DOCSLIB.ORG

Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome nutrients Review Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome 1, , 1, 2, 3 Piero Portincasa * y , Agostino Di Ciaula y , Gabriella Garruti y, Mirco Vacca , Maria De Angelis 3 and David Q.-H. Wang 4 1 Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; [email protected] 2 Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, Piazza G. Cesare 11, 70124 Bari, Italy; [email protected] 3 Dipartimento di Scienze del Suolo, Della Pianta e Degli Alimenti, Università degli Studi di Bari Aldo Moro, 70124 Bari, Italy; [email protected] (M.V.); [email protected] (M.D.A.) 4 Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; [email protected] * Correspondence: [email protected]; Tel.: +39-80-5478-893 These authors contributed equally to this work. y Received: 3 November 2020; Accepted: 26 November 2020; Published: 30 November 2020 Abstract: Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects. Keywords: bile; cholestasis; FXR; metabolic syndrome; nuclear receptors; TGR5; thermogenesis 1. Introduction Bile acids (BA) are amphipathic molecules made from cholesterol in the liver in the pericentral hepatocytes. BA are conjugated to taurine or glycine to increase their solubility, are actively secreted into the bile canaliculus, and become the major lipid components of bile. During fasting, bile is mostly diverted and stored in the gallbladder, where water is reabsorbed, and bile concentration occurs. During the interprandial phase, a low-grade secretion of bile occurs in the intestine. During the postcibal period, dietary fat in the upper intestine stimulates gallbladder contraction in response to the enterohormone cholecystokinin. This step releases highly concentrated bile into the duodenum. Nutrients 2020, 12, 3709; doi:10.3390/nu12123709 www.mdpi.com/journal/nutrients Nutrients 2020, 12, 3709 2 of 30 In the intestine, BA promote the emulsification and absorption of dietary fat, i.e., cholesterol, triglycerides,Nutrients 2020, 12, x andFOR PEER fat-soluble REVIEW vitamins. Following ileal and colonic reabsorption,2 of BA 30 undergo continuous enterohepatic circulation several times daily. In the liver and intestine, BA suppress their owntriglycerides, synthesis, and and fat-soluble recent evidence vitamins. shows Follow thating BAileal are and potent colonic signalling reabsorption, molecules BA undergo with modulatory continuous enterohepatic circulation several times daily. In the liver and intestine, BA suppress their effects on epithelial cell proliferation, gene expression, fibrogenesis, as well as lipid and glucose own synthesis, and recent evidence shows that BA are potent signalling molecules with modulatory metabolism. Such effects are the consequence of BA acting as endogenous ligands and activation effects on epithelial cell proliferation, gene expression, fibrogenesis, as well as lipid and glucose ofmetabolism. the nuclear Such farnesoid effects are X the receptor consequence (FXR of or BA NR1H4), acting as the endogenous membrane-associated ligands and activation G-protein-coupled of bilethe nuclear acid receptor-1 farnesoid (GPBAR-1,X receptor (FXR also or known NR1H4) as, the transmembrane membrane-associated G protein-coupled G-protein-coupled receptor bile 5, TGR5), andacid receptor-1 sphingosine-1-phosphate (GPBAR-1, also known receptor as transmembrane 2 (S1PR2) in G the protein-coupled liver, intestine, receptor muscle 5, TGR5), and brown and adipose tissuesphingosine-1-phosphate [1–3]. Physiologically, receptor BA 2 are(S1PR2) confined in the almost liver, intestine, completely muscle within and brown the enterohepatic adipose tissue circulation, as[1–3]. only Physiologically, traces escape inBA the are general confined circulation. almost completely [4] Integrity within of the enterohepatic circulation, circulation as is therefore centralonly traces to biliaryescape homeostasis.in the general circulation. [4] Integrity of the enterohepatic circulation is therefore centralThis to biliary review homeostasis. will discuss in detail the complex pathways underlying BA homeostasis in physiology This review will discuss in detail the complex pathways underlying BA homeostasis in and during BA overload, their role as signalling molecules in particular for GPBAR-1. We also discuss physiology and during BA overload, their role as signalling molecules in particular for GPBAR-1. We thealso multiplediscuss the eff multipleects of this effects receptor of this onreceptor bile composition, on bile composition, cell lines, cell inflammation,lines, inflammation, gene-environment gene- interaction,environment togetherinteraction, with together potential with therapeuticpotential therapeutic approaches. approaches. 2. BA BA Synthesis, Synthesis, Secretion, Secretion, Biotransformation, Biotransformation, and Absorption and Absorption TheThe complex complex pathways pathways leading leading to BA to BAhomeostasis homeostasis in liver in liverand intestine and intestine [1,5,6] [are1,5 ,summarized6] are summarized in Figurein Figure1. 1. Figure 1. Cont. Nutrients 2020, 12, 3709 3 of 30 Nutrients 2020, 12, x FOR PEER REVIEW 3 of 30 Figure 1. (A) Sites of synthesis and metabolism of primary, secondary, and tertiary bile acids (BA) in humans. Cholesterol in the liver undergoes modification of the sterol ring, oxidation, and shortening of the side chain. The classical “neutral” pathway involves the cytochrome P450 enzyme, cholesterol Figure 1. (A) Sites of synthesis and metabolism of primary, secondary, and tertiary bile acids (BA) in 7α-hydroxylase (CYP7A1), and contributes to about 75–90% of total BA pool consisting of cholic acid humans. Cholesterol in the liver undergoes modification of the sterol ring, oxidation, and shortening (CA) and chenodeoxycholic acid (CDCA). The alternative “acidic” pathway is mitochondrial and of the side chain. The classical “neutral” pathway involves the cytochrome P450 enzyme, cholesterol contributes to 10–25% of total BA pool [1,7] with the rate-limiting enzyme cholesterol 27α-hydroxylase 7α-hydroxylase (CYP7A1), and contributes to about 75–90% of total BA pool consisting of cholic acid (CYP27A1) and then 25-hydroxycholesterol 7-alpha-hydroxylase (CYP7B1) [8,9] to produce CDCA. (CA) and chenodeoxycholic acid (CDCA). The alternative “acidic” pathway is mitochondrial and BA in the liver undergo conjugation with amino acids, glycine or taurine (ratio of 3:1), via N-acyl contributes to 10–25% of total BA pool [1,7] with the rate-limiting enzyme cholesterol 27α- amidation at carbon 24 of the aliphatic side chain [10] and active biliary secretion. In the colon the hydroxylase (CYP27A1) and then 25-hydroxycholesterol 7-alpha-hydroxylase (CYP7B1) [8,9] to resident bacteria interact with primary BA by dehydroxylation, dehydrogenation, 7α-dehydroxylation produce CDCA. BA in the liver undergo conjugation with amino acids, glycine or taurine (ratio of and epimerization. By this pathway, secondary BA are the dihydroxy deoxycholic acid (DCA) and 3:1), via N-acyl amidation at carbon 24 of the aliphatic side chain [10] and active biliary secretion. In the monohydroxy lithocholic acid (LCA). The 7α-dehydrogenation of CDCA forms the dihydroxy the colon the resident bacteria interact with primary BA by dehydroxylation, dehydrogenation, 7α- 7α-oxo-LCA which is metabolized to the “tertiary” 7β-epimer, the dihydroxy ursodeoxycholic acid (UDCA).dehydroxylation In the liver, and a smallepimerization. amount ofBy LCA this ispath quicklyway, secondary transformed BA to are sulphonated the dihydroxy form deoxycholic (S-LCA). Inacid the terminal(DCA) and ileum, the BAmonohydroxy uptake is about lithocholic 80% by acid active (LCA). transport The 7 withinα-dehydrogenation the enterocytes. of InCDCA the colon,
Load more

Recommended publications
  • Pharmacy Prior Authorization Non-Formulary and Prior
    Pharmacy Prior Authorization Non-Formulary and Prior Authorization Guidelines Scroll down to see PA Criteria by drug class, or Ctrl+F to search document by drug name PA Guideline Requirements Duration of Approval if Requirements Are Met Non-Formulary Requests for Non-Formulary Medications that do not have specific Prior Authorization Initial Approval: Medication Guidelines will be reviewed based on the following: • Minimum of 3 months, Guideline • An appropriate diagnosis/indication for the requested medication, depending on the • An appropriate dose of medication based on age and indication, diagnosis, to determine • Documented trial of 2 formulary agents for an adequate duration have not been effective or adherence, efficacy and tolerated patient safety monitoring OR • All other formulary medications are contraindicated based on the patient’s diagnosis, other Renewal: medical conditions or other medication therapy, • Minimum of 6 months OR • Maintenance medications • There are no other medications available on the formulary to treat the patient’s condition may be approved Indefinite Maryland Physicians Care determines patient medication trials and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. Medications Requests for Medications requiring Prior Authorization (PA) will be reviewed based on the PA As documented in the requiring Prior Guidelines/Criteria for that medication. Scroll down to view the PA Guidelines for specific individual guideline Authorization medications. Medications that do not have a specific PA guideline will follow the Non-Formulary Medication Guideline. Additional information may be required on a case-by-case basis to allow for adequate review.
    [Show full text]
  • Drug Class Review Antianginal Agents
    Drug Class Review Antianginal Agents 24:12.08 Nitrates and Nitrites 24:04.92 Cardiac Drugs, Miscellaneous Amyl Nitrite Isosorbide Dinitrate (IsoDitrate ER®, others) Isosorbide Mononitrate (Imdur®) Nitroglycerin (Minitran®, Nitrostat®, others) Ranolazine (Ranexa®) Final Report May 2015 Review prepared by: Melissa Archer, PharmD, Clinical Pharmacist Carin Steinvoort, PharmD, Clinical Pharmacist Gary Oderda, PharmD, MPH, Professor University of Utah College of Pharmacy Copyright © 2015 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. Table of Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 4 Table 1. Antianginal Therapies .............................................................................................. 4 Table 2. Summary of Agents .................................................................................................. 5 Disease Overview ........................................................................................................................ 8 Table 3. Summary of Current Clinical Practice Guidelines .................................................... 9 Pharmacology ............................................................................................................................... 10 Table 4. Pharmacokinetic Properties
    [Show full text]
  • Vocabulario De Morfoloxía, Anatomía E Citoloxía Veterinaria
    Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) Servizo de Normalización Lingüística Universidade de Santiago de Compostela COLECCIÓN VOCABULARIOS TEMÁTICOS N.º 4 SERVIZO DE NORMALIZACIÓN LINGÜÍSTICA Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) 2008 UNIVERSIDADE DE SANTIAGO DE COMPOSTELA VOCABULARIO de morfoloxía, anatomía e citoloxía veterinaria : (galego-español- inglés) / coordinador Xusto A. Rodríguez Río, Servizo de Normalización Lingüística ; autores Matilde Lombardero Fernández ... [et al.]. – Santiago de Compostela : Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2008. – 369 p. ; 21 cm. – (Vocabularios temáticos ; 4). - D.L. C 2458-2008. – ISBN 978-84-9887-018-3 1.Medicina �������������������������������������������������������������������������veterinaria-Diccionarios�������������������������������������������������. 2.Galego (Lingua)-Glosarios, vocabularios, etc. políglotas. I.Lombardero Fernández, Matilde. II.Rodríguez Rio, Xusto A. coord. III. Universidade de Santiago de Compostela. Servizo de Normalización Lingüística, coord. IV.Universidade de Santiago de Compostela. Servizo de Publicacións e Intercambio Científico, ed. V.Serie. 591.4(038)=699=60=20 Coordinador Xusto A. Rodríguez Río (Área de Terminoloxía. Servizo de Normalización Lingüística. Universidade de Santiago de Compostela) Autoras/res Matilde Lombardero Fernández (doutora en Veterinaria e profesora do Departamento de Anatomía e Produción Animal.
    [Show full text]
  • Pharmacological Agents Currently in Clinical Trials for Disorders in Neurogastroenterology
    Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri J Clin Invest. 2013;123(10):4111-4120. https://doi.org/10.1172/JCI70837. Clinical Review Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in understanding the mechanisms of these disorders, through basic and translational research, and in targeting the receptors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastroparesis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain. Find the latest version: https://jci.me/70837/pdf Review Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA. Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in under- standing the mechanisms of these disorders, through basic and translational research, and in targeting the recep- tors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastropa- resis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain.
    [Show full text]
  • Does Your Patient Have Bile Acid Malabsorption?
    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 Carol Rees Parrish, MS, RDN, Series Editor Does Your Patient Have Bile Acid Malabsorption? John K. DiBaise Bile acid malabsorption is a common but underrecognized cause of chronic watery diarrhea, resulting in an incorrect diagnosis in many patients and interfering and delaying proper treatment. In this review, the synthesis, enterohepatic circulation, and function of bile acids are briefly reviewed followed by a discussion of bile acid malabsorption. Diagnostic and treatment options are also provided. INTRODUCTION n 1967, diarrhea caused by bile acids was We will first describe bile acid synthesis and first recognized and described as cholerhetic enterohepatic circulation, followed by a discussion (‘promoting bile secretion by the liver’) of disorders causing bile acid malabsorption I 1 enteropathy. Despite more than 50 years since (BAM) including their diagnosis and treatment. the initial report, bile acid diarrhea remains an underrecognized and underappreciated cause of Bile Acid Synthesis chronic diarrhea. One report found that only 6% Bile acids are produced in the liver as end products of of British gastroenterologists investigate for bile cholesterol metabolism. Bile acid synthesis occurs acid malabsorption (BAM) as part of the first-line by two pathways: the classical (neutral) pathway testing in patients with chronic diarrhea, while 61% via microsomal cholesterol 7α-hydroxylase consider the diagnosis only in selected patients (CYP7A1), or the alternative (acidic) pathway via or not at all.2 As a consequence, many patients mitochondrial sterol 27-hydroxylase (CYP27A1). are diagnosed with other causes of diarrhea or The classical pathway, which is responsible for are considered to have irritable bowel syndrome 90-95% of bile acid synthesis in humans, begins (IBS) or functional diarrhea by exclusion, thereby with 7α-hydroxylation of cholesterol catalyzed interfering with and delaying proper treatment.
    [Show full text]
  • Drugs That Require Prior Authorization
    Drugs That Require Prior Authorization (PA) Before Being Approved for Coverage You will need authorization by your HMSA Akamai Advantage (PPO) plan before filling prescriptions for the drugs shown in the chart below. The HMSA Akamai Advantage plan will only provide coverage after it determines that the drug is being prescribed according to the criteria specified in the chart. You, your appointed representative, or your prescriber can request prior authorization by calling HMSA at 1 (855) 479-3659, 24 hours a day, 7 days a week. Customer service is available in English and other languages. TTY/TDD users should call 711. PA Criteria Prior Authorization Group ACITRETIN Drug Names ACITRETIN, SORIATANE Covered Uses All FDA-approved indications not otherwise excluded from Part D, prevention of non-melanoma skin cancers in high risk individuals. Exclusion Criteria Required Medical Information Age Restrictions Prescriber Restrictions Coverage Duration Plan Year Other Criteria Prior Authorization Group ACTEMRA Drug Names ACTEMRA Covered Uses All FDA-approved indications not otherwise excluded from Part D, unicentric Castleman's disease, multicentric Castleman's disease. Exclusion Criteria Required Medical Information For moderately to severely active rheumatoid arthritis (new starts only): Inadequate response, intolerance or contraindication to a self-injectable tumor necrosis factor (TNF) inhibitor (e.g., adalimumab) or a targeted synthetic disease-modifying antirheumatic drug (DMARD) (e.g., tofacitinib). For active polyarticular juvenile idiopathic arthritis (new starts only): Inadequate response, intolerance or contraindication to a TNF inhibitor (e.g., adalimumab). For active systemic juvenile idiopathic arthritis (new starts only): Inadequate response to a corticosteroid monotherapy, methotrexate or leflunomide. Age Restrictions Prescriber Restrictions Coverage Duration Plan Year Other Criteria Prior Authorization Group ACTHAR HP Drug Names H.P.
    [Show full text]
  • Liver • Gallbladder
    NORMAL BODY Microscopic Anatomy! Accessory Glands of the GI Tract,! lecture 2! ! • Liver • Gallbladder John Klingensmith [email protected] Objectives! By the end of this lecture, students will be able to: ! • trace the flow of blood and bile within the liver • describe the structure of the liver in regard to its functions • indicate the major cell types of the liver and their functions • distinguish the microanatomy of exocrine and endocrine function by the hepatocytes • explain the functional organization of the gallbladder at the cellular level (Lecture plan: overview of structure and function, then increasing resolution of microanatomy and cellular function) Liver and Gallbladder Liver October is “Liver Awareness Month” -- http://www.liverfoundation.org Liver • Encapsulated by CT sheath and mesothelium • Lobes largely composed of hepatocytes in parenchyma • Receives blood from small intestine and general circulation Major functions of the liver • Production and secretion of digestive fluids to small intestine (exocrine) • Production of plasma proteins and lipoproteins (endocrine) • Storage and control of blood glucose • Detoxification of absorbed compounds • Source of embyronic hematopoiesis The liver lobule • Functional unit of the parenchyma • Delimited by CT septa, invisible in humans (pig is shown) • Surrounds the central vein • Bordered by portal tracts Central vein, muralia and sinusoids Parenchyma: Muralia and sinusoids • Hepatocyte basolateral membrane faces sinusoidal lumen • Bile canaliculi occur between adjacent hepatocytes • Cords anastomose Vascularization of the liver • Receives veinous blood from small intestine via portal vein • Receives freshly oxygenated blood from hepatic artery • Discharges blood into vena cava via hepatic vein Blood flow in the liver lobes • flows in via the portal vein and hepatic artery • oozes through the liver lobules to central veins • flows out via the hepatic vein Portal Tract! (aka portal triad) • Portal venule • Hepatic arteriole • Bile duct • Lymph vessel • Nerves • Connective tissue Central vein! (a.k.a.
    [Show full text]
  • Antianginal Drugs
    Antianginal Drugs Angina medications are used for angina pectoris or chest pain. The types of chest pain are chronic stable angina (which is associated with atherosclerosis), unstable angina (early stage of progressive coronary artery disease), and vasospastic angina (which results from spasms in the layer of smooth muscle that surrounds atherosclerotic coronary arteries). The three main classes of drugs used to treat angina pectoris are nitrates and nitrites, beta-blockers, and calcium channel blockers. The goal of the treatment is: 1. Minimize the frequency of attacks and decrease the duration and intensity of angina pain 2. Improve the patient’s functional capacity with as few adverse effects as possible 3. Increase blood flow to ischemic heart muscle and decrease myocardial oxygen demand 4. Prevent or delay the worst possible outcome, which is a myocardial infarction Nitrates and Nitrites Nitrates are available on many forms including sublingual, chewable tablets, oral capsules/tablets, IV solutions, transdermal patches, ointments and translingual sprays. They are broken down into rapid-acting forms and long-acting forms. The rapid-acting forms include sublingual and IV solutions. These are used to treat acute angina attacks. The long-acting forms are used to prevent angina episodes. Mechanism of Action Nitrates dilate all blood vessels; however, they predominately affect venous vascular beds and have a dose-dependent arterial vasodilator effect. This vasodilation happens because of relaxation of smooth muscle cells. 1. Vasodilation results in reduced myocardial oxygen demand and therefore more oxygen to ischemic myocardial tissue and reduction of angina symptoms. 2. By causing venous dilation, the nitrates reduce venous return and in turn reduce the leftventricular end-diastolic volume (preload) and results in a lower left ventricular pressure.
    [Show full text]
  • Effects of Vasodilation and Arterial Resistance on Cardiac Output Aliya Siddiqui Department of Biotechnology, Chaitanya P.G
    & Experim l e ca n i t in a l l C Aliya, J Clinic Experiment Cardiol 2011, 2:11 C f a Journal of Clinical & Experimental o r d l DOI: 10.4172/2155-9880.1000170 i a o n l o r g u y o J Cardiology ISSN: 2155-9880 Review Article Open Access Effects of Vasodilation and Arterial Resistance on Cardiac Output Aliya Siddiqui Department of Biotechnology, Chaitanya P.G. College, Kakatiya University, Warangal, India Abstract Heart is one of the most important organs present in human body which pumps blood throughout the body using blood vessels. With each heartbeat, blood is sent throughout the body, carrying oxygen and nutrients to all the cells in body. The cardiac cycle is the sequence of events that occurs when the heart beats. Blood pressure is maximum during systole, when the heart is pushing and minimum during diastole, when the heart is relaxed. Vasodilation caused by relaxation of smooth muscle cells in arteries causes an increase in blood flow. When blood vessels dilate, the blood flow is increased due to a decrease in vascular resistance. Therefore, dilation of arteries and arterioles leads to an immediate decrease in arterial blood pressure and heart rate. Cardiac output is the amount of blood ejected by the left ventricle in one minute. Cardiac output (CO) is the volume of blood being pumped by the heart, by left ventricle in the time interval of one minute. The effects of vasodilation, how the blood quantity increases and decreases along with the blood flow and the arterial blood flow and resistance on cardiac output is discussed in this reviewArticle.
    [Show full text]
  • Endogenous Estradiol in Elderly Individuals Cognitive and Noncognitive Associations
    ORIGINAL CONTRIBUTION Endogenous Estradiol in Elderly Individuals Cognitive and Noncognitive Associations V. Senanarong, MD; S. Vannasaeng, MD; N. Poungvarin, MD; S. Ploybutr, MSC; S. Udompunthurak, MSC; P. Jamjumras, RN; L. Fairbanks, PhD; J. L. Cummings, MD Objective: To investigate an association between en- the Functional Assessment Questionnaire was used to as- dogenous estradiol (E2) levels and cognition and behav- sess instrumental activities of daily living. ior in elderly individuals. Results: There was no correlation between age and level of E2 in either men or women. Individuals with lower estro- Patients: We studied 135 community-based men and genlevelshadmorebehavioraldisturbances(men:r=−0.467, women aged 52 to 85 years in urban Bangkok, Thai- n=45;P=.001;women:r=−0.384,n=90;PϽ.001)andworse land; 72 had dementia and 63 did not. cognition (men: r=0.316, n=45; P=.03; women: r=0.243, n=90; P=.02) and function (men: r=−0.417, n=45; P=.004; women: r=−0.437, n=90; PϽ.001). The threshold level of Materials and Methods: Dementia was diagnosed endogenous E2 in elderly individuals for the risk of devel- using Diagnostic and Statistical Manual of Mental Disor- oping dementia was less than 15 pg/mL (Ͻ55 pmol/L) in ders, Fourth Edition, criteria after appropriate investiga- men and less than 1 pg/mL (Ͻ4 pmol/L) in women. tions. Blood samples for assay were collected in the morn- ing after 6 hours of fasting. Levels of E2 were measured Conclusion: Lower E2 levels are correlated with poor cog- by radioimmunoassay (double antibody technique).
    [Show full text]
  • Major Products
    Data Section Major Products Innovative Pharmaceuticals Business Innovative Pharmaceuticals Business Brand Name (Generic Name) Efficacy Launched Remarks Brand Name (Generic Name) Efficacy Launched Remarks Japan [Daiichi Sankyo Co., Ltd.] US [Daiichi Sankyo Inc.] A first combination drug of the DPP-4 inhibitor teneligliptin and the SGLT2 inhibitor Opioid-induced First once-daily oral product approved by the FDA for the treatment of opioid-induced (teneligliptin / Type 2 diabetes mellitus MOVANTIK (naloxegol) 2015 CANALIA 2017 canagliflozin approved in Japan, which demonstrates blood glucose-lowering activity constipation treatment constipation (OIC) for adults with chronic non-cancer pain. canagliflozin) treatment through a complementary pharmacological effect. Orally active Factor Xa inhibitor. It is an anticoagulant that specifically, reversibly and directly inhibits the enzyme, Factor Xa, a clotting factor in the blood. Approved for indications to Sodium channel blocker. Suppresses the excessive excitation of nerves in the brain, and VIMPAT (lacosamide) Anti-epileptic agent 2016 SAVAYSA (edoxaban) Anticoagulant 2015 reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial reduces the occurrence of epileptic seizures. fibrillation (NVAF) and for the treatment of venous thromboembolism (VTE) (deep vein ADP receptor inhibitor. Inhibits platelet aggregation and reduces the incidence of artery thrombosis (DVT) and pulmonary embolism (PE)). Efient (prasugrel) Antiplatelet agent 2014 stenosis and occlusion due to thrombosis. Effient (prasugrel) Antiplatelet agent 2009 Inhibits platelet aggregation and reduces the incidence of artery stenosis and occlusion. Treatment for Benicar 2002 Benicar: Olmesartan osteoporosis / inhibitor Human monoclonal anti-RANKL antibody. Subcutaneous formulation which controls Benicar HCT 2003 Benicar HCT: A combination drug of olmesartan medoxomil and hydrochlorothiazide (diuretic) PRALIA (denosumab) for rheumatoid arthritis- 2013 bone resorption and bone destruction by specifically inhibiting RANKL.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]