DOCSLIB.ORG

Rheotaxis Guides Mammalian Sperm

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rheotaxis Guides Mammalian Sperm View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Current Biology 23, 443–452, March 18, 2013 ª2013 Elsevier Ltd All rights reserved http://dx.doi.org/10.1016/j.cub.2013.02.007 Article Rheotaxis Guides Mammalian Sperm Kiyoshi Miki1 and David E. Clapham1,2,* approach the egg [5, 6]. Another hypothesis, thermotaxy, is 1Howard Hughes Medical Institute, Department of Cardiology, based on ovulation-dependent small temperature gradients Manton Center for Orphan Disease Research, Boston between the isthmus and ampulla [7]. Children’s Hospital, 320 Longwood Avenue, Enders 1309, Rheotaxis, observed in many aquatic species, is the orienta- Boston, MA 02115, USA tion of cells and organisms within a gradient of fluid flow. Posi- 2Department of Neurobiology, Harvard Medical School, tive rheotaxis, the tendency of a cell to swim against the flow, Boston, MA 02115, USA was first reported for spermatozoa over 100 years ago [8]. While ciliary current toward the distal oviduct was observed in turtle, pigeon, and rabbit, central lumen counterflow pre- Summary vented a consensus about the physiological relevance of rheo- taxis, and it was concluded to be a laboratory artifact [9]. In Background: In sea urchins, spermatozoan motility is altered addition to cilia-directed flow, muscle contraction, tortuous by chemotactic peptides, giving rise to the assumption that geometry, the propensity of sperm to stick to surfaces, and mammalian eggs also emit chemotactic agents that guide high-viscosity fluids were recognized as factors complicating spermatozoa through the female reproductive tract to the sperm transport. Rothschild [10] noted that the sperm head mature oocyte. Mammalian spermatozoa indeed undergo is attracted to surfaces (the wall effect), and suggested that complex adaptations within the female (the process of capac- the ‘‘lighter’’ tail is subjected to more force in velocity gradi- itation) that are initiated by agents ranging from pH to proges- ents, resulting in the tail being dragged downstream with the terone, but these factors are not necessarily taxic. Currently, head pointed upstream [11]. More recent considerations chemotaxis, thermotaxis, and rheotaxis have not been defini- explain the wall effect as a consequence of hydrodynamics tively established in mammals. in tubes [12]. Results: Here, we show that positive rheotaxis, the ability of Fluid viscosity in the female reproductive tract varies, with organisms to orient and swim against the flow of surrounding the highest being in the cervical mucus (200 to 680 cP in hu- fluid, is a major taxic factor for mouse and human sperm. This mans [13]) and the oviductal isthmus [14]. Oviductal viscosity flow is generated within 4 hr of sexual stimulation and coitus in varies during the estrus cycle. Around ovulation, ciliated cells female mice; prolactin-triggered oviductal fluid secretion in the isthmus epithelium are covered by a dense, tenacious clears the oviduct of debris, lowers viscosity, and generates mucus that disappears after ovulation [14]; estrogen-regulated the stream that guides sperm migration in the oviduct. Rheo- secretion of oviductal fluid increases 2- to 3-fold at estrus [15]. taxic movement is demonstrated in capacitated and uncapaci- Fluid viscosity also affects sperm movement—as viscosity tated spermatozoa in low- and high-viscosity media. Finally, increases, sperm flagella propagation velocity, wave ampli- we show that a unique sperm motion, which we quantify using tude, and energy expenditure decrease [16]. Sperm angular the sperm head’s rolling rate, reflects sperm rotation that speed (rotation around the long axis of sperm) also decreases generates essential force for positioning the sperm in the at higher viscosities, resulting in more planar movement [17]. stream. Rotation requires CatSper channels, presumably by In the complex process of capacitation (that is, the changes enabling Ca2+ influx. that sperm undergo in the female reproductive tract that Conclusions: We propose that rheotaxis is a major determi- enable them to fertilize the egg), sperm develop hyperacti- nant of sperm guidance over long distances in the mammalian vated motility. Hyperactivation is characterized by higher- female reproductive tract. Coitus induces fluid flow to guide amplitude, asymmetric waveforms of reduced beat frequency sperm in the oviduct. Sperm rheotaxis requires rotational [18], which enables high flagellar swimming speeds in viscous motion during CatSper channel-dependent hyperactivated solutions [19]. motility. We have reinvestigated sperm taxis in vitro and in vivo using new tools that enable control of hyperactivated motility and Introduction enable the visualization of sperm movement in vivo. Here, we show that sexual intercourse in mice induces robust secretion Marine invertebrate spermatozoa, such as those of sea urchin, and fluid flow within the oviduct. Sperm are directed by, are guided by chemotaxis; egg-secreted peptides induce and swim against, this flow (positive rheotaxis). Importantly, changes in the arc of spermatozoan swimming paths that axial rotation requires CatSper channels for reorientation of increase fertilization success [1]. In mammals, the route to sperm in tangential flow. We conclude that rheotaxis is a major the egg is more restricted, but it is widely assumed that folli- influence in the long distance guidance of mammalian sperm cular fluid contains chemoattractants [2]. Prompted by reports to the egg. of the presence of a large number of putative odorant G protein-coupled receptors in spermatozoa, the synthetic odor- Results ants bourgeonal and lyral were proposed to mimic unknown native chemoattractants of human or mouse sperm, respec- Coitus Induces Fluid Flow from Oviduct to Uterus tively [3, 4]. However, because muscle contraction and ciliary Oviductal epithelia actively secrete fluid into the oviductal currents would disrupt gradients over long distances, chemo- lumen, as first reported in rabbits during estrus [20]. Uterine tactic guidance would likely be relevant only as sperm fluid is most abundant (91 6 26 ml) on the day of coitus [21]; however the origin of fluid and the mechanism of its production has not been well documented. We analyzed the accumulation *Correspondence: [email protected] of oviductal fluid in the uterus in mice. Although the uterus Current Biology Vol 23 No 6 444 A C Figure 1. Increased Fluid Production and Oviductal (i) (ii) (iii) (iv) (i) (ii) (iii) Flow after Mating (A) The mouse uterus swells after mating. No fluid was recovered from the uterus at ovulation (i). Fluid from uteri removed immediately after mating increased by 37 mg, consistent with the weight (volume) of sperm fluid (ii). Fluid volumes increased markedly in uteri 8 or 12 hr after mating (120 or B 100 mg, respectively) (iii and iv). Scale bar repre- sents 1 cm. (B) Accumulated uterine fluid was collected at the D times indicated after mating. Fluid weights (volumes) from mated (red) and unmated (blue) females are plotted. (C) Uterine fluid was collected from females 20 min (i), 4 hr (ii), or 8 hr (iii) after mating, and the fluids were centrifuged. (D) Fluid flow in the oviduct (ampulla) 4 hr after mating. Migration of globular cells and debris was traced over 3 s; the closed circle marks the endpoint. The central diagonal structure is a mucosal fold in the Recovered fluid (mg) oviductal wall. Oviductal isthmus is seen at bottom right. Scale bar represents 50 mm. See Movie S1. (E) Average globular cell migration speed = 18.0 6 Hours after mating 1.6 mm/s at 22 C. (F) Bromocriptine administration before mating E F p = 0.0007 G inhibits fluid secretion measured 8 hr after mating. p = 0.008 (G) DsRed2-expressing sperm counts in the ampulla in vitro and ex vivo. Ex vivo: a portion of ampulla was dissected from females 4–5 hr after mating, and DsRed2-expressing sperm were counted. Oviducts were removed and ligated, or left unligated, near the UTJ 60–90 min after mating and then incubated at 37C for 2–3 hr. The number of sperm reaching the ampulla in oviducts without an ovary averaged 31 6 6. The increase in sperm number over the in vivo situation may result from manipulation or a change in hormone status perhaps detaching some sperm # sperm / ampulla Flow speed (µm/s) from the isthmal crypts and facilitating sperm migra- Recovered fluid (mg) tion. All graphs: mean 6 SEM (black bars) and Vehicle BrCr in Unligated Ligated median with interquartile ranges (green boxes). vivo ex vivo noticeably swells at estrus, no appreciable fluid was recovered reducing the attachment of cells to the wall of the oviduct from ovulated females at any time point up to 24 hr after estrus (Figure 1D; Movie S1B). Ampullar flow, measured 3–4 hr after (Figure 1B). When females were mated with males, we coitus, was 18.0 6 1.6 mm/s (Figure 1E). In summary, coitus observed a slight swelling of the uterus 20 min after mating induces a dramatic increase in oviductal fluid secretion that and were able to collect 22 6 4.8 mg of fluid (primarily ejacu- lowers viscosity and clears debris from the oviduct. We then lated semen; Figures 1Aii and 1Ci). Moreover, fluid in the uterus asked what factors might mediate this increased oviductal increased over time to a peak of 87 6 13.9 mg at 8 hr (Figure 1B; secretion and flow. the rate of secretion appeared to be highest within the first Genital stimulation and coitus evoke complex neurological 4 hr after mating). This increase in secretion above baseline responses. To simplify our task of determining factors that at estrus required coitus; unmated control mice did not exhibit might increase oviductal flow, we considered known secreted a significant increase in uterine fluid. Because in vitro culture hormones that were (1) elevated in serum after sexual stimula- showed that the uterine accumulation included oviduct- tion or coitus, (2) known to effect fluid secretion across released cell debris and globular cells (see Figure S1A epithelia surfaces, or (3) known to alter fertilization success available online), we surmised that some portion of this fluid in mice in which the gene had been deleted.
Load more

Recommended publications
  • Bimodal Rheotactic Behavior Reflects Flagellar Beat Asymmetry in Human Sperm Cells
    Bimodal rheotactic behavior reflects flagellar beat asymmetry in human sperm cells Anton Bukatina,b,1, Igor Kukhtevichb,c,1, Norbert Stoopd,1, Jörn Dunkeld,2, and Vasily Kantslere aSt. Petersburg Academic University, St. Petersburg 194021, Russia; bInstitute for Analytical Instrumentation of the Russian Academy of Sciences, St. Petersburg 198095, Russia; cITMO University, St. Petersburg 197101, Russia; dDepartment of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139-4307; and eDepartment of Physics, University of Warwick, Coventry CV4 7AL, United Kingdom Edited by Charles S. Peskin, New York University, New York, NY, and approved November 9, 2015 (received for review July 30, 2015) Rheotaxis, the directed response to fluid velocity gradients, has whether this effect is of mechanical (20) or hydrodynamic (21, been shown to facilitate stable upstream swimming of mamma- 22) origin. Experiments (23) show that the alga’s reorientation lian sperm cells along solid surfaces, suggesting a robust physical dynamics can lead to localization in shear flow (24, 25), with mechanism for long-distance navigation during fertilization. How- potentially profound implications in marine ecology. In contrast ever, the dynamics by which a human sperm orients itself relative to taxis in multiflagellate organisms (2, 5, 18, 26, 27), the navi- to an ambient flow is poorly understood. Here, we combine micro- gation strategies of uniflagellate cells are less well understood. fluidic experiments with mathematical modeling and 3D flagellar beat For instance, it was discovered only recently that uniflagellate reconstruction to quantify the response of individual sperm cells in marine bacteria, such as Vibrio alginolyticus and Pseudoalteromonas time-varying flow fields. Single-cell tracking reveals two kinematically haloplanktis, use a buckling instability in their lone flagellum to distinct swimming states that entail opposite turning behaviors under change their swimming direction (28).
    [Show full text]
  • Thermotaxis Is a Robust Mechanism for Thermoregulation in Caenorhabditis Elegans Nematodes
    12546 • The Journal of Neuroscience, November 19, 2008 • 28(47):12546–12557 Behavioral/Systems/Cognitive Thermotaxis is a Robust Mechanism for Thermoregulation in Caenorhabditis elegans Nematodes Daniel Ramot,1* Bronwyn L. MacInnis,2* Hau-Chen Lee,2 and Miriam B. Goodman1,2 1Program in Neuroscience and 2Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 Many biochemical networks are robust to variations in network or stimulus parameters. Although robustness is considered an important design principle of such networks, it is not known whether this principle also applies to higher-level biological processes such as animal behavior. In thermal gradients, Caenorhabditis elegans uses thermotaxis to bias its movement along the direction of the gradient. Here we develop a detailed, quantitative map of C. elegans thermotaxis and use these data to derive a computational model of thermotaxis in the soil, a natural environment of C. elegans. This computational analysis indicates that thermotaxis enables animals to avoid temperatures at which they cannot reproduce, to limit excursions from their adapted temperature, and to remain relatively close to the surface of the soil, where oxygen is abundant. Furthermore, our analysis reveals that this mechanism is robust to large variations in the parameters governing both worm locomotion and temperature fluctuations in the soil. We suggest that, similar to biochemical networks, animals evolve behavioral strategies that are robust, rather than strategies that rely on fine tuning of specific behavioral parameters. Key words: behavior; C. elegans; temperature; neuroethology; computational models; robustness Introduction model to investigate the ability of thermotaxis to regulate Tb and its robustness to genetic and environmental perturbation.
    [Show full text]
  • Molecular Basis of Ligand Recognition and Activation of Human V2 Vasopressin Receptor
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.18.427077; this version posted January 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Molecular basis of ligand recognition and activation of human V2 vasopressin receptor Fulai Zhou1, 12, Chenyu Ye2, 12, Xiaomin Ma3, 12, Wanchao Yin1, Qingtong Zhou4, Xinheng He1, 5, Xiaokang Zhang6, 7, Tristan I. Croll8, Dehua Yang1, 5, 9, Peiyi Wang3, 10, H. Eric Xu1, 5, 11, Ming-Wei Wang1, 2, 4, 5, 9, 11, Yi Jiang1, 5, 1. The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 2. School of Pharmacy, Fudan University, Shanghai 201203, China 3. Cryo-EM Centre, Southern University of Science and Technology, Shenzhen 515055, China 4. School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 5. University of Chinese Academy of Sciences, 100049 Beijing, China 6. Interdisciplinary Center for Brain Information, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; 7. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China 8. Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, UK 9. The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203 Shanghai, China 10. Department of Biology, Southern University of Science and Technology, Shenzhen 515055, China 11. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China 12. These authors contributed equally: Fulai Zhou, Chenyu Ye, and Xiaomin Ma.
    [Show full text]
  • Tractocile, Atosiban
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Tractocile 6.75 mg/0.9 ml solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each vial of 0.9 ml solution contains 6.75 mg atosiban (as acetate). For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). Clear, colourless solution without particles. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: regular uterine contractions of at least 30 seconds duration at a rate of 4 per 30 minutes a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of 50% a gestational age from 24 until 33 completed weeks a normal foetal heart rate 4.2 Posology and method of administration Posology Treatment with Tractocile should be initiated and maintained by a physician experienced in the treatment of pre-term labour. Tractocile is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Tractocile 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of Tractocile 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Tractocile 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of Tractocile therapy should preferably not exceed 330.75 mg of atosiban.
    [Show full text]
  • Largescale Synthesis of Peptides
    Lars Andersson1 Lennart Blomberg1 Large-Scale Synthesis of Martin Flegel2 Ludek Lepsa2 Peptides Bo Nilsson1 Michael Verlander3 1 PolyPeptide Laboratories (Sweden) AB, Malmo, Sweden 2 PolyPeptide Laboratories SpoL, Prague, Czech Republic 3 PolyPeptide Laboratories, Inc., Torrance, CA, 90503 USA Abstract: Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, which, in turn, has provided a challenge to the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on scales of up to metric tons per year. This article focuses on chemical synthesis approaches for peptides, and presents an overview of the methods available and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions to some specific problems encountered during scale-up development. Finally, an overview is presented of issues common to all manufacturing methods, i.e., methods used for the large-scale purification and isolation of final bulk products and regulatory considerations to be addressed during scale-up of processes to commercial levels. © 2000 John Wiley & Sons, Inc. Biopoly 55: 227–250, 2000 Keywords: peptide synthesis; peptides as drug candidates; manufacturing; scale-up strategies INTRODUCTION and plants,5 have all combined to increase the avail- ability and lower the cost of producing peptides. For For almost half a century, since du Vigneaud first many years, however, the major obstacle to the suc- presented his pioneering synthesis of oxytocin to the cess of peptides as pharmaceuticals was their lack of world in 1953,1 the pharmaceutical community has oral bioavailability and, therefore, relatively few pep- been excited about the potential of peptides as “Na- tides reached the marketplace as approved drugs.
    [Show full text]
  • Hemmo Pharmaceuticals Private Limited
    Global Supplier of Quality Peptide Products Hemmo Pharmaceuticals Private Limited Corporate Presentation Privileged & Confidential Privileged & Confidential Corporate Overview Privileged & Confidential 2 Company at a glance • Commenced operations in 1966 as a Key Highlights trading house, focusing on Oxytocin amongst other products Amongst the largest Indian peptide manufacturing company • In 1979, ventured into manufacturing of Oxytocin Competent team of 154 people including 6 PhDs, 60+ chemistry graduates/post graduates and 3 engineers • Privately held family owned company Portfolio – Generic APIs, Custom Peptides for Research and Clinical Development and Peptide • Infrastructure Fragments − State of art manufacturing facility in Developed 21 generic products in-house. Navi Mumbai, 5 more in progress − R&D facilities at Thane and Spain − Corporate office at Worli First and the only independent Indian company to have a US FDA approved peptide manufacturing site Privileged & Confidential 3 Transition from a trading house to a research based manufacturing facility Commenced Commenced Investment in State of the Art Opened R& D Expanded operations manufacturing greenfield project facility at Navi Centre in manufacturing as a trading of peptides intended for Mumbai Girona,Spain capacity House regulated markets commissioned R&D center set up in Infrastructure Mumbai 1966 1979 2005 2007 2008 2010 2011 2012 2014 2015 Oxytocin Oxytocin Desmopressin Buserelin Triptorelin Goserelin Linaclotide Glatiramer amongst Gonadorelin Decapeptide Cetrorelix
    [Show full text]
  • Oxytocin Receptor OXTR
    Oxytocin Receptor OXTR The oxytocin receptor belongs to the G-protein-coupled seven-transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. The oxytocin receptors are activated in response to binding oxytocin and a similar nonapeptide, vasopressin. Oxytocin receptor triggers Gi or Gq protein-mediated signaling cascades leading to the regulation of a variety of neuroendocrine and cognitive functions. Oxytocin is a nonapeptide of the neurohypophyseal protein family that binds specifically to the oxytocin receptor to produce a multitude of central and peripheral physiological responses. In vivo, oxytocin acts as a paracrine and/or autocrine mediator of multiple biological effects. These effects are exerted primarily through interactions with G-protein-coupled oxytocin/vasopressin receptors, which, via Gq and Gi, stimulate phospholipase C-mediated hydrolysis of phosphoinositides. www.MedChemExpress.com 1 Oxytocin Receptor Agonists & Antagonists Atosiban Atosiban acetate (RW22164; RWJ22164) Cat. No.: HY-17572 (RW22164 acetate; RWJ22164 acetate) Cat. No.: HY-17572A Atosiban (RW22164; RWJ22164) is a nonapeptide Atosiban acetate (RW22164 acetate;RWJ22164 competitive vasopressin/oxytocin receptor acetate) is a nonapeptide competitive antagonist, and is a desamino-oxytocin analogue. vasopressin/oxytocin receptor antagonist, and is a Atosiban is the main tocolytic agent and has the desamino-oxytocin analogue. Atosiban is the main potential for spontaneous preterm labor research. tocolytic agent and has the potential for spontaneous preterm labor research. Purity: 99.09% Purity: 99.92% Clinical Data: Launched Clinical Data: Launched Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg Carbetocin Epelsiban Cat.
    [Show full text]
  • Proquest Dissertations
    INFORMATION TO USERS This manuscript has been reproduced from the microfihn master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6” x 9” black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. UMI A Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor MI 48106-1346 USA 313/761-4700 800/521-0600 STARVATION-INDUCED CHANGES IN MOTILITY AND SPONTANEOUS SWITCHING TO FASTER SWARMING BEHAVIOR OF SINORHIZOBIUM MELILOTI DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Graduate School at The Ohio State University By Xueming Wei.
    [Show full text]
  • < MOH Approved Drugs List >
    Ministry Of Health Directorate General of Medical Supplies Rep_Id : App_Drugs_List_Who.rdf < MOH Approved Drugs List > DATE : 12/08/2009 Page : 1 of 108 VED Flag <S.No> < Item Code > < I T E M D E S C ROF I P- T I O N > < U N I T > DATE : ABC Flag H/C Flag Category : DRUGS 1 Ph. System : GASTRO-INTESTINAL SYSTEM 1 Main Group : ANTACIDS 1 Sub Group : ALUMINIUM COMPOUNDS 1 03000000105 ALUMINIUM HYDROXIDE GEL, DRIED 475 MG. CAPSULE Desirable Cat_C Not H/C Item 2 Sub Group : ANTACID COMPOUND PREPARATIONS 2 02000000079 ANTACID SUSPENSION (ALUMINIUM HYDROXIDE + BOTTLE Desirable MAGNESIUM HYDROXIDE OR TRISILICATE) 100 - 200 Cat_A ML. B0TTLE. H/C Item 3 03000000173 ANTACID TABLET (ALUMINIUM HYDROXIDE + TABLET/CAP Desirable MAGNESIUM HYDROXIDE OR TRISILICATE). Cat_A H/C Item 2 Main Group : ANTISPASMODICS 1 Sub Group : ANTIMUSCARINICS 4 01000000304 HYOSCINE N BUTYLBROMIDE 20MG/ML. 1ML. AMPOULE Essantial Cat_A H/C Item 5 03000000640 HYOSCINE N BUTYL BROMIDE 10MG. TABLET/CAP Essantial Cat_A H/C Item 6 020D0000063 ANTISPASMODIC DROPS 15ML-25ML. BOTTLE Desirable Cat_C Not H/C Item 2 Sub Group : OTHER ANTISPASMODIC AND MOTILITY STIMULANT 7 03000001245 MEBEVERINE HYDROCHLORIDE 100 MG - 135 MG. TABLET/CAP Essantial Cat_B Not H/C Item Ministry Of Health Directorate General of Medical Supplies Rep_Id : App_Drugs_List_Who.rdf < MOH Approved Drugs List > DATE : 12/08/2009 Page : 2 of 108 VED Flag <S.No> < Item Code > < I T E M D E S C ROF I P- T I O N > < U N I T > DATE : ABC Flag H/C Flag Category : DRUGS 1 Ph.
    [Show full text]
  • List of Pharamaceutical Peptides Available from ADI
    List of Pharamaceutical Peptides Available from ADI ADI has highly purified research grade/pharma grade pharmaceutical peptides available for small research scale or in bulk (>Kg scale). (See Details at the website) http://4adi.com/commerce/catalog/spcategory.jsp?category_id=2704 Catalog# Product Description Catalog# Product Description PP-1000 Abarelix (Acetyl-Ser-Leu-Pro-NH2; MW:1416.06) PP-1410 Growth Hormone-releasing factor, GRF (human) PP-1010 ACTH 1-24 (Adrenocorticotropic Hormone human) Acetate PP-1420 Hexarelin PP-1020 Alarelin Acetate PP-1430 Histrelin Acetate PP-1030 Angiotensin PP-1440 Lepirudin PP-1040 Angiotensin II Acetate PP-1450 Leuprolide PP-1050 Antide Acetate PP-1460 Leuprorelin Acetate PP-1060 Argipressin Acetate PP-1470 Lipopeptide Acetate PP-1070 Argireline Acetate PP-1480 Lypressin PP-1080 Atosiban Acetate PP-1490 Lysipressin Acetate PP-1090 Aviptadil PP-1500 Matrixyl Acetate PP-1100 Bivalirudin Trifluoroacetate PP-1510 Melanotan I, Acetate PP-1110 Buserelin acetate PP-1520 Melanotan II, MT-II, Acetate PP-1120 Copaxone acetate (Glatiramer acetate) PP-1530 Mechano Growth Factor, MGF, TFA PP-1130 Carbetocin acetate PP-1540 Nafarelin Acetate PP-1140 Cetrorelix Acetate PP-1550 Nesiritide Acetate PP-1150 Corticotropin-releasing factor, CRF (human, rat) Acetate PP-1560 Octreotide Acetate PP-1160 Corticotropin-releasing factor, CRF (ovine) PP-1570 Ornipressin Acetate Trifluoroacetate PP-1580 Oxytocin Acetate PP-1170 Deslorelin Acetate PP-1590 Palmitoyl Pentapeptide PP-1180 Desmopressin Acetate PP-1610 Pentagastrin Ammonium
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances" WHO/EMP/RHT/TSN/2013.1
    INN Working Document 18.435 31/05/2018 Addendum1 to "The use of stems in the selection of International Nonproprietary names (INN) for pharmaceutical substances" WHO/EMP/RHT/TSN/2013.1 Programme on International Nonproprietary Names (INN) Technologies Standards and Norms (TSN) Regulation of Medicines and other health technologies (RHT) World Health Organization, Geneva © World Health Organization 2018 - All rights reserved. The contents of this document may not be reviewed, abstracted, quoted, referenced, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means, without explicit prior authorization of the WHO INN Programme. This document contains the collective views of the INN Expert Group and does not necessarily represent the decisions or the stated policy of the World Health Organization. Addendum1 to "The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances" - WHO/EMP/RHT/TSN/2013.1 1 This addendum is a cumulative list of all new stems selected by the INN Expert Group since the publication of "The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances" 2013. ------------------------------------------------------------------------------------------------------------ -apt- aptamers, classical and mirror ones (a) avacincaptad pegol (113), egaptivon pegol (111), emapticap pegol (108), lexaptepid pegol (108), olaptesed pegol (109), pegaptanib (88) (b) -vaptan stem: balovaptan (116), conivaptan
    [Show full text]
  • Salbutamol) in the Treatment of Preterm Labor
    AL-Qadisiya Medical Journal Vol.11 No.20 2015 Effectiveness and safety of the oxytocin antagonist( atosiban) versus beta-adrenergic agonists (salbutamol) in the treatment of preterm labor. Yasamin H. Sharif Al-Shibany* ,Saba M. Swadi Al- Thuwainy * *Obstetrics and Gynecology Department Medical college / Al-Qadisia University ,Email: [email protected] , Email: [email protected] (Received 7 / 4 /2015 , Accepted 19 / 4 / 2015) الخﻻصة : التأثيرات و اﻻعراض الجانبية ﻻستتداا عاتاا اﻻسيستيبا و عتي عاضتد ضﻻتاس لووينيتيستيي الب تر عنتا ضنتتابوت الدةيتتة قالنااانتة ضتتا عاتاا النتتالبييساضي وعتي عاضتتد ضالتي لننتتتابوت البيتتا تت الدةيتة الب تتر ة لعوج حاﻻت اليﻻسة النبكرة. الطر اة: أجر ت الاااسة ضنت لى اليﻻسة و اﻷطلا التعةين الا يانية-العراق , لةلترة ضتي هت ر يتاني الثان /4102 و لغا ة ه ر ياني الثان /4102 ( عةى 011 اضرأة حاضد قعنر 01-52 ستنة( و اسلةتي التى نت الطتياا ضتتا اعتتراض لةتتيﻻسة النبكتترة و يانتتت تتترة الانتتد ضتتي 42-52 أستتبي ( ضتتا وجتتيس انابالتتات لةتترح سنتغرق 51 ثانية قنعا ≤ أاقعة انابالات لو 01 س ياة و يا اسنا عنق الرح ضي 0الى 5 س (و 1التى 5 س (لةنياات عا نة اليﻻسة وسرعة نبض الجنيي طبيعية , س ساني النر ﻻات الى ضجنيعتيي: النجنيعة اﻷولتى و عاسعا 21 ضر ﻻتة عيلجتت قعاتاا النتالبييساضي عتي طر تق ضاةتي الااتي اليا تا و النجنيعتة الثانيتة 21 ضر ﻻة عيلجت قعااااﻻسيسيبا اليا ا ضا ضرا بة هاة اﻻنابالات و اﻻعراض الجانبية لكد عااا عةى اﻻ و الجنيي لغرض سألير اليﻻسة النبكرة و ساةيد النﻻاعلات النر ر ة و الي يات لاى النياليا الداج حا ث اليﻻسة. النتتتا: : لتت كتتي عنتتاف التتتو تت ستتألير حتتاﻻت التتيﻻسة النبكتترة لنتتاة 21 ستتاعة 22% ضااقتتد20%( و 7 أ تتا 41% ضااقتتد 54%( قتتيي النجنيعتتة اﻷولتتى و الثانيتتة عةتتى التتتيال و لكتتي اﻻعتتراض الجانبيتتة ضثتتد سنتتاا نبﻻات ةب اﻻ يانت ايثر عنا النجنيعة اﻷولى الت عيلجت قعاتاا النتالبييساضي 44% ضااقتد 1%(.لت سكتي عناف التو ات النتا: اﻹحصا:ية لةنﻻاعلات النر ر ة لاى النياليا الداج حا ث اليﻻسة قيي النجنيعتيي.
    [Show full text]