DOCSLIB.ORG

Androstenediol Stimulates Myelopoiesis and Enhances Resistance to Infection in Gamma-Irradiated Mice Mark H

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Androstenediol Stimulates Myelopoiesis and Enhances Resistance to Infection in Gamma-Irradiated Mice Mark H International Journal of Immunopharmacology 22 (2000) 1±14 www.elsevier.com/locate/ijimmpharm Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice Mark H. Whitnall a,*, Thomas B. Elliott a, Rita A. Harding a, Cynthia E. Inal a, Michael R. Landauer a, Catherine L. Wilhelmsen a, LuAnn McKinney a, Venita L. Miner a, William E. Jackson III a, Roger M. Loria b, G. David Ledney a, Thomas M. Seed a aRadiation Casualty Management Team, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA bVirginia Commonwealth University's Medical College of Virginia, Richmond, VA 23298, USA Abstract The ionizing radiation-induced hemopoietic syndrome is characterized by defects in immune function and increased mortality due to infections and hemorrhage. Since the steroid 5-androstene-3b,17b-diol (5-androstenediol, AED) modulates cytokine expression and increases resistance to bacterial and viral infections in rodents, we tested its ability to promote survival after whole-body ionizing radiation in mice. In unirradiated female B6D2F1 mice, sc AED elevated numbers of circulating neutrophils and platelets and induced proliferation of neutrophil progenitors in bone marrow. In mice exposed to whole-body 60Co gamma-radiation (3 Gy), AED injected 1 h later ameliorated radiation-induced decreases in circulating neutrophils and platelets and marrow granulocyte-macrophage colony- forming cells, but had no eect on total numbers of circulating lymphocytes or erythrocytes. In mice irradiated (0, 1 or 3 Gy) and inoculated four days later with Klebsiella pneumoniae, AED injected 2 h after irradiation enhanced 30- d survival. Injecting AED 24 h before irradiation or 2 h after irradiation increased survival to approximately the same extent. In K. pneumoniae-inoculated mice (irradiated at 3±7 Gy) and uninoculated mice (irradiated at 8±12 Gy), AED (160 mg/kg) injected 24 h before irradiation signi®cantly promoted survival with dose reduction factors (DRFs) of 1.18 and 1.26, respectively. 5-Androstene-3b-ol-17-one (dehydroepiandrosterone, DHEA) was markedly less ecacious than AED in augmenting survival, indicating speci®city. These results demonstrate for the ®rst time that a DHEA-related steroid stimulates myelopoiesis, and ameliorates neutropenia and thrombocytopenia and enhances resistance to infection after exposure of animals to ionizing radiation. # 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. * Corresponding author. Tel.: +1-301-295-9262; fax: +1- 707-922-0011. E-mail address: [email protected] (M.H. Whit- nall). 0192-0561/00/$20.00 # 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. PII: S0192-0561(99)00059-4 2 M.H. Whitnall et al. / International Journal of Immunopharmacology 22 (2000) 1±14 Keywords: Androst-5-ene-3 beta, 17 beta-diol; Prasterone; Hematopoiesis; Neutropenia; Experimental radiation injuries; Ionizing radiation; Gram-negative bacterial infections; Klebsiella pneumoniae 1. Introduction countermeasure to promote survival during the early phase of the hemopoietic syndrome are to Acute exposure to elevated doses of ionizing increase production of neutrophils and platelets radiation causes defects in hemopoiesis, resulting [32]. Very little is known about the eects of this in low numbers of circulating blood cells and pla- family of steroids on myelopoiesis and thrombo- telets and increased susceptibility to infection and cytopoiesis. One report indicated a slight inhibi- hemorrhage [1±3]. Past eorts to stimulate hemo- tory eect of 7±10 days of dietary DHEA poiesis in myelosuppressed animals have involved administration on granulopoiesis in irradiated administration of components of microbial cell mice [38]. AED increased formation of granulo- walls or their synthetic analogs [4±8], and natural mas during infection with Mycobacterium tuber- factors such as cytokines, prostaglandins, and culosis in mice [27]. In view of the ecacy of peptides or their synthetic analogs [9±12]. It AED and DHEA in promoting resistance to would be advantageous to develop a small-mol- infection in unirradiated animals, the limited in- ecule, nontoxic pharmacological agent that formation available on the eects of these ster- would ameliorate hemopoietic radiation injury. oids on myelopoiesis and thrombocytopoiesis, From the point of view of low toxicity, ease of and their modulation of expression of cytokines storage and administration, steroids would make known to be radioprotective, we tested their abil- attractive candidates. ity to enhance survival and reduce hemopoietic Administration of the adrenocortical steroid 5- injury after whole-body irradiation in mice. androstene-3b-ol-17-one (dehydroepiandroster- one, DHEA) or its metabolite 5-androstene- 3b,17b-diol (5-androstenediol, AED) to rodents 2. Experimental procedures results in increased immunocompetence and greater survival during infection [13±23]. AED is 2.1. Mice more potent than DHEA in promoting survival during bacterial or viral infection in rodents All studies were carried out in accordance with [14,15]. The DHEA-related steroids preserve the principles and procedures of the National immunocompetence after thermal injury [17] and Research Council Guide for the Care and Use of during aging [24]. They also modulate expression Laboratory Animals [71]. B6D2F1/J female mice of cytokines such as interleukin-1 (IL-1), IL-3, (Jackson Laboratory, Bar Harbor, ME), 18±24 IL-6, tumor necrosis factor (TNF) and inter- weeks of age, 22±30 g body weight, were held in feron-gamma (IFNg) [17,22,25±34]. These cyto- quarantine for two weeks. Mice were chosen for kines are known to aect recovery from these studies because of the similar responses of radiation-induced hemopoietic injury [32±34]. murine and human hemopoiesis to drugs and One report indicated small radioprotective or toxic insults [39]. Up to 10 mice were housed in radiosensitizing eects of ip DHEA pretreat- sanitized 46 24 15 cm polycarbonate boxes ments, depending on the interval between treat- with ®lter covers  (MicroIsolator; Lab Products, ment and irradiation [35]. Inc, Maywood, NJ) on autoclaved hardwood Although the DHEA-related steroids can chip bedding in a facility accredited by the As- stimulate proliferation or activation of lympho- sociation for Assessment and Accreditation of cytes, natural killer cells and macrophages Laboratory Animal Care International. Mice [16,20,22,24,31,36,37], the primary goals of a were given feed and acidi®ed (pH 2.5) water M.H. Whitnall et al. / International Journal of Immunopharmacology 22 (2000) 1±14 3 freely. The animal holding room was maintained 548 EtOH) and DHEA (melting point 149± À with conditioned fresh air that was changed at 1518C, rotation +138 EtOH) were purchased least 10 times per h at approximately 218C and from Steraloids (Wilton, NH). PEG-400 was 508 (210%) relative humidity and with a 12-h obtained from Sigma (St Louis, MO). PEG-400 light/dark full spectrum lighting cycle. All has been recommended as a nontoxic vehicle for research was approved by the Institutional Ani- administration of steroids, based on histopatho- mal Care and Use Committee of the Armed logical analysis of sc injection sites [42]. Forces Radiobiology Research Institute (AFRRI). 2.4. Peripheral blood element counts 2.2. Irradiation Blood (0.6±1.0 ml) was obtained from halothane-anesthetized mice by cardiac puncture Mice were placed in ventilated Plexiglas con- using a heparinized syringe attached to a 21- tainers and exposed bilaterally to gamma-radi- gauge needle. Blood was collected in EDTA-con- ation from the AFRRI 60Co source as described taining sample tubes. Mice were euthanized by previously [40]. Exposure time was adjusted so cervical dislocation after blood collection. White that each animal received a midline tissue- blood cell (WBC), red blood cell (RBC) and pla- absorbed dose of 1±12 Gy at a nominal dose rate telet (PLT) counts were performed using a of 0.4 Gy/min at ambient temperature. Using a Hematology System 9000 (Biochem Immunosys- standardized technique, the midline dose rate was tems). Wright-stained blood smears from the measured by placing a 0.5 cc tissue-equivalent same samples were made for dierential counts ionization chamber at the center of a 2.5-cm di- of neutrophils and lymphocytes by light mi- ameter cylindrical acrylic mouse phantom. The croscopy. calibration factor for the ionization chamber was calculated by means of a standard obtained from 2.5. Granulocyte-macrophage colony-forming cell an Accredited Dosimetry Calibration Laboratory (GM-CFC) assay (M.D. Anderson Cancer Center, Houston, TX) certi®ed by the National Institute of Standards Hemopoietic progenitor cells committed to and Technology. The tissue±air ratio, de®ned as granulocyte-macrophage dierentiation (GM- the ratio of the dose rate measured in the phan- CFC) were assayed by a single-layer modi®cation tom to the dose rate in free air, for this array of a double-layer semisolid agar technique was 0.96. Variation within the exposure ®eld was described by Patchen et al. [6]. Brie¯y, femoral less than 4% (unpublished results). Dosimetric marrow was extracted and cell suspensions were measurements were made in accordance with the prepared by ¯ushing with 3 ml of McCoy's 5A American Association of Physicists in Medicine medium containing 10% heat-inactivated fetal protocol for the determination of absorbed dose bovine serum (HIFBS; Hyclone, Logan,
Load more

Recommended publications
  • DHEA | Medchemexpress
    Inhibitors Product Data Sheet DHEA • Agonists Cat. No.: HY-14650 CAS No.: 53-43-0 Molecular Formula: C₁₉H₂₈O₂ • Molecular Weight: 288.42 Screening Libraries Target: Androgen Receptor; Endogenous Metabolite Pathway: Others; Metabolic Enzyme/Protease Storage: Please store the product under the recommended conditions in the Certificate of Analysis. SOLVENT & SOLUBILITY In Vitro DMSO : 50 mg/mL (173.36 mM; Need ultrasonic) Ethanol : 50 mg/mL (173.36 mM; Need ultrasonic) H2O : 1 mg/mL (3.47 mM; Need ultrasonic) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 3.4672 mL 17.3358 mL 34.6717 mL Stock Solutions 5 mM 0.6934 mL 3.4672 mL 6.9343 mL 10 mM 0.3467 mL 1.7336 mL 3.4672 mL Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: Cremophor EL Solubility: 14.29 mg/mL (49.55 mM); Clear solution; Need ultrasonic 2. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 3. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 4. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 5. Add each solvent one by one: 10% EtOH >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 6.
    [Show full text]
  • Us Anti-Doping Agency
    2019U.S. ANTI-DOPING AGENCY WALLET CARDEXAMPLES OF PROHIBITED AND PERMITTED SUBSTANCES AND METHODS Effective Jan. 1 – Dec. 31, 2019 CATEGORIES OF SUBSTANCES PROHIBITED AT ALL TIMES (IN AND OUT-OF-COMPETITION) • Non-Approved Substances: investigational drugs and pharmaceuticals with no approval by a governmental regulatory health authority for human therapeutic use. • Anabolic Agents: androstenediol, androstenedione, bolasterone, boldenone, clenbuterol, danazol, desoxymethyltestosterone (madol), dehydrochlormethyltestosterone (DHCMT), Prasterone (dehydroepiandrosterone, DHEA , Intrarosa) and its prohormones, drostanolone, epitestosterone, methasterone, methyl-1-testosterone, methyltestosterone (Covaryx, EEMT, Est Estrogens-methyltest DS, Methitest), nandrolone, oxandrolone, prostanozol, Selective Androgen Receptor Modulators (enobosarm, (ostarine, MK-2866), andarine, LGD-4033, RAD-140). stanozolol, testosterone and its metabolites or isomers (Androgel), THG, tibolone, trenbolone, zeranol, zilpaterol, and similar substances. • Beta-2 Agonists: All selective and non-selective beta-2 agonists, including all optical isomers, are prohibited. Most inhaled beta-2 agonists are prohibited, including arformoterol (Brovana), fenoterol, higenamine (norcoclaurine, Tinospora crispa), indacaterol (Arcapta), levalbuterol (Xopenex), metaproternol (Alupent), orciprenaline, olodaterol (Striverdi), pirbuterol (Maxair), terbutaline (Brethaire), vilanterol (Breo). The only exceptions are albuterol, formoterol, and salmeterol by a metered-dose inhaler when used
    [Show full text]
  • Effects of Aminoglutethimide on A5-Androstenediol Metabolism in Postmenopausal Women with Breast Cancer1
    [CANCER RESEARCH 42, 4797-4800, November 1982] 0008-5472/82/0042-0000802.00 Effects of Aminoglutethimide on A5-Androstenediol Metabolism in Postmenopausal Women with Breast Cancer1 Charles E. Bird,2 Valerie Masters, Ernest E. Sterns, and Albert F. Clark Departments of Medicine [C. E. B., V. M.], Surgery [E. E. S.J, and Biochemistry [A. F. C.], Queen s University and Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7 ABSTRACT women. More recently, we (8) and others (18) reported that the production of A5-androstene-3/8,17/8-diol in normal post- A5-Androstene-3/8,1 7/S-diol has potential estrogenic activity menopausal women is approximately 500 to 700 fig/24 hr. because it is known to bind to receptors and translocate to the AG, in combination with hydrocortisone, has been utilized to nucleus of certain estrogen target tissues. Its role in the biology inhibit estrogen production in patients with breast cancer (21 ). of breast cancer is unclear. Aminoglutethimide plus hydrocor This form of therapy has been termed "medical adrenalec tisone ("medical adrenalectomy") has been used to treat post- tomy," and studies suggest that it is as effective as surgical menopausal women with metastatic breast cancer. adrenalectomy. The hydrocortisone shuts off the basal adre- We studied A5-androstene-3/3,17/?-diol metabolism in post- nocortical production of estrogen precursors; AG not only menopausal women with breast cancer before and during slows down steroid biosynthesis at an early step but also aminoglutethimide-plus-hydrocortisone therapy, utilizing the specifically inhibits the aromatization of A4-androstenedione to constant infusion technique.
    [Show full text]
  • WO 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT (51) International Patent Classification: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, CI2Q 1/32 (2006.01) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (21) International Application Number: EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, PCT/US2018/021 109 MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (22) International Filing Date: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 06 March 2018 (06.03.2018) KM, ML, MR, NE, SN, TD, TG). (25) Filing Language: English Declarations under Rule 4.17: (26) Publication Langi English — as to applicant's entitlement to apply for and be granted a patent (Rule 4.1 7(H)) (30) Priority Data: — as to the applicant's entitlement to claim the priority of the 62/484,141 11 April 2017 ( 11.04.2017) US earlier application (Rule 4.17(Hi)) (71) Applicant: REGENERON PHARMACEUTICALS, Published: INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, — with international search report (Art. 21(3)) New York 10591-6707 (US). — with sequence listing part of description (Rule 5.2(a)) (72) Inventors: STEVIS, Panayiotis; 777 Old Saw Mill Riv er Road, Tarrytown, New York 10591-6707 (US).
    [Show full text]
  • Sex Hormone-Binding Globulin (SHBG) As an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome
    International Journal of Molecular Sciences Review Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome Xianqin Qu 1,* and Richard Donnelly 2 1 School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia 2 School of Medicine, University of Nottingham, Derby DE22 3DT, UK; [email protected] * Correspondence: [email protected]; Tel.: +61-2-95147852 Received: 1 October 2020; Accepted: 28 October 2020; Published: 1 November 2020 Abstract: Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and reports in the literature have suggested a negative correlation between circulating SHBG levels and markers of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Decreased SHBG levels increase the bioavailability of androgens, which in turn leads to progression of ovarian pathology, anovulation and the phenotypic characteristics of polycystic ovarian syndrome (PCOS). This review will use a case report to illustrate the inter-relationships between SHBG, NAFLD and PCOS. In particular, we will review the evidence that low hepatic SHBG production may be a key step in the pathogenesis of PCOS. Furthermore, there is emerging evidence that serum SHBG levels may be useful as a diagnostic biomarker and therapeutic target for managing women with PCOS. Keywords: adolescents; hepatic lipogenesis; human sex hormone-binding globulin; insulin resistance; non-alcoholic fatty liver disease; polycystic ovary syndrome 1. Introduction Polycystic ovary syndrome (PCOS) is a complex, common reproductive and endocrine disorder affecting up to 10% of reproductive-aged women [1].
    [Show full text]
  • In Human Prostate Cancer Cells (Ara70͞hydroxyflutamide͞casodex͞testosterone͞7-Oxo-DHEA)
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 11083–11088, September 1998 Biochemistry D5-Androstenediol is a natural hormone with androgenic activity in human prostate cancer cells (ARA70yhydroxyflutamideycasodexytestosteroney7-oxo-DHEA) HIROSHI MIYAMOTO*, SHUYUAN YEH*, HENRY LARDY†,EDWARD MESSING*, AND CHAWNSHANG CHANG*†‡ *George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642; and †Institute for Enzyme Research and Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792 Contributed by Henry Lardy, July 29, 1998 ABSTRACT It is known that androst-5-ene-3b,17b-diol presence of AR and ARA70. Our results suggest that Adiol (Adiol), a precursor of testosterone (T), can activate estrogen itself can activate AR transcriptional activity in human pros- target genes. The androgenic activity of Adiol itself, however, tate cancer cells, and that ARA70 can further enhance Adiol- is poorly understood. Using a transient transfection assay, we mediated activation of the AR. here demonstrate in human prostate cancer cells that Adiol can activate androgen receptor (AR) target genes in the MATERIALS AND METHODS presence of AR, and that AR coactivator ARA70 can further enhance this Adiol-induced AR transcriptional activity. In Chemicals and Plasmids. Adiol, DHEA, androst-5-ene- contrast to this finding, an active metabolite of dehydroepi- 7,17-dione (Adione), T, DHT, and E2 were purchased from androsterone, 7-oxo-dehydroepiandrosterone, does not acti- Sigma, 7-oxo-DHEA was synthesized from DHEA as de- vate AR target gene in the absence or presence of ARA70. Thin scribed (9), trilostane was provided by T.-M.
    [Show full text]
  • Appendix B Banned Drugs
    APPENDIX B BANNED DRUGS (This list complies with 2004-2005 NCAA Bylaw 31.2.3.1 Banned Drugs) A. Stimulants: amiphenazole amphetamine bemigride benzphetamine bromantan caffeine1 (guarana) chlorphentermine cocaine cropropamide crothetamide diethylpropion dimethylamphetamine doxapram ephedrine (ephedra, ma huang) ethamivan ethylamphetamine fencamfamine meclofenoxate methamphetamine methylene-dioxymethamphetamine [MDMA (ecstasy)] methylphenidate nikethamide pemoline pentetrazol phendimetrazine phenmetrazine phentermine phenylephrine phenylpropanolamine (ppa) picrotoxine pipradol prolintane strychnine synephrine (citrus aurantium, zhi shi, bitter orange) and related compounds Approved by Cabinet:1/31/05 Adopted by Board of Trustees:3/18/05 Page 12 of 15 B. Anabolic Agents: polythiazide anabolic steroids quinethazone androstenediol spironolactone androstenedione triamterene boldenone trichlormethiazide clostebol and related compounds dehydrochlormethyltestosterone dehydroepiandrosterone (DHEA) dihydrotestosterone (DHT) D. Street Drugs: dromostanolone heroin fluoxymesterone marijuana3 gestrinone THC mesterolone (tetrahydrocannabinol3 methandienone methenolone methyltestosterone nandrolone norandrostenediol norandrostenedione norethandrolone oxandrolone oxymesterone oxymetholone stanozolol testosterone2 tetrahydrogestrinone (THG) trenbolone and related compounds other anabolic agents clenbuterol C. Diuretics: acetazolamide bendroflumethiazide benzthiazide bumetanide chlorothiazide chlorthalidone ethacrynic acid flumethiazide furosemide hydrochlorothiazide
    [Show full text]
  • The Effects of 5-Androstenediol in Androgen-Dependent Prostate
    Characterization of Value Nutrition’s 5-Androstenediol Product and its Proliferative Effects on the LNCaP Cell Line A Thesis Submitted to the Faculty of Worcester Polytechnic Institute in partial fulfillment of the requirements for the Degree of Master of Science in Biology and Biotechnology by _______________________________ Jaime L. Grouf October 2007 APPROVED: Jill Rulfs, Ph.D., Major Advisor ________________________________ Theodore Crusberg, Committee Member ________________________________ JoAnn Whitefleet-Smith, Committee Member ________________________________ TABLE OF CONTENTS TABLE OF CONTENTS............................................................................................................................. 2 ABSTRACT .................................................................................................................................................. 3 ACKNOWLEDGEMENTS ......................................................................................................................... 5 DEDICATION.............................................................................................................................................. 6 INTRODUCTION........................................................................................................................................ 7 PROSTATE CANCER .................................................................................................................................. 7 PHYSIOLOGICAL ROLE OF ANDROGENS IN THE PROSTATE ...................................................................
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,383,154 B2 Bar-Shalom Et Al
    USOO8383154B2 (12) United States Patent (10) Patent No.: US 8,383,154 B2 Bar-Shalom et al. (45) Date of Patent: Feb. 26, 2013 (54) SWELLABLE DOSAGE FORM COMPRISING W W 2.3. A. 3. 2. GELLAN GUMI WO WOO1,76610 10, 2001 WO WOO2,46571 A2 6, 2002 (75) Inventors: Daniel Bar-Shalom, Kokkedal (DK); WO WO O2/49571 A2 6, 2002 Lillian Slot, Virum (DK); Gina Fischer, WO WO 03/043638 A1 5, 2003 yerlosea (DK), Pernille Heyrup WO WO 2004/096906 A1 11, 2004 Hemmingsen, Bagsvaerd (DK) WO WO 2005/007074 1, 2005 WO WO 2005/007074 A 1, 2005 (73) Assignee: Egalet A/S, Vaerlose (DK) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 JECFA, “Gellangum”. FNP 52 Addendum 4 (1996).* U.S.C. 154(b) by 1259 days. JECFA, “Talc”, FNP 52 Addendum 1 (1992).* Alterna LLC, “ElixSure, Allergy Formula', description and label (21) Appl. No.: 111596,123 directions, online (Feb. 6, 2007). Hagerström, H., “Polymer gels as pharmaceutical dosage forms'. (22) PCT Filed: May 11, 2005 comprehensive Summaries of Uppsala dissertations from the faculty of pharmacy, vol. 293 Uppsala (2003). (86). PCT No.: PCT/DK2OOS/OOO317 Lin, “Gellan Gum', U.S. Food and Drug Administration, www. inchem.org, online (Jan. 17, 2005). S371 (c)(1), Miyazaki, S., et al., “In situ-gelling gellan formulations as vehicles (2), (4) Date: Aug. 14, 2007 for oral drug delivery”. J. Control Release, vol. 60, pp. 287-295 (1999). (87) PCT Pub. No.: WO2005/107713 Rowe, Raymond C.
    [Show full text]
  • Pros and Cons Controversy on Molecular Imaging and Dynamic
    Open Access Archives of Biotechnology and Biomedicine Research Article Pros and Cons Controversy on Molecular Imaging and Dynamics of Double- ISSN Standard DNA/RNA of Human Preserving 2639-6777 Stem Cells-Binding Nano Molecules with Androgens/Anabolic Steroids (AAS) or Testosterone Derivatives through Tracking of Helium-4 Nucleus (Alpha Particle) Using Synchrotron Radiation Alireza Heidari* Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA *Address for Correspondence: Dr. Alireza Abstract Heidari, Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, In the current study, we have investigated pros and cons controversy on molecular imaging and dynamics USA, Email: of double-standard DNA/RNA of human preserving stem cells-binding Nano molecules with Androgens/ [email protected]; Anabolic Steroids (AAS) or Testosterone derivatives through tracking of Helium-4 nucleus (Alpha particle) using [email protected] synchrotron radiation. In this regard, the enzymatic oxidation of double-standard DNA/RNA of human preserving Submitted: 31 October 2017 stem cells-binding Nano molecules by haem peroxidases (or heme peroxidases) such as Horseradish Peroxidase Approved: 13 November 2017 (HPR), Chloroperoxidase (CPO), Lactoperoxidase (LPO) and Lignin Peroxidase (LiP) is an important process from Published: 15 November 2017 both the synthetic and mechanistic point of view. Copyright: 2017 Heidari A. This is an open access article distributed under the Creative
    [Show full text]
  • Identification of Genomic Alterations in Castration Resistant Prostate Cancer Using Next Generation Sequencing
    Identification of Genomic Alterations in Castration Resistant Prostate Cancer using Next Generation Sequencing Thesis Submitted for a Doctoral Degree in Natural Sciences (Dr. rer. nat) Faculty of Mathematics and Natural Sciences Rheinische Friedrich-Wilhelms- Submitted by Roopika Menon from Chandigarh, India Bonn 2013 Prepared with the consent of the Faculty of Mathematics and Natural Sciences at the Rheinische Friedrich-Wilhelms- 1. Reviewer: Prof. Dr. Sven Perner 2. Reviewer: Prof. Dr. Hubert Schorle Date of examination: 19 November 2013 Year of Publication: 2014 Declaration I solemnly declare that the work submitted here is the result of my own investigation, except where otherwise stated. This work has not been submitted to any other University or Institute towards the partial fulfillment of any degree. ____________________________________________________________________ Roopika Menon; Author Acknowledgements This thesis would not have been possible without the help and support of many people. I would like to dedicate this thesis to all the people who have helped make this dream a reality. This thesis would have not been possible without the patience, support and guidance of my supervisor, Prof. Dr. Sven Perner. It has truly been an honor to be his first PhD student. He has both consciously and unconsciously made me into the researcher that I am today. My PhD experience has truly been the ‘best’ because of his time, ideas, funding and most importantly his incredible sense of humor. He encouraged and gave me the opportunity to travel around the world to develop as a scientist. I cannot thank him enough for this immense opportunity, which stands as a stepping-stone to my career in science.
    [Show full text]
  • The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue After Androgen Deprivation Therapy and Activates Mutated Androgen Receptor
    [CANCER RESEARCH 64, 765–771, January 15, 2004] The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue after Androgen Deprivation Therapy and Activates Mutated Androgen Receptor Atsushi Mizokami,1 Eitetsu Koh,1 Hiroshi Fujita1, Yuji Maeda1, Masayuki Egawa,1 Kiyoshi Koshida,1 Seijiro Honma,2 Evan T. Keller,3 and Mikio Namiki1 1Department of Urology, Kanazawa University, Kanazawa, Japan; 2Teikoku Hormone MFG. Co., Kanagawa, Japan; and 3Unit for Laboratory Animal Medicine and Department of Pathology, University of Michigan, Ann Arbor, Michigan ABSTRACT adiol plasma concentration by only 50% (3). Although we have identified that adiol is the major metabolite of DHEA in human Despite an initial response to androgen deprivation therapy, prostate prostate homogenate in vitro (4), adiol levels in PCa tissues postorchi- cancer (PCa) progresses eventually from an androgen-dependent to an ectomy have not been reported. This may be important to the pro- androgen-independent phenotype. One of the mechanisms of relapse is antiandrogen withdrawal phenomenon caused by mutation of 877th gression of PCa because in addition to being converted to T and amino acid of androgen receptor (AR). In the present study, we estab- dihydrotestosterone (DHT), which activate the AR, adiol itself acti- lished a method to measure the concentration of androstenediol (adiol) in vates the AR (5). prostate tissue. We found that adiol maintains a high concentration in PCa On the basis of adiol’s ability to activate the AR and its presence in tissue even after androgen deprivation therapy. Furthermore, adiol is a prostate tissues, we explored the hypothesis that adiol provides an- stronger activator of mutant AR in LNCaP PCa cells and induces more drogenic stimulation of PCa even after androgen deprivation therapy.
    [Show full text]