Phosphatidylcholine
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Role of Citicoline in the Management of Traumatic Brain Injury
pharmaceuticals Review Role of Citicoline in the Management of Traumatic Brain Injury Julio J. Secades Medical Department, Ferrer, 08029 Barcelona, Spain; [email protected] Abstract: Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is a need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements in the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Moreover, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline is able to accelerate the recovery of consciousness and to improve the outcome of this kind of patient, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI. Keywords: CDP-choline; citicoline; pharmacological neuroprotection; brain ischemia; traumatic brain injury; head injury Citation: Secades, J.J. Role of 1. Introduction Citicoline in the Management of Traumatic brain injury (TBI) is among the most devastating types of injury and can Traumatic Brain Injury. result in a different profile of neurological and cognitive deficits, and even death in the most Pharmaceuticals 2021, 14, 410. -
Cell Membrane
John Lenyo Corrina Perez Hazel Owens Cell Membrane http://micro.magnet.fsu.edu/cells/plasmamembrane/plasmamembrane.html • Cell membranes are composed of proteins and lipids. • Since they are made up of mostly lipids, only certain substances can move through. spmbiology403.blogspot.com •Phospholipids are the most abundant type of lipid found in the membrane. Phospholipids are made up of two layers, the outer and inner layers. The inside layer is made of hydrophobic fatty acid tails, while the outer layer is made up of hydrophilic polar heads that are pointed toward the water. academic.brooklyn.cuny.edu •Membrane structure relies on the tendency of fatty acid molecules to spread on the surface of water. • Membrane proteins (which take up half of the membrane) determine what gets into and leaves the cell. •Glycolipids are found on the outer part of the cell membrane. Single Chain vs. Phospholipid • Single chain lipids were assumed to be the first of those to form cell membranes with the more complex phospholipids evolving later • Phospholipids can be synthesized in an abiotic environment without enzymes now • Phosphoplipid bilayers now make up the plasma cell membranes that regulate movement into and out of prokaryotic and eukaryotic cells. Single chain lipid http://web.nestucca.k12.or.us/nvhs/staff/whitehead/homewor http://clincancerres.aacrjournals.org/content/11/5/2018/F1. k.htm expansion Types of Lipids • Today Plasma Membranes are made primarily of phospholipids • It is thought that early membranes may have been made of simpler fatty acids. http://exploringorigins.org/fattyacids.html Properties of Fatty Acids • They are Ampipathic, meaning that they have a hydrophobic (“water hating”) end and a hydrophilic (water loving”) end. -
Endoplasmic Reticulum-Plasma Membrane Contact Sites Integrate Sterol and Phospholipid Regulation
RESEARCH ARTICLE Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation Evan Quon1☯, Yves Y. Sere2☯, Neha Chauhan2, Jesper Johansen1, David P. Sullivan2, Jeremy S. Dittman2, William J. Rice3, Robin B. Chan4, Gilbert Di Paolo4,5, Christopher T. Beh1,6*, Anant K. Menon2* 1 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada, 2 Department of Biochemistry, Weill Cornell Medical College, New York, New York, United States of a1111111111 America, 3 Simons Electron Microscopy Center at the New York Structural Biology Center, New York, New a1111111111 York, United States of America, 4 Department of Pathology and Cell Biology, Columbia University College of a1111111111 Physicians and Surgeons, New York, New York, United States of America, 5 Denali Therapeutics, South San a1111111111 Francisco, California, United States of America, 6 Centre for Cell Biology, Development, and Disease, Simon a1111111111 Fraser University, Burnaby, British Columbia, Canada ☯ These authors contributed equally to this work. * [email protected] (AKM); [email protected] (CTB) OPEN ACCESS Abstract Citation: Quon E, Sere YY, Chauhan N, Johansen J, Sullivan DP, Dittman JS, et al. (2018) Endoplasmic Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation. PLoS creating contact sites that are proposed to form platforms for regulating lipid homeostasis Biol 16(5): e2003864. https://doi.org/10.1371/ and facilitating non-vesicular lipid exchange. Sterols are synthesized in the ER and trans- journal.pbio.2003864 ported by non-vesicular mechanisms to the plasma membrane (PM), where they represent Academic Editor: Sandra Schmid, UT almost half of all PM lipids and contribute critically to the barrier function of the PM. -
Acetylcholine Signaling System in Progression of Lung Cancers
Pharmacology & Therapeutics 194 (2019) 222–254 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Acetylcholine signaling system in progression of lung cancers Jamie R. Friedman a,1, Stephen D. Richbart a,1,JustinC.Merritta,KathleenC.Browna, Nicholas A. Nolan a, Austin T. Akers a, Jamie K. Lau b, Zachary R. Robateau a, Sarah L. Miles a,PiyaliDasguptaa,⁎ a Department of Biomedical Sciences, Joan C. Edwards School of Medicine, 1700 Third Avenue, Huntington, WV 25755 b Biology Department, Center for the Sciences, Box 6931, Radford University, Radford, Virginia 24142 article info abstract Available online 3 October 2018 The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline Keywords: transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyl- Lung cancer transferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetyl- Acetylcholine cholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic Cholinergic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components Proliferation of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend Invasion Anti-cancer drugs is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic ciga- rettes considered by many as a “safe” alternative to smoking. -
An Overview of Lipid Membrane Models for Biophysical Studies
biomimetics Review Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies Alessandra Luchini 1 and Giuseppe Vitiello 2,3,* 1 Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark; [email protected] 2 Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Piazzale Tecchio 80, 80125 Naples, Italy 3 CSGI-Center for Colloid and Surface Science, via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy * Correspondence: [email protected] Abstract: Cell membranes are very complex biological systems including a large variety of lipids and proteins. Therefore, they are difficult to extract and directly investigate with biophysical methods. For many decades, the characterization of simpler biomimetic lipid membranes, which contain only a few lipid species, provided important physico-chemical information on the most abundant lipid species in cell membranes. These studies described physical and chemical properties that are most likely similar to those of real cell membranes. Indeed, biomimetic lipid membranes can be easily prepared in the lab and are compatible with multiple biophysical techniques. Lipid phase transitions, the bilayer structure, the impact of cholesterol on the structure and dynamics of lipid bilayers, and the selective recognition of target lipids by proteins, peptides, and drugs are all examples of the detailed information about cell membranes obtained by the investigation of biomimetic lipid membranes. This review focuses specifically on the advances that were achieved during the last decade in the field of biomimetic lipid membranes mimicking the mammalian plasma membrane. In particular, we provide a description of the most common types of lipid membrane models used for biophysical characterization, i.e., lipid membranes in solution and on surfaces, as well as recent examples of their Citation: Luchini, A.; Vitiello, G. -
Membrane Proteins Are Associated with the Membrane of a Cell Or Particular Organelle and Are Generally More Problematic to Purify Than Water-Soluble Proteins
Strategies for the Purification of Membrane Proteins Sinéad Marian Smith Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland. Email: [email protected] Abstract Although membrane proteins account for approximately 30 % of the coding regions of all sequenced genomes and play crucial roles in many fundamental cell processes, there are relatively few membranes with known 3D structure. This is likely due to technical challenges associated with membrane protein extraction, solubilization and purification. Membrane proteins are classified based on the level of interaction with membrane lipid bilayers, with peripheral membrane proteins associating non- covalently with the membrane, and integral membrane proteins associating more strongly by means of hydrophobic interactions. Generally speaking, peripheral membrane proteins can be purified by milder techniques than integral membrane proteins, whose extraction require phospholipid bilayer disruption by detergents. Here, important criteria for strategies of membrane protein purification are addressed, with a focus on the initial stages of membrane protein solublilization, where problems are most frequently are encountered. Protocols are outlined for the successful extraction of peripheral membrane proteins, solubilization of integral membrane proteins, and detergent removal which is important not only for retaining native protein stability and biological functions, but also for the efficiency of downstream purification techniques. Key Words: peripheral membrane protein, integral membrane protein, detergent, protein purification, protein solubilization. 1. Introduction Membrane proteins are associated with the membrane of a cell or particular organelle and are generally more problematic to purify than water-soluble proteins. Membrane proteins represent approximately 30 % of the open-reading frames of an organism’s genome (1-4), and play crucial roles in basic cell functions including signal transduction, energy production, nutrient uptake and cell-cell communication. -
Alpha-GPC Introduced 2003
Product Information Sheet – January 2015 Alpha-GPC Introduced 2003 What Is It? Are There Any Potential Drug Interactions? l-Alpha-glycerophophatidylcholine (GPC-choline, alpha-GPC) is a water- At this time, there are no known adverse reactions when taken in soluble phospholipid and neurotransmitter precursor naturally conjunction with medications. occurring in the body. Unlike most membrane phospholipids, alpha- GPC is water-soluble because it lacks the hydrophobic tail groups. Alpha-GPC Uses For Alpha-GPC each Caplique® Capsule contains v 0 • Memory And Cognitive Health: Alpha-GPC passes through the alpha-GPC (L-alpha-glycerophosphatidylcholine) ........................ 200 mg blood brain barrier providing a source of choline for acetylcholine other ingredients: glycerin, water, vegetarian Caplique® Capsule (cellulose, water) and phosphatidylcholine biosynthesis. By supporting cell membrane fluidity and integrity, phosphatidylcholine enhances Contains soy healthy neurotransmitter function and signal transduction. 6 Caplique® Capsules daily, in divided doses, with or Alpha-GPC may support healthy phospholipid turnover in the between meals. brain, helping to counteract age-related cellular breakdown of membrane phospholipids. Acetylcholine is a key neurotransmitter Caplique® Capsule is a registered trademark used by Pure Encapsulations in the brain supporting memory and learning. Optimal under license. phospholipid and acetylcholine levels support cognitive, mental Each Caplique® Capsule is preserved with a nitrogen bubble, which may give the and cerebrovascular health.* appearance of the capsule not being full. Contents may appear cloudy or thick and • Growth Hormone Support: Alpha-GPC has the ability to may settle or separate. potentiate growth hormone releasing hormone (GHRH), thereby supporting healthy growth hormone (GH) levels. The mechanism of support appears to involve increased cholinergic tone.* What Is The Source? Alpha-GPC is derived from highly purified soy lecithin. -
Présentation Powerpoint
Table S1- List of metabolites analyzed with the AbsoluteIDQ p180 kit Metabolite Short name Biochemical Name Metabolite Short name Biochemical Name Class Class C0 L-Carnitine Ala Alanine C10 Decanoyl-L-carnitine Arg Arginine C10:1 Decenoyl-L-carnitine Asn Asparagine C10:2 Decadienyl-L-carnitine Asp Aspartate C12 Dodecanoyl-L-carnitine Cit Citrulline C12:1 Dodecenoyl-L-carnitine Gln Glutamine C12-DC Dodecanedioyl-L-carnitine Glu Glutamate C14 Tetradecanoyl-L-carnitine Gly Glycine C14:1 Tetradecenoyl-L-carnitine His Histidine C14:1-OH Hydroxytetradecenoyl-L-carnitine acids Ile Isoleucine C14:2 Tetradecadienyl-L-carnitine Leu Leucine C14:2-OH Hydroxytetradecadienyl-L-carnitine Lys Lysine C16 Hexadecanoyl-L-carnitine C16:1 Hexadecenoyl-L-carnitine Met Methionine C16:1-OH Hydroxyhexadecenoyl-L-carnitine Orn Ornithine C16:2 Hexadecadienyl-L-carnitine Amino Phe Phenylalanine C16:2-OH Hydroxyhexadecadienyl-L-carnitine Pro Proline Ser Serine carnitines C16-OH Hydroxyhexadecanoyl-L-carnitine - C18 Octadecanoyl-L-carnitine Thr Threonine L - C18:1 Octadecenoyl-L-carnitine Trp Tryptophan C18:1-OH Hydroxyoctadecenoyl-L-carnitine Tyr Tyrosine C18:2 Octadecadienyl-L-carnitine Val Valine acyl C2 Acetyl-L-carnitine Ac-Orn Acetylornithine C3 Propionyl-L-carnitine ADMA Asymmetric dimethylarginine & C3:1 Propenyl-L-carnitine SDMA Symmetric dimethylarginine C3-DC / C4-OH Malonyl-L-carnitine / Hydroxybutyryl-L- alpha-AAA alpha-Aminoadipic acid carnitine Carnosine Carnosine C3-DC-M / C5-OH Methylmalonyl-L-carnitine / Creatinine Creatinine Hydroxyvaleryl-L-carnitine -
Spray-Dried Bioadhesive Formulations for Pulmonary Delivery
SPRAY-DRIED BIOADHESIVE FORMULATIONS FOR PULMONARY DELIVERY BY HUNER KAMAL OMER A THESIS SUBMITTED IN PARTIAL FULFILMENT FOR THE REQUIRMENTS OF THE DEGREE OF DOCTOR OF PHILOSOPHY AT THE UNIVERSITY OF CENTRAL LANCASHIRE July/2014 ABSTRACT This study describes developments and in vitro characterisation of lipid microparticles prepared using spray-drying for drug delivery to the lung via dry powder inhalers. Bioadhesive formulations such as prochitosome or chitosome powders have been introduced to overcome the drawbacks of liposome instability and potentially provide significant increase in the residence time of drug in the lung. Mannitol or lactose monohydrate (LMH) aqueous solutions were spray dried at inlet temperatures of 90, 130, 170 or 210ºC. Soy phosphatidylcholine and cholestrol (1:1 mole ratio) were used in all formulations. Cholesterol was added to increase vesicle membrane rigidity. Proliposomes containing salbutamol sulphate (SS) were prepared by incorporating various lipid:carrier (mannitol or LMH; 1:2, 1:4, 1:6, 1:8 and 1:10 w/w). Prochitosomes including SS or beclomethason dipropionate (BDP) were prepared by adding various chitosan glutamate:lipid ratios of 1:10, 2:10, 3:10 and 5:10 w/w. Chitosomes, including various cryoprotectants (mannitol, LMH, trehalose or sucrose), were prepared by including chitosan glutamate to liposomes generated from ethanol-based proliposomes in the ratio of 3:10 w/w chitosan to lipid. The spray-drying parameters for generation of dry powders were optimised by using an inlet temperature of 120ºC, outlet temperature of 73 ± 3°C, aspirator rate of 100%, suspension feed rate of 11%, and spray flow rate of 600 L/h using B-290 Buchi mini spray-dryer. -
Review Questions Plasma Membrane
Review Questions Plasma Membrane 1. What is the function of the plasma membrane? The plasma membrane forms the outer boundary of all cells. Described as semi-permeable, the membrane regulates the passage of atoms and molecules in and out of the cell. All membrane-bound organelles are also built of plasma membrane. 2. Draw a phospholipid bilayer and label the polar heads and the non-polar tails. The plasma membrane is made of a phospholipid bilayer. Phospholipids have a glycerol backbone attached to two fatty acid chains (one is unsaturated) and one phosphate group. The phosphate has a negative charge. The rest of the lipid is nonpolar. Water is attracted to the phosphate group and repelled by the rest of the molecule, so a phospholipid has a dual nature: a hydrophilic region (“head”) and a hydrophobic region (“tails”). When placed in water, the phospholipids form a bilayer. The heads face outward and the tails stay inside. The bilayer is semi-permeable barrier. Some substances can freely cross the membrane whereas others are stopped. 3. Why is the plasma membrane described as a “fluid mosaic”? The plasma membrane is a fluid because the phospholipid molecule is unsaturated. At room temperature, this causes the bilayer to have the consistency of salad oil. The term “mosaic” refers to the variety of embedded transmembrane proteins scattered throughout the membrane. 4. Why is cholesterol an important component of animal cell membranes? Cholesterol is a component of the cell membranes of animals. Cholesterol makes the membrane less fluid and therefore more impermeable to biological molecules. In a sense, cholesterol creates a more solid membrane and a more restrictive membrane. -
The Effects of Α-Gpc Supplementation On
THE EFFECTS OF -GPC SUPPLEMENTATION ON GROWTH HORMONE, FAT LOSS, AND BODY COMPOSITION IN OVERWEIGHT ADULTS by WILLIAM G. MALDONADO A thesis submitted to the School of Graduate Studies Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Master of Science Graduate Program in Kinesiology and Applied Physiology Written under the direction of Shawn M. Arent And approved by New Brunswick, New Jersey October, 2019 ABSTRACT OF THE THESIS The Effects of -GPC Supplementation on Growth Hormone, Fat Loss, and Body Composition in Overweight Adults By WILLIAM GERARD MALDONADO Thesis Director Shawn M. Arent In the United States, there is an increasing prevalence of obesity that is associated with health risks, and, as such, the need for effective weight loss methods is becoming increasingly more important. In the elderly, α-GPC has been shown to significantly increase growth hormone (GH) concentrations, a major stimulator of lipolysis and protein synthesis. However, very little work has been done in younger individuals. PURPOSE: to investigate if α-GPC, an acetylcholine precursor, could confer additional GH or weight loss benefits to active, overweight individuals while exercise and nutrition are maintained. METHODS: Participants were randomly assigned to either α-GPC (n=15, Mage=25.8±9.1y, MBF%=35.48±1.75%) or placebo (n=13 Mage=24.4±10.4y, MBF%=35.65±1.98%) after health/fitness screening. Both groups were instructed to consume two capsules of their respective supplement for a total of 1200 mg/day, one dose before their workout or on non-workout days with their midday meal, and the second dose before going to sleep, for eight weeks. -
The Guinea Pig Model for Organophosphate Toxicology and Therapeutic Development
THE GUINEA PIG MODEL FOR ORGANOPHOSPHATE TOXICOLOGY AND THERAPEUTIC DEVELOPMENT A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy By Christopher Ruark B.S., Miami University, 2007 M.S., Wright State University, 2010 ______________________________________ 2015 Wright State University WRIGHT STATE UNIVERSITY GRADUATE SCHOOL May 2, 2015 I HEREBY RECOMMEND THAT THE DISSERTATION PREPARED UNDER MY SUPERVISION BY Christopher Ruark ENTITLED The Guinea Pig Model for Organophosphate Toxicology and Therapeutic Development BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctor of Philosophy. __________________________ Jeffery M. Gearhart, Ph.D. Dissertation Director ___________________________ Mill W. Miller Ph.D. Director, Biomedical Sciences Ph.D. Program ___________________________ Robert E. W. Fyffe, Ph.D. Committee on Vice President for Research and Final Examination Dean of the Graduate School ___________________________ Jeffery M. Gearhart, Ph.D. ___________________________ Adrian M. Corbett, Ph.D. ___________________________ James B. Lucot, Ph.D. ___________________________ Mateen M. Rizki, Ph.D. ___________________________ Gerald M. Alter, Ph.D. ABSTRACT Ruark, Christopher Ph.D., Biomedical Sciences Ph.D. program, Wright State University, 2015. The Guinea Pig Model for Organophosphate Toxicology and Therapeutic Development. Organophosphates (OPs) are highly toxic insecticides and nerve agents that have been designed to inhibit the hydrolysis of acetylcholine by binding to the serine active site of acetylcholinesterase (AChE). They are one of the most common causes of human poisoning worldwide and are frequently intentionally used in suicides in agricultural areas. For this reason, there is a need for therapeutics to rescue those from intoxication. Obvious ethical concerns prevent humans from being subjected to OP exposure for therapeutic efficacy and safety testing.