DOCSLIB.ORG

5. New Therapeutic Targets in Atopic Eczema

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
5. New Therapeutic Targets in Atopic Eczema Acta Derm Venereol 2005; Suppl. 215: 25–27 5. New therapeutic targets in atopic eczema RICHARD LANGLEY The rationale for new targets in atopic eczema depends NEW THERAPEUTIC STATEGIES AND upon the results of basic research. For example, TARGETS assessment of data from gene research may indicate a Strategies to affect T cells are shown in Table I. new therapeutic target. Similarly, key results from new Alefacept binds to CD2 and FcyRII, a dual mechanism clinical trials in other atopic diseases including asthma of pathogenic T-cell inhibition leading to apoptosis of T can also be helpful in the search for new treatment cells. Alefacept has been investigated in psoriasis and strategies. will no doubt be tested in AD in the future. Alternative concepts involve binding to CD2 and intracellular NEW APPROACHES TO OLD TARGETS binding (4). Blocking of T-cell activation is best exemplified by the One of the recent developments is to treat the disease calcineurin inhibitors tacrolimus and pimecrolimus. very early in its development, exactly as is being done in Several studies have been conducted with these topical asthma. The aim is to evaluate whether it is possible to immunomodulators, which have shown good efficacy modify the disease with long-term management. Can in randomized double-blind studies (5, 6). Tacrolimus flare-ups be prevented? Is it possible to prevent the (0.03% and 0.1%) showed dose-related superiority over ‘atopic march’? The typical progress of a patient with vehicle during a 12-week study in moderate to severe atopic dermatitis (AD) was documented by Kissling & disease (5). Pimecrolimus cream (1%) similarly was more Wuthrich (1). They documented the development of effective than vehicle during a 6-week study in around eczema in 106 patients from the infantile phase, through 400 children and adolescents with mild to moderate childhood and adolescence into adulthood. The major- disease (6). An interesting aspect with these compounds ity of patients experienced recurrent cycles of flare-ups, is that lesions on the face tend to respond better than each of which was controlled by steroids. This recurrent those on the rest of the body. As with the study by cycle of events is distressing to parents who are Berth-Jones et al. (3) with fluticasone propionate, also concerned about the ‘atopic march’ (2). Atopic prevention of relapse has been investigated with eczema is in most cases the first manifestation of calcineurin inhibitors. Three controlled studies are atopic disposition; eczema in childhood, compounded under way with pimecrolimus in infants aged 3–24 by food allergy, leading to asthma and long-term months, in children aged 2–17 years, both with mild/ rhinitis. moderate disease, and in adults with severe disease. A The general approach to treating AD is to treat long-term disease-modification study is also under way relapses/flare-ups and when controlled to withdraw with pimecrolimus in approximately 1100 infants, who active treatment and use emollients (until the next flare-up). A recent trial has investigated whether Table I. Strategies to deplete T cells/T-cell subsets continued application of a steroid can prevent or Route of delay the cycle of relapses and treatment. Berth-Jones Agent administration Design Mechanism et al. (3) conducted a randomized vehicle (emollient) controlled trial in patients aged 12–65 with moderate to Alefacept IV Ig/receptor Binds CD2 and severe disease, to determine whether fluticasone propio- (Amevive) IM Fusion protein FCRIII nate (at two strengths of 0.05% and 0.005%) can prevent Apoptosis MEDI-507 IV Humanized Binds CD2 – relapses. There was a 1-month stabilization phase, (Siplizzumab) SC monoclonal ADCC followed by maintenance treatment of both ‘healed’ antibody skin and new areas. The primary end point of the study IL-2 DAB IV Cytokine/toxin DT introduced was the time to relapse. A significant (pv0.001) (Ontak) Fusion protein into T cells prolongation of remission with application of flutica- Anti-CD3a IV Humanized Binds activated T sone propionate 0.05% was seen. Significant benefit (Visilizumab) monoclonal cells – apoptosis was also seen with fluticasone propionate 0.005%, but antibody the benefit and statistical significance was reduced DT, diphtheria toxin; IM, intramuscular administration; IV, intra- (p50.01). venous administration; SC, subcutaneous administration. # 2005 Taylor & Francis. ISSN 0001-5555 Acta Derm Venereol Suppl. 215 DOI: 10.1080/03658340510046807 26 R. Langley are enrolled within 3 months of initial diagnosis. There eosinophils in volunteer studies and in patients across is a 3-year double-blind treatment period followed by an various diseases. open label extension for up to 6 years. The treatment Similarly, omalizumab is a humanized monoclonal regimen is flexible according to the severity of the antibody against IgE, which prevents IgE from attach- disease. Dose finding studies with systemic pimecroli- ing to mast cells and other effector cells. mus have been conducted in psoriasis and in AD. A Genome-based therapy is an emerging platform. clear dose response effect was seen. Unlike cyclosporine Antisense drugs could be an interesting area for future there is no effect on renal function (assessed by serum exploration. creatinine) and blood pressure. Although there was an increase in infections in the pimecrolimus group, these CONCLUSION were not serious. Oral pimecrolimus 30 mg daily has the potential to become a key systemic therapy for There is still the opportunity for control of AD to be inflammatory skin diseases. It is effective in controlling achieved with older targets and treatments. Enhanced signs and symptoms of atopic eczema and psoriasis. knowledge of the pathophysiology of AD is providing We have also worked with a cyclosporine analogue new therapeutic targets and preliminary results are ISA 247 (0.75 and 0.25 mg/kg twice daily) in psoriasis. promising. Reduction in the PASI was seen and the results compare Patients want a simple, effective and safe treatment favourably with cyclosporine itself. Preliminary data and this is the primary goal. indicate a less nephrotoxic effect than cyclosporine and ISA 247 compound will be studied in AD. DISCUSSION Immune deviation of T cells, shifting the Th1 and Thestrup-Pedersen; Oral pimecrolimus took around 4–5 Th2 balance, is exemplified by interferon-gamma. The weeks before there was any apparent benefit, is this rationale for its use is that AD is a prototypical Th2 correct? disease and interferon-gamma inhibits the Th2 response. The postulated benefit of recombinant interferon- Langley; These were severe cases, but benefit was seen gamma would be decreased IgE levels, decreased IL-4 from early in treatment at the higher dose. The patients levels, decrease in other Th2 responses, leading to were adults who show a somewhat slower response than restoration of the immune balance and clinical improve- children. ment. A double-blind study was done some years ago by Hanifin et al. (7). Some benefit was seen in some Diepgen; On what basis were the doses of ISA 247 parameters – erythema, oedema/induration, pruritus, selected? excoriations, dryness and lichenification and overall Langley; By extrapolation from the cyclosporine clinical benefit. However, there was no reduction in dosages. ISA 47 is a potent molecule. serum IgE levels as expected from the rationale. Little recent work has been done with interferon-gamma. Leung; Did you see any systemic immunosuppression? Another molecule that theoretically is interesting in Langley; This was a short-term 12-week study, but trying to cause a cytokine shift is M50367 (8). In vitro nothing was seen. Long-term data are pivotal of course. studies showed that it increases the Th1/Th2 ratio. An alternative way of looking at anticytokine effects Hamberg; How long is it before you see an effect? is to consider blocking IL-12 to shut down the Th1 response. Kauffman et al. (9) have looked at a human Langley; The onset is pretty quick: within 4–6 weeks. In monoclonal antibody to IL-12 in moderate to severe general these types of drugs can be classified as quick psoriasis. A reduction in PASI of 75% at 8 weeks was onset, e.g. ISA 247, pimecrolimus and cyclosporine, but seen following single doses, which were well tolerated. when withdrawn relapse is apparent. The Alefacept type There were reductions in CD16 and 56 counts (NK cells) takes 12–16 weeks to produce a response, but there is a and interferon-gamma levels in lesions were significantly long period before relapse. reduced within 2 weeks. Other studies are currently There are many new biotech companies emerging and under way. many have drug patents against specific immunological Mepolizumab, an anti-human IL-5 monoclonal anti- targets in AD and psoriasis. Whether such specific body, is an example of the strategy to bind inflamma- targets will be beneficial clinically remains to be seen. tory cytokines or immunoglobulins. The rationale is that The drugs which we know are effective and have a more IL-5 is the major haematopoietin responsible for growth broad spectrum of activity. and differentiation, recruitment, activation and survival of eosinophils. Mepolizumab blocks binding of human Bieber; Will we have enough patients for all these IL-5 to its receptor on the eosinophil cell surface and studies? All the study designs will have exactly the same demonstrates consistent and significant lowering of inclusion and exclusion criteria! Acta Derm Venereol Suppl. 215 New therapeutic targets in atopic eczema 27 Taieb; It is just the same in rheumatoid arthritis and it REFERENCES may be a technique to block the clinical trial procedure 1. Kissling S, Wuthrich B. Follow-up of atopic dermatitis and by that possible competitors. after early childhood. Hautartz 1993; 44: 569–573 [in German]. Leung; Interferon-gamma is very expensive and there are 2. Barnetson R, Rogers M. Childhood atopic eczema.
Load more

Recommended publications
  • Psoriasis and the New Biologic Agents: Interrupting a T-AP Dance
    Review Synthèse Psoriasis and the new biologic agents: interrupting a T-AP dance Scott R.A. Walsh, Neil H. Shear Abstract corticosteroids, tar, anthralin, calcipotriol or tazarotene be- come cumbersome to apply as lesional surface area increases. PSORIASIS IS AN IMMUNE-MEDIATED SKIN DISEASE in which chronic T- Furthermore, potential side effects of these therapies increase cell stimulation by antigen-presenting cells (APC) occurs in the with the level of application. Nevertheless, topical treatment skin. This interplay between the T-cell and APC has been likened remains an adjunct in more severe disease to limit the re- to a “T-AP dance” where specific steps must occur in sequence to quirement for more aggressive therapies. Phototherapy is a result in T-cell activation and the disease phenotype; otherwise T- popular option in the treatment of more widespread disease. cell anergy would occur. Several novel engineered proteins de- However, ultraviolet light is generally only available in larger signed to block specific steps in immune activation (biologic treatment centres, requires a major time commitment (2–3 agents) have demonstrated efficacy in the treatment of psoriasis. times per week for many months) and can be associated with These agents include fusion proteins, monoclonal antibodies and an increased risk of cutaneous neoplasms.6 For moderate to recombinant cytokines. These medications act at specific steps during the T-AP dance either to inhibit T-cell activation, costimu- severe disease, oral systemic immunosuppressives such as lation and subsequent proliferation of T-cells, lead to immune de- methotrexate and cyclosporine or oral retinoids are generally viation or induce specific cytokine blockades.
    [Show full text]
  • Infliximab, Adalimumab and Golimumab for Treating Moderately
    HEALTH TECHNOLOGY ASSESSMENT VOLUME 20 ISSUE 39 MAY 2016 ISSN 1366-5278 Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model Rachel Archer, Paul Tappenden, Shijie Ren, Marrissa Martyn-St James, Rebecca Harvey, Hasan Basarir, John Stevens, Christopher Carroll, Anna Cantrell, Alan Lobo and Sami Hoque DOI 10.3310/hta20390 Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model Rachel Archer,1* Paul Tappenden,1 Shijie Ren,1 Marrissa Martyn-St James,1 Rebecca Harvey,1 Hasan Basarir,1 John Stevens,1 Christopher Carroll,1 Anna Cantrell,1 Alan Lobo2 and Sami Hoque3 1Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK 2Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK 3Barts Health NHS Trust, London, UK *Corresponding author Declared competing interests of authors: none Published May 2016 DOI: 10.3310/hta20390 This report should be referenced as follows: Archer R, Tappenden P, Ren S, Martyn-St James M, Harvey R, Basarir H, et al. Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model. Health Technol Assess 2016;20(39). Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta Medica/EMBASE, Science Citation Index Expanded (SciSearch®) and Current Contents®/ Clinical Medicine.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • 10. M. P. MARTINEZ MONTIEL 23/5/06 08:40 Página 265
    10. M. P. MARTINEZ MONTIEL 23/5/06 08:40 Página 265 1130-0108/2006/98/4/265-291 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS REV ESP ENFERM DIG (Madrid) Copyright © 2006 ARÁN EDICIONES, S. L. Vol. 98. N.° 4, pp. 265-291, 2006 POINT OF VIEW Biologic therapies for chronic inflammatory bowel disease M. P. Martínez-Montiel and M. T. Muñoz-Yagüe Service of Digestive Diseases. Hospital Universitario 12 de Octubre. Madrid, Spain ABSTRACT Martínez-Montiel MP, Muñoz-Yagüe MT. Biologic therapies for chronic inflammatory bowel disease. Rev Esp Enferm Dig Crohn's disease (CD) and ulcerative colitis (UC) make up the 2006; 98: 265-291. so-called chronic inflammatory bowel disease (IBD). Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more INTRODUCTION specific management of this disease with fewer side effects. Cur- rently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission in- Crohn’s disease (CD) and ulcerative colitis (UC) make duction and maintenance, is infliximab. The role of other mono- up the so-called inflammatory bowel disease (IBD). Ad- clonal antibodies such as adalimumab is not clearly established. It vances in the knowledge of this condition’s etiopathogene- could be deemed an alternative for patients with allergic reactions sis have been correlated to the development of novel thera- to infliximab, and for those with lost response because of anti-in- peutic agents. Medical treatment is currently the fliximab antibody development.
    [Show full text]
  • Protein Design Labs, Inc. 2002 Annual Report Rti Einlb,Ic 2002Annual Report Protein Design Labs, Inc
    PROTEIN DESIGN LABS, INC. 2002 ANNUAL REPORT PROTEIN DESIGN LABS, INC. 2002 ANNUAL REPORT WE HAVE THE RIGHT ASSETS, RIGHT HERE, RIGHT NOW. HERE’S WHAT WE’RE GOING Protein Design Labs, Inc. 34801 Campus Drive Fremont, CA 94555 TO DO WITH THEM. www.pdl.com Protein Design Labs, Inc. is a leader in the development of humanized monoclonal antibodies to treat various disease conditions. We currently have antibodies in clinical development for autoimmune and inflammatory conditions, asthma and cancer. We hold fundamental patents that cover our antibody humanization technology. This technology is also used by numerous other pharmaceutical and biotechnology companies, many of which have licensed our patents, and have agreed to pay royalties to us on any sales of licensed products. We receive royalties on sales of four currently marketed humanized antibodies. Client: Protein Design Labs Acct. Director: Bob Prow (x21) Creative Director: Bob Prow (x21) Client: Protein Design Labs Acct. Director: Bob Prow (x21) Creative Director: Bob Prow (x21) Job No: PDL02-199F Client Contact: Jim Goff Designer: Kristin Ritchie Job No: PDL02-199F Client Contact: Jim Goff Designer: Kristin Ritchie 1 Job Title: 2002 Annual Report Client Phone: Revised By: Kristin Ritchie (x22) 7 Job Title: 2002 Annual Report Client Phone: Revised By: Kristin Ritchie (x22) Refine and focus our research and development processes for humanized antibody products by 2003. Place an average of two proprietary product candidates into clinical trials each year after 2004. Initiate at least one pivotal clinical trial by 2005. Validate our own commercial manufacturing facility by 2006. OUR STRATEGY: MARKET OUR OWN MEDICINE TO BRING FULLER LIVES TO PATIENTS BY 2007.
    [Show full text]
  • Antigen-Targeted Monoclonal Antibody Otelixizumab and C
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/10/17/jpet.115.224899.DC1 1521-0103/355/2/199–205$25.00 http://dx.doi.org/10.1124/jpet.115.224899 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 355:199–205, November 2015 Copyright ª 2015 by The American Society for Pharmacology and Experimental Therapeutics Temporal Pharmacokinetic/Pharmacodynamic Interaction between Human CD3« Antigen–Targeted Monoclonal Antibody Otelixizumab and CD3« Binding and Expression in Human Peripheral Blood Mononuclear Cell Static Culture s Kevin R. Page, Enrica Mezzalana, Alexander J. MacDonald, Stefano Zamuner, Giuseppe De Nicolao, and Andre van Maurik GlaxoSmithKline, Stevenage, United Kingdom (K.R.P., A.J.M., S.Z., A.vM.); University of Pavia, Pavia PV, Italy (E.M., G.D.N.) Received April 22, 2015; accepted August 17, 2015 Downloaded from ABSTRACT Otelixizumab is a monoclonal antibody (mAb) directed to human a shorter apparent half-life at low concentration. Correspondingly, CD3«, a protein forming part of the CD3/T-cell receptor (TCR) a rapid, otelixizumab concentration–, and time-dependent re- complex on T lymphocytes. This study investigated the temporal duction in CD3/TCR expression was observed. These combined interaction between varying concentrations of otelixizumab, bind- observations were consistent with the phenomenon known as jpet.aspetjournals.org ing to human CD3 antigen, and expression of CD3/TCR complexes target-mediated drug disposition (TMDD). A mechanistic, mathe- on lymphocytes in vitro, free from the confounding influence of matical pharmacokinetic/pharmacodynamic (PK/PD) model was changing lymphocyte frequencies observed in vivo.
    [Show full text]
  • INN Working Document 05.179 Update 2011
    INN Working Document 05.179 Update 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • 211 the Impact of Biological Interventions on Health-Related Quality of Life in Adults with Crohn's Disease
    211 The impact of biological interventions on health-related quality of life in adults with Crohn's disease The impact of biological interventions on health-related quality of life in adults with Crohn's disease Protocol information Review type: Intervention Review number: 211 Authors Mirjana Stanic Benic1, Vanja Giljaca2, Vera Vlahovic-Palcevski1 1Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, Rijeka, Croatia 2Directorate of Surgery, Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital, Birmingham, UK Citation example: Stanic Benic M, Giljaca V, Vlahovic-Palcevski V. The impact of biological interventions on health- related quality of life in adults with Crohn's disease. Cochrane Database of Systematic Reviews , Issue . Art. No.: . DOI: . Contact person Mirjana Stanic Benic resident in clinical pharmacology and toxicology Department of Clinical Pharmacology Clinical Hospital Centre Rijeka Krešimirova 42 Rijeka 51000 Croatia E-mail: [email protected] Dates Assessed as Up-to-date:Not provided Date of Search: Not provided Next Stage Expected: 28 February 2019 Protocol First Published:Not specified Review First Published: Not specified Last Citation Issue: Not specified What's new Date Event Description History Date Event Description Abstract Background Objectives Search methods Selection criteria Data collection and analysis Main results Authors' conclusions Plain language summary [Summary title] [Summary text] Background Description of the condition 1 / 20 211 The impact of biological interventions on health-related quality of life in adults with Crohn's disease Crohn’s disease (CD) is a relapsing-remitting transmural inflammatory bowel disease (IBD) that may involve any part of the gastrointestinal tract from mouth to anus as well as cause extraintestinal manifestations (skin lesions, arthritis).
    [Show full text]
  • IUPAC Glossary of Terms Used in Immunotoxicology (IUPAC Recommendations 2012)*
    Pure Appl. Chem., Vol. 84, No. 5, pp. 1113–1295, 2012. http://dx.doi.org/10.1351/PAC-REC-11-06-03 © 2012 IUPAC, Publication date (Web): 16 February 2012 IUPAC glossary of terms used in immunotoxicology (IUPAC Recommendations 2012)* Douglas M. Templeton1,‡, Michael Schwenk2, Reinhild Klein3, and John H. Duffus4 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; 2In den Kreuzäckern 16, Tübingen, Germany; 3Immunopathological Laboratory, Department of Internal Medicine II, Otfried-Müller-Strasse, Tübingen, Germany; 4The Edinburgh Centre for Toxicology, Edinburgh, Scotland, UK Abstract: The primary objective of this “Glossary of Terms Used in Immunotoxicology” is to give clear definitions for those who contribute to studies relevant to immunotoxicology but are not themselves immunologists. This applies especially to chemists who need to under- stand the literature of immunology without recourse to a multiplicity of other glossaries or dictionaries. The glossary includes terms related to basic and clinical immunology insofar as they are necessary for a self-contained document, and particularly terms related to diagnos- ing, measuring, and understanding effects of substances on the immune system. The glossary consists of about 1200 terms as primary alphabetical entries, and Annexes of common abbre- viations, examples of chemicals with known effects on the immune system, autoantibodies in autoimmune disease, and therapeutic agents used in autoimmune disease and cancer. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are toxicologists, pharmacologists, medical practitioners, risk assessors, and regu- latory authorities. In particular, it should facilitate the worldwide use of chemistry in relation to occupational and environmental risk assessment.
    [Show full text]
  • Trends and Developments in the Pharmacological Treatment of Psoriasis
    Acta Derm Venereol 2002; 82: 401± 410 REVIEW Trends and Developments in the Pharmacological Treatment of Psoriasis ROBERT GNIADECKI1, CLAUS ZACHARIAE2 and MARTIN CALVERLEY3 1Department of Dermatology, Bispebjerg Hospital, Copenhagen, 2Department of Dermatology, Gentofte Hospital, Hellerup and 3Chemical Research Department, Leo Pharmaceutical Products, Ballerup, Denmark Robert Gniadecki, Department of Dermatology D92, IMMUNOSUPPRESSIVE AND ANTI- Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 INFLAMMATORY DRUGS Copenhagen NV, Denmark. E-mail: rgniadecki@ The autoimmune cutaneous reaction is believed to play hotmail.com a causative role in the development of skin lesions in (Accepted August 19, 2002.) psoriasis (9). Most of the compounds under current development for psoriasis belong to different classes of Acta Derm Venereol 2002; 82: 401± 410. immunosuppressives and anti-in¯ ammatory drugs. The central cell in the current pathogenic model is the memory (CD45RO+ ) T-lymphocyte mediating the type 1 immune response. A type 1 immune response is mediated by T 1 and T 1 lymphocytes secreting a speci® c cytokine INTRODUCTION H C pro® le (IFN-g, TNF-a, IL-12). The recently reviewed In the history of psoriasis pharmacotherapy, the mile- immunopathogenesis of psoriasis (9, 10) will be men- stone developments have largely occurred by chance. tioned only to the extent necessary for an under- Serendipitous observations in single patients have led to standing of the mechanism of action of the drugs the discovery of such important treatments as metho- included here. The memory T-lymphocytes secrete three trexate (1), deltanoids (active form of vitamin D and major cytokines, IL-2, TNF-a and IFN-g. IL-2 acts at its analogues) (2), cyclosporin (3) and, most recently, the early stages of T-cell activation and clone expan- tumour necrosis factor alpha (TNF-a) inhibitors (4).
    [Show full text]
  • Uva-DARE (Digital Academic Repository)
    UvA-DARE (Digital Academic Repository) Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis Sandborn, W.J.; Colombel, J.F.; Frankel, M.; Hommes, D.; Lowder, J.N.; Mayer, L.; Plevy, S.; Stokkers, P.; Travis, S.; van Assche, G.; Baumgart, D.C.; Targan, S.R. DOI 10.1136/gut.2009.205443 Publication date 2010 Document Version Final published version Published in Gut Link to publication Citation for published version (APA): Sandborn, W. J., Colombel, J. F., Frankel, M., Hommes, D., Lowder, J. N., Mayer, L., Plevy, S., Stokkers, P., Travis, S., van Assche, G., Baumgart, D. C., & Targan, S. R. (2010). Anti- CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis. Gut, 59(11), 1485-1492. https://doi.org/10.1136/gut.2009.205443 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2020 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, following to be employed in commercial fishing or the commercial UST, MXT, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT, CPTPT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]