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Title Page Adrenergic Storm-Induced Warburg Effect in COVID-19
Title Page Adrenergic storm-induced Warburg effect in COVID-19: A hypothesis. Natesan Vasanthakumar School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, 613401, India. Corresponding author: Natesan Vasanthakumar, MD School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India. Email: [email protected]; Telephone: +91-6380831065 Current address: Natesan Vasanthakumar, MD Sagol Department of Neurobiology, University of Haifa, Israel. 3498838 Email: [email protected] Telephone: +91-6380831065 Word count: 1586 Declaration: Dr. Vasanthakumar has nothing to disclose. The author did not receive any funding. Abstract: At present, there is no treatment option available for COVID-19 condition and most importantly the underlying pathophysiology in COVID-19 is not known. No theory at present explains all the clinical features in COVID-19. In this article, I had proposed a hypothesis that explains the underlying pathophysiology in COVID-19 and based on it proposed treatment options for COVID-19. I propose that the adrenergic storm-induced Warburg effect (aerobic glycolysis) may be the underlying mechanism in the COVID-19 condition. I propose alpha1 adrenergic blockers in the early phase and beta-adrenergic blockers in the late phase of COVID-19 to inhibit the adrenergic storm and reverse the Warburg effect in COVID-19 condition. Keywords: COVID-19, SARS-CoV-2, Adrenergic storm, Warburg effect, Aerobic glycolysis, alpha1 adrenergic blockers, beta adrenergic blockers. Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused coronavirus disease 2019 (COVID-19) pandemic is causing damage all over the world. It is known that SARS-CoV-2 enters the host cell via angiotensin-converting enzyme 2 (ACE2) and CD147, which is also known as Basigin or extracellular matrix metalloproteinase inducer (EMMPRIN )1,2. -
Roll-In NCT Number: NCT02841241 Date of Document: 12/16/2016 ECASSS-ROLL-IN V3 12-16-16
Cover Page Official Title: Esmolol to Control Adrenergic Storm in Septic Shock - Roll-in NCT Number: NCT02841241 Date of Document: 12/16/2016 ECASSS-ROLL-IN V3 12-16-16 Consent Form What Esmolol to Control Adrenergic Storm in Septic Shock (ECASSS) – ROLL-IN Where Intermountain Medical Center Who PI: Samuel Brown, MD, MS (801) 507-6556 Co- investigators: Colin Grissom, MD Michael Lanspa, MD, MS Emily Wilson, MS Ithan Peltan, MD Ellie Hirshberg, MD Peter Crossno, MD Vivian Lee, MD Sarah Beesley, MD Samir Parikh, MD Sponsor: Intermountain Medical Center When Your participation will last until you are discharged from the hospital. Why This research study will evaluate the adequacy and efficiency of study protocols for the main ECASSS study. We are investigating a drug called esmolol as a treatment for serious infection (“septic shock”). How While you are receiving infusions of medicines like adrenalin to support your blood pressure, we will infuse a medication called esmolol that we think will help to control the negative effects of the body’s high stress state during serious infection. You will also have some blood drawn and have ultrasound pictures of your heart taken. We will monitor to see how long it takes for your body to improve from the serious infection. Page 1 of 12 Intermountain Healthcare IRB IRB NUMBER: 1050147 IRB APPROVAL DATE: 01/16/2017 IRB EXPIRATION DATE: 12/07/2017 ECASSS-ROLL-IN V3 12-16-16 Why is this study being done? We are asking you to take part in a research study about a drug called esmolol for use in septic shock. -
Manuscript for Discussant
Original article BETA-BLOCKER THERAPY IN SEVERE TRAUMATIC BRAIN INJURY: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL Short title: Beta-blocker in severe TBI Hosseinali Khalili MD; Rebecka Ahl MB BChir, Ph.D; Shahram Paydar MD; Gabriel Sjolin MD; Yang Cao, Ph.D; Hossein Abdolrahimzadeh Fard MD; Amin Niakan MD; Kamil Hanna MD; Bellal Joseph MD; Shahin Mohseni MD, Ph.D. Author Contact Information: Hosseinali Khalili, MD. Associate Professor of Neurosurgery, Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran Email: [email protected] Dr Rebecka Ahl, MB BChir, PhD. General Surgery Resident Department of Surgery, Karolinska University Hospital, Stockholm, Sweden Email: [email protected] Shahram Paydar, MD. Associate Professor of Surgery Trauma Research Center, Rajaee (emtiaz) trauma hospital, Shiraz University of Medical Sciences, Shiraz, Iran Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran Email: [email protected] Gabriel Sjolin, MD. Department of Surgery, Orebro University Hospital, 701 85 Orebro, Sweden School of Medical Sciences, Orebro University, 702 81 Orebro, Sweden Email: [email protected] Yang Cao, PhD. Professor of Epidemiology and Biostatistics Clinical Epidemiology and Biostatistics, School of Medical Sciences, Orebro University, Orebro 70182, Sweden Email: [email protected] Amin Niakan, MD. Assistant Professor of Neurosurgery, Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran Email: [email protected] Hossein Abdolrahimzadeh Fard, MD. Assistant Professor of Surgery Trauma Research Center, Rajaee (emtiaz) trauma hospital, Shiraz University of Medical Sciences, Shiraz, Iran Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran Email: Dr.h.a.fard@gmail Kamil Hanna, MD. -
Treatment of ARDS*
Treatment of ARDS* Roy G. Brower, MD; Lorraine B. Ware, MD; Yves Berthiaume, MD; and Michael A. Matthay, MD, FCCP Improved understanding of the pathogenesis of acute lung injury (ALI)/ARDS has led to important advances in the treatment of ALI/ARDS, particularly in the area of ventilator- associated lung injury. Standard supportive care for ALI/ARDS should now include a protective ventilatory strategy with low tidal volume ventilation by the protocol developed by the National Institutes of Health ARDS Network. Further refinements of the protocol for mechanical ventilation will occur as current and future clinical trials are completed. In addition, novel modes of mechanical ventilation are being studied and may augment standard therapy in the future. Although results of anti-inflammatory strategies have been disappointing in clinical trials, further trials are underway to test the efficacy of late corticosteroids and other approaches to modulation of inflammation in ALI/ARDS. (CHEST 2001; 120:1347–1367) Key words: acute lung injury; mechanical ventilation; pulmonary edema; ventilator-associated lung injury Abbreviations: ALI ϭ acute lung injury; APRV ϭ airway pressure-release ventilation; ECco R ϭ extracorporeal ϭ ϭ 2 carbon dioxide removal; ECMO extracorporeal membrane oxygenation; Fio2 fraction of inspired oxygen; HFV ϭ high-frequency ventilation; I:E ϭ ratio of the duration of inspiration to the duration of expiration; IL ϭ interleukin; IMPRV ϭ intermittent mandatory pressure-release ventilation; IRV ϭ inverse-ratio ventilation; LFPPV ϭ low-frequency positive-pressure ventilation; NIH ϭ National Institutes of Health; NIPPV ϭ noninvasive positive-pressure ventilation; NO ϭ nitric oxide; PEEP ϭ positive end-expiratory pressure; PSB ϭ protected specimen brushing; TGI ϭ tracheal gas insufflation; TNF ϭ tumor necrosis factor he syndrome of acute respiratory distress in Standard Supportive Therapy T adults was first described in 1967.1 Until re- cently, most reported mortality rates exceeded 50%. -
Β-Adrenergic Modulation in Sepsis Etienne De Montmollin, Jerome Aboab, Arnaud Mansart and Djillali Annane
Available online http://ccforum.com/content/13/5/230 Review Bench-to-bedside review: β-Adrenergic modulation in sepsis Etienne de Montmollin, Jerome Aboab, Arnaud Mansart and Djillali Annane Service de Réanimation Polyvalente de l’hôpital Raymond Poincaré, 104 bd Raymond Poincaré, 92380 Garches, France Corresponding author: Professeur Djillali Annane, [email protected] Published: 23 October 2009 Critical Care 2009, 13:230 (doi:10.1186/cc8026) This article is online at http://ccforum.com/content/13/5/230 © 2009 BioMed Central Ltd Abstract in the intensive care setting [4] – addressing the issue of its Sepsis, despite recent therapeutic progress, still carries unaccep- consequences in sepsis. tably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, could be an The present review summarizes current knowledge on the interesting new therapeutic target for septic shock. β-Adrenergic effects of β-adrenergic agonists and antagonists on immune, regulation of the immune function in sepsis is complex and is time cardiac, metabolic and hemostasis functions during sepsis. A dependent. However, β activation as well as β blockade seems 2 1 comprehensive understanding of this complex regulation to downregulate proinflammatory response by modulating the β system will enable the clinician to better apprehend the cytokine production profile. 1 blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen impact of β-stimulants and β-blockers in septic patients. consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. β-Blockers could also β-Adrenergic receptor and signaling cascade be of interest in the systemic catabolic response to sepsis, as they The β-adrenergic receptor is a G-protein-coupled seven- oppose epinephrine which is known to promote hyperglycemia, transmembrane domain receptor. -
Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive
brain sciences Review Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype/Presentation: Research Progress and Translational Studies Ike C. de la Peña 1,* , Michael C. Pan 2,3, Chau Giang Thai 1 and Tamara Alisso 1 1 Department of Pharmaceutical and Administrative Sciences, Loma Linda University School of Pharmacy, Loma Linda, CA 92350, USA; [email protected] (C.G.T.); [email protected] (T.A.) 2 Department of Psychology, Korea University, Seoul 02841, Korea; [email protected] 3 Division of Social Sciences, University of the Philippines Visayas Tacloban College, Tacloban 6500, Philippines * Correspondence: [email protected]; Tel.: +1-909-651-5995; Fax: +1-909-558-0446 Received: 23 April 2020; Accepted: 9 May 2020; Published: 14 May 2020 Abstract: Research on the predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI) subtype/presentation is important given its high prevalence, but paradoxically it is under-recognized and undertreated. The temporal stability of the inattention symptom could impact the high worldwide prevalence of ADHD-PI. Some evidence suggests differences in the nature of attentional deficit in ADHD-PI vs. that in other subtypes. Impairments in neuropsychological, neurocognitive, and social functioning are also evident in ADHD-PI, which could be specific to the subtype (e.g., processing speed, social perception, and skills), or differ from others in severity. Neuroimaging studies have also revealed ADHD-PI-specific neuropathological abnormalities and those that are shared with other subtypes. ADHD-PI is highly comorbid with learning and internalizing (e.g., anxiety and depression) disorders. There is no solid evidence for ADHD-PI-specific genetic etiologies and differential responses of subtypes to ADHD medications. -
Shaffer CV 010419.Pdf
CURRICULUM VITAE Name: Thomas H. Shaffer, MS.E., Ph.D. Office Address: Temple University School of Medicine Department of Physiology 3420 North Broad Street Philadelphia, PA 19140 Office Address: Nemours Research Lung Center Department of Biomedical Research Alfred I. duPont Hospital for Children 1600 Rockland Road, A/R 302 Wilmington, DE 19803 Present Academic and Hospital Appointments: 2004 – Present Director, Nemours Center for Pediatric Research Nemours Biomedical Research Alfred I duPont Hospital for Children 1600 Rockland Road Wilmington, DE 19803 2001 - Present Associate Director , Nemours Biomedical Research Nemours Children’s Clinic – Wilmington of The Nemours Foundation Alfred I. duPont Hospital for Children, Wilmington, DE 19803 Director, Nemours Pediatric Lung Center Nemours Children's Clinic - Wilmington of The Nemours Foundation Alfred I. duPont Hospital for Children, Wilmington, DE Director, Office of Technology Transfer Nemours Children's Clinic - Wilmington of The Nemours Foundation Alfred I. duPont Hospital for Children, Wilmington, DE Professor, Pediatrics, Department of Pediatrics Thomas Jefferson University, College of Medicine, Philadelphia, PA 2001-Present Professor Emeritus, Physiology and Pediatrics, Departments of Physiology and Pediatrics Temple University School of Medicine, Philadelphia, PA 1 Training, Awards, Societies, and Membership: Education: 1963-1968 B.S. Mechanical Engineering, Drexel University, Philadelphia, PA 1968 Mathematics, Pennsylvania State University, State College, PA 1969-1970 MSE. Applied -
Management of Pain, Agitation and Delirium in The
Controversies in Septic Shock Jerry Altshuler, PharmD, BCPS, BCCCP MICU Clinical Pharmacy Specialist PGY-2 Critical Care Residency Program Director The Mount Sinai Hospital Drayton A. Hammond, PharmD, MBA, BCPS, BCCCP MICU Clinical Pharmacy Specialist PGY-2 Critical Care Residency Program Director Rush University Medical Center @hockeypharmd and @drdraymba Disclosure No disclosures to provide. Objectives At the completion of this activity, pharmacists will be able to: 1. Determine the role of vasopressin in septic shock 2. Recommend appropriate clinical settings for corticosteroids in septic shock 3. Explain strengths and limitations regarding current angiotensin II data At the completion of this activity, pharmacy technicians will be able to: 1. Identify advantages of vasopressin over catecholamine vasopressor 2. List endpoints that may be improved by corticosteroids in septic shock 3. Describe adverse events associated with angiotensin II Vasopressin: PRO (catecholamine-sparing & vasopressin-deficiency) Catecholamine-sparing Strategy • Catecholamine derivatives (e.g., NE, Epi) associated with adverse events and tachyphylaxis • Increased catecholamine exposure associated with cardiotoxicity and greater mortality Chest. 2013;143(3):664-71. Sepsis-induced Myocardial Dysfunction • Occurs in 25-50% of septic shock • Left and right ventricular dysfunction • Potential sequelae of substantially elevated catecholamine levels (adrenergic storm) • Resultant downregulation of β-adrenoceptors • Exogenous catecholamines (e.g., NE) ensure available β- adrenoceptors stimulation but other receptors may be better target Crit Care Med. 2009;13(5):230. Vasopressin (AVP) • Effects: vasoconstriction, ACTH release, water retention • Endogenous AVP production rises rapidly then sharply declines in septic shock • Exogenous AVP (0.03-0.06 units/min) may resolve this relative AVP-deficient state Crit Care Med. -
Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review)
REVIEWS Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical illness (Review) DOI: 10.17691/stm2020.12.4.12 Received October 25, 2019 Y.Y. Kiryachkov, MD, DSc, Head of the Department of Surgical and Resuscitation Technologies1; S.A. Bosenko, Anesthesiologist1; B.G. Muslimov, Deputy Chief Physician for Anesthesiology and Intensive Care2; M.V. Petrova, MD, DSc, Professor, Deputy Director1 1Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25, Bldg 2, Petrovka St., Moscow, 107031, Russia; 2Konchalovsky Central City Hospital, 2, Bldg 1, Kashtanovaya Alley, Zelenograd, Moscow, 124489, Russia Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis. The parasympathetic part of the ANS modifies the inflammation through cholinergic receptors of internal organs, macrophages, and lymphocytes (the cholinergic anti- inflammatory pathway). The sympathetic part of ANS controls the activity of macrophages and lymphocytes by influencing β2-adrenergic receptors, causing the activation of intracellular genes encoding the synthesis of cytokines (anti-inflammatory beta2-adrenergic receptor interleukin-10 pathway, β2AR–IL-10). The interaction of ANS with infectious agents and the immune system ensures the maintenance of homeostasis or the appearance of a critical generalized infection. During inflammation, the ANS participates in the inflammatory response by releasing sympathetic or parasympathetic neurotransmitters and neuropeptides. It is extremely important to determine the functional state of the ANS in critical conditions, since both cholinergic and sympathomimetic agents can act as either anti- or pro-inflammatory stimuli. -
Program, We Have Added a Few New Themes to the Program, Increasing the Number of These Concurrent Sessions to 12 in 2017
Co-Hosted by : WELCOME DELEGATES Welcome to the 4th Annual Canadian National Perinatal Research Meeting (CNPRM). We are delighted that you have all decided to join us for exciting and novel science and great fun at the Fairmont Montebello, Quebec! As you may know, although the CNPRM is only in its fourth year, Canadian perinatal researchers have been meeting yearly for nearly 40 years as Western and Eastern groups, and in February 2014 we came together to form a Canadian National meeting that was held in Banff. It was so successful that this new national annual format was adopted for the 2015 (Montebello) and 2016 (Banff) meetings and has formed the basis for the 2017 meeting as well. The 2017 meeting has achieved record numbers of registrants and trainees, which is evidence of Canada’s vibrant and growing perinatal research community, and our immense contribution to perinatal research and our role in the global effort of supporting and maintaining maternal and child health and policy. This year we have 384 registered delegates and 275 submitted abstracts (65 oral and 210 poster trainee presentations - A big thank you to all the members of the Thematic Committees who judged the submission). We also have three world-class international Plenary speakers, and for this year’s scientific program, we have added a few new themes to the program, increasing the number of these concurrent sessions to 12 in 2017. As in previous years, the meeting in 2017 will host two evening poster sessions; as well, for the first time this year, eight special interest workshop sessions will be included, with topics ranging from how to secure that first faculty position to topics such as neonatal feeding and improving neonatal care with the help of veteran parents. -
DRUGS POTENTIALLY AFFECTING MIBG UPTAKE Rev. 26 Oct 2009
DRUGS POTENTIALLY AFFECTING MIBG UPTAKE rev. 26 Oct 2009 EXCLUDED MEDICATIONS DUE TO DRUG INTERACTIONS WITH ULTRATRACE I-131-MIBG Drug Class Generic Drug Name Within Class Branded Name Checked Cocaine Cocaine □ Dexmethylphenidate Focalin, Focalin XR □ CNS Stimulants (Norepinephrine Reuptake Inhibitor) Methylphenidate Concerta, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin LA, □ Ritalin-SR, Daytrana benzphetamine Didrex □ Diethylpropion Tenuate, Tenuate Dospan □ Phendimetrazine Adipost, Anorex-SR, Appecon, Bontril PDM, Bontril Slow Release, Melfiat, Obezine, CNS Stimulants (Norepinephrine and Dopamine Reuptake Inhibitor) □ Phendiet, Plegine, Prelu-2, Statobex Phenteramine Adipex-P, Ionamin, Obenix, Oby-Cap, Teramine, Zantryl □ Sibutramine Meridia □ Isocarboxazid Marplan □ Linezolid Zyvox □ Phenelzine Nardil □ Monoamine Oxidase Inhibitors selegiline (MAOa at doses > 15 mg qd) Eldepryl, Zelapar, Carbex, Atapryl, Jumex, Selgene, Emsam □ Tranylcypromine Parnate □ Reserpine Generic only. No brands available. Central Monoamine Depleting Agent □ labetolol Non-select Beta Adrenergic Blocking Agents Normodyne, Trandate □ Opiod Analagesic Tramadol Ultram, Ultram ER □ Pseudoephedrine Chlor Trimeton Nasal Decongestant, Contac Cold, Drixoral Decongestant Non- Drowsy, Elixsure Decongestant, Entex, Genaphed, Kid Kare Drops, Nasofed, Sympathomimetics : Direct Alpha 1 Agonist (found in cough/cold preps) Seudotabs, Silfedrine, Sudafed, Sudodrin, SudoGest, Suphedrin, Triaminic Softchews □ Allergy Congestion, Unifed amphetamine (various -
Liquid Ventilation
Oman Medical Journal (2011) Vol. 26, No. 1: 4-9 DOI 10. 5001/omj.2011.02 Review Article Liquid Ventilation Qutaiba A. Tawfic, Rajini Kausalya Received: 14 Aug 2010 / Accepted: 23 Nov 2010 © OMSB, 2011 Abstract 1-3,5 Mammals have lungs to breathe air and they have no gills to normal, premature and with lung injury. breath liquids. When the surface tension at the air-liquid Two primary techniques for liquid-assisted ventilation have interface of the lung increases, as in acute lung injury, scientists emerged; total liquid ventilation and partial liquid ventilation.1 started to think about filling the lung with fluid instead of air While total liquid ventilation remains as an experimental to reduce the surface tension and facilitate ventilation. Liquid technique, partial liquid ventilation could be readily applied, but ventilation (LV) is a technique of mechanical ventilation in which its implementation in clinical practice awaits results from ongoing the lungs are insufflated with an oxygenated perfluorochemical and future clinical trials that may define its effectiveness.6 liquid rather than an oxygen-containing gas mixture. The use The PFC liquids used to support pulmonary gas exchange are of perfluorochemicals, rather than nitrogen, as the inert carrier a type of synthetic liquid fluorinated hydrocarbon (hydrocarbons of oxygen and carbon dioxide offers a number of theoretical with the hydrogen replaced by fluorine, and for perflubron where advantages for the treatment of acute lung injury. In addition, a bromine atom is added as well) with high solubility for oxygen there are non-respiratory applications with expanding potential and carbon dioxide.3 These are chemically and biologically inert, including pulmonary drug delivery and radiographic imaging.