Non-Enzymatic Synthesis of the Coenzymes, Uridine Diphosphate
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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. -
We Have Previously Reported' the Isolation of Guanosine Diphosphate
VOL. 48, 1962 BIOCHEMISTRY: HEATH AND ELBEIN 1209 9 Ramel, A., E. Stellwagen, and H. K. Schachman, Federation Proc., 20, 387 (1961). 10 Markus, G., A. L. Grossberg, and D. Pressman, Arch. Biochem. Biophys., 96, 63 (1962). "1 For preparation of anti-Xp antisera, see Nisonoff, A., and D. Pressman, J. Immunol., 80, 417 (1958) and idem., 83, 138 (1959). 12 For preparation of anti-Ap antisera, see Grossberg, A. L., and D. Pressman, J. Am. Chem. Soc., 82, 5478 (1960). 13 For preparation of anti-Rp antisera, see Pressman, D. and L. A. Sternberger, J. Immunol., 66, 609 (1951), and Grossberg, A. L., G. Radzimski, and D. Pressman, Biochemistry, 1, 391 (1962). 14 Smithies, O., Biochem. J., 71, 585 (1959). 15 Poulik, M. D., Biochim. et Biophysica Acta., 44, 390 (1960). 16 Edelman, G. M., and M. D. Poulik, J. Exp. Med., 113, 861 (1961). 17 Breinl, F., and F. Haurowitz, Z. Physiol. Chem., 192, 45 (1930). 18 Pauling, L., J. Am. Chem. Soc., 62, 2643 (1940). 19 Pressman, D., and 0. Roholt, these PROCEEDINGS, 47, 1606 (1961). THE ENZYMATIC SYNTHESIS OF GUANOSINE DIPHOSPHATE COLITOSE BY A MUTANT STRAIN OF ESCHERICHIA COLI* BY EDWARD C. HEATHt AND ALAN D. ELBEINT RACKHAM ARTHRITIS RESEARCH UNIT AND DEPARTMENT OF BACTERIOLOGY, THE UNIVERSITY OF MICHIGAN Communicated by J. L. Oncley, May 10, 1962 We have previously reported' the isolation of guanosine diphosphate colitose (GDP-colitose* GDP-3,6-dideoxy-L-galactose) from Escherichia coli 0111-B4; only 2.5 umoles of this sugar nucleotide were isolated from 1 kilogram of cells. Studies on the biosynthesis of colitose with extracts of this organism indicated that GDP-mannose was a precursor;2 however, the enzymatically formed colitose was isolated from a high-molecular weight substance and attempts to isolate the sus- pected intermediate, GDP-colitose, were unsuccessful. -
Drug-Excipient Interaction and Its Importance in Dosage Form
Journal of Applied Pharmaceutical Science 01 (06); 2011: 66-71 ISSN: 2231-3354 Drug-excipient interacti on and its importance in Received: 29-07-2011 Revised on: 02-08-2011 Accepted: 04-08-2011 dosage form development Nishath Fathima, Tirunagari Mamatha, Husna Kanwal Qureshi, Nandagopal Anitha and Jangala Venkateswara Rao ABSTRACT Excipients are included in dosage forms to aid manufacture, administration or absorption. Although considered pharmacologically inert, excipients can initiate, propagate or participate in Nishath Fathima, Tirunagari chemical or physical interactions with drug compounds, which may compromise the effectiveness Mamatha, Husna Kanwal Qureshi, of a medication. Exicipients are not exquisitely pure. Even for the most commonly used excipients, Nandagopal Anitha and Jangala it is necessary to understand the context of their manufacture in order to identify potential active pharmaceutical ingredients interactions with trace components. Chemical interactions can lead to Venkateswara Rao Sultan-Ul-Uloom College of Pharmacy, degradation of the active ingredient, thereby reducing the amount available for therapeutic effect. Physical interactions can affect rate of dissolution, uniformity of dose or ease of administration. Banjara Hills, Hyderabad - 500034, A.P., India. Key words: Excipient, Drug, Interaction, Physical, Chemical. INTRODUCTION Pharmaceutical dosage form is a combination of active pharmaceutical ingredients (API) and excipients. Excipients are included in dosage forms to aid manufacture, administration or absorption (Crowley and Martini).The ideal excipients must be able to fulfill the important functions i.e. dose, stability and release of API from the formulation. Although considered pharmacologically inert, excipients can initiate, propagate or participate in chemical or physical interactions with drug compounds, which may compromise the effectiveness of a medication. -
Nucleotide Metabolism 22
Nucleotide Metabolism 22 For additional ancillary materials related to this chapter, please visit thePoint. I. OVERVIEW Ribonucleoside and deoxyribonucleoside phosphates (nucleotides) are essential for all cells. Without them, neither ribonucleic acid (RNA) nor deoxyribonucleic acid (DNA) can be produced, and, therefore, proteins cannot be synthesized or cells proliferate. Nucleotides also serve as carriers of activated intermediates in the synthesis of some carbohydrates, lipids, and conjugated proteins (for example, uridine diphosphate [UDP]-glucose and cytidine diphosphate [CDP]- choline) and are structural components of several essential coenzymes, such as coenzyme A, flavin adenine dinucleotide (FAD[H2]), nicotinamide adenine dinucleotide (NAD[H]), and nicotinamide adenine dinucleotide phosphate (NADP[H]). Nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), serve as second messengers in signal transduction pathways. In addition, nucleotides play an important role as energy sources in the cell. Finally, nucleotides are important regulatory compounds for many of the pathways of intermediary metabolism, inhibiting or activating key enzymes. The purine and pyrimidine bases found in nucleotides can be synthesized de novo or can be obtained through salvage pathways that allow the reuse of the preformed bases resulting from normal cell turnover. [Note: Little of the purines and pyrimidines supplied by diet is utilized and is degraded instead.] II. STRUCTURE Nucleotides are composed of a nitrogenous base; a pentose monosaccharide; and one, two, or three phosphate groups. The nitrogen-containing bases belong to two families of compounds: the purines and the pyrimidines. A. Purine and pyrimidine bases Both DNA and RNA contain the same purine bases: adenine (A) and guanine (G). -
DNA Modifications in Models of Alcohol Use Disorders
Alcohol 60 (2017) 19e30 Contents lists available at ScienceDirect Alcohol journal homepage: http://www.alcoholjournal.org/ DNA modifications in models of alcohol use disorders * Christopher T. Tulisiak a, R. Adron Harris a, b, Igor Ponomarev a, b, a Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, A4800, Austin, TX 78712, USA b The College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1900, Austin, TX 78712, USA article info abstract Article history: Chronic alcohol use and abuse result in widespread changes to gene expression, some of which Received 2 September 2016 contribute to the development of alcohol-use disorders (AUD). Gene expression is controlled, in part, by a Received in revised form group of regulatory systems often referred to as epigenetic factors, which includes, among other 3 November 2016 mechanisms, chemical marks made on the histone proteins around which genomic DNA is wound to Accepted 5 November 2016 form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has been shown to perturb the epigenetic machinery, leading to changes in gene expression and cellular functions characteristic of Keywords: AUD and, ultimately, to altered behavior. DNA modifications in particular are seeing increasing research Alcohol fi Epigenetics in the context of alcohol use and abuse. To date, studies of DNA modi cations in AUD have primarily fi fi fi DNA methylation looked at global methylation pro les in human brain and blood, gene-speci c methylation pro les in DNMT animal models, methylation changes associated with prenatal ethanol exposure, and the potential DNA hydroxymethylation therapeutic abilities of DNA methyltransferase inhibitors. -
A Previously Undescribed Pathway for Pyrimidine Catabolism
A previously undescribed pathway for pyrimidine catabolism Kevin D. Loh*†, Prasad Gyaneshwar*‡, Eirene Markenscoff Papadimitriou*§, Rebecca Fong*, Kwang-Seo Kim*, Rebecca Parales¶, Zhongrui Zhouʈ, William Inwood*, and Sydney Kustu*,** *Department of Plant and Microbial Biology, 111 Koshland Hall, University of California, Berkeley, CA 94720-3102; ¶Section of Microbiology, 1 Shields Avenue, University of California, Davis, CA 95616; and ʈCollege of Chemistry, 8 Lewis Hall, University of California, Berkeley, CA 94720-1460 Contributed by Sydney Kustu, January 19, 2006 The b1012 operon of Escherichia coli K-12, which is composed of tive N sources. Here we present evidence that the b1012 operon seven unidentified ORFs, is one of the most highly expressed codes for proteins that constitute a previously undescribed operons under control of nitrogen regulatory protein C. Examina- pathway for pyrimidine degradation and thereby confirm the tion of strains with lesions in this operon on Biolog Phenotype view of Simaga and Kos (8, 9) that E. coli K-12 does not use either MicroArray (PM3) plates and subsequent growth tests indicated of the known pathways. that they failed to use uridine or uracil as the sole nitrogen source and that the parental strain could use them at room temperature Results but not at 37°C. A strain carrying an ntrB(Con) mutation, which Behavior on Biolog Phenotype MicroArray Plates. We tested our elevates transcription of genes under nitrogen regulatory protein parental strain NCM3722 and strains with mini Tn5 insertions in C control, could also grow on thymidine as the sole nitrogen several genes of the b1012 operon on Biolog (Hayward, CA) source, whereas strains with lesions in the b1012 operon could not. -
A Single-Label Phenylpyrrolocytidine Provides a Molecular Beacon-Like Response Reporting HIV-1 RT Rnase H Activity Alexander S
1048–1056 Nucleic Acids Research, 2010, Vol. 38, No. 3 Published online 20 November 2009 doi:10.1093/nar/gkp1022 A single-label phenylpyrrolocytidine provides a molecular beacon-like response reporting HIV-1 RT RNase H activity Alexander S. Wahba1, Abbasali Esmaeili2, Masad J. Damha1 and Robert H. E. Hudson3,* 1Department of Chemistry, McGill University, Montreal, QC, H3A 2K6 Canada, 2Department of Chemistry, University of Birjand, Birjand, Iran and 3Department of Chemistry, University of Western Ontario, London, ON, N6A 5B7 Canada Downloaded from https://academic.oup.com/nar/article/38/3/1048/3112336 by guest on 27 September 2021 Received August 15, 2009; Revised and Accepted October 19, 2009 ABSTRACT identified as a potential target for antiretroviral therapy as it is required for virus infectivity (3); yet there are no 6-Phenylpyrrolocytidine (PhpC), a structurally con- antiRNase H agents in clinical use. Few inhibitors of HIV- servative and highly fluorescent cytidine analog, 1 RNase H were identified until the transition of testing was incorporated into oligoribonucleotides. The methods from gel-based techniques to fluorescent assays PhpC-containing RNA formed native-like duplex amenable to high-throughput screening (HTS) (4–8). The structures with complementary DNA or RNA. The most widely used assay was developed by Parniak and co- PhpC-modification was found to act as a sensitive workers (6) and utilizes a two label, molecular beacon reporter group being non-disruptive to structure and strategy (9) in which the RNA strand is labeled with a 0 the enzymatic activity of RNase H. A RNA/DNA 3 -terminal fluorophore (fluorescein, F) and a DNA 0 hybrid possessing a single PhpC insert was an strand with a quencher (dabcyl, Q) at the 5 -terminus excellent substrate for HIV-1 RT Ribonuclease H (Scheme 1). -
Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices
Journal of Neurochemi,enry Raven Press, Ltd ., New York © 1995 International Society for Neurochemistry Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices Vahide Savci and Richard J . Wurtman Delzcartrnent of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, U .S .A . Abstract : Using rat striatal slices, we examined the effect cell culture systems and in vivo experiments, exoge- of cytidine on the conversion of [ 3H]choline to [ 3H]- nous cytidine has been shown to be taken up into cells phosphatidylcholine ([ 3 H]PC), and on net syntheses of and converted sequentially to CMP, CDP, and CTP PC, phosphatidylethanolamine (PE), and phosphatidyl- (Plagemann, 1971a,b ; Trovarelli et al ., 1982 ; 1984 ; serine, when media did or did not also contain choline, Lopez G.-Coviella and Wurtman, 1992) . CTP is re- ethanolamine, or serine . Incubation of striatal slices with quired to form key intermediates in the biosynthesis cytidine (50-500 NM) caused dose-dependent increases in intracellular cytidine and cytidine triphosphate (CTP) of both phosphatidylcholine (PC) and phosphati- levels and in the rate of incorporation of [ 3H]choline into dylethanolamine (PE) (quantitatively the most sig- 3 membrane [ H] PC . In pulse-chase experiments, cytidine nificant phospholipids of eukaryotic cells) via the Ken- (200 N,M) also increased significantly the conversion of nedy pathway (Kennedy and Weiss, 1956 ; Pelech and [ 3H]choline to [ 3 H]PC during the chase period . When Vance, 1984 ; Vance, 1985) and also in the biosynthe- slices were incubated with this concentration of cytidine sis of phosphatidylinositol (Vance, 1985 ; Majerus, for 1 h, small (7%) but significant elevations were ob- 1992 ; Pike, 1992) . -
Effect of Uridine on Response of 5-Azacytidine-Resistant Human Leukemic Cells to Inhibitors of De Novo Pyrimidine Synthesis1
[CANCER RESEARCH 44, 5505-5510, December 1984] Effect of Uridine on Response of 5-Azacytidine-resistant Human Leukemic Cells to Inhibitors of de Novo Pyrimidine Synthesis1 S. Grant,2 K. Bhalla,3 and M. Gleyzer Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032 ABSTRACT activity is the most commonly encountered mode of resistance in animal systems (28). A uridine-cytidine kinase-deficient human promyelocytic leu- We have recently isolated a uridine-cytidine kinase-deficient, kemic subline (HL-60-5-aza-Cyd) has been isolated which is highly 5-aza-Cyd-resistant human promyelocytic leukemic sub- highly resistant to the antileukemic agent 5-azacytidine. Resist line (HL-60-5-aza-Cyd) (8) which is capable of surviving 5-aza- ant cells exposed to 10~5 M 5-azacytidine for 2 hr exhibit a Cyd concentrations (10~4 M) that exceed peak plasma levels in marked reduction in both the total ¡ntracellularaccumulation of humans (27). The purpose of the present studies was to assess 5-azacytidine (11.9 versus 156.0 pmol/106 cells) as well as its the metabolism of 5-aza-Cyd in these resistant cells and to incorporation into RNA (3.1 versus 43.4 pmol//ig o-ribose) com examine their response to a variety of clinically available inhibitors pared to the parent line. These biochemical changes are asso of de novo pyrimidine synthesis. Of the latter agents, PALA, an ciated with nearly a 100-fold decrease in sensitivity to the growth inhibitor of aspártele transcarbamylase (26), and pyrazofurin, an inhibitory effects of 5-azacytidine (concentration of drug associ ated with a 50% reduction in cell growth, 3.5 x 10~5 versus 5.0 inhibitor of orotidylate decarboxylase (5), are of particular inter x 10"7 M). -
Polymeric Derivative of Cytidine Metabolic Antagonist Polymer-Derivat Von Cytidin Metabolit Antagonist Derive Polymere D’Un Antagoniste Metabolique De La Cytidine
(19) & (11) EP 1 881 020 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C08G 65/08 (2006.01) A61K 38/00 (2006.01) 11.08.2010 Bulletin 2010/32 C08G 65/333 (2006.01) C08G 69/48 (2006.01) (21) Application number: 06745754.9 (86) International application number: PCT/JP2006/308826 (22) Date of filing: 27.04.2006 (87) International publication number: WO 2006/120914 (16.11.2006 Gazette 2006/46) (54) POLYMERIC DERIVATIVE OF CYTIDINE METABOLIC ANTAGONIST POLYMER-DERIVAT VON CYTIDIN METABOLIT ANTAGONIST DERIVE POLYMERE D’UN ANTAGONISTE METABOLIQUE DE LA CYTIDINE (84) Designated Contracting States: • MASHIBA, Hiroko, AT BE BG CH CY CZ DE DK EE ES FI FR GB GR NIPPON KAYAKU KABUSHIKI KAISHA HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI Tokyo 1150042 (JP) SK TR • YAMAMOTO, Keiichirou, Designated Extension States: c/o NIPPON KAYAKU K.K. AL BA HR MK YU Tokyo 1150042 (JP) • TAKASHIO, Kazutoshi, (30) Priority: 11.05.2005 JP 2005138249 NIPPON KAYAKU K.K. Tokyo 1150042 (JP) (43) Date of publication of application: 23.01.2008 Bulletin 2008/04 (74) Representative: Wablat, Wolfgang Patentanwalt (73) Proprietor: NIPPON KAYAKU KABUSHIKI KAISHA Dr. Dr. W. Wablat Tokyo 102-8172 (JP) Potsdamer Chaussee 48 14129 Berlin (DE) (72) Inventors: • MASUDA, Akira, (56) References cited: c/o NIPPON KAYAKU KABUSHIKI KAISHA EP-A- 0 097 307 EP-A- 0 685 504 Tokyo 1150042 (JP) WO-A-01/21135 WO-A-02/065988 • ONDA, Takeshi, JP-A- 6 206 832 JP-A- 02 300 133 c/o NIPPON KAYAKU KABUSHIKI KAISHA JP-A- 06 206 832 JP-A- 08 048 766 Tokyo 1150042 (JP) JP-A- 2003 524 028 JP-A- 2004 532 289 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. -
Nucleotide Metabolism Pathway: the Achilles' Heel for Bacterial Pathogens
REVIEW ARTICLES Nucleotide metabolism pathway: the achilles’ heel for bacterial pathogens Sujata Kumari1,2,* and Prajna Tripathi1,3 1National Institute of Immunology, New Delhi 110 067, India 2Present address: Department of Zoology, Magadh Mahila College, Patna University, Patna 800 001, India 3Present address: Institute of Molecular Medicine, Jamia Hamdard, New Delhi 110 062, India de novo pathway, the nucleotides are synthesized from Pathogens exploit their host to extract nutrients for their survival. They occupy a diverse range of host simple precursor molecules. In the salvage pathway, the niches during infection which offer variable nutrients preformed nucleobases or nucleosides which are present accessibility. To cause a successful infection a patho- in the cell or transported from external environmental gen must be able to acquire these nutrients from the milieu to the cell are utilized to form nucleotides. host as well as be able to synthesize the nutrients on its own, if required. Nucleotides are the essential me- tabolite for a pathogen and also affect the pathophysi- Purine biosynthesis pathway ology of infection. This article focuses on the role of nucleotide metabolism of pathogens during infection The purine biosynthesis pathway is universally conserved in a host. Nucleotide metabolism and disease pathoge- in living organisms (Figure 1). As an example, we here nesis are closely related in various pathogens. Nucleo- present the pathway derived from well-studied Gram- tides, purines and pyrimidines, are biosynthesized by positive bacteria Lactococcus lactis. In the de novo the de novo and salvage pathways. Whether the patho- pathway the purine nucleotides are synthesized from sim- gen will employ the de novo or salvage pathway dur- ple molecules such as phosphoribosyl pyrophosphate ing infection is dependent on various factors, like (PRPP), amino acids, CO2 and NH3 by a series of enzy- availability of nucleotides, energy condition and pres- matic reactions. -
Non-Utilization of Radioactive Lodinated Uracil, Uridine, and Orotic Acid by Animal Tissues in Vivo W
Non-utilization of Radioactive lodinated Uracil, Uridine, and Orotic Acid by Animal Tissues in Vivo W. H. PRUSOFF,WL. HOLMES,tANDA. D. WELCH Department of Pharmacology, School of Medicine, Western Reserve University, Cleveland, Ohio) Adenine (1, 6), guanine (1, 3, 5), cytidine (13), lometric localization of brain tumors. Further desoxycytidine (18), thymidine (18), and orotic more, an I'3-labeled oxazine dye had a significant acid (2), can be utilized by certain mammalian or effect in prolonging the life of mice bearing trans ganisms for the synthesis of nucleic acids ; and the planted tumors (19). If an effective and easily syn rate of incorporation of many of these compounds thesized radioactive iodine-labeled compound into the nucleic acids of rapidly growing tissues, could be found, the possibility might be afforded of such as regenerating liver or neoplastic tissues, is the comparable use of compounds labeled with greater than into those of resting tissues (10, 21). eka-iodine (astatine2@), a potent emitter of alpha Although 8-azaguanine is not a naturally occur particles, although this element is prepared with ring compound, evidence that it can be incorpo difficulty and has the inconveniently short half rated to a small extent into mammalian nucleic life of 7.5 hours (12). acids has been presented (16). This analog of gua Three P3-labeled pyrimidines, iodouridine-5- nine markedly inhibited the growth of Tetrahy I'S', iodouracil-5-I'31, and iodoorotic acid-5-P31, mena geleii, a guanine-requiring protozoan, and of were synthesized, and their incorporation into nor certain experimental tumors. Kidder et al.