DOCSLIB.ORG

Pathophysiology and Management of Diabetic Gastroenteropathy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pathophysiology and Management of Diabetic Gastroenteropathy TAG0010.1177/1756284819852047Therapeutic Advances in GastroenterologyT Meldgaard, J Keller 852047review-article20192019 Therapeutic Advances in Gastroenterology Review Ther Adv Gastroenterol Pathophysiology and management of 2019, Vol. 12: 1–17 DOI:https://doi.org/10.1177/1756284819852047 10.1177/ diabetic gastroenteropathy 1756284819852047https://doi.org/10.1177/1756284819852047 © The Author(s), 2019. Article reuse guidelines: Theresa Meldgaard, Jutta Keller, Anne Estrup Olesen, Søren Schou Olesen, Klaus Krogh, sagepub.com/journals- Mette Borre, Adam Farmer, Birgitte Brock, Christina Brock and Asbjørn Mohr Drewes permissions Abstract: Polyneuropathy is a common complication to diabetes. Neuropathies within the Correspondence to: Theresa Meldgaard enteric nervous system are associated with gastroenteropathy and marked symptoms that Mech-Sense, Department of Gastroenterology and severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, Hepatology, Aalborg dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The University Hospital, aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying Denmark Department of Clinical diabetic gastroenteropathy. Secondly to give an overview of the diagnostic methods. Thirdly, to Medicine, Aalborg University, Denmark provide clinicians with a focussed overview of current and future methods for pharmacological [email protected] and nonpharmacological treatment modalities. Pharmacological management is categorised Jutta Keller Israelitic Hospital in according to symptoms arising from the upper or lower gut as well as sensory dysfunctions. Hamburg, Academic Dietary management is central to improvement of symptoms and is discussed in detail, and Hospital University of neuromodulatory treatment modalities and other emerging management strategies for Hamburg, Germany Anne Estrup Olesen diabetic gastroenteropathy are discussed. Finally, we propose a diagnostic/investigation Mech-Sense, Department of Gastroenterology algorithm that can be used to support multidisciplinary management. and Hepatology and Department of Clinical Medicine, Aalborg Keywords: diabetes mellitus, complications, diabetic neuropathies, enteric nervous system, University Hospital, Denmark gastrointestinal motility, gastrointestinal transit, pharmacology, enteropathy Department of Clinical Medicine, Aalborg University, Denmark Received: 5 February 2019; revised manuscript accepted: 26 April 2019. Søren Schou Olesen Mech-Sense, Department of Gastroenterology and Hepatology and Department of Clinical Introduction Although often overlooked, effects in the auto- Medicine, Aalborg University Hospital, The development of diabetic polyneuropathy can nomic nervous system most likely occur concur- Denmark potentially alter neuronal structure and function rently with those observed in the somatic nervous Department of Clinical anywhere in the peripheral, central and enteric system. For example it is plausible that early dam- Medicine, Aalborg University, Denmark nervous systems. Where small and large fibres age to small fibres, preceding large fibre neuropa- Christina Brock (unmyelinated C and myelinated Aβ and Aδ fibres) thy, of the somatic nerves, which can be observed Mech-Sense, Department 4 of Gastroenterology in the somatic sensory nervous system are affected, in skin biopsies also take place in other small fibres and Hepatology and the typical manifestation is a distal symmetrical such as in the enteric nervous system. Autonomic Department of Clinical 1 Medicine, Aalborg polyneuropathy. Importantly, these symptoms neuropathy can be clinically silent and is often pre- University Hospital, can also be found in people with prediabetes.2 The sent when polyneuropathy of the somatic nerves is Denmark somatic polyneuropathy is characterised by altera- present. The diagnosis is typically based on cardio- Department of Clinical Medicine, Aalborg tions in the sensory system, and classically presents vascular abnormalities. In particular, studies of University, Denmark with marked changes in a number of sensations RR-complexes in electrocardiograms have been Asbjørn Mohr Drewes (including temperature and fine touch, balance, used to describe heart rate variability, leading to Mech-Sense, Department of Gastroenterology etc.) and can be painful or painless, although the the diagnosis of cardiac autonomic neuropathy. and Hepatology and former predominates.2 In community samples However, autonomic neuropathy also leads to gas- Department of Clinical Medicine, Aalborg with diabetes, the prevalence of clinical symptoms trointestinal (GI) complications such as diabetic University Hospital, is in the order of 30%, although this is likely to gastroenteropathy, which may affect the entire Denmark represent an underestimate as many people are not length of the GI tract. The underlying pathophysi- Department of Clinical Medicine, Aalborg formally diagnosed.3 ology, which is driven by a multitude of factors, University, Denmark journals.sagepub.com/home/tag 1 Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Therapeutic Advances in Gastroenterology 12 Klaus Krogh Department of Hepatology including microenvironmental factors such as cues from interstitial cells of Cajal (which are also and Gastroenterology, hyperglycaemia, have a negative impact on the reduced in number).9 This link between reduced Aarhus University Hospital, Denmark enteric motor and sensory functions and manifest numbers of interstitial cells of Cajal and smooth Mette Borre as symptoms related to, e.g., motility and secretory muscle myopathy has been observed in animal Department of Hepatology dysfunctions.5–7 Hence, people with diabetic gas- models of diabetic gastroparesis and likely con- and Gastroenterology, Aarhus University Hospital, troenteropathy may experience a variety of bur- tributes to abnormal motility. Denmark densome symptoms, including dysphagia, Adam Farmer dyspepsia, pain, bloating, diarrhoea, constipation The autonomic nervous system comprises (a) Department of Gastroenterology, and faecal incontinence, all of which adversely the sympathetic nervous system, (b) the para- University Hospitals of influences quality of life. sympathetic nervous system (whose main neural North Midlands, Stoke on Trent, Staffordshire, UK substrate is the vagus nerve) and, according to Centre for Digestive Although the focus of this review is diabetic gas- the early and recently re-established definition, Diseases, Blizard Institute troenteropathy, it should be emphasized that (c) the enteric nervous system.10,11 Alterations in of Cell and Molecular Science, Wingate Institute functional GI disorders are prevalent in the com- either of these systems are involved in the under- of Neurogastroenterology, munity. Hence, the presentation of diabetic gas- lying mechanism of burdensome GI complica- Barts and the London School of Medicine and troenteropathy and functional disorders such as tions in diabetes. As both the enteric nervous Dentistry, Queen Mary functional dyspepsia and irritable bowel syn- system and central nervous system (CNS) are University of London, UK Birgitte Brock drome overlap and cannot be distinguished on involved in the bidirectional regulation and con- Department of Clinical the basis of symptoms or medical history (i.e. trol of the GI homeostasis, any changes in either Research, Steno Diabetes Center Copenhagen diabetes) alone. In fact, examinations of small of these interconnected systems may result in (SDCC), Denmark bowel biopsies from patients with diabetes altered GI function. revealed neuropathy and myopathy only in a minority of patients.8 It is also clear that indi- viduals with chronic disease have a higher preva- Changes at the level of the enteric nervous lence of psychiatric disorders and are exposed to system more stress than healthy subjects. These factors In diabetes, the microenvironment within the play an important role in the presentation and enteric nervous system is significantly altered due perceived severity of functional GI diseases. to the effect of e.g. long-term hyperglycaemia; oxi- dative stress; inflammation; reduced levels of neuro The aims of this review are, however, to describe transmitters, local hormones and nerve growth fac- the pathophysiology of GI complications to dia- tors; and increased levels of fatty acids.12,13 betic neuropathy (gastroenteropathy) and to out- Recently, altered gut luminal microbiota has also line diagnostics and recent pharmacological and been proposed to exert an influence. For example, nonpharmacological treatment modalities for this lowered numbers of bacteria involved in produc- burdensome condition. tion of short chain fatty acids have been observed in diabetes. Short chain fatty acids have anti- inflammatory effects in the GI wall and promote Pathophysiology of diabetes-induced the secretion of the incretin hormone glucagon- gastrointestinal complications like peptide-1 (GLP-1). Lower levels of GLP-1 The term diabetic gastroenteropathy encom- influence glucose metabolism and can increase passes the cumulative
Load more

Recommended publications
  • Pathophysiology and Management of Diabetic Gastroenteropathy
    Pathophysiology and management of diabetic gastroenteropathy Meldgaard, Theresa; Keller, Jutta; Olesen, Anne Estrup; Olesen, Søren Schou; Krogh, Klaus; Borre, Mette; Farmer, Adam; Brock, Birgitte; Brock, Christina; Drewes, Asbjørn Mohr Published in: Therapeutic Advances in Gastroenterology DOI: 10.1177/1756284819852047 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Document license: CC BY-NC Citation for published version (APA): Meldgaard, T., Keller, J., Olesen, A. E., Olesen, S. S., Krogh, K., Borre, M., Farmer, A., Brock, B., Brock, C., & Drewes, A. M. (2019). Pathophysiology and management of diabetic gastroenteropathy. Therapeutic Advances in Gastroenterology, 12, 1-17. https://doi.org/10.1177/1756284819852047 Download date: 01. Oct. 2021 TAG0010.1177/1756284819852047Therapeutic Advances in GastroenterologyT Meldgaard, J Keller 852047review-article20192019 Therapeutic Advances in Gastroenterology Review Ther Adv Gastroenterol Pathophysiology and management of 2019, Vol. 12: 1–17 DOI:https://doi.org/10.1177/1756284819852047 10.1177/ diabetic gastroenteropathy 1756284819852047https://doi.org/10.1177/1756284819852047 © The Author(s), 2019. Article reuse guidelines: Theresa Meldgaard, Jutta Keller, Anne Estrup Olesen, Søren Schou Olesen, Klaus Krogh, sagepub.com/journals- Mette Borre, Adam Farmer, Birgitte Brock, Christina Brock and Asbjørn Mohr Drewes permissions Abstract: Polyneuropathy is a common complication to diabetes. Neuropathies within the Correspondence to: Theresa Meldgaard enteric nervous system are associated with gastroenteropathy and marked symptoms that Mech-Sense, Department of Gastroenterology and severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, Hepatology, Aalborg dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The University Hospital, aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying Denmark Department of Clinical diabetic gastroenteropathy.
    [Show full text]
  • Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats
    J Neurogastroenterol Motil, Vol. 25 No. 2 April, 2019 pISSN: 2093-0879 eISSN: 2093-0887 https://doi.org/10.5056/jnm18202 JNM Journal of Neurogastroenterology and Motility Original Article Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats Susana Díaz-Ruano,1 Ana E López-Pérez,1,5 Rocío Girón,2,3,4,5 Irene Pérez-García,2 María I Martín-Fontelles,2,3,4,5 and Raquel Abalo2,3,4,5* 1Unidad de Dolor, Servicio de Anestesiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; 3Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain; 4Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Madrid, Spain; and 5Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain Background/Aims Gastrointestinal adverse effects have a major impact on health and quality of life in analgesics users. Non-invasive methods to study gastrointestinal motility are of high interest. Fluoroscopy has been previously used to study gastrointestinal motility in small experimental animals, but they were generally anesthetized and anesthesia itself may alter motility. In this study, our aim is to determine, in conscious rats, the effect of increasing doses of 2 opioid (morphine and loperamide) and 1 cannabinoid (WIN 55,212-2) agonists on colonic motility using fluoroscopic recordings and spatio-temporal maps. Methods Male Wistar rats received barium sulfate intragastrically, 20-22 hours before fluoroscopy, so that stained fecal pellets could be seen at the time of recording.
    [Show full text]
  • Akt Phosphorylation of Neuronal Nitric Oxide Synthase Regulates Gastrointestinal Motility in Mouse Ileum
    Akt phosphorylation of neuronal nitric oxide synthase regulates gastrointestinal motility in mouse ileum Damian D. Guerraa, Rachael Boka, Vibhuti Vyasa, David J. Orlickyb, Ramón A. Lorcaa, and K. Joseph Hurta,c,1 aDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; bDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; and cDivision of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved July 15, 2019 (received for review April 5, 2019) Nitric oxide (NO) is a major inhibitory neurotransmitter that mediates receptor activation (18–20). Some evidence suggests that phosphor- nonadrenergic noncholinergic (NANC) signaling. Neuronal NO syn- ylation of the equivalent Akt/PKA consensus site in nNOS, ser- + thase (nNOS) is activated by Ca2 /calmodulin to produce NO, which ine1412 (S1412), also stimulates neuronal NO synthesis (21). Because + causes smooth muscle relaxation to regulate physiologic tone. nNOS nNOS activity is more sensitive to [Ca2 ](21),andnNOSismore serine1412 (S1412) phosphorylation may reduce the activating rapidly dephosphorylated than eNOS (22), it is technically difficult to 2+ Ca requirement and sustain NO production. We developed and evaluate nNOS S1412 phosphorylation in vivo. Nonetheless, studies S1412A characterized a nonphosphorylatable nNOS knock-in mouse implicate nNOS S1412 phosphorylation in hippocampal excitotoxicity and evaluated its enteric neurotransmission and gastrointestinal (4), penile erection (22), and luteinizing hormone release (23). (GI) motility to understand the physiologic significance of nNOS Enteric neurons express high levels of nNOS, Akt, and PKA S1412 phosphorylation.
    [Show full text]
  • Gastrointestinal Motility Disorders
    Gastrointestinal Motility Disorders Jassin M. Jouria, MD Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serve as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology. Abstract The muscles of the gastrointestinal (GI) tract perform an important job. The GI tract peristalsis, or contractions, mix the contents of the stomach and propel contents throughout the entire GI tract until they exit as waste. When these muscles underperform or fail to perform, it can create serious and painful consequences, diagnosed as GI motility disorders. Although these disorders are rarely fatal, they can cause physical and emotional effects that negatively impact a patient's quality of life.
    [Show full text]
  • The Plasmapheresis in the Treatment of Guillain-Barré Syndrome
    Merit Research Journal of Medicine and Medical Sciences (ISSN: 2354-323X) Vol. 7(2) pp. 066-072, February, 2019 Available online http ://www.meritresearchjournals.org/mms/index.htm Copyright © 2019 Merit Research Journals Case Report The Plasmapheresis in the Treatment of Guillain-Barre ́ Syndrome Associated with Primary Enteric Neuropathy, Case Report. Up-Date Data from Literature Lungu Mihaela 1* and Sapira Violeta 2 Abstract 1Assoc. Prof., Head of Neurological The article presents a case with a particular clinical situation that has Department, Emergency Clinical associated an enteric neuropathy with an evolution of over two months, with Hospital Galati, Romania; Faculty of a Guillain-Barré syndrome (Landry type), both remitted after Medicine and Pharmacy, “Dunarea de plasmapheresis. A 53 year old male patient has been admitted in our Jos” University of Galati, Romania Neurological Department with dehydration, syncope and orthostatic 2Assist. Prof., Neurological hypotention, due to an enteric neuropathie, complicated in 8 days with a Department, Emergency Clinical Guillain Barré syndrome-GBS. This type of associated diseases is rarely Hospital Galati, Romania; Faculty of described in the literature, being well known that GBS can be precede with Medicine and Pharmacy, “Dunarea de two weeks in advance by a diarrheic episode. In our case, a chronic Jos” University of Galati, Romania diarrheic sufferance was involved- an enteric neuropathy. Both types of neurological manifestations had an obvious improvement after *Corresponding Author’s
    [Show full text]
  • Chronic Intestinal Pseudo-Obstruction As an Expression Of
    GE Port J Gastroenterol. 2014;21(6):254---257 www.elsevier.pt/ge CLINICAL CASE Chronic intestinal pseudo-obstruction as an expression of inflammatory enteric neuropathy a,∗ a a b a Rita Pimentel , Marta Salgado , Maria João Magalhães , Ana Accarino , Isabel Pedroto a Gastroenterology Department, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal b Gastroenterology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain Received 22 December 2013; accepted 28 July 2014 Available online 22 November 2014 KEYWORDS Abstract Chronic intestinal pseudo-obstruction (CIPO) is characterised by inadequate diges- tive tract motility and can lead to severely disordered motility. CIPO manifests as recurrent Chronic intestinal pseudo-obstruction; episodes of intestinal sub-occlusion without an anatomical obstruction. We present the case Neuropathy; of a 41-year-old female, with severe chronic constipation and several episodes of intesti- Bowel nal sub-occlusion. Investigation revealed colonic inertia and marked distension of the small bowel and colon with no evidence of stenosis or obstructive lesions, compatible with CIPO. After several treatments were tried (domperidone, erythromycin, cisapride, octreotide, total enteral nutrition), with partial or no response, further work-up was done trying to identify an etiology. Gastrointestinal manometry showed neuropathic type abnormalities, transmural biopsy of the jejunum revealed degenerative enteric neuropathy and anti-HU antineuronal antibody screen was positive, suggesting an autoimmune type neuropathy with diffuse involve- ment of the digestive tract. Corticosteroids showed partial improvement of short duration and azathioprine was also tried but discontinued due to intolerance. Marked dietary intolerance and malnutrition lead to total parenteral nutrition (TPN) at home since October 2011.
    [Show full text]
  • Irinotecan-Induced Gastrointestinal Dysfunction Is Associated with Enteric Neuropathy, but Increased Numbers of Cholinergic Myenteric Neurons
    ORIGINAL RESEARCH published: 08 June 2017 doi: 10.3389/fphys.2017.00391 Irinotecan-Induced Gastrointestinal Dysfunction Is Associated with Enteric Neuropathy, but Increased Numbers of Cholinergic Myenteric Neurons Rachel M. McQuade 1, Vanesa Stojanovska 1, Elizabeth L. Donald 1, Ahmed A. Rahman 1, Dean G. Campelj 1, 2, 3, Raquel Abalo 4, Emma Rybalka 1, 2, 3, Joel C. Bornstein 5 and Kulmira Nurgali 1* 1 College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia, 2 Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, VIC, Australia, 3 Australian Institute of Musculoskeletal Science, Western Health, Edited by: Melbourne, VIC, Australia, 4 Área de Farmacología y Nutrición y Unidad Asociada al Instituto de Química Médica y al Instituto L. Ashley Blackshaw, de Investigación en Ciencias de la Alimentación del Consejo Superior de Investigaciones Científicas, Grupo de Excelencia Queen Mary University of London, Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor, Universidad Rey United Kingdom Juan Carlos, Alcorcón, Spain, 5 Department of Physiology, Melbourne University, Melbourne, VIC, Australia Reviewed by: Patrick Anthony Hughes, Gastrointestinal dysfunction is a common side-effect of chemotherapy leading to dose University of Adelaide, Australia Rainer Viktor Haberberger, reductions and treatment delays. These side-effects may persist up to 10 years Flinders University, Australia post-treatment. A topoisomerase I inhibitor, irinotecan (IRI), commonly used for the *Correspondence: treatment of colorectal cancer, is associated with severe acute and delayed-onset Kulmira Nurgali [email protected] diarrhea. The long-term effects of IRI may be due to damage to enteric neurons innervating the gastrointestinal tract and controlling its functions.
    [Show full text]
  • Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives
    Journal of Clinical Medicine Review Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives Ditte S. Kornum 1,2,* , Astrid J. Terkelsen 3, Davide Bertoli 4, Mette W. Klinge 1, Katrine L. Høyer 1,2, Huda H. A. Kufaishi 5, Per Borghammer 6, Asbjørn M. Drewes 4,7, Christina Brock 4,7 and Klaus Krogh 1,2 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; [email protected] (M.W.K.); [email protected] (K.L.H.); [email protected] (K.K.) 2 Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark 3 Department of Neurology, Aarhus University Hospital, DK8200 Aarhus, Denmark; [email protected] 4 Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; [email protected] (D.B.); [email protected] (A.M.D.); [email protected] (C.B.) 5 Steno Diabetes Centre Copenhagen, Gentofte Hospital, DK2820 Gentofte, Denmark; [email protected] 6 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, DK8200 Aarhus, Denmark; [email protected] 7 Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark * Correspondence: [email protected] Abstract: The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastroin- Citation: Kornum, D.S.; Terkelsen, testinal tract is a common finding in AD, but no commercially available method exists for direct A.J.; Bertoli, D.; Klinge, M.W.; Høyer, K.L.; Kufaishi, H.H.A.; Borghammer, verification of enteric dysfunction.
    [Show full text]
  • Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems
    International Journal of Molecular Sciences Review Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems Weixia Zhong 1, Omar Shahbaz 2, Garrett Teskey 1, Abrianna Beever 3, Nala Kachour 3, Vishwanath Venketaraman 1,3 and Nissar A. Darmani 1,* 1 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766, USA; [email protected] (W.Z.); [email protected] (G.T.); [email protected] (V.V.) 2 School of Medicine, Universidad Iberoamericana, Av. Francia 129, Santo Domingo 10203, Dominican Republic; [email protected] 3 Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] (A.B.); [email protected] (N.K.) * Correspondence: [email protected]; Tel.: +1-909-469-5654 Abstract: Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems. Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi enter the body either via the enteral (e.g., the gastrointestinal tract) or parenteral routes, including the blood, skin, and respiratory systems. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is believed to be a subjective sensation that is more difficult to study in nonhuman species. In this review, the authors discuss the anatomical structures, neurotransmitters/mediators, Citation: Zhong, W.; Shahbaz, O.; and corresponding receptors, as well as intracellular emetic signaling pathways involved in the Teskey, G.; Beever, A.; Kachour, N.; processes of nausea and vomiting in diverse animal models as well as humans.
    [Show full text]
  • Pediatric Enteric Neuropathies: Diagnosis and Current Management
    CE: Swati; COPE-D-17-00007; Total nos of Pages: 7; COPE-D-17-00007 REVIEW CURRENT OPINION Pediatric enteric neuropathies: diagnosis and current management Maggie L. Westfala and Allan M. Goldsteinb,c Purpose of review Neurointestinal diseases are increasingly recognized as causes of significant gastrointestinal morbidity in children. This review highlights the most common pediatric enteric neuropathies and their diagnosis and management, emphasizing insights and discoveries from the most recent literature available. Recent findings The embryologic and histopathologic causes of enteric neuropathies are varied. They range from congenital aganglionosis in Hirschsprung disease, to autoimmune-mediated loss of neuronal subtypes in esophageal achalasia and Chagas disease, to degenerative neuropathies in some cases of chronic intestinal pseudo-obstruction and gastroparesis. Increased awareness of the clinical presentation and diagnostic evaluation of these conditions is essential as it allows for earlier initiation of treatment and improved outcomes. Most current therapies, which include medical management, neurostimulation, and operative intervention, aim to minimize the symptoms caused by these conditions. The evidence base for many of these treatments in children is poor, and multiinstitutional prospective studies are needed. An innovative therapy on the horizon involves using neuronal stem cell transplantation to treat the underlying disorder by replacing the missing or damaged neurons in these diseases. Summary Although recent advances in basic and clinical neurogastroenterology have significantly improved our awareness and understanding of enteric neuropathies, the efficacy of current treatment approaches is limited. The development of novel therapies, including pharmacologic modulators of neurointestinal function, neurostimulation to enhance gut motility, and neuronal cell-based therapies, is essential to improve the long-term outcomes in children with these disorders.
    [Show full text]
  • Gastrointestinal Neuromuscular Pathology: Guidelines for Histological Techniques and Reporting on Behalf of the Gastro 2009 International Working Group
    Acta Neuropathol (2009) 118:271–301 DOI 10.1007/s00401-009-0527-y CONSENSUS PAPER Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group Charles H. Knowles Æ Roberto De Giorgio Æ Raj P. Kapur Æ Elisabeth Bruder Æ Gianrico Farrugia Æ Karel Geboes Æ Michael D. Gershon Æ John Hutson Æ Greger Lindberg Æ Joanne E. Martin Æ William A. Meier-Ruge Æ Peter J. Milla Æ Virpi V. Smith Æ Jean Marie Vandervinden Æ Be´la Veress Æ Thilo Wedel Received: 22 January 2009 / Revised: 19 March 2009 / Accepted: 22 March 2009 / Published online: 10 April 2009 Ó Springer-Verlag 2009 Abstract The term gastrointestinal neuromuscular dis- abnormalities have been demonstrated by a variety of ease describes a clinically heterogeneous group of methods in these conditions, standards for histopatholo- disorders of children and adults in which symptoms are gical reporting remain relatively neglected. Significant presumed or proven to arise as a result of neuromuscular, differences in methodologies and expertise continue to including interstitial cell of Cajal, dysfunction. Such dis- confound the reliable delineation of normality and speci- orders commonly have impaired motor activity, i.e. slowed ficity of particular pathological changes for disease. Such or obstructed transit with radiological evidence of transient issues require urgent clarification to standardize acquisition or persistent visceral dilatation. Whilst sensorimotor and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thick- ness tissue biopsy of bowel or other diagnostic procedures. Electronic supplementary material The online version of this Such information will also allow increased certainty of article (doi:10.1007/s00401-009-0527-y) contains supplementary material, which is available to authorized users.
    [Show full text]
  • Pseudo-Obstruction, Enteric Dysmotility and Irritable Bowel Syndrome
    Best Practice & Research Clinical Gastroenterology 40-41 (2019) 101635 Contents lists available at ScienceDirect Best Practice & Research Clinical Gastroenterology journal homepage: https://ees.elsevier.com/ybega/default.asp Pseudo-obstruction, enteric dysmotility and irritable bowel syndrome Greger Lindberg Karolinska Institutet, Department of Medicine, Huddinge and Karolinska University Hospital Huddinge, Patient Area Gastroenterology, Dermatology, and Rheumatology, SE-14186, Stockholm, Sweden article info abstract Article history: New diagnostic techniques have advanced our knowledge about the irritable bowel syndrome. The Received 25 March 2019 majority of patients that we believed to have a psychosomatic disorder have received other diagnoses Accepted 18 July 2019 explaining their symptoms. Endoscopy makes it possible to diagnose celiac disease before it leads to malnutrition and allows the detection of microscopic colitis as a cause of watery diarrhea. At the severe Keywords: end of the symptom spectrum enteric dysmotility marks the border at which IBS ceases to be a functional Irritable bowel syndrome disorder and becomes a genuine motility disorder. Joint hypermobility or Ehlers-Danlos syndrome is Enteric dysmotility present in a substantial proportion of patients with enteric dysmotility. Chronic intestinal pseudo- Chronic intestinal pseudo-obstruction Bile acid diarrhea obstruction is the end-stage of a large number of very rare disorders in which failed peristalsis is the Joint hypermobility common denominator. Nutritional
    [Show full text]