DOCSLIB.ORG

Thymopentin and Splenopentin As Immunomodulators Current Stutus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thymopentin and Splenopentin As Immunomodulators Current Stutus Immunologic Research 1998;17/3:345-368 Thymopentin and Splenopentin as Immunomodulators Current Stutus 1Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India. 2Division of Biopolymers, Central Drug Research Institute, Lucknow, India. 3Department of Microbiology, RML Awadh University, Faizabad, India. Abstract Key Words Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Immunomodulation Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides Splenin corresponding to the region 32-34 of a splenic product called splenin Splenopentin (SP) and the thymic hormone thymopoietin (TP), respectively. TP Thymopoietin was originally isolated as a 5-kDa (49-amino acids) protein from Thymopentin bovine thymus while studying effects of the thymic extracts on neuro- muscular transmission and was subsequently observed to affect T cell differentiation and function. TP I and II are two closely related polypeptides isolated from bovine thymus. A radioimmunoassay for TP revealed a crossreaction with a product found in spleen and lymph node. This product, named splenin, differs from TP only in position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5), reproduce the biological activities of TP and SP, respectively. It is now evident that various forms of TPs were created by proteolytic cleavage of larger proteins during isolation, cDNA clones have been isolated for three alternatively spliced mRNAs that encodes three distinct human T cell TPs. The immunomodulatory properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in the literature have been briefly reviewed. Dr. V. K. Singh 9 1998 345 Laboratory of Molecular Immunology Humana Press Inc. Department of Immunology 0257-277X/98/ Sanjay Gandhi Post-Graduate Institute of Medical Sciences 17/3:345 368/$14.00 Lucknow - 226 014, India E-mail: vksingh @sgpgi.ren.nic.in Introduction nity and decrease the morbidity of immuno- "hnmunomodulators" are substances that compromised individuals (1-3). Similar have the ability to influence various compo- observations were also made in the case of nents of the immune system. They can be used experimental animals (4,5). One of the thymic therapeutically for correcting pathological hormones called thymopoietin (TP) is a aberrations of the immune response in condi- polypeptide consisting of 49 amino acids (6, 7). tions such as immunodeficiency, chronic TP has pleiotropic biological actions includ- infections, autoimmunity, organ transplant ing effects on neuromuscular transmission and neoplasia, and so on. Such substances are (8,9), T and B cell differentiation (10,11) and often referred to as "Biological Response regulation of the immune response (12-17). Modifiers" as well. The action of immuno- The biological activity to TP is reproduced by modulators may be specific or nonspecific. a synthetic pentapeptide thymopentin (TP-5) The pharmacological modulation of the whose amino acid sequence corresponds to the immune response is essentially dependent region 32-36 of the native hormone (Arg-Lys- upon the dose of the substance applied, the Asp-Val-Tyr). Since the pentapeptide (TP-5) mode of its application, and the prevailing sta- exhibits all the biological activities of TP, the tus of the immune system of the host. former is considered to be the active site of the Endeavors to develop chemically well- native hormone (18). Recently, a closely defined compounds possessing immuno- related pentapeptide called splenopentin modulating properties have resulted in the (SP-5), has been reported to exhibit a particu- identification of several classes of compounds larly interesting biological profile. The amino that can act as immunostimulants or immuno- acid sequence ofSP-5 (Arg-Lys-Glu-Val-Tyr) suppressors. Several peptides and their deriva- corresponds to the segment 32-36 of a splenic tives such as muramyl dipeptide (MDP), hormone called "splenin" (also referred as lauroyl tetrapeptide (LTP), enkephalins and TP-III). SP-5 differs from TP-5 only at posi- thymic hormones, are quite well known for tion 3 due to the presence of Glu residue in their immunostimulating activities. Likewise, place of Asp. SP-5 is known to influence both cyclosporin A, FK-506, and rapamycin are early T and B cell differentiation (19), to well-established immunosuppressive agents. increase the number of antibody-forming cells In addition, many substances such as saponins, in mice after gamma irradiation (20,21). This non-ionic block polymers, monophosphoryl pentapeptide accelerates the repopulation of A and cytokines, which stimulate T cell sub- epidermal Langerhans cells at skin sites sets responsible for the manifestation of the depleted with these cells (22,23). Several syn- specific immune responses, are termed thetic analogs of TP-5 and SP-5 have been immunoadjuvants. Interleukin-1 (IL-1) hap- studied for their immunomodulatory activity pens to be the first cytokine that has been used with a view to identify a compound that would as an adjuvant. Administration of interferon-], be more suitable for pharmaceutical applica- (IFN-],) is also known to activate helper T cells tion in terms of stability, biodisposition, and for antibody and delayed-type hypersensi- receptor affinity. Short synthetic peptide tivity responses. sequences of this type may turn out to be ideal In recent years, thymic preparations have candidates as adjuvants for human vaccines been widely used for boosting the natural and could also be utilized as immunothera- defense system of the host. Thymic hormones peutic and immunoprophylactic agents in case have been reported to reverse altered immu- of infectious diseases, immunodeficiencies, 346 Singh et al. Table !. Summary of immunomodulatory activities of TP In vitro studies T cell differentiation Induced prothymocyte to thymocyte differentiation 10 B cell differentiation Inhibited B cell differentiation 11 Lymphocyte proliferation Stronger inducer than synthetic TP-II 48 In vivo studies Neuromuscular transmission Impaired 6 T cells Induced T cell differentiation 50 autoimmune diseases, and cancers. This arti- later found to be wholly crossreactive with cle constitutes an attempt to highlight the TP-I (26). Subsequent studies with synthetic recent developments relating to TP-5 and fragments showed that the pentapeptide SP-5, and to give an idea about their current sequence Arg-Lys-Asp-Val-Tyr, corre- status as immunomodulators. sponding to residues 32-36, was the minimal fragment that reproduced the biologic proper- Thymopoietin ties of TP, both in vitro and in vivo, and this TP is a polypeptide hormone of the thymus synthetic pentapeptide was termed TP-5 (18,19). that induces differentiation of prothymocytes TP is a linear polypeptide hormone secreted to thymocytes and also has secondary by the epithelial cells of the thymus and is effects on neuromuscular transmission (6). Its readily detected in the thymus and absent in immunomodulatoryproperties are summarized control tissues, such as, liver, kidney, thyroid, in Table 1. and muscle (6,27). The isolation of TP-reac- tive material in fetal bovine skin was moni- Isolation and Structure of TP tored by means of a radioimmunoassay. The The similarity of the signs and symptoms of amino acid sequence of this material was myasthenia gravis with those of curare poi- found to be identical with that of TP isolated soning prompted an extensive search for a from the thymus. Experimental evidence sug- curare-like substance in the serum of myas- gests that TP in the circulation is derived from thenic patients or in thymus extracts. How- the thymus and not from the skin, suggesting ever, in the absence of such a substance this that the TP in keratinocytes has a local function, conundrum was solved when the molecules either apocrine or immunoregulatory (28). responsible for the delayed neuromuscular The TP gene is expressed predominantly in impairment in mice were identified following lymphatic tissues. The lymphatic tissue with the injection of thymic extracts or purified the highest levels was observed in thymocytes polypeptides. Two biochemically homoge- and not in thymic stroma. Lower but still sig- neous thymic polypeptides, TP-I and -II were nificant amounts were present in the tonsils, isolated (7). The complete amino acid neck lymph nodes, and small intestines (prob- sequence of TP-II was determined and the bio- ably because of its lymphatic component-- logical activity was shown to reside in seg- Peyer's patches), whereas cultured spleen ment 29-41 by chemical synthesis (24,25). A stromal cells and peripheral blood mono- radioimmunoassay developed for TP-II was nuclear cells displayed a low level of TP lmmunomodu|ationwith TP-5 and SP-5 347 mRNA. The TP gene expression in all other mRNA expression is demonstrated in lympho- (nonlymphatic) tissues tested was weak, cytes from all the differentiation stages inves- barely detectable, or virtually absent (29). tigated, as well as in the myeloid cell line, Harris et al. (30) reported the isolation of K562. The findings suggest a further expan- cDNA clones for three alternatively spliced sion of the proposed ATP functions (33). mRNAs that encode three distinct human TP. A TP-related peptide gene was identified and Proteins encoded by these mRNAs, named cloned from a human cDNA library (34) and TPc~ (75 kDa), 13 (51 kDa), and y (39 kDa), novel TP responsive proteins 1 and 2, related to contained similar N-terminal regions, includ- signal transduction, were also identified (35). ing sequences nearly identical to that of the TP levels in the serum have been found to originally isolated TP, but had divergent be high in normal humans until the fourth C-terminal regions (31). It is now evident that decade of life, after that the levels decline pro- 49-amino acid TPs were created by proteolytic gressively and are below detection limits by cleavage of a larger protein during isolation 70 yr of age (36). These findings parallel the and represent the N-terminal sequences of known anatomic involution of the thymus and these proteins.
Load more

Recommended publications
  • Thymic Peptides and Preparations: an Update
    ¡ Archivum Immunologiae et Therapiae Experimentalis, 1999, 47¢ , 77–82 £ PL ISSN 0004-069X Review Thymic Peptides and Preparations: an Update ¤ O. J. Cordero et al.: Thymic Peptides ¦ ¨ § OSCAR J. CORDERO, A¥ LICIA PIÑEIRO and MONTSERRAT NOGUEIRA Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain Abstract. The possibilities of thymic peptides in human therapy are still being described. Here, we focus on their © general characteristics and on recent advances in this area. Key words: thymus; thymic peptides; preclinical investigation; therapeutic use; clinical trials. Thymic peptides, as well as a variety of other purified from porcine and human serum and from calf modulators (IL-1, IL-3, IL-6, GM-CSF) and cell-cell thymus, and named “facteur thymique serique”11. interactions, regulate the process known as thymic se- According to the classical criteria, TH is the unique lection by which pro-thymocytes become mature and peptide that can be recognized as a hormone. Its secre- functional T cells. tion by a subpopulation of thymic epithelial cells (TEC) Several polypeptides have been extracted, mainly is controlled by a pleiotropic mechanism involving its from young calves, and some of them have been suc- own levels and those of prolactine (PRL), growth hor- cessfully isolated and prepared synthetically (Fig. 1). mone (GH) through insulin growth factor 1 (IGF-1) se- The precise role of much of these factors purported to cretion, adrenocorticotropin (ACTH), thyroxin (T4), β- have intrathymic effects is still unknown, although endorphin and β-leukencephalin and IL-1α and β8. many of these compounds exhibit immunobiological Furthermore, reciprocal regulatory actions on the activity.
    [Show full text]
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
    [Show full text]
  • Pulmonary Delivery of Biological Drugs
    pharmaceutics Review Pulmonary Delivery of Biological Drugs Wanling Liang 1,*, Harry W. Pan 1 , Driton Vllasaliu 2 and Jenny K. W. Lam 1 1 Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China; [email protected] (H.W.P.); [email protected] (J.K.W.L.) 2 School of Cancer and Pharmaceutical Sciences, King’s College London, 150 Stamford Street, London SE1 9NH, UK; [email protected] * Correspondence: [email protected]; Tel.: +852-3917-9024 Received: 15 September 2020; Accepted: 20 October 2020; Published: 26 October 2020 Abstract: In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery.
    [Show full text]
  • Thymopentin Ameliorates Dextran Sulfate Sodium-Induced Colitis by Triggering
    1 Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering 2 the production of IL-22 in both innate and adaptive lymphocytes 3 Qiuhua Cao1, 2*, Xinghua Gao1, 2*, Yanting Lin1, 2, Chongxiu Yue1, 2, Yue Wang1, 2, Fei 4 Quan1, 2, Zixuan Zhang1, 2, Xiaoxuan Liu1, 2, Yuan Lu1, 2, Yanling Zhan1, 2, Hongbao 5 Yang1, 2, Xianjing Li1, 2, Di Qin5, Lutz Birnbaumer4, Kun Hao3 & Yong Yang1, 2 6 7 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, 8 Nanjing, Jiangsu 211198, PR China 9 2. Center for New Drug Safety Evaluation and Research, China Pharmaceutical 10 University, Nanjing, Jiangsu 211198, PR China 11 3. Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical 12 University, Nanjing, Jiangsu 210009, PR China 13 4. Neurobiology Laboratory, National Institute of Environmental Health Sciences, 14 Research Triangle Park, North Carolina 27709, USA, and Institute of Biomedical 15 Research (BIOMED), Catholic University of Argentina, Buenos Aires C1107AFF, 16 Argentina 17 5. School of Sports and Health, Nanjing sport institute, Nanjing, Jiangsu 210001, PR 18 China 19 *These authors contributed equally to this work. 20 Corresponding author: Yong Yang and Kun Hao, China Pharmaceutical University, 21 Nanjing, China. Phone and Fax: 86-025-86185622. E-mail: [email protected] or 22 [email protected]. 1 23 Abstract 24 Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, 25 notoriously challenging to treat. Previous studies have found a positive correlation 26 between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate 27 the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active 28 domain of the thymopoietin, on colitis.
    [Show full text]
  • Aspects of the Usage of Antineoplastic and 1Mmunomodulating Agents in a Section of the Private Health Care Sector
    ASPECTS OF THE USAGE OF ANTINEOPLASTIC AND 1MMUNOMODULATING AGENTS IN A SECTION OF THE PRIVATE HEALTH CARE SECTOR Wilmarie Rheeders B. Pharm Dissertation submitted in Pharmacy Practice, School of Pharmacy at the Faculty of Health Sciences of the North-West University, Potchefstroom, in partial fulfilment of the requirements for the degree Magister Pharmaciae. Supervisor: Prof M.S. Lubbe Co-supervisor: Dr. J.L. Duminy Co-supervisor: Prof. M.P. Stander Potchefstroom November 2008 For all things are from Him, by Him, and for Him. Glory belongs to Him forever! Amen. (Rom. 11:36) ACKNOWLEDGEMENTS To my Lord and Father whom I love, all the Glory! He gave me the strength, insight and endurance to finish this study. 1 also want to express my sincere appreciation to the following people that have contributed to this dissertation: • To Professor M.S. Lubbe, in her capacity as supervisor of this dissertation, my appreciation for her expert supervision, advice and time she invested in this study. • To Dr. J.L Duminy, oncologist and co-supervisor, for all the useful advice, assistance and time he put aside in the interest of this dissertation. • To Professor M.P. Stander, in his capacity as co-supervisor of this study. • To Professor J.H.P. Serfontein, for his guidance, time, effort and advice. • To the Department of Pharmacy Practice as well as the NRF for the technical and financial support. • To Anne-Marie, thank you for your patience, time and continuous effort you put into the data. • To the Pharmacy Benefit Management company for providing the data for this dissertation.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available
    BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] BMJ Open Pediatric drug utilization in the Western Pacific region: Australia, Japan, South Korea, Hong Kong and Taiwan Journal: BMJ Open ManuscriptFor ID peerbmjopen-2019-032426 review only Article Type: Research Date Submitted by the 27-Jun-2019 Author: Complete List of Authors: Brauer, Ruth; University College London, Research Department of Practice and Policy, School of Pharmacy Wong, Ian; University College London, Research Department of Practice and Policy, School of Pharmacy; University of Hong Kong, Centre for Safe Medication Practice and Research, Department
    [Show full text]
  • Alphabetical Listing of ATC Drugs & Codes
    Alphabetical Listing of ATC drugs & codes. Introduction This file is an alphabetical listing of ATC codes as supplied to us in November 1999. It is supplied free as a service to those who care about good medicine use by mSupply support. To get an overview of the ATC system, use the “ATC categories.pdf” document also alvailable from www.msupply.org.nz Thanks to the WHO collaborating centre for Drug Statistics & Methodology, Norway, for supplying the raw data. I have intentionally supplied these files as PDFs so that they are not quite so easily manipulated and redistributed. I am told there is no copyright on the files, but it still seems polite to ask before using other people’s work, so please contact <[email protected]> for permission before asking us for text files. mSupply support also distributes mSupply software for inventory control, which has an inbuilt system for reporting on medicine usage using the ATC system You can download a full working version from www.msupply.org.nz Craig Drown, mSupply Support <[email protected]> April 2000 A (2-benzhydryloxyethyl)diethyl-methylammonium iodide A03AB16 0.3 g O 2-(4-chlorphenoxy)-ethanol D01AE06 4-dimethylaminophenol V03AB27 Abciximab B01AC13 25 mg P Absorbable gelatin sponge B02BC01 Acadesine C01EB13 Acamprosate V03AA03 2 g O Acarbose A10BF01 0.3 g O Acebutolol C07AB04 0.4 g O,P Acebutolol and thiazides C07BB04 Aceclidine S01EB08 Aceclidine, combinations S01EB58 Aceclofenac M01AB16 0.2 g O Acefylline piperazine R03DA09 Acemetacin M01AB11 Acenocoumarol B01AA07 5 mg O Acepromazine N05AA04
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0135901 A1 Moller Et Al
    US 20100135901A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0135901 A1 Moller et al. (43) Pub. Date: Jun. 3, 2010 (54) COMBINATION THERAPY now abandoned, which is a continuation of application No. PCT/DK2004/000683, filed on Oct. 8, 2004. (76) Inventors: Niels Peter Hundahl Moller, (60) Provisional application No. 60/513,422, filed on Oct. Kobenhavn O (DK); Kresten Skak, 22, 2003, provisional application No. 60/569,566, Soborg (DK); Jorn Roland Miller, filed on May 10, 2004. Virum (DK) (30) Foreign Application Priority Data Correspondence Address: WOODCOCKWASHIBURN LLP Oct. 17, 2003 (DK) ............................. PA2OO3O1529 CIRA CENTRE, 12TH FLOOR, 2929 ARCH May 4, 2004 (DK) ............................. PA2004OO707 STREET PHILADELPHIA, PA 19104-2891 (US) Publication Classification (51) Int. Cl. (21) Appl. No.: 12/637,109 A6II 5L/00 (2006.01) A638/20 (2006.01) (22) Filed: Dec. 14, 2009 A6IP35/00 (2006.01) (52) U.S. Cl. ....................................... 424/1.11; 424/85.2 Related U.S. Application Data (57) ABSTRACT (63) Continuation of application No. 12/112,452, filed on Apr. 30, 2008, now abandoned, which is a continuation The invention provides combination treatments with IL-21, of application No. 1 1/404,733, filed on Apr. 14, 2006, analogues and derivatives thereof. US 2010/0135901 A1 Jun. 3, 2010 COMBINATION THERAPY cells have been shown to kill some types of tumor cells via KIR ligand dependent activation. CROSS-REFERENCE TO RELATED PATENT 0007. The immunology involved in cancer disease APPLICATIONS includes a variety of different cells derived from the immune system. Compounds which stimulate Such responses may be 0001.
    [Show full text]
  • Granulocyte Colony-Stimulating Factors for Febrile
    Cooper et al. BMC Cancer 2011, 11:404 http://www.biomedcentral.com/1471-2407/11/404 RESEARCHARTICLE Open Access Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis Katy L Cooper1*, Jason Madan2, Sophie Whyte1, Matt D Stevenson1 and Ron L Akehurst1 Abstract Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G- CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim.
    [Show full text]
  • Overcoming the Intestinal Barrier a Look Into Targeting Approaches for Improved Oral Drug Delivery Systems
    Journal of Controlled Release 322 (2020) 486–508 Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel Review article Overcoming the intestinal barrier: A look into targeting approaches for improved oral drug delivery systems T ⁎ Yining Xu, Neha Shrestha, Véronique Préat, Ana Beloqui Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, UCLouvain, Université catholique de Louvain, 1200 Brussels, Belgium ARTICLE INFO ABSTRACT Keywords: Oral drug administration is one of the most preferred and simplest routes among both patients and formulation Oral delivery scientists. Nevertheless, orally delivery of some of the most widely used therapeutic agents (e.g., anticancer Targeting drugs, peptides, proteins and vaccines) is still a major challenge due to the limited oral bioavailability associated Enterocytes with them. The poor oral bioavailability of such drugs is attributed to one or many factors, such as poor aqueous Goblet cells solubility, poor permeability, and enzymatic degradation. Various technological strategies (such as permeation M cells enhancers, prodrugs and nanocarriers) have been developed to enhance the bioavailability of these drugs after L cells ff Transporters oral administration. Among the di erent approaches, advanced and innovative drug delivery systems, especially targeting-based strategies, have garnered tremendous attention. Furthermore, the presence of numerous types of cells and solute carrier transporters throughout the gastrointestinal tract represents numerous potential targeting sites for successful oral delivery that have not yet been exploited for their full potential. This review describes different targeting strategies towards different targeting sites in the gastrointestinal tract. Additionally, exciting improvements in oral drug delivery systems with different targeting strategies (e.g., M cells for oral vaccination and L cells for type 2 diabetes mellitus) are also discussed.
    [Show full text]