DOCSLIB.ORG

Antibody-Induced Pregnancy Loss

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antibody-Induced Pregnancy Loss TNF-α Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss This information is current as Jessica Berman, Guillermina Girardi and Jane E. Salmon of September 24, 2021. J Immunol 2005; 174:485-490; ; doi: 10.4049/jimmunol.174.1.485 http://www.jimmunol.org/content/174/1/485 Downloaded from References This article cites 48 articles, 7 of which you can access for free at: http://www.jimmunol.org/content/174/1/485.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 24, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology TNF-␣ Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss1 Jessica Berman, Guillermina Girardi, and Jane E. Salmon2 The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, intrauterine growth restriction, and vascular thrombosis in the presence of antiphospholipid (aPL) Abs. Our studies in a murine model of APS induced by passive transfer of human aPL Abs have shown that activation of complement and recruitment of neutrophils into decidua are required for fetal loss, and emphasize the importance of inflammation in aPL Ab-induced pregnancy loss. In this study, we examine the role of TNF-␣ in pregnancy complications associated with aPL Abs in a murine model of APS. We show that aPL Abs are specifically targeted to decidual tissue and cause a rapid increase in decidual and systemic TNF-␣ levels. We identify the release of TNF-␣ as a critical intermediate that acts downstream of C5 activation, based on the fetal protective effects of TNF-␣ deficiency and TNF blockade ␣ ␣ and on the absence of increased TNF- levels in C5-deficient mice treated with aPL Abs. Our results suggest that TNF- links Downloaded from pathogenic aPL Abs to fetal damage and identify TNF blockade as a potential therapy for the pregnancy complications of APS. The Journal of Immunology, 2005, 174: 485–490. he antiphospholipid syndrome (APS)3 is characterized by Evidence from human pregnancy studies points to a strong as- arterial and venous thromboses and pregnancy loss that sociation between maternal Th2-type immunity and successful occur in the presence of antiphospholipid (aPL) Abs (1). pregnancy, whereas Th1-type immune reactivity is associated with T http://www.jimmunol.org/ APS is common in patients with systemic lupus erythematous, and pregnancy loss (5). Mitogen-stimulated PBMC, harvested at the it is also found in individuals without other autoimmune features. end of the first trimester, have consistently been shown to produce Although it is clear that the specific antigenic reactivity of aPL Abs higher levels of IL-4, IL-5, IL-6, and IL-10 in patients who went and their targeting to decidual tissue are critical to their effect, the on to have normal pregnancies than in those who had recurrent pathogenic mechanisms that result in fetal injury in vivo are in- spontaneous miscarriages. In contrast, levels of TNF-␣, IL-2, and completely understood. IFN-␥ were uniformly higher in patients who subsequently had Therapy for pregnant women with APS is focused on preventing miscarriages (6, 7). Indeed, the preponderance of Th2 cytokines thrombosis, but anticoagulation is only partially successful in relative to Th1 cytokines in the local milieu of the fetus is con- averting miscarriage and carries risks for fetus and mother. Al- sidered to be essential for its survival. The proinflammatory Th1- by guest on September 24, 2021 though experimental models have emphasized the role of throm- dominant response that underlies clinical pregnancy failure is de- bosis in placental tissue, histopathologic findings in placentas from pendent on immunologic factors that may be amplified by women with APS argue that proinflammatory factors may contrib- environmental stimuli, such as LPS, autoantibodies, including aPL ute to injury (2, 3). Our recent studies showing that activation of Abs, and stress (8, 9). Importantly, TNF-␣ is sensitive to modu- complement and recruitment of neutrophils into decidua are re- lation by such environmental factors. quired for fetal loss in a murine model of APS underscore the TNF-␣ is a multifunctional Th1 cytokine with roles in regulat- importance of inflammation in aPL Ab-induced pregnancy loss (4). ing hormone synthesis, placental architecture, and embryonic de- However, the specific effectors of fetal injury remain unknown. velopment (10), and elevated TNF-␣ levels are associated with Because TNF-␣ is released when infiltrating inflammatory cells miscarriage (11) and pre-eclampsia (12). Patients with recurrent are activated by complement split products and elevated levels of pregnancy loss, both with and without aPL Abs, evidence enrich- TNF-␣ have been associated with pregnancy failures, we consid- ment of TNF-␣ promoter alleles associated with increased cyto- ered the possibility that TNF-␣ may have a role in pregnancy com- kine levels (11, 13). Increased placental levels of TNF-␣ have been plications associated with APS. associated with pregnancy failure in mice (14), administration of TNF-␣ increases abortion rates (6), and blockade of TNF-␣ has been shown to prevent stress-induced miscarriage in murine mod- Department of Medicine, Hospital for Special Surgery-Weill Medical College of Cor- els of abortion (15). That TNF-␣ can directly promote tissue dam- nell University, New York, NY 10021 age in pregnancy has been suggested by in vitro studies in which Received for publication July 8, 2004. Accepted for publication October 4, 2004. TNF-␣-activated maternal monocytes bind to LFA-1 on placental The costs of publication of this article were defrayed in part by the payment of page syncytiotrophoblasts and induce apoptosis (16). charges. This article must therefore be hereby marked advertisement in accordance In this study, we examine the role of TNF-␣ in aPL Ab-induced with 18 U.S.C. Section 1734 solely to indicate this fact. fetal injury in a murine model of APS in which pregnant mice 1 This work was supported in part by a grant from the National Institutes of Health (AI055007) and by the Alliance for Lupus Research and the Mary Kirkland Center for receive human IgG containing aPL Abs. Passive transfer of IgG Lupus Research at Hospital for Special Surgery. from women with recurrent miscarriage and aPL Abs results in 2 Address correspondence and reprint requests to Dr. Jane E. Salmon, Hospital for fetal loss and growth restriction (17). The frequency of fetal re- Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address: sorption in aPL Ab-treated mice is ϳ40% compared with Ͻ10% in [email protected] mice treated with IgG from healthy individuals, and the average 3 Abbreviations used in this paper: APS, antiphospholipid syndrome; aPL, antiphos- pholipid; aPL-IgG, human IgG containing aPL Abs; NH-IgG, normal human IgG; weight of surviving aPL Ab-treated fetuses is reduced by 50% (4, PEG, polyethylene glycol; sTNFRI, soluble TNF-␣R type I; aCL, anticardiolipin. 13). We have shown that activation of complement, specifically Copyright © 2005 by The American Association of Immunologists, Inc. 0022-1767/05/$02.00 486 TNF-␣ IN aPL Ab-MEDIATED PREGNANCY LOSS C5a-C5a receptor interactions, is a necessary intermediary step for Statistical analyses these clinically relevant deleterious effects of aPL Abs (4). How- Data are expressed as mean Ϯ SD. Student’s t test was used to compare ever, the downstream pathogenic mediators of placental and fetal fetal resorption rates and fetal weights between groups. A probability of damage induced by aPL Abs and the sites and agents for optimal Ͻ0.05 was used to reject the null hypothesis. therapeutic interventions to prevent APS are not yet clear. In this study, we test the hypotheses that aPL Abs targeted to decidual Results tissue lead to the release of TNF-␣, that TNF-␣ is a critical me- APL Abs localize to decidual tissue in pregnant mice diator in aPL Ab-induced damage, and that blockade of TNF-␣ We have previously shown that passive transfer of human IgG might be an effective treatment to prevent pregnancy loss. from APS patients into pregnant mice causes inflammation within deciduae and fetal resorption or growth restriction (4, 13). These in Materials and Methods vivo studies demonstrated a direct pathogenic role for aPL Abs. In vitro studies in human and murine placentas have shown that tro- Mice phoblast cell membranes are targets for ␤2GPI-dependent and Adult mice (6–8 wk) were used in all experiments. BALB/c mice were ␤2GPI-independent aPL Abs (23), suggesting that these Abs are purchased from Taconic Farms. TNF-␣-deficient, TNFtm1Gkl/J (TNFϪ/Ϫ) ϩ ϩ specifically targeted to the placenta. In this study, we investigated mice and TNF / background strain (B6129S6) were obtained from The Jackson Laboratory (18). C5-deficient mice (C5Ϫ/Ϫ) (B10.D2-H2dH2-T18c the tissue localization and kinetics of aPL Ab handling in an in Hco/o2SnJ) and C5-sufficient mice (C5ϩ/ϩ) (C57BL/10SnJ) were also ob- vivo model. BALB/c mice were treated with human aPL-IgG (10 tained from The Jackson Laboratory (19, 20). Procedures that involved mg, i.p.) or NH-IgG on day 8 of pregnancy, and the presence of mice were approved by the local Committee on Animal Use in Research human IgG was assessed in tissue by immunohistochemistry.
Load more

Recommended publications
  • Comparative Transcriptome Analysis of Embryo Invasion in the Mink Uterus
    Placenta 75 (2019) 16–22 Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta Comparative transcriptome analysis of embryo invasion in the mink uterus T ∗ Xinyan Caoa,b, , Chao Xua,b, Yufei Zhanga,b, Haijun Weia,b, Yong Liuc, Junguo Caoa,b, Weigang Zhaoa,b, Kun Baoa,b, Qiong Wua,b a Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China b State Key Laboratory for Molecular Biology of Special Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Changchun, China c Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province, College of Biological and Food Engineering, Fuyang Teachers College, Fuyang, China ABSTRACT Introduction: In mink, as many as 65% of embryos die during gestation. The causes and the mechanisms of embryonic mortality remain unclear. The purpose of our study was to examine global gene expression changes during embryo invasion in mink, and thereby to identify potential signaling pathways involved in implantation failure and early pregnancy loss. Methods: Illumina's next-generation sequencing technology (RNA-Seq) was used to analyze the differentially expressed genes (DEGs) in implantation (IMs) and inter- implantation sites (inter-IMs) of uterine tissue. Results: We identified a total of 606 DEGs, including 420 up- and 186 down-regulated genes in IMs compared to inter-IMs. Gene annotation analysis indicated multiple biological pathways to be significantly enriched for DEGs, including immune response, ECM complex, cytokine activity, chemokine activity andprotein binding. The KEGG pathway including cytokine-cytokine receptor interaction, Jak-STAT, TNF and the chemokine signaling pathway were the most enriched.
    [Show full text]
  • IL-10-Null Mice Inflammation-Induced Fetal Demise in Uterine NK Cells Mediate
    Uterine NK Cells Mediate Inflammation-Induced Fetal Demise in IL-10-Null Mice This information is current as Shaun P. Murphy, Loren D. Fast, Nazeeh N. Hanna and of September 27, 2021. Surendra Sharma J Immunol 2005; 175:4084-4090; ; doi: 10.4049/jimmunol.175.6.4084 http://www.jimmunol.org/content/175/6/4084 Downloaded from References This article cites 52 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/175/6/4084.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Uterine NK Cells Mediate Inflammation-Induced Fetal Demise in IL-10-Null Mice Shaun P. Murphy,* Loren D. Fast,† Nazeeh N. Hanna,‡ and Surendra Sharma2* Specialized NK cells are recruited in high numbers to the mammalian embryo implantation sites, yet remain pregnancy com- patible.
    [Show full text]
  • Role of Some Cytokines on Reproduction
    Middle East Fertility Society Journal (2011) 16, 220–223 Middle East Fertility Society Middle East Fertility Society Journal www.mefsjournal.com www.sciencedirect.com ORIGINAL ARTICLE Role of some cytokines on reproduction Batool Mutar Mahdi * Department of Microbiology, Al-Kindy College of Medicine, Baghdad University, AL-Nahda Square, Baghdad, Iraq Received 11 December 2010; accepted 13 March 2011 Available online 9 April 2011 KEYWORDS Abstract Background: The etiology of female reproductive failure may be very complex owing to Infertility; a neuro-endocrine-immune association. Dysregulated immunity has been implicated in reproductive Cytokines; failure. Lower TH1 cytokines is supportive for physiological pregnancy. IL-10; Aim of the study: To measure serum levels of pro-inflammatory cytokines (tumor necrosis factor IL-6; (TNF-a), interferon-gamma (IFN-c) and anti-inflammatory cytokines (IL-10 and IL-6) in repro- IFN-c; ductive failure women. TNF-a Patients and methods: A cross- sectional study was carried out in Kammal El-Sammrari Hospital from 2008 to 2010. Forty-five women with reproductive failure participated in the study. Serum lev- els of cytokines (IL-6, IL-10, TNF-alpha and IFN-gamma) were done by Enzyme Linked Immuno Sorbent Assay (ELISA) and compared with age, body mass index and ethnicity matched thirty fer- tile women. Results: There is a significant increase in IL-10 (18.09) (p = 0.002) and IFN-c (49.62) (p = 0.0001) in women with reproductive failure. TNF-a and IL-6 showed no significance different with fertile group. Conclusions: There is increase in IL-10 and IFN-c in women with reproductive failure.
    [Show full text]
  • For Review Only 19 10 Telephone: +44 1223 333729 20 21 Fax: +44 1223 333346
    Submitted to Phil. Trans. R. Soc. B - Issue The role of the maternal immune system in the regulation of human birth weight For ReviewJournal: Philosophical Only Transactions B Manuscript ID: RSTB-2014-0071.R1 Article Type: Review Date Submitted by the Author: n/a Complete List of Authors: Moffett, Ashley; University of Cambridge, Pathology Hiby, Susan; University of Cambridge, Pathology Sharkey, Andrew; University of Cambridge, Pathology Issue Code: Click <a href=http://rstb.royalsocietypublishing.org/site/misc/issue- BIRTH codes.xhtml target=_new>here</a> to find the code for your issue.: Developmental biology < BIOLOGY, Evolution Subject: < BIOLOGY, Genetics < BIOLOGY, Immunology < BIOLOGY Birth weight, Natural Killer (NK) cells, Keywords: Immunology, pre-eclampsia, fetal growth restriction, placental development http://mc.manuscriptcentral.com/issue-ptrsb Page 1 of 27 Submitted to Phil. Trans. R. Soc. B - Issue 1 1 2 3 4 5 The role of the maternal immune system in the regulation of 6 7 human birth weight 8 9 10 1,2 1 1 11 5 Ashley Moffett , Susan E . Hiby and Andrew Sharkey 12 1 Department of Pathology and Centre for Trophoblast Research, 13 14 University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK 15 16 17 2Corresponding author. E-mail address: [email protected] (A. Moffett). 18 For Review Only 19 10 Telephone: +44 1223 333729 20 21 Fax: +44 1223 333346. 22 23 24 Summary 25 26 Human birth weight is subject to stabilizing selection. Large babies are at 27 15 risk of obstetric complications such as obstructed labour, which endangers 28 29 both mother and child.
    [Show full text]
  • Early Pregnancy Diagnosis and Embryo/Fetus Mortality
    EARLY PREGNANCY DIAGNOSIS AND EMBRYO/FETUS MORTALITY IN CATTLE A Dissertation by JUAN EDUARDO ROMANO Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY December 2004 Major Subject: Physiology of Reproduction EARLY PREGNANCY DIAGNOSIS AND EMBRYO/FETUS MORTALITY IN CATTLE A Dissertation by JUAN EDUARDO ROMANO Submitted to Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved as to style and content by: _____________________________ _________________________________ Duane C. Kraemer David W. Forrest (Co-Chair of Committee) (Co-Chair of Committee) _____________________________ _________________________________ Mark E. Westhusin James A. Thompson (Member) (Member) _____________________________ John W. McNeill (Head of Department) December 2004 Major Subject: Physiology of Reproduction iii ABSTRACT Early Pregnancy Diagnosis and Embryo/Fetus Mortality in Cattle. (December 2004) Juan Eduardo Romano, D.V.M., University of Uruguay; M.S., University of Minnesota Co-Chairs of Advisory Committee: Dr. Duane C. Kraemer Dr. David W. Forrest Pregnancy diagnosis by transrectal ultrasonography (using a 5 MHZ linear probe) presented the maximum sensitivity and negative predictive values at day 26 and day 29 after estrus in heifers and cows, respectively. Palpation per rectum using the fetal membrane slip for pregnancy diagnosis did not increase embryo/fetus mortality when compared with a positive control group of non-palpated females. The use of a controlled randomized block design was a useful approach to study this problem. Blocking for category and number of embryos allowed us to remove these confounding factors. Factors that affected pregnancy loss during the first four months of pregnancy were: period of pregnancy, age of the animal, number of previous lactations and number of embryos.
    [Show full text]
  • Seminal CD38 Is a Pivotal Regulator for Fetomaternal Tolerance
    Seminal CD38 is a pivotal regulator for fetomaternal tolerance Byung-Ju Kima,b, Yun-Min Choia,b, So-Young Raha,b, Dae-Ryoung Parka,b, Seon-Ah Parka, Yun-Jo Chunga, Seung-Moon Parkc, Jong Kwan Parkd, Kyu Yun Jange, and Uh-Hyun Kima,b,f,1 + aNational Creative Research Laboratory for Ca2 Signaling Network and Departments of bBiochemistry, dUrology, and ePathology, Chonbuk National University Medical School, Jeonju, 561-180, Korea; cDivision of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan, 570-752, Korea; and fInstitute of Cardiovascular Research, Chonbuk National University, Jeonju, 561-180, Korea Edited by John J. Eppig, The Jackson Laboratory, Bar Harbor, ME, and approved December 22, 2014 (received for review July 16, 2014) A successful pregnancy depends on a complex process that estab- a variety of inflammatory diseases (20–23). For example, recombi- lishes fetomaternal tolerance. Seminal plasma is known to induce nant CD38 inhibits LPS-induced inflammatory signals in mouse maternal immune tolerance to paternal alloantigens, but the seminal macrophages and human DCs through an interaction with CD31 factors that regulate maternal immunity have yet to be characterized. (24, 25). Here, we show that a soluble form of CD38 (sCD38) released from In this study, we found that CD38 is truncated and released seminal vesicles to the seminal plasma plays a crucial role in inducing into the seminal plasma from seminal vesicles (SVs) as a soluble + + + tolerogenic dendritic cells and CD4 forkhead box P3 (Foxp3 )reg- form (sCD38) in humans and mice. This finding prompted us to ulatory T cells (Tregs), thereby enhancing maternal immune tolerance examine whether CD38 plays a role in maternal immune toler- and protecting the semiallogeneic fetus from resorption.
    [Show full text]
  • Preterm Birth and Preeclampsia Fetal
    The Journal of Immunology TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia Andrea Scharfe-Nugent,*,1 Sine´ad C. Corr,†,1 Susan B. Carpenter,‡ Louise Keogh,x Brendan Doyle,{ Cara Martin,{ Katherine A. Fitzgerald,‡ Sean Daly,* John J. O’Leary,{,2 and Luke A. J. O’Neill†,2 Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflam- mation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in sponta- neous preterm birth. Fetal DNA activates NF-kB, shown by IkBa degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 mg/dam) on gestational day 10–14. In contrast, TLR92/2 mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of preg- nancy. The Journal of Immunology, 2012, 188: 5706–5712. retermbirth(PTB),definedasdeliverybefore37wk disorders of pregnancy. TLRs are an important class of pathogen gestation, has become an epidemic in developed countries. recognition receptors, which signal during infection to bring about P Indeed, PTB and preeclampsia (PEC) are leading causes of immune reactions that have been implicated in PTB (3).
    [Show full text]
  • Amended Safety Assessment of Hydroquinone and P-Hydroxyanisole As Used in Cosmetics
    Amended Safety Assessment of Hydroquinone and p-Hydroxyanisole as Used in Cosmetics Status: Draft Amended Report for Public Comment Release Date: November 15, 2013 Panel Meeting Date: December 9-10, 2013 The 2013 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A. Hill, Ph.D. James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1101 17th Street, NW, Suite 412 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 cirinfo@cir- safety.org Distributed for Comment Only -- Do Not Cite or Quote Commitment & Credibility since 1976 MEMORANDOM To: CIR Expert Panel and Liaisons From: Lillian C. Becker, M.S. Scientific Analyst and Writer Date: November 15, 2013 Subject: Hydroquinone & p-Hydroxyanisole As Used In Nail Products in Cosmetics This is the Draft Report of hydroquinone and p-hydroxyanisole as used in nail products. In March, 2013, the Panel decided to review submitted data accompanying a request to amend the 2010 conclusion to include the use of nail polishes that require UV curing. This data, as well as relevant literature on the use of UV nail lamps, are included in this report. The Panel is to review the presented data and decide if there is sufficient information to come to a conclusion on the use of hydroquinone and p-hydroxyanisole in nail products that require UV curing.
    [Show full text]
  • Amended Safety Assessment of Hydroquinone As Used in Cosmetics
    Amended Safety Assessment of Hydroquinone as Used in Cosmetics Status: Draft Amended Report for Panel Review Release Date: February 21, 2014 Panel Meeting Date: March 17-18, 2014 The 2014 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A. Hill, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected] i Commitment & Credibility since 1976 MEMORANDOM To: CIR Expert Panel and Liaisons From: Lillian C. Becker, M.S. Scientific Analyst and Writer Date: February 21, 2014 Subject: Hydroquinone As Used In in Cosmetics In December 2013, the Panel tabled the Draft Amended Report of hydroquinone and p- hydroxyanisole as used in nail products for the purpose of collecting more data on the use of UV nail lamps. The papers that were requested have been sent to you by email and are summarized in the appropriate section of the report. A paper that Dr. Liebler asked to review (Hansch et al. 2000) is also included in the email. The previous safety assessments on these ingredients are also included in case more information than what is provided in the summaries is needed.
    [Show full text]
  • Recurrent Pregnancy Loss
    Recurrent Pregnancy Loss November 2017 Version 2 0 ESHRE Early Pregnancy Guideline Development Group [1] Version 2 was published 1 April 2019 and includes a correction in the numbers mentioned in section 4.2 on page 39 (changes were marked in green). No further changes were made as compared to version 1 (published November 2017) DISCLAIMER The European Society of Human Reproduction and Embryology (hereinafter referred to as 'ESHRE') developed the current clinical practice guideline, to provide clinical recommendations to improve the quality of healthcare delivery within the European field of human reproduction and embryology. This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. The aim of clinical practice guidelines is to aid healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients. However, adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not override the healthcare professional's clinical judgment in diagnosis and treatment of particular patients. Ultimately, healthcare professionals must make their own clinical decisions on a case-by-case basis, using their clinical judgment, knowledge, and expertise, and taking into account the condition, circumstances, and wishes of the individual patient, in consultation with that patient and/or the guardian or carer. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose.
    [Show full text]
  • The Vanishing Triplet
    her and ot C M h il n d i H s e c i a l n t i l h Chen, Clinics Mother Child Health 2015, 12:4 C Clinics in Mother and Child Health ISSN: 2090-7214 DOI: 10.4172/2090-7214.1000196 Case Report Open Access The Vanishing Triplet Pi-Hua Chen Department of Obstetrics and Gynecology, Shuang Ho Hospital , Taipei Medical University, Taipei, Taiwan Corresponding author: Pi-Hua Chen, Department of Obstetric and Gynecology, Shuang-Ho Hospital, Zhonghe District, New Taipei City, Taiwan,Tel: +886222490088; E-mail: [email protected] Received date: October 8, 2015; Accepted date: October 19, 2015; Published date: October 25, 2015 Copyright: © 2015 Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Vanishing fetuses are frequently encountered in pregnancies results from in vitro fertilization. Ultrasound scans taken at the 4-5th weeks showed multiple gestation has occurred, it frequently happens that more than one amniotic sac can be seen in early pregnancy, whereas a few weeks later there is only one to be seen and the other has disappeared. Whereas the triplet pregnancy evolved into a normal twin gestation, and may further evolve into a singleton gestation. These very high resorption rates, which can be explained on the basis of the intense fetal competition for space, nutrition, or other factors during early gestation with frequent loss of the other fetus. Here, we report a case of a vanishing triplet of spontaneous pregnancy, one fetus vanished in the first month of pregnancy while another fetus disappeared at the end of second month.
    [Show full text]
  • The Success of Early Pregnancy Is Determined by the Action of Fundamental Processes That Take Place in the First Week After Fert
    1 Just Accepted 2 This article has been peer reviewed and accepted for publication. It is in production 3 and has not been edited, so may differ from the final published form. 4 Endogenous lysophosphatidic acid participates in 5 vascularization and decidualization at the maternal- 6 fetal interface in the rat 7 Micaela Sordelli , Jimena Beltrame , Elsa Zotta , Natalia Gomez , Ganna Dmytrenko , 8 Maria Sales , Sandra Blois , Carlos Davio , SilvinaPerez 9 Martinez , Ana Franchi , Maria Ribeiro 10 Abstract 11 Lysophosphatidic acid (LPA) influences several female reproductive functions through 12 G protein-coupled receptors. LPA contributes to embryo implantation via 13 lysophosphatidic type 3 receptor (LPA3). In this study, we investigated the participation 14 of endogenous LPA signaling through LPA3 in vascularization and decidualization, two 15 crucial events at the maternal-fetal interface. Pregnant rats were treated with 16 diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA3, in day 5 17 of gestation. DGPP treatment produced aberrant embryo spacing and increased 18 embryo resorption. Also, LPA3 antagonist decreased the cross sectional length of the 19 uterine and arcuate arteries and induced histological anomalies in the decidua and 20 placentas. Marked hemorrhagic processes, infiltration of immune cells and tissue 21 disorganization were observed in the decidual and placental tissues from resorpted 22 sites. The mRNA expression of interleukin 10 (Il-10), vascular endothelial growth factor 23 (Vegf-a) and vascular endothelial growth factor receptor 1 (Vegf-r1), three 24 vascularization markers, was reduced in resorpted sites from day 8. Our results show 25 that the disruption of endogenous LPA signaling by blocking LPA3 modified the 26 development of uterine vessels with consequences in the formation of the decidua and 27 placenta and in the growth of the embryos.
    [Show full text]