILITY OF RETINOIDS ageing treatments was the introduction of The amount of biological activity will differ with each substrate retinoic acid by Albert M Kligman, MD, PhD in of vitamin A. Retinoic acid is the only form of retinol the body 1986. Since then, the world of vitamin A has can use, therefore, the body uses specialised enzymes in exploded and many new compounds have been the skin cells to convert vitamin A into retinoic acid. Not all Wdeveloped to treat a host of skin conditions. forms of vitamin A are created equally. Some are more easily There are many different types of vitamin A which vary in converted to retinoic acid than others. A typical conversion strength and action. These can be seen in the table below. pathway looks like this: VITAMIN A SUBSTRATES – By strength Retinyl palmitate <=> Retinol <=> Retinaldehyde => Retinoic acid Retinoic Acid Tretinoin It takes two and three metabolic steps, correspondingly, (All-Trans-Retnoic-Acid/ (prescription only) to convert retinol and retinyl palmitate to retinoic acid. ATRA) The overall rate of conversion of retinol to retinoic Retinyl Retinoate Chemically joined Retinoic acid is low and that of retinyl palmitate is lower still. Acid and Retinol Molecules Therefore, a relatively large amount of retinol and Retinal / Retinaldehyde Can convert to Retinoic Acid even larger amount of retinyl palmitate needs to be or Retinol delivered into a cell to boost retinoic acid levels and Retinol Entire Vitamin A Molecule produce clinically meaningful effects.
    [Show full text]
  • Submission for Vitamin A
    MCC submission – Vitamin A Submission for Vitamin A Part A 1. International Non-proprietary Name (or British Approved Name or US Adopted Name) of the medicine. Retinol (Vitamin A) - includes retinol acetate [synonym retinol acetate], retinol palmitate [synonym retinyl palmitate], retinol propionate. 2. Proprietary name(s). Not applicable. 3. Name of the company / organisation / individual requesting a reclassification. Not applicable. This request is made on behalf of the natural health products industry. 4. Dose form(s) and strength(s) for which a change is sought. Not applicable. This request is made on behalf of the natural health products industry. 5. Pack size and other qualifications. Not applicable. This request is made on behalf of the natural health products industry. 6. Indications for which change is sought. Not applicable. This request is made on behalf of the natural health products industry. 7. Present classification of the medicine. At the present time, Vitamin A is: • Unscheduled when in products for external use containing 1 percent or less. • Unscheduled when in products for internal use containing 3 milligrams or less of retinol equivalents per recommended daily dose [ie 10,000 IU]. • Unscheduled when in parenteral nutrition replacement preparations. • A prescription medicine except in the situations above. 8. Classification sought. It is proposed that the classification of Vitamin A is changed to: • Unscheduled when in products for external use containing 1 percent or less. • Unscheduled when in products for internal use containing 6 milligrams or less of retinol equivalents or less per recommended daily dose [ie 20,000 IU]. • Unscheduled when in parenteral nutrition replacement preparations.
    [Show full text]