DOCSLIB.ORG

32120 Journal.Qxd

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
32120 Journal.Qxd SLEEP PHYSIOLOGY Prostaglandin D Synthase (β-trace) in Healthy Human Sleep Wolfgang Jordan, MD1; Hayrettin Tumani, MD, PhD2; Stefan Cohrs, MD1; Sebastian Eggert1; Andrea Rodenbeck, DSc1; Edgar Brunner, MD, PhD3; Eckart Rüther, MD, PhD1; Göran Hajak, MD, PhD1,4 1Department of Psychiatry and Psychotherapy, University of Göttingen; 2Department of Neurology, Universitiy of Ulm; 3Department of Medical Statistics, University of Göttingen; 4Department of Psychiatry and Psychotherapy, University of Regensburg, Germany Study Objectives: The prostaglandin D system plays an important role in Results: Serum L-PGDS concentrations showed marked time-dependent animal sleep. In humans, alterations in the prostaglandin D system have changes with evening increases and the highest values at night (P< been found in diseases exhibiting sleep disturbances as a prominent .0005). This nocturnal increase was suppressed during total sleep depri- symptom, such as trypanosoma infection, systemic mastocytosis, bacteri- vation (P< .05), independent of external light conditions and melatonin Downloaded from https://academic.oup.com/sleep/article/27/5/867/2708439 by guest on 28 September 2021 al meningitis, major depression, or obstructive sleep apnea. Assessment secretion. Rapid eye movement sleep deprivation had no impact on cir- of this system’s activity in relation to human physiologic sleep was the tar- culating L-PGDS levels. get of the present study. Conclusions: The circadian L-PGDS pattern and its suppression by total Design: Serum concentrations of lipocalin-type prostaglandin D synthase sleep deprivation indicate an interaction of the prostaglandin D system (L-PGDS, former β-trace), and plasma levels of the pineal hormone mela- and human sleep regulation. L-PGDS measurements may well provide tonin were measured in 20 healthy humans (10 women, 10 men; aged: new insights into physiologic and pathologic sleep regulation in humans. 23.3 ± 2.39 years) at 4-hour intervals over a period of 5 days and nights, Abbreviations: CSF,cerebrospinal fluid; L-PGDS, lipocalin-type which included physiologic sleep, rapid eye movement sleep deprivation, prostaglandin-D-synthase; PGD2, prostaglandin D2; REM, rapid eye and total sleep deprivation. In addition, the serum L-PGDS and plasma movement; SWS, slow wave sleep melatonin levels of 6 subjects were determined under conditions of bright Key Words: Lipocalin-type prostaglandin D synthase (EC 5.3.99.2), β- white (10,000 lux) or dark red light (< 50 lux) in a crossover design during trace, PGD2, melatonin, human physiologic sleep regulation, sleep depri- total sleep deprivation. Nocturnal blood sampling was performed by a vation, hypersomnia through-the-wall tube system. L-PGDS was measured by an automated Citation: Jordan W; Tumani H; Cohrs S et al. Prostaglandin D synthase immunonephelometric assay, and melatonin was analyzed by direct (β-trace) in healthy human sleep. SLEEP 2004;27(5):867-874. radioimmunoassay. INTRODUCTION Additionally, the impact of the prostaglandin D system on sleep regulation could also be demonstrated in primates.17 In humans, PROSTAGLANDINS ARE UBIQUITOUSLY DISTRIBUTED the prostaglandin D system seems to be involved in several dis- IN VIRTUALLY ALL MAMMALIAN TISSUES AND eases presenting hypersomnia as a prominent symptom, such as ORGANS.Prostaglandin D (PGD ) is unique among the 2 2 African sleeping sickness,18 systemic mastocytosis,19 or severe prostaglandins in being present in relatively high concentrations obstructive sleep apnea syndrome.20 Alterations in the in the mammalian brain. Among the 3 enzymes catalyzing the prostaglandin D system have been also associated with bacterial conversion of prostaglandin H2 to PGD2, the lipocalin-type meningitis21 or major depression,22,23 which are usually accom- prostaglandin D synthase (L-PGDS) (Enzyme Commission panied by sleep disturbances. However, the prostaglandin D sys- Number: EC 5.3.99.2) is responsible for the biosynthesis of tem has not yet been investigated in human physiologic sleep. PGD2 in the brain. L-PGDS itself is mainly synthesized in the Therefore, serum L-PGDS and plasma melatonin, a known deter- choroid plexus, leptomeninges, and oligodendrocytes of the cen- minant of the sleep-wake rhythm, were simultaneously measured tral nervous system and is secreted into the cerebrospinal fluid in healthy subjects during physiologic sleep and in conditions of (CSF).1,2 Based on the results of amino-acid sequencing, L- total and rapid eye movement (REM) sleep deprivation. PGDS has been identified as β-trace.3,4 β-trace is the second most abundant protein in human CSF after albumin, representing 8% METHODS of the total CSF protein.4 A 32:1 CSF-serum concentration gradi- ent indicates that the β-trace protein in the serum originates pre- Study Subjects 5 dominantly from the brain. The study was approved by the local Research Ethical A large number of studies has demonstrated a crucial role for Committee. A total of 20 medical students (10 women, 10 men; 2,6-16 the prostaglandin D system in rodent sleep regulation. mean age ± SD 23.3 ± 2.39 years) were included in the study after obtaining their written informed consent. All were nor- Disclosure Statement motensive and found to be healthy by medical history and phys- No significant financial interest/other relationship to disclose. ical examination. In particular, they had no history of smoking, drug intake, affective disorder, allergy, hypertension, or pul- Submitted for publication September 2003 monary, renal, neurologic, or cerebrovascular disease. Routine Accepted for publication February 2004 laboratory tests included blood cell count, coagulating properties, Address correspondence to: Dr. W. Jordan, Department of Psychiatry and electrolytes, liver enzymes, creatinine, and urea. Normal renal Psychotherapy, Georg-August-University of Göttingen, von Sieboldstr. 5, 37075 function was assessed by serum and urine creatinine and noctur- Göttingen, Germany; Tel: 49 551 396761; Fax: 49 551 393887; nal creatinine clearance. Absence of any inflammation was con- E-mail: [email protected] SLEEP, Vol. 27, No. 5, 2004 867 Prostaglandin D Synthase (β-trace) in Healthy Human Sleep—Jordan et al firmed by laboratory results. Screening of volunteers involved Behring Nephelometer Analyzer (BNA). The test kit employs blood-pressure determination, electrocardiogram, electroen- affinity-purified polyclonal rabbit antibodies coupled to latex cephalogram, and polysomnography. Subjects with more than 10 particles and is sensitive enough (analytical sensitivity of 0.05 sleep-related breathing disturbances or more than 5 periodic leg mg/L) to reliably measure serum concentrations. The interassay movements per hour were excluded from the investigation. coefficient of variation of a control sample was 4.7% at 0.262 ± During the entire study period, subjects stayed in the sleep lab- 0.012 mg/L. The validity data of the L-PGDS assay have been oratory and were given a protein-carbohydrate balanced lunch reported previously.20,21 and a light morning and evening meal, which was a standardized Plasma melatonin concentrations were measured by direct feature of the study. The mealtimes remained unchanged during radioimmunoassay using a highly specific antibody (GS 704- total sleep deprivation; this included overnight fasting until after 6483) from Guildhay antisera (Guildford, United Kingdom). The the morning blood sampling. detection limit of this assay (at which 5% of the ligand is dis- placed) was 3.33 pg/mL. Intraassay and interassay variance were Study Design 6% and 12%, respectively.26 Concentrations of serum L-PGDS and plasma melatonin were Downloaded from https://academic.oup.com/sleep/article/27/5/867/2708439 by guest on 28 September 2021 Analysis measured in 20 healthy subjects at 4-hour intervals (4:00 PM, 8:00 PM, midnight, 4:00 AM, 8:00 AM, and noon) over a period Sleep stages and arousal data were manually determined in 30- of 5 days and nights covering physiologic sleep (baseline), REM second epochs and added to the data stored on a personal com- sleep deprivation, and total sleep deprivation, as well as a recov- puter system. Standard parameters included time in bed, sleep ery night between the nights of sleep deprivation. Sleep was period time (time from sleep onset to final awakening), total polysomnographically monitored every night except for the night sleep time (sleep period time minus time spent awake), sleep effi- of total sleep deprivation. Overnight cardiorespiratory ciency (total sleep time divided by the time in bed), percentage polysomnography followed international guidelines using stan- wake of sleep period time, sleep latencies to stage 2 sleep and dard methods.24,25 All recordings were made on a polysomno- slow wave sleep (SWS), REM latency (time from first epoch of graph (Nihon Kohden; Tokyo, Japan) and simultaneously stored stage 2 sleep until the first epoch of REM sleep), percentage of on a personal computer system (Sagura Polysomnograph 2000, sleep stages (stage 1, stage 2, SWS, REM sleep) of total sleep Sagura Medizintechnik GmbH, 63165 Mühlheim, Germany). time, REM sleep duration, and total number of transitions from Each session started with an adaptation night with the complete sleep stages. In order to get more information about the efficien- montage for polysomnographic recordings, followed by baseline cy of the REM sleep deprivation induced by acoustic stimuli, sleep during which sequential blood sampling started. Nocturnal REM sleep duration per number of transitions were
Load more

Recommended publications
  • Prostaglandin D2 Synthase: Apoptotic Factor in Alzheimer Plasma, Inducer of Reactive Oxygen Species, Inflammatory Cytokines and Dialysis Dementia
    www.nephropathol.com DOI:10.12860/JNP.2013.28 J Nephropathology. 2013; 2(3): 166-180 Journal of Nephropathology Prostaglandin D2 synthase: Apoptotic factor in alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines and dialysis dementia John K. Maesaka1,*, Bali Sodam1, Thomas Palaia1, Louis Ragolia1,Vecihi Batuman2, Nobuyuki Miyawaki 1, Shubha Shastry1, Steven Youmans3, Marwan El-Sabban4 1Department of Medicine, Winthrop-University Hospital, Mineola, N.Y., SUNY Medical School at Stony Brook, N.Y. USA. 2Department of Medicine, Tulane University School of Medicine. USA. 3Department of Biomedical Sciences, New York Institute of Technology, Westbury, N.Y. USA. 4Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon. ARTICLE INFO ABSTRACT Article type: Background: Apoptosis, reactive oxygen species (ROS) and inflammatory cytokines Original Article have all been implicated in the development of Alzheimer’s disease (AD). Article history: Objectives: The present study identifies the apoptotic factor that was responsible Received: 7 February 2013 for the fourfold increase in apoptotic rates that we previously noted when pig Accepted: 1 March 2013 proximal tubule, LLC-PK1, cells were exposed to AD plasma as compared to Published online: 1 July 2013 plasma from normal controls and multi-infarct dementia. Patients and Methods: The apoptotic factor was isolated from AD urine and identi- fied as lipocalin-type prostaglandin D2 synthase (L-PGDS). L-PGDS was found Keywords: Original Article Dialysis Dementia to be the major apoptotic factor in AD plasma as determined by inhibition of Alzheimer’s disease apoptosis approximating control levels by the cyclo-oxygenase (COX) 2 inhibitor, Apoptosis NS398, and the antibody to L-PGDS.
    [Show full text]
  • 615 Neuroscience-Cayman-Bertin
    Thomas G. Brock, Ph.D. Introduction to Neuroscience In our first Biology classes, we learned that lipids form the membranes around cells. For many students, interests quickly moved to the intracellular constituents ‘that really matter’, or to how cells or systems work in health and disease. If there was further thought about lipids, it might have been limited to more personal issues, like an expanding waistline. It was easy to forget about lipids in the complexities of, say, Alzheimer’s Disease, where tau protein is hyperphosphorylated by a host of kinases before forming neurofibrillary tangles and amyloid precursor protein is processed by assorted secretases, ultimately aggregating to form neurodegenerating plaques. What possible role could lipids have in all this? After all, lipids just form the membranes around cells. Fortunately, neuroscientists study complex systems. Whether working at the molecular, cellular, or organismal level, the research focus always returns to the intricately interconnected bigger picture. Perhaps surprisingly, lipids keep emerging as part of the bigger picture. At least, the smaller lipids do. Many of the smaller lipids, including the cannabinoids and eicosanoids, act as paracrine hormones, modulating cell functions in a receptor-mediated fashion. In this sense, they are rather like the peptide hormones in their diversity and actions. In the neurosystem, this means that these signaling lipids determine if synapses fire or not, when cells differentiate or die, and whether tissues remain healthy or become inflamed. Returning to the question posed above about lipids in Alzheimer’s, these mediators have roles at many levels in the course of the disease, as presented in an article on page 42 of this catalog.
    [Show full text]
  • Midwives Exemption and Administration of Medicines by Midwives Guideline
    Midwives Exemption and Administration of Medicines by Midwives Guideline Document Control Title Midwives Exemptions and Administration of Medicines by Midwives Guideline Author Author’s job title Lead Pharmacist Women’s and Children’s Directorate Department Women’s and Children’s Maternity Services Date Version Status Comment / Changes / Approval Issued Mar 0.1 Draft Amended following consultation 2009 Feb To DTG -to be reformulated into trust template and 0.3 Draft 2010 amendments needed Sep 0.6 Draft Agreed to amend list to comply with DTG 2010 Nov Ratified by DTG with minor amendments to 0.7 Draft 2010 nomenclature for rhesus negative Nov Meeting with Frances Goodhind (Pharmacist) and review 1.0 Ratified 2010 of Midwives exemptions Meeting with Rachel Nestel (Pharmacist) and review of Sep Review 1.2 Midwives exemptions. Co-codamol no longer used and 2013 and Draft has been removed Jan Reviewed by DTC and changes requested re doses of 1.3 Draft 2014 Anti D injections Changes made as requested by DTC, Anti D doses Oct 1.4 Draft reviewed with Maggie Webb (Blood Bank Manager) 2014 Hartmann’s removed, Ibuprofen and Instillagel added Oct 1.5 Draft Changes made to format by Rachel Nestel 2014 Nov 2.0 Ratified Ratified by DTG 2014 Reviewed by J Self & A Patel. Reference added in re student midwives. Removed Anusol, Carboprost, Oct 2.1 Review Pethidine, Peptac. Amended oxytocin & sodium chloride 2017 0.9% entries. Change in author Reviewed by Maternity Guidelines group Nov 2.2 Draft Review by DTC 2017 Dec 2.3 Draft Responded to DTC feedback
    [Show full text]
  • Dentists Knowledge About Over the Counter-Nsaids: an Emerging Need for NSAID-Avoidance Education
    Journal of Applied Pharmaceutical Science Vol. 10(1), pp 070-076, January, 2020 Available online at http://www.japsonline.com DOI: 10.7324/JAPS.2020.101009 ISSN 2231-3354 Dentists knowledge about over the counter-NSAIDs: An emerging need for NSAID-avoidance education Malvina Hoxha1*, Visar Malaj2, Erila Spahiu3, Mishel Spahiu3 1Department of Chemical, Toxicological and Pharmacological Evaluation of Drugs, Catholic University Our Lady of Good Counsel, Tirana, Albania. 2Department of Economics, Faculty of Economics, University of Tirana, Rruga Arben Broci, Tirana, Albania. 3Spahiu Dental Clinic, Rruga Him Kolli, Tirana, Albania. ARTICLE INFO ABSTRACT Received on: 21/08/2019 Objectives of the study: Non-steroidal anti-inflammatory drugs (NSAIDs) belong to a group of drugs used in the Accepted on: 12/10/2019 management of pain. The aim of this study is to assess dentists’ knowledge of NSAIDs risks and to determine the most Available online: 03/01/2020 prescribed NSAIDs by dentists. Materials and Methods: We collected information concerning the dentists’ knowledge of NSAIDs use and adverse effects. A questionnaire consisting of 22 questions was distributed to 123 Albanian dentists reached in different dental Key words: clinics, out of which only 87 agreed to participate. Only 70.73% of the distributed questionnaires were completed. Dentist, education, Results: Respondents demonstrated poor knowledge of NSAIDs. Most of the respondents did not respond correctly knowledge, non-steroidal to the questions with 39.08% of incorrect answers regarding the implications of NSAIDs in elderly patients and only anti-inflammatory drugs, 3.44% responded correctly to the contraindication of NSAIDs. The most common prescriptions were ketoprofen, risk factors, pain, survey.
    [Show full text]
  • A Systematic Review on the Role of Eicosanoid Pathways in Rheumatoid Arthritis
    Advances in Medical Sciences 63 (2018) 22–29 Contents lists available at ScienceDirect Advances in Medical Sciences journal homepage: www.elsevier.com/locate/advms Review article A systematic review on the role of eicosanoid pathways in rheumatoid arthritis a,b, Malvina Hoxha * a Department of Chemical-Toxicological and Pharmacological Evaluation of Drugs, Catholic University Our Lady of Good Counsel, Tirana, Albania b Department of Pharmacological and Biomolecular Sciences, Università degli studi di Milano, Milan, Italy A R T I C L E I N F O A B S T R A C T Article history: Background: Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion Received 28 March 2017 molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the Accepted 18 June 2017 cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, Available online 14 August 2017 however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid Keywords: arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the Rheumatoid arthritis corticosteroids, the NSAIDs and biological agents. Inflammation Methods: PubMed, Cochrane, and Embase electronic database were used as the main sources for Arachidonic acid pathway extracting several articles, reviews, original papers in English for further review and analysis on the Prostaglandins Leukotrienes implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients.
    [Show full text]
  • Apolipoprotein D Overexpression Alters Hepatic Prostaglandin and Omega Fatty 2 Acid Metabolism During the Development of a Non-Inflammatory Hepatic Steatosis
    1 Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty 2 acid metabolism during the development of a non-inflammatory hepatic steatosis 3 Frederik Desmarais, Karl-F. Bergeron, Eric Rassart, Catherine Mounier 4 Molecular Metabolism of Lipids Laboratory, BioMed Research Center, Biological Sciences 5 Department, University of Quebec in Montreal (UQAM) 6 7 8 Abstract 9 Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid 10 metabolism. Overexpression of ApoD in mouse neural tissue induces the development of a non- 11 inflammatory hepatic steatosis in 12-month-old transgenic animals. Previous data indicates that 12 accumulation of arachidonic acid, ApoD’s preferential ligand, and overactivation of PPARγ are 13 likely the driving forces in the development of the pathology. However, the lack of inflammation 14 under those conditions is surprising. Hence, we further investigated the apparent repression of 15 inflammation during hepatic steatosis development in aging transgenic animals. The earliest 16 modulation of lipid metabolism and inflammation occurred at 6 months with a transient 17 overexpression of L-PGDS and concomitant overproduction of 15d-PGJ2, a PPARγ agonist. 18 Hepatic lipid accumulation was detectable as soon as 9 months. Inflammatory polarization 19 balance varied in time, with a robust anti-inflammatory profile at 6 months coinciding with 15d- 20 PGJ2 overproduction. Omega-3 and omega-6 fatty acids were preferentially stored in the liver of 21 12-month-old transgenic mice and resulted in a higher omega-3/omega-6 ratio compared to wild 22 type mice of the same age. Thus, inflammation seems to be controlled by several mechanisms 23 in the liver of transgenic mice: first by an increase in 15d-PGJ2 production and later by a 24 beneficial omega-3/omega-6 ratio.
    [Show full text]
  • New Insights Into the Use of Currently Available Non-Steroidal Anti-Inflammatory Drugs
    Journal of Pain Research Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW New insights into the use of currently available non-steroidal anti-inflammatory drugs Kay Brune1 Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the Paola Patrignani2 cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and 1Department of Experimental and Clinical Pharmacology and COX-2 isozymes have different biological functions; analgesic activity is primarily (although Toxicology, Friedrich-Alexander not exclusively) associated with inhibition of COX-2, while different side effects result from University Erlangen-Nuremberg, Erlangen, Germany; 2Department of the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and Neuroscience, Imaging and Clinical aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular Sciences, Center of Excellence on effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their Aging, G d’Annunzio University, Chieti, Italy therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination), and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (∼80% inhibition of COX-2) while minimizing COX-1 inhibition and associ- ated side effects, such as gastrointestinal toxicity.
    [Show full text]
  • (Я-Trace) in Human Arachnoid and Meningioma Cells
    The Journal of Neuroscience, April 1, 1997, 17(7):2376–2382 Prostaglandin D Synthase (b-Trace) in Human Arachnoid and Meningioma Cells: Roles as a Cell Marker or in Cerebrospinal Fluid Absorption, Tumorigenesis, and Calcification Process Tetsumori Yamashima,1 Kazushige Sakuda,1 Yasuo Tohma,1 Junkoh Yamashita,1 Hiroshi Oda,2 Daisuke Irikura,3 Naomi Eguchi,4 Carsten T. Beuckmann,3 Yoshihide Kanaoka,3 Yoshihiro Urade,3 and Osamu Hayaishi3 1Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa 920, Japan, 2Department of Biological Chemistry, Central Research Institute, Maruha Corporation, Tsukuba 300-42, Japan, 3Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565, Japan, and 4Department of Precursory Research for Embryonic Science and Technology, Osaka 590-02, Japan Glutathione-independent prostaglandin D synthase (PGDS) is tron microscopic data, when compared with the ultrastructure, an enzyme responsible for biosynthesis of prostaglandin D2 in showed that PGDS was localized at rough endoplasmatic re- the CNS and is identical to a major cerebrospinal fluid protein, ticulum of arachnoid and meningioma cells. Western blot b-trace. Although PGDS has been identified recently in rat showed a 29 kDa immunoreactive band indicating PGDS, but leptomeninges, little information is available about human me- the extent of expression was variable from case to case, which ninges or meningiomas. Here, we report PGDS to be expressed was compatible with immunohistochemical data. RT-PCR re- consistently in 10 human arachnoid and arachnoid villi and in vealed PGDS gene expression in all meningiomas studied, 21 meningiomas by immunohistochemistry, Western blot, and regardless of histological subtypes, and also in human arach- reverse transcription (RT)-PCR analyses.
    [Show full text]
  • Review Article Omega-3 Pufas Lower the Propensity for Arachidonic Acid Cascade Overreactions
    Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 285135, 8 pages http://dx.doi.org/10.1155/2015/285135 Review Article Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions Bill Lands 6100WestchesterParkDrive,Apartment1219,CollegePark,MD20740,USA Correspondence should be addressed to Bill Lands; [email protected] Received 22 September 2014; Revised 18 December 2014; Accepted 22 December 2014 Academic Editor: Achille Cittadini Copyright © 2015 Bill Lands. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid hasa very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes.
    [Show full text]
  • Effects of Conjugated Linoleic Acid Isomers on Eicosanoid Metabolism in Kidney
    Effects of Conjugated Linoleic Acid Isomers on Eicosanoid Metabolism in Kidney and Liver Tissues of Obese Zucker Rats by Hong Shi A Thesis submitted to the Faculty of Graduate Studies of The University of Manitoba in partial fulfilment of the requirements of the degree of MASTER OF SCIENCE Department of Human Nutritional Sciences University of Manitoba Winnipeg Copyright © 2011 by Hong Shi TABLE OF CONTENTS ABSTRACT .................................................................................................................... v ACKNOWLEDGEMENTS ......................................................................................... vi LISTOF ABBREVIATIONS ....................................................................................... vii LIST OF TABLES ......................................................................................................... xi LIST OF FIGURES .................................................................................................... xiii INTRODUCTION.......................................................................................................... 1 1. LITERATURE REVIEW .......................................................................................... 1 1-A. Introduction ..................................................................................................... 1 1-A-1. Inflammation – disease link ................................................................. 2 1-A-1-1. Inflammation ................................................................................
    [Show full text]
  • Prostaglandin D Synthase in the Prenatal Ovine Brain and Effects of Its Inhibition with Selenium Chloride on Fetal Sleep/Wake Activity in Utero
    The Journal of Neuroscience, July 1, 2002, 22(13):5679–5686 Prostaglandin D Synthase in the Prenatal Ovine Brain and Effects of Its Inhibition with Selenium Chloride on Fetal Sleep/Wake Activity In Utero Brenda Lee, Jonathan J. Hirst, and David W. Walker Department of Physiology, Monash University, Clayton, Melbourne, Victoria, Australia, 3800 It has been proposed that prostaglandin (PG) D2 induces phys- breathing movements during low-amplitude electrocortical ac- iological sleep in mammals by acting on sleep centers located tivity, increased from 3.8 Ϯ 1 min/hr to 6.6 Ϯ 0.5 and 7.0 Ϯ 0.3 in the anterior hypothalamus. In fetal sheep, definitive rapid- min/hr at doses of 100 and 500 pmol/min, respectively ( p Ͻ eye-movement and non-rapid-eye-movement sleep states ap- 0.05). SeCl4 at 25 and 1000 pmol/min had no significant effect ϳ ϳ pear at 125 d gestation (term is 147 d). In adult animals, on arousal activity. Infusion of PGD2 at 500 pmol/min intracere- PGD synthase (PGDS) (functionally and structurally homolo- broventricularly for 4 hr decreased the incidence of arousal gous to ␤-trace protein) is secreted into CSF with a circadian from 3.8 Ϯ 0.5 min/hr to 0.7 Ϯ 0.3 min/hr ( p Ͻ 0.05). When 500 pattern, with the highest concentrations present during sleep. pmol/min PGD2 was infused immediately aftera4hrinfusion of ␤ In this study we show that PGDS/ -trace protein is present in SeCl4 (500 pmol/min), the SeCl4-induced increase in arousal fetal sheep CSF at 125 and 135 d gestation but not at 90 d behavior was abolished.
    [Show full text]
  • Applied Pharmaceutical Practice APP Prelims 22/8/08 1:15 Pm Page 2 APP Prelims 22/8/08 1:15 Pm Page 3
    APP prelims 22/8/08 1:15 pm Page 1 Applied Pharmaceutical Practice APP prelims 22/8/08 1:15 pm Page 2 APP prelims 22/8/08 1:15 pm Page 3 Applied Pharmaceutical Practice Christopher A Langley Senior Lecturer in Pharmacy Practice Aston University School of Pharmacy, Birmingham, UK and Dawn Belcher Teaching Fellow, Pharmacy Practice, Aston University School of Pharmacy, Birmingham, UK London • Chicago APP prelims 22/8/08 1:15 pm Page 4 Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Grayslake, IL 60030–7820, USA © Pharmaceutical Press 2009 is a trade mark of RPS Publishing RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great Britain First published 2009 Typeset by Photoprint Typesetters, Torquay, Devon Printed in Great Britain by Cambridge University Press, Cambridge ISBN 978 0 85369 746 6 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without the prior written permission of the copyright holder. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. The right of Christopher A Langley and Dawn Belcher to be identified as the authors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988. A catalogue record for this book is available from the British Library.
    [Show full text]