DOCSLIB.ORG

Retinoic Acid and Its Derivatives in Skin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Retinoic Acid and Its Derivatives in Skin cells Review Retinoic Acid and Its Derivatives in Skin Łukasz Szyma ´nski 1, Rafał Skopek 1, Małgorzata Palusi ´nska 1, Tino Schenk 2,3, Sven Stengel 4, Sławomir Lewicki 5,6,* , Leszek Kraj 7 , Paweł Kami ´nski 8 and Arthur Zelent 1,* 1 Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Post˛epu36A, 05-552 Magdalenka, Poland; [email protected] (Ł.S.); [email protected] (R.S.); [email protected] (M.P.) 2 Department of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, 07747 Jena, Germany; [email protected] 3 Institute of Molecular Cell Biology, Center for Molecular Biomedicine Jena (CMB), Jena University Hospital, 07747 Jena, Germany 4 Department of Internal Medicine IV, Division of Gastroenterology, Hepatology and Infectious Disease, Jena University Hospital, Friedrich Schiller University of Jena, 07747 Jena, Germany; [email protected] 5 Department of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland 6 Department of Medicine, Faculty of Medical Sciences and Health Sciences, Kazimierz Pulaski University of Technology and Humanities, 26-600 Radom, Poland 7 Department of Oncology, Medical University of Warsaw, 01-163 Warsaw, Poland; [email protected] 8 Department of Gynecology and Oncological Gynecology, Military Institute of Medicine, 01-163 Warsaw, Poland; [email protected] * Correspondence: [email protected] or [email protected] (S.L.); [email protected] (A.Z.); Tel.: +48-261-816-108 (S.L.); Fax: +48-261-816-141 (S.L.) Received: 27 October 2020; Accepted: 7 December 2020; Published: 11 December 2020 Abstract: The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions. Here, we provide a synopsis of the main advances in understanding the role of ATRA and its receptors in dermatology. Keywords: vitamin A; all-trans-retinoic acid; retinoic acid receptors; dermatology 1. Introduction Retinoids are defined as synthetic or natural derivatives of vitamin A that were first discovered in 1913. Retinol and retinyl ester are dietary forms of what is commonly known as vitamin A. These forms of vitamin A are not biologically active and require transformation, by cytosolic alcohol dehydrogenases (ADHs) and microsomal retinol dehydrogenases (MDHs), to become retinaldehyde, and subsequent oxidation by retinaldehyde dehydrogenases RALDH1, RALDH2, and RALDH3 to retinoic acid (RA) [1]. While the reverse transformation of retinaldehyde to retinol is possible through the DHRS3 enzyme Cells 2020, 9, 2660; doi:10.3390/cells9122660 www.mdpi.com/journal/cells CellsCells2020 2020, 9, ,9 2660, x FOR PEER REVIEW 22 of of 14 15 the DHRS3 enzyme activity, the retinaldehyde to RA conversion is irreversible [2]. RA exists in activity,several theisoforms retinaldehyde of which to the RA most conversion common is are irreversible all-trans [retinoic2]. RA existsacid and in several 9-cis retinoic isoforms acid of [2]. which All- thetrans-retinoic most common acid are (ATRA) all-trans is retinoicalso one acid of andthe main 9-cis retinoicphysiologically acid [2]. All-trans-retinoicactive metabolites acid of vitamin (ATRA) isA. alsoRetinoids, one of thewhich main are physiologically hydrophobic activecompounds, metabolites require of vitaminretinoid-binding A. Retinoids, proteins which for are stabilization hydrophobic in compounds,aqueous media. require Depending retinoid-binding on the localization, proteins for the stabilization stabilization in aqueousof retinoids media. is achieved Depending by binding on the localization,to different proteins the stabilization such as cellular of retinoids retinol-binding is achieved proteins by binding (CRBPs) to diff orerent cellular proteins retinoic such acid-binding as cellular retinol-bindingproteins (CRABPs), proteins the (CRBPs) interstitial or cellular retinol-bind retinoicing acid-binding protein (RBP proteins 3), and (CRABPs), plasma-retinol the interstitial binding retinol-bindingprotein (RBP 4) protein [3]. The (RBP half-life 3), and of plasma-retinol RA is around binding 1 h beca proteinuse (RBPit is rapidly 4) [3]. The metabolized half-life of by RA the is aroundcytochrome 1 h because P450 itenzymes is rapidly (CYP26s) metabolized [2]. byCYPs the cytochromeare involved P450 in enzymesATRA hydroxylation (CYP26s) [2]. CYPsand thus are involvedinactivation in ATRA of its hydroxylationfunction. RAs are and not thus only inactivation substrates of for its CYP26 function. enzymes RAs are but not are only also substrates potent CYP26 for CYP26inducers, enzymes therefore but creating are also potenta negativeCYP26 feedbackinducers, loop therefore [4]. creating a negative feedback loop [4]. ItIt is is believed believed that that ATRA ATRA deficiency, deficiency, mediated mediated by by CYPs CYPs or or other other mechanisms, mechanisms, is is associated associated with with cancercancer progression progression and and various various dermatological dermatological diseases diseases [5 [5].]. RetinoidsRetinoids are are usually usually classified classified in one in ofone the of three the generations;three generations; however, however, some researchers some researchers consider pyranonesconsider pyranones derivatives derivatives as the fourth as the generation. fourth gene Briefly,ration. naturally Briefly, occurring,naturally occurring, non-aromatic non-aromatic retinoids areretinoids classified are as classified the first generation,as the first generation, monoaromatic monoaromatic vitamin A derivatives vitamin A arederivatives the second are generation, the second whereasgeneration, retinoids whereas containing retinoids a cycliccontaining polyene a cyclic side-chain polyene are theside-chain third generation are the third [3]. Moregeneration detailed [3]. informationMore detailed about information retinoic acidabout and retinoic its signaling acid and pathways its signaling may pathways be found may in abe recent found reviewin a recent by Ghyselinckreview by Ghyselinck and Duester and (2019) Duester [2]. (2019) [2]. 2.2. Retinoic Retinoic Acid Acid Receptors Receptors and and Molecular Molecular Mechanism Mechanism of of Their Their Action Action RetinoicRetinoic acid acid receptors receptors are are key key developmental developmental regulators regulators and, and, as as such, such, function function as as a a molecular molecular switchswitch in in many many developmental developmental processes processes including including skin skin development. development. In the In absence the absence of a ligand, of a ligand, RARs repressRARs transcriptionrepress transcription through recruiting through histonerecruiting deacetylases histone deacetylases (HDAC) complexes (HDAC) such complexes as HDAC-N-CoR such as (negativeHDAC-N-CoR co-regulator) (negative or HDAC-SMRT co-regulator) (silencing or HDAC-SMRT mediator (silencing for retinoid mediator and thyroid for retinoid hormone and receptors) thyroid (Figurehormone1)[ 6receptors)]. (Figure 1) [6]. FigureFigure 1. 1.Mechanism Mechanism of of all-trans-retinoic all-trans-retinoic acid acid (ATRA) (ATRA) action. action. (A ()A In) In the the absence absence of aof ligand, a ligand, retinoid retinoid X (orX rexinoid)(or rexinoid) receptors receptors and retinoic and retinoic acid receptors acid receptor (RXR-RAR)s (RXR-RAR) heterodimers heterodimers bind to retinoic bind to acid retinoic response acid elementsresponse (RAREs) elements in the(RAREs) regulatory in the regions regulatory of target re genesgions andof target repress genes transcription and repress through transcription recruiting histonethrough deacetylases recruiting (HDAC)histone /deacetco-repressorylases (negative(HDAC)/co-repressor co-regulator (negative (N-CoR) orco-regulator silencing mediator (N-CoR) for or retinoidsilencing and mediator thyroid for hormone retinoid receptors and thyroid (SMRT)) hormone complexes. receptors HDACs (SMRT)) remove complexes. acetyl HDACs groups remove from nucleosomalacetyl groups histones from nucleosomal causing chromatin histones condensationcausing chromatin that precludes condensation binding that ofprecludes other factors binding and of ultimatelyother factors results and in ultimately the silencing results of gene in the expression. silencing ( Bof) Upongene expression. ligand binding, (B) Upon RAR undergoes ligand binding, structural RAR changeundergoes leading structural to dissociation change ofleading the co-repressor to dissociation complex of the and co-repressor association of complex co-activators and association
Load more

Recommended publications
  • In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
    In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning.
    [Show full text]
  • Detailed Review Paper on Retinoid Pathway Signalling
    1 1 Detailed Review Paper on Retinoid Pathway Signalling 2 December 2020 3 2 4 Foreword 5 1. Project 4.97 to develop a Detailed Review Paper (DRP) on the Retinoid System 6 was added to the Test Guidelines Programme work plan in 2015. The project was 7 originally proposed by Sweden and the European Commission later joined the project as 8 a co-lead. In 2019, the OECD Secretariat was added to coordinate input from expert 9 consultants. The initial objectives of the project were to: 10 draft a review of the biology of retinoid signalling pathway, 11 describe retinoid-mediated effects on various organ systems, 12 identify relevant retinoid in vitro and ex vivo assays that measure mechanistic 13 effects of chemicals for development, and 14 Identify in vivo endpoints that could be added to existing test guidelines to 15 identify chemical effects on retinoid pathway signalling. 16 2. This DRP is intended to expand the recommendations for the retinoid pathway 17 included in the OECD Detailed Review Paper on the State of the Science on Novel In 18 vitro and In vivo Screening and Testing Methods and Endpoints for Evaluating 19 Endocrine Disruptors (DRP No 178). The retinoid signalling pathway was one of seven 20 endocrine pathways considered to be susceptible to environmental endocrine disruption 21 and for which relevant endpoints could be measured in new or existing OECD Test 22 Guidelines for evaluating endocrine disruption. Due to the complexity of retinoid 23 signalling across multiple organ systems, this effort was foreseen as a multi-step process.
    [Show full text]
  • 1 Structure and Function of the Skin
    Go Back to the Top To Order, Visit the Purchasing Page for Details 1 Chapter 1 Structure and Function of the Skin The skin is the human body’s its largest organ, covering 1.6 m2 of surface area and accounting for approximate- ly 16% of an adult’s body weight. In direct contact with the outside environment, the skin helps to maintain four essential bodily functions: ① retention of moisture and prevention of permeation or loss of other molecules, ② regulation of body temperature, ③ protection of the body from microbes and harmful external influences, and ④ sensation. To understand cutaneous biology and skin diseases, it is very important to learn the structure and functions of normal human skin. A. Skin surface The skin surface is not smooth, but is laced with multiple net- works of fine grooves called sulci cutis. These can be deep or shallow. The slightly elevated areas that are surrounded by shal- lower areas of sulci cutis are called cristae cutis. Sweat pores fed crista cutis by the sweat glands open to the cristae cutis (Fig. 1.1). The orientation of the sulci cutis, which differs depending on body location, is called the dermal ridge pattern. Fingerprints and sulcus cutis patterns on the palms and soles, which are unique to each person, are formed by the sulci cutis. Elastic fibers also run in specific directions in deeper parts of the skin, with the direction depend- aabcdefg h i j klmnopqr ing on the site. Some skin diseases, such as epidermal nevus, are known to occur along specific lines distributed over the body, the Blaschko lines (Fig.
    [Show full text]
  • Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products
    Research Article Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products Jeri Kim,1 Peiying Yang,2 Milind Suraokar,3 Anita L. Sabichi,3 Norma D. Llansa,3 Gabriela Mendoza,3 Vemparalla Subbarayan,3 Christopher J. Logothetis,1 Robert A. Newman,2 Scott M. Lippman,3 and David G. Menter3 Departments of 1Genitourinary Medical Oncology, 2Experimental Therapeutics, and 3Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Abstract seminal fluid (10). Once PGD2 is made, it forms derivative Stromal-epithelial interactions and the bioactive molecules compounds, most of which can transactivate the peroxisome g g produced by these interactions maintain tissue homeostasis proliferator–activated receptor (PPAR ). One PGD2 derivative, 15-deoxy-D12,14-prostaglandin J (15-d-PGJ ), can slow the growth and influence carcinogenesis. Bioactive prostaglandins pro- 2 2 duced by prostaglandin synthases and secreted by the prostate and induce the partial differentiation of selected cancer cells (12). D12,14 into seminal plasma are thought to support reproduction, but Another PGD2 derivative, 15-deoxy- -PGD2 (15-d-PGD2), has g their endogenous effects on cancer formation remain unre- also been shown to stimulate PPAR transactivation in RAW 264.7 solved. No studies to date have examined prostaglandin cell macrophage cultures as effectively as 15-d-PGJ2 (13). L-PGDS enzyme production or prostaglandin metabolism in normal also binds tritiated testosterone and may play a role in androgen prostate stromal cells. Our results show that lipocalin-type transport (14). In castrated rats, testosterone proprionate induces prostaglandin D synthase (L-PGDS) and prostaglandin D L-PGDS synthesis in the epididymis (15).
    [Show full text]
  • Outpatient Acne Care Guideline
    Outpatient Acne Care Guideline Severity Mild Moderate Severe < 20 comedones or < 20-100 comedones or 15-50 > 5 cysts, >100 comedones, or inflammatory lesions inflammatory lesions >50 inflammatory lesions Initial Treatment Initial Treatment Initial Treatment Benzoyl Peroxide (BP) or Topical Combination Therapy Combination Therapy Topical Retinoid Retinoid + BP Oral antibiotic or OR + (Retinoid + Antibiotic) + BP Topical retinoid Topical Combination Therapy or + BP + Antibiotic Retinoid + (BP + Antibiotic) or OR BP Retinoid + BP Oral antibiotic + topical retinoid + +/- or BP Topical antibiotic Retinoid + Antibiotic + BP or Topical Dapsone IF Inadequate Response IF Inadequate Response IF Inadequate Consider dermatology Response referral Change topical retinoid Consider changing oral concentrations, type and/or antibiotic formulation AND or Add BP or retinoid, if not already Change topiocal combination Consider isotretinoin prescribed therapy Consider hormone therapy or and/or (females) Change topical retinoid Add or change oral antibiotic concentrations, type and/or or formulation Consider isotretinoin Additional Considerations or Consider hormone therapy (females) Change topical comination Previous treatment/history Side effects therapy Costs Psychosocial impact Vehicle selection Active scarring Ease of use Regimen complexity Approved Evidence Based Medicine Committee 1-18-17 Reassess the appropriateness of Care Guidelines as condition changes. This guideline is a tool to aid clinical decision making. It is not a standard of care. The physician should deviate from the guideline when clinical judgment so indicates. GOAL: Pediatricians should initiate treatment for cases of “Mild” to “Severe” acne (see algorithms attached). Pediatricians should also counsel patients in order to maximize adherence to acne treatment regimens: 1. Realistic expectations. Patients should be counseled that topical therapies typically take up to 6-8 weeks to start seeing results.
    [Show full text]
  • Liarozole Hydrochloride (BANM, USAN, Rinnm) Kinetin Hidrocloruro De Liarozol; Liarozole, Chlorhydrate De; Liarozoli 1
    Isotretinoin/Liarozole 1603 Malignant neoplasms. Retinoids such as isotretinoin have 9. Matthay KK, et al. Treatment of high-risk neuroblastoma with Profile been studied in the treatment of various neoplastic or preneoplas- intensive chemotherapy, radiotherapy, autologous bone marrow Kinetin is a plant growth hormone that has been promoted in transplantation, and 13-cis-retinoic acid. N Engl J Med 1999; tic disorders. Although oral tretinoin is used for remission induc- 341: 1165–73. products for the management of photodamaged skin and hyper- tion in acute promyelocytic leukaemia (see p.1619), other retin- 10. Kohler JA, et al. A randomized trial of 13-cis retinoic acid in pigmentation but good evidence of efficacy appears to be lack- oids do not have an established role in the treatment of cancer. children with advanced neuroblastoma after high-dose therapy. ing. There may, however, be a place for the use of retinoids in the Br J Cancer 2000; 83: 1124–7. Preparations chemoprevention of some malignancies. Skin disorders. Apart from its established role in the treatment Proprietary Preparations (details are given in Part 3) There has been particular interest in the potential for retinoids to of acne (above), isotretinoin has been tried in many other skin Arg.: Kinerase†; Braz.: Kinerase; Hong Kong: Kinerase; Malaysia: Kin- prevent the formation of skin cancers (p.672) in patients at in- disorders not responding to usual therapy.1,2 Clinical responses to erase†; Mex.: Kinerase; Singapore: Kinerase; USA: Kinerase. creased risk. Maintenance immunosuppression may increase the oral isotretinoin have been reported1 in small numbers of patients incidence of pre-malignant and malignant skin lesions in solid with anogenital warts (p.1584), rosacea (p.1583), and lichen pla- organ transplant recipients; large numbers of lesions can develop nus (p.1580).
    [Show full text]
  • 4-Hydroxyphenyiretinamide
    Handbook 4 4-Hydroxyphenyiretinamide 1. Chemical and Physical Melting-point Characteristics 173-175 °C (Shealy etal., 1984; Budavari etal., 1996) 1.1. Nomenclature Solubility See General Remarks, section 1.4. Soluble in most organic solvents, fats, oils and aqueous micellar solutions; sparingly soluble in 1.2 Name water, e.g. 13 nmol/L at pH 6.5 (Li et al., 1996). Chemical Abstracts Services Registry Number 65646-68-6 Spectroscopy 1% UV and visible: ? 362 (methanol), E 1 IUPAC systematic name 1225, EM 47 900 (Budavari et al., 1996; Barua & N-[4-(all-E)-9, 13-Dimethyl-7-(1, 1,5-trimethylcy- Fun, 1998). Higher EM values, i.e. 57 100 and 56 clohex-5 -en-6-yl)nona- 7,9,11,1 3-tetraen- 15- 400, have also been reported (Formelli et al., 1996). oyl]aminophenol or N-[4-(all E)-3, 7-dimethyl-9- (2,2,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8- Nuclear magnetic resonance: tetraen-1-oyl]aminophenol 'H-NMR [(CD3)SO4, 100 MHz]: 8 1.03 (1,1-CH3), 1.3-1.8 (2-CH2, 3-CH), 1.70 (5-CH), 1.8-2.2 Synonyms (4-CH2), 1.99 (9-CH), 2.36 (13-CH), 6.03 (14-H), Fenretinide, 4-HPR, N-(4-hydroxyphenyl)reti- 6.1-6.6 (7-H, 8-H, 10-H, 12-H), 6.99 (11-H), namide, hydroxyphenyl-retinamide, N-(4-hydro- 6.6-6.8 and 7.3-7.6 (benzene ring -H), 9.15 (NH), xyphenyl)retinamide, N-(4-hydroxyphenyl)-all- 9.74 (OH) (Coburn et al., 1983; Shealy et al., tnins-retinamide 1984).
    [Show full text]
  • Dermoscopy of Aplasia Cutis Congenita: a Case Report and Review of the Literature
    Dermatology Practical & Conceptual Dermoscopy of Aplasia Cutis Congenita: A Case Report and Review of the Literature Rasna Neelam1, Mio Nakamura2, Trilokraj Tejasvi2 1 University of Michigan Medical School, Ann Arbor, MI, USA 2 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA Key words: aplasia cutis congenita, alopecia, dermoscopy, trichoscopy Citation: Neelam R, Nakamura M, Tejasvi T. Dermoscopy of aplasia cutis congenita: a case report and review of the literature. Dermatol Pract Concept. 2021;11(1):e2021154. DOI: https://doi.org/10.5826/dpc.1101a154 Accepted: September 28, 2020; Published: January 29, 2021 Copyright: ©2021 Neelam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License BY-NC-4.0, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. Authorship: All authors have contributed significantly to this publication. Corresponding author: Trilokraj Tejasvi, MD, Department of Dermatology, University of Michigan, 1910 Taubman Center, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA Email: [email protected] Introduction throbbing, and point tenderness in one of the patches of alo- pecia. The alopecic patch had been present on the right pari- Aplasia cutis congenita (ACC) is a rare heterogeneous con- etal-occipital scalp since birth and has been stable in size and genital disorder characterized by focal or widespread absence appearance for years. Three other round patches of alopecia of the skin. had also been present since birth and remained asymptomatic.
    [Show full text]
  • Pathway Development Via Retinoid X Receptor Vitamin a Enhances In
    Vitamin A Enhances in Vitro Th2 Development Via Retinoid X Receptor Pathway This information is current as Charles B. Stephensen, Reuven Rasooly, Xiaowen Jiang, of September 24, 2021. Michael A. Ceddia, Casey T. Weaver, Roshantha A. S. Chandraratna and R. Patterson Bucy J Immunol 2002; 168:4495-4503; ; doi: 10.4049/jimmunol.168.9.4495 http://www.jimmunol.org/content/168/9/4495 Downloaded from References This article cites 40 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/168/9/4495.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Vitamin A Enhances in Vitro Th2 Development Via Retinoid X Receptor Pathway1 Charles B. Stephensen,2* Reuven Rasooly,* Xiaowen Jiang,* Michael A. Ceddia,3* Casey T. Weaver,† Roshantha A. S. Chandraratna,‡ and R. Patterson Bucy† Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances such responses.
    [Show full text]
  • Nurse-Led Drug Monitoring Clinic Protocol for the Use of Systemic Therapies in Dermatology for Patients
    Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT) Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Lead Author: Dawn Lavery Dermatology Advanced Nurse Practitioner Additional author(s) N/A Division/ Department:: Dermatology, Clinical Support and Tertiary Medicine Applies to: (Please delete) Salford Royal Care Organisation Approving Committee Dermatology clinical governance committee Salford Royal Date approved: 13 February 2019 Expiry date: February 2022 Contents Contents Section Page Document summary sheet 1 Overview 2 2 Scope & Associated Documents 2 3 Background 3 4 What is new in this version? 3 5 Policy 4 Drugs monitored by nurses 4 Acitretin 7 Alitretinoin Toctino 11 Apremilast 22 Azathioprine 26 Ciclosporin 29 Dapsone 34 Fumaric Acid Esters – Fumaderm and Skilarence 36 Hydroxycarbamide 39 Hydroxychloroquine 43 Methotrexate 50 Mycophenolate moefetil 57 Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 1 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version Standards 67 6 Roles and responsibilities 67 7 Monitoring document effectiveness 67 8 Abbreviations and definitions 68 9 References 68 10 Appendices N/A 11 Document Control Information 71 12 Equality Impact Assessment (EqIA) screening tool 73 Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT) 1. Overview (What is this policy about?) The dermatology directorate specialist nurses are responsible for ensuring prescribing and monitoring for patients under their care, is in accordance with this protocol.
    [Show full text]
  • TAZORAC® (Tazarotene) Gel 0.05% (Tazarotene) Gel 0.1%
    NDA 020600 ® TAZORAC (tazarotene) Gel 0.05% (tazarotene) Gel 0.1% FOR DERMATOLOGIC USE ONLY NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE DESCRIPTION TAZORAC® Gel is a translucent, aqueous gel and contains the compound tazarotene, a member of the acetylenic class of retinoids. It is for topical dermatologic use only. The active ingredient is represented by the following structural formula: O OCH2CH3 N S TAZAROTENE C21H21NO2S Molecular Weight: 351.46 Chemical Name: Ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate Contains: Active: Tazarotene 0.05% or 0.1% (w/w) Preservative: Benzyl alcohol 1% (w/w) Inactives: Ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, carbomer 934P, edetate disodium, hexylene glycol, poloxamer 407, polyethylene glycol 400, polysorbate 40, purified water, and tromethamine. CLINICAL PHARMACOLOGY Tazarotene is a retinoid prodrug which is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299), by rapid deesterification in animals and man. AGN 190299 (“tazarotenic acid”) binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings is unknown. Psoriasis: The mechanism of tazarotene action in psoriasis is not defined. Topical tazarotene blocks induction of mouse epidermal ornithine decarboxylase (ODC) activity, which is associated with cell proliferation and hyperplasia. In cell culture and in vitro models of skin, tazarotene suppresses expression of MRP8, a marker of inflammation present in the epidermis of psoriasis patients at high levels. In human keratinocyte cultures, it inhibits cornified envelope formation, whose build-up is an element of the psoriatic scale.
    [Show full text]
  • Microencapsulation of Amorphous Solid Dispersions of Fenretinide Enhances Drug Solubility and Release from PLGA in Vitro and in Vivo T ⁎ Kari Nietoa, Susan R
    International Journal of Pharmaceutics 586 (2020) 119475 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Microencapsulation of amorphous solid dispersions of fenretinide enhances drug solubility and release from PLGA in vitro and in vivo T ⁎ Kari Nietoa, Susan R. Malleryb, Steven P. Schwendemana,c, a Department of Pharmaceutical Sciences and The Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States b Division of Oral Maxillofacial Pathology & Radiology, College of Dentistry, Ohio State University, Columbus, OH, United States c Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States ARTICLE INFO ABSTRACT Keywords: The purpose of this study was to develop solid dispersions of fenretinide(4HPR), incorporate them into poly Fenretinide (4HPR) (lactic-co-glycolic)(PLGA) millicylindrical implants, and evaluate the resulting implants in vitro and in vivo for polyvinylpyrrolidone (PVP) future applications in oral cancer chemoprevention. Due to the extreme hydrophobicity of 4HPR, 4HPR-poly- amorphous solid dispersion (ASD) vinylpyrrolidone (PVP) amorphous solid dispersions(ASDs) were prepared for solubility enhancement. The Solubility enhancement optimal PVP-4HPR ratio of 9/1(w/w) provided a 50-fold solubility enhancement in aqueous media, which was Poly(lactic-co-glycolic) (PLGA) sustained over 1 week. PVP-4HPR ASD particles were loaded into PLGA millicylinders and drug release was In vivo release long-acting release (LAR) evaluated in vitro in PBST and in vivo by recovery from subcutaneous injection in rats. While initial formulations of PLGA PVP-4HPR millicylinders only released 10% 4HPR in vitro after 28 days, addition of the plasticizer triethyl-o-acetyl-citrate(TEAC) into PVP-4HPR ASDs resulted in a 5.6-fold total increase in drug release.
    [Show full text]