WorldWideScience

Sample records for human placental inside-out

  1. Fungal Biofilms: Inside Out.

    Science.gov (United States)

    Lagree, Katherine; Mitchell, Aaron P

    2017-04-01

    We focus this article on turning a biofilm inside out. The "inside" of the biofilm comprises the individual biofilm-related phenotypes, their environmental drivers and genetic determinants, and the coordination of gene functions through transcriptional regulators. Investigators have viewed the inside of the biofilm through diverse approaches, and this article will attempt to capture the essence of many. The ultimate goal is to connect the inside to the "outside," which we view as biofilm structure, development, pharmacological attributes, and medical impact.

  2. Ligation of the beta4 integrin triggers adhesion behavior of human keratinocytes by an "inside-out" mechanism.

    Science.gov (United States)

    Kippenberger, Stefan; Loitsch, Stefan; Müller, Jutta; Guschel, Maike; Kaufmann, Roland; Bernd, August

    2004-09-01

    Carcinogenesis is considered as a multistep process involving functional changes in the hemidesmosomal organization. In normal skin keratinocytes, expression of the alpha(6)beta(4) integrin is restricted to the proliferative basal layer and mediates stable adhesion to the underlying basement membrane. Observations in carcinoma cells show a functional and spatial dissociation of the alpha(6)beta(4) integrin from the hemidesmosomal complex, which stimulates cell migration and, therefore, may contribute to carcinoma invasion. We now have evaluated the adhesion behavior of epithelial cells at different stages of transformation in response to activation of the beta(4) integrin. It is demonstrated that ligation of the beta(4) integrin augmented adhesion of carcinoma and pre-carcinoma cells to non-modified plastic. In contrast, adhesion behavior of normal human keratinocytes was not influenced by ligation of the beta(4) integrin. In order to explain the mechanism of beta(4)-mediated adhesion, the hypothesis of an "inside-out" activation of integrins was tested. Evidence is given that for cells expressing the alpha(6)beta(4) integrin, ligation of the beta(4) integrin increased beta(1) integrin-mediated adhesion. Furthermore, ligation of the beta(4) integrin led to phosphorylation of PKB/Akt at both phosphorylation sites. Functional blocking of PKB/Akt by dominant-negative overexpression decreased cell adhesion in response to beta(4) integrin ligation. Taken together, the present data establish a link between the ligation of the beta(4) integrin and beta(1) integrin-mediated cell adhesion in carcinoma and pre-carcinoma cells. Hence, these findings provide further insight into the conversion processes during carcinogenesis and show the beta(4) integrin to be a key regulator of cellular adhesion.

  3. Manganese superoxide dismutase-mediated inside-out signaling in HaCaT human keratinocytes and SKH-1 mouse skin.

    Science.gov (United States)

    Holley, Aaron K; Xu, Yong; Noel, Teresa; Bakthavatchalu, Vasudevan; Batinic-Haberle, Ines; St Clair, Daret K

    2014-05-20

    Inside-out signaling occurs when changes in organellar activity lead to alterations in cell signaling that culminate at the cell surface. Mitochondria are vital signaling platforms in cells that participate in radiation-induced inside-out signaling. However, the importance of the reactive oxygen species (ROS)-scavenging ability of mitochondria through manganese superoxide dismutase (MnSOD) is not established. Here, we used MnSOD heterozygous knockout and transgenic SKH-1 hairless, albino mice and MnSOD knockdown and overexpressing HaCaT human keratinocytes to study the effects of MnSOD on ultraviolet (UV) radiation-induced inside-out signaling. There is an inverse correlation between MnSOD expression and UV-induced activation of epidermal growth factor receptor (EGFR), as determined by phosphorylation at Tyr1068, both in vitro and in vivo, which correlates with increased ROS production (as measured by dihydroethidium fluorescence). EGFR activation is dependent on Nox4 expression and Src kinase activation, with Src activation upstream of Nox4 in regulation of EGFR activation. Enhanced EGFR activation in MnSOD knockdown cells is abrogated by treatment with the SOD mimetic MnTnBuOE-2-PyP(5+). Our data demonstrate that the ROS-scavenging ability of mitochondria, through the expression of MnSOD, is important for UV-induced inside-out signaling. Decreased MnSOD expression enhances UV-induced activation of different oncogenic signaling pathways through an inside-out signaling-mediated mechanism. Inhibition of inside-out signaling by MnTnBuOE-2-PyP(5+) mimics the effect of endogenous MnSOD, suggesting that pharmacological intervention by SOD mimetics could play an important role in the prevention of aberrant cell signaling, which may contribute to carcinogenesis and may prove valuable for the treatment or prevention of cancer in the future.

  4. Inside-out meniscus repair.

    Science.gov (United States)

    Nelson, Clay G; Bonner, Kevin F

    2013-01-01

    Meniscus repair over resection, when feasible, should be strongly considered in an effort to preserve meniscus integrity and function, especially in younger patients. Currently, a number of techniques and implants may be used to achieve a successful result. Although all-inside meniscus repair devices have evolved significantly since their introduction and have become the repair technique of choice for many surgeons, the classic inside-out repair technique is still very useful to have in one's armamentarium. Though less popular because of the ease of current-generation fixators, the inside-out technique can still offer advantages for those surgeons who are proficient. With the versatility to address most tear patterns, the ability to deliver sutures with smaller needle diameters, and proven long-term results, it has been considered the gold standard in meniscus repair. We review the inside-out repair technique for both a medial and lateral meniscus tear with some helpful tips when performing the technique, and we present a video demonstration of the lateral meniscus repair technique.

  5. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  6. Poetry Inside Out: Bridging Cultures through Language

    Science.gov (United States)

    Rutherford, Marty

    2009-01-01

    This paper is about a writing and literary translation program called Poetry Inside Out (PIO). Students in the PIO program study poetic form and structure, figurative language, and the fundamentals of literary translation in an extended workshop format. During a typical Poetry Inside Out workshop, participants read, discuss, translate and recite…

  7. Inside-out electrical capacitance tomography

    DEFF Research Database (Denmark)

    Kjærsgaard-Rasmussen, Jimmy; Meyer, Knud Erik

    2011-01-01

    ; allowing the inside-out sensor to move inside the outer tube. A test sensor was constructed and capacitances were measured using the charge transfer technique. Sensitivity matrices for the inside-out sensor were calculated with a finite element approach and some special issues with the sensitivity matrices...

  8. Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles.

    Science.gov (United States)

    Xie, Wensheng; Gao, Qin; Wang, Dan; Wang, Wei; Yuan, Jie; Guo, Zhenhu; Yan, Hao; Wang, Xiumei; Sun, Xiaodan; Zhao, Lingyun

    2017-01-01

    With the wide recognition of oncostatic effect of melatonin, the current study proposes a potential breast cancer target multimodality treatment based on melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). Melatonin-MNPs were fabricated by the single emulsion solvent extraction/evaporation method. Based on the facilitated transport of melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can be more favorably uptaken by MCF-7 cells compared with the melatonin-free nanocomposite particles, which indicates the cancer targeting ability of melatonin molecule. Inductive heating can be generated by exposure to the Melatonin-MNPs internalized within cancer cells under alternative magnetic field, so as to achieve the "inside-out" magnetic nano-thermotherapy. In addition to demonstrating the superior cytotoxic effect of such nano-thermotherapy over the conventional exogenous heating by metal bath, more importantly, the sustainable release of melatonin from the Melatonin-MNPs can be greatly promoted upon responsive to the magnetic heating. The multimodality treatment based on Melatonin-MNPs can lead to more significant decrease in cell viability than any single treatment, suggesting the potentiated effect of melatonin on the cytotoxic response to nano-thermotherapy. This study is the first to fabricate the precisely engineered melatonin-loaded multifunctional nanocomposite particles and demonstrate the potential in breast cancer target multimodality treatment.

  9. Windows Server® 2008 Inside Out

    CERN Document Server

    Stanek, William R

    2009-01-01

    Learn how to conquer Windows Server 2008-from the inside out! Designed for system administrators, this definitive resource features hundreds of timesaving solutions, expert insights, troubleshooting tips, and workarounds for administering Windows Server 2008-all in concise, fast-answer format. You will learn how to perform upgrades and migrations, automate deployments, implement security features, manage software updates and patches, administer users and accounts, manage Active Directory® directory services, and more. With INSIDE OUT, you'll discover the best and fastest ways to perform core a

  10. From Inside Out: Beyond Teaching about Leadership

    Science.gov (United States)

    Posner, Barry Z.

    2009-01-01

    We begin this special issue focusing on the theoretical framework issues in leadership education. As always, Barry Posner has us thinking about the broader context of leadership education, namely what matters most in individual leadership development. In his article, "From Inside Out: Beyond Teaching 'About' Leadership," what matters…

  11. Inside Out--Reflection from Newtown

    Science.gov (United States)

    Connelly, Susan

    2013-01-01

    Trauma can turn anyone inside out. But when an entire community experiences the same trauma in a matter of minutes, it shatters the rhythm of everyday life and forces a redefinition of "normal." In this article, a school counselor in Newtown who experienced the massacre at Sandy Hook Elementary School shares her perspectives on the…

  12. Inside-out formation of massive galaxies

    Science.gov (United States)

    de la Rosa, I. G.

    2017-03-01

    A significant fraction of the present day massive galaxies have compact cores embedded inside their disks or halos. Strikingly, those compact cores are similar to the massive high-redshift quiescent compact galaxies, nicknamed red-nuggets. We present observational evidence supporting an inside-out formation scenario, where present-day massive galaxies can begin as dense spheroidal cores (red-nuggets), around which either a spheroidal halo or a disk are accreted later. This contribution is based on the paper by de la Rosa et al. (2016).

  13. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  14. Inside-out neuropharmacology of nicotinic drugs.

    Science.gov (United States)

    Henderson, Brandon J; Lester, Henry A

    2015-09-01

    Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    and represents a supplement and alternative to animal testing, bypassing the animal to human extrapolation. Placentas are readily obtainable from most births upon informed consent from the mothers and are considered a promising tissue alternative/supplement to animal experiments. The system is validated...

  16. Inside-out growth or inside-out quenching? Clues from colour gradients of local galaxies

    Science.gov (United States)

    Lian, Jianhui; Yan, Renbin; Blanton, Michael; Kong, Xu

    2017-12-01

    We constrain the spatial gradient of star formation history (SFH) within galaxies using the colour gradients in NUV - u (where NUV stands for near-ultraviolet) and u - i for a local spatially resolved galaxy sample. By splitting each galaxy into an inner and an outer part, we find that most galaxies show negative gradients in these two colours. We first rule out dust extinction gradient and metallicity gradient as the dominant source for the colour gradient. Then using stellar population models, we explore variations in SFH to explain the colour gradients. As shown by our earlier work, a two-phase SFH consisting of an early secular evolution (growth) phase and a subsequent rapid evolution (quenching) phase is necessary to explain the observed colour distributions among galaxies. We explore two different inside-out growth models and two different inside-out quenching models by varying parameters of the SFH between inner and outer regions of galaxies. Two of the models can explain the observed range of colour gradients in NUV - u and u - i colours. We further distinguish them using an additional constraint provided by the u - i colour gradient distribution, under the assumption of constant galaxy formation rate and a common SFH followed by most galaxies. We find the best model is an inside-out growth model in which the inner region has a shorter e-folding time-scale in the growth phase than the outer region. More spatially resolved UV observations are needed to improve the significance of the result.

  17. Human placental alkaline phosphatase in liver and intestine.

    OpenAIRE

    Garattini, E; Margolis, J; Heimer, E; Felix, A.; Udenfriend, S

    1985-01-01

    Three distinct forms of human alkaline phosphatase, presumably isozymes, are known, each apparently associated with a specific tissue. These are placental, intestinal, and liver (kidney and bone). We have used a specific immunoassay and HPLC to show that placental alkaline phosphatase is also present in extracts of liver and intestine in appreciable amounts.

  18. Prevalence and predictors of placental malaria in human ...

    African Journals Online (AJOL)

    2016-02-16

    Feb 16, 2016 ... Background: Human immunodeficiency virus (HIV)‑infected pregnant women have alterations in cellular and humoral immunity that increase the risks to placental malaria infection. Aim: This study aimed at determining the prevalence and predictors of placental malaria among HIV‑positive women.

  19. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry

  20. Prevalence and predictors of placental malaria in human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV)‑infected pregnant women have alterations in cellular and humoral immunity that increase the risks to placental malaria infection. Aim: This study aimed at determining the prevalence and predictors of placental malaria among HIV‑positive women in Nigeria. Materials and ...

  1. Inside-Out Manufacturing of Composite Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Demonstrate the inside-out manufacturing process by manufacturing a complex shaped composite structure with imbedded wiring and fluid handling without the use of a...

  2. Inside-Out Meniscal Repair: Medial and Lateral Approach.

    Science.gov (United States)

    Chahla, Jorge; Serra Cruz, Raphael; Cram, Tyler R; Dean, Chase S; LaPrade, Robert F

    2016-02-01

    Preservation of meniscal tissue has been proven to be the best approach in most cases of meniscal tears. Currently available techniques for treating a peripheral meniscal tear include inside-out, outside-in, and all-inside techniques. Each of these techniques present potential advantages and disadvantages. Despite technologic advances in all-inside devices, because of implant-related complications, cost concerns, and device availability, the inside-out technique is still the preferred method among many surgeons. Although the inside-out repair technique is considered more technically demanding and requires additional incisions, it has several advantages such as the possibility for an increased number of sutures, creating a stronger construct, and greater versatility in their placement. This article describes the inside-out meniscal repair technique with its corresponding posterolateral and posteromedial surgical approaches.

  3. At All Hours: Learning from the Inside Out.

    Science.gov (United States)

    Balliro, Lenore

    2003-01-01

    One English-as-a-Second-Language teacher talks about her opportunity to experience language learning from the inside out: She enrolled in a beginning level Spanish course at a local community college. (Author/VWL)

  4. Inside-Out Repair of Meniscal Ramp Lesions.

    Science.gov (United States)

    DePhillipo, Nicholas N; Cinque, Mark E; Kennedy, Nicholas I; Chahla, Jorge; Geeslin, Andrew G; Moatshe, Gilbert; Engebretsen, Lars; LaPrade, Robert F

    2017-08-01

    Meniscal ramp lesions have been reported to be present in 9% to 17% of patients undergoing anterior cruciate ligament reconstruction. Detection at the time of arthroscopy can be accomplished based upon clinical suspicion and careful evaluation without the use of an accessory posteromedial portal. Options for surgical treatment include arthroscopic repair using an all-inside or inside-out technique. The purpose of this Technical Note is to detail our arthroscopic inside-out repair technique for meniscal ramp lesions.

  5. A Journey of Learning Mathematics through Inside-Out Approach

    Science.gov (United States)

    Belbase, Shashidhar

    2010-01-01

    In this paper I discussed an episode of inside-out approach of learning mathematics that started from my deeply held values, feelings, thoughts, and experiences making them starting point of learning process. I was engaged in a brief learning session with a geometrical problem as context within the session. Data from video record of the learning…

  6. From the inside Out: Group Work with Women of Color

    Science.gov (United States)

    Short, Ellen L.; Williams, Wendi S.

    2014-01-01

    This article will present two models for conducting group work with Women of Color (WOC): the SisterCircle Approach and the Group Relations Model. The authors contend that the models, when used together, combine an internal and external focus ("inside out") of group work that can assist group workers to conduct individual and group-level…

  7. Time and Space Complexity of Inside-Out Macro Grammars

    NARCIS (Netherlands)

    Asveld, P.R.J.

    1980-01-01

    Starting form Fischer's IO Standard Form Theorem we show that for each inside-out (or IO-) macro language $L$ there exists a $\\lambda$-free IO macro grammar with the following property: for each $x$ in $L$ there is a derivation of $x$ of length at most linear in the length of $x$. Then we construct

  8. Time and Space Complexity of Inside-Out Macro Languages

    NARCIS (Netherlands)

    Asveld, P.R.J.

    1981-01-01

    Starting from Fischer's IO Standard Form Theorem we show that for each inside-out (or IO-) macro language $L$, there is a $\\lambda$-free IO-macro grammar with the following property: for each $x$ in $L$, there is a derivation of $x$ of length at most linear in the length of $x$. Then we construct a

  9. Paraquat inhibits progesterone synthesis in human placental mitochondria.

    Science.gov (United States)

    Milczarek, Ryszard; Sokołowska, Ewa; Rybakowska, Iwona; Kaletha, Krystian; Klimek, Jerzy

    2016-07-01

    Human placenta mitochondria produces huge amounts of progesterone necessary for maintaining the pregnancy. Lipid peroxidation in human placental mitochondria inhibits progesterone synthesis and that inhibition can be reversed by superoxide dismutase and other antioxidants. Paraquat (PQ) a highly toxic herbicide generates superoxide radical inside cells and induces lipid peroxidation. Hence, it is supposed to stimulate lipid peroxidation in human placental mitochondria and in consequence to inhibit a placental mitochondrial steroidogenesis. Placentas were obtained from normal pregnancies. All experiments were done using isolated human placental mitochondria. Mitochondrial lipid peroxidation was determined as tiobarbituric acid reactive substances (TBARS). A conversion of cholesterol to pregnenolone or pregnenolone to progesterone was measured using radiolabeled steroids and thin layer chromatography. PQ enhanced the iron-dependent lipid peroxidation as also PQ heightened the inhibitory action of this process on progesterone synthesis in isolated human placental mitochondria. Paradoxically, a superoxide dismutase (SOD) reversed the inhibition of progesterone synthesis only minimally although it strongly inhibited PQ stimulated iron-dependent lipid peroxidation. When iron was absent, PQ stimulated only negligible lipid peroxidation but strongly inhibited progesterone synthesis. SOD had no effect on inhibition of progesterone synthesis by PQ. PQ strongly inhibited of the conversion of cholesterol to pregnenolone but had not got any influence on the enzymatic activity of mitochondrial 3β-hydroxysteroid dehydrogenase. PQ strongly decreased the efficiency of NADPH-dependent cytochrome P450 reduction as well as it promoted the rapid oxidation of the pre-reduced mitochondrial cytochrome P450. However PQ has not inhibited combined activity of adrenodoxin reductase and adrenodoxin. We conclude that the most important reason of the inhibition of progesterone synthesis by PQ

  10. Medial epicanthoplasty using the "inside-out" technique.

    Science.gov (United States)

    Seo, Jae Don; Kim, Ji Hoon; Pak, Chang Sik; Heo, Chan-Yeong

    2014-04-01

    The epicanthal fold, a skin remnant covering the medial canthal region, is especially common in Asians. Although numerous surgical techniques for the treatment of the epicanthal fold have been developed, the results.in terms of scars and a natural look remain controversial. In this regard, the authors have developed a new method for medial epicanthoplasty. From January 2005 to December 2011, medial epicanthoplasty was performed on 1132 patients using a technique in which the skin flap inside of the medial epicanthal fold is moved outward (the "Inside-Out" technique). Preoperative and postoperative (2 months) interepicanthal distance was measured. Satisfactory results were achieved in the majority of cases. While nine patients complained of visible scarring after the operation, the scar formation spontaneously resolved within 6 months. This new "Inside-Out" technique for the treatment of the epicanthal fold is easy, simple, and delivers good aesthetic results.

  11. Time and Space Complexity of Inside-Out Macro Grammars

    OpenAIRE

    Asveld, P.R.J.

    1980-01-01

    Starting form Fischer's IO Standard Form Theorem we show that for each inside-out (or IO-) macro language $L$ there exists a $\\lambda$-free IO macro grammar with the following property: for each $x$ in $L$ there is a derivation of $x$ of length at most linear in the length of $x$. Then we construct a nondeterministic log-space bounded auxiliary pushdown automaton which accepts $L$ in polynomial time. Therefore the IO-macro languages are (many-one) log-space reducible to the context-free langu...

  12. Inside-Out Repair for Radial Meniscus Tears.

    Science.gov (United States)

    Pareek, Ayoosh; O'Malley, Michael P; Levy, Bruce A; Stuart, Michael J; Krych, Aaron J

    2016-08-01

    Understanding of meniscal function through basic science, natural history, and biomechanics has highlighted the importance of preserving the meniscus to maintain normal knee biomechanics. Tears that may alter these biomechanics can contribute to the progressive nature of degenerative joint disease in the knee. Radial tears result in the disruption of the circumferential fibers causing inability of the native meniscus to resist normal hoop stresses, thereby leading to increased focal areas of pressure that cause complications such as early onset arthrosis. In this technical note, we describe our preferred operative technique to repair radial meniscal tears using an arthroscopic inside-out approach with satisfactory clinical outcomes and healing response.

  13. Windows Sharepoint Services 3.0 Inside Out

    CERN Document Server

    O' Connor, Errin

    2008-01-01

    Dig in-and learn how the experts use Windows SharePoint Services 3.0-from the inside out! This book packs hundreds of time-saving solutions, troubleshooting tips, and workarounds-all in concise, fast-answer format. You will learn how to simplify information sharing, make team collaboration more efficient, and improve your personal productivity. You'll discover how to design workflows and projects for SharePoint sites, manage design teams and source control, and use cascading style sheets to control site appearance. You'll get to explore new features for using Windows SharePoint Services with

  14. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jinghua [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Zhang, Jianyun [Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Feixue [Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Liu, Jing, E-mail: jliue@zju.edu.cn [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-05-05

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  15. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    Science.gov (United States)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Integrin αIIbβ3 Inside-out Activation

    Science.gov (United States)

    Kurtz, Lisa; Kao, Liyo; Newman, Debra; Kurtz, Ira; Zhu, Quansheng

    2012-01-01

    Integrins are a family of heterodimeric adhesion receptors that transmit signals bi-directionally across the plasma membranes. The transmembrane domain (TM) of integrin plays a critical role in mediating transition of the receptor from the default inactive to the active state on the cell surfaces. In this study, we successfully applied the substituted cysteine scanning accessibility method to determine the intracellular border of the integrin αIIbβ3 TM in the inactive and active states in living cells. We examined the aqueous accessibility of 75 substituted cysteines comprising the C terminus of both αIIb and β3 TMs, the intracellular membrane-proximal regions, and the whole cytoplasmic tails, to the labeling of a membrane-permeable, cysteine-specific chemical biotin maleimide (BM). The active state of integrin αIIbβ3 heterodimer was generated by co-expression of activating partners with the cysteine-substituted constructs. Our data revealed that, in the inactive state, the intracellular lipid/aqueous border of αIIb TM was at Lys994 and β3 TM was at Phe727 respectively; in the active state, the border of αIIb TM shifted to Pro998, whereas the border of β3 TM remained unchanged, suggesting that complex conformational changes occurred in the TMs upon αIIbβ3 inside-out activation. On the basis of the results, we propose a new inside-out activation mechanism for integrin αIIbβ3 and by inference, all of the integrins in their native cellular environment. PMID:22613710

  17. Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Rytting, Erik; Mose, Tina

    2009-01-01

    . Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport......The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008...... across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare...

  18. The transperiosteal "inside-out" occipital artery harvesting technique.

    Science.gov (United States)

    Benet, Arnau; Tabani, Halima; Ding, Xinmin; Burkhardt, Jan-Karl; Rodriguez Rubio, Roberto; Tayebi Meybodi, Ali; Nisson, Peyton; Kola, Olivia; Gandhi, Sirin; Yousef, Sonia; Lawton, Michael T

    2018-01-26

    OBJECTIVE The occipital artery (OA) is a frequently used donor vessel for posterior circulation bypass procedures due to its proximity to the recipient vessels and its optimal caliber, length, and flow rate. However, its tortuous course through multiple layers of suboccipital muscles necessitates layer-by-layer dissection. The authors of this cadaveric study aimed to describe a landmark-based novel anterograde approach to harvest OA in a proximal-to-distal "inside-out" fashion, which avoids multilayer dissection. METHODS Sixteen cadaveric specimens were prepared for surgical simulation, and the OA was harvested using the classic (n = 2) and novel (n = 14) techniques. The specimens were positioned three-quarters prone, with 45° contralateral head rotation. An inverted hockey-stick incision was made from the spinous process of C-2 to the mastoid tip, and the distal part of the OA was divided to lift up a myocutaneous flap, including the nuchal muscles. The OA was identified using the occipital groove (OG), the digastric muscle (DM) and its groove (DG), and the superior oblique muscle (SOM) as key landmarks. The OA was harvested anterogradely from the OG and within the flap until the skin incision was reached (proximal-to-distal technique). In addition, 35 dry skulls were assessed bilaterally (n = 70) to study additional craniometric landmarks to infer the course of the OA in the OG. RESULTS The OA was consistently found running in the OG, which was found between the posterior belly of the DM and the SOM. The mean total length of the mobilized OA was 12.8 ± 1.2 cm, with a diameter of 1.3 ± 0.1 mm at the suboccipital segment and 1.1 ± 0.1 mm at the skin incision. On dry skulls, the occipitomastoid suture (OMS) was found to be medial to the OG in the majority of the cases (68.6%), making it a useful landmark to locate the OG and thus the proximal OA. CONCLUSIONS The anterograde transperiosteal inside-out approach for harvesting the OA is a fast and easy technique

  19. Estudio de las emociones en los personajes animados de Inside Out/ Study of emotions in the animated characters from Inside Out

    Directory of Open Access Journals (Sweden)

    Leticia Porto Pedrosa

    2016-01-01

    Full Text Available Este artículo pretende mostrar la importancia de investigar las emociones a partir del cine de animación y su influencia en la audiencia infantil. Para ello, se lleva a cabo un recorrido a lo largo del tratamiento y la representación de las emociones encarnadas en los personajes animados de los largometrajes de Pixar. A través de la revisión bibliográfica y el análisis de contenido de la película Inside Out (2015, se profundiza en las principales emociones como la tristeza y la alegría para comprender cuál es el papel social de esta dimensión esencial en el ser humano. The purpose of this paper is to discuss about the importance of investigating the emotions from the cartoon movies and its influence on the child audience. For this, in this article studies the treatment and representation of emotions on the characters of films Pixar Studios. Through literature review and analysis of content of the cartoon movie Inside Out (2015, it delves into the main emotions like sadness and joy to understand what the social role of this essential dimension of the human being.

  20. Red nuggets grow inside-out: evidence from gravitational lensing

    Science.gov (United States)

    Oldham, Lindsay; Auger, Matthew W.; Fassnacht, Christopher D.; Treu, Tommaso; Brewer, Brendon J.; Koopmans, L. V. E.; Lagattuta, David; Marshall, Philip; McKean, John; Vegetti, Simona

    2017-03-01

    We present a new sample of strong gravitational lens systems where both the foreground lenses and background sources are early-type galaxies. Using imaging from Hubble Space Telescope (HST)/Advanced Camera for Studies (ACS) and Keck/NIRC2, we model the surface brightness distributions and show that the sources form a distinct population of massive, compact galaxies at redshifts 0.4 ≲ z ≲ 0.7, lying systematically below the size-mass relation of the global elliptical galaxy population at those redshifts. These may therefore represent relics of high-redshift red nuggets or their partly evolved descendants. We exploit the magnifying effect of lensing to investigate the structural properties, stellar masses and stellar populations of these objects with a view to understanding their evolution. We model these objects parametrically and find that they generally require two Sérsic components to properly describe their light profiles, with one more spheroidal component alongside a more envelope-like component, which is slightly more extended though still compact. This is consistent with the hypothesis of the inside-out growth of these objects via minor mergers. We also find that the sources can be characterized by red-to-blue colour gradients as a function of radius which are stronger at low redshift - indicative of ongoing accretion - but that their environments generally appear consistent with that of the general elliptical galaxy population, contrary to recent suggestions that these objects are pre-dominantly associated with clusters.

  1. Observational evidence for an inside-out substorm onset scenario

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Michael G [Los Alamos National Laboratory

    2008-01-01

    We present observations which provide strong support for a substorm onset scenario in which a localized inner magnetospheric instability developed first and was later followed by the development of a Near Earth Neutral Line (NENL) farther down-tail. Specifically, we find that the onset began as a localized brightening of an intensified growth phase arc which developed as a periodic series of arc-aligned (i.e. azimuthally arrayed) bright spots. As the disturbance grew, it evolved into vortical structures that propagated poleward and eventually morphed into an east-west aligned arc system at the poleward edge of the auroral substorm bulge. The auroral intensification shows an exponential growth with an estimated e-folding time of around 188 seconds (linear growth rate, {gamma} of 5.33 x 10{sup -3} s{sup -1}). During the initial breakup, no obvious distortions of auroral forms to the north were observed. However, during the expansion phase, intensifications of the poleward boundary of the expanding bulge were observed together with the equatorward ejection of auroral streamers into the bulge. A strong particle injection was observed at geosynchronous orbit, but was delayed by several minutes relative to onsel. Ground magnetometer data also shows a two phase development of mid-latitude positive H-bays, with a quasi-linear increase in H between the onset and the injection. We conclude that this event provides strong evidence in favor of the so-called 'inside-out' substorm onset scenario in which the near Earth region activates first followed at a later time by the formation of a near-to-mid tail substorm X-line. The ballooning instability is discussed as a likely mechanism for the initial onset.

  2. Bacteria versus selenium: A view from the inside out

    Science.gov (United States)

    Staicu, Lucian; Oremland, Ronald S.; Tobe, Ryuta; Mihara, Hisaaki

    2017-01-01

    Bacteria and selenium (Se) are closely interlinked as the element serves both essential nutrient requirements and energy generation functions. However, Se can also behave as a powerful toxicant for bacterial homeostasis. Conversely, bacteria play a tremendous role in the cycling of Se between different environmental compartments, and bacterial metabolism has been shown to participate to all valence state transformations undergone by Se in nature. Bacteria possess an extensive molecular repertoire for Se metabolism. At the end of the 1980s, a novel mode of anaerobic respiration based on Se oxyanions was experimentally documented for the first time. Following this discovery, specific enzymes capable of reducing Se oxyanions and harvesting energy were found in a number of anaerobic bacteria. The genes involved in the expression of these enzymes have later been identified and cloned. This iterative approach undertaken outside-in led to the understanding of the molecular mechanisms of Se transformations in bacteria. Based on the extensive knowledge accumulated over the years, we now have a full(er) view from the inside out, from DNA-encoding genes to enzymes and thermodynamics. Bacterial transformations of Se for assimilatory purposes have been the object of numerous studies predating the investigation of Se respiration. Remarkable contributions related to the understating of the molecular picture underlying seleno-amino acid biosynthesis are reviewed herein. Under certain circumstances, Se is a toxicant for bacterial metabolism and bacteria have evolved strategies to counteract this toxicity, most notably by the formation of elemental Se (nano)particles. Several biotechnological applications, such as the production of functional materials and the biofortification of crop species using Se-utilizing bacteria, are presented in this chapter.

  3. Arrangement of collagen fibers in human placental stem villi.

    Science.gov (United States)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry was performed in order to localize collagen types I, III, IV, V and cytokeratin 7 on tissue sections. Parallel tissue samples were examined by transmission electron microscopy. Semi-quantitative analysis of immunolabeling intensities was also performed to determine the distribution of fibers in stem villi stroma. All collagen types, especially collagen type V, were strongly immunopositive in the triangular areas of the stem villi stroma. However, there was no collagen type I or type III immunolabeling in the sub-trophoblastic regions. Membrane collagen type IV immunolabeling was also observed in the stroma of stem villi. Ultrastructurally, collagen fibers showed different configurations in cross, longitudinal, circular, oblique and parallel directions compared to the villous axis. We conclude that the organization of collagen fiber bundles in stem villi shows a very specific arrangement: a compact coat formed by fibrillar bundles between the vascular wall and extravascular stroma of stem villi correlated with the functional activity.

  4. Virus-Free Human Placental Cell Lines To Study Genetic Functions | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.

  5. Anatomical variability in the trajectory of the inside-out transobturator vaginal tape technique (TVT-O)

    NARCIS (Netherlands)

    Hinoul, Piet; Vanormelingen, Linda; Roovers, Jan-Paul; de Jonge, Eric; Smajda, Stéfan

    2007-01-01

    An experimental surgical study on human cadavers was undertaken to assess variability in the trajectory followed by the needle during application of the inside-out transobturator tape suspension (TVT-O) technique. The TVT-O surgical procedures were performed on six fresh female cadavers according to

  6. Placental transport of large molecules –a study using human ex vivo placental perfusion

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    and extrapolation to the in vivo situation critical. In my PhD study I have focused on validation and studies with placental perfusion of substances with a high molecular weight, which require transport or carrier molecules to be transported from the maternal to the fetal side, and longer perfusion time demanding...... nutrients, gas and waste transport between the maternal blood and the developing fetus and maintaining pregnancy by producing hormones. The placenta consists of cells of both maternal and fetal origin and forms a complex barrier between the maternal and fetal blood that allows for passage of different...... within two hours of perfusion with a fetal flow rate of 3 mL/min. Negative controls are added to ensure that substance transfer is not due to leakage, e.g. high molecular weight substances that only pass the placental barrier with bulk flow through a leakage in the fetal system. Dextran (40kD) can...

  7. Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

    Directory of Open Access Journals (Sweden)

    Adjimon Gatien Lokossou

    2014-11-01

    Full Text Available Human endogenous retroviruses (ERVs represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs, a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.

  8. Placental glucose transfer: a human in vivo study.

    Directory of Open Access Journals (Sweden)

    Ane M Holme

    Full Text Available The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply determines the fetal venous-arterial glucose difference (reflecting fetal consumption.Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein and outgoing vessels (uterine vein and umbilical artery.There were significant mean (SD uteroplacental arterio-venous 0.29 (0.23 mmol/L and fetal venous-arterial 0.38 (0.31 mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42 mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001, but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001 and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004. Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001, but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly

  9. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  10. Economic feasibility of producing inside-out beams from small-diameter logs

    Science.gov (United States)

    David W. Patterson; Richard A. Kluender; James E. Granskog

    2002-01-01

    Previous work has shown that it is technically feasible to produce inside-out (ISO) beams by taking small-diameter (5 to 7 in.) logs, slabbing four sides, quartering the cant, and turning the quarters inside out and gluing them together. After drying, the beams were found to be straight, with no cracks, and of equal or better mechanical properties than solid sawn...

  11. Analysis of a new all-inside versus inside-out technique for repairing radial meniscal tears.

    Science.gov (United States)

    Beamer, Brandon S; Masoudi, Aidin; Walley, Kempland C; Harlow, Ethan R; Manoukian, Ohan S; Hertz, Ben; Haeussler, Claudia; Olson, Jeffrey J; Deangelis, Joseph P; Nazarian, Ara; Ramappa, Arun J

    2015-02-01

    The purpose of this study was to compare gap formation, strength, and stiffness of repaired radial tears of the meniscus treated using a new all-inside technique versus a traditional inside-out suture technique. Radial tears were created in 36 fresh-frozen porcine menisci. Repairs were performed using a novel all-inside suture-based meniscal repair device or an inside-out technique. The repairs were tested for cyclic loading and load to failure. The displacement, response to cyclic loading (100, 300, and 500 cycles), and mode of failure were recorded, and the construct's stiffness was calculated. The all-inside repairs using the novel device resulted in a significantly lower displacement (gap formation) after 100, 300, and 500 cycles (P = .002, P = .001, and P = .001, respectively). The ultimate load to failure was significantly greater for the all-inside repairs (111.61 N v 95.01 N; P = .03). The all-inside repairs showed greater stiffness (14.53 N/mm v 11.19 N/mm; P = .02). The all-inside repairs failed most often by suture breakage (suture failure). The inside-out repairs failed most commonly when the suture pulled through the tissue (tissue failure) (P inside technique resulted in lower displacement, higher load to failure, and greater stiffness compared with the horizontal inside-out technique. In a porcine specimen meniscus repair model, the biomechanical properties of a vertical all-inside technique were superior to that of a horizontal inside-out technique. Future studies of biomechanical and clinical outcomes in human meniscal repairs with this device are warranted to explore whether this repair method is valuable to clinical practice and patient outcomes. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  12. Effects of human placental extract on brain monoamines and monoamine oxidase activity in rats.

    Science.gov (United States)

    Banerjee, K K; Bishayee, A; Chatterjee, M

    1995-05-01

    Human placental extract, an agent clinically used world-wide in a number of physiological anomalies, has been claimed to be effective in children of slow learners. Since the monoaminergic neurotransmitter systems in the brain play an important role in the processes of learning and memory, we examined the effects of human placental extract on the levels of norepinephrine, dopamine and serotonine in rat brain as an attempt to evaluate the possible underlying biochemical mechanism of action of the extract. We also determined the changes of brain monoamine oxidase (MAO) activity following placental extract treatment. The results showed that subchronic (5, 10, 15 or 20) administration of placental extract (2-4 ml/kg/day) had the effect of increasing all the monoamines and decreasing the MAO activity which could be the possible mode of action of the extract in slow learners.

  13. MicroRNAs in Human Placental Development and Pregnancy Complications

    Directory of Open Access Journals (Sweden)

    Chun Peng

    2013-03-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies.

  14. Inside Out

    Science.gov (United States)

    Jennings, Matt

    2011-01-01

    In a world ruled by digital communications, it can seem like there are almost as many methods, tools, and platforms to communicate with internal audiences as there are opinions and perspectives on how to do it effectively. Organizations of various sizes are struggling with how to reach their audiences' divided attention, and higher education…

  15. Comparative Study of Management of Attico-antral CSOM by Conventional Mastoidectomy with Inside Out Technique.

    Science.gov (United States)

    Vaidya, Sudhakar; Gupta, Shobhit

    2017-09-01

    This prospective study was undertaken to compare the different aspects of inside out and conventional mastoidectomy techniques in attico-antral type of chronic suppurative otitis media. 100 cases of unsafe ear selected in this study were divided in 2 groups-(1) Group A-50 patients operated by conventional technique of canal wall down mastoidectomy. (2) Group B-50 patients operated by inside out technique of canal wall down mastoidectomy. The patients in our series were regularly followed to assess the condition of the postoperative cavity for three months. Post operative results were better by inside out as compared to conventional technique of mastoidectomy. Hearing and air-bone gap improvement was more in patients operated by inside out mastoidectomy. Less number of patients suffered with post operative residual disease like cholesteatoma, granulation, discharge and residual perforation as compared to conventional mastoidectomy.

  16. Interconversion of molecular face-rotating polyhedra through turning inside out.

    Science.gov (United States)

    Wang, Yu; Fang, Hongxun; Zhang, Wei; Zhuang, Yongbin; Tian, Zhongqun; Cao, Xiaoyu

    2017-08-08

    We report the post-synthesis interconversion of two enantiomeric organic cages through turning inside out. By scrutinizing the thermodynamics and kinetics, we are able to control the racemization rate by various reaction conditions and reveal that the turning-inside-out interconversion is realized through a partial disassembly pathway. The kinetics investigation also provides insight into the dynamic essence of imine chemistry using different solvents and catalysts.

  17. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

    DEFF Research Database (Denmark)

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara

    2016-01-01

    in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated...... placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry...

  18. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    to consider animal models with longer gestations and well-developed neonates. Placentation in different orders of mammal is surveyed and their proximity to humans described in an evolutionary context. Animal models are then compared with the human in terms of the functional anatomy, physiology, and immunology......This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... have brief gestations resulting in the birth of poorly developed young. They can provide useful insights on placental development and function relevant to early human pregnancy. However, to model the events of a 9-month gestation, which imposes added requirements on the placenta, it is necessary...

  19. Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion

    DEFF Research Database (Denmark)

    Obel, E B; Madsen, Mette

    1980-01-01

    concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate......Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean...... an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy....

  20. Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion.

    Science.gov (United States)

    Obel, E B; Madsen, M

    1980-01-01

    Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy.

  1. Estudio de las emociones en los personajes animados de Inside Out/ Study of emotions in the animated characters from Inside Out

    OpenAIRE

    Leticia Porto Pedrosa

    2016-01-01

    Este artículo pretende mostrar la importancia de investigar las emociones a partir del cine de animación y su influencia en la audiencia infantil. Para ello, se lleva a cabo un recorrido a lo largo del tratamiento y la representación de las emociones encarnadas en los personajes animados de los largometrajes de Pixar. A través de la revisión bibliográfica y el análisis de contenido de la película Inside Out (2015), se profundiza en las principales emociones como la ...

  2. A Contact Pressure Analysis Comparing an All-Inside and Inside-Out Surgical Repair Technique for Bucket-Handle Medial Meniscus Tears.

    Science.gov (United States)

    Marchetti, Daniel Cole; Phelps, Brian M; Dahl, Kimi D; Slette, Erik L; Mikula, Jacob D; Dornan, Grant J; Bucci, Gabriella; Turnbull, Travis Lee; Singleton, Steven B

    2017-10-01

    To directly compare effectiveness of the inside-out and all-inside medial meniscal repair techniques in restoring native contact area and contact pressure across the medial tibial plateau at multiple knee flexion angles. Twelve male, nonpaired (n = 12), fresh-frozen human cadaveric knees underwent a series of 5 consecutive states: (1) intact medial meniscus, (2) MCL tear and repair, (3) simulated bucket-handle longitudinal tear of the medial meniscus, (4) inside-out meniscal repair, and (5) all-inside meniscal repair. Knees were loaded with a 1,000-N axial compressive force at 5 knee flexion angles (0°, 30°, 45°, 60°, 90°), and contact area, mean contact pressure, and peak contact pressure were calculated using thin film pressure sensors. No significant differences were observed between the inside-out and all-inside repair techniques at any flexion angle for contact area, mean contact pressure, and peak contact pressure (all P > .791). Compared with the torn meniscus state, inside-out and all-inside repair techniques resulted in increased contact area at all flexion angles (all P inside-out technique at angles ≥45° (all P inside technique in contact area at 60° and 90° and peak contact pressure at 90° (both P inside and inside-out repair techniques at any tested flexion angle. Both techniques adequately restored native meniscus biomechanics near an intact level. An all-inside repair technique provided similar, native-state-restoring contact mechanics compared with an inside-out repair technique for the treatment of displaced bucket-handle tears of the medial meniscus. Thus, both techniques may adequately decrease the likelihood of cartilage degeneration. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  3. Mesenchymal stem cells in human placental chorionic villi reside in a vascular Niche

    NARCIS (Netherlands)

    Castrechini, N. M.; Murthi, P.; Gude, N. M.; Erwich, J. J. H. M.; Gronthos, S.; Zannettino, A.; Brennecke, S. R.; Kalionis, B.; Brennecke, S.P.

    The chorionic villi of human term placentae are a rich source of mesenchymal stem cells (PMSCs) The stem cell "niche" within the chorionic villi regulates how PMSCs participate in placental tissue generation, maintenance and repair, but the anatomic location of the niche has not been defined A

  4. Inside-Out Versus All-Inside Repair of Isolated Meniscal Tears: An Updated Systematic Review.

    Science.gov (United States)

    Fillingham, Yale A; Riboh, Jonathan C; Erickson, Brandon J; Bach, Bernard R; Yanke, Adam B

    2017-01-01

    Meniscal tears are common in the young, active population. In this group of patients, repair is advised when possible. While inside-out repair remains the standard technique, recent advances in all-inside repair devices have led to a growth in their popularity. Previous reviews on the topic have focused on outdated implants of limited clinical relevance. To determine the difference in failure rates, functional outcomes, and complications between inside-out and modern all-inside repairs. Systematic review. A systematic review was registered with PROSPERO and performed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines using the MEDLINE, EMBASE, and Cochrane databases. Inclusion criteria were (1) clinical study reporting on all-inside or inside-out repair, (2) evidence levels 1 to 4, and (3) use of modern all-inside implants for all-inside repairs. Exclusion criteria were (1) use of meniscal arrows or screws and (2) concomitant surgical procedures. Study characteristics, subjects, surgical technique, clinical outcomes, and complications were collected and analyzed. A total of 481 studies were screened and assessed for eligibility, which identified 27 studies for review. Studies defined clinical failure as persistent mechanical symptoms, effusion, or joint line tenderness, while anatomic failure was incomplete or no healing on MRI or second-look arthroscopy. There were no significant differences in clinical or anatomic failure rates between inside-out and all-inside repairs (clinical failure: 11% vs 10%, respectively, P = .58; anatomic failure: 13% vs 16%, respectively, P = .63). Mean ± SD Lysholm and Tegner scores for inside-out repair were 88.0 ± 3.5 and 5.3 ± 1.2, while the respective scores for all-inside repair were 90.4 ± 3.7 and 6.3 ± 1.3. Complications occurred at a rate of 5.1% for inside-out repairs and 4.6% for all-inside repairs. The quality of the evidence comparing inside-out and all-inside meniscal

  5. Comparison of arthroscopic medial meniscal suture repair techniques: inside-out versus all-inside repair.

    Science.gov (United States)

    Choi, Nam-Hong; Kim, Tae-Hyung; Victoroff, Brian N

    2009-11-01

    There are no reports comparing meniscal healing between inside-out and all-inside repairs using sutures. No difference in healing rate exists between meniscal repairs with inside-out and all-inside suture repair in conjunction with anterior cruciate ligament reconstruction with hamstring tendon. Cohort study; Level of evidence, 2. Forty-eight consecutive patients underwent meniscal repairs of longitudinal tears of the posterior horn of the medial meniscus combined with anterior cruciate ligament reconstructions. All-inside repair was attempted when the tears were located in the red-red zone or the ramp area of the meniscus. If a tear that was in the ramp area or red-red zone extended to the midbody of the meniscus, or if there was a tear in red-white zone, the inside-out repair technique was used. Fourteen patients had all-inside meniscal repairs, and 34 patients had inside-out meniscal repairs with absorbable sutures. Identical postoperative rehabilitation protocols were used. Postoperative evaluations included Lysholm knee scoring scale, Tegner activity levels, Lachman and pivot-shift tests, and KT-1000 arthrometer. Assessment of meniscal status was performed using joint line tenderness, McMurray test, and range of motion. Follow-up magnetic resonance imaging scans were obtained on all patients. Mean follow-up was 35.7 months. No patient had joint line tenderness or reported pain or clicking on McMurray test. There was no significant difference in range of motion between groups. Follow-up magnetic resonance imaging scans demonstrated that 10 (71.4%) menisci were healed and 4 (28.6%) partially healed in the all-inside group; 24 (70.6%) menisci were healed and 10 (29.4%) partially healed in the inside-out group. There was no significant difference in meniscal healing between groups. There were no differences in Lachman test, KT-1000 arthrometer side-to-side differences measurements, Lysholm scores, and Tegner activity scales. There was a significant difference in

  6. My Dance and the Ideal Body: Looking at Ballet Practice from the Inside Out

    Science.gov (United States)

    Jackson, Jennifer

    2005-01-01

    This paper argues for a change of thinking about the "ideal body" in relation to ballet as a dance form and how it is studied. It distinguishes between spectator and practitioner perspectives on ballet, and draws on the practice of established dance artists and that of the author to write about the first-person experience--from the inside out.…

  7. Pathways to Faculty Learning and Pedagogical Improvement. Inside Out. Volume 1, Issue 3

    Science.gov (United States)

    Bickerstaff, Susan; Edgecombe, Nikki

    2012-01-01

    This issue of "Inside Out," a publication of Community College Research Center's (CCRC's) Scaling Innovation project, explores how developmental education reforms can create opportunities for faculty to engage in professional learning related to instruction. The authors present a case study at Fullerton College, where the process of…

  8. The Inside-Out Prison Exchange Program: The Impact of Structure, Content, and Readings

    Science.gov (United States)

    Allred, Sarah L.

    2009-01-01

    This study examines qualitative and quantitative data from a fifteen-week experiential course held in a county jail. The course was modeled after the Inside-Out Prison Exchange Program, and included college students and people who were incarcerated at the time. Survey data and comments gleaned from student papers were used to assess the impact of…

  9. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

    Science.gov (United States)

    Lorenc, Chris; Saurí, Josep; Moser, Arvin; Buevich, Alexei V; Williams, Antony J; Williamson, R Thomas; Martin, Gary E; Peczuh, Mark W

    2015-10-01

    Invited for this month's cover picture is the group of Professor Mark Peczuh at the University of Connecticut. The cover picture compares the rearrangement of a small molecule to the process of turning a stuffed animal inside out. The recycled, inside-out stuffed animals are both artistic and philosophically provocative. They capture the essence of the rearrangement reaction because the compounds themselves turn inside out over the course of the reaction, extending the diversity of products that can arise from simple starting materials. Small molecules often have functional groups with latent reactivity; under the appropriate conditions, those groups can react with other compounds (e.g., reagents) and also with other groups in the same molecule in an intramolecular reaction. The research team found that the epoxidation of some highly functionalized spiroketal compounds promoted rearrangements of their structures that turned them inside out. Some of the features of the products led them to use X-ray crystallography or a combination of computer-assisted structure elucidation, computation, and a new version of the 1,1-ADEQUATE NMR experiment to determine their structures. For more details, see the Communication on p. 577 ff.

  10. Turning Schools Inside Out: Connecting Schools and Communities through Public Arts and Literacies

    Science.gov (United States)

    Charest, Brian C.; Bell, Lauren D.; Gonzalez, Marialuisa; Parker, Veronica L.

    2014-01-01

    In this paper we tell a story about how we partnered with a Chicago high school in order to turn the school inside out by displaying larger-than-life teacher portraits and statements at street level throughout the community. This paper explores how public art and activism can help teachers and students develop notions of civic literacy and…

  11. Proximal Ethnography: "Inside-Out-Inside" Research and the Impact of Shared Metaphors of Learning

    Science.gov (United States)

    Price, Fiona

    2013-01-01

    This paper examines the way Higher Education (HE) students use metaphors to make tangible the lived and living experience of learning. The article provides a contemporary development of the ethnographic paradigm by offering a new model termed "proximal ethnography" to capture the sense of inside-out-inside research, of being what one has…

  12. Creating Community from the Inside Out: A Concentric Perspective on Collective Artmaking

    Science.gov (United States)

    Blatt-Gross, Carolina

    2017-01-01

    As the original antidote to social alienation (and its tragic repercussions), community art through its large-scale, public, and collaborative nature has the potential to rebuild a sense of community from the inside out. This concentric notion of community art is addressed at both the individual and classroom level, exploring the origins of…

  13. Cholesteatoma surgery in children: long-term results of the inside-out technique.

    Science.gov (United States)

    Roth, Thomas N; Ziglinas, Panagiotis; Haeusler, Rudolf; Caversaccio, Marco D

    2013-05-01

    To present the anatomical and functional results of the inside-out technique applied in pediatric cholestetaoma surgery and to evaluate functionality with good hearing results against radicality with lower recurrence rate. Retrospective analysis and evaluation of the postoperative outcome in a consecutive series of 126 children or 130 ears operated between 1992 and 2008. With the inside-out technique, cholesteatoma is eradicated from the epitympanum toward the mastoid and, as a single stage procedure, functional reconstruction of the middle ear is achieved by tympanoossiculoplasty. In 89.2% of all cases, the ear was dry postoperatively. 80.9% of the ears reached a postoperative air-bone gap of 30 dB or less and the median air conduction hearing threshold was 29 dB; in 60.9% of all cases, hearing was postoperatively improved. The recurrence rate was 16.2% in a mean postoperative follow-up 8.5 years. Altogether, 48 ears (36.9%) underwent revision surgery. The complication rate was 3.1% and involved only minor complications. The inside-out technique allows a safe removal of cholesteatoma from the epitympanum toward the mastoid with a single-stage reconstruction of the ossicular chain. For this reason we support our individual approach, which allows creation of the smallest possible cavity for the size of the cholesteatoma. Our results confirm that the inside-out technique is effective in the treatment of pediatric cholesteatoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Affective Films for the Hearing Impaired Child: A Test of Captioned Inside/Out Programs.

    Science.gov (United States)

    Middleton, John

    Two captioned affective films from the AIT series Inside/Out were tested with 14 intermediate (ages 13 to 15) and 39 elementary (ages 11 and 12) hearing impaired children at the Hawaii School for the Deaf and Blind. Measures of attention, post-film discussion, student comprehension, and student and teacher opinions were taken to determine the…

  15. Comparison of all-inside meniscal repair devices with matched inside-out suture repair.

    Science.gov (United States)

    Rosso, Claudio; Kovtun, Konstantin; Dow, William; McKenzie, Brett; Nazarian, Ara; DeAngelis, Joseph P; Ramappa, Arun J

    2011-12-01

    All-inside meniscal repairs are performed with increasing frequency because of the availability of newly developed devices. A comparison of their biomechanical characteristics may aid physicians in selecting a method of meniscal repair. All-inside meniscal repairs will be superior to their inside-out controls in response to cyclic loading and load-to-failure testing. Controlled laboratory study. Sixty-six bucket-handle tears in matched porcine menisci were repaired using the Ultra FasT-Fix, Meniscal Cinch, Ultrabraid No. 0, and FiberWire 2-0 sutures. Initial displacement, cyclic loading (100, 300, and 500 cycles), and load-to-failure testing were performed. The displacement, response to cyclic loading, and mode of failure were recorded. The stiffness was calculated. The Meniscal Cinch demonstrated a significantly higher initial displacement than the other methods tested (P = .04). No significant difference was found among the methods in response to cyclic loading. The inside-out FiberWire repair demonstrated the highest load to failure (120.8 ± 23.5 N) and was significantly higher than both the Meniscal Cinch (64.8 ± 24.1 N, P inside-out Ultrabraid suture repair (98.8 ± 29.2 N). The inside-out FiberWire repair had the highest stiffness (28.7 ± 7.8 N/mm). It was significantly higher than the Meniscal Cinch (18.0 ± 8.8 N/mm, P = .01). The most common mode of failure in all methods was suture failure. An inside-out suture repair affords surgeons the best overall biomechanical characteristics of the devices tested (initial displacement, response to cyclic loading, and load to failure). For an all-inside repair, the Ultra FasT-Fix reproduces the characteristics of its matched inside-out suture repair more closely than the Meniscal Cinch. Inside-out sutures and all-inside devices have similar responses to cyclic loading.

  16. Differential expression of human placental PAPP-A2 over gestation and in preeclampsia.

    Science.gov (United States)

    Kramer, Anita W; Lamale-Smith, Leah M; Winn, Virginia D

    2016-01-01

    Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia. Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera. PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood. PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation. Published by Elsevier Ltd.

  17. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Tuuli, Methodius G; Longtine, Mark S; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D

    2012-05-15

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

  18. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts

    Science.gov (United States)

    Tuuli, Methodius G.; Longtine, Mark S.; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D.

    2012-01-01

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus. PMID:22374759

  19. Intermedin/adrenomedullin 2 is associated with implantation and placentation via trophoblast invasion in human pregnancy.

    Science.gov (United States)

    Havemann, Dara; Balakrishnan, Meena; Borahay, Mostafa; Theiler, Regan; Jennings, Kristofer; Endsley, Janice; Phelps, John; Hankins, Gary D V; Yallampalli, Chandra; Chauhan, Madhu

    2013-02-01

    Intermedin (IMD) is a novel peptide expressed in trophoblast cells in human placenta and enhances the invasion, migration, and human leukocyte antigen class I, G (HLA-G) expression in first-trimester HTR-8SV/neo cells. We recently reported that infusion of IMD antagonist in pregnant rats is detrimental to pregnancy outcome, resulting in impaired fetoplacental growth and deformed placental vasculature. This study was undertaken to assess expression of IMD and its involvement in human implantation and early placentation and assess whether its expression is altered in spontaneous abortion. We demonstrate for the first time that IMD is present in day 5 embryonic secretome; villous and decidual expression of IMD is higher at 6-8 weeks after a decline as gestation advances toward the second trimester; first-trimester spontaneous abortion is associated with a lower expression of IMD in serum, villi, and decidua; IMD stimulates the invasive capacity of first-trimester primary Extravillous cytotrophoblast cells; and IMD decreases elevated levels of tumor suppressor Kangia-1 in decidual explants from first-trimester spontaneous abortion. In conclusion, this study is the first to demonstrate a potential involvement of IMD in human embryo implantation and placental development via regulation of trophoblast invasion at the maternal-fetal interface and suggests a physiological role for this novel peptide in establishment of human pregnancy.

  20. Modeling oxygen transport in human placental terminal villi.

    Science.gov (United States)

    Gill, J S; Salafia, C M; Grebenkov, D; Vvedensky, D D

    2011-12-21

    Oxygen transport from maternal blood to fetal blood is a primary function of the placenta. Quantifying the effectiveness of this exchange remains key in identifying healthy placentas because of the great variability in capillary number, caliber and position within the villus-even in placentas deemed clinically "normal". By considering villous membrane to capillary membrane transport, stationary oxygen diffusion can be numerically solved in terminal villi represented by digital photomicrographs. We aim to provide a method to determine whether and if so to what extent diffusional screening may operate in placental villi. Segmented digital photomicrographs of terminal villi from the Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a geometric basis for solving the stationary diffusion equation. Constant maternal villous oxygen concentration and perfect fetal capillary membrane absorption are assumed. System efficiency is defined as the ratio of oxygen flux into a villus and the sum of the capillary areas contained within. Diffusion screening is quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong link between various measures of villous oxygen transport efficiency and the number of capillaries within a villus is established. The strength of diffusional screening is also related to the number of capillaries within a villus. Our measures of diffusional efficiency are shown to decrease as a function of the number of capillaries per villus. This low efficiency, high capillary number relationship supports our hypothesis that diffusional screening is present in this system. Oxygen transport per capillary is reduced when multiple capillaries compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and villus areas is obtainable and presents an opportunity for future work. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Maternal-fetal transport kinetics of manganese in perfused human placental lobule in vitro.

    Science.gov (United States)

    Nandakumaran, Moorkath; Al-Sannan, Baydaa; Al-Sarraf, Hameed; Al-Shammari, Majed

    2016-01-01

    There have been no detailed reports relating to maternal-fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro. Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters. Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student's t-test, p manganese compared to reference marker were significantly different (ANOVA test, p manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental

  2. Expressional regulation of genes linked to immunity & programmed development in human early placental villi

    Directory of Open Access Journals (Sweden)

    M A Khan

    2014-01-01

    Full Text Available Background & objectives: During 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation. Methods: Transcriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays. Quantitative RT-PCR validation of copy numbers of transcripts for selected 15 genes and exploratory analysis of the microarray data revealed a high degree of quality assurance supportive of further clustering and differential analyses. Immunoblot and immunohistochemical analysis of selected five candidate proteins (CAGE1, CD9, SLC6A2, TANK and VEGFC based on transcript profiles were done to assess the pattern of down stream informational flow. Results: A large number (~9K of genes with known functions were expressed in the experimental samples. The clustering analysis identified three major expression clusters with gestational age, and four co-expressional clusters. Differential analysis identified a highly discrete regulatory process involving only about 160 genes. Immunochemical analysis of selected candidate proteins based on transcript profiles revealed generally synchronous expression in human early placental villi. Interpretation & conclusions: Several signaling pathways linked to immunity (COL1, JAK2, JAK3, IL12, IL13, IL15, IL27, STAT3 and STAT5 were downregulated, while genes of the enriched category of antiviral immunity (ATF/AP1, IL10R and OAS were clearly over-expressed. Transcriptional integration supportive of programmed development was observed in first

  3. The impact on growth of outside-in and inside-out innovation in SME networks

    DEFF Research Database (Denmark)

    Brink, Tove

    2014-01-01

    The purpose of this paper is to reveal what impact the dual approaches of outside-in and inside-out innovation have on growth in turnover in small and medium sized enterprises (SMEs) working together in network context. This is illustrated through research in three informal, Danish food industry...... networks with 60 SMEs responding. The research employs structural equation modelling for statistical analyses. The findings reveal that both the outside-in and the inside-out approaches have a significant positive impact on innovation and growth. The findings shed light on the need for combined dual...... organising of both to enable innovation and growth. Moreover, the network context does not significantly utilise theoretical insights on loose coupled systems. A contribution is made to innovation theory on the duality of the outside-in and the insideout approaches for a combined understanding of the impact...

  4. Repairing Posteromedial Meniscocapsular Separation: A Technique Using Inside-Out Meniscal Repair Needles.

    Science.gov (United States)

    Joshi, Anant; Usman, Sajeer; Sabnis, Bhushan; Kini, Abhishek

    2016-02-01

    Posteromedial meniscocapsular separation of the knee has received renewed interest, with many articles describing a high incidence in association with anterior cruciate ligament injury. Various techniques have been described to address these lesions using all-inside meniscal repair sutures or using rotator cuff repair instruments through the posteromedial portal. Most orthopaedic surgeons are accustomed to using the "inside-out" meniscal repair technique with a double-armed suture. This technique is cost-effective and, in our opinion, more efficient in repairing such tears. We present our technique of repairing peripheral meniscocapsular lesions using an inside-out meniscal repair system. We believe that this technique is easily reproducible, is less time-consuming, and ensures a good "bite" of the capsular tissue, producing a robust repair.

  5. Modified Inside-Out Technique for Continued Use of Chronically Occluded Upper Central Veins.

    Science.gov (United States)

    Hadziomerovic, Adnan; Hirji, Zameer; Coffey, Niamh

    2017-05-01

    This report describes a 2-step, inside-out procedure for upper body central venous access in patients with chronic central venous occlusions. Blunt cephalad dissection through the mediastinum was achieved with a curved metal cannula and guide wire followed by percutaneous puncture of an open snare from a right supraclavicular approach and dilation of the tract for a tunneled central venous catheter insertion. Of 9 patients, all had a successful placement of a tunneled central venous catheter using this method. Although this 2-step, inside-out technique is effective for creating access in the presence of central venous occlusion, further clinical evaluation is warranted. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  6. An integrative view on the physiology of human early placental villi.

    Science.gov (United States)

    Huppertz, Berthold; Ghosh, Debabrata; Sengupta, Jayasree

    2014-01-01

    The placenta is an indispensable organ for intrauterine protection, development and growth of the embryo and fetus. It provides tight contact between mother and conceptus, enabling the exchange of gas, nutrients and waste products. The human placenta is discoidal in shape, and bears a hemo-monochorial interface as well as villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the paradoxical nature of the mother-fetus relationship in 1953, substantial knowledge in the domain of placental physiology has been gathered. In the present essay, an attempt has been made to build an integrated understanding of morphological dynamics, cell biology, and functional aspects of genomic and proteomic expression of human early placental villous trophoblast cells followed by a commentary on the future directions of research in this field. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Infectious Achilles Tendinitis After Local Injection of Human Placental Extracts: A Case Report.

    Science.gov (United States)

    Kim, Yoon-Chung; Ahn, Jae Hoon; Kim, Man-Soo

    2015-01-01

    Local injections of corticosteroids or human placental extracts are sometimes used for the treatment of resistant tendinitis or fasciitis. We report a case of infectious Achilles tendinitis complicated by calcaneal osteomyelitis after injection of human placental extracts for the Achilles tendinitis. She was treated with excision of the infected bone and tendon, followed by V-Y lengthening of the proximal portion of the Achilles tendon in a single stage. At 2 years postoperative, she remained symptom free without any signs of recurrence, and the follow-up magnetic resonance imaging scan demonstrated a well-maintained Achilles tendon with normal signal intensity. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  8. FasT-Fix versus inside-out suture meniscal repair in the goat model.

    Science.gov (United States)

    Hospodar, Steven J; Schmitz, Matthew R; Golish, S Raymond; Ruder, Craig R; Miller, Mark D

    2009-02-01

    Recent all-inside meniscal repair devices are available, but in vivo studies with these devices are sparse. The FasT-Fix has inferior meniscal healing compared with the inside-out suture technique in the goat model. Controlled laboratory study. After Institutional Review Board approval, 73 male castrated goats (Capra hircus) underwent a 2-cm meniscal incision and subsequent repair with the FasT-Fix device on one knee and inside-out meniscal repair on the contralateral knee. Both repairs used a vertical mattress suture technique. Access to the menisci was via an open technique with an extra-articular osteotomy of the medial collateral ligament origin on the femur. The animals were then allowed to ambulate unrestricted in a pasture after a 7-day stay in cages. Necropsy was carried out 6 months postoperatively, and the menisci and articular cartilage were studied with gross and microscopic inspection. Nine of the 73 animals were excluded before necropsy. A total of 64 animals underwent necropsy, gross measurement of residual lesions, gross evaluation for chondral damage, histologic evaluation of meniscal repair, histologic evaluation of any adjacent inflammatory reaction to implants, and data analysis. Compared with the inside-out group, the FasT-Fix group had longer residual full-thickness defects (1.2 +/- 2.9 mm vs 0.2 +/- 1.1 mm; P = .011) and longer residual partial-thickness defects (8.4 +/- 6.3 mm vs 3.6 +/- 5.5 mm; P inside-out meniscal repair technique in the goat model. The clinical significance of this finding is not known. Further clinical study of the FasT-Fix implant is warranted.

  9. Common peroneal nerve neuropraxia after arthroscopic inside-out lateral meniscus repair.

    Science.gov (United States)

    Anderson, Anthony W; LaPrade, Robert F

    2009-01-01

    Common peroneal nerve injury caused by suture entrapment is a complication of arthroscopic inside-out lateral meniscus repair. In the literature, the treatment of this complication has been described as immediate reexploration. We present a case of recovery after late neurolysis performed 7 months postoperatively for a common peroneal nerve neuropraxia. In addition to describing return of function after late exploration, we discuss the management and prevention of this complication.

  10. COMBINED INSIDE-OUT AND ALL-INSIDE TECHNIQUE IN BUCKET-HANDLE MENISCUS TEARS.

    Science.gov (United States)

    Yılmaz, Serdar; Cankaya, Deniz; Fırat, Ahmet; Devecı, Alper; Ozkurt, Bulent; Bozkurt, Murat

    2016-01-01

    To determine the outcomes after combined inside-out and all-inside repair technique of bucket-handle meniscus tears. A retrospective review was made of patients with bucket-handle meniscus tears repaired with combined techniques, using the all-inside technique in posterior meniscal tears and the inside-out technique in the middle part of the meniscal tears. Meniscal healing was assessed clinically using Barrett's criteria and MRI. The study comprised 52 patients with a mean age of 28.4 years old (range, 19-52 years old). The mean follow-up period was 31.3 months (range, 24-59 months). Two patients had ACL re-rupture, and complete meniscal healing was achieved in all but one patient. Although improved from preoperative status, Tegner and Lysholm scores were lower in the ACL reconstructed patients than in the intact ACL patients. Combined inside-out and all-inside meniscal repair technique is a successful and cost-effective treatment method in bucket-handle meniscus tears. Level of Evidence IV, Therapeutic Study.

  11. Inside-Out Radial Migration Facilitates Lineage-Dependent Neocortical Microcircuit Assembly.

    Science.gov (United States)

    He, Shuijin; Li, Zhizhong; Ge, Shaoyu; Yu, Yong-Chun; Shi, Song-Hai

    2015-06-03

    Neocortical excitatory neurons migrate radially along the glial fibers of mother radial glial progenitors (RGPs) in a birth-date-dependent inside-out manner. However, the precise functional significance of this well-established orderly neuronal migration remains largely unclear. Here, we show that strong electrical synapses selectively form between RGPs and their newborn progeny and between sister excitatory neurons in ontogenetic radial clones at the embryonic stage. Interestingly, the preferential electrical coupling between sister excitatory neurons, but not that between RGP and newborn progeny, is eliminated in mice lacking REELIN or upon clonal depletion of DISABLED-1, which compromises the inside-out radial neuronal migration pattern in the developing neocortex. Moreover, increased levels of Ephrin-A ligand or receptor that laterally disperse sister excitatory neurons also disrupt preferential electrical coupling between radially aligned sister excitatory neurons. These results suggest that RGP-guided inside-out radial neuronal migration facilitates the initial assembly of lineage-dependent precise columnar microcircuits in the neocortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The "Inside-out" Technique for Hernia Repair with Mesh Underlay.

    Science.gov (United States)

    Berhanu, Aaron E; Talbot, Simon G

    2015-06-01

    An improved method for mesh repair of ventral/incisional hernias after component separation is presented. The use of a Carter-Thomason suture passer (Cooper Surgical, http://www.coopersurgical.com) allows for safe passage of preplaced sutures on the mesh from within the abdominal cavity through the anterior rectus sheath. This "inside-out" method makes the underlay of mesh fast and easy by improving visualization and control of sharp instruments as they are passed through the abdominal cavity. Preplacement of sutures circumferentially on the mesh also improves the distribution of tension around the repair, which may ultimately reduce the risk of hernia recurrence. The "inside-out" technique was performed on 23 patients at a single tertiary academic medical center from November 2011 to February 2014. We have followed these patients for a median of 24.5 months to assess for postoperative complications and hernia recurrence. We report an acceptable hernia recurrence rate (2 of 23 = 8.7%). One recurrence was observed in a patient who underwent repair of a recurrent ventral hernia and the other had significant loss of domain requiring an inlay mesh. The "inside-out" technique for ventral hernia repair with a mesh underlay after component separation using a Carter-Thomason suture passer is easy, safe, and reliable. We have observed no hernia recurrence in patients who underwent repair for a primary ventral hernia with an underlay technique.

  13. Inside-out method to develop volar arthroscopic portals of the wrist in cadaver specimens.

    Science.gov (United States)

    Naroura, I; Zemirline, A; Taleb, C; Lebailly, F; Facca, S; Hidalgo Díaz, J J; Collon, S; Liverneaux, P

    2016-06-01

    Three direct volar portals for wrist arthroscopy have been described previously: two radiocarpal and one midcarpal. The aim of this study was to systematically describe four volar arthroscopic portals through minimally invasive incisions using an inside-out approach from known dorsal portals. Four volar arthroscopic wrist portals were studied on six hand specimens using an inside-out technique: a radial radiocarpal approach (RRCA), an ulnar radiocarpal approach (URCA), a radial midcarpal approach (RMCA) and an ulnar midcarpal approach (UMCA). Each volar approach corresponded to a dorsal approach: the 3/4 portal for RRCA, 4/5 portal for URCA, dorsal radial midcarpal approach for RMCA, and dorsal ulnar midcarpal approach for UMCA. The average range of motion of the scope through the RRCA was 65° in radial deviation and 72° in ulnar deviation; through the URCA it was 62° in radial deviation and 64° in ulnar deviation; through the RMCA it was 62° in radial deviation and 60° in ulnar deviation, and through the UMCA it was 59° in radial deviation and 68° in radial deviation. No iatrogenic injuries to important anatomical structures were noted. Based on these results, it is possible to perform these four volar portals through an inside-out technique with incisions mirroring the dorsal portals. They were easy to perform, safe and should be useful in ligament or bony intracarpal repair indications. Copyright © 2016 SFCM. Published by Elsevier Masson SAS. All rights reserved.

  14. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tetz, Lauren M., E-mail: ltetz@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Cheng, Adrienne A.; Korte, Cassandra S. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Giese, Roger W.; Wang, Poguang [Department of Pharmaceutical Sciences, Northeastern University, 360 Huntingon Ave, Boston, MA 02115 (United States); Harris, Craig; Meeker, John D.; Loch-Caruso, Rita [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States)

    2013-04-01

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a gene

  15. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy.

    Science.gov (United States)

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara; Desoye, Gernot; Hansson, Stefan; Kenna, Gerry; Knudsen, Lisbeth E; Markert, Udo R; Powles-Glover, Nicola; Schneider, Henning; Leach, Lopa

    2016-09-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.

    Science.gov (United States)

    Cox, Brian; Kotlyar, Max; Evangelou, Andreas I; Ignatchenko, Vladimir; Ignatchenko, Alex; Whiteley, Kathie; Jurisica, Igor; Adamson, S Lee; Rossant, Janet; Kislinger, Thomas

    2009-01-01

    Placental abnormalities are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting approximately 5% of all pregnancies. An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities, but there have been no systematic attempts to assess their molecular similarities or differences. We collected protein and mRNA expression data through shot-gun proteomics and microarray expression analysis of the highly vascular exchange region, microdissected from the human and mouse near-term placenta. Over 7000 ortholog genes were detected with 70% co-expressed in both species. Close to 90% agreement was found between our human proteomic results and 1649 genes assayed by immunohistochemistry for expression in the human placenta in the Human Protein Atlas. Interestingly, over 80% of genes known to cause placental phenotypes in mouse are co-expressed in human. Several of these phenotype-associated proteins form a tight protein-protein interaction network involving 15 known and 34 novel candidate proteins also likely important in placental structure and/or function. The entire data are available as a web-accessible database to guide the informed development of mouse models to study human disease.

  17. Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies.

    Science.gov (United States)

    McCarthy, R; Orsi, N M; Treanor, D; Moran, O; Vernooij, M; Magee, D R; Roberts, N; Stahlschmidt, J; Simpson, N A B

    2016-02-01

    This study aimed to examine the use of digital technology in the three-dimensional reconstruction of human placentas. Placentas obtained at term elective caesarean section were sampled, formalin-fixed and embedded in paraffin. Two hundred 5 μm consecutive sections were cut from each specimen and the resultant slides stained with haematoxylin and eosin. Slides were then scanned and the digitised images reconstructed using customised software. Three-dimensional reconstructions were successfully achieved in placentas from normal pregnancies and those complicated by pre-eclampsia, growth restriction, and gestational diabetes. Marked morphological differences were readily identifiable, most clearly in the stem villus architecture. This method is an emerging research tool for examining placental histoarchitecture at high resolution and gaining clinically relevant insight into the placental pathology allied to pregnancy complications such as PET, IUGR and GD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signalling

    Directory of Open Access Journals (Sweden)

    Martin eKnöfler

    2013-09-01

    Full Text Available Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signalling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signalling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β-catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signalling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signalling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β-catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signalling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodelling. Moreover, changes in Wnt signalling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signalling in physiological and abnormal

  19. Comparing human and macaque placental transcriptomes to disentangle preterm birth pathology from gestational age effects.

    Science.gov (United States)

    Eidem, Haley R; Rinker, David C; Ackerman, William E; Buhimschi, Irina A; Buhimschi, Catalin S; Dunn-Fletcher, Caitlin; Kallapur, Suhas G; Pavličev, Mihaela; Muglia, Louis J; Abbot, Patrick; Rokas, Antonis

    2016-05-01

    A major issue in the transcriptomic study of spontaneous preterm birth (sPTB) in humans is the inability to collect healthy control tissue at the same gestational age (GA) to compare with pathologic preterm tissue. Thus, gene expression differences identified after the standard comparison of sPTB and term tissues necessarily reflect differences in both sPTB pathology and GA. One potential solution is to use GA-matched controls from a closely related species to tease apart genes that are dysregulated during sPTB from genes that are expressed differently as a result of GA effects. To disentangle genes whose expression levels are associated with sPTB pathology from those linked to GA, we compared RNA sequencing data from human preterm placentas, human term placentas, and rhesus macaque placentas at 80% completed gestation (serving as healthy non-human primate GA-matched controls). We first compared sPTB and term human placental transcriptomes to identify significantly differentially expressed genes. We then overlaid the results of the comparison between human sPTB and macaque placental transcriptomes to identify sPTB-specific candidates. Finally, we overlaid the results of the comparison between human term and macaque placental transcriptomes to identify GA-specific candidates. Examination of relative expression for all human genes with macaque orthologs identified 267 candidate genes that were significantly differentially expressed between preterm and term human placentas. 29 genes were identified as sPTB-specific candidates and 37 as GA-specific candidates. Altogether, the 267 differentially expressed genes were significantly enriched for a variety of developmental, metabolic, reproductive, immune, and inflammatory functions. Although there were no notable differences between the functions of the 29 sPTB-specific and 37 GA-specific candidate genes, many of these candidates have been previously shown to be dysregulated in diverse pregnancy-associated pathologies. By

  20. Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

    Science.gov (United States)

    Paakki, P; Stockmann, H; Kantola, M; Wagner, P; Lauper, U; Huch, R; Elovaara, E; Kirkinen, P; Pasanen, M

    2000-01-01

    We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy. PMID:10656854

  1. Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

    Science.gov (United States)

    Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Soydemir, Fatimah; Baumann, Marc; Surbek, Daniel; Hediger, Matthias; Brownbill, Paul; Albrecht, Christiane

    2014-08-01

    Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (Ppreeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

  2. Human placental lipid induces mitogenesis and melanogenesis in ...

    Indian Academy of Sciences (India)

    A hydroalcoholic extract of fresh term human placenta was found to be mitogenic as well as melanogenic on B16F10 mouse melanoma in an in vitro culture. The extract, a reservoir of a large number of bioactive molecules, was resolved to get the lipid fraction. Its activity was evaluated on B16F10 mouse melanoma by ...

  3. Human placental lipid induces mitogenesis and melanogenesis in ...

    Indian Academy of Sciences (India)

    Unknown

    cascade of stress activated protein kinase (Coroneos et al. 1996). Human placenta is an enriched reservoir of .... as compared to the control (100%) (figure 2A). However, at concentrations higher than 10 µg/ml, ..... phosphate phosphatase: A key regulator of sphingolipid metabolism and stress response; Proc. Natl. Acad.

  4. Podocyte directed therapy of nephrotic syndrome-can we bring the inside out?

    Science.gov (United States)

    Müller-Deile, Janina; Schiffer, Mario

    2016-03-01

    Several of the drugs currently used for the treatment of glomerular diseases are prescribed for their immunotherapeutic or anti-inflammatory properties, based on the current understanding that glomerular diseases are mediated by immune responses. In recent years our understanding of podocytic signalling pathways and the crucial role of genetic predispositions in the pathology of glomerular diseases has broadened. Delineation of those signalling pathways supports the hypothesis that several of the medications and immunosuppressive agents used to treat glomerular diseases directly target glomerular podocytes. Several central downstream signalling pathways merge into regulatory pathways of the podocytic actin cytoskeleton and its connection to the slit diaphragm. The slit diaphragm and the cytoskeleton of the foot process represent a functional unit. A breakdown of the cytoskeletal backbone of the foot processes leads to internalization of slit diaphragm molecules, and internalization of slit diaphragm components in turn negatively affects cytoskeletal signalling pathways. Podocytes display a remarkable ability to recover from complete effacement and to re-form interdigitating foot processes and intact slit diaphragms after pharmacological intervention. This ability indicates an active inside-out signalling machinery which stabilizes integrin complex formations and triggers the recycling of slit diaphragm molecules from intracellular compartments to the cell surface. In this review we summarize current evidence from patient studies and model organisms on the direct impact of immunosuppressive and supportive drugs on podocyte signalling pathways. We highlight new therapeutic targets that may open novel opportunities to enhance and stabilize inside-out pathways in podocytes.

  5. Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique.

    Science.gov (United States)

    Zarket, Brady C; Raghavan, Srinivasa R

    2017-08-04

    Diverse structures in nature, such as the spinal disc and the onion have many concentric layers, and are created starting from the core and proceeding outwards. Here, we demonstrate an inside-out technique for creating multilayered polymer capsules. First, an initiator-loaded gel core is placed in a solution of monomer 1. The initiator diffuses outward and induces polymerization, leading to a shell of polymer 1. Thereafter, the core-shell structure is loaded with fresh initiator and placed in monomer 2, which causes a concentric shell of polymer 2 to form around the first shell. This process can be repeated to form multiple layers, each of a distinct polymer, and of controlled layer thickness. We show that these multilayered capsules can exhibit remarkable mechanical resilience as well as stimuli-responsive properties. The release of solutes from these capsules can be tailored to follow specific profiles depending on the chemistry and order of adjacent layers.Multiple concentric layers are present in a variety of structures present in nature, including the onion. Here, the authors show an inside-out strategy to synthesize multilayered polymer capsules, with different layers having specific composition and thereby specific responses to stimuli such as pH and temperature.

  6. Star Formation Quenching, How Fast And How Frequently? Inside-Out Or Not?

    Science.gov (United States)

    Lian, Jianhui; Yan, Renbin; Blanton, Michael; Zhang, Kai; Kong, Xu

    2017-06-01

    Star formation quenching is a critical process that drive galaxies evolving from blue star-forming to red passive stage. This rapid quenching process is necessary in galaxy evolution models to explain the galaxy distribution in NUV-optical colour-colour diagrams1,2 and the buildup of red-sequence from z = 1 to z = 03,4,5. Yet, the mechanism of this quenching process is not fully understood and is of hot debate. Many candidate scenarios, such as strangulation due to shock heating in massive halos, AGN feedback or gas stripping due to environmental effect, have been proposed. To differentiate these scenarios, more constraints on the quenching process and thus the potential physical mechanism are badly needed. The first result we show in this poster is the properties of quenching process we obtained from the galaxy distribution in NUV-optical colour-colour diagrams. Aside from the unclear integrated star formation history (SFH) of galaxies, how the SFH of galaxies varies internally is still poorly understood. One direct probe of the internal variation of SFH is the spatial distribution of colours, i.e. the colour gradient. In the second part of the results of this poster, we explicitly illustrate the definition of 'inside-out growth' and 'inside-out quenching' scenarios and utilize the galaxy distribution in the u-I colour gradients to see which one is more observationally favoured.

  7. "Inside-Out" PEGylation of Bovine β-Cross-Linked Hemoglobin.

    Science.gov (United States)

    Webster, Kyle D; Dahhan, Dana; Otto, Abigail M; Frosti, Cheyanne L; Dean, William L; Chaires, Jonathan B; Olsen, Kenneth W

    2017-04-01

    The development of a blood substitute is urgent due to blood shortages and potential communicable diseases. A novel method, inside-out PEGylation, has been used here to conjugate a multiarm maleimide-PEG (Mal-PEG) to β-cross-linked (βXL-Hb) hemoglobin (Hb) tetramers through the Cys β93 residues. This method produces a polymer with a single PEG backbone that is surrounded by multiple proteins, rather than coating a single protein with multiple PEG chains. Electrophoresis under denaturing conditions showed a large molecular weight species. Gel filtration chromatography and analytical ultracentrifugation determined the most prevalent species had three βXL-Hb to one Mal-PEG. Thermal denaturation studies showed that the cross-linked and PEGylated species were more stable than native Hb. Cross-linking under oxy-conditions produced a high oxygen affinity Hb species (P50  = 9.18 Torr), but the oxygen affinity was not significantly altered by PEGylation (P50  = 9.67 Torr). Inside-out PEGylation can be used to produce a hemoglobin-based oxygen carrier and potentially for other multiprotein complexes. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  8. A proposed study on the transplacental transport of parabens in the human placental perfusion model.

    Science.gov (United States)

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H; Knudsen, Lisbeth E

    2013-12-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy. 2013 FRAME.

  9. Identification of Epigenetic Factor Proteins Expressed in Human Embryonic Stem Cell-Derived Trophoblasts and in Human Placental Trophoblasts.

    Science.gov (United States)

    Sarkar, Prasenjit; Mischler, Adam; Randall, Shan M; Collier, Timothy S; Dorman, Karen F; Boggess, Kim A; Muddiman, David C; Rao, Balaji M

    2016-08-05

    Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins. Importantly, the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B were downregulated. Additionally, we hypothesized that nuclear proteomics of hESC-derived trophoblasts may be used for screening epigenetic factor proteins expressed by primary trophoblasts in human placental tissue. Accordingly, we conducted immunohistochemistry analysis of six epigenetic factor proteins identified from hESC-derived trophoblasts-DNMT1, DNMT3B, BAF155, BAF60A, BAF57, and ING5-in 6-9 week human placentas. Indeed, expression of these proteins was largely, though not fully, consistent with that observed in 6-9 week placental trophoblasts. Our results support the use of hESC-derived trophoblasts as a model for placental trophoblasts, which will enable further investigation of epigenetic factors involved in human trophoblast development.

  10. Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

    Science.gov (United States)

    Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

    2014-08-01

    The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope.

    Science.gov (United States)

    Otsuka, Shotaro; Bui, Khanh Huy; Schorb, Martin; Hossain, M Julius; Politi, Antonio Z; Koch, Birgit; Eltsov, Mikhail; Beck, Martin; Ellenberg, Jan

    2016-09-15

    The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the nuclear envelope. How the NPC assembles into this double membrane boundary has remained enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence microscopy revealed the molecular maturation of the intermediates, which initially contained the nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament component Nup358. EM particle averaging showed that the evagination base was surrounded by an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroom-shaped density was continuously associated with the deforming membrane. Quantitative structural analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of the INM.

  12. The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular 'Inside-Out' Approach.

    Science.gov (United States)

    Scharnagel, Dagmar; Goller, Jessica; Deibl, Nicklas; Milius, Wolfgang; Breuning, Matthias

    2018-01-23

    Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an alpha,N-fused 2-pyridone, an endo- or exo-alpha,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular 'inside-out' approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C2-symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the alpha,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Thigh abscess and necrotizing fasciitis following an inside-out transobturator tape intervention: a case report.

    Science.gov (United States)

    Kerbaj, Jad; Aubry, Camille; Prost, Caroline; Brouqui, Philippe

    2016-06-02

    Tension-free vaginal transobturator tapes are used worldwide in the treatment of urinary incontinence in women. Very few severe complications have been described following this procedure, with no standard treatment yet established. We present the case of a 36-year-old French white woman with no remarkable medical history, presenting with an abscess and necrotizing fasciitis 48 hours after an inside-out tension-free transobturator procedure. Samples were collected by guided puncture from the abscess, retrieving Staphylococcus aureus and Citrobacter koseri. Severe complications following this procedure are rare, although it can have the potential for significant morbidity and even mortality, which is worth highlighting. We recommend early surgical treatment in combination with broad-spectrum antibiotics and coverage for Staphylococcus aureus, which may be a causative agent.

  14. Fc receptor inside-out signaling and possible impact on antibody therapy.

    Science.gov (United States)

    Brandsma, Arianne M; Jacobino, Shamir R; Meyer, Saskia; ten Broeke, Toine; Leusen, Jeanette H W

    2015-11-01

    Fc receptors (FcR) are expressed on immune cells and bind to the Fc tail of antibodies. This interaction is essential for FcR-mediated signaling and triggering of cellular effector functions. FcR activation is tightly regulated to prevent immune responses by non-antigen bound antibodies or in the absence of 'danger signals'. FcR activity may be modulated at the plasma membrane via cross-talk with integrins. In addition, cytokines at the site of infection/inflammation can increase FcR avidity, a process referred to as inside-out signaling. This regulatory mechanism has been described for FcγRI (CD64), FcγRIIa (CD32a), and FcαRI (CD89) and is also well-known for integrins. Key cellular events during inside-out signaling are (de)phosphorylation, clustering, cytoskeleton rearrangements, and conformational changes. The latter can be studied with antibodies that specifically recognize epitopes exposed by the active (high affinity) or inactive (low affinity) state of the FcR. These antibodies are important tools to investigate the role of FcR activation in disease settings. Research on FcR has gained momentum with the rise of monoclonal antibodies (mAb) entering the clinic for the treatment of cancer and other diseases. The clinical outcome of mAb therapy may be improved by increasing FcR avidity by cytokine stimulation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Distal Inside-Out Epineural Sliding Technique to Repair Segmental Nerve Defects.

    Science.gov (United States)

    Luokkala, Toni; Ryhänen, Jorma; Näpänkangas, Juha; Karjalainen, Teemu V

    2016-09-01

    Background: The repair of a segmental peripheral nerve injury is a clinical challenge. Several studies have been performed to determine superior methods for overcoming nerve gaps. The purpose of this study was to investigate if the inside-out slided epineurium of the distal segment of an injured nerve can serve as a conduit to bridge a short nerve defect (10 mm). Methods: Nineteen sciatic nerves in Sprague-Dawley rats were transected, and a 10-mm gap was left between the ends. A section of distal epineurium was pulled inside out to bridge the gap. Walking track analysis was performed, and the sciatic function index (SFI) was calculated. Wet muscle mass and withdrawal reflex were measured. The density of axon fibers at different levels of repaired nerves was determined, and histological analysis was performed at 16 weeks. Results: The mean SFI improved from -81.0 at 4 weeks to 36.3 at 16 weeks. The axon densities showed regeneration through the epineural tube, and 5 of the rats demonstrated a withdrawal reflex. The weight of the tibialis anterior muscle of the injured limb at 16 weeks was 59% that of the uninjured side. Conclusions: The distal epineural sheath tube provided a size-matched conduit between the nerve stumps, with no histological donor-site morbidity. Histologically, regeneration occurred through the epineural tube without neuroma formation, and functional recovery was comparable to that of previous studies of nerve repair techniques. Technique may be an addition to the armamentarium of tools used to treat segmental nerve defects.

  16. Polyclonal antibodies directed against human placental Fcgamma receptor. Characterization of the antibodies and their interaction with the receptor.

    Science.gov (United States)

    Mikulska, J; Lisowski, J

    1987-01-01

    Antibodies to the putative Fc gamma receptor (Fc gamma R) of human placenta were raised by immunization of rabbits with the receptor purified form syncytiotrophoblast plasma membranes of human placenta. The rabbit antibodies were of IgG class and their F(ab')2 fragment interacted with Fc receptors in solubilized form and membrane-bound, as well. Immunological reactivity of the antibodies with Fc gamma R was demonstrated using immunodiffusion, solid-phase immunoassay, and ELISA. Studies on interaction of the antibodies with the isolated placental Fc gamma R showed that antigenic determinants of the receptor were different from the IgG-binding site. Rabbit anti-human placental Fc gamma R crossreacted, to various extent, with Fc gamma R-positive human cell lines showing antigenic relatedness of the placental receptor with Fc gamma R on other cell types. The antibodies showed only a weak crossreactivity with guinea pig peritoneal macrophage Fc gamma R. SDS-PAGE analysis of immunoprecipitates obtained by treatment of detergent lysates of 3H-labeled human placental trophoblasts membranes with the rabbit antibodies or with human IgG showed the presence of the some components which were observed in the case of the isolated, purified placental Fc gamma R: Mr of 123,000 and 52,000-56,000 under nonreducing conditions, and Mr of 64,000-67,000, 52,000-56,000, and 26,000-29,000, under reducing conditions. The polypeptide chains of the purified human placental receptor resolved in SDS-PAGE and transferred on nitrocellulose strips were able to interact both with the rabbit anti-placental receptor IgG F(ab')2 fragments and with human IgG. This gives an evidence that human placental Fc gamma R polypeptide chains Mr of approx. 64,000, 54,000, and 28,000 contain antigenic determinants of the receptor and binding sites for the Fc region of IgG, as well.

  17. Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

    Science.gov (United States)

    Bayer, Avraham; Lennemann, Nicholas J; Ouyang, Yingshi; Bramley, John C; Morosky, Stefanie; Marques, Ernesto Torres De Azeved; Cherry, Sara; Sadovsky, Yoel; Coyne, Carolyn B

    2016-05-11

    During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A Comparative Pathophysiological Study of Normal and Growth Retarded Human Placental Tissue

    Directory of Open Access Journals (Sweden)

    Adam Moyosore Afodun

    2014-01-01

    Full Text Available This study compares the pathophysiology of normal and growth retarded human placental tissues. Female patients were recruited from the Antenatal Clinic of Dolu Specialist Hospital, Mafoluku, Oshodi, Lagos, between 2008 and 2012. A total of 48 normal term placentas and 15 placentas of known IUGR cases were used for this study. IUGR cases were confirmed on the basis of ultrasound follow-up and diagnosis. Normal term placentas were collected at the point of delivery by a consultant gynaecologist, the cords were clamped, and membranes were then carefully trimmed after which each placenta was weighed. About 1 cm thickness of both normal and growth retarded placenta tissues was cut, processed for hematoxylin and eosin stain, while tissues for enzyme (ALP assay were homogenized in cold 0.5 M sucrose solution. Comparative analysis of the data was done using ANOVA; P<0.05 was taken as significant. The photomicrographs were observed/studied under light microscope, using the X150 and X600 magnifications. It was revealed therein that placental tissues are homogenous (regionally, compromised of maternal spiral arterioles and deregulated villous vasculogenesis, and that there is a significant difference in the level of alkaline phosphatase enzyme. We therefore concluded that there is a distinct difference between the normal and growth retarded human placenta tissue.

  19. Evolution of invasive placentation with special reference to non-human primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Pijnenborg, Robert

    2011-01-01

    It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae...... and even tarsiers and New World monkeys show restricted trophoblast invasion. Moreover, a truly villous placenta occurs only in Old World monkeys and great apes. The two latter groups of haplorhine primates show varying degrees of trophoblast-uterine interaction, including differences in the extent...... of decidualization, formation and disintegration of a cytotrophoblastic shell, degree of interstitial trophoblast invasion and depth of trophoblast invasion into spiral arteries. Recently, the occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees. As the still enigmatic disease of pre...

  20. Sexually Dimorphic Impact of Chromium Accumulation on Human Placental Oxidative Stress and Apoptosis.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Taylor, Robert J; Sivakumar, Kirthiram K; Arosh, Joe A; Zeng, Lixia; Pennathur, Subramaniam; Padmanabhan, Vasantha

    2017-10-23

    Environmental contamination with CrVI is a growing problem both in the U.S and developing countries. CrVI is widely used in numerous industries. Environmental exposure to hexavalent chromium (CrVI) adversely affects pregnancy outcomes and subsequent health of two generations, resulting in higher pregnancy loss, spontaneous abortion and low birth rate. Pregnant women exposed to CrVI through occupational settings experience increased risk of spontaneous abortion, stillbirth, preterm birth, and neonatal death. Children of the CrVI exposed women experience respiratory problems, perinatal jaundice, and increased birth defects. Since placental dysfunction may have a role in such adverse pregnancy outcome, we tested the hypothesis that environmental Cr exposure in pregnant women results in Cr accumulation in the human placenta, which could increase placental oxidative stress by disrupting antioxidant machinery and inducing apoptosis . Studies using frozen, deidentified human term placenta samples indicated that: (i) Cr accumulates in human term placenta tissues and (ii) increase in Cr accumulation is positively correlated with oxidative stress and apoptotic markers, and altered antioxidants levels. Interestingly, there was a sexual dimorphism in the correlation between Cr accumulation and oxidative stress, and expression of apoptotic and antioxidant markers. Mechanistic in vitro studies using human trophoblast cells BeWo confirmed the detrimental effects of Cr in altering antioxidant genes. For the first time, the current study provides evidence in support of a positive correlation between Cr accumulation in the human placenta and accelerated oxidative stress, with a gender bias towards the male sex. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Radial transport from the Io plasma torus: driven from the inside out or outside in?

    Science.gov (United States)

    Morgenthaler, J. P.; Marconi, M.; Oliversen, R. J.; Woodward, R. C., Jr.

    2016-12-01

    The Io plasma torus (IPT) is much more massive than it should be assuming radial transport was driven by centrifugally driven interchange instability. Two competing hypotheses have been proposed that provide the necessary impounding effect to radial transport of plasma: velocity shear impound and ring current impound. The velocity shear impound hypothesis suggests that the region of subcorotational plasma seen at the outer edge of the IPT impounds the progress of outward-moving flux tubes and processes near the IPT, such as Rayleigh-Taylor instabilities, would govern mass loss from the IPT ("inside out"). The ring current impound mechanism suggests that a population of energetic electrons on the inner edge of the ring current are distributed in energy and density in just the right way to balance the outward pressure of IPT material and processes in the magnetotail, such as reconnection after plasmoid release, would inject energetic particles that would perturb the ring current and let IPT material leak out ("outside in"). In support of the ring current impound mechanism, Louarn et al. (2014) found that roughly half of the time Galileo was sensitive to detecting them, energetic particle injections were coincident with Jovian hectometeric radio radiation (HOM), associated with auroral activity, and new bursts of narrow-band kilometric radiation (nKOM), associated with plasma leaving the vicinity of the IPT. We present new analyses of a large database of ground-based observations of Io's exosphere in [OI] 6300A. Using the IPT model of Smyth & Marconi (1998, 2000), Oliversen et al. (2001) showed the [OI] flux is a reliable proxy for the thermal electron density at Io's position. The Smyth & Marconi model (triangles in Figure) describes Io's [OI] flux well on most nights, except the two for which we have contemporaneous coverage with that of Louarn et al. (2014). These nights show strong evidence of missing mass from the IPT. We suggest that our observations can be used

  2. Outcomes of Inside-out Meniscal Repair in the Setting of Multiligament Reconstruction in the Knee.

    Science.gov (United States)

    Chahla, Jorge; Dean, Chase S; Matheny, Lauren M; Mitchell, Justin J; Cinque, Mark E; LaPrade, Robert F

    2017-07-01

    Limited evidence exists for meniscal repair outcomes in a multiligament reconstruction setting. Purpose/Hypothesis: The purpose of this study was to assess outcomes and failure rates of meniscal repair in patients who underwent multiligament reconstruction compared with patients who underwent multiligament reconstruction but lacked meniscal tears. The authors hypothesized that the outcomes of meniscal repair associated with concomitant multiligament reconstruction would significantly improve from preoperatively to postoperatively at a minimum of 2 years after the index surgery. Secondarily, they hypothesized that this cohort would demonstrate similar outcomes and failure rates compared with the cohort that did not have meniscal lesions at the time of multiligament reconstruction. Cohort study; Level of evidence, 3. Inclusion criteria for the study included radiographically confirmed skeletally mature patients of at least 16 years of age who underwent multiligamentous reconstruction of the knee without previous ipsilateral osteotomy, intra-articular infections, or intra-articular fractures. Patients were included in the experimental group if they underwent inside-out meniscal suture repair with concurrent multiligament reconstruction. Those included in the control group (multiligament reconstruction without a meniscal tear) underwent multiligament reconstruction but did not undergo any type of meniscal surgery. Lysholm, Western Ontario and McMaster Universities Osteoarthritis Index, Short Form-12 physical component summary and mental component summary, Tegner activity scale, and patient satisfaction scores were recorded preoperatively and postoperatively. The failure of meniscal repair was defined as a retear of the meniscus that was confirmed arthroscopically. There were 43 patients (16 female, 27 male) in the meniscal repair group and 62 patients (25 female, 37 male) in the control group. Follow-up was obtained in 93% of patients with a mean of 3.0 years (range, 2

  3. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

    Science.gov (United States)

    Ambühl, Lea M M; Leonhard, Anne K; Widen Zakhary, Carina; Jørgensen, Annemette; Blaakaer, Jan; Dybkaer, Karen; Baandrup, Ulrik; Uldbjerg, Niels; Sørensen, Suzette

    2017-10-01

    Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. Human placental growth hormone in ectopic pregnancy: Detection in maternal blood, immunohistochemistry and potential clinical implication.

    Science.gov (United States)

    Hübener, Christoph; Bidlingmaier, Martin; Wu, Zida; Diebold, Joachim; Strasburger, Christian J; Mahner, Sven; Hasbargen, Uwe; Delius, Maria

    2017-12-01

    To investigate human placental growth hormone (hGH-V) in ectopic pregnancy (EP): detection in maternal blood, correlation with immunohistochemistry and possible role as a marker for the course of EP. Women presenting in the outpatient or emergency department of a tertiary care university hospital with a positive pregnancy test and strong suspicion of EP by ultrasound and/or symptoms were eligible for the study (n=70). Tissue specimens from the surgically treated patients (n=50) were examined by histopathology as well as by a hGH-V specific immohistochemistry set-up. A highly sensitive hGH-V specific immunoassay was used to analyse serum samples collected before treatment, day 1 post surgery samples and serial samples for medical treatment. In EP patients' sera hGH-V was shown to be measurable for the first time (n=18). HGH-V however could not be detected in all patients' sera. HCG levels were significantly higher in the hGH-V serum positive group (p 0.001). HGH-V was localized to the syncytiotrophoblast in all specimens of EP examined by immunohistochemistry (n=10) regardless of the detection in the patient's blood. Placental growth hormone (hGH-V) was shown to be present both in ectopic pregnancy patients' sera and tissue. It may serve as a biomarker for monitoring the course and treatment of EP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system

    DEFF Research Database (Denmark)

    Myllynen, Päivi; Mathiesen, Line; Weimer, Marc

    2010-01-01

    As a part of EU-project ReProTect, a comparison of the dual re-circulating human placental perfusion system was carried out, by two independent research groups. The detailed placental transfer data of model compounds [antipyrine, benzo(a)pyrene, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b......)pyridine) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline] has been/will be published separately. For this project, a comparative re-analysis was done, by curve fitting the data and calculating two endpoints: AUC(120), defined as the area under the curve between time 0 and time 120min and as t(0.5), defined...... as the time when the fetal to maternal concentration ratio is expected to be 0.5. The transport of the compounds from maternal to fetal circulation across the perfused placenta could be ranked in the order of antipyrine>IQ>PhIP in terms of both t(0.5) and AUC(120) by both partners. For benzo...

  6. Valproic acid transfer across human placental cotyledon during dual perfusion in vitro.

    Science.gov (United States)

    Semczuk-Sikora, Anna; Czuczwar, Stanislaw; Semczuk, Andrzej; Kwasniewska, Anna; Semczuk, Marian

    2010-01-01

    Valproic acid (VPA ) is a well-known antiepileptic drug with a significant teratogenic effect when administered during pregnancy. To investigate the transplacental transport of VPA, we used an in vitro experiment of dual perfusion of a human placental cotyledon. Eighteen normal placentas at term were investigated; ten were treated with a therapeutic dose of VPA (initial level at maternal circulation 75 microgram/ml), while the remaining eight were supplied with toxic VPA doses (initial level at maternal circulation 225 microgram/ml). VPA concentrations in fetal compartment were lower than those in the maternal compartment at all timepoints with both doses applied. The maternal and foetal VPA concentrations were stable at 60 min and 120 min for the therapeutic dose of VPA (transfer percentages from the maternal to the fetal circulation were 22.7 +- 9.1 percent and 22.7 +- 7.1 percent, respectively). Interestingly, a significant decrease of VPA level in the maternal perfusate was observed after 120 min due to the slightly higher transfer of the drug to the foetal compartment. In conclusion, our data confirmed an easy and rapid transfer of VPA accross the placental barrier. Since the incidence of congenital malformations in infants correlates positively with VPA concentrations in maternal serum, monitoring of VPA should be mandatory due to possible harmful effects on the foetus.

  7. Pharmacology and placental transfer of a human alphav integrin monoclonal antibody in rabbits.

    Science.gov (United States)

    Martin, Pauline L; Zhou, Zhao; Van den Bulck, Kathleen; Kwok, Deborah; Powers, Gordon; Jiao, Qun; Schantz, Allen; Treacy, George

    2010-04-01

    Intetumumab is a human IgG1 anti-alphav-integrin monoclonal antibody that inhibits angiogenesis. Integrin binding and angiogenesis are important in reproduction including fertilization, implantation, and embryofetal development. These studies were designed to determine the pharmacological relevance of the rabbit for the evaluation of potential effects on embryofetal development and to evaluate the placental transfer of intetumumab in rabbits. In vitro pharmacology studies evaluated the binding of intetumumab to rabbit cells and the inhibition of vessel sprouting from rabbit aorta. For the evaluation of placental transfer, pregnant rabbits (8/group) were injected intravenously with intetumumab 50 or 100 mg/kg every 2 days from Gestation Day (GD)7 to GD19. Maternal sera, fetal homogenates/sera, and amniotic fluid were collected at necropsy on GD19 or GD28 for evaluation of intetumumab concentrations. Clinical condition of the dams was monitored and fetuses were screened for abnormalities. Intetumumab (5-40 microg/mL) inhibited aortic cell adhesion to vitronectin and vessel sprouting from rabbit aortic rings. Immunohistochemical staining of rabbit tissues demonstrated binding of intetumumab to placenta. Administration of intetumumab to pregnant rabbits was well tolerated by the dams and the fetuses did not show major abnormalities. Fetal exposure to intetumumab relative to maternal exposure was rabbit is a pharmacologically relevant species for evaluation of potential developmental effects of intetumumab. Intetumumab crosses the rabbit placenta during the fetal period (GD 19-28). 2010 Wiley-Liss, Inc.

  8. Triamcinolone up-regulates GLUT 1 and GLUT 3 expression in cultured human placental endothelial cells.

    Science.gov (United States)

    Kipmen-Korgun, Dijle; Ozmen, Asli; Unek, Gozde; Simsek, Mehmet; Demir, Ramazan; Korgun, Emin Turkay

    2012-01-01

    The placenta is a glucocorticoid target organ, and glucocorticoids (GCs) are essential for the development and maturation of fetal organs. They are widely used for treatment of a variety of diseases during pregnancy. In various tissues, GCs have regulated by glucose transport systems; however, their effects on glucose transporters in the human placental endothelial cells (HPECs) are unknown. In the present study, HPECs were cultured 24 h in the presence or absence of 0.5, 5 and 50 µmol · l(-1) of synthetic GC triamcinolone (TA). The glucose carrier proteins GLUT 1, GLUT 3 and GC receptor (GR) were detected in the HPECs. We showed increased expression of GLUT 1 and GLUT 3 proteins and messenger RNA (mRNA) levels (p GLUT 1 and GLUT 3 expression through GR. Excessive exposure to GCs causes maternal and fetal hypoglycemia and diminished fetal growth. We speculate that to compensate for fetal hypoglycemia and diminished fetal growth, the expression of placental endothelial glucose transporters might be increased. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.

    Science.gov (United States)

    Azzaroli, F; Mennone, A; Feletti, V; Simoni, P; Baglivo, E; Montagnani, M; Rizzo, N; Pelusi, G; DE Aloysio, D; Lodato, F; Festi, D; Colecchia, A; Roda, E; Boyer, J L; Mazzella, G

    2007-10-15

    The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

  10. Placental exosomes during gestation: liquid biopsies carrying signals for the regulation of human parturition.

    Science.gov (United States)

    Salomon, Carlos; Nuzhat, Zarin; Dixon, Christopher L; Menon, Ramkumar

    2018-01-25

    Parturition is defined as the action or process of giving birth to offspring. Normal term human parturition ensues following the maturation of fetal organ systems typically between 37 and 40 weeks of gestation. Our conventional understanding of how parturition initiation is signaled revolves around feto-maternal immune and endocrine changes occurring in the intrauterine cavity. These changes in turn correlate with the sequence of fetal growth and development. These important physiological changes also result in homeostatic imbalances which result in heightened inflammatory signaling. This disrupts the maintenance of pregnancy, thus leading to labor-related changes. However, the precise mechanisms of the signaling cascades that lead to the initiation of parturition remain unclear, although exosomes may be a mediator of this process. Exosomes are a subtype of extracellular vesicles characterised by their endocytic origin. This involves the trafficking of intraluminal vesicles into multivesicular bodies (MVB) and then exocytosis via the plasmatic membranes. Exosomes are highly stable nanovesicles that are released by a wide range of cells and organs including the human placenta and fetal membranes. Interestingly, exosomes from placental origin have been uncovered in maternal circulation across gestation. In addition, their concentration is higher in pregnancies with complications such as gestational diabetes and preeclampsia. In normal gestation, the concentration of placental exosomes in maternal circulation correlates with placental weight at third trimester. The role of placental exosomes across gestation has not been fully elucidated, although recent studies suggest that placental exosomes are involved in maternal-fetal inmmuno-tolerance, maternal systemic inflammation and nutrient transport. The content of exosomes is of particular importance, encompassing a large range of molecules such as mRNA, miRNAs, DNA, lipids, cell-surface receptors, and protein mediators

  11. Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

    Directory of Open Access Journals (Sweden)

    Maia Blomhoff Holm

    Full Text Available The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample.This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein and fetal (umbilical vein and artery sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations.In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake for 14 amino acids and a negative venoarterial difference (fetal release for glutamic acid (p<0.001. In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake for leucine (p = 0.005, isoleucine (p = 0.01, glutamic acid (p<0.001 and arginine (p = 0.04 and a negative arteriovenous difference (uteroplacental release for tyrosine (p = 0.002, glycine (p = 0.01 and glutamine (p = 0.02. The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake.Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is

  12. Inside-Out access strategy using new trans-vascular catheter approach

    Directory of Open Access Journals (Sweden)

    Boese Axel

    2016-09-01

    Full Text Available Image guided minimal invasive treatment can have large benefits for patient recovery and is lowering hospitalisation costs. But an access path, minimizing patient’s risk, is needed to reach the target structure inside of the body. Beside the use of natural orifices like oral, vaginal or anal cavities, a percutaneous puncture is common to enter the body. Also an interstitial path can be selected but if the pathological structure is situated in the deep, a long accesses path is required. Thereby the risk of additional damage and affecting organ functionality is increased. A possible option to come closer to the target structure with less organ damage is by using the vascular system. Entering the vessel from an uncritical point, the vasculature can be used as “highway” to the target structures. For the treatment of these nearby structures, the vessel has to be punctured and occluded afterwards by a save procedure. We propose an Inside-Out access strategy using a new trans-vascular catheter approach.

  13. A short report on knowledge exchange through research-based theatre: 'inside out of mind'.

    Science.gov (United States)

    Schneider, Justine; Lowe, Stephen; Myers, Tanya; Scales, Kezia; Bailey, Simon; Middleton, Joanne

    2014-10-01

    The short report describes the development from page to stage of a work of theatre based on an ethnographic study. The originating research focused on the work of health care assistants (nurse's aides) whose direct impact on the quality of life of highly dependent people is often overlooked. The research followed hospital personnel on wards specialising in the 'challenging behaviour' associated with dementia in central England. Conventional research outputs failed to engage the health care assistants themselves, so we turned to theatre to remedy this. The development of the field notes into theatre was characterised by the artistic freedom given to the playwright, in contrast to more data-led approaches to theatre making. The account of the process of creating the play, Inside Out of Mind, is followed a description of how the work was received by specialist and general audiences totalling 2000+. The discussion seeks to locate the whole enterprise in relation to the field of research-based theatre and explores how the production and its associated learning events relate to definitions of research-based theatre in the light of recent attempts to encapsulate this broad and diverse methodology. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. The inside-out supercapacitor: induced charge storage in reduced graphene oxide.

    Science.gov (United States)

    Martin, Samuel T; Akbari, Abozar; Chakraborty Banerjee, Parama; Neild, Adrian; Majumder, Mainak

    2016-11-30

    Iontronic circuits are built using components which are analogous to those used in electronic circuits, however they involve the movement of ions in an electrolyte rather than electrons in a metal or semiconductor. Developments in these circuits' performance have led to applications in biological sensing, interfacing and drug delivery. While transistors, diodes and elementary logic circuits have been demonstrated for ionic circuits if more complex circuits are to be realized, the precident set by electrical circuits suggests that a component which is analogous to an electrical capacitor is required. Herein, an ionic supercapacitor is reported, our experiments show that charge may be stored in a conductive porous reduced graphene oxide film that is contacted by two isolated aqueous solutions and that this concept extends to an arbitrary polarizable sample. Parametric studies indicate that the conductivity and porosity of this film play important roles in the resultant device's performance. This ionic capacitor has a specific capacitance of 8.6 F cm-3 at 1 mV s-1 and demonstrates the ability to filter and smooth signals in an electrolyte at a variety of low frequencies. The device has the same interfaces as a supercapacitor but their arrangement is changed, hence the name inside-out supercapacitor.

  15. Inside-out Z rings - constriction with and without GTP hydrolysis

    Science.gov (United States)

    Osawa, Masaki; Erickson, Harold P.

    2011-01-01

    Summary The bacterial tubulin homolog FtsZ forms a ring-like structure called the Z ring that drives cytokinesis. We showed previously that FtsZ-YFP-mts, which has a short amphipathic helix (mts) on its C terminus that inserts into the membrane, can assemble contractile Z rings in tubular liposomes without any other protein. Here we study mts-FtsZ-YFP, where the membrane tether is switched to the opposite side of the protofilament. This assembled “inside-out” Z rings that wrapped around the outside surface of tubular liposomes. The inside-out Z rings were highly dynamic, and generated a constriction force that squeezed the tubular liposomes from outside. This is consistent with models where the constriction force is generated by curved protofilaments bending the membrane. We used this system to test how GTP hydrolysis by FtsZ is involved in Z-ring constriction. Without GTP hydrolysis, Z rings could still assemble and generate an initial constriction. However, the constriction quickly stopped, suggesting that Z rings became rigidly stabilized in the absence of GTP hydrolysis. We propose that remodeling of the Z ring, mediated by GTP hydrolysis and exchange of subunits, is necessary for the continuous constriction. PMID:21631604

  16. Inside-out Ultraviolet-C Sterilization of Pseudomonas aeruginosa Biofilm In Vitro.

    Science.gov (United States)

    Jones, Cameron C; Valdeig, Steffi; Sova, Raymond M; Weiss, Clifford R

    2016-11-01

    Biofilms are difficult to eradicate due to a protective architecture and create major challenges in patient care by diminishing both host immune response and therapeutic approaches. This study investigated a new strategy for treating surface-attached biofilms by delivering germicidal UV through a material surface in a process referred to as "inside-out sterilization" (IOS). Mature Pseudomonas aeruginosa (ATCC® 27853™ ) biofilms were irradiated with up to 1400 mJ cm-2 of germicidal UV from both ambient and IOS configurations. The lethal dose for the ambient exposure group was 461 mJ cm-2 95% CI [292, 728] compared to the IOS treatment group of 247 mJ cm-2 95% CI [187, 325], corresponding to 47% less UV dosage for the IOS group (P < 0.05). This study demonstrated that with IOS, a lower quantal dosage of UV energy is required to eradicate biofilm than with ambient exposure by leveraging the organizational structure of the biofilm. © 2016 The American Society of Photobiology.

  17. B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk.

    Science.gov (United States)

    Kläsener, Kathrin; Maity, Palash C; Hobeika, Elias; Yang, Jianying; Reth, Michael

    2014-06-24

    Binding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10-20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation.DOI: http://dx.doi.org/10.7554/eLife.02069.001. Copyright © 2014, Kläsener et al.

  18. Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR.

    Science.gov (United States)

    Chen, Yi-Yung; Rosario, Fredrick J; Shehab, Majida Abu; Powell, Theresa L; Gupta, Madhulika B; Jansson, Thomas

    2015-12-01

    Placental amino acid transport is decreased in intrauterine growth restriction (IUGR); however, the underlying mechanisms remain largely unknown. We have shown that mechanistic target of rapamycin (mTOR) signalling regulates system A amino acid transport by modulating the ubiquitination and plasma membrane trafficking of sodium-coupled neutral amino acid transporter 2 (SNAT-2) in cultured primary human trophoblast cells. We hypothesize that IUGR is associated with (1) inhibition of placental mTORC1 and mTORC2 signalling pathways, (2) increased amino acid transporter ubiquitination in placental homogenates and (3) decreased protein expression of SNAT-2 in the syncytiotrophoblast microvillous plasma membrane (MVM). To test this hypothesis, we collected placental tissue and isolated MVM from women with pregnancies complicated by IUGR (n=25) and gestational age-matched women with appropriately grown control infants (n=19, birth weights between the twenty-fifth to seventy-fifth percentiles). The activity of mTORC1 and mTORC2 was decreased whereas the protein expression of the ubiquitin ligase NEDD4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2; +72%, Pcauses down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. © 2015 Authors; published by Portland Press Limited.

  19. Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1.

    Science.gov (United States)

    Schwartz, Christine; Fischer, Martina; Mamchaoui, Kamel; Bigot, Anne; Lok, Thevy; Verdier, Claude; Duperray, Alain; Michel, Richard; Holt, Ian; Voit, Thomas; Quijano-Roy, Suzanna; Bonne, Gisèle; Coirault, Catherine

    2017-04-28

    LINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls. Inhibition of Rho-associated kinase (ROCK) prevented cytoskeletal defects, while inhibiting myosin light chain kinase or phosphorylation of focal adhesion kinase was ineffective. Depletion or inactivation of a ROCK-dependent regulator of actin remodelling, the formin FHOD1, largely rescued morphology in mutant cells. The functional integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity and the inside-out mechanical coupling that tunes the cell internal stiffness to match that of its soft, physiological-like environment.

  20. Human placentation from nidation to 5 weeks of gestation. Part II: Tools to model the crucial first days

    DEFF Research Database (Denmark)

    James, J L; Carter, Anthony Michael; Chamley, L W

    2012-01-01

    Human pregnancy is unusual with respect to monthly spontaneous decidualisation as well as the degree of placental invasion and interaction with the decidualised endometrial stroma. This review covers in vivo animal models and in vitro cell culture models that have been used to study the earliest...... stages of human implantation and placentation from nidation to 5 weeks of gestation. The field has expanded rapidly in recent years due to the generation of human embryonic stem cell lines and the ability of some scientists to culture human blastocysts. These models have enabled researchers to begin...... to elucidate the interactions involved in human blastocyst apposition, adhesion and implantation. However, we still understand very little about the differentiation processes involved in the formation of the placenta. Continued improvements to current models, including the potential isolation of a human...

  1. Comparison of inside-out and all-inside techniques for the repair of isolated meniscal tears: a systematic review.

    Science.gov (United States)

    Grant, John A; Wilde, Jeff; Miller, Bruce S; Bedi, Asheesh

    2012-02-01

    Arthroscopic meniscal repair techniques are continuing to evolve. Most studies to date comparing the healing rate of inside-out to all-inside meniscal repair techniques are confounded by associated anterior cruciate ligament reconstruction or deficiency. This review was conducted to compare the effectiveness and complications of the inside-out repair technique to that of the all-inside repair technique in isolated unstable peripheral longitudinal ("bucket-handle") meniscal tears. Systematic review. Computerized keyword searches of MEDLINE, EMBASE, CINAHL, ACP Journal Club, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were performed. Two reviewers independently performed searches and article reduction. Studies that included stratified data for isolated unstable longitudinal meniscal tears in stable knees, repaired with either an inside-out or all-inside repair technique, were selected. Data on clinical failure, subjective outcome measures, and complications were summarized. Nineteen studies included data specific to isolated meniscal tears. The rate of clinical failure was 17% for inside-out repairs and 19% for all-inside repairs. Lysholm scores and Tegner activity scores were similar between the 2 repair methods (87.8 vs 90.2 and 5.6 vs 5.5, respectively). The prevalence of nerve injury/irritation was higher with the inside-out technique (9% vs 2%). All-inside techniques had a higher rate of local soft tissue irritation, swelling, and implant migration or breakage. The use of older generation, rigid, all-inside implants is associated with chondral injury. There are no differences in clinical failure rate or subjective outcome between inside-out and all-inside meniscus repair techniques. Complications are associated with both techniques. More nerve symptoms are associated with the inside-out repair and more implant-related complications are associated with the all-inside technique. Rates of structural healing

  2. Comparative placental transfer, localization, and effects of radionuclides in experimental animal and human pregnancies

    Energy Technology Data Exchange (ETDEWEB)

    Sikov, M.R.; Meznarich, H.K.; Traub, R.J.

    1991-11-01

    Estimating radiation doses to the human embryo/fetus from radionuclides and predicting effects requires extrapolation of data from studies of laboratory species, with scaling for species-specific developmental stage and gestational time relationships and maturities at birth. Combinations of fetal-to-maternal ratios of concentrations, patterns of deposition, transfer kinetics, and compartmental and physiologic models are used to predict radioactivity levels and radiation doses to the conceptus. There is agreement between values expressing fractional transfer across the placenta ({theta}) with tabulated values for fractional absorption (f{sub 1}) from gastrointestinal (GI) tract or lung for most substances commonly involved in metabolic processes. A tendency toward disagreement for some other materials is thought to involve explanations based on their physicochemistry, toxicity, or the influence of target tissue development on placental transfer kinetics.

  3. Spontaneous contractility of human placental vessels in vitro axipetal and isometric recording.

    Science.gov (United States)

    Gonzalez Panizza, V H; Benedetti, W L; Alvarez, H

    1980-01-01

    In vitro contractility of isolated cylindrical segments of chorial arteries and veins from 40 human term placentas was studied. Contractility was recorded by an isometrical and axipetal method. Spontaneous contractility was observed in 75% of the arteries and in 45% of veins. In both types of vessels, contractility was similar and characterized by development of tonic circumferential tension, between 100 and 200 mg/mm. Clonic activity consisting of rhythmic contractions with an average frequency between 0.7 and 0.9/min and an average intensity of 5--40 mg/min was superimposed. Vasoconstrictor drugs (PGF2 alpha, histamine and adrenaline) increase tonic tension without modifying the frequency of clonic activity. It is suggested that spontaneous contractility may be the expression of myogenic excitability related to the regulation of fetal placental blood flow.

  4. [The experimental study on inside-out vein graft for repairing inferior alveolar nerve defect in the rabbit].

    Science.gov (United States)

    Chen, P; Li, H; Zhang, G

    2000-10-01

    This study describes a modification of the vein graft technique inside-out vein graft, creates an autogenous vein conduct with the collagen-rich and Schwann cells exposed to regenerating axons. To compare regeneration of inferior alveolar nerves through two conduits: inside-out vein graft and the standard vein graft. 18 adult white rabbits were selected and vena facialises of both sides were harvested. Turned the right vena facialis into inside-out vein and used to bridge an 8 mm defect created in the right inferior alveolar nerve. An 8 mm defect of the left inferior alveolar nerve was bridged by the standard vein graft. After rabbits sacrificed at 8, 14 and 20 weeks, the regenerating nerve cables were harvested from the conduits and performed histologic study. At 20 weeks, performed also electrophysiologic studies and statistical analysis of conductive velocities and histological results. Regenerating nerves connected with proximal and distal nerve stumps on both sides postoperation 8 weeks, a number of regenerating nerve fibers and thickness of axon were gradually increasing. At 20 weeks regenerating nerve on the inside-out vein graft side showed superior function results--faster conduction velocities (P nerve regeneration by an environment with collagen-rich and Schwann cells. The inside-out vein graft is an original way to repair inferior alveolar nerve.

  5. Silicon anode materials with ultra-low resistivity from the inside out for lithium ion batteries

    Science.gov (United States)

    Xu, Guojun; Jin, Chenxin; Liu, Liekai; Lan, Yu; Yue, Zhihao; Li, Xiaomin; Sun, Fugen; Huang, Haibin; Zhou, Lang

    2017-12-01

    Broken silicon (Si) wafers with electrical resistivity of 1 and 0.001 Ω cm were respectively ball-milled to Si particles with median diameters of less than 1 μm. Both these two types of Si particles were deposited with silver (Ag) nanoparticles by self-selective electroless deposition method. 1-Ω cm-Si particles, 0.001-Ω cm-Si particles, Ag-deposited 1-Ω cm-Si particles and Ag-deposited 0.001-Ω cm-Si particles were, respectively, mixed with graphite particles in weight ratio of 1:9 to form four types of Si-C anode materials and then they were assembled into coin cells. The experimental results indicate that the Ag-deposited 0.001-Ω cm-Si sample shows the higher capacity, better rate and cycle performance than other three samples, due to the high conductivity of Ag-deposited 0.001-Ω cm-Si sample from the inside out. At the current density of 750 mA g-1, the discharge capacity gap of Ag-deposited 0.001-Ω cm-Si sample and 0.001-Ω cm-Si sample is as high as 141.7 mA h g-1, which is almost equal to the discharge capacity of the latter. Besides, the discharge capacity retention ratio of Ag-deposited 0.001-Ω cm-Si sample after 50 cycles is 70%, which is 23.5% higher than that of 0.001-Ω cm-Si sample.

  6. Decreased expression of phosphorylated placental heat shock protein 27 in human and ovine intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Bahr, B; Galan, H L; Arroyo, J A

    2014-06-01

    Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. HSP27 has been shown to be involved in the control of apoptosis. Our objective is to determine the expression of phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27 during gestation in an ovine hyperthermia induced model of IUGR. Human placenta tissue samples were collected at term to quantify p-HSP27. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days gestational age (dGA) to determined phosphorylated and total HSP27 across the development of IUGR. Phosphorylated HSP27 was significantly reduced in human placenta IUGR compared to controls at term. HSP27 was increased throughout gestation during the development of IUGR in the sheep. P-HSP27 was increased in early gestation (55 dGA), and decreased near term (130 dGA). The near term decrease was localized to the trophoblast cells of the placenta. We conclude that decreased p-HSP27 at term is present when placental apoptosis is increased during IUGR. This could be a factor leading to the decreased placental weight observed during IUGR. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Laeverin/aminopeptidase Q induces trophoblast invasion during human early placentation.

    Science.gov (United States)

    Horie, Akihito; Fujiwara, Hiroshi; Sato, Yukiyasu; Suginami, Koh; Matsumoto, Hisanori; Maruyama, Masato; Konishi, Ikuo; Hattori, Akira

    2012-05-01

    In primate placenta, extravillous trophoblast (EVT) invades maternal tissue in temporally- and spatially-regulated fashions. We previously identified a novel placenta-specific cell-surface aminopeptidase, laeverin/aminopeptidase Q, which is expressed on EVT-lineage cells in the fetal membrane. Laeverin possesses a peptide-binding site that is evolutionally unique to primates, suggesting possible involvement of laeverin in a primate-specific phenomenon during placentation. Thus, this study was designed to elucidate the molecular characteristics and physiological roles of laeverin in human EVT. Placental tissues of various developmental stages were subjected to immunostaining and western blotting. Effects of siRNA and a soluble form of recombinant laeverin on EVT cells isolated from primary villous explant cultures were examined using Matrigel invasion assays and cell proliferation assays. Laeverin was specifically immunolocalized to HLA-G-positive EVT in placentas from early and term pregnancy. In primary villous explant cultures, laeverin expression was induced on the cell surface of the outgrowing EVT. In western blotting, laeverin protein was detected as two distinct bands at 130 and 160 kDa along with a broad band ranging from 200 to 270 kDa. De-glycosylation treatment showed that these native laeverin isotypes are N-linked glycoproteins sharing a common 115-kDa core protein. In invasion assays, the reduction of laeverin expression by siRNA suppressed migration of the isolated EVT, while the soluble form of recombinant laeverin enhanced its migration. Laeverin is a specific cell-surface marker for human EVT and plays a regulatory role in EVT migration.

  8. A proposed study on the transplacental transport of parabens in the human placental perfusion model

    DEFF Research Database (Denmark)

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H

    2013-01-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the......Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment......, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance......, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim...

  9. Inside-out versus outside-in transobturator tension-free vaginal tape: a 5-year prospective comparative study.

    Science.gov (United States)

    Cheung, Rachel Yau Kar; Chan, Symphorosa Shing Chee; Yiu, Ka Wah; Chung, Tony Kwok Hung

    2014-01-01

    To compare the 1-year and 5-year outcomes of transobturator tension-free vaginal tape with outside-in and inside-out approaches in women with urinary stress incontinence, and to identify risk factors for treatment failure at 5 years. A prospective observational study was carried out for women with urinary stress incontinence who underwent transobturator tension-free vaginal tape from September 2004 to March 2008 in a tertiary urogynecology center. Women (n = 213) had either an outside-in (n = 124) or inside-out (n = 89) procedure. They were followed up annually until 5 years after the operation. Subjective cure was defined as women not experiencing any urine loss on physical activity. Objective cure was defined as no urine leak at cough during a standard urodynamic study. At a mean follow up of 59.2 months, the subjective cure rates were 81.7% and 84.1%; the objective cure rate were 82.6% and 82.5% for the outside-in and inside-out approach, respectively. There was no statistically significant difference between the procedures. De novo overactive bladder syndrome (10.6% in outside-in and 14.6% in inside-out approach; P = 0.40) and de novo detrusor overactivity (5.8% in outside-in and 15% in inside-out approach; P = 0.11) was also comparable between the two groups. Complications at the fifth year were low and not significantly different among both methods. The outside-in approach and inside-out approach are both safe and effective in treating women with urinary stress incontinence up to 5 years. © 2013 The Japanese Urological Association.

  10. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Prouillac, Caroline, E-mail: c.prouillac@vetagro-sup.fr [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Rodriguez, Frédéric; Baltas, Michel [Université Paul Sabatier, SPCMIB-UMR5068, Laboratoire de Synthèse et de Physicochimie des Molécules d' Intérêt Biologique, 118 route de Narbonne, 31062 TOULOUSE cedex 9 (France); Lecoeur, Sylvaine [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France)

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  11. In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

    Science.gov (United States)

    Ikeda, Kenji; Utoguchi, Naoki; Tsutsui, Hidenobu; Yamaue, Satoko; Homemoto, Manami; Nakao, Erina; Hukunaga, Yumi; Yamasaki, Kyohei; Myotoku, Michiaki; Hirotani, Yoshihiko

    2011-02-01

    Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  12. Editorial Commentary: Feeling the Pressure! A Biomechanical Analysis of All-Inside and Inside-Out Knee Meniscus Repair.

    Science.gov (United States)

    Barber, F Alan

    2017-10-01

    A biomechanical, time-zero comparison found that both No. 2-0 UltraBraid inside-out sutures and FasT-Fix 360 all-inside devices used to repair a displaced bucket handle knee meniscus tear increased the contact area in deeper flexion angles (at 45°-60°) and reduced the peak contact pressure (at 45°-90°). No significance difference was observed between the inside-out and all-inside repair techniques. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  13. Arthroscopic Inside-Out Repair of a Meniscus Bucket-Handle Tear Augmented With Bone Marrow Aspirate Concentrate.

    Science.gov (United States)

    Muckenhirn, Kyle J; Kruckeberg, Bradley M; Cinque, Mark E; Chahla, Jorge; DePhillipo, Nicholas N; Godin, Jonathan A; LaPrade, Robert F

    2017-08-01

    Bucket-handle tears of the meniscus comprise nearly 10% of all meniscus tears and commonly affect the young male population. Displacement of the free segment can lead to significant pain and disability, necessitating reduction and surgical treatment. General contraindications include malalignment, severe arthritis, significant comorbidities, or chronic asymptomatic tears, but otherwise repair should almost always be performed. Options for surgical treatment include partial meniscectomy and arthroscopic repair using an all-inside, outside-in, or inside-out technique. The purpose of this Technical Note is to detail our arthroscopic inside-out repair technique augmented with bone marrow aspirate concentrate.

  14. Anatomic femoral tunnels in posterior cruciate ligament reconstruction: inside-out versus outside-in drilling.

    Science.gov (United States)

    Tompkins, Marc; Keller, Thomas C; Milewski, Matthew D; Gaskin, Cree M; Brockmeier, Stephen F; Hart, Joseph M; Miller, Mark D

    2013-01-01

    During posterior cruciate ligament (PCL) reconstruction, the placement and orientation of the femoral tunnel is critical to postoperative PCL function. To compare the ability of outside-in (OI) versus inside-out (IO) femoral tunnel drilling in placing the femoral tunnel aperture within the anatomic femoral footprint of the PCL, and to evaluate the orientation of the tunnels within the medial femoral condyle. Controlled laboratory study. Ten matched pairs of cadaver knees were randomized such that within each pair, 1 knee underwent arthroscopic OI drilling and the other underwent IO drilling. All knees underwent computed tomography (CT) both pre- and postoperatively with a technique optimized for ligament evaluation (80 keV with maximum mAs). Commercially available third-party software was used to fuse the pre- and postoperative CT scans, allowing comparison of the PCL footprint to the drilled tunnel. The percentage of tunnel aperture contained within the native footprint, as well as the distance from the center of the tunnel aperture to the center of the footprint, were measured. In addition, the orientation of the tunnels in the coronal and axial planes was evaluated. The OI technique placed 70.4% ± 23.7% of the tunnel within the native femoral footprint compared with 79.8% ± 16.7% for the IO technique (P = .32). The OI technique placed the center of the femoral tunnel 4.9 ± 2.2 mm from the center of the native footprint compared to 5.3 ± 2.0 mm for the IO technique (P = .65). The femoral tunnel angle in the coronal plane was 21.0° ± 9.9° for the OI technique and 37.0° ± 10.3° for the IO technique (P = .002). The tunnel angle in the axial plane was 27.3° ± 4.8° for the OI technique and 39.1° ± 11.5° for the IO technique (P = .01). This study demonstrates no difference in the ability of the OI and IO techniques to place the femoral tunnel within the PCL femoral footprint during PCL reconstruction. With the technique parameters used in this study

  15. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

    Science.gov (United States)

    Mizuuchi, Masahito; Cindrova-Davies, Tereza; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J; Yung, Hong Wa

    2016-03-01

    Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p pregnancy complications. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  16. A 2D-DIGE approach to identify proteins involved in inside-out control of integrins.

    NARCIS (Netherlands)

    Langereis, J.D.; Prinsen, B.H.; Sain-van der Velden, M.G. de; Coppens, C.J.; Koenderman, L.; Ulfman, L.H.

    2009-01-01

    Leukocyte integrins are functionally regulated by "inside-out" signaling, meaning that stimulus-induced signaling pathways act on the intracellular integrin tail and induce activation of the receptor at the outside. Both a change in conformation (affinity) and in clustering (avidity/valency) of the

  17. A 2D-DIGE Approach To Identify Proteins Involved in Inside-Out Control of Integrins

    NARCIS (Netherlands)

    Langereis, Jeroen D.; Prinsen, Berthil H. C. M. T.; de Sain-van der Velden, Monique G. M.; Coppens, Cornelis J. C.; Koenderman, Leo; Ulfman, Laurien H.

    Leukocyte integrins are functionally regulated by "inside-out" signaling, meaning that stimulus-induced signaling pathways act on the intracellular integrin tail and induce activation of the receptor at the outside. Both a change in conformation (affinity) and in clustering (avidity/valency) of the

  18. Calcium-dependant binding proteins associated with human placental syncytiotrophoblast microvillous cytoskeleton.

    Science.gov (United States)

    Webb, P D; Mahadevan, L C

    1987-12-18

    Isolated human placental syncytiotrophoblast microvillous plasma membrane vesicles were extracted with Triton X-100 to yield a detergent-insoluble residue. The residue contained approx. 50% of the total membrane protein and was qualitatively different from untreated trophoblast on SDS-polyacrylamide gel electrophoresis, Western blots and dot-immunobinding assay. Three major proteins, with molecular weights of 68, 36 and 34 kDa, dissociated from this non-ionic detergent-insoluble submembranous cytoskeletal fraction in the presence of calcium chelators. They were immunologically related to human lymphocyte cytoskeletal calcium-binding proteins, and the 36 kDa component reacted with antisera to the phospholipase A2 inhibitor, lipocortin II. Anti-lipocortin I sera did not recognise the 34 kDa protein, but did react with a series of trophoblast cytoskeletal proteins in the 34-37 kDa region. Incubation of epidermal growth factor with isolated trophoblast membrane vesicles stimulated the phosphorylation of a 36 kDa protein on tyrosine residues. Immunoprecipitation studies further showed there was no phosphorylation of the 34 kDa protein, but the 68 kDa protein was a major phosphorylated component of isolated syncytiotrophoblast membranes. p68 was principally phosphorylated on serine with slight tyrosine phosphorylation which showed an apparent increase after epidermal growth factor treatment. These results indicate a family of calcium-dependant binding proteins, some of which are phosphorylated, associated with the submembranous cytoskeleton of syncytiotrophoblast microvilli.

  19. Characterization of human placental alkaline phosphatase by activity and protein assays, capillary electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

    NARCIS (Netherlands)

    Eriksson, H J; Somsen, G W; Hinrichs, W L; Frijlink, H W; de Jong, G J

    2001-01-01

    Placental alkaline phosphatase (PLAP) that had been isolated from human placenta was further purified using subsequent ion-exchange chromatography (IEC), affinity chromatography (AC) and centrifugal membrane concentration (CMC). During the process, the PLAP samples from the different stages of

  20. L-carnitine is synthesized in the human fetal-placental unit: potential roles in placental and fetal metabolism

    NARCIS (Netherlands)

    Oey, N. A.; van Vlies, N.; Wijburg, F. A.; Wanders, R. J. A.; Attie-Bitach, T.; Vaz, F. M.

    2006-01-01

    Carnitine plays an indispensable role in fatty acid oxidation. Previous studies revealed that fetal carnitine is derived from the mother via transplacental transfer. Recent studies demonstrated the presence and importance of an active fatty acid oxidation system in the human placenta and in the

  1. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Visvader, J.; Verma, I.M. (Salk Inst. for Biological Studies, San Diego, CA (USA))

    1989-03-01

    Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage or promoters, separated by approximately 25 kilobases, in cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts.

  2. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes.

    Science.gov (United States)

    Visvader, J; Verma, I M

    1989-01-01

    Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage of promoters, separated by approximately 25 kilobases, in a cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts. Images PMID:2524648

  3. Gas chromatography-mass spectrometric study of 19-oxygenation of the aromatase inhibitor 19-methylandrostenedione with human placental microsomes.

    Science.gov (United States)

    Numazawa, Mitsuteru; Nagaoka, Masao; Handa, Wakako; Yamada, Akane

    2006-06-01

    To gain insight into the catalytic function of aromatase, we studied 19-oxygenation of 19-methyl-substituted derivative of the natural substrate androstenedione (AD), compound 1, with human placental aromatase by use of gas chromatography-mass spectrometry (GC-MS). Incubation of the 19-methyl derivative 1 with human placental microsomes in the presence of NADPH under an aerobic condition did not yield a detectable amount of [19S]19-hydroxy product 2 or its [19R]-isomer 3 when the product was analyzed as the bis-methoxime-trimethylsilyl (TMS) derivative by GC-MS; moreover, the production of estrogen was not detected as the bis-TMS derivative of estradiol (detection limit: about 3 ng and 10 pg per injection for the 19-ol and estradiol, respectively). The results reveal that the 19-methyl steroid 1 does not serve as a substrate of aromatase, although it does serve as a powerful inhibitor of the enzyme.

  4. Characterization of human placental glycosaminoglycans and regional binding to VAR2CSA in malaria infected erythrocytes

    DEFF Research Database (Denmark)

    Beaudet, Julie M; Mansur, Leandra; Joo, Eun Ji

    2014-01-01

    Placental malaria is a serious problem in sub-Saharan Africa. Young women are particular susceptible to contracting this form of malaria during their first or second pregnancy despite previously acquired immunity from past infections. Placental malaria is caused by Plasmodium falciparum parasites...... expressing VAR2CSA on the erythrocyte surface. This protein adheres to a low-sulfated chondroitin sulfate-A found in placental tissue causing great harm to both mother and developing fetus. In rare cases, the localization of infected erythrocytes to the placenta can even result in the vertical transmission...... of malaria. In an effort to better understand this infection, chondroitin sulfate was isolated from the cotyledon part of the placenta, which should be accessible for parasite adhesion, as well as two non-accessible parts of the placenta to serve as controls. The placental chondroitin sulfate structures...

  5. Chromosomal Mosaicism in Human Feto-Placental Development: Implications for Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Francesca Romana Grati

    2014-07-01

    Full Text Available Chromosomal mosaicism is one of the primary interpretative issues in prenatal diagnosis. In this review, the mechanisms underlying feto-placental chromosomal mosaicism are presented. Based on the substantial retrospective diagnostic experience with chorionic villi samples (CVS of a prenatal diagnosis laboratory the following items are discussed: (i The frequency of the different types of mosaicism (confined placental, CPM, and true fetal mosaicisms, TFM; (ii The risk of fetal confirmation after the detection of a mosaic in CVS stratified by chromosome abnormality and placental tissue involvement; (iii The frequency of uniparental disomy for imprinted chromosomes associated with CPM; (iv The incidence of false-positive and false-negative results in CVS samples analyzed by only (semi-direct preparation or long term culture; and (v The implications of the presence of a feto-placental mosaicism for microarray analysis of CVS and non-invasive prenatal screening (NIPS.

  6. Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: Implications for trophoblastic invasion of the placental bed

    OpenAIRE

    Sinai Talaulikar, V; Kronenberger, K; Bax, BE; Moss, R; Manyonda, I

    2014-01-01

    AIM:\\ud The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis.\\ud METHODS:\\ud We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 1...

  7. Heightened pro-inflammatory effect of preeclamptic placental microvesicles on peripheral blood immune cells in humans.

    Science.gov (United States)

    Holder, Beth S; Tower, Clare L; Jones, Carolyn J P; Aplin, John D; Abrahams, Vikki M

    2012-04-01

    Normal pregnancy is associated with the presence of circulating placental microvesicles (MVs). Increased MV shedding and altered immune activation are seen in patients with preeclampsia, suggesting that placental MVs may play a role in the pathophysiology of this disease. Therefore, the aim of this study was to investigate the activation of peripheral blood mononuclear cells (PBMCs) by MVs shed by first-trimester, normal term, and preeclamptic term placenta. First-trimester and preeclamptic term, but not normal term, placental-derived MVs activated PBMCs, as evidenced by elevated IL1B. Significant changes were also seen with several other cytokines and chemokines, and in general when compared to normal term MVs, preeclamptic MVs induced a greater pro-inflammatory response in PBMCs. Pretreatment of PBMCs with first-trimester or normal term placental MVs resulted in a dampened IL1B response to a subsequent lipopolysaccharide (LPS) challenge. In contrast, treatment of PBMCs with preeclamptic term placental MVs exacerbated the LPS response. This was also the case for several other cytokines and chemokines. These studies suggest that placental MVs can modulate basal peripheral immune cell activation and responsiveness to LPS during normal pregnancy, and that in preeclampsia this effect is exacerbated.

  8. All-Inside Versus Inside-Out Meniscal Repair With Concurrent Anterior Cruciate Ligament Reconstruction: A Meta-regression Analysis .

    Science.gov (United States)

    Westermann, Robert W; Duchman, Kyle R; Amendola, Annunziato; Glass, Natalie; Wolf, Brian R

    2017-03-01

    Meniscal tears are frequently repaired during anterior cruciate ligament reconstruction (ACLR). To systematically evaluate differences in clinical failures between all-inside and inside-out meniscal repairs performed during ACLR. Meta-analysis; Level of evidence, 4. A systematic review was perfomed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases queried included MEDLINE, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials. All English-language studies reporting failure rates after meniscal repair with either the all-inside or inside-out technique performed in conjunction with ACLR were identified between 1980 and 2015. Studies with a minimum 2-year follow-up were included. Reported outcomes, clinical meniscal repair failures, and complications were assessed. Studies were weighted according to the size of the clinical series and mean follow-up length. Inverse-variance-weighted mixed models were used to evaluate whether there was a significant difference in pooled reoperation rates between repair techniques. In total, 21 studies met inclusion criteria. Of these, 13 studies reported outcomes after all-inside repair, and 10 studies reported outcomes after inside-out repair (2 studies reported both). A total of 1126 patients were included in the analysis. The mean (±SD) follow-up for all-inside repair was 58.64 ± 22.24 months versus 76.25 ± 31.69 months for inside-out repair ( P = .13). The clinical failure rate for all-inside meniscal repair performed concurrently with ACLR was 16% (121/744) compared with 10% (39/382) for inside-out repair, and this was found to be significant ( P = .016). Implant irritation and device migration were the most common complications reported for all-inside repair; complication rates did not differ between the groups. There may be fewer early clinical failures when the inside-out technique is utilized for meniscal repair at the time of concomitant ACLR

  9. Raft partitioning and dynamic behavior of human placental alkaline phosphatase in giant unilamellar vesicles.

    Science.gov (United States)

    Kahya, Nicoletta; Brown, Deborah A; Schwille, Petra

    2005-05-24

    Much attention has recently been drawn to the hypothesis that cellular membranes organize in functionalized platforms called rafts, enriched in sphingolipids and cholesterol. The notion that glycosylphosphatidylinositol (GPI)-anchored proteins are strongly associated with rafts is based on their insolubility in nonionic detergents. However, detergent-based methodologies for identifying raft association are indirect and potentially prone to artifacts. On the other hand, rafts have proven to be difficult to visualize and investigate in living cells. A number of studies have demonstrated that model membranes provide a valuable tool for elucidating some of the raft properties. Here, we present a model membrane system based on domain-forming giant unilamellar vesicles (GUVs), in which the GPI-anchored protein, human placental alkaline phosphatase (PLAP), has been functionally reconstituted. Raft morphology, protein raft partitioning, and dynamic behavior have been characterized by fluorescence confocal microscopy and fluorescence correlation spectroscopy (FCS). Approximately 20-30% of PLAP associate with sphingomyelin-enriched domains. The affinity of PLAP for the liquid-ordered (l(o)) phase is compared to that of a nonraft protein, bacteriorhodopsin. Next, detergent extraction was carried out on PLAP-containing GUVs as a function of temperature, to relate the lipid and protein organization in distinct phases of the GUVs to the composition of detergent resistant membranes (DRMs). Finally, antibody-mediated cross-linking of PLAP induces a shift of its partition coefficient in favor of the l(o) phase.

  10. Regulation of progesterone receptor A and B expression in human preterm, term, and postterm placental villi.

    Science.gov (United States)

    Ziyan, Jiang; Huaibin, Ren; Xiaotian, Ma; Guangtong, She; Xiaoqing, Chen; Zijiang, Dong; Ziyue, Jiang; We, De; Lizhou, Sun

    2010-05-01

    The progesterone receptor (PR)-A/B ratio in the myometrium is reported to be closely related to labor onset. This might represent a potential target for therapeutic interventions for postterm and preterm deliveries, though the mechanisms currently remain unknown. The aim of this study was to investigate the regulation mechanism of PR-A and B expression in human preterm, term, and postterm placental villi. Experimental study. People's Hospital of Jiangsu Province, China. Singleton women of preterm (PRNIL, not in labor, n = 10), term (TNIL, not in labor, n = 10; TIL, in labor, n = 10), and postterm (PONIL, not in labor, n = 10) cesarean deliveries. The PR-A/PR-B mRNA and protein ratios were analyzed using real-time reverse transcription-polymerase chain reaction and western blots in villi from preterm, term, postterm groups. PONIL and PRNIL villi were incubated with prostaglandin F(2alpha) (PG) and indomethacin for 72 hours, respectively, and the PR-A/PR-B mRNA and protein ratios and p38 signaling pathway were explored. The PR-A/PR-B ratio was highest in TIL, followed by PRNIL, PONIL and TNIL. Indomethacin significantly up-regulated PR-B expression, thereby decreasing the PR-A/PR-B ratio (p postterm deliveries.

  11. Expression of human placental lactogen and variant growth hormone genes in placentas.

    Science.gov (United States)

    Martinez-Rodriguez, H G; Guerra-Rodriguez, N E; Iturbe-Cantu, M A; Martinez-Torres, A; Barrera-Saldaña, H A

    1997-01-01

    Previous studies comparing the expression levels of human placental lactogen (hPL) genes have shown varying results, due to, perhaps, the fact that in all of them only one placenta was being analyzed. Here, the expression of hPL and growth hormone variant (hGH-V) genes in fifteen term placentas was comparatively analyzed at the RNA level, using reverse transcription coupled to polymerase chain reaction (RT-PCR). The abundance of the combined RNA transcripts derived from these genes varied from one placenta to another. The authors found that hPL-4 transcripts were more abundant than those of hPL-3 in most samples (ratios from 1:1 to 6:1), transcripts from the putative hPL-1 pseudogene were more abundant at the unprocessed stage while those of the hGH-V gene were mostly processed. Again, the authors of this study observed wide variation from placenta to placenta in the abundance of both of these types of transcripts. The same was observed when a group of six placentas from abortuses and nine from pregnancies complicated by preclampsia, diabetes and hypertension was studied. The authors conclude that the disagreeing results reported in the literature which are not in agreement concerning the expression levels of hPL genes could be explained by normal variations of their expression levels among the different placentas analyzed.

  12. Placental chorangioma

    African Journals Online (AJOL)

    nonimmune fetal hydrops, fetal heart failure, cardiomegaly, intrauterine growth restriction, fetal anemia, thrombocytopenia, and fetal demise. Maternal complications such as preeclampsia, ... Key words: Kano; live birth; placental chorangioma; Pregnancy. Introduction. Placental chorangioma is a rare tumor of the placenta ...

  13. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    Directory of Open Access Journals (Sweden)

    Elisavet Vasilopoulou

    Full Text Available Monocarboxylate transporter 8 (MCT8 is a well-established thyroid hormone (TH transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05 and primary cytotrophoblast (15%, P<0.05. MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05. Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05. Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05 and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05. In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05 but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05. However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in

  14. Ectopic Reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex.

    Science.gov (United States)

    Kubo, Ken-ichiro; Honda, Takao; Tomita, Kenji; Sekine, Katsutoshi; Ishii, Kazuhiro; Uto, Asuka; Kobayashi, Kazuma; Tabata, Hidenori; Nakajima, Kazunori

    2010-08-18

    Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Reln(rl)). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.

  15. Reinforcement of integrin-mediated T-Lymphocyte adhesion by TNF-induced Inside-out Signaling.

    Science.gov (United States)

    Li, Qian; Huth, Steven; Adam, Dieter; Selhuber-Unkel, Christine

    2016-07-28

    Integrin-mediated leukocyte adhesion to endothelial cells is a crucial step in immunity against pathogens. Whereas the outside-in signaling pathway in response to the pro-inflammatory cytokine tumour necrosis factor (TNF) has already been studied in detail, little knowledge exists about a supposed TNF-mediated inside-out signaling pathway. In contrast to the outside-in signaling pathway, which relies on the TNF-induced upregulation of surface molecules on endothelium, inside-out signaling should also be present in an endothelium-free environment. Using single-cell force spectroscopy, we show here that stimulating Jurkat cells with TNF significantly reinforces their adhesion to fibronectin in a biomimetic in vitro assay for cell-surface contact times of about 1.5 seconds, whereas for larger contact times the effect disappears. Analysis of single-molecule ruptures further demonstrates that TNF strengthens sub-cellular single rupture events at short cell-surface contact times. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte initial adhesion machinery.

  16. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta.

    Science.gov (United States)

    Malek, Antoine

    2010-01-01

    An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the

  17. The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens

    Directory of Open Access Journals (Sweden)

    Yong Mao

    2018-01-01

    Full Text Available Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

  18. The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens.

    Science.gov (United States)

    Mao, Yong; Singh-Varma, Anya; Hoffman, Tyler; Dhall, Sandeep; Danilkovitch, Alla; Kohn, Joachim

    2018-01-08

    Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers) clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM) resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT) on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

  19. Turning Ideologies inside Out: Developing Young Readers' Empathy for Critical Voices in Narrative Fiction

    Science.gov (United States)

    Pereira, Íris Susana Pires; Campos, Ângela

    2014-01-01

    This article is located at the crossroads between two distinctive human traits, empathy and rational thought, with narrative emerging as a particularly powerful means to enable young readers to bring them together. Specifically, we discuss the role that critical literary exegesis plays in the development of empathic consciousness in literary…

  20. An inside-out vein graft filled with platelet-rich plasma for repair of a short sciatic nerve defect in rats.

    Science.gov (United States)

    Kim, Ji Yeong; Jeon, Woo Joo; Kim, Dong Hwee; Rhyu, Im Joo; Kim, Young Hwan; Youn, Inchan; Park, Jong Woong

    2014-07-15

    Platelet-rich plasma containing various growth factors can promote nerve regeneration. An inside-out vein graft can substitute nerve autograft to repair short nerve defects. It is hypothesized that an inside-out vein graft filled with platelet-rich plasma shows better effects in the repair of short sciatic nerve defects. In this study, an inside-out vein autograft filled with platelet-rich plasma was used to bridge a 10 mm-long sciatic nerve defect in rats. The sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better improved than that of rats with a simple inside-out vein autograft. At 6 and 8 weeks, the sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better than that of rats undergoing nerve autografting. Compared with the sciatic nerve repaired with a simple inside-out vein autograft, the number of myelinated axons was higher, axon diameter and myelin sheath were greater in the sciatic nerve repaired with an inside-out vein autograft filled with platelet-rich plasma and they were similar to those in the sciatic nerve repaired with nerve autograft. These findings suggest that an inside-out vein graft filled with platelet-rich plasma can substitute nerve autograft to repair short sciatic nerve defects.

  1. In vivo assessment of putative functional placental tissue volume in placental intrauterine growth restriction (IUGR) in human fetuses using diffusion tensor magnetic resonance imaging.

    Science.gov (United States)

    Javor, D; Nasel, C; Schweim, T; Dekan, S; Chalubinski, K; Prayer, D

    2013-08-01

    Intrauterine growth restriction (IUGR) is a diagnostic challenge, since ultrasound fetal biometry (UFB) provides only a 50% detection rate for IUGR. This may be attributable to the fact that UFB does not allow a direct evaluation of functional placental tissue. We hypothesized that direct assessment, using magnetic resonance diffusion tensor imaging (DT-MRI), can provide better detection of IUGR by reliably distinguishing between normal and non-functional placental tissue. Patients with normal placenta function (n = 21) and suspected IUGR (n = 14) according to UFB were examined. DT-MRI-based properties of areas of the placenta that were judged to represent normal functional tissue, in normal pregnancies, were used to perform volumetry of the putative functional placental tissue (PFPT) in a control- and an IUGR-group. Fractional anisotropy (FRC), as well as maximum and mean diffusivity were also calculated. PFPT volumetry showed a significant reduction of functional placental tissue in the IUGR group of up to 33%. Analysis of global PFPT, maximum diffusivity, mean diffusivity, and FRC also showed a significant difference. PFPT volume is dramatically reduced in IUGR. Several DT-MRI parameters suggest an additional placental micro-architecture disturbance in IUGR. PFPT volumetry appears to be a promising tool for improving the detection of IUGR. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Modelling nutrient transfer based on 3D imaging of the human placental microstructure.

    Science.gov (United States)

    Perazzolo, S; Lewis, R M; Sengers, B G

    2016-08-01

    Impaired transfer of nutrients from mother to fetus can affect pregnancy outcomes. The placenta has a complex microstructure, including the maternal intervillous space and fetal capillaries. Previous computational models of placental transfer either assumed a simplified idealized local geometry or were based on 2D imaging. In this study, we present a novel 3D computational model to assess the placental transfer of nutrients at the microscale in interaction with the maternal flow environment. A stack of confocal microscopy images of the placental terminal villi was collected and reconstructed. The 3D simulation framework was tested for the transport of oxygen. Preliminary results identified local stagnant zones, as well as areas of high nutrient transfer into the fetal capillaries in the most exposed branches of the villi as a result of better perfusion, combined with a smaller thickness of the tissue barrier. Overall, the current model may serve as a tool for assessing pregnancy conditions affected by inefficient nutrient transfer due to altered microscale placental morphology.

  3. Reactivity of human placental chorionic plate vessels from pregnancies complicated by intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Wareing, Mark; Greenwood, Susan L; Fyfe, Gregor K; Baker, Philip N

    2006-10-01

    A successful pregnancy is dependent on liberal placental perfusion via the maternal and fetal circulations. Doppler waveform analyses of umbilical arteries suggest increased resistance to flow in the fetoplacental circulation of pregnancies complicated by intrauterine growth restriction (IUGR). Neither the site nor the mediators responsible for this altered vascular reactivity are known, to date. In placentas in normal pregnancy, reduced oxygenation promotes contraction of the in vitro-perfused placental cotyledon and modulates agonist-induced contraction of chorionic plate arteries and veins. Placental oxygenation has also been suggested to be reduced in IUGR. We tested the hypothesis that oxygen tension could directly modify placental chorionic plate vessel vasoreactivity in IUGR. Small arteries and veins from the chorionic plate were dissected from biopsies from placentas of pregnancies complicated by IUGR and were studied using parallel wire myography. Vasoconstriction at 20%, 7%, and 2% oxygen was assessed utilizing the thromboxane mimetic U46619. Experiments were also performed in the presence of 4-aminopyridine (4AP), a blocker of voltage-gated potassium channels. Increased oxygenation reduced venous vasoconstriction but did not modify arterial vasoconstriction. 4AP increased basal tone in arteries and veins. We suggest that venoconstriction in response to hypoxia may provide a mechanism for increased fetoplacental vascular resistance associated with IUGR.

  4. DREAM mediated regulation of GCM1 in the human placental trophoblast.

    Science.gov (United States)

    Baczyk, Dora; Kibschull, Mark; Mellstrom, Britt; Levytska, Khrystyna; Rivas, Marcos; Drewlo, Sascha; Lye, Stephen J; Naranjo, Jose R; Kingdom, John C P

    2013-01-01

    The trophoblast transcription factor glial cell missing-1 (GCM1) regulates differentiation of placental cytotrophoblasts into the syncytiotrophoblast layer in contact with maternal blood. Reduced placental expression of GCM1 and abnormal syncytiotrophoblast structure are features of hypertensive disorder of pregnancy--preeclampsia. In-silico techniques identified the calcium-regulated transcriptional repressor--DREAM (Downstream Regulatory Element Antagonist Modulator)--as a candidate for GCM1 gene expression. Our objective was to determine if DREAM represses GCM1 regulated syncytiotrophoblast formation. EMSA and ChIP assays revealed a direct interaction between DREAM and the GCM1 promoter. siRNA-mediated DREAM silencing in cell culture and placental explant models significantly up-regulated GCM1 expression and reduced cytotrophoblast proliferation. DREAM calcium dependency was verified using ionomycin. Furthermore, the increased DREAM protein expression in preeclamptic placental villi was predominantly nuclear, coinciding with an overall increase in sumolylated DREAM and correlating inversely with GCM1 levels. In conclusion, our data reveal a calcium-regulated pathway whereby GCM1-directed villous trophoblast differentiation is repressed by DREAM. This pathway may be relevant to disease prevention via calcium-supplementation.

  5. DREAM mediated regulation of GCM1 in the human placental trophoblast.

    Directory of Open Access Journals (Sweden)

    Dora Baczyk

    Full Text Available The trophoblast transcription factor glial cell missing-1 (GCM1 regulates differentiation of placental cytotrophoblasts into the syncytiotrophoblast layer in contact with maternal blood. Reduced placental expression of GCM1 and abnormal syncytiotrophoblast structure are features of hypertensive disorder of pregnancy--preeclampsia. In-silico techniques identified the calcium-regulated transcriptional repressor--DREAM (Downstream Regulatory Element Antagonist Modulator--as a candidate for GCM1 gene expression. Our objective was to determine if DREAM represses GCM1 regulated syncytiotrophoblast formation. EMSA and ChIP assays revealed a direct interaction between DREAM and the GCM1 promoter. siRNA-mediated DREAM silencing in cell culture and placental explant models significantly up-regulated GCM1 expression and reduced cytotrophoblast proliferation. DREAM calcium dependency was verified using ionomycin. Furthermore, the increased DREAM protein expression in preeclamptic placental villi was predominantly nuclear, coinciding with an overall increase in sumolylated DREAM and correlating inversely with GCM1 levels. In conclusion, our data reveal a calcium-regulated pathway whereby GCM1-directed villous trophoblast differentiation is repressed by DREAM. This pathway may be relevant to disease prevention via calcium-supplementation.

  6. Turning body and self inside out: visualized heartbeats alter bodily self-consciousness and tactile perception.

    Science.gov (United States)

    Aspell, Jane Elizabeth; Heydrich, Lukas; Marillier, Guillaume; Lavanchy, Tom; Herbelin, Bruno; Blanke, Olaf

    2013-12-01

    Prominent theories highlight the importance of bodily perception for self-consciousness, but it is currently not known whether bodily perception is based on interoceptive or exteroceptive signals or on integrated signals from these anatomically distinct systems. In the research reported here, we combined both types of signals by surreptitiously providing participants with visual exteroceptive information about their heartbeat: A real-time video image of a periodically illuminated silhouette outlined participants' (projected, "virtual") bodies and flashed in synchrony with their heartbeats. We investigated whether these "cardio-visual" signals could modulate bodily self-consciousness and tactile perception. We report two main findings. First, synchronous cardio-visual signals increased self-identification with and self-location toward the virtual body, and second, they altered the perception of tactile stimuli applied to participants' backs so that touch was mislocalized toward the virtual body. We argue that the integration of signals from the inside and the outside of the human body is a fundamental neurobiological process underlying self-consciousness.

  7. A biomechanical evaluation of all-inside 2-stitch meniscal repair devices with matched inside-out suture repair.

    Science.gov (United States)

    Ramappa, Arun J; Chen, Alvin; Hertz, Benjamin; Wexler, Michael; Grimaldi Bournissaint, Leandro; DeAngelis, Joseph P; Nazarian, Ara

    2014-01-01

    Many all-inside suture-based devices are currently available, including the Meniscal Cinch, FasT-Fix, Ultra FasT-Fix, RapidLoc, MaxFire, and CrossFix System. These different devices have been compared in various configurations, but to our knowledge, the Sequent meniscal repair device, which applies running sutures, has not been compared with the Ultra FasT-Fix, nor has it been compared with its suture, No. 0 Hi-Fi, using an inside-out repair technique. To assess the quality of the meniscal repair, all new devices should be compared with the gold standard: the inside-out repair. To that end, this study aims to compare the biomechanical characteristics of running sutures delivered by the Sequent meniscal repair device with 2 vertical mattress sutures applied using the Ultra FasT-Fix device and with 2 vertical mattress sutures using an inside-out repair technique with No. 0 Hi-Fi suture. Controlled laboratory study. Paired (medial and lateral), fresh-frozen porcine menisci were randomly assigned to 1 of 3 groups: Sequent (n = 17), Ultra FasT-Fix (n = 19), and No. 0 Hi-Fi inside-out repair (n = 20). Bucket-handle tears were created in all menisci and were subjected to repair according to their grouping. Once repaired, the specimens were subjected to cyclic loading (100, 300, and 500 cycles), followed by loading to failure. The Sequent and Ultra FasT-Fix device repairs and the suture repair exhibited low initial displacements. The Sequent meniscal repair device demonstrated the lowest displacement in response to cyclic loading. No. 0 Hi-Fi suture yielded the highest load to failure. With the development of the next generation of all-inside meniscal repair devices, surgeons may use these findings to select the method best suited for their patients. The Sequent meniscal repair device displays the least amount of displacement during cyclic loading but has a similar failure load to other devices.

  8. Can washing socks without flipping inside out cause hair tourniquet syndrome? A claim with two case reports.

    Science.gov (United States)

    Uygur, Esat; Çarkçi, Engin; Ünkar, Ethem

    2017-03-01

    Hair tourniquet syndrome (HTS) is a rare, painful condition that results when hair or pieces of thread become wrapped tightly around toes, fingers, or other appendages, occluding blood flow and causing strangulation or amputation. Although the aetiology of HTS is unclear, we postulate that washing baby socks in a washing machine without turning them inside out might be a cause. Mothers should be informed about HTS and this simple prevention method should be suggested to them. Here, we present two cases of HTS and discuss possible causes.

  9. Prevalence of asymptomatic and electrically undetectable intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST implantable cardioverter-defibrillator leads.

    Science.gov (United States)

    Schmutz, Mathieu; Delacrétaz, Etienne; Schwick, Nicola; Roten, Laurent; Fuhrer, Jürg; Boesch, Claudia; Tanner, Hildegard

    2013-07-15

    Recently, several cases of symptomatic and/or electrically detectable intracardiac inside-out abrasions in silicon-coated Riata® and Riata® ST leads have been described. However, the prevalence in asymptomatic patients with unremarkable implantable cardioverter defibrillator (ICD) interrogation is unknown. The aim of this study was to determine the prevalence of asymptomatic and electrically undetectable intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST leads. All 52 patients with an active silicone-coated Riata® and Riata® ST lead followed up in our outpatient clinic were scheduled for a premature ICD interrogation and a biplane chest radiograph. When an intracardiac inside-out abrasion was suspected, this finding was confirmed by fluoroscopy. Mean time since implantation was 71 ± 18 months. An intracardiac inside-out abrasion was confirmed by fluoroscopy in 6 patients (11.5%). Mean time from lead implantation to detection of intracardiac inside-out abrasion was 79 ± 14 months. In all patients with an intracardiac inside-out abrasion, ICD interrogation showed normal and stable electrical parameters. Retrospectively, in 4 of these 6 patients, a coronary angiography performed 25 ± 18 months before diagnosis of intracardiac inside-out abrasion already showed the defect. Despite undetected intracardiac inside-out abrasion, 2 of these 4 patients experienced adequate antitachycardia pacing and ICD-shocks. ICD leads were replaced in all 6 patients. The prevalence of asymptomatic intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST leads is higher than 10% when assessed by fluoroscopy, and most intracardiac inside-out abrasions are not detectable by ICD interrogation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Coumestrol induces mitochondrial dysfunction by stimulating ROS production and calcium ion influx into mitochondria in human placental choriocarcinoma cells.

    Science.gov (United States)

    Lim, Whasun; Yang, Changwon; Jeong, Muhah; Bazer, Fuller W; Song, Gwonhwa

    2017-11-01

    Does coumestrol inhibit proliferation of human placental choriocarcinoma cells? Coumestrol promotes cell death in the choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways and through disruption of Ca2+ and ROS homeostasis. A number of patients who suffer from choriocarcinomas fail to survive due to delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy using platinum-based agents and methotrexate. To overcome these limitations, it is important to discover novel compounds which have no adverse effects yet can inhibit the expression of a target molecule to develop, as a novel therapeutic for prevention and/or treatment of choriocarcinomas. Effects of coumestrol on human placental choriocarcinoma cell lines, JAR and JEG3, were assessed in diverse assays in a dose- and time-dependent manner. Effects of coumestrol on cell proliferation, apoptosis (annexin V expression, propidium iodide staining, TUNEL and invasion assays), mitochondria-mediated apoptosis, production of reactive oxygen species (ROS), lipid peroxidation, glutathione levels and endoplasmic reticulum (ER) stress proteins in JAR and JEG3 cells were determined. Signal transduction pathways in JAR and JEG3 cells in response to coumestrol were determined by western blot analyses. Results of the present study indicated that coumestrol suppressed proliferation and increased apoptosis in JAR and JEG3 cells by inducing pro-apoptotic proteins, Bax and Bak. In addition, coumestrol increased ROS production, as well as lipid peroxidation and glutathione levels in JAR and JEG3 cells. Moreover, coumestrol-induced depolarization of mitochondrial membrane potential (MMP) and increased cytosolic and mitochondrial Ca2+ levels in JAR and JEG3 cells. Consistent with those results, treatment of JAR and JEG3 cells with a Ca2+ chelator and an inhibitor of IP3 receptor decreased coumestrol-induced depolarization of MMP and increased proliferation in JAR and JEG3 cells. N/A. A

  11. The effect of pH and ion channel modulators on human placental arteries.

    Directory of Open Access Journals (Sweden)

    Tayyba Y Ali

    Full Text Available Chorionic plate arteries (CPA are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4-6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n = 9 relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n = 6, pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n = 6; p<0.001 at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM gave a maximum relaxation of 72±5% (n = 8; p<0.01 which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6. Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

  12. Stem cell collection filter system for human placental/umbilical cord blood processing.

    Science.gov (United States)

    Yasutake, M; Sumita, M; Terashima, S; Tokushima, Y; Nitadori, Y; Takahashi, T A

    2001-02-01

    The hydroxyethyl starch method and the Top & Bottom method have been used worldwide for the volume reduction of human placental/umbilical cord blood (PCB) units. To simplify the preparation of nucleated cell (NC) concentrates, we developed a new filter device--the stem cell collection filter system (SCF SYSTEM)--which can collect mononuclear cells (MNC) at a high recovery rate. The SCF SYSTEM consisted of a filter and two bags. Multilayered polyethylene terephthalate non-wovens, coated with a hydrophilic polymer, were used as filter media. PCB units were filtered by gravity (n = 12). Red blood cells, platelets and plasma were drained into the drain bag, and the NC trapped on the filter media was collected in the recovery bag by reverse washing. Recovered cell fractions were evaluated. The volume of cell concentrate recovered was 27.4 +/- 2.2 ml (mean +/- SD, n = 12). The whole time required for processing was less than 30 min, and handling was very simple. The viability of recovered NC was 97.8 +/- 3.2%. The recovery of lymphocytes, monocytes and granulocytes was 79.5 +/- 16.9%, 79.8 +/- 20.4% and 39.0 +/- 19.5%, respectively. The recovery rate of granulocytes was significantly lower than that of monocytes and lymphocytes (P < or = 0.0001). The recovery rates of CD3+ cells, CD19+ cells and CD56+ cells were almost the same as that of MNC. The recovery rates of CD34+ cells, total colony-forming cells and long-term culture-initiating cells were 81.7 +/- 27.0% (n = 11), 80.8 +/- 27.7% (n = 12) and 75.0 +/- 18.4% (n = 2), respectively. The new filter system was shown to be efficient for PCB processing, encompassing a very simple handling procedure with a good recovery of haematopoietic progenitor cells. Hence, the SCF SYSTEM is potentially useful for the volume reduction of PCB units for cord blood banking.

  13. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

    Science.gov (United States)

    Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

    2017-11-07

    Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in

  14. From the Inside Out

    Science.gov (United States)

    Fillingim, Jennifer G.; Barlow, Angela T.

    2010-01-01

    Mathematics educators promote student engagement in the Process Standards and create problem-solving tasks and facilitate discussions to help their students develop strengths in explaining their methods, using and interpreting multiple representations, and making connections between topics. They are excited and encouraged when they see students…

  15. Inside out Vessels

    Science.gov (United States)

    Fatimi, Safia

    2008-01-01

    The author finds clay a wonderful introductory medium for high-school studio art. It is not intimidating and gives students the opportunity to express directly with their hands. This article describes the author's clay project that she introduced to her students. The clay project required students to portray their inside and outside personalities…

  16. Zika virus damages the human placental barrier and presents marked fetal neurotropism

    Directory of Open Access Journals (Sweden)

    Lucia de Noronha

    2016-01-01

    Full Text Available An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

  17. Assessing drug transport across the human placental barrier: from in vivo and in vitro measurements to the ex vivo perfusion method and in silico techniques.

    Science.gov (United States)

    Giaginis, Constantinos; Tsantili-Kakoulidou, Anna; Theocharis, Stamatios

    2011-05-01

    Assessing drug transport across the human placental barrier is of vital importance in order to guarantee drug safety during pregnancy. However, due to ethical reasons, in vivo fetal development risk assessment studies related to maternal drugs and chemicals exposure remain extremely limited. To overcome any ethical issues, several in vitro models applying primary trophoblastic cells, immortal cell lines and tissue explants of placental origin have recently been advanced. Alternatively, ex vivo human placental perfusion seems to be a more representative and highly informative method, which offers better insights into the different drug transporters, xenobiotic metabolism and tissue binding. Recently, in silico techniques have further been advanced as complementary tools to validate experimental placental transfer data, offering an attractive alternative for high throughput screening of potential fetotoxicity at the early stages of drug design. The present review scrutinizes, from a critical point of view, the current trends and perspectives in the emerging topic of drug transport across the human placental barrier. The special characteristics of the recently developed biopharmaceuticals on the transplacental transfer process are also discussed.

  18. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturb......Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium....... Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human...... arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged...

  19. Placental economies

    DEFF Research Database (Denmark)

    Lee, Jieun

    2016-01-01

    Thinking with the vital materiality of placentas as it is evinced in a placental stem cell research lab in Korea, this article explores the relations and practices of care that are essential to the circulation of biological matters as infrastructure of tissue economies. I attend to the flows...... of care that sustain tissue economies with the notion of ‘placental economies’. Shifting attention from donor subjects and tissue objects to practices and relations of care as an infrastructure for the circulation of tissues, I explore how the vitality of biological matters is an achievement made...

  20. Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism

    DEFF Research Database (Denmark)

    Immonen, E; Kummu, M; Petsalo, A

    2010-01-01

    Metabolizing enzymes and transporters affect toxicokinetics of foreign compounds (e.g. drugs and carcinogens) in human placenta. The heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a food-borne carcinogen being metabolically activated by cytochrome P450 (CYP) enzymes, especially...... by CYP1A1/2. IQ is also a substrate for ABCG2 transporter. Placental transfer of (14)C-IQ was evaluated in 4-6 h ex vivo human placental perfusions in Finland and Denmark. In Finland placentas were perfused with (14)C-IQ alone (0.5 muM, n = 6) or in combination with GF120918 (inhibitor of ABCG2, 1 muM, n...... = 6) or Ko143 (specific inhibitor of ABCG2, 2 muM, n = 4) to study the role of ABCG2 inhibition in transfer while in Denmark perfusions were performed with (14)C-IQ alone. Critical parameters (leak from fetal to maternal circulation, pH values, blood gases, glucose consumption, the production of h...

  1. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  2. Galaxy evolution. Evidence for mature bulges and an inside-out quenching phase 3 billion years after the Big Bang.

    Science.gov (United States)

    Tacchella, S; Carollo, C M; Renzini, A; Förster Schreiber, N M; Lang, P; Wuyts, S; Cresci, G; Dekel, A; Genzel, R; Lilly, S J; Mancini, C; Newman, S; Onodera, M; Shapley, A; Tacconi, L; Woo, J; Zamorani, G

    2015-04-17

    Most present-day galaxies with stellar masses ≥10(11) solar masses show no ongoing star formation and are dense spheroids. Ten billion years ago, similarly massive galaxies were typically forming stars at rates of hundreds solar masses per year. It is debated how star formation ceased, on which time scales, and how this "quenching" relates to the emergence of dense spheroids. We measured stellar mass and star-formation rate surface density distributions in star-forming galaxies at redshift 2.2 with ~1-kiloparsec resolution. We find that, in the most massive galaxies, star formation is quenched from the inside out, on time scales less than 1 billion years in the inner regions, up to a few billion years in the outer disks. These galaxies sustain high star-formation activity at large radii, while hosting fully grown and already quenched bulges in their cores. Copyright © 2015, American Association for the Advancement of Science.

  3. Inside-out flowers of Lacandonia brasiliana (Triuridaceae) provide new insights into fundamental aspects of floral patterning.

    Science.gov (United States)

    Rudall, Paula J; Alves, Marccus; Sajo, Maria das Graças

    2016-01-01

    Background and Aims. A recently described Brazilian species, Lacandonia brasiliana, shares with its longer established putative sister species from Mexico, L. schismatica, inverted floral patterning (carpels surrounding stamens) that is almost unique among angiosperms. We present a detailed ontogenetic study of L. brasiliana for comparison with other members of the tribe Triurideae (Triuridaceae) to explore the possible evolutionary origins of "inside-out" flowers. Methods. Wild-source populations of L. brasiliana were compared morphologically and ontogenetically with related species of Triurideae, using light and scanning electron microscopy. Key Results. Relatively few morphological differences separate flowers of L. brasiliana and L. schismatica. Both species have tepals with late-developing subapical appendages. In both species, the three central (almost sessile) anthers develop precociously with respect to the carpels; the anthers remain closed, and fertilization is achieved via pollen-tube growth from germinating pollen grains of the same cleistogamous flower. Carpels are initiated on fascicles. Conclusions. The close similarity between the two Lacandonia species makes it unlikely that they arose independently from two separate homeotic transformation events; they could either represent sister species or two populations of a single disjunct species. Our study underlines the problematic generic and species boundaries within Triurideae. We present an evolutionary scenario of character evolution in Triuridaceae. The inside-out Lacandonia flower could have resulted from a stabilized homeotic transformation; this hypothesis is not in conflict with constrasting theories of the origin of the Triuridaceae flower, which coincided with a shift to unisexuality. The unisexual yet highly plastic flowers that are typical of Triuridaceae could have pre-adapted the origin of the extraordinary Lacandonia morphology.

  4. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Alejandra Perez-Sepulveda

    Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

  5. Human placental growth hormone: a potential new biomarker in gestational trophoblastic disease.

    Science.gov (United States)

    Hübener, Christoph; Bidlingmaier, Martin; Wu, Zida; Diebold, Joachim; Delius, Maria; Friese, Klaus; Strasburger, Christian J; Hasbargen, Uwe

    2015-02-01

    Gestational trophoblastic disease (GTD) involves a spectrum of abnormal proliferations arising from the placental villous trophoblast. Although the incidence is low, a biomarker with short serum half-life would be a major clinical advance to monitor surgical and medical treatment reducing the socioeconomic burden of multiple control visits as well as patient's anxiety. Placental growth hormone (hGH-V) plays an important role in the regulation of normal placental growth and has shown angiogenic effects. We aimed to determine by immunohistochemistry (IHC) whether hGH-V is expressed in GTD and whether it can be detected in the patient's blood for potential monitoring of surgical or medical treatment procedures. Tissue and sera were collected from women undergoing treatment for GTD in a tertiary care university hospital. We evaluated partial and complete hydatidiform moles, invasive moles and choriocarcinoma, n=16. Trophoblast specimens were examined by a newly developed IHC set-up for hGH-V in addition to gross morphologic and histopathological examination. Serum samples were analyzed by a highly sensitive hGH-V specific immunoassay. hGH-V was localized in all entities of GTD to the syncytiotrophoblast by immunohistochemistry. Serum hGH-V was detected for the first time in GTD and was present in a high percentage of all analyzed entities. hGH-V can be detected in all entities of GTD by IHC as well as by serum analysis and may therefore serve as a novel biomarker for the disease. Its clinical utility in diagnosis of GTD and monitoring surgical or medical treatment needs to be determined in further studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Longtine, Mark S; Nelson, D Michael

    2013-11-15

    Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that punicalagin limits trophoblast injury in vitro by regulating the levels of p53. We examined the expression of p53, mouse double minute 2 homolog, p21, hypoxia-inducible factor (HIF) α, and selected members of the B cell lymphoma 2 (BCL2) family of proteins in cultured syncytiotrophoblasts exposed to ≤1% oxygen in the absence or presence of punicalagin. We found that punicalagin attenuated hypoxia-induced apoptosis in syncytiotrophoblasts, as quantified by levels of cleaved poly-ADP ribose polymerase. This protective effect was in part mediated by reduced p53 activity shown by decreased expression of p21, lower HIF1α expression, and limited activity of caspases 9 and 3. There was no change in expression of proteins in the BCL2 family, which are also important in apoptosis. The data support a role for downregulation of p53 in the protection of human trophoblasts by punicalagin.

  7. Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage.

    Science.gov (United States)

    Lorenzi, Teresa; Turi, Angelo; Lorenzi, Maria; Paolinelli, Francesca; Mancioli, Francesca; La Sala, Lucia; Morroni, Manrico; Ciarmela, Pasquapina; Mantovani, Angelo; Tranquilli, Andrea Luigi; Castellucci, Mario; Marzioni, Daniela

    2012-01-01

    The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8(th) and 12(th) week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38-40 weeks of gestation was also studied. CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

  8. Placental Expression of CD100, CD72 and CD45 Is Dysregulated in Human Miscarriage

    Science.gov (United States)

    Lorenzi, Maria; Paolinelli, Francesca; Mancioli, Francesca; La Sala, Lucia; Morroni, Manrico; Ciarmela, Pasquapina; Mantovani, Angelo; Tranquilli, Andrea Luigi; Castellucci, Mario; Marzioni, Daniela

    2012-01-01

    Context and Objective The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Patients Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8th and 12th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38–40 weeks of gestation was also studied. Results CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Conclusions Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure. PMID:22606231

  9. Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage.

    Directory of Open Access Journals (Sweden)

    Teresa Lorenzi

    Full Text Available CONTEXT AND OBJECTIVE: The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. PATIENTS: Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8(th and 12(th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38-40 weeks of gestation was also studied. RESULTS: CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. CONCLUSIONS: Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

  10. A prospective trial comparing tension-free vaginal tape and transobturator vaginal tape inside-out for the surgical treatment of female stress urinary incontinence: 1-year followup.

    Science.gov (United States)

    Lee, Kyu-Sung; Han, Deok Hyun; Choi, Yang Su; Yum, Seung Hee; Song, Seung Hun; Doo, Chin Kyung; Choo, Myung-Soo

    2007-01-01

    We prospectively compared the efficacy and safety of tension-free vaginal tape and transobturator vaginal tape inside-out for female stress urinary incontinence. A total of 120 women with stress urinary incontinence were alternately assigned to the tension-free vaginal tape group (60) or the transobturator vaginal tape inside-out group (60). Preoperative evaluation included urodynamic study and a Korean version of the incontinence quality of life questionnaire. One year after operation the surgical result, patient satisfaction, incontinence quality of life questionnaire, long-term complications and uroflowmetry were evaluated in the 2 groups. Patient characteristics were comparable in the 2 groups. Mean +/- SD operative time was significantly shorter in the transobturator vaginal tape inside-out vs the tension-free vaginal tape group (11 +/- 1.4 vs 15 +/- 1.8 minutes). In the transobturator vaginal tape inside-out and the tension-free vaginal tape groups the rates of cure (86.8% and 86.8%), improvement (6.6% and 8.2%) and failure (6.6% and 5.0%, respectively) were similar. Incontinence quality of life questionnaire parameters 1 year after surgery were improved significantly in each group and there was no difference between the 2 groups (p 0.05, respectively). There was no long-term complication in either group. Preoperative urge incontinence resolved in 80% of the tension-free vaginal tape group and in 100% of the transobturator vaginal tape inside-out group. De novo urgency developed in 4 patients (6.6%) in the transobturator vaginal tape inside-out group. The tension-free vaginal tape and transobturator vaginal tape inside-out procedures were minimally invasive and similar in operation related morbidity. Transobturator vaginal tape inside-out appeared to be as effective and safe as tension-free vaginal tape for the surgical treatment of stress urinary incontinence in women at 1-year followup.

  11. Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

    Science.gov (United States)

    Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-01-01

    Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles

  12. Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.

    Science.gov (United States)

    Segond, Nadine; Degrelle, Séverine A; Berndt, Sarah; Clouqueur, Elodie; Rouault, Christine; Saubamea, Bruno; Dessen, Philippe; Fong, Keith S K; Csiszar, Katalin; Badet, Josette; Evain-Brion, Danièle; Fournier, Thierry

    2013-01-01

    Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) plays a major role in placental development, and activation of PPARγ by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARγ target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARγ agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARγ. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by β-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARγ targets and that LOX activity is a negative regulator of trophoblastic cell invasion.

  13. Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.

    Directory of Open Access Journals (Sweden)

    Nadine Segond

    Full Text Available Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ plays a major role in placental development, and activation of PPARγ by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARγ target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARγ agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12, connexin 43 (CX43, deleted in liver cancer 1 (DLC1, dipeptidyl peptidase 4 (DPP4, heme oxygenase 1 (HMOX-1, lysyl oxidase (LOX, plasminogen activator inhibitor 1 (PAI-1 and PPARγ. Among the upregulated genes, lysyl oxidase (LOX was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by β-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARγ targets and that LOX activity is a negative regulator of trophoblastic cell invasion.

  14. Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.

    Directory of Open Access Journals (Sweden)

    Evgeniya E Burkova

    Full Text Available Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.

  15. A short report on knowledge exchange through research-based theatre: ‘Inside out of mind’

    Science.gov (United States)

    Schneider, Justine; Lowe, Stephen; Myers, Tanya; Scales, Kezia; Bailey, Simon; Middleton, Joanne

    2014-01-01

    The short report describes the development from page to stage of a work of theatre based on an ethnographic study. The originating research focused on the work of health care assistants (nurse's aides) whose direct impact on the quality of life of highly dependent people is often overlooked. The research followed hospital personnel on wards specialising in the 'challenging behaviour' associated with dementia in central England. Conventional research outputs failed to engage the health care assistants themselves, so we turned to theatre to remedy this. The development of the field notes into theatre was characterised by the artistic freedom given to the playwright, in contrast to more data-led approaches to theatre making. The account of the process of creating the play, Inside Out of Mind, is followed a description of how the work was received by specialist and general audiences totalling 2000+. The discussion seeks to locate the whole enterprise in relation to the field of research-based theatre and explores how the production and its associated learning events relate to definitions of research-based theatre in the light of recent attempts to encapsulate this broad and diverse methodology. PMID:25103152

  16. Bacterial Genotoxins Promote Inside-Out Integrin β1 Activation, Formation of Focal Adhesion Complexes and Cell Spreading

    Science.gov (United States)

    Levi, Laura; Toyooka, Tatsushi; Patarroyo, Manuel; Frisan, Teresa

    2015-01-01

    Integrins are membrane bound receptors that regulate several cellular processes, such as cell adhesion, migration, survival and proliferation, and may contribute to tumor initiation/progression in cells exposed to genotoxic stress. The extent of integrin activation and its role in cell survival upon intoxication with bacterial genotoxins are still poorly characterized. These toxins induce DNA strand breaks in the target cells and activate the DNA damage response (DDR), coordinated by the Ataxia Telangectasia Mutated (ATM) kinase. In the present study, we demonstrate that induction of DNA damage by two bacterial genotoxins promotes activation of integrin β1, leading to enhanced assembly of focal adhesions and cell spreading on fibronectin, but not on vitronectin. This phenotype is mediated by an ATM-dependent inside-out integrin signaling, and requires the actin cytoskeleton remodeler NET1. The toxin-mediated cell spreading and anchorage-independent survival further relies on ALIX and TSG101, two components of the endosomal sorting complex required for transport (ESCRT), known to regulate integrin intracellular trafficking. These data reveal a novel aspect of the cellular response to bacterial genotoxins, and provide new tools to understand the carcinogenic potential of these effectors in the context of chronic intoxication and infection. PMID:25874996

  17. Development of a novel automated ion channel recording method using "inside-out" whole-cell membranes.

    Science.gov (United States)

    Vasilyev, Dmitry V; Merrill, Thomas L; Bowlby, Mark R

    2005-12-01

    Efforts to develop novel methods for recording from ion channels have been receiving increased attention in recent years. In this study, the authors report a unique "inside-out" whole-cell configuration of patch-clamp recording that has been developed. This method entails adding cells into a standard patch pipette and, with positive pressure, obtaining a gigaseal recording from a cell at the inside tip of the electrode. In this configuration, the cell may be moved through the air, first rupturing part of the cellular membrane and enabling bath access to the intracellular side of the membrane, and then into a series of wells containing differing solutions, enabling robotic control of all the steps in an experiment. The robotic system developed here fully automates the electrophysiological experiments, including gigaseal formation, obtaining whole-cell configuration, data acquisition, and drug application. Proof-of-principle experiments consisting of application of intracellularly acting potassium channel blockers to K+ channel cell lines resulted in a very rapid block, as well as block reversal, of the current. This technique allows compound application directly to the intracellular side of ion channels and enables the dissociation of compound in activities due to cellular barrier limitations. This technique should allow for parallel implementation of recording pipettes and the future development of larger array-based screening methods.

  18. Transobturator vaginal tape inside out for treatment of urethral sphincter mechanism incompetence: preliminary results in 7 female dogs.

    Science.gov (United States)

    Claeys, Stéphanie; de Leval, Jean; Hamaide, Annick

    2010-12-01

    To evaluate the clinical efficacy of the transobturator vaginal tape inside-out (TVT-O) in incontinent female dogs affected with urethral sphincter mechanism incompetence (USMI) and to determine its urodynamic and morphologic effects. Case series. Incontinent spayed female dogs (n=7). TVT-O tape was inserted in 7 incontinent female dogs diagnosed with USMI. Urethral pressure profilometry (UPP) and vaginourethrograms were performed preoperatively, and 1 and 3 months postoperatively. Clinical efficacy of the technique was evaluated and complications reported. Follow-up information was evaluated by a telephone questionnaire. All dogs were continent immediately after the procedure. Incontinence recurred 2 months after surgery in 1 dog and was treated by phenylpropanolamine administration. At mean follow-up time of 11.3 months, 6 of 7 dogs were continent. An iatrogenic urethral tear occurred intraoperatively in 1 dog. No postoperative complications were encountered. The postoperative UPPs showed significantly increased maximal urethral closure pressure and integrated pressure. Postoperative vaginourethrograms were unremarkable. The surgical procedure did not modify the location of the urinary bladder neck in dogs with a "pelvic urinary bladder" preoperatively. TVT-O was efficient in maintaining short term continence in 6 of 7 dogs affected with USMI. © Copyright 2010 by The American College of Veterinary Surgeons.

  19. [Effect of hydrogen peroxide on human leukocyte antigen-G expression in placental trophoblasts in pre-eclampsia].

    Science.gov (United States)

    Zhou, Xue; Sun, Li-zhou; Yin, Yin

    2010-05-01

    To explore the effect of hydrogen peroxide (H2O2) on the expression of human leukocyte antigen-G (HLA-G) in placental trophoblasts in pregnant women with pre-eclampsia. Forty pregnant women, delivered through cesarean section in the Department of Obstetrics of and Gynecology, the First Affiliated Hospital of Nanjing Medical University from October 2008 to October 2009, were enrolled, including 20 women with pre-eclampsia and 20 healthy gravidas (control group). Colorimetry and western blot were applied, respectively, to determine the level of H2O2 and the expression of HLA-G protein in placental tissues and the correlation between them were analyzed. After 24 hours of seeding, JEG-3 cells (the HLA-G positive cell line of choriocarcinoma) were divided into two groups: intervention group (exposure to 175 micromol/L H2O2) and control group (without H2O2). Immunofluorescence and western blot were used to investigate the expression of HLA-G protein in JEG-3 cells at 24 hours and 48 hours after incubation. (1) The level of H2O2 in placenta in the pre-eclampsia group was significantly higher than that in control group [(105+/-13) nmolxmg(-1)xprot(-1) vs (62+/-18) nmol.mg(-1)xprot(-1), PHLA-G protein in placenta of the pre-eclampsia group was reduced by 88% compared with that of the control (0.20+/-0.08 vs 1.67+/-0.65, PHLA-G level and H2O2 expression in the placenta in both groups (r=-0.895, P=0.000). (4) Compared with the control group, the expression of HLA-G protein in JEG-3 cells, after 24 hours and 48 hours exposure to H2O2, reduced by 39% and 80%, respectively, (3.21+/-0.33 vs 1.95+/-0.25 and 0.65+/-0.08, PHLA-G in JEG-E cells in the intervention group at 48 hours compared to the control group (PHLA-G expression in the placental trophoblasts in pre-eclampsia which may be involved in the pathogenesis of pre-eclampsia.

  20. Effect of human placental extract in the management of biofilm mediated drug resistance - A focus on wound management.

    Science.gov (United States)

    Goswami, Sutapa; Sarkar, Ratul; Saha, Pritam; Maity, Amit; Sarkar, Tridib; Das, Debmalya; Chakraborty, Piyali Datta; Bandyopadhyay, Subhasri; Ghosh, Chandan Kumar; Karmakar, Sanmoy; Sen, Tuhinadri

    2017-10-01

    Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration

  1. Star formation is boosted (and quenched) from the inside-out: radial star formation profiles from MaNGA

    Science.gov (United States)

    Ellison, Sara L.; Sánchez, Sebastian F.; Ibarra-Medel, Hector; Antonio, Braulio; Mendel, J. Trevor; Barrera-Ballesteros, Jorge

    2018-02-01

    The tight correlation between total galaxy stellar mass and star formation rate (SFR) has become known as the star-forming main sequence. Using ˜487 000 spaxels from galaxies observed as part of the Sloan Digital Sky Survey Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, we confirm previous results that a correlation also exists between the surface densities of star formation (ΣSFR) and stellar mass (Σ⋆) on kpc scales, representing a `resolved' main sequence. Using a new metric (ΔΣSFR), which measures the relative enhancement or deficit of star formation on a spaxel-by-spaxel basis relative to the resolved main sequence, we investigate the SFR profiles of 864 galaxies as a function of their position relative to the global star-forming main sequence (ΔSFR). For galaxies above the global main sequence (positive ΔSFR) ΔΣSFR is elevated throughout the galaxy, but the greatest enhancement in star formation occurs at small radii (<3 kpc, or 0.5Re). Moreover, galaxies that are at least a factor of 3 above the main sequence show diluted gas phase metallicities out to 2Re, indicative of metal-poor gas inflows accompanying the starbursts. For quiescent/passive galaxies that lie at least a factor of 10 below the star-forming main sequence, there is an analogous deficit of star formation throughout the galaxy with the lowest values of ΔΣSFR in the central 3 kpc. Our results are in qualitative agreement with the `compaction' scenario in which a central starburst leads to mass growth in the bulge and may ultimately precede galactic quenching from the inside-out.

  2. INSIDE OUT AND UPSIDE DOWN: TRACING THE ASSEMBLY OF A SIMULATED DISK GALAXY USING MONO-AGE STELLAR POPULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Bird, Jonathan C.; Kazantzidis, Stelios; Weinberg, David H. [Department of Astronomy, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Guedes, Javiera [Institute for Astronomy, ETH Zuerich, Wolgang-Pauli-Strasse 27, CH-8093 Zuerich (Switzerland); Callegari, Simone [Anthropology Institute and Museum, University of Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich (Switzerland); Mayer, Lucio [Institute for Theoretical Physics, University of Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich (Switzerland); Madau, Piero [Department of Astronomy and Astrophysics, University of California, 1156 High Street, Santa Cruz, CA 95064 (United States)

    2013-08-10

    We analyze the present day structure and assembly history of a high-resolution hydrodynamic simulation of the formation of a Milky-Way-(MW)-like disk galaxy, from the ''Eris'' simulation suite, dissecting it into cohorts of stars formed at different epochs of cosmic history. At z = 0, stars with t{sub form} < 2 Gyr mainly occupy the stellar spheroid, with the oldest (earliest forming) stars having more centrally concentrated profiles. The younger age cohorts populate disks of progressively longer radial scale lengths and shorter vertical scale heights. At a given radius, the vertical density profiles and velocity dispersions of stars vary smoothly as a function of age, and the superposition of old, vertically extended and young, vertically compact cohorts gives rise to a double-exponential profile like that observed in the MW. Turning to formation history, we find that the trends of spatial structure and kinematics with stellar age are largely imprinted at birth, or immediately thereafter. Stars that form during the active merger phase at z > 3 are quickly scattered into rounded, kinematically hot configurations. The oldest disk cohorts form in structures that are radially compact and relatively thick, while subsequent cohorts form in progressively larger, thinner, colder configurations from gas with increasing levels of rotational support. The disk thus forms ''inside out'' in a radial sense and ''upside down'' in a vertical sense. Secular heating and radial migration influence the final state of each age cohort, but the changes they produce are small compared to the trends established at formation. The predicted correlations of stellar age with spatial and kinematic structure are in good qualitative agreement with the correlations observed for mono-abundance stellar populations in the MW.

  3. Differential lead component pulling as a possible mechanism of inside-out abrasion and conductor cable externalization.

    Science.gov (United States)

    Lau, Ernest W

    2013-09-01

    Conductor cable externalization with protrusion (CCE*) is highly prevalent among the Riata 8F and ST 7F defibrillation (DF) leads and infrequently present in the QuickSite and the QuickFlex coronary sinus (CS) leads (St. Jude Medical, Sylmar, CA, USA). A model for CCE* based on differential lead component pulling and conjugate extension with reciprocal compression-bending was developed. Extension of a proximal lead body segment by pectoral or cardiac movements causes reciprocal compression-bending of a distal lead body segment mediated by inextensible conductor cables running down a lead body fixed at various points by fibrous adhesions. The "sawing" action of these cables under tension causes inside-out abrasion of insulation leading to CCE*. DF leads from different manufacturers and the QuickFlex and QuickFlex μ CS leads were subjected to simulated differential pulling. Restitution from differential pulling followed three patterns: complete, partial without escalation, and incomplete with escalation. Only the last pattern (only shown by the Riata 8F and ST 7F leads) was associated with an increased risk to CCE*. For CS leads, deformation concentrated on the more flexible segment when the lead body did not have a uniform construction. The Durata, Riata ST Optim, QuickFlex μ, and Quartet leads should be relatively immune to CCE*. The Durata leads are extremely resistant to longitudinal deformation and probably cause mediastinal displacement rather than differential pulling in response to pectoral movements in vivo. Implantation techniques and lead designs can be used to minimize the risk of CCE*. A bench test for CCE* can be constructed. ©2013, The Author. Journal compilation ©2013 Wiley Periodicals, Inc.

  4. Inside-out flowers of Lacandonia brasiliana (Triuridaceae provide new insights into fundamental aspects of floral patterning

    Directory of Open Access Journals (Sweden)

    Paula J. Rudall

    2016-02-01

    Full Text Available Background and Aims. A recently described Brazilian species, Lacandonia brasiliana, shares with its longer established putative sister species from Mexico, L. schismatica, inverted floral patterning (carpels surrounding stamens that is almost unique among angiosperms. We present a detailed ontogenetic study of L. brasiliana for comparison with other members of the tribe Triurideae (Triuridaceae to explore the possible evolutionary origins of “inside-out” flowers. Methods. Wild-source populations of L. brasiliana were compared morphologically and ontogenetically with related species of Triurideae, using light and scanning electron microscopy. Key Results. Relatively few morphological differences separate flowers of L. brasiliana and L. schismatica. Both species have tepals with late-developing subapical appendages. In both species, the three central (almost sessile anthers develop precociously with respect to the carpels; the anthers remain closed, and fertilization is achieved via pollen-tube growth from germinating pollen grains of the same cleistogamous flower. Carpels are initiated on fascicles. Conclusions. The close similarity between the two Lacandonia species makes it unlikely that they arose independently from two separate homeotic transformation events; they could either represent sister species or two populations of a single disjunct species. Our study underlines the problematic generic and species boundaries within Triurideae. We present an evolutionary scenario of character evolution in Triuridaceae. The inside-out Lacandonia flower could have resulted from a stabilized homeotic transformation; this hypothesis is not in conflict with constrasting theories of the origin of the Triuridaceae flower, which coincided with a shift to unisexuality. The unisexual yet highly plastic flowers that are typical of Triuridaceae could have pre-adapted the origin of the extraordinary Lacandonia morphology.

  5. Tibiofemoral contact pressures in radial tears of the meniscus treated with all-inside repair, inside-out repair and partial meniscectomy.

    Science.gov (United States)

    Zhang, Alan L; Miller, Stephanie L; Coughlin, Dezba G; Lotz, Jeffrey C; Feeley, Brian T

    2015-10-01

    To test contact pressures in the knee after treatment of a radial meniscus tear with an all-inside meniscal repair technique and compare the results with inside-out repair and partial meniscectomy. Six non-paired cadaveric knees were analyzed with intra-compartment pressures measured at loads of 250 N, 500 N and 1000 N at 0°, eight degrees, 15°, and 30° of knee flexion. Compartmental contact pressures were measured for the intact medial meniscus, radial tear in the posterior horn, all-inside repair using the NovoStitch suture passer device (Ceterix Orthopaedics Inc., Menlo Park, CA), inside-out repair method, and partial meniscectomy. One-way ANOVA was used for statistical analysis. The greatest differences in peak pressures between treatments were observed under 1000 N load at 30° flexion (0.8± (SD) 0.1 MPa (intact meniscus), 0.8± (SD) 0.1 MPa (all-inside), 0.9± (SD) 0.1 MPa (inside-out) and 1.6± (SD) 0.2 MPa (partial meniscectomy)). Treatment with partial meniscectomy resulted in the highest peak pressures compared to all other states (pinside technique as well as the inside-out technique resulted in significantly decreased compartment pressures compared to partial meniscectomies (pinside or inside-out techniques. An all-inside repair technique using the NovoStitch suture passer can decrease contact pressures for a radial meniscus tear similarly to the inside-out repair technique when compared to partial meniscectomy. This novel arthroscopic suture passer warrants further analysis in the clinical setting as it may be a reliable method for repair of radial meniscal tears through an arthroscopic all-inside technique. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. The placental transfer of erythromycin in human pregnancies with group B streptococcal infection.

    Science.gov (United States)

    Bulska, Magdalena; Szcześniak, Piotr; Pięta-Dolińska, Agnieszka; Oszukowski, Przemysław; Orszulak-Michalak, Daria

    2015-01-01

    The aim of this study was to investigate the effectiveness of erythromycin in preventing fetal and intrauterine group B streptococcal (GBS) infections. The study evaluated the penetration of erythromycin through the placenta, by comparing umbilical vein and maternal serum erythromycin concentrations. The study subjects were 42 pregnant women, with GBS-positive screening or whose laboratory screening was not available, who delivered between 17th April 2013 and 22nd July 2013. The women were given 600 mg of erythromycin intravenously. After delivery blood was drawn from the mother's antecubital vein and umbilical cord vein. Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. The percentage and correlation between umbilical vein and maternal serum erythromycin concentration were calculated. Based on regression function parameters selected factors: maternal age, maternal body weight, gestational age at delivery related to the umbilical vein serum erythromycin concentration, were investigated. Results: A total of 42 umbilical vein-maternal serum pairs were included in the analysis. The mean umbilical vein-maternal serum erythromycin concentration percentage was 2.64 ± 1.55%. There was a moderate correlation between umbilical vein serum and maternal serum erythromycin concentration. Pregnancy complications and selected variables of mothers in control group had no effect on the serum erythromycin concentration in the umbilical vein. Intravenous application of erythromycin at a dose of 600 mg, allowed to achieve therapeutic concentration in maternal serum. However, when it comes to placental transfer of erythromycin, the lack of therapeutic concentration in umbilical vein serum was observed. The limited transplacental transfer of erythromycin, which was approximately 2.6%, suggests compromised efficacy in the treatment of intrauterine fetal infections. On the other hand, the placenta seems to produce an effective barrier

  7. The inside-out growth of the most massive galaxies at 0.3 < z < 0.9

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Lei; Yee, H. K. C.; Li, I. H. [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, Ontario M5S 3H4 (Canada); Yan, Renbin [Department of Physics and Astronomy, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055 (United States); Lee, Eve [Astronomy Department, University of California at Berkeley, Berkeley, CA 94720 (United States); Gilbank, David G. [South African Astronomical Observatory, P.O. Box 9, Observatory 7935 (South Africa); Ellingson, E. [Center for Astrophysics and Space Astronomy, Department of Astrophysical and Planetary Science, UCB-389, University of Colorado, Boulder, CO 80309 (United States); Barrientos, L. F. [Instituto de Astrofísica, Pontificia Universidad Católica de Chile, Avenida Vicuña Mackenna 4860, Macul, Santiago (Chile); Gladders, M. D. [Department of Astronomy and Astrophysics, University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637 (United States); Hsieh, B. C., E-mail: leibai@gmail.com [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 106, Taiwan (China)

    2014-07-10

    We study the surface brightness profiles of a sample of brightest cluster galaxies (BCGs) with 0.3 < z < 0.9. The BCGs are selected from the first Red-sequence Cluster Survey and an X-ray cluster survey. The surface brightness profiles of the BCGs are measured using HST ACS images, and the majority of them can be well modeled by a single Sérsic profile with a typical Sérsic index n ∼ 6 and a half-light radius ∼30 kpc. Although the single Sérsic model fits the profiles well, we argue that the systematics in the sky background measurement and the coupling between the model parameters make the comparison of the best-fit model parameters ambiguous. Direct comparison of the BCG profiles, on the other hand, has revealed an inside-out growth for these most massive galaxies: as the mass of a BCG increases, the central mass density of the galaxy increases slowly (ρ{sub 1kpc}∝M{sub ∗}{sup 0.39}), while the slope of the outer profile grows continuously shallower (α{sub r{sup 1}{sup /}{sup 4}}∝M{sub ∗}{sup −2.5}). Such a fashion of growth continues down to the less massive early-type galaxies (ETGs) as a smooth function of galaxy mass, without apparent distinction between BCGs and non-BCGs. For the very massive ETGs and BCGs, the slope of the Kormendy relation starts to trace the slope of the surface brightness profiles and becomes insensitive to subtle profile evolution. These results are generally consistent with dry mergers being the major driver of the mass growth for BCGs and massive ETGs. We also find strong correlations between the richness of clusters and the properties of BCGs: the more massive the clusters are, the more massive the BCGs (M{sub bcg}{sup ∗}∝M{sub clusters}{sup 0.6}) and the shallower their surface brightness profiles. After taking into account the bias in the cluster samples, we find the masses of the BCGs have grown by at least a factor of 1.5 from z = 0.5 to z = 0, in contrast to the previous findings of no evolution. Such an

  8. Retropubic tension-free vaginal tape and inside-out transobturator tape: a long-term randomized trial.

    Science.gov (United States)

    Zhang, Zhibo; Zhu, Lan; Xu, Tao; Lang, Jinghe

    2016-01-01

    The tension-free vaginal tape (TVT) and inside-out transobturator tape (TVT-O) are first-line surgical treatments for stress urinary incontinence (SUI). However, there is a lack of information regarding the long-term comparative safety of these procedures. A total of 140 SUI patients were randomized to the TVT or TVT-O procedure and were interviewed by an independent investigator at the follow-up. The primary outcomes were the proportions of patients with long-term postoperative complications. The secondary outcomes included the cure rates, quality of life (QOL) and sexual function based on validated questionnaires. One hundred and twenty (85.71%) patients completed the long-term follow-up. More TVT patients experienced perioperative complications (P < 0.05). However, in a mean follow-up of 95 months, no significant between-group difference was found in the proportions of patients with long-term complications or in the variety of reported complications. The long-term complication rates for TVT and TVT-O were 43.1% and 27.4% respectively (P = 0.07). De novo voiding (15.8%) and storage symptoms (10.8%) were the primary long-term complications. Tape exposure was possible up to 7 years after TVT-O. The objective cure rates of TVT and TVT-O procedures were 79.30 and 69.35% respectively, which were not significantly higher than the subjective rates. The Pelvic Floor Impact Questionnaire (PFIQ-7) scores remained improved (P < 0.001) after both procedures, even at the 95-month follow-up. No difference was observed in the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire Short Form (PISQ-12) scores after either procedure. In the long term, the proportion of patients with complications and the cure rates of the two procedures did not differ significantly. The long-term complication rates were high, but morbidity was low, and the QOL remained improved.

  9. Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples.

    Science.gov (United States)

    Reiman, Mario; Laan, Maris; Rull, Kristiina; Sõber, Siim

    2017-08-01

    RNA degradation is a ubiquitous process that occurs in living and dead cells, as well as during handling and storage of extracted RNA. Reduced RNA quality caused by degradation is an established source of uncertainty for all RNA-based gene expression quantification techniques. RNA sequencing is an increasingly preferred method for transcriptome analyses, and dependence of its results on input RNA integrity is of significant practical importance. This study aimed to characterize the effects of varying input RNA integrity [estimated as RNA integrity number (RIN)] on transcript level estimates and delineate the characteristic differences between transcripts that differ in degradation rate. The study used ribodepleted total RNA sequencing data from a real-life clinically collected set (n = 32) of human solid tissue (placenta) samples. RIN-dependent alterations in gene expression profiles were quantified by using DESeq2 software. Our results indicate that small differences in RNA integrity affect gene expression quantification by introducing a moderate and pervasive bias in expression level estimates that significantly affected 8.1% of studied genes. The rapidly degrading transcript pool was enriched in pseudogenes, short noncoding RNAs, and transcripts with extended 3' untranslated regions. Typical slowly degrading transcripts (median length, 2389 nt) represented protein coding genes with 4-10 exons and high guanine-cytosine content.-Reiman, M., Laan, M., Rull, K., Sõber, S. Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples. © FASEB.

  10. [BAME-Esterase activity in plasmas from blood of human placental interveillous space and umbilical cord vessels (author's transl)].

    Science.gov (United States)

    Matheus, M; Salles Meirelles, R

    1976-01-01

    The authors studied an enzymatic activity (BAME-esterase) from human plasma, intimately related with the bradykinin release mechanisms. The optimal conditions of evaluation of the different plasmas were determined. Lately, the authors showed the results obtained with plasma from maternal peripheral blood, umbilical vessels blood and human placental intervillous space blood. It was concluded: 1. The study of enzymatic kinetics allows to establish a reaction time of 30 minutes, and the enzymatic concentration contained within 0.5 ml. of plasma, as ideal parameters to determine the enzymatic activities into the different compartments. 2. In the cases studied, considered clinically normals, the enzymatic activity in plasma from the interveillous space, before and after the detachment of the placenta, was greater than in peripheral maternal and umbilical vessels bloods. The activity in umbilical artery plasma was greater than in umbilical vein and practically the same as in maternal plasma. 3. The esterase activity values into the compartments studied in pre-eclamptics, were similar to that found in the cases considered clinically normal.

  11. The anti-aging properties of a human placental hydrolysate combined with dieckol isolated from Ecklonia cava.

    Science.gov (United States)

    Jang, Su Kil; Lee, Do Ik; Kim, Seung Tae; Kim, Gwang Hoon; Park, Da Woon; Park, Jung Youl; Han, Daehee; Choi, Jae Kwon; Lee, Yoon-bok; Han, Nam-Soo; Kim, Yun Bae; Han, Jeongsu; Joo, Seong Soo

    2015-10-05

    In the present study, we aimed to examine the anti-aging properties of human placental hydrolysate (HPE) and dieckol (DE) from Ecklonia cava against free radical scavenging, muscle hypertrophy-related follistatin mRNA expression, amelioration of cognition-related genes and proteins, inhibition of collagenase-regulating genes, and elastinase activity. The anti-aging effects were examined in human fibroblast (CCD986sk), mouse myoblast (C2C12), and neuroblastoma (N2a) cell models, by employing various assays such as 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) scavenging, hydroxyl radical-mediated oxidation, quantitative real-time polymerase chain reaction, enzyme activity, and immunocytochemistry observation. Our results show that HPE combined with DE (HPE:DE) strongly scavenged DPPH radicals and protected proteins against degradation by hydroxyl radical attack. HPE:DE effectively inhibited matrix metalloproteinase-1 expression, protein kinase C alpha expression, and elastinase activity. Furthermore, HPE:DE improved the expression of cognition-related genes (choline acetyltransferase and vesicular acetylcholine transporter). These events may proactively contribute to retard the aging processes and the abrupt physiological changes probably induced by mitochondrial dysfunction with aging. Based on these findings, we conclude that the combined treatment of HPE:DE may be useful for anti-aging therapy in which the accumulation of oxidative damage is the main driving force.

  12. Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity.

    Science.gov (United States)

    Murayama, Norie; Kazuki, Yasuhiro; Satoh, Daisuke; Arata, Kazuya; Harada, Tasuku; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-01-01

    Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. Human placental BeWo cells, cultured in the recommended media, also indicated detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. To reduce any masking effects by endogenous hormones used in the recommended media, induction of P450 3A4/5 mRNA and oxidation activities were measured in placental BeWo cells cultured with a modified medium containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold, but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media conditions. Under these modified conditions, thalidomide also significantly induced midazolam 1´-hydroxylation and thalidomide 5-hydroxylaion activities 3-fold but not bupropion hydroxylation activity. Taken together, activation of thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in human placentas, as well as livers, is suggested in vivo.

  13. Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

    Science.gov (United States)

    Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S. Ananth; Hennessy, Annemarie

    2016-01-01

    An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia due to endothelial dysfunction. Circulating sFLT-1 (soluble fms-like tyrosine kinase 1) increases and PlGF (placental growth factor) reduces prior to and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of an 182 day pregnancy). Two weeks after uteroplacental ischemia (UPI), rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100μg/kg/day) for 5 days. Blood pressure (BP) was monitored by intra-arterial radiotelemetry, sFLT-1 and PlGF by ELISA. UPI resulted in experimental preeclampsia evidenced by increased BP, proteinuria and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after UPI. rhPlGF reduced SBP in the treated group (-5.2mmHg+0.8mmHg;from 132.6+6.6mmHg to 124.1+7.6mmHg) compared to an increase in SBP in controls (6.5mmHg+3mmHg; from 131.3+1.5mmHg to 138.6+1.5mmHg). Proteinuria reduced in the treated group (-72.7±55.7mg/mmol) but increased in the control group. Circulating sFLT-1 was not affected by the administration of PlGF, however a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference in the weights or lengths of the neonates in the rhPlGF or control group, however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. PMID:27091894

  14. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    Directory of Open Access Journals (Sweden)

    Frederiksen Marie

    2010-07-01

    Full Text Available Abstract Background Polybrominated diphenyl ethers (PBDEs have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very high concern due to critical windows in fetal development. Methods A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored in the maternal and fetal compartments. In addition, the perfused cotyledon, the surrounding placental tissue as well as pre-perfusion placental tissue and umbilical cord plasma were also analysed. The PBDE analysis included Soxhlet extraction, clean-up by adsorption chromatography and GC-MS analysis. Results and Discussion Placental transfer of BDE-47 was faster and more extensive than for BDE-99. The fetal-maternal ratios (FM-ratio after four hours of perfusion were 0.47 and 0.25 for BDE-47 and BDE-99, respectively, while the indicative permeability coefficient (IPC measured after 60 minutes of perfusion was 0.26 h-1 and 0.10 h-1, respectively. The transport of BDE-209 seemed to be limited. These differences between the congeners may be related to the degree of bromination. Significant accumulation was observed for all congeners in the perfused cotyledon as well as in the surrounding placental tissue. Conclusion The transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which should be included in risk assessment of PBDE exposure of women of child-bearing age.

  15. CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity*

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A.

    2013-01-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in “normal” pregnancy. Maternal obesity can exacerbate this “resistance,” suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m2) versus lean (BMI 20–25 kg/m2) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development. PMID:23782703

  16. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A

    2013-08-02

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in "normal" pregnancy. Maternal obesity can exacerbate this "resistance," suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m(2)) versus lean (BMI 20-25 kg/m(2)) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development.

  17. Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts

    OpenAIRE

    Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

    2013-01-01

    Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that puni...

  18. Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure.

    Science.gov (United States)

    Perazzolo, S; Lewis, R M; Sengers, B G

    2017-12-01

    A healthy pregnancy depends on placental transfer from mother to fetus. Placental transfer takes place at the micro scale across the placental villi. Solutes from the maternal blood are taken up by placental villi and enter the fetal capillaries. This study investigated the effect of maternal blood flow on solute uptake at the micro scale. A 3D image based modelling approach of the placental microstructures was undertaken. Solute transport in the intervillous space was modelled explicitly and solute uptake with respect to different maternal blood flow rates was estimated. Fetal capillary flow was not modelled and treated as a perfect sink. For a freely diffusing small solute, the flow of maternal blood through the intervillous space was found to be limiting the transfer. Ignoring the effects of maternal flow resulted in a 2.4 ± 0.4 fold over-prediction of transfer by simple diffusion, in absence of binding. Villous morphology affected the efficiency of solute transfer due to concentration depleted zones. Interestingly, less dense microvilli had lower surface area available for uptake which was compensated by increased flow due to their higher permeability. At super-physiological pressures, maternal flow was not limiting, however the efficiency of uptake decreased. This study suggests that the interplay between maternal flow and villous structure affects the efficiency of placental transfer but predicted that flow rate will be the major determinant of transfer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Editorial Commentary: All-Inside or Inside-Out Meniscal Repair for the Posterior Thirds in Meniscus Allograft Transplantation? Which to Choose and What Difference It Makes.

    Science.gov (United States)

    Ohuchi, Hiroshi

    2016-02-01

    Performing an all-inside repair or inside-out fixation for the posterior third in meniscus allograft transplantation is discussed. Less invasiveness is always important when the results are the same, and surgeons' personal experience may be a determining factor for this procedure. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  20. Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

    Science.gov (United States)

    Moore, Julie M.; Chaisavaneeyakorn, Sujittra; Perkins, Douglas J.; Othoro, Caroline; Otieno, Juliana; Nahlen, Bernard L.; Shi, Ya Ping; Udhayakumar, Venkatachalam

    2004-01-01

    Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-γ), with less of an effect on tumor necrosis factor alpha (TNF-α) and interleukin-10, in human immunodeficiency virus-seronegative (HIV−) women. In contrast, IFN-γ and TNF-α production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-γ in HIV− women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women. PMID:15557625

  1. Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: implications for trophoblastic invasion of the placental bed.

    Science.gov (United States)

    Sinai Talaulikar, Vikram; Kronenberger, Katrin; Bax, Bridget E; Moss, Raymond; Manyonda, Isaac

    2014-01-01

    The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis. We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 11 women undergoing pregnancy termination in the first trimester. The biopsies were subjected to light, transmission and scanning electron microscopy, and immunohistochemical studies using mouse monoclonal antibodies against cytokeratin 7 and collagen types I, III and V. Collagen fibrils in the stroma of decidua basalis were significantly thicker when compared to those in decidua parietalis (56.48 ± 1.37 nm vs 45.64 ± 0.85 nm; P collagen fibrils between basalis and parietalis, with thicker and disrupted fibrils within abundant amorphous tissue in basalis, and thinner uniform fibrils in parietalis. These differences may reflect an adaptive response by decidua or a direct consequence of the invading trophoblast cells. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  2. Aromatization of 16alpha-hydroxyandrostenedione by human placental microsomes: effect of preincubation with suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Tachibana, Mii; Mutsumi, Ayako; Yoshimura, Akiko; Osawa, Yoshio

    2002-06-01

    Estrogen synthase (aromatase) catalyzes the aromatization of androstenedione (AD) as well as 16alpha-hydroxyandrostenedione (16alpha-OHAD) leading to estrone and estriol, respectively. We found that several steroid analogs including 4-hydroxyandrostenedione (1), 6-oxoandrostenedione (6-oxoAD, 2) and its 19-hydroxy analog (3), 10beta-acetoxyestr-5-ene-7,17-dione (4), androst-5-ene-4,7,17-trione (5), and 17alpha-ethynyl-19-norteststerone (6), which are known suicide inactivators of AD aromatization, are not effective in inactivating 16alpha-OHAD aromatization in a time-dependent manner. The compounds were tested with the use of human placental microsomes and 1beta-tritiated-16alpha-OHAD as the substrate. The results of the tritium water method of 16alpha-OHAD aromatization was confirmed by the gas chromatography-mass spectrometry (GC-MS) method of estriol formation. The 1beta-tritiated-AD was used to measure AD aromatization as a positive control for these experiments. The compounds were tested at concentrations up to 40-fold higher than the K(i)'s determined for inhibition of AD aromatization. These studies suggest that differences exist in the binding site structures responsible for aromatization of 16alpha-OHAD and AD.

  3. Toxic and therapeutic effects of Nifurtimox and Benznidazol on Trypanosoma cruzi ex vivo infection of human placental chorionic villi explants.

    Science.gov (United States)

    Rojo, Gemma; Castillo, Christian; Duaso, Juan; Liempi, Ana; Droguett, Daniel; Galanti, Norbel; Maya, Juan Diego; López-Muñoz, Rodrigo; Kemmerling, Ulrike

    2014-04-01

    Nifurtimox (Nfx) and Benznidazole (Bnz) are the only available drugs in use for the treatment of Chagas disease. These drugs are recommended but not fully validated in evidence-based medicine and reports about the differential toxicity of both drugs are controversial. Here, we evaluated the toxic and therapeutic effects of Nfx and Bnz on human placental chorionic villi explants (HPCVE) during ex vivo infection of Trypanosoma cruzi, performing histopathological, histochemical, immunohistochemical as well as immunofluorescence analysis of the tissue. Additionally, we determined the effect of both drugs on parasite load by real time PCR. Bnz prevents the parasite induced tissue damage in ex vivo infected HPCVE compared to Nfx, which is toxic per se. The presence of T. cruzi antigens and DNA in infected explants suggests that these drugs do not impair parasite invasion into the HPCVE. Additionally, our results confirm reports suggesting that Bnz is less toxic than Nfx and support the need for the development of more effective and better-tolerated drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells

    Directory of Open Access Journals (Sweden)

    Ute Wölfle

    2016-03-01

    Full Text Available Bitter taste receptors (TAS2Rs are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting.

  5. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  6. High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C.

    Science.gov (United States)

    Zhou, Huilei; Wang, Lin; Huang, Juxiang; Jiang, Minghu; Zhang, Xiaoyu; Zhang, Liyuan; Wang, Yangming; Jiang, Zhenfu; Zhang, Zhongjie

    2015-01-01

    48 different Pearson mutual-positive-correlation epidermal growth factor receptor (EGFR_1)-activatory molecular feedback, up- and down-stream network was constructed from 171 overlapping of 366 GRNInfer and 223 Pearson under EGFR_1 CC ≥0.25 in high lung adenocarcinoma compared with low human normal adjacent tissues. Our identified EGFR_1 inside-out upstream activated molecular network showed SLC2A1 (solute carrier family 2 (facilitated glucose transporter) member 1), CCNB2 (cyclin B2), HMMR (hyaluronan-mediated motility receptor (RHAMM)), KIF11 (kinesin family member 11), NUSAP1 (nucleolar and spindle associated protein 1), PRC1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin-conjugating enzyme E2C) in high lung adenocarcinoma. EGFR_1 inside-out upstream activated terms network includes intracellular, membrane fraction, cytoplasm, plasma membrane, integral to membrane, basolateral plasma membrane, transmembrane transport, nucleus, cytosol, cell surface; T cell homeostasis, inflammation; microtubule cytoskeleton, embryonic development (sensu Mammalia), cell cycle, mitosis, thymus development, cell division, regulation of cell cycle, Contributed--cellular process--Hs cell cycle KEGG, cytokinesis, M phase, M phase of mitotic cell cycle, estrogen-responsive protein Efp controls cell cycle and breast tumors growth, cell motility, locomotion, locomotory behavior, neoplasm metastasis, spindle pole, spindle microtubule, microtubule motor activity, microtubule-based movement, mitotic spindle organization and biogenesis, mitotic centrosome separation, spindle pole body organization and biogenesis, microtubule-based process, microtubule, cytokinesis after mitosis, mitotic chromosome condensation, establishment of mitotic spindle localization, positive regulation of mitosis, mitotic spindle elongation, spindle organization and biogenesis, positive regulation of exit from mitosis, regulation of cell proliferation, positive regulation of cell proliferation based on

  7. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Guo Yingqiang

    2010-05-01

    Full Text Available Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF is a member of the vascular endothelial growth factor (VEGF family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs and smooth muscle cells (VSMCs. Results In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2 in these cells. The Ang II type I receptor (AT1R antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2 and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

  8. Epidermal Growth Factor-Like Growth Factors Prevent Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells1

    Science.gov (United States)

    Wolff, Garen S.; Chiang, Po Jen; Smith, Susan M.; Romero, Roberto; Armant, D. Randall

    2007-01-01

    Maternal alcohol abuse during pregnancy can produce an array of birth defects comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is intrauterine growth retardation, which is associated with elevated apoptosis of placental cytotrophoblast cells. Using a human first trimester cytotrophoblast cell line, we examined the relationship between exposure to ethanol and cytotrophoblast survival, as well as the ameliorating effects of epidermal growth factor (EGF)-like growth factors produced by human cytotrophoblast cells. After exposure to 0–100 mM ethanol, cell death was quantified by the TUNEL method, and expression of the nuclear proliferation marker, Ki67, was measured by immunohistochemistry. The mode of cell death was determined by assessing annexin V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol significantly reduced proliferation and increased cell death approximately 2.5-fold through the apoptotic pathway within 1–2 h of exposure to 50 mM alcohol. Exposure to 25–50 mM ethanol significantly increased transforming growth factor alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting activity required ligation of either of its cognate receptors, HER1 or HER4. These findings reveal the potential for ethanol to rapidly induce cytotrophoblast apoptosis. However, survival factor induction could provide cytotrophoblasts with an endogenous cytoprotective mechanism. PMID:17392498

  9. Pregnancy Complications: Placental Abruption

    Science.gov (United States)

    ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ...

  10. Combination Effects of (TriAzole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line

    Directory of Open Access Journals (Sweden)

    Svenja Rieke

    2014-09-01

    Full Text Available Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (triazole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this

  11. Comparison of outside-in and inside-out technique for tibial fixation of a soft-tissue graft in ACL reconstruction using the Shim technique.

    Science.gov (United States)

    Lenschow, S; Schliemann, B; Schulze, M; Raschke, M; Kösters, C

    2014-09-01

    The aim of this study was to compare the biomechanical properties of tibial fixation of a free tendon graft in ACL reconstruction using the Shim, a new wedge-shaped implant, in an outside-in technique to fixation by the Shim used in an inside-out technique and fixation by interference screw in a porcine model. Porcine tibia and flexor tendons were used. In Group 1, the Shim was applied outside-in. In Group 2, the Shim was inserted inside-out. In the Group 3, an 8-mm interference screw was used. Ten specimens were tested in each group. Load-to-failure, elongation, stiffness and failure mode were recorded. Cyclic loading was performed between 5 and 250 N for 1,000 cycles, followed by a load to failure testing. Mean maximum load-to-failure was 629.53 N in Group 1,648.54 N in Group 2 and 749.53 N in Group 3. There was no significant difference between the groups. Stiffness varied between 127.34 N/mm in Group 1, 151.27 N/mm in Group 2 and 182.25 N/mm in Group 3. No significant differences were found between outside-in Shim and interference screw fixation. No significant difference was found for elongation among the three groups. The main failure mode was a rupture of the tendon in the IFS group and a slippage of either the implant or the tendon in both groups using the Shim. As no statistically significant difference could be seen concerning load to failure, stiffness and elongation between the inside-out and the outside-in techniques, the Shim can be used for tibial fixation in an outside-in or inside-out technique depending on the preference of the surgeon. To prevent slippage of the graft a hybrid fixation should be considered.

  12. All-inside meniscal repair devices compared with their matched inside-out vertical mattress suture repair: introducing 10,000 and 100,000 loading cycles.

    Science.gov (United States)

    Rosso, Claudio; Müller, Sebastian; Buckland, Daniel M; Schwenk, Tanja; Zimmermann, Simon; de Wild, Michael; Valderrabano, Victor

    2014-09-01

    All-inside arthroscopic meniscal repairs are favored by most clinicians because of their lower complication rate and decreased morbidity compared with inside-out techniques. Until now, only 1000 cycles have been used for biomechanical testing. All-inside meniscal repairs will show inferior biomechanical response to cyclic loading (up to 100,000 cycles) and load-to-failure testing compared with inside-out suture controls. Controlled laboratory study. Bucket-handle tears in 72 porcine menisci were repaired using the Omnispan and Fast-Fix 360 (all-inside devices) and Orthocord 2-0 and Ultrabraid 2-0 sutures (matched controls). Initial displacement, displacement after cyclic loading (100, 500, 1000, 2000, 5000, 10,000, and 100,000 cycles) between 5 and 20 N, ultimate load to failure, and mode of failure were recorded, as well as stiffness. Initial displacement and displacement after cyclic loading were not different between the groups. The Omnispan repair demonstrated the highest load-to-failure force (mean ± SD, 151.3 ± 21.5 N) and was significantly stronger than all the other constructs (Orthocord 2-0, 105.5 ± 20.4 N; Ultrabraid 2-0, 93.4 ± 22.5 N; Fast-Fix 360, 76.6 ± 14.2 N) (P inside-out mattress repair was significantly stronger than the Fast-Fix 360 repair (P = .003). The Omnispan (30.8 ± 3.5 N/mm) showed significantly higher stiffness compared with the Ultrabraid 2-0 (22.9 ± 6.9 N/mm, P inside meniscal devices show comparable biomechanical properties compared with inside-out suture repair in cyclic loading, even after 100,000 cycles. Eight to 10 weeks of rehabilitation might not pose a problem for all repairs in this worst-case scenario. © 2014 The Author(s).

  13. Inside-out and standard vein grafts associated with platelet-rich plasma (PRP) in sciatic nerve repair. A histomorphometric study.

    Science.gov (United States)

    Roque, José Sidney; Pomini, Karina Torres; Buchaim, Rogério Leone; Buchaim, Daniela Vieira; Andreo, Jesus Carlos; Roque, Domingos Donizeti; Rodrigues, Antonio de Castro; Rosa, Geraldo Marco; Moraes, Luis Henrique Rapucci; Viterbo, Fausto

    2017-08-01

    To evaluated the tubulization technique with standard and inside-out vein, filled or not with platelet-rich plasma (PRP), in sciatic nerve repair. Seventy male Wistar rats were randomly divided into five groups: IOVNF (Inside-Out Vein with No Filling); IOVPRP (Inside-Out Vein filled with PRP); SVNF (Standard Vein with No Filling); SVPRP (Standard Vein filled with PRP); Sham (Control). The left external jugular vein was used as graft in a 10 mm nervous gap. In the morphological analysis of all groups, myelinated nerve fibers with evident myelin sheath, neoformation of the epineurium and perineurium, organization of intraneural fascicles and blood vessels were observed. In the morphometry of the distal stump fibers, SVPRP group had the highest means regarding fiber diameter (3.63±0.42 μm), axon diameter (2.37±0.31 μm) and myelin sheath area (11.70±0.84 μm2). IOVPRP group had the highest means regarding axon area (4.39±1.16 μm2) and myelin sheath thickness (0.80±0.19 μm). As for values of the fiber area, IOVNF group shows highest means (15.54±0.67 μm2), but are still lower than the values of the Sham group. The graft filled with platelet-rich plasma, with use standard (SVPRP) or inside-out vein (IOVPRP), promoted the improvement in axonal regeneration on sciatic nerve injury.

  14. [Distribution of collagen types III and IV in human placental villi].

    Science.gov (United States)

    Nanaev, A K; Rukosuev, V S; Milovanov, A P; Fokin, E I; Shirinskiĭ, V P

    1989-02-01

    Immunofluorescent examination showed more significant accumulation of interstitial collagen type III in the stroma of mature placenta compared with immature one. Localization of membrane collagen type IV was found neither in basal membranes of epithelium and villous vessels of mature term placenta, nor in their stroma. The described patterns of distribution of collagen types III and IV in human placenta villi were proved by immunoelectronmicroscopic method.

  15. The dual structural roles of the membrane distal region of the α-integrin cytoplasmic tail during integrin inside-out activation.

    Science.gov (United States)

    Liu, Jiafu; Wang, Zhengli; Thinn, Aye Myat Myat; Ma, Yan-Qing; Zhu, Jieqing

    2015-05-01

    Studies on the mechanism of integrin inside-out activation have been focused on the role of β-integrin cytoplasmic tails, which are relatively conserved and bear binding sites for the intracellular activators including talin and kindlin. Cytoplasmic tails for α-integrins share a conserved GFFKR motif at the membrane-proximal region and this forms a specific interface with the β-integrin membrane-proximal region to keep the integrin inactive. The α-integrin membrane-distal regions, after the GFFKR motif, are diverse both in length and sequence and their roles in integrin activation have not been well-defined. In this study, we report that the α-integrin cytoplasmic membrane-distal region contributes to maintaining integrin in the resting state and to integrin inside-out activation. Complete deletion of the α-integrin membrane-distal region diminished talin- and kindlin-mediated integrin ligand binding and conformational change. A proper length and suitable amino acids in α-integrin membrane-distal region was found to be important for integrin inside-out activation. Our data establish an essential role for the α-integrin cytoplasmic membrane-distal region in integrin activation and provide new insights into how talin and kindlin induce the high-affinity integrin conformation that is required for fully functional integrins. © 2015. Published by The Company of Biologists Ltd.

  16. Comparative study between standard and inside-out vein graft techniques on sciatic nerve repair of rats. Muscular and functional analysis.

    Science.gov (United States)

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Aparecido, Idvaldo; Buchaim, Rogerio Leone; Andreo, Jesus Carlos; Rodrigues, Antônio de Castro; Marco, Geraldo

    2017-04-01

    To compare the functional result of standart vein grafts and inside-out vein graft technique on sciatic nerve repair. We used 24 male Wistar rats divided into 4 groups: control group (CG), standard vein graft group (SVG), Inside-out vein graft group (IOVG) and denervated Group (DG). SVG, IOVG and DG underwent total section of the sciatic nerve, SVG and IOVG however underwent nerve repair surgery using a graft with normal jugular vein and inside-out jugular vein, respectively. Histological analysis of the soleus and Extensor Digitorum Longus (EDL), and Sciatic Functional Index were used to compare the results after 6 weeks. Both grafts acted favorably in muscle recovery and improved functionality; They were similar in all parameters, however, in more points SVG achieved similar to the CG, in the other hand IOVG more times was similar to DG. Fact that makes the graft with normal vein the most viable option between the two options. Both types of grafts acted beneficially wherein the graft normal vein has proved to be the best option.

  17. A Comparative Prospective Study of Two Different Treatment Sequences i.e. Bottom Up-Inside Out and Topdown-Outside in, in the Treatment of Panfacial Fractures.

    Science.gov (United States)

    Degala, Saikrishna; Sundar, S Shyam; Mamata, K S

    2015-12-01

    To compare the sequence bottom-up inside-out with top-down outside-in, in the treatment of pan facial fractures and to evaluate the outcome of these approaches. The data from 11 patients with panfacial fracture are prospectively analysed. Five cases are treated with bottom-up approach and six patients with top-down approach. There were 11 male patients (six in top-down approach and five in bottom-up approach), ranging in age from 24 to 50 years. All injuries were result of RTA (n = 11, 100 %). Final treatment outcome was excellent in 3 (50 %), 1 (16 %) good and 2 (32 %) cases were fair in topdown approach, 3 (60 %) excellent and 2 (40 %) fair in bottom up approach with contingency coefficient value (P inside-out and top-down outside-in approaches have similar clinical outcomes. Hence it could be suggestive to start fixation of least disrupted (more stable) facial half as a guide for reconstruction of the remaining. Choice of the bottom-up inside-out or top-down outside-in sequence should be according to the pattern of fractures and preference of the surgeon. However, further controlled clinical trials, comparative studies with a larger sample size would be better to evaluate the final clinical outcome of individual techniques.

  18. Antibodies to Placental Immunoregulatory Ferritin with Transfer of Polyclonal Lymphocytes Arrest MCF-7 Human Breast Cancer Growth in a Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Marisa Halpern

    2007-06-01

    Full Text Available The recently cloned human gene named “placental immunoregulatory ferritin” (PLIF is a pregnancyrelated immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells, both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, antiC48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.

  19. Cyclic test comparison of all-inside device and inside-out sutures for radial meniscus lesion repair: an in vitro porcine model study.

    Science.gov (United States)

    Lee, Yee Han Dave; Nyland, John; Burden, Robert; Caborn, David N M

    2012-12-01

    To compare biomechanical fixation and gapping characteristics of a new all-inside meniscus repair method for radial meniscus lesion repair versus conventional inside-out suture repair under submaximal cyclic loading and load-to-failure test conditions. Fresh-frozen porcine tibiae with attached lateral menisci and joint capsules were harvested and stored for 48 hours at -20°C. After thawing for 12 hours, equivalent-size healthy specimens were randomly assigned to 2 groups of 8 specimens each. Standardized radial lesions were repaired with the Sequent device (ConMed Linvatec, Largo, FL) (group 1) or conventional inside-out suturing with No. 2-0 braided polyester suture (group 2). Repaired specimens were placed in custom clamps and mounted on a servohydraulic device. After a 2-N preload, specimens were cycled from 5 to 20 N (0.1 Hz), before undergoing 1,000 submaximal loading cycles between 5 and 20 N (0.5 Hz). A 40-second delay at 100, 500, and 1,000 cycles enabled digital photographs to be taken for gapping measurement determination. Specimens then underwent load-to-failure testing (12.5 mm/s). Fixation failure mode was documented. Group displacement did not differ after 1, 100, 500, and 1,000 submaximal loading cycles. Group peak gapping did not differ at 100, 500, and 1,000 submaximal loading cycles. Load at failure and displacement and stiffness during load-to-failure testing did not differ between groups. During load-to-failure testing, all-inside specimens failed by implant dislodgement from the meniscus periphery whereas the inside-out repaired specimens failed by suture rupture. Under controlled in vitro biomechanical test conditions, the all-inside device provided radial meniscus lesion fixation that was comparable, but not superior, to conventional inside-out suturing. The all-inside radial lateral meniscus lesion repair method may provide comparable fixation to conventional inside-out suturing without the need for additional incisions and their associated

  20. Globalization from the Bottom up, inside out, and outside in: Indigenous Language Planning and Policy from an Indigenous Perspective

    Science.gov (United States)

    Romero-Little, Mary Eunice

    2012-01-01

    "Globalization", a prominent and ubiquitous term in the academy associated with linguistic human rights, power, hypercapitalism, socio-political constraints, and social justice, is defined as powerful dynamic global forces stemming from the new world economy that constrict and restrict local contexts, progress, and possibilities--in this…

  1. Placenta Maps: In Utero Placental Health Assessment of the Human Fetus.

    Science.gov (United States)

    Miao, Haichao; Mistelbauer, Gabriel; Karimov, Alexey; Alansary, Amir; Davidson, Alice; Lloyd, David F A; Damodaram, Mellisa; Story, Lisa; Hutter, Jana; Hajnal, Joseph V; Rutherford, Mary; Preim, Bernhard; Kainz, Bernhard; Groller, M Eduard

    2017-06-01

    The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.

  2. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  3. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Mathiesen, Line

    2010-01-01

    BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very...... high concern due to critical windows in fetal development. METHODS: A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored...... should be included in risk assessment of PBDE exposure of women of child-bearing age....

  4. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  5. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies.

    Science.gov (United States)

    Apps, Richard; Murphy, Shawn P; Fernando, Raymond; Gardner, Lucy; Ahad, Tashmeeta; Moffett, Ashley

    2009-05-01

    Human trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class-I (HLA-I) loci has made it difficult to generate locus-specific monoclonal antibodies (mAbs). The problem of defining an antibody's reactivity against the thousands of existing HLA-I allotypes has often made it impossible to determine the HLA bound by a mAb in biological samples from a normal outbred population. Here we have used commercially available beads coated with individual HLA-I to characterize experimentally the reactivity of nine mAb against 96 common HLA-I allotypes. In conjunction with donor HLA-I genotyping, we could then define the specific HLA molecules bound by these antibodies in normal individuals. We used this approach to analyse the HLA expression of primary trophoblast cells from normal pregnancies; the choriocarcinoma cells JEG-3 and JAR; and the placental cell lines HTR-8/SVneo, Swan-71 and TEV-1. We confirm that primary villous trophoblast cells are HLA null whereas extravillous trophoblast cells express HLA-C, HLA-G and HLA-E, but not HLA-A, HLA-B or HLA-DR molecules in normal pregnancy. Tumour-derived JEG-3 and JAR cells reflect extravillous and villous trophoblast HLA phenotypes, respectively, but the HLA repertoire of the in vitro derived placental cell lines is not representative of either in vivo trophoblast phenotype. This study raises questions regarding the validity of using the placental cell lines that are currently available as model systems for immunological interactions between fetal trophoblast and maternal leucocytes bearing receptors for HLA molecules.

  6. The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

    Science.gov (United States)

    Garcia-Valdes, L; Campoy, C; Hayes, H; Florido, J; Rusanova, I; Miranda, M T; McArdle, H J

    2015-04-01

    Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, PMaternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

  7. The inside-out transobturator male sling for the surgical treatment of stress urinary incontinence after radical prostatectomy: midterm results of a single-center prospective study.

    Science.gov (United States)

    Leruth, Julie; Waltregny, David; de Leval, Jean

    2012-03-01

    Transobturator slings are currently promoted for the treatment of stress urinary incontinence (SUI) after radical prostatectomy (RP), but data on outcome remain limited. To assess, at midterm, the efficacy and safety of the inside-out transobturator male sling for treating post-RP SUI and to determine factors associated with failure. Prospective one-center trial involving 173 consecutive patients without detrusor overactivity, treated between 2006 and 2011 for SUI following RP. Placement of an inside-out transobturator sling. Baseline and follow-up evaluations included uroflowmetry and continence and quality-of-life (QoL) questionnaires. Cure was defined as no pad use and improvement as a number of pads per day reduced by ≥50% and two or fewer pads. Complications were recorded, and factors associated with treatment failure were evaluated. Preoperatively, 21%, 35%, and 44% of the patients were using two, three to five, and more than five pads per day, respectively. After a median follow-up of 24 mo (range: 12-60 mo), 49% were cured, 35% improved, and 16% not improved. QoL was enhanced (p6 mo (3%), and sling infection (2%); all were managed conservatively. Severe SUI before sling surgery was not associated with a worse outcome, whereas obesity and a history of pelvic irradiation or bladder neck stenosis were independent risk factors of failure, with risk ratios of 7.9 (95% confidence interval [CI], 3.3-18.9), 3.3 (95% CI, 1.4-7.8), and 2.6 (95% CI, 1.1-6.5), respectively. The inside-out transobturator male sling is an efficient and safe treatment for post-RP SUI at midterm. Patients with prior pelvic irradiation may not be suitable candidates. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  8. Negative-stain electron microscopy of inside-out FtsZ rings reconstituted on artificial membrane tubules show ribbons of protofilaments.

    Science.gov (United States)

    Milam, Sara L; Osawa, Masaki; Erickson, Harold P

    2012-07-03

    FtsZ, the primary cytoskeletal element of the Z ring, which constricts to divide bacteria, assembles into short, one-stranded filaments in vitro. These must be further assembled to make the Z ring in bacteria. Conventional electron microscopy (EM) has failed to image the Z ring or resolve its substructure. Here we describe a procedure that enabled us to image reconstructed, inside-out FtsZ rings by negative-stain EM, revealing the arrangement of filaments. We took advantage of a unique lipid that spontaneously forms 500 nm diameter tubules in solution. We optimized conditions for Z-ring assembly with fluorescence light microscopy and then prepared specimens for negative-stain EM. Reconstituted FtsZ rings, encircling the tubules, were clearly resolved. The rings appeared as ribbons of filaments packed side by side with virtually no space between neighboring filaments. The rings were separated by variable expanses of empty tubule as seen by light microscopy or EM. The width varied considerably from one ring to another, but each ring maintained a constant width around its circumference. The inside-out FtsZ rings moved back and forth along the tubules and exchanged subunits with solution, similarly to Z rings reconstituted outside or inside tubular liposomes. FtsZ from Escherichia coli and Mycobacterium tuberculosis assembled rings of similar structure, suggesting a universal structure across bacterial species. Previous models for the Z ring in bacteria have favored a structure of widely scattered filaments that are not in contact. The ribbon structure that we discovered here for reconstituted inside-out FtsZ rings provides what to our knowledge is new evidence that the Z ring in bacteria may involve lateral association of protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Systematic review and meta-analysis of "inside-out" versus "outside-in" transobturator tapes in management of stress urinary incontinence in women.

    Science.gov (United States)

    Madhuvrata, Priya; Riad, Mohamed; Ammembal, Manjunath K; Agur, Wael; Abdel-Fattah, Mohamed

    2012-05-01

    To directly compare the current evidence for the efficacy, complications, quality of life and cost to health services of both transobturator tension free vaginal tape procedures - "inside-out" versus "outside-in" - in the surgical treatment of female stress urinary incontinence. A prospective peer-reviewed protocol was prepared a priori, and a systematic search of relevant databases from 1966 to January 2011 was performed. Meta-analyses of five randomised trials and three cohort studies were performed separately in accordance with PRISMA and MOOSE, respectively. There was no significant difference in patient-reported cure/improvement (OR 1.25, 95%CI 0.78, 1.99; p=0.35) nor in objective cure/improvement (OR 1.66, 95%CI 0.8, 3.43, p=0.17) between the two groups at 12-month follow-up. Vaginal angle injuries were significantly higher with the outside-in route (OR 0.14, 95%CI 0.05, 0.41, p=0.0003). Groin/thigh pain and de-novo urgency were non-significantly higher with the inside-out route (OR 1.42, 95%CI 0.94, 2.13, p=0.10 and OR 1.46, 95%CI 0.63, 3.36, p=0.38, respectively). There was no significant difference in postoperative quality of life scores between the two groups (WMD -1.65; 95% CI -5.76, 2.46, p=0.43). None of the trials reported a "health-cost" analysis. Meta-analysis of cohort studies confirmed similar results. This is the first reported direct meta-analysis comparing both routes of transobturator tapes. It showed no evidence of significant differences in the efficacy and impact on women's quality of life between "inside-out" and "outside-in" transobturator tapes up to one-year follow-up. The "inside-out" route was associated with significantly fewer vaginal angle injuries but with trends towards higher risk of postoperative groin pain. Long-term follow-up of adequately powered RCTs is required to assess if these results pertain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

    Directory of Open Access Journals (Sweden)

    Plante Julie

    2007-07-01

    Full Text Available Abstract Background During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2 was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2. Methods We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium. Results High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium. Conclusion

  11. Placental Adaptations in Growth Restriction

    Science.gov (United States)

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  12. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

    Full Text Available The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.

  13. PLACENTAL SIZE AND PERINATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Nagamani

    2015-03-01

    Full Text Available BACKGROUND : The human placenta, a transient organ or pregnancy provides information about fetal well - being and pregnancy outcome . AIMS: To study the placental ultrasound characters in relation to perinatal outcomes . SETTINGS: Tertiary care hospital in southern India . METHODS AND MATERIAL S: The study sample comprised 500 consecutive women who presented to the Depart ment of Obstetrics and Gynecology at the King George Hospital who met the inclusion criteria. Ultrasonographic study was performed using a transabdominal 3.5 MHz volume transducer. Post natally the weight of the baby and of the placenta was recorded. Perina tal outcome was assessed by birth weight, APGAR score and the need for admission in neonatal intensive care unit. STATISTICAL ANALYSIS : Pearson’s correlation analysis and Chi square test was used. Statistical significance was considered at a p value <0.05 . RESULTS: The mean placental thickness was 3.10 cm; 76% (n:380 had normal thickness. Mean placental diameter was 21.306 cm, and its weight varied from 310 women 62% (n:310. Correlation of placental thickness (normal and abnormal, with birth weight, the difference was significant ( <0.001. CONCLUSION: Ultrasound forms a readily available, fairly safe, effective non - invasive method to identify and prevent fetal malnutrition in a cost - effective way.

  14. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  15. Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome

    Directory of Open Access Journals (Sweden)

    Grozdea Jean J

    2002-01-01

    Full Text Available Abstract Background In humans, there are four alkaline phosphatases, and each form exibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnent with a trisomy 21 fetus (Down's syndrome displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. Results To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate, allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60–80% of activity. Conclusion Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome.

  16. Advanced inside-out tracking approach for real-time combination of MRI and US images in the radio-frequency shielded room using combination markers.

    Science.gov (United States)

    Nagaraj, Yeshaswini; Benedicks, Christian; Matthies, Philipp; Friebe, Michael

    2016-08-01

    For the real-time fusion of different modalities, a variety of tracking methods are available including the optical, electromagnetic (EM) and image-based tracking. But as a drawback optical tracking suffers from line of sight issues and EM tracking requires the manual referencing for the fusion procedure and is not usable in Magnetic Resonance Imaging (MRI) environment. To avoid these issues, we propose a real-time setup containing a camera capable of inside-Out tracking using combined circular markers attached to Ultrasound (US) probe and a suitable platform for automatic overlay of MRI and US image using markers. This new approach could help clinicians carry out successful surgical procedures by requiring least system interaction and solving line of sight issues. As a proof-of-concept, we show our first result by mimicking common liver tumor intervention using framed marker fusion technique in a candle gel phantom. We evaluated the tracking error distances using the combination of special markers with Inside-Out approach and conventional optical tracking. The results achieved show comparable performance to the standard Outside-In tracking and manual reference approach, while easing the interventional procedure in terms of hardware and line of sight requirements.

  17. Novel experience of laser-assisted 'inside-out' central venous access in a patient with bilateral subclavian vein occlusion requiring pacemaker implantation.

    Science.gov (United States)

    Aye, Thandar; Phan, Thanh Trung; Muir, Douglas Findlay; Linker, Nicholas John; Hartley, Richard; Turley, Andrew John

    2017-10-01

    This new laser facilitated 'inside-out' technique was used for transvenous pacemaker insertion in a pacemaker-dependent patient with bilateral subclavian occlusion and a failed epicardial system who is not suitable for a transfemoral approach. Procedure was undertaken under general anaesthesia with venous access obtained from right femoral vein and left axillary vein. 7F multipurpose catheter was used to enter proximal edge of the occluded segment of subclavian vein via femoral approach, which then supported stiff angioplasty wires and microcatheters to tunnel into the body of occlusion. When encountered with impenetrable resistance, 1.4 mm Excimer laser helped delivery of a Pilot 200 wire, which then progressed towards the distal edge of occlusion. Serial balloon dilatations allowed wire tracked into subintimal plane, advanced towards left clavicle using knuckle wire technique, which was then externalized with blunt dissection from infraclavicular pocket area. It was later changed to Amplatz superstiff wire exiting from both ends to form a rail, which ultimately allowed passage of pacing leads after serial balloon dilatation from clavicular end. Our hybrid 'inside-out' technique permitted transvenous pacemaker insertion without complication and this is, to our knowledge, the first case using laser in this context.

  18. Behaviour of hybrid inside/out Janus nanotubes at an oil/water interface. A route to self-assembled nanofluidics?

    Science.gov (United States)

    Picot, P; Taché, O; Malloggi, F; Coradin, T; Thill, A

    2016-10-06

    Imogolites are natural aluminosilicate nanotubes that have a diameter of a few nanometers and can be several microns long. These nanotubes have different chemical groups on their internal (Si-OH) and external (Al-OH-Al) surfaces, that can be easily functionalised independently on both surfaces. Here we show that taking advantage of the particular shape and chemistry of imogolite, it is possible to prepare inside/out Janus nanotubes. Two kinds of symmetric Janus nanotubes are prepared: one with an external hydrophilic surface and an internal hydrophobic cavity (imo-CH3) and one with an external hydrophobic surface and a hydrophilic internal cavity (OPA-imo). The behaviour of such inside/out Janus nanotubes at oil/water interfaces is studied. The OPA-imo adsorbs strongly at the oil/water interface and is very efficient in stabilising water-in-oil emulsions through an arrested coalescence mechanism. Imo-CH3 also adsorbs at the oil/water interface. It stabilises oil-in-water emulsions by inducing slow oil-triggered modifications of the viscosity of the continuous phase. The possible transport of small molecules inside the imo-CH3 nanotubes is evidenced, opening up routes towards self-assembled nanofluidics.

  19. Polarity reversal of inside-out thyroid follicles cultured within collagen gel: structure of the junctions assessed by freeze-fracture and lanthanum permeability.

    Science.gov (United States)

    Barriere, H; Chambard, M; Selzner, J P; Mauchamp, J; Gabrion, J

    1988-01-01

    The organization of tight junctional complexes (TJs) was studied in cultured porcine thyroid cells during the inversion of polarity induced by collagen-embedding of inside-out follicles, using freeze-fracture replicas and lanthanum penetration. During the early steps of polarity reversal, freeze-fractures showed that TJs generally persisted. They increased in width and progressively branched out into the basolateral surfaces, towards the basal pole. Later, the number of TJ strands decreased and gap junctions inserted within TJ networks were found between cells in reversed follicles, in the same manner as in typically polarized follicles, embedded in collagen or in suspension. The de novo formation of TJ complexes was rarely found in the reversing structures. Despite the heterogeneity of TJs assessed by freeze-fracture, impermeability to lanthanum tracer was noted in inside-out structures. During the reversal process, some TJs remained unstained, whereas others displayed permeability to lanthanum. This heterogeneity might be due to the "opening" of a small number of junctions (perhaps only one by aggregate). When the process was achieved after 48 hr in collagen, the tightness of the junctions was complete, confirmed by the absence of lanthanum in luminal cavities of newly formed follicles.

  20. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Science.gov (United States)

    Oliveira, Ryan D; Mousel, Michelle R; Pabilonia, Kristy L; Highland, Margaret A; Taylor, J Bret; Knowles, Donald P; White, Stephen N

    2017-01-01

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such as

  1. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Directory of Open Access Journals (Sweden)

    Ryan D Oliveira

    Full Text Available Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05. Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%. While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted

  2. Green from the inside out

    Science.gov (United States)

    Seydel, Jennifer

    2011-01-01

    "Green school" is an umbrella term that covers a number of educational approaches, such as environment-based curricula, environment-integrated curricula, education for sustainability, and education for sustainable development. Green schools enrich the traditional secondary curriculum by relating it to practical issues of environmental…

  3. The Inside-Out Approach

    Science.gov (United States)

    Lindsey, Delores B.; MacDonell, Linda

    2011-01-01

    Linda MacDonell is the assistant superintendent of the Instructional Services Division of the Orange County (California) Department of Education and over the years, Delores Lindsey served as MacDonell's leadership coach. In this article, they talk about their experiences as external/internal partners building internal capacity for culturally…

  4. Listening from the Inside Out.

    Science.gov (United States)

    Joiner, Elizabeth G.

    1984-01-01

    Examines studies in brain research which are closely related to language learning. Discusses Asher's Total Physical Response and Lozanov's Suggestopedia as approaches which activate the right brain hemisphere and involve it in the language learning process. Discusses practical applications for what is currently known about listening. (SED)

  5. Aromatization of androstenedione and 16alpha-hydroxyandrostenedione in human placental microsomes. Kinetic analysis of inhibition by the 19-oxygenated and 3-deoxy analogs.

    Science.gov (United States)

    Numazawa, Mitsuteru; Watari, Yoko; Komatsu, Sachiko; Yamashita, Kouwa; Nagaoka, Masao

    2008-11-01

    Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16alpha-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1beta-(3)H]AD as a substrate and compared to that with [1beta-(3)H]16alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1beta-(3)H]AD aromatization whereas other 16alpha-hydroxy steroids 2, 3, 5, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1beta-(3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16alpha-hydroxy-17-one steroids 5 and 3-deoxy-16alpha,17beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-carbonyl and 16alpha-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site.

  6. Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice.

    Directory of Open Access Journals (Sweden)

    Piyali Chatterjee

    Full Text Available Preeclampsia (PE is a pregnancy-specific hypertensive syndrome characterized by excessive maternal immune system activation, inflammation, and endothelial dysfunction. Toll-like receptor (TLR 3 activation by double-stranded RNA (dsRNA and TLR7/8 activation by single-stranded RNA (ssRNA expressed by viruses and/or released from necrotic cells initiates a pro-inflammatory immune response; however it is unknown whether viral/endogenous RNA is a key initiating signal that contributes to the development of PE. We hypothesized that TLR3/7/8 activation will be evident in placentas of women with PE, and sufficient to induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women. Treatment of human trophoblasts with the TLR3 agonist polyinosine-polycytidylic acid (poly I:C, the TLR7-specific agonist imiquimod (R-837, or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels. Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent hypertension, endothelial dysfunction, splenomegaly, and placental inflammation. These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a key role in the development of PE.

  7. Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.

    Science.gov (United States)

    Lui, Sylvia; Jones, Rebecca L; Robinson, Nathalie J; Greenwood, Susan L; Aplin, John D; Tower, Clare L

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol) and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6). The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, pcell line: 5% at 20 mM and 40 mM, pcells in both experiments (explants at 40 µM pcell line at 10 µM and 40 µM; pcell line at 20 µM acetaldehyde demonstrated increased apoptosis (pcells at 10 mM and 40 mM (p<0.05; N = 6), and in placenta at 40 mM (p<0.05; N = 7). Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6). Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6). Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of FASD by reducing placental growth. Alcohol also reduces the transport of taurine, which is vital for developmental neurogenesis.

  8. Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.

    Directory of Open Access Journals (Sweden)

    Sylvia Lui

    Full Text Available Fetal alcohol spectrum disorder (FASD describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6. The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, p<0.05, N = 8-9 (cell line: 5% at 20 mM and 40 mM, p<0.05, N = 6. Acetaldehyde also reduced Ki67-positive cells in both experiments (explants at 40 µM p<0.05; N = 6 (cell line at 10 µM and 40 µM; p<0.05; N = 7. Only in the cell line at 20 µM acetaldehyde demonstrated increased apoptosis (p<0.05; N = 6. Alcohol inhibited taurine transport in BeWo cells at 10 mM and 40 mM (p<0.05; N = 6, and in placenta at 40 mM (p<0.05; N = 7. Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6. Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6. Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of

  9. Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.

    Science.gov (United States)

    Chang, Seok-Woo; Kim, Ji-Youn; Kim, Mi-Joo; Kim, Ga-Hyun; Yi, Jin-Kyu; Lee, Deok-Won; Kum, Kee-Yeon; Kim, Eun-Cheol

    2016-01-01

    The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.

  10. Placental pathology and hypospadias.

    Science.gov (United States)

    Chen, Yan; Sun, Luming; Geng, Hongquan; Lei, Xiaoping; Zhang, Jun

    2017-03-01

    Studies have shown that hypospadias is associated with placenta-mediated pregnancy complication (PMPC). The role of placental lesions is still unclear. We aimed to examine the association between hyposadias and placental pathology, and the effect of PMPC. Using data from the US Collaborative Perinatal Project in 1959-1966, we identified 15,780 male subjects (167 hypospadias) for analysis. Detailed placental examinations were conducted following a standard protocol. Subjects were divided into two groups according to whether they had PMPC, including small-for-gestational-age, pre-eclampsia/eclampsia or placental abruption. Logistic regression models were used to explore the association. The prevalence of hypospadias was two times higher in subjects with PMPC than those without. Compared to pregnancies with PMPC but no hypospadias, those with both PMPC and hypospadias had significant higher prevalence of placental lesions, such as low placental weight, vascular lesions, villous lesions, and membranous insertion of cord (adjusted odds ratio (OR) ranging from 2.6 to 5.2) after adjusting for potential confounders. In subjects without PMPC, no significant difference of placental pathology was found between those with or without hypospadias. About one third of hypospadias cases were complicated with PMPC and had a higher risk of placental lesions, suggesting heterogeneity of hypospadias etiology and mechanisms.

  11. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator.

    Science.gov (United States)

    Höhn, Stephanie; Hallmann, Armin

    2011-12-29

    Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in

  12. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

    Directory of Open Access Journals (Sweden)

    Höhn Stephanie

    2011-12-01

    Full Text Available Abstract Background Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities

  13. Simplified matrix solid phase dispersion procedure for the determination of parabens and benzophenone-ultraviolet filters in human placental tissue samples.

    Science.gov (United States)

    Vela-Soria, F; Rodríguez, I; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Cela, R; Navalón, A

    2014-12-05

    In recent decades, the industrial development has resulted in the appearance of a large amount of new chemicals that are able to produce disorders in the human endocrine system. These substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens and benzophenone-UV filters. Taking into account the demonstrated biological activity of these compounds, it is necessary to develop new analytical procedures to assess the exposure in order to establish, in an accurate way, relationships between EDCs and harmful health effects in population. In the present work, a new method based on a simplified sample treatment by matrix solid phase dispersion (MSPD) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated for the determination of four parabens (methyl-, ethyl-, propyl- and butylparaben) and six benzophenone-UV filters (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) in human placental tissue samples. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-13C6 and benzophenone-d10 were used as surrogates. The found limits of quantification ranged from 0.2 to 0.4 ng g(-1) and inter-day variability (evaluated as relative standard deviation) ranged from 5.4% to 12.8%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 96% to 104%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at the moment of delivery from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Integrin αII b tail distal of GFFKR participates in inside-out αII b β3 activation.

    Science.gov (United States)

    Li, A; Guo, Q; Kim, C; Hu, W; Ye, F

    2014-07-01

    Increases in ligand binding to integrins (activation) play critical roles in platelet and leukocyte function. Integrin activation requires talin and kindlin binding to integrin β cytoplasmic tails. Research has focused on the conserved GFFKR motif in integrin αII b tails, integrin β cytoplasmic tails and the binding partners of β tails. However, the roles of αII b tail distal of GFFKR motif are unexplored. To investigate the role of αII b tail distal of GFFKR in talin-mediated inside-out integrin signaling. We used model cell systems to examine the role of αII b tail distal of GFFKR in bidirectional αII b β3 signaling and αII b β3 -talin interactions. Deletion of amino acid residues after the GFFKR motif in αII b tail moderately decreased β3 (D723R)-induced activation, abolished talin-induced αII b β3 activation in model cells, and inhibited agonist-induced αII b β3 activation in megakaryocytic cells. Furthermore, residues in αII b tail distal of GFFKR did not affect outside-in αII b β3 signaling or αII b β3 -talin interaction. Addition of non-homologous or non-specific amino acids to the GFFKR motif restored αII b β3 activation in model cells and in megakaryocytic cells. Molecular modeling indicates that β3 -bound talin sterically clashes with the αII b tail in the αII b β3 complexes, potentially disfavoring the α-β interactions that keep αII b β3 inactive. The αII b tail sequences distal of GFFKR participate in talin-mediated inside-out αII b β3 activation through its steric clashes with β3 -bound talin. © 2014 International Society on Thrombosis and Haemostasis.

  15. Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations.

    Science.gov (United States)

    Provasi, Davide; Negri, Ana; Coller, Barry S; Filizola, Marta

    2014-12-01

    Platelet aggregation is the consequence of the binding of extracellular bivalent ligands such as fibrinogen and von Willebrand factor to the high affinity, active state of integrin αIIbβ3. This state is achieved through a so-called "inside-out" mechanism characterized by the membrane-assisted formation of a complex between the F2 and F3 subdomains of intracellular protein talin and the integrin β3 tail. Here, we present the results of multi-microsecond, all-atom molecular dynamics simulations carried on the complete transmembrane (TM) and C-terminal (CT) domains of αIIbβ3 integrin in an explicit lipid-water environment, and in the presence or absence of the talin-1 F2 and F3 subdomains. These large-scale simulations provide unprecedented molecular-level insights into the talin-driven inside-out activation of αIIbβ3 integrin. Specifically, they suggest a preferred conformation of the complete αIIbβ3 TM/CT domains in a lipid-water environment, and testable hypotheses of key intermolecular interactions between αIIbβ3 integrin and the F2/F3 domains of talin-1. Notably, not only do these simulations give support to a stable left-handed reverse turn conformation of the αIIb juxtamembrane motif rather than a helical turn, but they raise the question as to whether TM helix separation is required for talin-driven integrin activation. © 2014 Wiley Periodicals, Inc.

  16. Urate crystal deposition and bone erosion in gout: 'inside-out' or 'outside-in'? A dual-energy computed tomography study.

    Science.gov (United States)

    Towiwat, Patapong; Doyle, Anthony J; Gamble, Gregory D; Tan, Paul; Aati, Opetaia; Horne, Anne; Stamp, Lisa K; Dalbeth, Nicola

    2016-09-15

    It is currently unknown whether bone erosion in gout occurs through an 'inside-out' mechanism due to direct intra-osseous crystal deposition or through an 'outside-in' mechanism from the surface of bone. The aim of this study was to examine the mechanism ('outside-in' vs. 'inside-out') of monosodium urate (MSU) crystal deposition in bone erosion in gout. Specifically, we used three-dimensional dual-energy computed tomography (DECT) to analyse the positional relationship between bone and MSU crystal deposition in tophaceous gout, and to determine whether intra-osseous crystal deposition occurs in the absence of erosion. One hundred forty-four participants with gout and at least one palpable tophus had a DECT scan of both feet. Two readers independently scored all metatarsal heads (1433 bones available for scoring). For bones in contact with urate, the bone was scored for whether urate was present within an erosion, on the surface of bone or within bone only (true intra-osseous deposit). Data were analysed using generalised estimating equations. Urate in contact with bone was present in 370 (54.3 %) of 681 joints with urate deposition. For those bones in contact with urate, deposition was present on the surface of bone in 143 (38.6 %) of 370 joints and within erosion in 227 (61.4 %) of 370. True intra-osseous urate deposition was not observed at any site (p < 0.0001). For all bones with apparent intra-osseous deposition in one plane, examination in other planes revealed urate deposition within an en face erosion. In tophaceous gout, MSU crystal deposition is present within the joint, on the bone surface and within bone erosion, but it is not observed within bone in the absence of a cortical break. These data support the concept that MSU crystals deposit outside bone and contribute to bone erosion through an 'outside-in' mechanism.

  17. Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa is mandatory for TCR-mediated inside-out signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion, and migration of T cells.

    Science.gov (United States)

    Horn, Jessica; Wang, Xiaoqian; Reichardt, Peter; Stradal, Theresia E; Warnecke, Nicole; Simeoni, Luca; Gunzer, Matthias; Yablonski, Deborah; Schraven, Burkhart; Kliche, Stefanie

    2009-11-01

    Engagement of the TCR or of chemokine receptors such as CXCR4 induces adhesion and migration of T cells via so-called inside-out signaling pathways. The molecular processes underlying inside-out signaling events are as yet not completely understood. In this study, we show that TCR- and CXCR4-mediated activation of integrins critically depends on the membrane recruitment of the adhesion- and degranulation-promoting adapter protein (ADAP)/Src kinase-associated phosphoprotein of 55 kDa (SKAP55)/Rap1-interacting adapter protein (RIAM)/Rap1 module. We further demonstrate that the Src homology 2 domain containing leukocyte-specific phosphoprotein of 76 kDa (SLP76) is crucial for TCR-mediated inside-out signaling and T cell/APC interaction. Besides facilitating membrane recruitment of ADAP, SKAP55, and RIAM, SLP76 regulates TCR-mediated inside-out signaling by controlling the activation of Rap1 as well as Rac-mediated actin polymerization. Surprisingly, however, SLP76 is not mandatory for CXCR4-mediated inside-out signaling. Indeed, both CXCR4-induced T cell adhesion and migration are not affected by loss of SLP76. Moreover, after CXCR4 stimulation, the ADAP/SKAP55/RIAM/Rap1 module is recruited to the plasma membrane independently of SLP76. Collectively, our data indicate a differential requirement for SLP76 in TCR- vs CXCR4-mediated inside-out signaling pathways regulating T cell adhesion and migration.

  18. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Leonhard, Anne Katrine; Zakhary, Carina Widen

    2017-01-01

    deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. 12 different HPV-types were detected and placental HPV infection was associated to a disease history of cervical cancer. HPV DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells...

  19. Two-Tunnel Transtibial Repair of Radial Meniscus Tears Produces Comparable Results to Inside-Out Repair of Vertical Meniscus Tears.

    Science.gov (United States)

    Cinque, Mark E; Geeslin, Andrew G; Chahla, Jorge; Dornan, Grant J; LaPrade, Robert F

    2017-08-01

    Radial meniscus tears disrupt the circumferential fibers and thereby compromise meniscus integrity. Historically, radial tears were often treated with meniscectomy because of an incomplete understanding of the biomechanical consequences of these tears, limited information regarding the biomechanical performance of repair, and the technical difficulty associated with repair. There is a paucity of studies on the outcomes of the repair of radial meniscus tears. Purpose/Hypothesis: The purpose was to determine the outcomes of 2-tunnel transtibial repair of radial meniscus tears and compare these results to the outcomes of patients who underwent the repair of vertical meniscus tears with a minimum of 2-year follow-up. The hypothesis was that radial and vertical meniscus tear repair outcomes were comparable. Cohort study; Level of evidence, 3. Patients who underwent 2-tunnel transtibial pullout repair for a radial meniscus tear were included in this study and compared with patients who underwent inside-out repair for a vertical meniscus tear. Subjective questionnaires were administered preoperatively and at a minimum of 2-year follow-up, including the Lysholm score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Short Form-12 (SF-12) physical component summary (PCS), the Tegner activity scale, and patient satisfaction. Analysis of covariance was used to compare postoperative outcome scores between the meniscus repair groups while accounting for baseline scores. Adjusted mean effects relative to the radial repair group were reported with 95% CIs. Twenty-seven patients who underwent 2-tunnel transtibial pullout repair for radial meniscus tears and 33 patients who underwent inside-out repair for vertical meniscus tears were available for follow-up at a mean of 3.5 years (range, 2.0-5.4 years). No preoperative outcome score significantly differed between the groups. There were no significant group differences for any of the 2-year

  20. Placental Growth during Normal Pregnancy - A Magnetic Resonance Imaging Study

    DEFF Research Database (Denmark)

    Langhoff, Lasse; Grønbeck, Lene; von Huth, Sebastian

    2017-01-01

    OBJECTIVE: To investigate normal human placental growth longitudinally throughout the second and third trimesters using MRI. METHODS: Twenty normal, first-time singleton pregnancies were scanned 7 times between the 14th and 38th week of gestation, at 4-week intervals, using MRI. Placental volumes...

  1. Placental transport and in vitro effects of Bisphenol A

    DEFF Research Database (Denmark)

    Mørck, Thit J; Sorda, Giuseppina; Bechi, Nicoletta

    2010-01-01

    Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion...

  2. A SYSTEMATIC REVIEW OF PLACENTAL PATHOLOGY IN MATERNAL DIABETES MELLITUS

    Science.gov (United States)

    Huynh, J.; Dawson, D.; Roberts, D.; Bentley-Lewis, R.

    2014-01-01

    During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. In order to clarify these distinctions, we conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords “diabetes”, “placenta”, AND “pathology”. Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function. PMID:25524060

  3. Elevated Placental Adenosine Signaling Contributes to the Pathogenesis of Preeclampsia

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F.; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A.; Blackwell, Sean C.; Sibai, Baha M.; Chan, Lee-Nien L.; Chan, Teh-Sheng; Hicks, M. John; Blackburn, Michael R.; Kellems, Rodney E.; Xia, Yang

    2016-01-01

    Background Preeclampsia (PE) is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be due to placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways leading to impaired placentas and maternal disease development remain elusive. Methods and Results By using two independent animal models of PE—1) genetically-engineered pregnant mice with elevated adenosine exclusively in placentas, and 2) a pathogenic autoantibody-induced PE mouse model—we demonstrated here that chronically elevated placental adenosine was sufficient to induce hallmark features of PE including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacologic approaches revealed that elevated placental adenosine coupled with excessive A2B adenosine receptor (ADORA2B) signaling contributed to the development of these features of PE. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to PE. Conclusions We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for PE. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of PE, and, thereby highlight novel therapeutic targets. PMID:25538227

  4. A systematic review of placental pathology in maternal diabetes mellitus.

    Science.gov (United States)

    Huynh, J; Dawson, D; Roberts, D; Bentley-Lewis, R

    2015-02-01

    During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. We conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords "diabetes", "placenta", AND "pathology". Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  6. Do Young Galaxies Grow Inside-Out? The Deepest Probe of this Open Question Using New WFC3 Images of the Ultra Deep Field from HST

    Science.gov (United States)

    Mozena, Mark; Faber, S. M.; Koo, D. C.; Dutton, A. A.

    2010-01-01

    The recent release of the deepest (limiting magnitudes 29 AB mag) WFC3 images of the UDF provides an exciting new opportunity for studying galaxy structure at z 1-3. Previously, the highest spatial resolution data of distant galaxies were limited to the visible wavelength bands of ACS from HST. These optical wavebands shift to rest-frame UV bands (at z 1-3), which trace young stellar populations. In order to probe the mature stellar populations in galaxies, rest-frame optical to NIR bands are needed. WFC3's Y, J, and H filters allow us to observe rest-frame optical and NIR wavelengths at high redshifts with high spatial resolution and thus study a galaxy's structure, formation history, and formation mechanism in terms of its underlying stellar mass and not just its most luminous young stars. Using the galaxy fitting package GIM2D, we measure the sizes and Sersic profiles of 150 distant galaxies (z 1-3) in the UDF in ACS (bviz) and WFC3 (Y, J, H) bands. We present the deepest measurements of the radial gradient of young versus old stars of these distant galaxies and compare them to local galaxies to track inside-out galaxy growth and their evolution.

  7. Comparison of the clinical and quality-of-life outcomes after the inside-out TVT-O procedure with or without concomitant transvaginal gynaecological surgery.

    Science.gov (United States)

    Cho, M K; Kim, C H; Kang, W D; Kim, J W; Kim, S M; Kim, Y H

    2012-04-01

    The study was undertaken to compare the clinical and quality-of-life (QoL) outcomes of the inside-out transobturator vaginal tape (TVT-O)-only procedures and TVT-O procedures with concomitant transvaginal gynaecological surgery for the treatment of stress urinary incontinence (SUI). A review of charts from January 2006 to March 2010 identified 305 patients with urodynamic stress incontinence for whom we performed the TVT-O. Of the initial 305 patients, 272 (89.2%) were re-examined for complications 1 month, 4 months, 1 year and 2-4 years postoperatively (122 TVT-O only; 150 TVT-O + other transvaginal gynaecological surgery). They were also evaluated with the Urogenital Distress Inventory Questionnaire (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7) 1-4 years after the procedure. The median follow-up was 37.3 months. The success rate was 89.3% in the TVT-O-only group vs 93.3% in the TVT-O with concomitant gynaecological surgery group (p =0.729). The QoL score was quite good for 91.8% of the TVT-O-only patients and for 96.7% of the TVT-O with concomitant gynaecologic surgery patients (p =0.405). In conclusion, gynaecological operations performed concomitantly with the TVT-O procedure do not affect the clinical and QoL outcomes of the TVT-O procedure.

  8. The "inside out" transforaminal technique to treat lumbar spinal pain in an awake and aware patient under local anesthesia: results and a review of the literature.

    Science.gov (United States)

    Gore, Satishchandra; Yeung, Anthony

    2014-01-01

    Surgical management of back and leg pain is evolving and changing due to a better understanding of the patho-anatomy well correlated with its pathophysiology. Pain is better understood with in vivo visualization and probing of the pain generators using an endoscopic access rather than just relying on symptoms diagram and image correlation. This has resulted in a shared decision making involving patient and surgeon, focused on a broader spectrum of surgical as well as non-surgical treatments, and not just masking the pain generator. It has moved away from decisions based on diagnostic images alone, that, while noting the image alterations, cannot explain the pain experienced by each individual as images do not always show variations in nerve supply and patho-anatomy. The ability to isolate and visualize "pain" generators in the foramen and treating persistent pain by visualizing inflammation and compression of nerves, serves as the basis for transforaminal endoscopic (TFE) surgery. This has also resulted in better pre surgical planning with more specific and defined goals in mind. The "Inside out" philosophy of TFE surgery is safe and precise. It provides basic access to the disc and foramen to cover a large spectrum of painful pathologies.

  9. Mothering From the Inside Out: Results of a second randomized clinical trial testing a mentalization-based intervention for mothers in addiction treatment.

    Science.gov (United States)

    Suchman, Nancy E; DeCoste, Cindy L; McMahon, Thomas J; Dalton, Rachel; Mayes, Linda C; Borelli, Jessica

    2017-05-01

    Mothers with histories of alcohol and drug addiction have shown greater difficulty parenting young children than mothers with no history of substance misuse. This study was the second randomized clinical trial testing the efficacy of Mothering From the Inside Out (MIO), a 12-week mentalization-based individual therapy designed to address psychological deficits commonly associated with chronic substance use that also interfere with the capacity to parent young children. Eighty-seven mothers caring for a child between 11 and 60 months of age were randomly assigned to receive 12 sessions of MIO versus 12 sessions of parent education (PE), a psychoeducation active control comparison. Maternal reflective functioning, representations of caregiving, mother-child interaction quality, and child attachment were evaluated at baseline and posttreatment and 3-month follow-up. Mother-child interaction quality was assessed again at 12-month follow-up. In comparison with PE mothers, MIO mothers demonstrated a higher capacity for reflective functioning and representational coherence at posttreatment and 3-month follow-up. At 12-month follow-up, compared to PE cohorts, MIO mothers demonstrated greater sensitivity, their children showed greater involvement, and MIO dyads showed greater reciprocity. As addiction severity increased, MIO also appeared to serve as a protective factor for maternal reflective functioning, quality of mother-child interactions, and child attachment status. Results demonstrate the promise of mentalization-based interventions provided concomitant with addiction treatment for mothers and their young children.

  10. Low BIK outside-inside-out interactive inflammation immune-induced transcription-dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384.

    Science.gov (United States)

    Huang, Juxiang; Wang, Lin; Jiang, Minghu; Chen, Qingchun; Zhang, Xiaoyu; Wang, Yangming; Jiang, Zhenfu; Zhang, Zhongjie

    2016-04-01

    Eighteen different Pearson mutual-positive-correlation BIK-activatory molecular feedback upstream and downstream networks were constructed from 79 overlapping of 376 GRNInfer and 98 Pearson under BIK CC ≥ 0.25 in low normal adjacent tissues of Taiwan compared with high lung adenocarcinoma. Our identified BIK interactive total feedback molecular network showed FUT3 [fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase Lewis blood group)], PMM2 (phosphomannomutase 2), SQSTM1 (sequestosome 1), SFN_2 [REX2 RNA exonuclease 2 homolog (S. cerevisiae)] and ZNF384 (zinc finger protein 384) in low normal adjacent tissues of lung adenocarcinoma. BIK interactive total feedback terms included mitochondrial envelope, endomembrane system, integral to membrane, Golgi apparatus, cytoplasm, nucleus, cytosol, intracellular signaling cascade, mitochondrion, extracellular space, inflammation, immune response, apoptosis, cell differentiation, cell cycle, regulation of cell cycle, cell proliferation, estrogen-responsive protein Efp controls cell cycle and breast tumors growth, induction or regulation of apoptosis based on integrative GO, KEGG, GenMAPP, BioCarta and disease databases in low normal adjacent tissues of lung adenocarcinoma. Therefore, we propose low BIK outside-inside-out interactive inflammation immune-induced transcription-dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384 in normal adjacent tissues of lung adenocarcinoma.

  11. Mothering from the Inside Out: results of a pilot study testing a mentalization-based therapy for mothers enrolled in mental health services.

    Science.gov (United States)

    Suchman, Nancy E; Ordway, Monica R; de Las Heras, Lourdes; McMahon, Thomas J

    2016-12-01

    Mothers who are involved with mental health services (for themselves or their children) rarely receive adequate support for their role as parents. Mental illness in a parent or child often exacerbates the challenges of managing psychological distress that is germane to the parenting roll. Mentalization-based approaches to psychotherapy for parents have the potential to address challenges of emotional regulation in parents by supporting their capacity to recognize and modulate negative affect during stressful parenting situations. In this study, we piloted Mothering from the Inside Out (MIO) with 17 mothers receiving services at a community-based mental health clinic. MIO is a 12-week, mentalization-based parenting intervention that demonstrated efficacy in two previous randomized controlled trials with substance using mothers. In this study, we were interested in determining whether community-based clinicians could deliver MIO with sustained fidelity. We were also interested in examining the preliminary feasibility, acceptability and efficacy of MIO when delivered by clinicians in a community mental health center. Finally, we were interested in replicating prior tests of the proposed treatment mechanisms. Treatment outcomes included maternal reflective functioning, psychiatric and parenting stress, and mother-child interaction quality. Our findings indicated that MIO was feasible and acceptable when delivered in the community-based setting and that all maternal indices improved. However, no improvement in mother-child interaction quality was found, possibly because of insufficient time for these changes to consolidate.

  12. Low-cost transobturator vaginal tape inside-out procedure for the treatment of female stress urinary incontinence using ordinary polypropylene mesh.

    Science.gov (United States)

    ElSheemy, Mohammed S; Elsergany, Ragheb; ElShenoufy, Ahmed

    2015-04-01

    The aim of this study is to describe the use of ordinary polypropylene mesh and our modified helical passers through a transobturator vaginal tape inside-out technique (TVT-O) as a low-cost alternative to available commercial kits in the treatment of stress urinary incontinence (SUI) with evaluation of its long-term safety and efficacy. This is important in developing countries due to limited health care resources. Tailored (11 × 1.5 cm) polypropylene tape was inserted in 59 women from June 2006 to June 2009 at the Urology Department, Cairo University Hospitals as an open prospective study. SUI was diagnosed by positive cough stress test (CST) and abdominal leak point pressure (ALPP). Patients with post-void residual urine (PVRU) > 100 ml, bladder capacity polypropylene suture (1 %) and felt subcutaneous polypropylene sutures (3 %). We had no cases of erosions or de novo urgency. SUIQQ indices improved significantly, while urodynamic parameters showed no significant difference postoperatively. Of the patients, 54 (91 %) were cured and 3 (5 %) improved, while failure was detected in 2 (3 %) patients. Our technique is safe with excellent 5-year results. It should be considered as a low-cost alternative to available commercial kits in the treatment of SUI mainly for public health systems with few financial resources.

  13. Transobturator vaginal tape inside out for treatment of urethral sphincter mechanism incompetence in female dogs: cadaveric study and preliminary study in continent female dogs.

    Science.gov (United States)

    Claeys, Stéphanie; Ruel, Hélène; de Leval, Jean; Heimann, Marianne; Hamaide, Annick

    2010-12-01

    (1) To describe a surgical technique adapted from the "transobturator vaginal tape inside-out" (TVT-O) used in women and to define the trajectory of the tape on canine cadavers, and (2) to determine the urodynamic and morphological effects of the TVT-O in continent bitches. Cadaveric and experimental in vivo study. Fresh female canine cadavers (n=12) and spayed female Beagle dogs (2). (1) TVT-O was inserted in 12 cadavers. Dissection was performed and distances between the tape and neighboring structures were recorded. (2) TVT-O was inserted in 2 continent female Beagle dogs. Urethral pressure profilometry and vaginourethrograms were performed preoperatively, immediately after surgery, and 2, 4, and 6 months postoperatively. Histopathology was performed 6 months after surgery. (1) TVT-O tape was consistently located in a perineal space before entering the obturator foramina and was located at a safe distance from major neurovascular structures including the femoral vessels and obturator nerve. (2) TVT-O was performed without any surgical or postoperative complications in 2 continent bitches. Histopathologic examination of the tissues surrounding the tape revealed a mild fibroblastic proliferation with a mild to minimal lymphoplasmacytic inflammatory infiltration. TVT-O is a feasible and accurate procedure that can be performed in continent bitches with a low risk of complications. © Copyright 2010 by The American College of Veterinary Surgeons.

  14. Evolution of placental function in mammals

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2012-01-01

    gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from...... and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally......, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation....

  15. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

    Mathiesen, Line; Mose, Tina; Mørck, Thit Juul

    2010-01-01

    Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting the plac......Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting...... the placental perfusion model in Copenhagen including control substances. The positive control substance antipyrine shows no difference in transport regardless of perfusion media used or of terms of delivery (n=59, p

  16. [Expression of contractile proteins alpha-actin and myosin of smooth muscle cells and collagen of IV type in human placenta at placental insufficiency in III trimester of pregnancy].

    Science.gov (United States)

    Khozhaĭ, L I; Otellin, V A; Pozharisskiĭ, K M; Pavlova, N G

    2010-01-01

    Changes of expression of contractile proteins (alpha-actin and myosin of smooth muscle cell) and of collagen of IV type in stroma of human placental villi were studied at the diagnosed placental insufficiency (PI) in III trimester of pregnancy. The study revealed pronounced disturbances of expression of contractile proteins and collagen of IV type at PI. It is shown that in perivascular envelopes of vessels of stem and intermediate villi there is present a much greater amount of cells expressing smooth muscle actin and myosin. These cells are arranged by the denser concentric layers and more compactly than in norm and fill the intervascular space inside the villi. The width of perivascular envelopes of vessels is higher, while vascular lumens are lower than in norm. In terminal villi the capillary walls are thickened and the number of pericytes immunopositive against the smooth muscle cell alpha-actin and myosin as well as collagen of IV type is increased. The change of synthesis of the cytoskeletal contractile proteins and collagen of IV type is shown to lead to structural disturbances of villi of different types and of perivascular areas and vessels, which doubtlessly indicates their participation in pathogenesis of placental dysfunction and of disturbance of placental hemodynamics.

  17. Placental adaptation: what can we learn from birthweight:placental weight ratio?

    Directory of Open Access Journals (Sweden)

    Christina Elizabeth Hayward

    2016-02-01

    Full Text Available Appropriate fetal growth relies upon adequate placental nutrient transfer. Birthweight:placental weight ratio (BW:PW ratio is often used as a proxy for placental efficiency, defined as the grams of fetus produced per gram placenta. An elevated BW:PW ratio in an appropriately grown fetus (small placenta is assumed to be due to up-regulated placental nutrient transfer capacity i.e. a higher nutrient net flux per gram placenta. In fetal growth restriction (FGR, where a fetus fails to achieve its genetically pre-determined growth potential, placental weight and BW:PW ratio are often reduced which may indicate a placenta that fails to adapt its nutrient transfer capacity to compensate for its small size. This review considers the literature on BW:PW ratio in both large cohort studies of normal pregnancies and those studies offering insight into the relationship between BW:PW ratio and outcome measures including stillbirth, FGR and subsequent postnatal consequences. The core of this review is the question of whether BW:PW ratio is truly indicative of altered placental efficiency, and whether changes in BW:PW ratio reflect those placentas which adapt their nutrient transfer according to their size. We consider this question using data from mice and humans, focusing upon studies that have measured the activity of the well characterized placental system A amino acid transporter, both in uncomplicated pregnancies and in FGR. Evidence suggests that BW:PW ratio is reduced both in FGR and in pregnancies resulting in a small for gestational age (SGA, birthweight <10th centile infant but this effect is more pronounced earlier in gestation (<28 weeks. In mice, there is a clear association between increased BW:PW ratio and increased placental system A activity. Additionally, there is good evidence in wild-type mice that small placentas upregulate placental nutrient transfer to prevent fetal undergrowth. In humans, this association between BW:PW ratio and

  18. Effectiveness of Retropubic Tension-Free Vaginal Tape and Transobturator Inside-Out Tape Procedures in Women With Overactive Bladder and Stress Urinary Incontinence

    Science.gov (United States)

    Han, Ji-Yeon; Choo, Myung-Soo; Lee, Young-Suk; Seo, Ju Tae; Kim, Jang Hwan; Kim, Young Ho

    2013-01-01

    Purpose We compared the effectiveness of the retropubic tension-free vaginal tape (TVT) and the transobturator inside-out tape (TVT-O) in treating symptoms of overactive bladder (OAB) in women with stress urinary incontinence (SUI). Methods Women with urodynamic SUI and OAB (mean urgency episodes ≥1 and frequency ≥8/24 hours on a 3-day voiding diary) were assigned to the TVT or TVT-O group. Preoperative measures were based on a urodynamic study, 3-day voiding diary, the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTSSF), and the urgency perception scale (UPS). At 12 postoperative months, the 3-day voiding diary, symptoms questionnaire, patient satisfaction, and standing stress test were assessed. The primary endpoint was change in the number of urgency episodes/24 hours from baseline to 12 months. Results In this group of 132 women, 42 received TVT and 90 received TVT-O. The mean urgency episodes/24 hours decreased from 6.3±5.5 to 1.6±3.2 in the TVT group and from 5.1±4.4 to 1.8±3.0 in the TVT-O group. The mean percent change was significantly greater after TVT than after TVT-O (73% vs. 60%, P=0.049). All subscales of BFLUTSSF and UPS were significantly improved using either method, with significantly greater improvement seen in the quality of life (QoL) domain after TVT (P=0.002). There were no significant differences in the cure and satisfaction rates between the two groups. Conclusions Intervention with the TVT or the TVT-O significantly improved symptoms of OAB in women with SUI and OAB. Urgency and QoL significantly improved after TVT compared with that after TVT-O. PMID:24143294

  19. Inside-out Regulation of Ectodomain Cleavage of Cluster-of-Differentiation-44 (CD44) and of Neuregulin-1 Requires Substrate Dimerization.

    Science.gov (United States)

    Hartmann, Monika; Parra, Liseth M; Ruschel, Anne; Lindner, Christina; Morrison, Helen; Herrlich, Andreas; Herrlich, Peter

    2015-07-10

    Ectodomain shedding of transmembrane precursor proteins generates numerous life-essential molecules, such as epidermal growth factor receptor ligands. This cleavage not only releases the regulatory growth factor, but it is also the required first step for the subsequent processing by γ-secretase and the release of gene regulatory intracellular fragments. Signaling within the cell modifies the cytoplasmic tails of substrates, a step important in starting the specific and regulated cleavage of a large number of studied substrates. Ectodomain cleavage occurs, however, on the outside of the plasma membrane and is carried out by membrane-bound metalloproteases. How the intracellular domain modification communicates with the ectodomain of the substrate to allow for cleavage to occur is unknown. Here, we show that homodimerization of a cluster-of-differentiation-44 or of pro-neuregulin-1 monomers represents an essential pre-condition for their regulated ectodomain cleavage. Both substrates are associated with their respective metalloproteases under both basal or cleavage-stimulated conditions. These interactions only turn productive by specific intracellular signal-induced intracellular domain modifications of the substrates, which in turn regulate metalloprotease access to the substrates' ectodomain and cleavage. We propose that substrate intracellular domain modification induces a relative rotation or other positional change of the dimerization partners that allow metalloprotease cleavage in the extracellular space. Our findings fill an important gap in understanding substrate-specific inside-out signal transfer along cleaved transmembrane proteins and suggest that substrate dimerization (homo- or possibly heterodimerization) might represent a general principle in ectodomain shedding. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Repair of the Posterior Third of the Meniscus During Meniscus Allograft Transplantation: Conventional Inside-Out Repair Versus FasT-Fix All-Inside Repair.

    Science.gov (United States)

    Ahn, Ji Hyun; Kim, Chang Hee; Lee, Sung Hyun

    2016-02-01

    To compare conventional inside-out (IO) repair and all-inside (AI) repair for the posterior third of the meniscus during meniscus allograft transplantation (MAT). Among the 64 enrolled patients, 31 patients underwent MAT with conventional IO repair, and 33 patients underwent MAT with AI repair using the FasT-Fix instrument for the posterior third of the meniscus allograft. All of the patients were retrospectively evaluated through clinical assessment at the last follow-up (54.3 months in the IO group and 55.4 months in the AI group) and through magnetic resonance imaging assessment for meniscal extrusion at 1 year postoperatively. Thirty patients (15 in each group) were evaluated through second-look arthroscopy at 1 year postoperatively. There was no significant difference in the mean Lysholm score (91.3 in the IO group and 92.3 in the AI group; P = .358) or the mean Tegner activity scale (7.1 in each group; P = .885) between the 2 groups. There was no significant difference in the mean meniscal extrusion (2.6 mm in the IO group and 2.8 mm in the AI group; P = .454), relative percentage of extrusion value (25.6% in the IO group and 24.7% in the AI group; P = .721), or meniscal healing on second-look arthroscopy (P = .796) between the 2 groups. The difference in operative time between the 2 groups was found to be statistically significant (169.9 minutes in the IO group and 123.3 minutes in the AI group; P < .001). Our comparative study on the different techniques for posterior repair of meniscus allograft suggested that AI posterior repair using FasT-Fix could be an alternative method to conventional IO repair as it gives a similar postoperative result and requires a shorter operative time. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  1. Contact area between femoral tunnel and interference screw in anatomic rectangular tunnel ACL reconstruction: a comparison of outside-in and trans-portal inside-out techniques.

    Science.gov (United States)

    Hiramatsu, Kunihiko; Mae, Tatsuo; Tachibana, Yuta; Nakagawa, Shigeto; Shino, Konsei

    2017-10-20

    The purpose of this study was to compare the femoral tunnel length, the femoral graft bending angle at the femoral tunnel aperture, and the contact area between the femoral tunnel wall and an interference screw used for fixation in anatomic rectangular tunnel anterior cruciate ligament (ACL) reconstruction (ART ACLR). The study included 149 patients with primary ACL injury who underwent ART ACLR. Preoperatively, flexion angle of the index knee was checked under general anaesthesia. Those of less than 130° of passive flexion were assigned to the outside-in (OI) technique (78 patients), while the others to the trans-portal inside-out (TP) technique (71 patients). The patients underwent computed tomography with multiplanar reconstruction at 3-5 weeks post-operatively. Femoral tunnel length, graft bending angle, and contact ratio between the IFS and femoral tunnel were assessed. P < 0.05 was considered statistically significant. The femoral tunnel length in the OI technique was significantly longer than that in the TP technique (P < 0.001). The femoral graft bending angle in the OI technique was significantly more acute than that in the TP technique (P < 0.001). The contact ratio in the OI technique was significantly larger than that in the TP technique at every point in the femoral tunnel (P < 0.001). The OI technique resulted in a more acute femoral graft bending angle, longer mean femoral tunnel length, and larger contact ratio than the TP technique after ART ACLR. Retrospective comparative study, Level III.

  2. Aromatase reaction of 3-deoxyandrogens: steric mode of the C-19 oxygenation and cleavage of the C10-C19 bond by human placental aromatase.

    Science.gov (United States)

    Numazawa, Mitsuteru; Nagaoka, Masao; Sohtome, Norishige

    2005-08-16

    Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone and formic acid through three sequential oxygenations of the 19-methyl group. To gain insight into the catalytic function of aromatase as well as the mechanism of the hitherto uncertain third oxygenation step, we focused on the aromatase-catalyzed 19-oxygenation of 3-deoxyandrogens: 3-deoxy-AD (1), which is a very powerful competitive inhibitor but poor substrate of aromatase, and its 5-ene isomer 4, which is a good competitive inhibitor and effective substrate of the enzyme. In incubations of their 19S-(3)H-labeled 19-hydroxy derivatives 2 and 5 and the corresponding 19R-(3)H isomers with human placental microsomes in the presence of NADPH under air, the radioactivity was liberated in both water and formic acid. The productions of (3)H(2)O and (3)HCOOH were blocked by the substrate AD or the inhibitor 4-hydroxy-AD, indicating that these productions are due to a catalytic function of aromatase. A comparison of the (3)H(2)O production from S-(3)H substrates 2 and 5 with that from the corresponding R-(3)H isomers revealed that the 19-pro-R hydrogen atom was stereospecifically (pro-R:pro-S = 100:0) removed in the conversion of 5-ene substrate 5 into the 19-oxo product 6, whereas 75:25 stereoselectivity for the loss of the pro-R and pro-S hydrogen atoms was observed in the oxygenation of the other substrate, 2. The present results reveal that human placental aromatase catalyzes three sequential oxygenations at C-19 of 3-deoxyandrogens 1 and 4 to cause the cleavage of the C(10)-C(19) bond through their 19-hydroxy (2 and 5) and 19-oxo (3 and 6) intermediates, respectively, where there is a difference in the stereochemistry between the two androgens in the second 19-hydroxylation. It is implied that the aromatase-catalyzed 19-oxygenation of 5-ene steroid 4 but not the 4-ene isomer 1 would proceed in the same steric mechanism as that involved in the AD

  3. l-Methionine Placental Uptake

    Science.gov (United States)

    Araújo, João R.; Correia-Branco, Ana; Ramalho, Carla; Gonçalves, Pedro; Pinho, Maria J.; Keating, Elisa

    2013-01-01

    Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process. PMID:23653387

  4. Risk factors of placental abruption

    OpenAIRE

    Ghaheh, Hooria Seyedhosseini; Feizi, Awat; Mousavi, Maryam; Sohrabi, Davood; Mesghari, Leila; Hosseini, Zahra

    2013-01-01

    Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case ? control study birth records included 78 cases with placental abruption and 780 randomly selected co...

  5. Linkages to Public Land Framework: toward embedding humans in ecosystem analyses by using “inside-out social assessment.”

    Science.gov (United States)

    Joanna Endter-Wada; Dale J. Blahna

    2011-01-01

    This article presents the " Linkages to Public Land" (LPL) Framework, a general but comprehensive data-gathering and analysis approach aimed at informing citizen and agency decision making about the social environment of public land. This social assessment and planning approach identifies and categorizes various types of linkages that people have to public...

  6. Cigarette smoke extract induces placental growth factor release from human bronchial epithelial cells via ROS/MAPK(ERK-1/2/Egr-1 axis

    Directory of Open Access Journals (Sweden)

    Wu D

    2016-12-01

    Full Text Available Dong Wu,1,* Yalian Yuan,1,* Zhixiu Lin,2,* Tianwen Lai,1 Min Chen,1 Wen Li,1 Quanchao Lv,1 Binfan Yuan,1 Dongmin Li,1 Bin Wu1 1Department of Respiratory, Institute of Respiratory Diseases, 2Department of Pharmacy, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS-dependent activation of the mitogen-activated protein kinase (MAPK (extracellular signal-regulated kinase1/2 [ERK-1/2]/early growth response-1 (Egr-1 pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE. The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2 cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking

  7. Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

    Directory of Open Access Journals (Sweden)

    Gabor Szalai

    Full Text Available Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1 not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1 develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a in preeclampsia; 2 determine blood pressures in non-stressed conditions; and 3 develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP monitoring.Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11 or green fluorescent protein (GFP; n = 9 on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18. Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2; GD18. Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2. Placental and fetal weights did not differ between the groups

  8. Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

    Science.gov (United States)

    Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S; Hernandez-Andrade, Edgar; Than, Nandor Gabor

    2015-01-01

    Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One

  9. Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice

    Science.gov (United States)

    Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L.; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor

    2015-01-01

    Objective Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10-2). Placental and fetal weights did not differ between the

  10. Two-way regulation between cells and aligned collagen fibrils: local 3D matrix formation and accelerated neural differentiation of human decidua parietalis placental stem cells.

    Science.gov (United States)

    Li, Wen; Zhu, Bofan; Strakova, Zuzana; Wang, Rong

    2014-08-08

    It has been well established that an aligned matrix provides structural and signaling cues to guide cell polarization and cell fate decision. However, the modulation role of cells in matrix remodeling and the feedforward effect on stem cell differentiation have not been studied extensively. In this study, we report on the concerted changes of human decidua parietalis placental stem cells (hdpPSCs) and the highly ordered collagen fibril matrix in response to cell-matrix interaction. With high-resolution imaging, we found the hdpPSCs interacted with the matrix by deforming the cell shape, harvesting the nearby collagen fibrils, and reorganizing the fibrils around the cell body to transform a 2D matrix to a localized 3D matrix. Such a unique 3D matrix prompted high expression of β-1 integrin around the cell body that mediates and facilitates the stem cell differentiation toward neural cells. The study offers insights into the coordinated, dynamic changes at the cell-matrix interface and elucidates cell modulation of its matrix to establish structural and biochemical cues for effective cell growth and differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Kinetic analysis of reversible inhibition of 16alpha-hydroxyandrostenedione aromatization in human placental microsomes by suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Mutsumi, Ayako; Tachibana, Mii; Yoshimura, Akiko

    2003-06-01

    To gain insight into the catalytic function of aromatase and its substrate specificity, we studied reversible inhibition of 16alpha-hydroxyandrostenedione (16alpha-OHAD) aromatization in human placental microsomes by several suicide substrates of androstenedione (AD) aromatization, including 4-hydroxyAD (1), 6-oxoAD (2) and its 19-hydroxy analogue 3, androst-5-ene-4,7,17-trione (4), and 10beta-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a suicide inactivation of 16alpha-OHAD aromatization. All inhibitors examined blocked 16alpha-OHAD aromatization in a competitive manner with apparent K(i) values ranging from 0.50 to 980 nM. The relative K(i) values between inhibitors 1-5 obtained in the 16alpha-OHAD aromatization experiments were markedly different from those obtained in the AD aromatization experiments. The results predict that all inhibitors examined bind to the 16alpha-OHAD binding site in a manner that does not cause suicide inactivation of 16alpha-OHAD aromatization. These findings would be useful for understanding the active (binding) site structure as well as the catalytic function of aromatase.

  12. Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue.

    Science.gov (United States)

    Hara, A; Sakai, N; Yamada, H; Yoshimi, N; Tanaka, T; Mori, H

    1993-01-01

    Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.

  13. Exposure to a MRI-type high-strength static magnetic field stimulates megakaryocytic/erythroid hematopoiesis in CD34+ cells from human placental and umbilical cord blood.

    Science.gov (United States)

    Monzen, Satoru; Takahashi, Kenji; Toki, Tsutomu; Ito, Etsuro; Sakurai, Tomonori; Miyakoshi, Junji; Kashiwakura, Ikuo

    2009-05-01

    The biological response after exposure to a high-strength static magnetic field (SMF) has recently been widely discussed from the perspective of possible health benefits as well as potential adverse effects. To clarify this issue, CD34+ cells from human placental and umbilical cord blood were exposed under conditions of high-strength SMF in vitro. The high-strength SMF exposure system was comprised of a magnetic field generator with a helium-free superconducting magnet with built-in CO2 incubator. Freshly prepared CD34 cells were exposed to a 5 tesla (T) SMF with the strongest magnetic field gradient (41.7 T/m) or a 10 T SMF without magnetic field gradient for 4 or 16 h. In the harvested cells after exposure to 10 T SMF for 16 h, a significant increase of hematopoietic progenitors in the total burst-forming unit erythroid- and megakaryocytic progenitor cells-derived colony formation was observed, thus producing 1.72- and 1.77-fold higher than the control, respectively. Furthermore, early hematopoiesis-related and cell cycle-related genes were found to be significantly up-regulated by exposure to SMF. These results suggest that the 10 T SMF exposure may change gene expressions and result in the specific enhancement of megakaryocytic/erythroid progenitor (MEP) differentiation from pluripotent hematopoietic stem cells and/or the proliferation of bipotent MEP. Copyright 2009 Wiley-Liss, Inc.

  14. The all-inside meniscal repair technique has less risk of injury to the lateral geniculate artery than the inside-out repair technique when suturing the lateral meniscus.

    Science.gov (United States)

    Cuéllar, Adrián; Cuéllar, Ricardo; Heredia, Jorge Díaz; Cuéllar, Asier; García-Alonso, Ignacio; Ruiz-Ibán, Miguel Angel

    2017-03-13

    To evaluate the risk of injury to the inferior lateral geniculate artery with two different techniques for lateral meniscus repair. Eight cadaveric knees were used. Inside-out sutures and an all-inside suture device were placed at the most lateral edge of the popliteal hiatus, and 15 and 30 mm anterior to this point. The minimum distances between the sutures and the inferior lateral geniculate artery were measured through a limited lateral arthrotomy. Artery penetration or collapse due to the sutures was also evaluated. The median distance between the sutures and the artery when inserted at the lateral edge of the popliteal hiatus was 1.5 mm (interquartile range: 1.3) for the inside-out technique and 1.5 mm (1.3) for the all-inside technique (differences not significant, n.s.). When the sutures were inserted 15 mm anterior to the popliteal hiatus the distances were 1.0 mm (1.1) and 1.3 mm (1.0) for the inside-out technique and the all-inside technique, respectively (n.s.). When the sutures were inserted 30 mm anterior to the popliteal hiatus the distances were 1.0 mm (1.0) and 1.5 mm (1.0) for the inside-out technique and the all-inside technique, respectively (n.s.). The artery was punctured with two of the inside-out sutures placed 15 mm from the popliteal hiatus, no puncturing occurred in the all-inside technique (n.s.). Tying of the inside-out sutures resulted in obliteration of the artery in four of eight sutures placed at 15 mm from the popliteal hiatus and three of eight sutures at 30 mm; no obliteration of the artery was found using the all-inside device (significant differences, p = 0.002). Although both all-inside and inside-out lateral meniscal repair techniques place sutures very close to the lateral geniculate artery, the inside-out technique is riskier as extra-articular knot tying can cause artery obliteration when suturing the part of the meniscus immediately lateral to the popliteal hiatus. Therefore, all-inside meniscal repair

  15. Graft Bending Angle at the Intra-articular Femoral Tunnel Aperture After Single-Bundle Posterior Cruciate Ligament Reconstruction: Inside-Out Versus Outside-In Techniques.

    Science.gov (United States)

    Jang, Ki-Mo; Park, Sung-Chul; Lee, Dae-Hee

    2016-05-01

    To date, no in vivo 3-dimensional computed tomography (3D-CT) studies have compared graft bending angles at the femoral tunnel aperture and femoral tunnel length in patients who underwent posterior cruciate ligament (PCL) reconstruction with outside-in (OI) and inside-out (IO) techniques. This study used in vivo 3D-CT analysis to compare graft bending angles at the femoral tunnel aperture and femoral tunnel lengths after OI and IO femoral drilling techniques in single-bundle PCL reconstruction. It was hypothesized that the graft bending angle at the femoral tunnel aperture would be less acute with the OI compared with the IO technique, with no difference in femoral tunnel lengths. Cross-sectional study; Level of evidence, 3. Immediate postoperative in vivo 3D-CT and curved planar reformation were used to assess the graft bending angles and femoral tunnel lengths in the sagittal, axial, and coronal planes in 67 patients who underwent single-bundle PCL reconstruction with the OI (n = 37) and IO (n = 30) techniques. The mean graft bending angles on the sagittal and axial planes were 8.2° more acute (23.5° vs 15.3°, P = .011) and 5.3° more acute (49.0° vs 43.7°, P = .013), respectively, with the IO compared with the OI technique, but the difference in the coronal plane was not statistically significant (25.3° vs 24.8°, P = .623). Femoral tunnel length was similar in the 2 groups. The graft bending angles in single-bundle PCL reconstruction were more acute in the sagittal and axial planes with the IO compared with the OI technique, but there was no difference in the coronal plane. In addition, femoral tunnel lengths did not differ significantly in patients who underwent OI and IO single-bundle PCL reconstructions. Although further biomechanical studies are needed to evaluate the effect on graft failure of a <10° difference in graft bending angle, the small magnitude of this difference would likely have little adverse effect on graft survival. © 2016 The Author(s).

  16. Fetal gender specific expression of tandem-repeat galectins in placental tissue from normally progressed human pregnancies and intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Hutter, Stefan; Knabl, Julia; Andergassen, Ulrich; Mayr, Doris; Hofmann, Simone; Kuhn, Christina; Mahner, Sven; Arck, Petra; Jeschke, Udo

    2015-12-01

    The tandem-repeat type galectins, which comprise of gal-4, -6, -8, -9, and -12, form a sub-family of galectins. Gal-6 is expressed only in rodents, whereas the other four galectins, tandem-repeat galectins, are also detectable in human tissue. The placental expression of individual members of the tandem-repeat gal family is increasingly known, however, systematic, comparative analysis especially in the human placenta from normal or pathological pregnancies is still lacking. Within this study, third trimester placentas obtained at delivery (n = 14 IUGR, n = 15 controls, equally divided in placentas from male and female fetuses) were analyzed for the expression of gal-4, -8, -9 and -12 by immunohistology and immunofluorescence, data were obtained by using a semiquantitative scoring system. Double immune-fluorescence with trophoblast specific markers was used to identify co-expression in the decidua. We identified dysregulation of tandem repeat galectins in IUGR placentas with a strong connection to the fetal gender. We identified a significantly lower expression of gal-4 and gal-9 in villous trophoblast tissue of IUGR placentas with male fetuses and a downregulation of gal-4 and gal-8 in extravillous trophoblast (EVT) from IUGR and male fetuses. Conversely, expression of gal-9 and gal-12 was higher in EVT of IUGR cases in placentas with female fetuses. Double immunofluorescence using cytokeratin-7 confirmed the expression of tandem-repeat galectins in EVT. The human placenta expresses tandem-repeat type galectins in villous trophoblasts, EVT, endothelial cells and decidual stromal cells. Summarizing all effects, there is significant down-regulation of gal-4, -8 and gal-9 in the IUGR trophoblast of male fetuses. In contrast, in IUGR pregnancies with female fetus gal-9 and gal-12 are upregulated in the EVT and in endothelial cells in the cases of gal-12. Therefore we propose a fetal-gender specific action of tandem repeat galectins in IUGR placentas. Copyright © 2015

  17. The nature of placental steroid sulphatase deficiency in man

    NARCIS (Netherlands)

    van der Loos, C. M.; van Breda, A. J.; van den Berg, F. M.; Jöbsis, A. C.

    1983-01-01

    Human placental steroid sulphatase was partially purified from microsome suspensions of control and steroid sulphatase deficient placentae. After polyacrylamidegel electrophoresis, staining for protein and enzymatic activity revealed that steroid sulphatase from control placenta migrates at Rf =

  18. Placentation in mammals

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    An overview is given of variations in placentation with particular focus on yolk sac, paraplacenta, and other structures important to histotrophic nutrition. The placenta proper varies in general shape, internal structure, and the number of tissues in the interhemal barrier. Yolk sac membranes...

  19. In Vitro Infection of Trypanosoma cruzi Causes Decrease in Glucose Transporter Protein-1 (GLUT1 Expression in Explants of Human Placental Villi Cultured under Normal and High Glucose Concentrations

    Directory of Open Access Journals (Sweden)

    Luciana Mezzano

    2012-01-01

    Full Text Available Trypanosoma cruzi, the etiologic Chagas' disease agent, induces changes in protein pattern of the human placenta syncytiotrophoblast. The glucose transporter protein-1 (GLUT1 is the primary isoform involved in transplacental glucose transport. We carried out in vitro assays to determine if T. cruzi infection would induce changes in placental GLUT1 protein expression under normal and high concentration of glucose. Using Western blot and immunohistological techniques, GLUT1 expression was determined in normal placental villi cultured under normal or high concentrations of glucose, with or without in vitro T. cruzi infection, for 24 and 48 hours. High glucose media or T. cruzi infection alone reduced GLUT1 expression. A yet more accentuated reduction was observed when infection and high glucose condition took place together. We inform, for the first time, that T. cruzi infection may induce reduction of GLUT1 expression under normal and high glucose concentrations, and this effect is synergic to high glucose concentrations.

  20. Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice

    NARCIS (Netherlands)

    E. Vasilopoulou (Elisavet); L.S. Loubière (Laurence); H. Heuer (Heike); M. Trajkovic-Arsic (Marija); V.M. Darras (Veerle); T.J. Visser (Theo); G.E. Lash (Gendie); G.S. Whitley (Guy); C.J. McCabe (Christopher); J.A. Franklyn (Jayne); M.D. Kilby (Mark); S.Y. Chan (Shiao)

    2013-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation,

  1. Evaluation of Placental Blood Flow in Patients with Placental Insufficiency

    Directory of Open Access Journals (Sweden)

    Julia E. Dobrokhotova

    2017-03-01

    Full Text Available Background: Placental insufficiency is a major problem of modern obstetrics due to its link to maternal and perinatal morbidity and mortality. Placental microcirculatory disorders play a decisive role in the pathogenesis of this condition. Thus, an evaluation of placental blood flow is of particular importance and crucial for appropriate diagnosis. The aim of this study was to evaluate placental blood flow in patients with placental insufficiency. SMI (superb microvascular imaging was compared to color Doppler for that purpose. Materials and Methods: Primigravida patients (n=91 at 15 to 16 weeks of gestation were enrolled. Inclusion criteria were spontaneous singleton pregnancy, age from 18 to 45 years. All participants were divided into 2 groups: Group 1 – control group (n=27 and Group 2 – threatened miscarriage group (n=64. Transvaginal ultrasound and color Doppler were performed to assess uteroplacental circulation. Placental blood flow was evaluated using a Toshiba Aplio™ 500 machine equipped with an SMI tool. Results: Placental blood flow assessment in patients with normal pregnancy revealed homogenous placental tissue, normal distribution of vessels, and active blood flow; in patients with pregnancy complications, we found inhomogeneous placenta, decreased blood flow, sporadic vessels, and avascular areas. SMI demonstrated several benefits compared to color Doppler imaging. Color Doppler allows us to assess superficial vessels only, whereas SMI provides more comprehensive data on the overall vascularization of the placenta. Conclusion: SMI by Aplio™ 500 (Toshiba may be an effective tool in the assessment of placental blood flow and the diagnosis and prognosis of placental insufficiency.

  2. Mtd Bok takes a swing: proapoptotic Mtd Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

    National Research Council Canada - National Science Library

    Ray, J E; Garcia, J; Jurisicova, A; Caniggia, I

    2010-01-01

    We have previously reported that matador/Bcl-2 ovarian killer (Mtd/Bok), a proapoptotic member of the Bcl-2 family, regulates human trophoblast apoptosis and that its levels are elevated in severe preeclamptic pregnancy...

  3. Human placental IGF-I and IGF-II expression: correlating maternal and infant anthropometric variables and micronutrients at birth in the Pakistani population.

    Science.gov (United States)

    Akram, S K; Akram, M; Bhutta, Z A; Soder, O

    2008-10-01

    To correlate infant birth weight with maternal and infant biometric data, including the expression of placental IGF-I and IGF-II at birth, and levels of serum zinc and ferritin. The data consisted of observations from 89 women from Karachi, Pakistan. Placental and cord blood samples were taken immediately following delivery and were subsequently divided into two groups, small and large for gestational age (SGA and LGA). The mean birth weight was 2.79 kg; the prevalence of SGA being 13.4% ( or =90th percentile). Placental IGF-I and IGF-II mRNA expression was greater in the LGA group (p importance of these growth factors for birth weight outcomes. The higher zinc levels in the LGA group also suggest the importance of this micronutrient in foetal growth. Our results suggest that growth problems have a multifactorial aetiology arising from within the infant rather than due to maternal constraint alone.

  4. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  5. Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.

    Science.gov (United States)

    Pang, Vincent; Bates, David O; Leach, Lopa

    2017-12-01

    The human placenta nourishes and protects the developing foetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the vascular endothelial growth factor (VEGF) family including the pro-angiogenic/pro-permeability VEGF-A 165 a isoform, the anti-angiogenic VEGF-A 165 b, placental growth factor (PIGF) and their receptors, VEGFR1 and VEGFR2. Alterations in the ratio of these factors during gestation and in complicated pregnancies have been reported; however, the impact of this on feto-placental endothelial barrier integrity is unknown. The present study investigated the interplay of these factors on junctional occupancy of VE-cadherin and macromolecular leakage in human endothelial monolayers and the perfused placental microvascular bed. Whilst VEGF-A 165 a (50 ng/ml) increased endothelial monolayer albumin permeability ( P 0.05) or PlGF ( P >0.05) did not. Moreover, VEGF-A 165 b (100 ng/ml; P 0.05) inhibited VEGF-A 165 a-induced permeability when added singly. PlGF abolished the VEGF-A 165 b-induced reduction in VEGF-A 165 a-mediated permeability ( P >0.05); PlGF was found to compete with VEGF-A 165 b for binding to Flt-1 at equimolar affinity. Junctional occupancy of VE-cadherin matched alterations in permeability. In the perfused microvascular bed, VEGF-A 165 b did not induce microvascular leakage but inhibited and reversed VEGF-A 165 a-induced loss of junctional VE-cadherin and tracer leakage. These results indicate that the anti-angiogenic VEGF-A 165 b isoform does not increase permeability in human placental microvessels or HUVEC primary cells and can interrupt VEGF-A 165 a-induced permeability. Moreover, the interplay of these isoforms with PIGF (and s-flt1) suggests that the ratio of these three factors may be important in determining the placental and endothelial barrier in normal and complicated pregnancies. © 2017 The Author(s).

  6. Evaluation of transobturator tapes (E-TOT) study: randomised prospective single-blinded study comparing inside-out vs. outside-in transobturator tapes in management of urodynamic stress incontinence: short term outcomes.

    Science.gov (United States)

    Abdel-fattah, Mohamed; Ramsay, Iain; Pringle, Stewart; Hardwick, Chris; Ali, Hassan

    2010-03-01

    To compare the "inside-out (TVT-O)" vs. "outside-in (ARIS)" transobturator tapes in the management of female urodynamic stress incontinence (USI) and to identify independent risk factors of failure of transobturator tapes. A prospective, single blinded, randomised trial. Women undergoing transobturator tapes as sole procedure in the period April 2005 and April 2007 were randomised to TVT-O for the inside-out approach and TOT-ARIS for the outside-in approach. The primary outcome measure at 6 months was the absence of USI on urodynamics. Secondary outcomes included; patient-reported success rates, overall patient satisfaction and peri-operative complications. 341 women were recruited: 171 in the outside-in group and 170 in the inside-out. Severe post-operative thigh pain was twice as common in the inside-out group but this was not statistically significant (6.7% vs. 3.5%, p=0.19). 317 women completed the 6 months follow-up; objective cure rates and patient-reported success rates were 85.4 and 80.5%, respectively, with no significant difference between the groups (p=0.28 and p=0.138, respectively). On multivariate analysis: low maximum urethral closure pressure (MUCP) (inside-out (TVT-O)" and "outside-in (ARIS)" transobturator tape procedures in the management of female USI at 6 months follow-up. Previous incontinence surgery and low MUCP were significant risk factors for failure of transobturator tapes. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  7. Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition.

    Science.gov (United States)

    Hackmon, Rinat; Pinnaduwage, Lakmini; Zhang, Jianhong; Lye, Stephen J; Geraghty, Daniel E; Dunk, Caroline E

    2017-06-01

    The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration. HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized. Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Placental site trophoblastic tumor

    Directory of Open Access Journals (Sweden)

    Jean eBouquet De Jolinière

    2014-08-01

    Full Text Available Trophoblastic tumors of placental site (PSTT are rare. They represent a rare form of gestational trophoblastic disease. (GTD. They occur mainly in women who have a history of miscarriage, termination of pregnancy, or even a normal or pathological ongoing pregnancy. The clinical course is unpredictable. This malignancy has different characteristics from other gestational trophoblastic tumors.Following a clinical case that we encountered and treated, we conducted a literary research and review, focusing primarily on prognostic factors and treatment.

  9. Placental Nutrient Transport and Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Francesca eGaccioli

    2016-02-01

    Full Text Available Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as pre-eclampsia and young maternal age.

  10. Placental apoptosis in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Tarek A. Atia

    2017-09-01

    Full Text Available Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM. Placental tissue samples were collected from 40 women with RM (study group and 30 women with sporadic spontaneous abortion (control group. Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53 and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53 protein was significantly increased in the placental tissues of the RM group (p = 0.003. By contrast, the expression of anti-apoptotic (Bcl-2 antibodies was significantly increased in the placental tissues of the control group (p = 0.025. We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation.

  11. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  12. The Effects of Vasopressin and Oxytocin on the Fetoplacental Distal Stem Arteriolar Vascular Resistance of the Dual-Perfused, Single, Isolated, Human Placental Cotyledon.

    Science.gov (United States)

    Downing, John W; Baysinger, Curtis L; Johnson, Raymond F; Paschall, Ray L; Shotwell, Matthew S

    2016-09-01

    Vasoactive agents administered to counter maternal hypotension at cesarean delivery may theoretically intensify the hypoxemic fetoplacental vasoconstrictor response and, hence, negatively impact transplacental oxygen delivery to the fetus. Yet, this aspect of their pharmacodynamic profiles is seldom mentioned, let alone investigated. We hypothesized that vasopressin, a potent systemic vasoconstrictor, and oxytocin, a uterotonic agent administered routinely at cesarean delivery, which, in contrast to vasopressin, possesses significant systemic vasodilator properties, would not influence distal stem villous arteriolar resistance. The dual-perfused, single, isolated cotyledon, human placental perfusion model was used to examine the resistance response of the fetoplacental circulation to oxytocin and vasopressin in placentae harvested from healthy women. Twelve of a total of 17 individual experiments were conducted successfully during which either oxytocin (n = 6) or vasopressin (n = 6) was introduced into the fetal reservoir in concentration increments of 10 M. Fetoplacental distal stem villous arteriolar perfusion pressure (FAP) was measured continuously. The fetal circuit concentration of either oxytocin or vasopressin was raised in a stepwise fashion from 10 to 10 M or 10 to 10 M, respectively. Both reservoirs were then purged of drug, after which 1-mL 1.0 mM 5-hydroxytryptamine (2.5 µM), an agent well known to manifestly increase fetoplacental distal stem villous arteriolar resistance, was introduced into the fetal circuit. A significant increase in FAP from baseline in response to exposure to 5-hydroxytryptamine confirmed that the fetoplacental vasoconstrictor response remained reactive. The primary outcome of this study was changes in FAP after incremental dosing of vasopressin and oxytocin. No changes in FAP were observed with either oxytocin or vasopressin regardless of the drug concentration tested. For each drug and concentration, a mean pressure change

  13. Human Wharton’s jelly-derived mesenchymal stem cells express oocyte developmental genes during co-culture with placental cells

    Directory of Open Access Journals (Sweden)

    Hamid Reza Asgari

    2015-01-01

    Conclusion: Placental cell supplementsTransforming growth factor (TGF α, β and basic fibroblast growth factor (bFGF in a co-culture model can provide proper environment for induction of HUMSCs into PGCs and expression of oocyte-like markers.

  14. Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens

    DEFF Research Database (Denmark)

    Soerli, J; Barfod, L; Lavstsen, T

    2009-01-01

    Pregnancy-associated Plasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show...

  15. Randomised prospective single-blinded study comparing 'inside-out' versus 'outside-in' transobturator tapes in the management of urodynamic stress incontinence: 1-year outcomes from the E-TOT study.

    Science.gov (United States)

    Abdel-Fattah, M; Ramsay, I; Pringle, S; Hardwick, C; Ali, H; Young, D; Mostafa, A

    2010-06-01

    To compare the 'inside-out' versus 'outside-in' routes for transobturator tape insertion for urodynamic stress incontinence, and to identify independent risk factors for failure at 1 year. Prospective single-blinded randomised trial. Tertiary urogynaecology centre. A cohort of 341 women undergoing transobturator tape procedures between April 2005 and April 2007. Women were randomised to tension-free vaginal tape-obturator (TVT)-O for the 'inside-out' route (n = 170) and transobturator tape (TOT)-ARIS for the 'outside-in' route (n = 171). Participants completed validated symptom-severity, quality-of-life and sexual-function questionnaires before and after surgery. In addition, they completed the patient global impression of improvement questionnaire (PGI-I) and standard 1-hour pad test postoperatively. The primary outcome was the patient-reported success rate reported on the PGI-I scale. Secondary outcomes included objective cure rate and improvement in King's Health Questionnaire scores. A total of 341 women were recruited: 171 women to the 'outside-in' (TOT-ARIS) group and 170 to the 'inside-out' (TVT-O) group; 299 completed the 1-year follow up. The patient-reported success rate was 80% with no statistically significant differences between the groups ('outside-in' 77.6% versus 'inside-out' 81.2%; OR 1.25; 95% CI 0.71, 2.20; P = 0.54). The objective cure rate was 91% with no statistically significant difference between the groups ('outside-in' 88% versus 'inside-out' 94%; OR 2.21; 95% CI 0.85, 5.75; P = 0.157). Previous incontinence surgery (OR 1.41; 95% CI 1.18, 1.91; P = 0.029) and preoperative urgency incontinence (OR 1.78; 95% CI 1.21, 3.91, P = 0.048) were significant risk factors for failure of transobturator tape at the 1-year follow up. There are no significant differences in patient reported and objective cure rates between 'inside-out' and 'outside-in' transobturator tapes. Quality of life and sexual function significantly improved following surgery

  16. [Human placental mesenchymal stem cells of fetal origin relieves mouse pulmonary fibrosis via downregulating MyD88 and TGF-β signaling pathway].

    Science.gov (United States)

    Tao, Jin; Li, Qinglun; Ma, Xiaowei; Han, Fei; Liu, Xiaoming; Wei, Jun; Zhu, Yongzhao

    2016-10-01

    Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation. The mice in negative control group were instilled with PBS (50 μL) through the same manner of the other two groups. Three days post-modelling, 200 μL containing 5×10(5) hfPMSCs were injected into hfPMSCs transplantation group via tail vein. All the mice were sacrificed at day 21 after modeling in batch. Lung tissues were collected for analyzing the pathological changes by HE staining and Masson staining as well as detecting collagen content. The total protein of lung tissues was extracted for observing the expressions of myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β); the level of TGF-β in sera was determined by Western blotting. Results The hfPMSCs possessed the morphology of mesenchymal stem cells and expressed the surface markers CD73, CD90 and CD105, but did not express CD14, CD34 and CD45. HE and Masson staining showed that hfPMSCs transplantation significantly reduced the degree of pulmonary fibrosis compared with bleomycin treatment group. The collagen content and the expression levels of MyD88 and TGF-β in bleomycin treatment group were obviously higher than those in hfPMSCs transplantation group and negative control group. Conclusion hfPMSCs possess the capability of alleviating pulmonary fibrosis by down-regulating the expressions of MyD88 and TGF-β.

  17. Placental growth factor enhances angiogenesis in human intestinal microvascular endothelial cells via PI3K/Akt pathway: Potential implications of inflammation bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi, E-mail: mondayzy@126.com; Tu, Chuantao, E-mail: tu.chuantao@zs-hospital.sh.cn; Zhao, Yuan, E-mail: zhao.yuan@zs-hospital.sh.cn; Liu, Hongchun, E-mail: liuhch@aliyun.com; Zhang, Shuncai, E-mail: zhang.shuncai@zs-hospital.sh.cn

    2016-02-19

    Background: Angiogenesis plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Placental growth factor (PlGF) is a specific regulator of pathological angiogenesis and is upregulated in the sera of IBD patients. Therefore, the role of PlGF in IBD angiogenesis was investigated here using HIMECs. Methods: The expression of PlGF and its receptors in human intestinal microvascular endothelial cells (HIMECs) and inflamed mucosa of IBD patients were examined using quantitative PCR and western blot analysis and the role of PlGF in IBD HIMECs was further explored using small interfering RNA (siRNA). The induction of pro-inflammatory cytokine by PlGF in HIMECs was confirmed by ELISA. The capacity of PlGF to induce angiogenesis in HIMECs was tested through proliferation, cell-migration, matrigel tubule-formation assays and its underlying signaling pathway were explored by western blot analysis of ERK1/2 and PI3K/Akt phosphorylation. Results: mRNA and protein expression of PlGF and its receptor NRP-1 were significantly increased in IBD HIMECs. Inflamed mucosa of IBD patients also displayed higher expression of PIGF. The production of IL-6 and TNF-α in culture supernatant of HIMECs treated with exogenous recombinant human PlGF-1 (rhPlGF-1) were increased. Furthermore, rhPlGF-1 significantly induced HIMECs migration and tube formation in a dose-dependent manner and knockdown of endogenous PlGF in IBD HIMECs using siRNA substantially reduced these angiogenesis activities. PlGF induced PI3K/Akt phosphorylation in HIMECs and pretreatment of PlGF-stimulated HIMECs with PI3K inhibitor (LY294002) significantly inhibited the PlGF-induced cell migration and tube formation. Conclusion: Our results demonstrated the pro-inflammatory and angiogenic effects of PlGF on HIMECs in IBD through activation of PI3K/Akt signaling pathway. PlGF/PI3K/Akt signaling may serve as a potential therapeutic target for IBD. - Highlights: • Expression of PlGF and its receptor NRP-1

  18. Placental Protein 13 (PP13 – a placental immunoregulatory galectin protecting pregnancy

    Directory of Open Access Journals (Sweden)

    Nandor Gabor Than

    2014-08-01

    Full Text Available Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13. It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing

  19. Placental Protein 13 (PP13) – A Placental Immunoregulatory Galectin Protecting Pregnancy

    Science.gov (United States)

    Than, Nándor Gábor; Balogh, Andrea; Romero, Roberto; Kárpáti, Éva; Erez, Offer; Szilágyi, András; Kovalszky, Ilona; Sammar, Marei; Gizurarson, Sveinbjorn; Matkó, János; Závodszky, Péter; Papp, Zoltán; Meiri, Hamutal

    2014-01-01

    Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure

  20. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

    Directory of Open Access Journals (Sweden)

    Helen N Jones

    Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

  1. Risk factors of placental abruption

    Directory of Open Access Journals (Sweden)

    Hooria Seyedhosseini Ghaheh

    2013-01-01

    Full Text Available Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson ′ s Chi-square test along with presenting relevant odds ratio (OR. Results: From 7301 deliveries included in the study, 78 (1% was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83 and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41 were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01. Conclusion: The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency.

  2. Metabolism of bupropion by baboon hepatic and placental microsomes

    Science.gov (United States)

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB. PMID:21570381

  3. Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

    Science.gov (United States)

    Gelber, Shari E; Brent, Elyssa; Redecha, Patricia; Perino, Giorgio; Tomlinson, Stephen; Davisson, Robin L; Salmon, Jane E

    2015-08-01

    Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation. Copyright © 2015 by The American Association of Immunologists, Inc.

  4. SOBRE ESTELIONATOS E HOMICÍDIOS: A RESERVA DO POSSÍVEL ÀS AVESSAS / ABOUT STELLIONATE AND HOMICIDE: RESERVE OF POSSIBLE INSIDE OUT

    Directory of Open Access Journals (Sweden)

    Rosivaldo Toscano dos Santos Júnior

    2016-04-01

    Full Text Available The study of a real case serves as a guide to reflect on how, in the country where killings happens the most in the whole world, the criminal justice system prioritizes the protection of purely financial interests, often corporations that paradoxically act, unharmed, regardless of the will of the law. Reigns whatever the text calls “reserve of the possible in reverse”. Thus, it disregards human life for the benefit of capital. The legal actors submitted to the theoretical common sense and lost in everydayness do not realize that, instead of being part of the solution, they become part of the problem and are day by day spinning people’s grinder machine. From the metaphor of Matrix, it is to wake up and hear the claim of Adorno, to stop the barbarism in which legal actors attached to the habitus participate passively, so they can let the Other live.

  5. In vitro dual perfusion of human placental lobules as a flow phantom to investigate the relationship between fetoplacental flow and quantitative 3D power doppler angiography.

    Science.gov (United States)

    Jones, N W; Hutchinson, E S; Brownbill, P; Crocker, I P; Eccles, D; Bugg, G J; Raine-Fenning, N J

    2009-02-01

    Flow phantoms have been used to investigate and quantify three-dimensional power Doppler data but this is the first study to use the in vitro, dual perfused, placental perfusion model. We used this model to investigate and quantify the effect of variation in fetal-side flow rates and attenuation on 3D power Doppler angiography. Perfusion of a placental lobule was commenced within 30 min of delivery and experimentation was successful in 8 of the 18 placenta obtained. Fetal and maternal perfusate was modified Earle's bicarbonate buffer which, following equilibration, was supplemented on the fetal side with whole heparinised cord blood. Imaging was performed with a Voluson-i ultrasound machine. A 'vascular biopsy' the thickness of the placental lobule was defined and signal quantified within using VOCAL (GE Medical Systems, Zipf, Austria). Three vascular indices are generated: vascularisation index (VI) defined as the percentage of power Doppler data within a volume of interest; flow index (FI), the mean signal intensity of the power Doppler information; and vascularisation flow index (VFI), a combination of both factors derived through their multiplication. Attenuation was investigated in this model with the addition of tissue mimic blocks. Our results showed a predictable relationship between flow rates and the vascular indices VI and VFI. However the FI was a less reliable predictor of flow; thus it should be interpreted with caution. The power Doppler signal was markedly affected by attenuation leading to a complete loss of information at a depth of 6 cm in the model used. In conclusion this model can be adapted to provide a phantom to analyse and quantify 3D power Doppler signals and demonstrates that vascular indices within a tissue remain related to volume flow. This model provides further evidence that depth dependent attenuation of signal needs to be accounted for in any in vivo work where the probe is not in direct contact with the tissue of interest.

  6. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woo; Park, Il Hwan; Kwon, Woo Cheol; Eom, Min Seob; Kim, Young Ju; Hwan, Joong Hwan [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2013-12-15

    Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

  7. Regulation of pregnancy-associated plasma protein A2 (PAPPA2 in a human placental trophoblast cell line (BeWo

    Directory of Open Access Journals (Sweden)

    Christians Julian K

    2011-04-01

    Full Text Available Abstract Background Pregnancy-associated plasma protein A2 (PAPPA2 is an insulin-like growth factor-binding protein (IGFBP protease expressed at high levels in the placenta and upregulated in pregnancies complicated by preeclampsia and HELLP (Hemolytic anemia, Elevated Liver enzymes, and Low Platelet count syndrome. However, it is unclear whether elevated PAPPA2 expression causes abnormal placental development, or whether upregulation compensates for placental pathology. In the present study, we investigate whether PAPPA2 expression is affected by hypoxia, oxidative stress, syncytialization factors or substances known to affect the expression of PAPPA2's paralogue, PAPPA. Methods BeWo cells, a model of placental trophoblasts, were treated with one of the following: hypoxia (2% O2, oxidative stress (20 microM hydrogen peroxide, forskolin (10 microM and 100 microM, TGF-beta (10 and 50 ng/mL, TNF-alpha (100 ng/mL, IL-1beta (100 ng/mL or PGE2 (1 microM. We used quantitative RT-PCR (qRT-PCR to quantify the mRNA levels of PAPPA2, as well as those of PAPPA and ADAM12 since these proteases have similar substrates and are also highly expressed in the placenta. Where we observed significant effects on PAPPA2 mRNA levels, we tested for effects at the protein level using an in-cell Western assay. Results Hypoxia, but not oxidative stress, caused a 47-fold increase in PAPPA2 mRNA expression, while TNF-alpha resulted in a 6-fold increase, and both of these effects were confirmed at the protein level. PGE2 resulted in a 14-fold upregulation of PAPPA2 mRNA but this was not reflected at the protein level. Forskolin, TGF-beta and IL-1beta had no significant effect on PAPPA2 mRNA expression. We observed no effects of any treatment on PAPPA or ADAM12 expression. Conclusion Our study demonstrates that factors previously known to be highly expressed in preeclamptic placentae (PGE2 and TNF-alpha, contribute to the upregulation of PAPPA2. Hypoxia, known to occur in

  8. Challenges in the Management of Placental Site Trophoblastic Tumor

    African Journals Online (AJOL)

    Mubeen

    Reproductive Health Research Center, Alzahra Hospital Guilan University of Medical Sciences, 1Department of Pathology, Poursina Hospital, ... Beta human chorionic gonadotropin (β-HCG) level was 110 mIU/mL and uterus was diffusely enlarged. Total ... two substances, namely human placental lactogen (HPL) and.

  9. Placental Gas Exchange and the Oxygen Supply to the Fetus

    DEFF Research Database (Denmark)

    Carter, Anthony M

    2015-01-01

    is slowed, although oxygen consumption is unaltered when corrected for fetal mass. Similarly, birth weight is reduced in humans living at high altitude even if the effect is tempered in those with a long highland ancestry. Placental mass changes little during sustained hypoxia in sheep or humans at high...

  10. Placental STAT3 signaling is activated in women with polycystic ovary syndrome.

    Science.gov (United States)

    Maliqueo, M; Sundström Poromaa, I; Vanky, E; Fornes, R; Benrick, A; Åkerud, H; Stridsklev, S; Labrie, F; Jansson, T; Stener-Victorin, E

    2015-03-01

    Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling? Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS. Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth. In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy. Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry. Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Inside-Out or Outside-In Suturing Should Not Be Considered the Standard Repair Method for Radial Tears of the Midbody of the Lateral Meniscus: A Systematic Review and Meta-Analysis of Biomechanical Studies.

    Science.gov (United States)

    Alentorn-Geli, Eduard; Choi, J H James; Stuart, Joseph J; Toth, Alison P; Garrett, William E; Taylor, Dean C; Moorman, Claude T

    2016-10-01

    The purpose was to evaluate which meniscal repair technique for radial tears of the midbody of the lateral meniscus demonstrates the best biomechanical properties. An electronic literature search was conducted using PubMed, EMBASE, CINAHL, and ScienceDirect databases. Biomechanical studies investigating the repair characteristics of radial tears in the midbody of the lateral meniscus were included. After appropriate screening, a total of 54 studies were reviewed in detail (full text), and 6 met inclusion criteria. The most common cause of exclusion was the investigation of longitudinal tears. Only two studies could be meta-analyzed. Stiffness was significantly higher for all-inside compared with inside-out repair techniques (p = 0.0009). No significant differences were observed between both suture methods for load to failure (p = 0.45). However, both studies used different all-inside devices and suture constructs. No clear conclusions can be drawn from the comparison of both types of repairs for displacement, site of failure, or contact pressure changes. Overall, there are no conclusive data to suggest that inside-out or outside-in suture repair has better load to failure or stiffness, less displacement, or different site of failure compared with all-inside repair. According to biomechanical data, it is under surgeon's preference to elect one repair technique over the other. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Imaging and assessment of placental function.

    LENUS (Irish Health Repository)

    Moran, Mary

    2011-09-01

    The placenta is the vital support organ for the developing fetus. This article reviews current ultrasound (US) methods of assessing placental function. The ability of ultrasound to detect placental pathology is discussed. Doppler technology to investigate the fetal, placental, and maternal circulations in both high-risk and uncomplicated pregnancies is discussed and the current literature on the value of three-dimensional power Doppler studies to assess placental volume and vascularization is also evaluated. The article highlights the need for further research into three-dimensional ultrasound and alternative methods of placental evaluation if progress is to be made in optimizing placental function assessment.

  13. Queering Educational Leadership from the inside out

    Science.gov (United States)

    Rottmann, Cindy

    2006-01-01

    This article draws from poststructuralist, feminist and identity-based political foundations of queer theory to construct a conceptual lens which complements other critical, anti-oppression frameworks. It reveals some of the internal struggles in the field of queer studies, describes the social context for issues related to sexuality in North…

  14. Educational Professionalism: An Inside-Out View

    Science.gov (United States)

    Glazer, Joshua L.

    2008-01-01

    The past two decades have witnessed numerous efforts to enhance educational professionalism, such as more stringent requirements for entry, increased autonomy, and higher pay. Yet, these types of initiatives typically target aspects of the profession external to the work of teaching. In this article, I expand the view of professionalism implicit…

  15. Inside out Studio: Hope Arts Providence Project

    Science.gov (United States)

    Gerdts, Nadine

    2008-01-01

    The construction and infrastructure of a city provide the foundation of an ideal urban lab for high school students to discover how to dissect the multifaceted layers of a place and make it their own. For six weeks in the winter of 2008, ninth-grade students in Providence, Rhode Island's Hope High School/Hope Arts Community learned to look closely…

  16. Turning Our World of Learning Inside Out!

    Science.gov (United States)

    Monsalvatge, Laura; Long, Kris; DiBello, Lilia

    2013-01-01

    Early childhood professionals constantly reflect upon how to improve the quality of educational experiences for young children. They are often encouraged to create centers that support the development of language, literacy and mathematical concepts inside the classroom, but they often forget that there is an untapped world of learning just outside…

  17. Making a difference from the inside out.

    Science.gov (United States)

    Heilemann, Marysue V; Brown, Theresa; Deutchman, Larry

    2012-01-01

    Nursing leaders, researchers, and activists have called for change in mass media depictions of nurses since the 1980s, but some nurses are not sure they should make any effort. This article offers a focused look at the trajectories of 2 individuals: Theresa Brown, a clinical nurse and author who writes for the New York Times, and Larry Deutchman, the Executive Vice President of Marketing and Industry Relations at Entertainment Industries Council, Inc. Both Brown and Deutchman were motivated to acquire skills and to take risks to think creatively, and/or to collaborate with other professionals in media to benefit nursing and health. Analysis of their paths offers ideas for action, growth, learning, and collaboration for nurses in relation to the ways that nursing is represented in written and visual media. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Microsoft Office Excel 2003 Inside Out

    CERN Document Server

    Stinson, Craig

    2003-01-01

    Hey, you know your way around a spreadsheet-so now dig into Excel 2003 and really put your data to work! This supremely organized reference packs hundreds of timesaving solutions, troubleshooting tips, and handy workarounds in concise, fast-answer format. It's all muscle and no fluff. Discover the best and fastest ways to perform everyday tasks, and challenge yourself to new levels of Excel mastery! Build on what you already know about Excel and quickly dive into what's newLearn how the experts design more powerful spreadsheetsSharpen your core to advanced document editing and formatting skil

  19. Inside/Out: Interventionen in Raum

    Directory of Open Access Journals (Sweden)

    Sabine Hark

    2005-11-01

    Full Text Available Die erstmals in deutscher Übersetzung vorliegenden Aufsätze dieses Bandes, allesamt Klassiker der US-amerikanischen Queer Theory, thematisieren den komplexen Zusammenhang von Sexualität, Identität und räumlicher Verortung. Ausgehend von der Kritik an der vorgeblichen Eindeutigkeit der Trennung von privat/öffentlich sowie an den räumlichen Bildern des Closet und Coming-Out soll das Verhältnis von Sexualität und Raum neu gedacht werden. Die Beiträgerinnen und Beiträger plädieren für ein Denken, das den vielgestaltigen Praxen, queere Räume zu eröffnen, zu bewohnen und zu erfahren, Rechnung trägt, – und führen es zugleich in inspirierender und aufregender Weise vor.

  20. Information and Communication Technology Inside Out

    DEFF Research Database (Denmark)

    Riis, Søren

    2017-01-01

    Information and communication technology (ICT) has become the great technological fix of our time and not the least in the education system. There seems to be no end to the hype of ICT and the accompanying promises that education will be revolutionized—“smart” pupils will be made and the so...

  1. Self-Esteem: From the inside Out.

    Science.gov (United States)

    Johnson, Christopher

    1993-01-01

    Argues that students' self-esteem must come from within. Provides strategies to help teachers create a classroom environment that allows students to build their own self-esteem, including (1) encouraging instead of praising; (2) building self-reliance; (3) creating a positive atmosphere of belonging; (4) recognizing individuality; and (5) modeling…

  2. Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes

    DEFF Research Database (Denmark)

    Fuglsang, Jens; Lauszus, Finn; Flyvbjerg, Allan

    2003-01-01

    between hPGH and IGF-I in type 1 diabetes mellitus has not been investigated thoroughly. Furthermore, hPGH may be involved in the development of insulin resistance during pregnancy. In this prospective, longitudinal study, 51 type 1 diabetic subjects were followed with repeated blood sampling during...... influence of hPGH on placental weight was found. Serum IGF-I values decreased significantly from the first to the second trimester (P changes in IGF-I followed the increase in hPGH between wk 26-35 (r(s) = 0.53; P ...-II (r(s) = 0.37; P = 0.008). Changes in IGF-I and IGF-II between wk 26-35 also correlated to the birth weight z-score (P

  3. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

    Springer, M.S.; Stanhope, M.J.; Madsen, O.; Jong, W.W.W. de

    2004-01-01

    Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and

  4. Placental villous stroma as a model system for myofibroblast differentiation.

    Science.gov (United States)

    Kohnen, G; Kertschanska, S; Demir, R; Kaufmann, P

    1996-06-01

    Different subtypes of myofibroblasts have been described according to their cytoskeletal protein patterns. It is quite likely that these different subtypes represent distinct steps of differentiation. We propose the human placental stem villi as a particularly suitable model to study this differentiation process. During the course of pregnancy, different types of placental villi develop by differentiation of the mesenchymal stroma surrounding the fetal blood vessels. In order to characterise the differentiation of placental stromal cells in the human placenta, the expression patterns of the cytoskeletal proteins vimentin, desmin, alpha- and gamma-smooth muscle actin, pan-actin, smooth muscle myosin, and the monoclonal antibody GB 42, a marker of myofibroblasts, were investigated on placental tissue of different gestational age (7th-40th week of gestation). Proliferation patterns were assessed with the proliferation markers MIB 1 and PCNA. Additionally, dipeptidyl peptidase IV distribution was studied in term placenta and the ultrastructure of placental stromal cells was assessed by electron microscopy. Different subpopulations of extravascular stromal cells were distinguished according to typical co-expression patterns of cytoskeletal proteins. Around the fetal stem vessels in term placental villi they were arranged as concentric layers with increasing stage of differentiation. A variable layer of extravascular stromal cells lying beneath the trophoblast expressed vimentin (V) or vimentin and desmin (VD). They were mitotically active. The next layer co-expressed vimentin, desmin, and alpha-smooth muscle actin (VDA). More centrally towards the fetal vessels, extravascular stromal cells co-expressed vimentin, desmin, alpha- and gamma-smooth muscle actin, and GB 42 (VDAG). Cells close to the fetal vessels additionally co-expressed smooth muscle myosin (VDAGM). Ultrastructurally, V cells resembled typical mesenchymal cells. VD cells corresponded to fibroblasts, while

  5. Early studies of placental ultrastructure by electron microscopy

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted...... many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University....... CONCLUSIONS: Prior to the introduction of better fixation techniques, TEM images were of modest technical quality. Nevertheless they gave important insights into placental ultrastructure, particularly the nature of the maternal-fetal interface....

  6. Intrapritoneal Hemorrhage after Placental Abruption

    Directory of Open Access Journals (Sweden)

    Nahid Sakhavar

    2012-06-01

    Full Text Available A placental abruption or abruptio placentae (where in the placental lining has separated from the uterus of the mother is one of the complications caused by trauma during pregnancy. It lets the blood flow to infiltrate in the uterine lining and to develop Couvelaire uterus (also known as uteroplacental apoplexy and uterine atony (a condition in which a woman's uterine muscles lose the ability to contract after childbirth; however, it rarely develops considerable hemoperitoneum which needs hysterectomy. In this report, a unique case of placental abruption caused by trauma in a 28-year-old Afghan woman is introduced in which severity and duration of trauma because of delay in reaching health equipped center led to developing massive hemoperitoneum (infiltration of great amount of blood into the abdominal cavity and its complications.

  7. Effect of pregestational diabetes mellitus on first trimester placental characteristics: three-dimensional placental volume and power Doppler indices.

    Science.gov (United States)

    Gonzalez Gonzalez, N L; Gonzalez Davila, E; Castro, A; Padron, E; Plasencia, W

    2014-03-01

    To investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester. This was a prospective case-control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β human chorionic gonadotrophin (β-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group. 3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p effect is independent of the later development of PAHC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Interleukin-11 alters placentation and causes preeclampsia features in mice.

    Science.gov (United States)

    Winship, Amy L; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J; Dimitriadis, Evdokia

    2015-12-29

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE.

  9. Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier

    DEFF Research Database (Denmark)

    Correia Carreira, S; Cartwright, L; Mathiesen, L

    2011-01-01

    Currently, toxicology and toxicokinetics of purified non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are poorly characterised. Transplacental kinetics of NDL-PCBs can be studied in a variety of models, but careful validation of each model is crucial. We aimed to develop a standard operating...... procedure for establishing an in vitro model of the human placental barrier. Using this model, we sought to investigate placental transport kinetics of two NDL-PCB congeners. Firstly, we compared the BeWo cell line of the American Type Culture Collection with the BeWo b30 clone and determined parameters...... for monolayer formation. Secondly, we performed placental perfusions to validate the in vitro model. To that end, the transport of radiolabelled PCB52 and 180 was investigated in both models. We were not able to grow the ATCC cell line to confluency, but determined monolayer formation using BeWo b30...

  10. Levels of Macrophage Inflammatory Protein 1α (MIP-1α) and MIP-1β in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Chaisavaneeyakorn, Sujittra; Moore, Julie M.; Mirel, Lisa; Othoro, Caroline; Otieno, Juliana; Chaiyaroj, Sansanee C.; Shi, Ya Ping; Nahlen, Bernard L.; Lal, Altaf A.; Udhayakumar, Venkatachalam

    2003-01-01

    Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1β concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1β than HIV-positive PM-negative women. The MIP-1α level was not altered in association with either infection. The IVB plasma levels of MIP-1α and MIP-1β positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1β compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1β and MIP-1α levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1β level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1β was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma. PMID:12853396

  11. Placental diversity in malagasy tenrecs

    DEFF Research Database (Denmark)

    Enders, A.C.; Blankenship, T.N.; Goodman, S.M.

    2007-01-01

    Placentation in tenrecs of the subfamily Oryzorictinae, family Tenrecidae, has not been described previously. The structure of the placenta of this group and especially of the genus Microgale was investigated to determine its similarity or dissimilarity to previously described placentas of the te...

  12. Oxygen and tissue culture affect placental gene expression.

    Science.gov (United States)

    Brew, O; Sullivan, M H F

    2017-07-01

    Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip® Human Genome U133 Plus 2.0 arrays (Affymetrix). We uncovered sub-sets of genes that regulate response to stress, induction of apoptosis programmed cell death, mis-regulation of cell growth, proliferation, cell morphogenesis, tissue viability, and protection from apoptosis in cultured placental explants. We also identified a sub-set of genes with highly unstable pattern of expression after exposure to tissue culture. Tissue culture irrespective of oxygen concentration induced dichotomous increase in significant gene expression and increased enrichment of significant pathways and transcription factor targets (TFTs) including HIF1A. The effect was exacerbated by culture at atmospheric oxygen concentration, where further up-regulation of TFTs including PPARA, CEBPD, HOXA9 and down-regulated TFTs such as JUND/FOS suggest intrinsic heightened key biological and metabolic mechanisms such as glucose use, lipid biosynthesis, protein metabolism; apoptosis, inflammatory responses; and diminished trophoblast proliferation, differentiation, invasion, regeneration, and viability. These findings demonstrate that gene expression patterns differ between pre-culture and cultured explants, and the gene expression of explants cultured at atmospheric oxygen concentration favours stressed, pro-inflammatory and increased apoptotic transcriptomic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Conversion of human placental alkaline phosphatase from a high Mr form to a low Mr form during butanol extraction. An investigation of the role of endogenous phosphoinositide-specific phospholipases.

    Science.gov (United States)

    Malik, A S; Low, M G

    1986-12-01

    Alkaline phosphatase in a wide range of tissues has been shown to be anchored in the membrane by a specific interaction with the polar head group of phosphatidylinositol. It has previously been suggested that the production of low Mr alkaline phosphatase during the commonly used butanol extraction procedure may result from the activation of an endogenous phosphoinositide-specific phospholipase C which removes the 1,2-diacylglycerol responsible for membrane anchoring. This conversion process was investigated in greater detail with human placenta used as the source of alkaline phosphatase. Mr and hydrophobicity of the alkaline phosphatase were determined by gel filtration on TSK-250 and partitioning in Triton X-114, respectively. Alkaline phosphatase extracted from human placental particulate fraction with butanol at pH 5.4 or released by incubation with Staphylococcus aureus phosphatidylinositol-specific phospholipase C produced a form of alkaline phosphatase of Mr approx. 170,000 and relatively low hydrophobicity. By contrast, the butanol extract prepared at pH 8.3 was an aggregated form of Mr approx. 600,000 and was relatively hydrophobic. The effect of a variety of inhibitors and activators on the amount of low Mr alkaline phosphatase produced during butanol extraction revealed that it was a Ca2+- and thiol-dependent process. Proteinase inhibitors had no effect. [3H]Phosphatidylinositol hydrolysis by the particulate fraction, unlike low Mr alkaline phosphatase production, was relatively sensitive to heat inactivation, indicating that the phosphoinositide-specific phospholipases C from cytosol and lysosomes were unlikely to be responsible for conversion. A butanol-stimulated activity which removed the [3H]myristic acid from the variant surface glycoprotein ( [3H]mfVSG) of Trypanosoma brucei was detectable in the human placental particulate fraction. Since this activity was acid active, Ca2+- and thiol-dependent and relatively heat stable, it may be the same as

  14. Incidental placental choriocarcinoma in a term pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Chung Christopher

    2008-10-01

    Full Text Available Abstract Introduction Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario. Case presentation The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well. Conclusion Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.

  15. Notch signalling in placental development and gestational diseases.

    Science.gov (United States)

    Haider, S; Pollheimer, J; Knöfler, M

    2017-08-01

    Activation of Notch signalling upon cell-cell contact of neighbouring cells controls a plethora of cellular processes such as stem cell maintenance, cell lineage determination, cell proliferation, and survival. Accumulating evidence suggests that the pathway also critically regulates these events during placental development and differentiation. Herein, we summarize our present knowledge about Notch signalling in murine and human placentation and discuss its potential role in the pathophysiology of gestational disorders. Studies in mice suggest that Notch controls trophectoderm formation, decidualization, placental branching morphogenesis and endovascular trophoblast invasion. In humans, the particular signalling cascade promotes formation of the extravillous trophoblast lineage and regulates trophoblast proliferation, survival and differentiation. Expression patterns as well as functional analyses indicate distinct roles of Notch receptors in different trophoblast subtypes. Altered effects of Notch signalling have been detected in choriocarcinoma cells, consistent with its role in cancer development and progression. Moreover, deregulation of Notch signalling components were observed in pregnancy disorders such as preeclampsia and fetal growth restriction. In summary, Notch plays fundamental roles in different developmental processes of the placenta. Abnormal signalling through this pathway could contribute to the pathogenesis of gestational diseases with aberrant placentation and trophoblast function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A Case of Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Shigeki Taga

    2013-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

  17. Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotensive, preeclamptic and intrauterine growth restricted pregnancies.

    Science.gov (United States)

    Hnat, Michael D; Meadows, Juliana W; Brockman, Diane E; Pitzer, Brad; Lyall, Fiona; Myatt, Leslie

    2005-09-01

    The purpose of this study was to compare immunohistochemical expression of heat shock protein-70 (hsp70), a marker for oxidative stress, and 4-hydroxy-2-nonenal adducts (HNE), a marker for lipid peroxidation, in placental villous tissue of normotensive, preeclampsia, and intrauterine growth restricted (IUGR) pregnancies. Placentas were collected and flash frozen in liquid nitrogen after delivery from normotensive pregnancies (n=5), and pregnancies complicated by preeclampsia (n=5), IUGR (n=5), and preeclampsia plus IUGR (n=4). Cryosections were cut and immunostained with polyclonal anti-hsp70 and monoclonal anti-HNE antibodies using Vectastain Elite ABC kit. Normal rabbit serum or mouse IgG were used as negative controls. Three independent observers, blinded to identity of tissue, examined each slide to identify cellular localization and intensity of the immunostaining. Western blot analysis and scanning densitometry were used to quantify and compare the amount of hsp70 and HNE adducts present in tissue homogenates. Positive immunostaining for both antibodies was observed in cytoplasm of syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle, and endothelial cells for all groups. Expression of hsp70 and HNE adducts was reported as observers' mean stained intensity. Overall, kappa showed good agreement between observers. Immunostaining intensity was similar in all tissue types for each group with the exception that immunostaining was significantly more intense in the vascular endothelium of the preeclamptic group for HNE adducts (P=.02) and significantly less intense in the IUGR group for hsp70 (P=.013). Scanning densitometric analysis of the Western blots showed no significant difference in total hsp70 and HNE adducts expression in all 4 tissue groups. Immunohistochemistry showed local changes for oxidative stress and lipid peroxidation in the vascular endothelium from placentas of preeclamptic and IUGR pregnancies. However, these changes were

  18. Maternal fructose drives placental uric acid production leading to adverse fetal outcomes

    Science.gov (United States)

    Asghar, Zeenat A.; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L.; Moley, Kelle H.

    2016-01-01

    Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans. PMID:27125896

  19. Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

    DEFF Research Database (Denmark)

    Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud

    2006-01-01

    . A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have...

  20. Does improvement in maternal attachment representations predict greater maternal sensitivity, child attachment security and lower rates of relapse to substance use? A second test of Mothering from the Inside Out treatment mechanisms.

    Science.gov (United States)

    Suchman, Nancy E; DeCoste, Cindy; Borelli, Jessica L; McMahon, Thomas J

    2018-02-01

    In this study, we replicated a rigorous test of the proposed mechanisms of change associated with Mothering from the Inside out (MIO), an evidence-based parenting therapy that aims to enhance maternal reflective functioning and mental representations of caregiving in mothers enrolled in addiction treatment and caring for young children. First, using data from 84 mothers who enrolled in our second randomized controlled trial, we examined whether therapist fidelity to core MIO treatment components predicted improvement in maternal reflective functioning and mental representations of caregiving, even after taking fidelity to non-MIO components into account. Next, we examined whether improvement in directly targeted outcomes (e.g., maternal mentalizing and mental representations of caregiving) led to improvements in the indirectly targeted outcome of maternal caregiving sensitivity, even after controlling for other plausible competing mechanisms (e.g., improvement in maternal psychiatric distress and substance use). Third, we examined whether improvement in targeted parenting outcomes (e.g., maternal mentalizing, mental representations of caregiving and caregiving sensitivity) was associated in improvement in child attachment status, even after controlling for competing mechanisms (e.g., improvement in maternal psychiatric distress and substance use). Finally, we examined whether improvement in maternal mentalizing and caregiving representations was associated with a reduction in relapse to substance use. Support was found for the first three tests of mechanisms but not the fourth. Implications for future research and intervention development are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  2. Congenital neuroblastoma with placental involvement

    OpenAIRE

    Kume, Ayako; Morikawa, Teppei; Ogawa, Makiko; Yamashita, Aki; Yamaguchi, Shunichi; Fukayama, Masashi

    2014-01-01

    We describe an extremely rare case of congenital neuroblastoma with placental involvement. A fetus with a left abdominal mass detected during ultrasonography at 23 weeks’ gestation developed hydrops fetalis by 26 weeks’ gestation. The mother developed hypertension at 26 5/7 weeks’ gestation. Based on a clinical diagnosis of pregnancy-induced hypertension, labor was induced at 26 6/7 weeks. However, intrauterine fetal death was diagnosed during delivery. Postmortern examination revealed a soli...

  3. Placental and serum levels of carotenoids in preeclampsia.

    Science.gov (United States)

    Palan, P R; Mikhail, M S; Romney, S L

    2001-09-01

    We compared placental tissue, maternal serum, and umbilical cord venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene, lycopene, and canthaxanthin) in normal pregnant women and those with preeclampsia. Levels of alpha-carotene, beta-carotene, lycopene, and canthaxanthin were measured in placental tissue, maternal serum, and umbilical cord venous blood from 22 normal pregnant women and 19 women with preeclampsia. The criteria for recruitment included gestational age of 30-42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Carotenoids were measured using high-pressure liquid chromatography. All four carotenoids were detectable in human placental tissue, maternal serum, and umbilical cord venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in placentas from preeclamptic women were significantly lower (P =.032, .009, and .013, respectively, by Mann-Whitney test) than those from normal pregnant women. Maternal serum levels of beta-carotene and lycopene were significantly lower (P =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia. However, umbilical cord venous blood levels of these carotenoids were not significantly different between the two groups. Lower placental tissue and maternal serum carotenoid levels in women with preeclampsia suggest that oxidative stress or a dietary antioxidant influence might have an effect on the pathophysiology of preeclampsia.

  4. Altered fetal growth, placental abnormalities, and stillbirth.

    Science.gov (United States)

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in

  5. Altered fetal growth, placental abnormalities, and stillbirth.

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

    Full Text Available Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth.Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile for gestational age at death (stillbirth or delivery (live birth using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate. Five patterns were observed: placental findings associated with (1 stillbirth but not fetal growth abnormalities; (2 fetal growth abnormalities in stillbirths only; (3 fetal growth abnormalities in live births only; (4 fetal growth abnormalities in stillbirths and live births in a similar manner; (5 a different pattern of fetal growth

  6. Inside/Out: Interventionen in Raum Inside/Out: Interventions in Space

    Directory of Open Access Journals (Sweden)

    Sabine Hark

    2005-11-01

    Full Text Available Die erstmals in deutscher Übersetzung vorliegenden Aufsätze dieses Bandes, allesamt Klassiker der US-amerikanischen Queer Theory, thematisieren den komplexen Zusammenhang von Sexualität, Identität und räumlicher Verortung. Ausgehend von der Kritik an der vorgeblichen Eindeutigkeit der Trennung von privat/öffentlich sowie an den räumlichen Bildern des Closet und Coming-Out soll das Verhältnis von Sexualität und Raum neu gedacht werden. Die Beiträgerinnen und Beiträger plädieren f��r ein Denken, das den vielgestaltigen Praxen, queere Räume zu eröffnen, zu bewohnen und zu erfahren, Rechnung trägt, – und führen es zugleich in inspirierender und aufregender Weise vor.The essays in the volume at hand comprise the first translations into German of US-American Queer Theory classics. They explore the complex interrelation of sexuality, identity, and spatial positioning. The essays intentions are to reconceive the relationship between sexuality and space, taking as their points of departure both the critique of the supposed transparency of the separation between private and public as well as the spatial images of the closet and coming out. The authors plead for a thinking that allows for the complex praxis of opening, occupying, and experiencing queer spaces—and at the same time they present this in an inspiring and exciting manner.

  7. Evaluating the Femoral-Side Critical Corner in Posterior Cruciate Ligament Reconstruction: The Effect of Outside-In Versus Inside-Out Creation of Femoral Tunnels on Graft Contact Pressure in a Synthetic Knee Model.

    Science.gov (United States)

    Narvy, Steven J; Hatch, George F; Ihn, Hansel E; Heckmann, Nathanael D; McGarry, Michelle H; Tibone, James E; Lee, Thay Q

    2017-07-01

    To characterize and compare the graft contact characteristics of outside-in (OI) and inside-out (IO) femoral tunnels during single-bundle reconstruction of the anterolateral bundle of the posterior cruciate ligament in a synthetic knee model. Femoral tunnels were separately made in 16 synthetic femora (8 OI and 8 IO). Achilles tendon allografts were fixed using suspensory fixation with a pressure sensor between the allograft and femoral tunnel. Grafts were cyclically loaded; force, contact area, contact pressure, and peak pressure at the aperture were measured. This process was repeated using the same allograft to assess the other tunnel angle in a separate specimen. IO specimens showed higher mean contact pressure at all loading cycles, with significance shown at 50 N (P = .02). Peak pressure was also greater in IO specimens at all loading cycles and reached statistical significance at 100 N (P = .04). IO specimens had a lower contact area at 150 N (P = .04). No statistically significant differences in force were observed between the 2 groups. OI creation of the femoral tunnel for anterolateral bundle reconstruction of the posterior cruciate ligament resulted in decreased mean and peak contact pressures at the femoral aperture compared with IO tunnel creation at the specific trajectories and loading parameters tested in this synthetic femoral model. These biomechanical data suggest that OI creation of the femoral tunnel may help reduce in vivo graft contact pressure at the femoral aperture. These data suggest that a tunnel drilled from OI may result in less graft pressure at the femoral aperture, which may prevent graft elongation and optimize graft survival. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  8. IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics.

    Science.gov (United States)

    Abad, C; Antczak, D F; Carvalho, J; Chamley, L W; Chen, Q; Daher, S; Damiano, A E; Dantzer, V; Díaz, P; Dunk, C E; Daly, E; Escudero, C; Falcón, B; Guillomot, M; Han, Y W; Harris, L K; Huidobro-Toro, J P; Illsley, N; Jammes, H; Jansson, T; Johnson, G A; Kfoury, J R; Marín, R; Murthi, P; Novakovic, B; Myatt, L; Petroff, M G; Pereira, F T V; Pfarrer, C; Redman, C W G; Rice, G; Saffery, R; Tolosa, J M; Vaillancourt, C; Wareing, M; Yuen, R; Lash, G E

    2011-03-01

    Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Placentation in different mammalian species.

    Science.gov (United States)

    Chavatte-Palmer, Pascale; Tarrade, Anne

    2016-06-01

    The placenta is a complex, transient organ associated with viviparity, which is located at the interface of the dam and fetus during pregnancy. It is formed after attachment, or implantation, of the blastocyst on the uterine lining and derives from complex cellular and molecular interactions between uterine and embryonic tissues. In mammals, there are many forms of placentation but this organ has the same function in all species: it is responsible for orchestrating materno-fetal exchanges, together with endocrine and immunological functions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

    textabstractIron transport in pregnancy is an active one-way process, from mother to fetus. Early in gestation fetal iron needs are low, and so is trans-placental transport, but as erythropoiesis develops, rising fetal iron needs are met by trans-placental iron transport. Apparently, the fetus

  11. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    Hans Strahl, a contemporary of Duval and Hubrecht, made many important contributions to comparative placentation. Despite this he is not well known and some of his original observations tend to be attributed to later authors. Strahl published a classification of placental types based on their sha...

  12. Microparasites and Placental Invasiveness in Eutherian Mammals.

    Directory of Open Access Journals (Sweden)

    Isabella Capellini

    Full Text Available Placental invasiveness-the number of maternal tissue layers separating fetal tissues from maternal blood-is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness.

  13. Domestic sheep show average coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes

    Science.gov (United States)

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small rumina...

  14. Plasmodium vivax adherence to placental glycosaminoglycans.

    Directory of Open Access Journals (Sweden)

    Kesinee Chotivanich

    Full Text Available Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions.P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours.Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

  15. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Directory of Open Access Journals (Sweden)

    Noura Abd Ellah

    Full Text Available Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1. Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

  16. HST/WFC3 CONFIRMATION OF THE INSIDE-OUT GROWTH OF MASSIVE GALAXIES AT 0 < z < 2 AND IDENTIFICATION OF THEIR STAR-FORMING PROGENITORS AT z {approx} 3

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shannon G.; Franx, Marijn; Muzzin, Adam [Leiden Observatory, Leiden University, P.O. Box 9513, NL-2300 AA Leiden (Netherlands); Van Dokkum, Pieter G. [Department of Astronomy, Yale University, New Haven, CT 06520-8101 (United States); Quadri, Ryan F.; Williams, Rik J. [Observatories of the Carnegie Institution of Washington, Pasadena, CA 91101 (United States); Marchesini, Danilo [Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Holden, Bradford P. [UCO/Lick Observatory, University of California, Santa Cruz, CA 95064 (United States); Stefanon, Mauro, E-mail: patel@strw.leidenuniv.nl [Observatori Astronomic de la Universitat de Valencia, E-46980 Paterna, Valencia (Spain)

    2013-03-20

    We study the structural evolution of massive galaxies by linking progenitors and descendants at a constant cumulative number density of n{sub c} = 1.4 Multiplication-Sign 10{sup -4} Mpc{sup -3} to z {approx} 3. Structural parameters were measured by fitting Sersic profiles to high-resolution CANDELS HST WFC3 J{sub 125} and H{sub 160} imaging in the UKIDSS-UDS at 1 < z < 3 and ACS I{sub 814} imaging in COSMOS at 0.25 < z < 1. At a given redshift, we selected the HST band that most closely samples a common rest-frame wavelength so as to minimize systematics from color gradients in galaxies. At fixed n{sub c}, galaxies grow in stellar mass by a factor of {approx}3 from z {approx} 3 to z {approx} 0. The size evolution is complex: galaxies appear roughly constant in size from z {approx} 3 to z {approx} 2 and then grow rapidly to lower redshifts. The evolution in the surface mass density profiles indicates that most of the mass at r < 2 kpc was in place by z {approx} 2, and that most of the new mass growth occurred at larger radii. This inside-out mass growth is therefore responsible for the larger sizes and higher Sersic indices of the descendants toward low redshift. At z < 2, the effective radius evolves with the stellar mass as r{sub e} {proportional_to}M {sup 2.0}, consistent with scenarios that find dissipationless minor mergers to be a key driver of size evolution. The progenitors at z {approx} 3 were likely star-forming disks with r{sub e} {approx} 2 kpc, based on their low Sersic index of n {approx} 1, low median axis ratio of b/a {approx} 0.52, and typical location in the star-forming region of the U - V versus V - J diagram. By z {approx} 1.5, many of these star-forming disks disappeared, giving rise to compact quiescent galaxies. Toward lower redshifts, these galaxies continued to assemble mass at larger radii and became the local ellipticals that dominate the high-mass end of the mass function at the present epoch.

  17. SPATIALLY RESOLVED H{alpha} MAPS AND SIZES OF 57 STRONGLY STAR-FORMING GALAXIES AT z {approx} 1 FROM 3D-HST: EVIDENCE FOR RAPID INSIDE-OUT ASSEMBLY OF DISK GALAXIES

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Erica June; Van Dokkum, Pieter G.; Skelton, Rosalind E.; Bezanson, Rachel; Lundgren, Britt [Astronomy Department, Yale University, New Haven, CT 06511 (United States); Brammer, Gabriel [European Southern Observatory, Alonson de Cordova 3107, Casilla 19001, Vitacura, Santiago (Chile); Foerster Schreiber, Natascha [Max-Planck-Institut fuer extraterrestrische Physik, Giessenbachstrasse, D-85748 Garching (Germany); Franx, Marijn; Fumagalli, Mattia; Patel, Shannon; Labbe, Ivo [Leiden Observatory, Leiden University, Leiden (Netherlands); Rix, Hans-Walter; Da Cunha, Elisabete; Schmidt, Kasper B. [Max Planck Institute for Astronomy (MPIA), Koenigstuhl 17, 69117 Heidelberg (Germany); Kriek, Mariska [Department of Astronomy, University of California, Berkeley, CA 94720 (United States); Quadri, Ryan [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States)

    2012-03-10

    We investigate the buildup of galaxies at z {approx} 1 using maps of H{alpha} and stellar continuum emission for a sample of 57 galaxies with rest-frame H{alpha} equivalent widths >100 A in the 3D-HST grism survey. We find that the H{alpha} emission broadly follows the rest-frame R-band light but that it is typically somewhat more extended and clumpy. We quantify the spatial distribution with the half-light radius. The median H{alpha} effective radius r{sub e} (H{alpha}) is 4.2 {+-} 0.1 kpc but the sizes span a large range, from compact objects with r{sub e} (H{alpha}) {approx} 1.0 kpc to extended disks with r{sub e} (H{alpha}) {approx} 15 kpc. Comparing H{alpha} sizes to continuum sizes, we find =1.3 {+-} 0.1 for the full sample. That is, star formation, as traced by H{alpha}, typically occurs out to larger radii than the rest-frame R-band stellar continuum; galaxies are growing their radii and building up from the inside out. This effect appears to be somewhat more pronounced for the largest galaxies. Using the measured H{alpha} sizes, we derive star formation rate surface densities, {Sigma}{sub SFR}. We find that {Sigma}{sub SFR} ranges from {approx}0.05 M{sub Sun} yr{sup -1} kpc{sup -2} for the largest galaxies to {approx}5 M{sub Sun} yr{sup -1} kpc{sup -2} for the smallest galaxies, implying a large range in physical conditions in rapidly star-forming z {approx} 1 galaxies. Finally, we infer that all galaxies in the sample have very high gas mass fractions and stellar mass doubling times <500 Myr. Although other explanations are also possible, a straightforward interpretation is that we are simultaneously witnessing the rapid formation of compact bulges and large disks at z {approx} 1.

  18. Placental histopathology of congenital syphilis.

    Science.gov (United States)

    Sheffield, Jeanne S; Sánchez, Pablo J; Wendel, George D; Fong, David W I; Margraf, Linda R; Zeray, Fiker; McIntire, Donald D; Barton Rogers, Beverly

    2002-07-01

    To evaluate the contribution of placental histopathology to the diagnosis of congenital syphilis. From January 1, 1986, through December 31, 1998, all pregnant women presenting to a large, urban Dallas County labor and delivery unit with untreated syphilis at delivery and who had placental evaluation performed were identified. Women were clinically staged, and the infants were evaluated for congenital syphilis using a standard protocol. Each placenta was evaluated by two independent pathologists. Histologic characteristics of the placenta related to congenital syphilis in live-born and stillborn infants were then analyzed. Sixty-seven women met the study criteria: 33 (49%) stillborn and 18 (27%) live-born infants with congenital syphilis, 15 (22%) uninfected live-born infants, and one uninfected stillborn fetus diagnosed by current criteria. There were no differences between the groups with regard to demographic characteristics, prenatal care, or stage of syphilis. Stillborn infants were more likely to deliver preterm (P gestational age, histopathology revealed necrotizing funisitis, villous enlargement, and acute villitis associated with congenital syphilis. Erythroblastosis was more common in stillborn infants with congenital syphilis than all live-born infants (odds ratio 16, 95% confidence interval 1, 370). The addition of histologic evaluation to conventional diagnostic evaluations improved the detection rate for congenital syphilis from 67% to 89% in live-born infants, and 91% to 97% in stillborn infants. Our results show that histopathologic examination of the placenta is a valuable adjunct to the contemporary diagnostic criteria used to diagnose congenital syphilis.

  19. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.R. [Univ. of Maryland, Baltimore, MD (United States); Stabin, M.G.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  20. Placental Extracellular Vesicles and Feto-Maternal Communication

    Science.gov (United States)

    Tong, M.; Chamley, L.W.

    2015-01-01

    The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems. PMID:25635060

  1. Hyperemesis gravidarum and placental dysfunction disorders.

    Science.gov (United States)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-11-25

    Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenatal care visits from July 2012 until October 2014 were included at their first clinic visit. For women without, with mild and with severe hyperemesis, placental dysfunction disorders (gestational hypertension, preeclampsia (PE), stillbirth, miscarriage), neonatal outcomes (birth weight, small for gestational age (SGA), low birth weight (LBW), Apgar score at 5 min, gestational age at delivery) and placental outcomes (placental weight and placental-weight-to-birth-weight ratio (PW/BW ratio)) were studied. Compared to newborns of women without hyperemesis, newborns of women with severe hyperemesis had a 172 g lower birth weight in adjusted analysis (95%CI -333.26; -10.18; p = 0.04). There were no statistically significant effects on placental dysfunction disorders or other neonatal outcome measures. The results of our study suggest that hyperemesis gravidarum does not seem to induce placental dysfunction disorders, but does, if severe lead to lower birth weight.

  2. Gestational diabetes is associated with changes in placental microbiota and microbiome.

    Science.gov (United States)

    Bassols, Judit; Serino, Matteo; Carreras-Badosa, Gemma; Burcelin, Rémy; Blasco-Baque, Vincent; Lopez-Bermejo, Abel; Fernandez-Real, José-Manuel

    2016-12-01

    The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines. Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy. Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P microbiota profile and microbiome is present in GDM. Acinetobacter has been recently shown to induce IL-10 in mice. GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiota a new target for therapy in GDM.

  3. Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic diseases.

    Science.gov (United States)

    Marzioni, Daniela; Quaranta, Alexia; Lorenzi, Teresa; Morroni, Manrico; Crescimanno, Caterina; De Nictolis, Michele; Toti, Paolo; Muzzonigro, Giovanni; Baldi, Alfonso; De Luca, Antonio; Castellucci, Mario

    2009-10-01

    HtrA1 is a secreted protein which behaves as a molecular chaperone at low temperatures and as a serine protease at high temperatures. When the placenta escapes the normal growth control mechanisms, which are present during normal pregnancy, it may develop trophoblastic diseases, such as hydatidiform mole and choriocarcinoma. The aim of the study is to investigate the expression of HtrA1 in these gestational trophoblastic diseases and evaluate whether different HtrA1 expression might be associated with increasingly severe forms of disease. We used immunohistochemistry to assess the expression of HtrA1 in normal human placenta, hydatidiform mole (partial and complete) and choriocarcinoma. In addition to that we used the western blotting technique to quantify HtrA1 immunoreaction in normal human placentas. The most striking finding of our investigation is the decrease in immunostaining of this protease with increasing severity of gestational trophoblastic disease. For instance, in partial and complete moles HtrA1 is weakly expressed in the trophoblast. Moreover, absence of immunoreaction for HtrA1 is observable in the choriocarcinoma cells. In conclusion, we suggest that HtrA1 may play an important role in the pathogenesis and progression of hydatidiform moles and choriocarcinomas, and that HtrA1 may play an important role during the normal development of the placenta, as well as in trophoblastic diseases.

  4. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic...... that epitheliochorial placentation is a derived state and that the common ancestor of placental mammals probably had a placenta of the endotheliochorial type. Where evolutionary trends are implied for mammals as a whole or within orders such as primates they often accompany a switch in reproductive strategy...

  5. Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

    Directory of Open Access Journals (Sweden)

    Hae-Miru Lee

    2017-07-01

    Full Text Available Cigarette smoke (CS causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In this study, the effects of formaldehyde (FA and benzene (Bz, the main components of CS, on cell proliferation and epithelial mesenchymal transition (EMT of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS components and placenta carcinoma. Upon MTT assay, FA (10−8 M to 10−5 M and Bz (10−11 M to 10−8 M increased JEG-3 cell proliferation. Western blot assay revealed that the protein expression of cyclin D1 and E1 increased, while the levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10−8 M and 10−5 M and Bz (10−11 M and 10−8 M increased migration of JEG-3 cells at 24 h and 48 h compared with that at 0 h. In addition, the expression of the epithelial marker, E-cadherin, was significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by FA (10−8 M and 10−5 M and Bz (10−11 M and 10−8 M. snail and slug transcriptional factors were associated with EMT, which were also up-regulated by FA and Bz, indicating that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma cells. We further evaluated reactive oxygen species (ROS and activation of antioxidant effect using dichlorofluorescin diacetate (DCFH-DA and Western blot assay. FA and Bz increased the ROS production and an antioxidant related marker, Nrf2, in JEG-3 cells. However, eIF2α levels were reduced by FA and Bz via activation of the antioxidant reaction. Taken together, these results indicated that FA and Bz induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and EMT and activation of ROS and antioxidant related markers.

  6. Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.

    Science.gov (United States)

    Kholodenko, I V; Yarygin, K N; Gubsky, L V; Konieva, A A; Tairova, R T; Povarova, O V; Kholodenko, R V; Burunova, V V; Yarygin, V N; Skvortsova, V I

    2012-11-01

    Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.

  7. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

    OpenAIRE

    Chunfang, Qiu; GELAYE, Bizu; Denis, Marie; Tadesse, Mahlet G.; Enquobahrie, Daniel A.; Ananth, Cande V.; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E.; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to e...

  8. Evolutionary perspectives into placental biology and disease.

    Science.gov (United States)

    Chuong, Edward B; Hannibal, Roberta L; Green, Sherril L; Baker, Julie C

    2013-12-01

    In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal-fetal conflict shapes both basic placental and reproductive biology - in all species - will provide key insights into diseases of pregnancy.

  9. Evolutionary perspectives into placental biology and disease

    Directory of Open Access Journals (Sweden)

    Edward B. Chuong

    2013-12-01

    Full Text Available In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal–fetal conflict shapes both basic placental and reproductive biology – in all species – will provide key insights into diseases of pregnancy.

  10. A placental phenotype for intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Geenes, V L; Lim, Y-H; Bowman, N; Tailor, H; Dixon, P H; Chambers, J; Brown, L; Wyatt-Ashmead, J; Bhakoo, K; Williamson, C

    2011-12-01

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. A novel bridge between oxidative stress and immunity: the interaction between hydrogen peroxide and human leukocyte antigen G in placental trophoblasts during preeclampsia.

    Science.gov (United States)

    Zhou, Xue; Zhang, Guo-ying; Wang, Jue; Lu, Shou-lian; Cao, Jun; Sun, Li-zhou

    2012-05-01

    The aim of this study was to investigate a possible association between hydrogen peroxide and human leukocyte antigen G (HLA-G) in preeclampsia. We explored the correlation between HLA-G and hydrogen peroxide in preeclamptic (n = 30) and normotensive (n = 30) placentas, which was confirmed by in vitro experiments. Furthermore, RNA interference was used to explore the influence of HLA-G on the proliferation, apoptosis and invasion of HTR-8/SVneo cells when exposed to hydrogen peroxide. We found an inverse correlation between hydrogen peroxide and HLA-G expression in preeclamptic placentas. High levels of hydrogen peroxide could down-regulate HLA-G expression in HTR-8/SVneo. Compared with HLA-G knockdown HTR-8/SVneo, increased proliferation inhibition, higher apoptosis, and decreased cell invasion were found in the cell expressing HLA-G when exposed to hydrogen peroxide. Our findings highlight that high levels of hydrogen peroxide can down-regulate HLA-G expression in trophoblasts during preeclampsia and trophoblasts expressing HLA-G are vulnerable to oxidative stress. Copyright © 2012 Mosby, Inc. All rights reserved.

  12. Excess LIGHT contributes to placental impairment, increased secretion of vasoactive factors, hypertension, and proteinuria in preeclampsia.

    Science.gov (United States)

    Wang, Wei; Parchim, Nicholas F; Iriyama, Takayuki; Luo, Renna; Zhao, Cheng; Liu, Chen; Irani, Roxanna A; Zhang, Weiru; Ning, Chen; Zhang, Yujin; Blackwell, Sean C; Chen, Lieping; Tao, Lijian; Hicks, M John; Kellems, Rodney E; Xia, Yang

    2014-03-01

    Preeclampsia, a prevalent hypertensive disorder of pregnancy, is believed to be secondary to uteroplacental ischemia. Accumulating evidence indicates that hypoxia-independent mediators, including inflammatory cytokines and growth factors, are associated with preeclampsia, but it is unclear whether these signals directly contribute to placental damage and disease development in vivo. We report that LIGHT, a novel tumor necrosis factor superfamily member, is significantly elevated in the circulation and placentas of preeclamptic women compared with normotensive pregnant women. Injection of LIGHT into pregnant mice induced placental apoptosis, small fetuses, and key features of preeclampsia, hypertension and proteinuria. Mechanistically, using neutralizing antibodies specific for LIGHT receptors, we found that LIGHT receptors herpes virus entry mediator and lymphotoxin β receptor are required for LIGHT-induced placental impairment, small fetuses, and preeclampsia features in pregnant mice. Accordingly, we further revealed that LIGHT functions through these 2 receptors to induce secretion of soluble fms-like tyrosine kinase-1 and endothelin-1, 2 well-accepted pathogenic factors in preeclampsia, and thereby plays an important role in hypertension and proteinuria in pregnant mice. Lastly, we extended our animal findings to human studies and demonstrated that activation of LIGHT receptors resulted in increased apoptosis and elevation of soluble fms-like tyrosine kinase-1 secretion in human placental villous explants. Overall, our human and mouse studies show that LIGHT signaling is a previously unrecognized pathway responsible for placental apoptosis, elevated secretion of vasoactive factors, and subsequent maternal features of preeclampsia, and reveal new therapeutic opportunities for the management of the disease.

  13. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L|info:eu-repo/dai/nl/413640671; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E|info:eu-repo/dai/nl/071889256; Uiterwaal, Cuno S P M|info:eu-repo/dai/nl/136603947

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was

  14. Abnormal umbilical artery Doppler velocimetry and placental ...

    African Journals Online (AJOL)

    stromal fibrosis and calcification). The placental lesions were then compared with DV findings (at delivery) and prospectively with neonatal outcome. Statistical analysis. Statistical software SPSS version 20.0 (IBM Corp., USA) was used for statistical ...

  15. Pregnancy Complications: Placental Accreta, Increta and Percreta

    Science.gov (United States)

    ... If the bleeding is severe, go to the hospital right way. How are these placental conditions diagnosed? These conditions usually are diagnosed using ultrasound . In some cases, your provider may use magnetic resonance imaging (MRI). MRI is a medical test ...

  16. Comparative aspects of trophoblast development and placentation

    Directory of Open Access Journals (Sweden)

    Enders Allen C

    2004-07-01

    Full Text Available Abstract Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it

  17. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned...

  18. Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model

    NARCIS (Netherlands)

    Kuehnel, Elisabeth; Kleff, Veronika; Stojanovska, Violeta; Kaiser, Stephanie; Waldschuetz, Ralph; Herse, Florian; Plosch, Torsten; Winterhager, Elke; Gellhaus, Alexandra

    Since it is known that placental overexpression of the human anti-angiogenic molecule sFlt-1, the main candidate in the progression of preeclampsia, lead to intrauterine growth restriction (IUGR) in mice by lentiviral transduction of mouse blastocysts, we hypothesize that sFlt-1 influence placental

  19. Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia.

    Science.gov (United States)

    Lacko, Lauretta A; Massimiani, Micol; Sones, Jenny L; Hurtado, Romulo; Salvi, Silvia; Ferrazzani, Sergio; Davisson, Robin L; Campagnolo, Luisa; Stuhlmann, Heidi

    2014-08-01

    The mammalian placenta is the site of nutrient and gas exchange between the mother and fetus, and is comprised of two principal cell types, trophoblasts and endothelial cells. Proper placental development requires invasion and differentiation of trophoblast cells, together with coordinated fetal vasculogenesis and maternal vascular remodeling. Disruption in these processes can result in placental pathologies such as preeclampsia (PE), a disease characterized by late gestational hypertension and proteinuria. Epidermal Growth Factor Like Domain 7 (EGFL7) is a largely endothelial-restricted secreted factor that is critical for embryonic vascular development, and functions by modulating the Notch signaling pathway. However, the role of EGFL7 in placental development remains unknown. In this study, we use mouse models and human placentas to begin to understand the role of EGFL7 during normal and pathological placentation. We show that Egfl7 is expressed by the endothelium of both the maternal and fetal vasculature throughout placental development. Importantly, we uncovered a previously unknown site of EGFL7 expression in the trophoblast cell lineage, including the trophectoderm, trophoblast stem cells, and placental trophoblasts. Our results demonstrate significantly reduced Egfl7 expression in human PE placentas, concurrent with a downregulation of Notch target genes. Moreover, using the BPH/5 mouse model of PE, we show that the downregulation of Egfl7 in compromised placentas occurs prior to the onset of characteristic maternal signs of PE. Together, our results implicate Egfl7 as a possible factor in normal placental development and in the etiology of PE. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. The Placental Microbiota Is Altered among Subjects with Gestational Diabetes Mellitus: A Pilot Study.

    Science.gov (United States)

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Mao, Lili; Yu, Miao; Xu, Jianping; Wang, Tong

    2017-01-01

    Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother and child. However, the associations between human placental microbiota and GDM are poorly understood. We aimed to profile the placental microbiota of GDM and further define whether or not certain placental microbiota taxon correlates with specific clinical characteristics. Placenta were collected from GDM women and women with normal pregnancies (n = 10, in each group) consecutively recruited at Peking Union Medical College Hospital. The anthropometric parameters of mother and infant, and cord blood hormones, including insulin, leptin and insulin-like growth factor-1 (IGF-1) were measured. Bacterial genomic DNA was isolated using magnetic beads and the human placental microbiota was analyzed using the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. It showed there was no statistical difference in the clinical characteristics of mothers and infants, such as BMI at the beginning of pregnancy and gestational weight gain (GWG), birth weight, and cord blood hormones, including insulin, leptin and IGF-1. We found that the placental microbiota is composed of four dominant phyla from Proteobacteria (the most abundant), Bacteroidetes, Actinobacteria and Firmicutes, with the proportion of Proteobacteria increased, and Bacteroidetes and Firmicutes were decreased of women with GDM. Further analyses suggested that bacterial taxonomic composition of placentas from the phylum level down to the bacteria level, differed significantly between women with GDM and non-GDM women with normal pregnancies. Regression analysis showed a cluster of key operational taxonomic units (OTUs), phyla and genera were significantly correlated with GWG during pregnancy of mothers, and cord blood insulin, IGF-1 and leptin concentrations. In conclusion, our novel study showed that a distinct placental microbiota profile is present in GDM, and is associated

  1. The distinct proteome of placental malaria parasites.

    Energy Technology Data Exchange (ETDEWEB)

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  2. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpa......In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings...

  3. Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?

    Science.gov (United States)

    Greenwood, Susan L.; Sibley, Colin P.; Baker, Philip N.; Challis, John R. G.; Jones, Rebecca L.

    2012-01-01

    Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activity would be affected by maternal age and/or growth status. Placentas from teenagers and adults were collected. Teenagers were defined as growing or nongrowing based on knee height measurements. System A amino acid transporter activity was quantified as sodium-dependent uptake of [14C]methylaminoisobutyric acid into placental fragments. Teenagers had lower placental system A activity than adults (P teenagers, AGA and SGA infants had lower placental system A activity than AGA infants born to adults (P teenagers than in nongrowing teenagers (P teenagers than in adults (P teenagers. There was no difference in transporter protein expression/localization between cohorts. Teenagers have inherently reduced placental transport, which may underlie their susceptibility to delivering SGA infants. Growing teenagers appear to overcome this susceptibility by stimulating the activity, but not expression, of system A transporters. PMID:22028413

  4. Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?

    Science.gov (United States)

    Hayward, Christina E; Greenwood, Susan L; Sibley, Colin P; Baker, Philip N; Challis, John R G; Jones, Rebecca L

    2012-01-15

    Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activity would be affected by maternal age and/or growth status. Placentas from teenagers and adults were collected. Teenagers were defined as growing or nongrowing based on knee height measurements. System A amino acid transporter activity was quantified as sodium-dependent uptake of [(14)C]methylaminoisobutyric acid into placental fragments. Teenagers had lower placental system A activity than adults (P teenagers, AGA and SGA infants had lower placental system A activity than AGA infants born to adults (P teenagers than in nongrowing teenagers (P teenagers than in adults (P teenagers. There was no difference in transporter protein expression/localization between cohorts. Teenagers have inherently reduced placental transport, which may underlie their susceptibility to delivering SGA infants. Growing teenagers appear to overcome this susceptibility by stimulating the activity, but not expression, of system A transporters.

  5. Peripheral and placental biomarkers in women with placental malaria: a systematic review

    NARCIS (Netherlands)

    Ruizendaal, Esmée; van Leeuwen, Elisabeth; Mens, Petra F.

    2015-01-01

    Placental malaria (PM) causes significant morbidity in mothers and infants. Diagnosis of PM during pregnancy is however problematic due to placental sequestration of parasites. Host biomarkers may therefore be used as a diagnostic method. In this systematic review most studies focused on

  6. Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Farley, D M; Choi, J; Dudley, D J; Li, C; Jenkins, S L; Myatt, L; Nathanielsz, P W

    2010-08-01

    HYPOTHESIS AND STUDY OBJECTIVES: We hypothesized that maternal obesity is associated with increased placental amino acid transport and hyperleptinemia. Our objectives were to study placental amino acid transport and the effect of leptin on placental amino acid transport in vitro in the setting of maternal obesity. Seven lean, BMI at entry 22.4, and seven obese, BMI at entry 31.5 (p leptin-stimulated placental system A sodium-dependent neutral amino acid transporter (SNAT) activity, placental immunoreactive protein expression of SNAT, leptin and leptin receptor, and maternal and fetal plasma leptin concentrations, with significance set at p leptin receptor (p = 0.01) and SNAT-4 (p leptin in the lean group as compared to the obese group. Maternal weight gain and offspring birth weights were not different between groups. Maternal obesity was accompanied by decreased placental SNAT activity associated with maternal hyperleptinemia and placental leptin resistance in spite of appropriate maternal weight gain and normally grown neonates. These findings suggest altered placental function that may have clinical implications in obese pregnant women.

  7. Human Placental-Derived Stem Cell Transplantation

    Science.gov (United States)

    2017-12-20

    Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Adrenoleukodystrophy; Niemann-Pick Disease; Metachromatic Leukodystrophy; Wolman Disease; Krabbe's Disease; Gaucher's Disease; Fucosidosis; Batten Disease; Severe Aplastic Anemia; Diamond-Blackfan Anemia; Amegakaryocytic Thrombocytopenia; Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia

  8. Deoxynivalenol transport across the human placental barrier

    DEFF Research Database (Denmark)

    Nielsen, Jeanette K S; Vikström, Anna C; Turner, Paul

    2011-01-01

    with the ex vivo dual perfusion model. The concentration of DON on the foetal side after 4h was about 21% of that on the maternal side at t=0. These results support the data from the BeWo monolayer model in respect to the transport rate of DON, and are consistent with our hypothesis of foetal exposure to DON...

  9. Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In Vivo.

    Science.gov (United States)

    Tong, Mancy; Stanley, Joanna L; Chen, Q; James, Joanna L; Stone, Peter R; Chamley, Larry W

    2017-11-01

    How do nano-vesicles extruded from normal first trimester human placentae affect maternal vascular function? Placental nano-vesicles affect the ability of systemic mesenteric arteries to undergo endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant mice. Dramatic cardiovascular adaptations occur during human pregnancy, including a substantial decrease in total peripheral resistance in the first trimester. The human placenta constantly extrudes extracellular vesicles that can enter the maternal circulation and these vesicles may play an important role in feto-maternal communication. Human placental nano-vesicles were administered into CD1 mice via a tail vein and their localization and vascular effects at 30 min and 24 h post-injection were investigated. Nano-vesicles from normal first trimester human placentae were collected and administered into pregnant (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all major organs were dissected for imaging (n = 7 at each time point) while uterine and mesenteric arteries were dissected for wire myography (n = 6 at each time point). Additional in vitro studies using HMEC-1 endothelial cells were also conducted to investigate the kinetics of interaction between placental nano-vesicles and endothelial cells. Nano-vesicles from first trimester human placentae localized to the lungs, liver and kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory response of mesenteric arteries to acetylcholine, while exposure for 24 h had the opposite effect (P nano-vesicles did not affect the function of uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano-vesicles rapidly interacted with endothelial cells via a combination of phagocytosis, endocytosis and cell surface binding in vitro. N/A. As it is not ethical to administer labelled placental nano-vesicles to

  10. Of mice and women: rodent models of placental malaria

    DEFF Research Database (Denmark)

    Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

    2010-01-01

    expressed in placental malaria (PM) and specific for chondroitin sulfate A (CSA). In Plasmodium falciparum, these VSA(PM) appear largely synonymous with the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family variant VAR2CSA. As rodent malaria parasites do not possess PfEMP1 homologs......, the usefulness of experimental mouse PM models remains controversial. However, many features of murine and human PM are similar, including involvement of VSAs analogous to PfEMP1. It thus appears that rodent model studies can further the understanding of VSA-dependent malaria pathogenesis and immunity....

  11. Evolution of factors affecting placental oxygen transfer.

    Science.gov (United States)

    Carter, A M

    2009-03-01

    A review is given of the factors determining placental oxygen transfer and the oxygen supply to the fetus. In the case of continuous variables, such as the rate of placental blood flow, it is not possible to trace evolutionary trends. Discontinuous variables, for which we can define character states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic gene yielded HBG-T2, a gene that is expressed in the fetus and confers high oxygen affinity on its haemoglobin. A separate event in ruminants involved duplication of an adult gene, again resulting in a fetally expressed variant (HBB-T3) that conveys high oxygen affinity. In rodents and lagomorphs, where fetal and adult haemoglobin are not different, developmental regulation of 2, 3-diphosphoglycerate ensures the high oxygen affinity of fetal blood. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the type of interhaemal barrier. It has been shown that epitheliochorial placentation is a derived state and that the common ancestor of placental mammals probably had a placenta of the endotheliochorial type. Where evolutionary trends are implied for mammals as a whole or within orders such as primates they often accompany a switch in reproductive strategy that is manifested in a change of newborn state from poorly developed (altricial) to well developed (precocial).

  12. Ascending placentitis in the mare: A review

    Directory of Open Access Journals (Sweden)

    Cummins C

    2008-05-01

    Full Text Available Abstract Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal. Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane. Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support. Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.

  13. Placental vascular dysfunction in diabetic pregnancies: intimations of fetal cardiovascular disease?

    Science.gov (United States)

    Leach, Lopa

    2011-05-01

    In the human placenta, the angioarchitecture of fetal vessels lying in maternal blood is useful for nutrient uptake, but it makes the synthesis, maturation and functioning of placental vessels vulnerable to any alterations in the fetal and maternal environment. This review discusses how the maternal diabetic milieu, and the resultant fetal hyperglycemia and hyperinsulinemia, may act together to produce an altered placental vascular phenotype, which includes increased angiogenesis, altered junctional maturity, increased vascular endothelial-like growth factor (VEGF), altered VEGF and insulin receptor profiles, and upregulation of genes involved in signal transduction, transcription and mitosis in placental endothelial cells. The placental vascular dysfunction does extend to other fetal vascular beds including endothelial cells from umbilical vessels, where there are reports of elevated basal iNOS activity and altered sensitivity to insulin. There is emerging evidence of epigenetic modulation of fetal endothelial genes in diabetes and long-term vascular consequences of this. Thus, placental vascular dysfunction in diabetes may be contributing to and describing disturbances in the fetal vasculature, which may produce an overt pathological response in later life if challenged with additional cardiovascular stresses. © 2011 John Wiley & Sons Ltd.

  14. Short-Term Exposure to Urban Air Pollution and Influences on Placental Vascularization Indexes.

    Science.gov (United States)

    Hettfleisch, Karen; Bernardes, Lisandra Stein; Carvalho, Mariana Azevedo; Pastro, Luciana Duzolina Manfré; Vieira, Sandra Elisabete; Saldiva, Silvia R D M; Saldiva, Paulo; Francisco, Rossana Pulcineli Vieira

    2017-04-01

    It has been widely demonstrated that air pollution can affect human health and that certain pollutant gases lead to adverse obstetric outcomes, such as preeclampsia and fetal growth restriction. We evaluated the influence of individual maternal exposure to air pollution on placental volume and vascularization evaluated in the first trimester of pregnancy. This was a cross-sectional study on low-risk pregnant women living in São Paulo, Brazil. The women carried passive personal NO2 and O3 monitors in the week preceding evaluation. We employed the virtual organ computer-aided analysis (VOCAL) technique using three-dimensional power Doppler ultrasound to evaluate placental volume and placental vascular indexes [vascularization index (VI), flow index (FI), and vascularization flow index (VFI)]. We analyzed the influence of pollutant levels on log-transformed placental vascularization and volume using multiple regression models. We evaluated 229 patients. Increased NO2 levels had a significant negative association with log of VI (p = 0.020 and beta = -0.153) and VFI (p = 0.024 and beta = -0.151). NO2 and O3 had no influence on the log of placental volume or FI. NO2, an estimator of primary air pollutants, was significantly associated with diminished VI and VFI in the first trimester of pregnancy.

  15. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain.

    Science.gov (United States)

    Bonnin, A; Levitt, P

    2011-12-01

    In addition to its role in neurotransmission, embryonic serotonin (5-HT) has been implicated in the regulation of neurodevelopmental processes. For example, we recently showed that a subset of 5-HT1-receptors expressed in the fetal forebrain mediate a serotonergic modulation of thalamocortical axons response to axon guidance cues, both in vitro and in vivo. This influence of 5-HT signaling on fetal brain wiring raised important questions regarding the source of the ligand during pregnancy. Until recently, it was thought that 5-HT sources impacting brain development arose from maternal transport to the fetus, or from raphe neurons in the brainstem of the fetus. Using genetic mouse models, we uncovered previously unknown differences in 5-HT accumulation between the fore- and hindbrain during early and late fetal stages, through an exogenous source of 5-HT. Using additional genetic strategies, a new technology for studying placental biology ex vivo, and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source and uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor, in both mice and humans. These results implicate a new, direct role for placental metabolic pathways in modulating fetal brain development and suggest an important role for maternal-placental-fetal interactions and 5-HT in the fetal programming of adult mental disorders. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Placental hormones and the control of maternal metabolism and fetal growth.

    Science.gov (United States)

    Newbern, Dorothee; Freemark, Michael

    2011-12-01

    To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression. The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.

  17. [Antenatal diagnosis of placental acretism-percretism].

    Science.gov (United States)

    Haghenbeck-Altamirano, Francisco Javier; Leis-Márquez, Teresa; Ayala-Yáñez, Rodrigo; Juárez-García, Luz del Carmen; García-Moreno, Carla

    2013-05-01

    Placental acretism is an adherencial pathology associated with a high maternal morbidity and mortality rates. Antepartum diagnosis is essential to plan a proper management and reduce serious complications. Risk factors in these patients include prior cesarean sections, uterine scars and placenta previa. Second level ultrasonography may detect placental acretism with high sensitivity and specificity; magnetic resonance imaging may play a complimentary role in the diagnosis of placental acretism when ultrasonographic findings are non-conclusive, specially when determining miometrium invasion in placental acretism (incretism, percretism). This paper reports the case of a patient treated at the ABC Medical Center of Santa Fe, in her second gestation with the diagnosis of an arcuate uterus, previous cesarean section and placenta previa who presented a vaginal bleeding during pregnancy; ultrasound evaluation, in the second trimester, identified a probable placental acretism, in the third trimester, the same technology suggested placenta percreta, complimentary magnetic resonance imaging supported this diagnosis, with probable invasion to bladder, bowel and abdominal wall muscles. Imaging studies were performed at the Hospital Angeles Lomas (Maternal Fetal Clinic). A diagnosis of placenta acreta-percreta, called for a multidisciplinary surgical team, availability of blood products and other resources to face probable complications associated to the obstetrical resolution. Maternal results were optimal since histopathological evaluation reported miometrial incretism, with placental invasion millimeters away from the uterine serosa. Most ultrasonographic studies evaluating the invasion degree of the placenta have small sample sizes, generating a greater degree of false positive or false negative observations. Therefore, we agree with other authors that in all acretism cases (independent of their invasion degree), a multidisciplinary surgical team should be assembled in

  18. Cesarean Delivery for a Life‑threatening Preterm Placental Abruption

    African Journals Online (AJOL)

    Placental abruption is one of the major life‑threatening obstetric conditions. The fetomaternal outcome of a severe placental abruption depends largely on prompt maternal resuscitation and delivery. A case of severe preterm placental abruption with intrauterine fetal death. Following a failed induction of labor with a ...

  19. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

    Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...... immunity with multiple infections. Placental malaria (PM) is caused by P. falciparum sequestering in the placenta of pregnant women due to the presence of novel receptors in the placenta. An estimated 200,000 infants die a year as a result of PM. In 2004 the specific protein responsible...... and development in the field of placental malaria vaccine development....

  20. Emotions Inside Out: 130 Years after Darwin's "The Expression of the Emotions in Man and Animals". Proceedings of a conference. November 16-17, 2002, New York City, New York, USA.

    Science.gov (United States)

    2003-12-01

    In The Expression of Emotions in Man and Animals Darwin argued that emotions are not unique to humans, but can be found in many species; that many of the same social occasions that generate emotions in humans do so in other animals. He asked why this particular expression for a particular emotion, and his answer formed part of his demonstration of the continuity of the species and was thus crucial to his evolutionary theory. Darwin was one of the first scientists to use photographs as illustrations and to use the judgment method for studying the signal value of an expression-which has become the most frequently used method in the psychology of expression. The contents of the present volume extend, support, and sometimes contradict Darwin's remarkable contribution to the field of the expression of emotions.

  1. Placental malaria and immunity to infant measles

    NARCIS (Netherlands)

    Owens, S.; Harper, G.; Amuasi, J.; Offei-Larbi, G.; Ordi, J.; Brabin, B. J.

    2006-01-01

    The efficiency of transplacental transfer of measles specific antibody was assessed in relation to placental malaria. Infection at delivery was associated with a 30% decrease in expected cord measles antibody titres. Uninfected women who received anti-malarial drugs during pregnancy transmitted 30%

  2. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

  3. Abnormal umbilical artery Doppler velocimetry and placental ...

    African Journals Online (AJOL)

    Background. Doppler velocimetry (DV) is widely used to assess the vascular formation of the placenta in fetal growth restriction (FGR) and to estimate the haemodynamic condition of the growth-restricted fetus. Umbilical artery (UA) flow is essentially placental, rather than fetal. Hence, DV provides information about the fetal ...

  4. Placental growth factor and pre-eclampsia

    Science.gov (United States)

    Chau, K; Hennessy, A; Makris, A

    2017-01-01

    Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the feto-placental circulation and supports trophoblast growth. Mechanisms by which PlGF expression is regulated continue to be investigated. Low circulating PlGF precedes the manifestation of clinical disease in pre-eclamptic pregnancies and intrauterine growth restriction. This suggests that low PlGF is a marker of abnormal placentation, but it remains uncertain whether this is a cause or consequence. Prediction of pre-eclampsia using PlGF is promising and may assist in the targeting of resources to women at highest risk of adverse pregnancy outcomes. Promisingly, experimental animal models of pre-eclampsia have been successfully treated with supplemental PlGF. Treatment of pre-eclampsia with PlGF is a potential therapeutic option requiring further exploration. This review focuses specifically on the role of PlGF in normal and pathological placental development and in the clinical management of pre-eclampsia. PMID:29115294

  5. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

    nutrition involving columnar trophoblast cells. These range from areolae in moles through complexly folded hemophagous regions in tenrecs to the trophoblastic annulus in shrews. Of these placental characters, few offer support to current phylogenies. However, the case for placing hedgehogs and gymnures...

  6. Diagnosis of foetal membrane ruptures: Placental alpha ...

    African Journals Online (AJOL)

    Context: Pre‑labour rupture of membranes (PROM) is a common obstetric complication which presents a diagnostic challenge, especially in equivocal cases. Standard methods of diagnosis are limited by high false positives and negatives. This study compared the accuracy of a biomarker placental alpha microglobulin‑1 ...

  7. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption.

    Science.gov (United States)

    Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrendcircadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome.

  8. PP128. Placental Caspase-3 gene polymorphisms is associated with preeclampsia.

    Science.gov (United States)

    Hsu, C-D; Polavarapu, S; Parton, L

    2012-07-01

    Increased placental trophoblastic apoptosis (programmed cell death) was previously reported in pregnancies complicated by preeclampsia. Caspase-3 is one of the key executioners of apoptosis. Caspase are expressed in many tissues including human placental trophoblast and other tissues. Variations in the promoter area of the Caspase genes may modulate apoptotic signaling, contributing to an increased risk of preeclampsia To determine if gene polymorphisms of Caspase 3 proteins differ between patient with and without preeclampsia. Forty-three singleton placentas were studied. Twenty-two placentas were with preeclampsia and 21 were normotensive controls. DNA was extracted from placentas using QIAAmp DNA Minikit. Genotyping of Caspase 3 +567 was determined by real-time PCR using the Applied Biosystems Prism 7900 HT SDS machine. Chi-square and Fisher's exact tests were used for statistical analysis. There were no significant differences in maternal age, parity or race between the two groups. Preeclamptic placentas had higher frequency of wild type TT of Caspase-3 SNP (+567) as compared with normotensive controls (59% versus 28.5%). Preeclamptic placentas expressed significantly more genotype of TT of Caspase-3 SNP (+567) than normotensive patients when compared to CC (p=0.02). The alle frequencies of the Caspase SNP (+567) in preeclampstic placentas were 0.77 and 0.23 for T and C, respectively, as compared to 0.52 and 0.48, respectively, in placentas from normotensive pregnancies. Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Increased of placental apoptosis was reported in pregnancy complicated with preeclamsia. Our findings indicate placental Caspase 3 (+567) gene polymorphisms is associated with preeclampsia. Altered placental alle frequencies and caspase-3 SNP (+567) in preeclampsia further suggests preeclampsia is a trophoblastic disorder. Copyright © 2012. Published by Elsevier B.V.

  9. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya.

    Science.gov (United States)

    Cumberland, Phillippa; Shulman, Caroline E; Maple, P A Chris; Bulmer, Judith N; Dorman, Edgar K; Kawuondo, Ken; Marsh, Kevin; Cutts, Felicity T

    2007-08-15

    In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-than-expected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%-67%) in newborns of HIV-infected women and by 48% (95% CI, 26%-62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.

  10. Evidence that fetal death is associated with placental aging.

    Science.gov (United States)

    Maiti, Kaushik; Sultana, Zakia; Aitken, Robert J; Morris, Jonathan; Park, Felicity; Andrew, Bronwyn; Riley, Simon C; Smith, Roger

    2017-10-01

    The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the

  11. ATG16L1 governs placental infection risk and preterm birth in mice and women.

    Science.gov (United States)

    Cao, Bin; Macones, Colin; Mysorekar, Indira U

    2016-12-22

    The placenta is a barrier against maternal-fetal transmission of pathogens. Placental infections can cause several adverse pregnancy outcomes, including preterm birth (PTB). Yet, we have limited knowledge regarding the mechanisms the placenta uses to control infections. Here, we show that autophagy, a cellular recycling pathway important for host defense against pathogens, and the autophagy gene Atg16L1 play a key role in placental defense and are negatively associated with PTB in pregnant women. First, we demonstrate that placentas from women who delivered preterm exhibit reduced autophagy activity and are associated with higher infection indicators. Second, we identify the cellular location of the autophagy activity as being in syncytial trophoblasts. Third, we demonstrate that higher levels of autophagy and ATG16L1 in human trophoblasts were associated with increased resistance to infection. Accordingly, loss of autophagy or ATG16L1 impaired trophoblast antibacterial defenses. Fourth, we show that Atg16l1-deficient mice gave birth prematurely upon an inflammatory stimulus and their placentas were significantly less able to withstand infection. Finally, global induction of autophagy in both mouse placentas and human trophoblasts increased infection resistance. Our study has significant implications for understanding the etiology of placental infections and prematurity and developing strategies to mitigate placental infection-induced PTB.

  12. Implementation of a quality system (ISO 9000 series) for placental blood banking.

    Science.gov (United States)

    Sirchia, G; Rebulla, P; Lecchi, L; Mozzi, F; Crepaldi, R; Parravicini, A

    1998-02-01

    Although placental blood has recently become a new source of hematopoietic progenitors for marrow replacement, limited attention has been given to systems suitable to ensure the short-term and long-term quality of placental blood units used for transplantation. In this article, we describe a quality system for placental blood banking developed in accord with ISO 9002 norms at Milano Cord Blood Bank. The quality system is the organizational structure, procedures, processes, and resources needed to implement quality management. ISO 9002 is a model for quality assurance in production, installation, and servicing, which includes a number of clauses providing guidance for the implementation of the quality system. The quality system was started by the bank medical director with step 1: the general quality plan, which included (a) the written description of mission, objectives, technical and organizational policies, and staff organization chart of the placental blood bank, (b) the definition and acquisition of adequate financial, human, and structural resources, (c) the appointment of a quality system head independent from the production laboratory and reporting directly to the medical director. Tasks of the quality system head were (a) to identify the placental blood banking process together with the placental blood bank personnel, (b) to implement a documentation plan finalized at the production and maintenance of (i) the quality manual, which provides a summary on how the bank operates with a quality system in compliance with the ISO 9002 clauses, (ii) the general procedures (or quality system procedures), which provide more detail on selected clauses, including at least those prescribed by the ISO 9002 standard, (iii) the operative procedures (or process procedures), which describe in detail the process of placental blood banking and how technical activities must be performed, (iv) the work instructions, which provide stepwise descriptions of individual activities, (v

  13. Polychlorinated biphenyls (PCBs) decrease the placental syncytiotrophoblast volume and increase Placental Growth Factor (PlGF) in the placenta of normal pregnancy.

    Science.gov (United States)

    Tsuji, M; Aiko, Y; Kawamoto, T; T Hachisuga; Kooriyama, C; Myoga, M; Tomonaga, C; Matsumura, F; Anan, A; Tanaka, M; Yu, H S; Fujisawa, Y; Suga, R; Shibata, E

    2013-07-01

    Polychlorinated biphenyls (PCBs) are a class of biologically active, highly stable compounds. Exposure risks include consumption of fatty fish, meat, dairy products and human breast milk, as well as environmental and occupational settings. Numerous reports have described PCB-dependent adverse effects on human fetal growth, including increased risk for IUGR, changes in endocrine function and hormone metabolism, and immunosuppressive and neurological deficits. Here we test the prediction that in utero PCB exposure adversely effects placental morphology, potentially leading to placental insufficiency en route to fetal growth restriction. PCB homologs (10) were measured in the maternal and fetal blood of a small cohort of normotensive pregnancies (22) by gas chromatography-mass spectrometry. PCB levels were compared with angiogenesis associated proteins Placental Growth Factor (PlGF) and sFlt-1, determined by ELISA, and the total estimated syncytiotrophoblast (ST) volume. Significant associations between PCB exposure and both PlGF and ST volume were identified. PCB effects on placenta morphology and predicted function are discussed. These results demonstrate that the human placenta, including ST, is a target of PCB toxicity, and that current environmental PCB exposure levels are a risk to reproductive health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Placental mesenchymal dysplasia: chronological observation of placental images during gestation and review of the literature.

    Science.gov (United States)

    Ohira, Satoshi; Ookubo, Nao; Tanaka, Kyoko; Takatsu, Akiko; Kobara, Hisanori; Kikuchi, Norihiko; Ohya, Ayumi; Kanai, Makoto; Shiozawa, Tanri

    2013-01-01

    Placental mesenchymal dysplasia (PMD) is characterized by multiple hypoechoic vesicles which are similar to molar changes in the placenta; however, the process of such morphological changes of PMD during pregnancy has not been fully understood. We performed a review of all PMD cases published in English and identified 49 articles including 110 cases. With regard to the gestational age at which the multicystic pattern was seen, approximately 70% of cases were diagnosed at 13-20 weeks of gestation. Another characteristic feature of PMD is varicose dilation of fetal chorionic vessels. As many as 90% of cases were diagnosed as placenta with dilated fetal chorionic vessels in the third trimester. We also report a case of PMD which was found at 10 weeks of gestation according to ultrasonic molar patterns. Serial observations of the placenta using ultrasound and magnetic resonance imaging revealed that multicystic lesions became smaller after 23 weeks. In contrast, dilated placental vessels on the fetal side became apparent at 38 weeks. The present review highlights that placental vesicular lesions of PMD may precede dilation of fetal chorionic vessels during pregnancy. It also indicates the potential of a gradual reduction in size of PMD's placental vesicular lesions by serial study of placental images. Copyright © 2013 S. Karger AG, Basel.

  15. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

    Carter, A M; Miglino, M A; Ambrosio, C E

    2008-01-01

    Evidence from several sources supports a close phylogenetic relationship between elephants and sirenians. To explore whether this was reflected in similar placentation, we examined eight delivered placentae from the Amazonian manatee using light microscopy and immunohistochemistry. In addition......, the fetal placental circulation was described by scanning electron microscopy of vessel casts. The manatee placenta was zonary and endotheliochorial, like that of the elephant. The interhaemal barrier comprised maternal endothelium, cytotrophoblasts and fetal endothelium. We found columnar trophoblast...... beneath the chorionic plate and lining lacunae in this region, but there was no trace in the term placenta of haemophagous activity. The gross anatomy of the cord and fetal membranes was consistent with previous descriptions and included a four-chambered allantoic sac, as also found in the elephant...

  16. Hyperemesis gravidarum and placental dysfunction disorders

    OpenAIRE

    Koudijs, Heleen M.; Savitri, Ary I.; Browne, Joyce L.; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E.; Uiterwaal, Cuno S. P. M.

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenata...

  17. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. [Maternal-placental interactions and fetal programming].

    Science.gov (United States)

    Kadyrov, M; Moser, G; Rath, W; Kweider, N; Wruck, C J; Pufe, T; Huppertz, B

    2013-06-01

    Pregnancy-related complications not only represent a risk for maternal and fetal morbidity and mortality, but are also a risk for several diseases later in life. Many epidemiological studies have shown clear associations between an adverse intrauterine environment and an increased risk of diabetes, hypertension, cardiovascular disease, depression, obesity, and other chronic diseases in the adult. Some of these syndromes could be prevented by avoiding adverse stimuli or insults including psychological stress during pregnancy, intake of drugs, insufficient diet and substandard working conditions. Hence, all of these stimuli have the potential to alter health later in life. The placenta plays a key role in regulating the nutrient supply to the fetus and producing hormones that control the fetal as well as the maternal metabolism. Thus, any factor or stimulus that alters the function of the hormone producing placental trophoblast will provoke critical alterations of placental function and hence could induce programming of the fetus. The factors that change placental development may interfere with nutrient and oxygen supply to the fetus. This may be achieved by a direct disturbance of the placental barrier or more indirectly by, e. g., disturbing trophoblast invasion. For both path-ways, the respective pathologies are known: while preeclampsia is caused by alterations of the villous trophoblast, intra-uterine growth restriction is caused by insufficient invasion of the extravillous trophoblast. In both cases the effect can be undernutrition and/or fetal hypoxia, both of which adversely affect organ development, especially of brain and heart. However, the mechanisms responsible for disturbances of trophoblast differentiation and function remain elusive. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs).

    Science.gov (United States)

    Klaffenbach, D; Friedrich, D; Strick, R; Strissel, P L; Beckmann, M W; Rascher, W; Gessner, A; Dötsch, J; Meissner, U; Schnare, M

    2011-11-01

    The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human β-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Jennifer R Robbins

    2010-01-01

    Full Text Available Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta.

  1. Prediction and prevention of ischemic placental disease.

    Science.gov (United States)

    Friedman, Alexander M; Cleary, Kirsten L

    2014-04-01

    Preeclampsia, intrauterine growth restriction (IUGR), and placental abruption are obstetrical conditions that constitute the syndrome of ischemic placental disease or IPD, the leading cause of indicated preterm birth and an important cause of neonatal morbidity and mortality. While the phenotypic manifestations vary significantly for preeclampsia, IUGR, and abruption, these conditions may share a common underlying etiology as evidenced by: (1) shared clinical risk factors, (2) increased recurrence risk across pregnancies as well as increased co-occurrence of IPD conditions within a pregnancy, and (3) findings that suggest the underlying pathophysiologic processes may be similar. IPD is of major clinical importance and accounts for a large proportion of indicated preterm delivery ranging from the periviable to late preterm period. Successful prevention of IPD and resultant preterm delivery could substantially improve neonatal and maternal outcomes. This article will review the following topics: (1) The complicated research literature on aspirin and the prevention of preeclampsia and IUGR. (2) Research evidence on other medical interventions to prevent IPD. (3) New clinical interventions currently under investigations, including statins. (4) Current clinical recommendations for prevention of ischemic placental disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Intrauterine growth restriction and placental angiogenesis

    Directory of Open Access Journals (Sweden)

    Harma Muge

    2010-04-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF, basic-fibroblast growth factor (b-FGF, and endothelial nitric oxide synthase (eNOS are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas. Methods The expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55 and IUGR (n = 55. Results were evaluated in a semi-quantitative manner. Results The expression of all the markers was significantly higher (p Conclusion Increased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR.

  3. Placental mesenchymal dysplasia: What every radiologist needs to know

    Directory of Open Access Journals (Sweden)

    Disha Mittal

    2017-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD is an uncommon vascular anomaly of the placenta characterized by placentomegaly with multicystic placental lesion on ultrasonography and mesenchymal stem villous hyperplasia on histopathology. Placental mesenchymal dysplasia should be considered in the differential diagnosis of cases of multicystic placental lesion such as molar pregnancy, chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic placental changes. However, lack of high-velocity signals inside the lesion and a normal karyotype favor a diagnosis of PMD. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ. We report the case of an 18-year-old female at 15 weeks of gestation with sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis was confirmed on histopathology.

  4. Microsoft® Exchange Server 2010 Inside Out

    CERN Document Server

    Redmond, Tony

    2010-01-01

    Dive into Exchange Server 2010 and SP1-and discover how to really put your messaging solutions to work! This well-organized and in-depth reference packs all the details you need to deploy and manage Exchange 2010, including hundreds of timesaving solutions, expert tips, and workarounds.Topics include preparing for the deployment of Exchange 2010; new features of Service Pack 1; using Remote PowerShell and the Exchange Management Shell; understanding how the new Role Based Access Control (RBAC) permissions model works and how to customize it to your requirements; the new high availability mode

  5. Microsoft® Office Access™ 2007 Inside Out

    CERN Document Server

    Viescas, John

    2009-01-01

    You're beyond the basics, so dive right in and really put your database skills to work! This supremely organized reference is packed with hundreds of timesaving solutions, troubleshooting tips, and workarounds. It's all muscle and no fluff. Discover how the experts tackle Access 2007-and challenge yourself to new levels of mastery! Create tables that support your database design strategyImport and link to data from spreadsheets, text files, databases, and other ODBC data sourcesBuild simple to complex queries to manipulate dataLearn advanced techniques for building and customizing user inter

  6. Turning Groups Inside Out: A Social Network Perspective

    NARCIS (Netherlands)

    Rienties, Bart; Tempelaar, Dirk

    2017-01-01

    Most research related to learning in groups focuses on the unit of the group and/or its group members. However, students may benefit from crossing the boundaries of their own group, as st