DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2010/0172909 A1 Nishibori Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2010/0172909 A1 Nishibori Et Al US 20100172909A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0172909 A1 Nishibori et al. (43) Pub. Date: Jul. 8, 2010 (54) CEREBRAL EDEMA SUPPRESSANT (30) Foreign Application Priority Data (76) Inventors: Masahiro Nishibori, Okayama-shi Oct. 24, 2005 (JP) ................................. 2005-3O8949 (JP); Shuji Mori, Okayama-shi (JP); Hideo Takahashi, Okayama-shi (JP); Yasuko Publication Classification Tomono, Okayama-shi (JP): Naoto (51) Int. Cl. Adachi, Kyoto-shi (JP); Keyue Liu, A 6LX 39/395 (2006.01) Touon-shi (JP) A6IP 43/00 (2006.01) Correspondence Address: WENDEROTH, LIND & PONACK, L.L.P. (52) U.S. Cl. ..................................................... 424/139.1 1030 15th Street, N.W., Suite 400 East Washington, DC 20005-1503 (US) (21) Appl. No.: 12/634,790 (57) ABSTRACT (22) Filed: Jan. 4, 2010 The objective to be solved by the present invention is to provide a method for effectively suppressing cerebral edema. Related U.S. Application Data The method for Suppressing cerebral edema according to the (63) Continuation-in-part of application No. 12/084,044, present invention is characterized in comprising a step of filed on Apr. 24, 2008, now abandoned, filed as appli administering an anti-HMGB 1 antibody recognizing cation No. PCT/JP2006/320436 on Oct. 13, 2006. 208EEEDDDDE215 (SEQID NO: 1) as an HMGB1 epitope. 8:38-3::::::isis: 88 grogg A:::::::::38: 38t:3{xy 38:::::sier88 gro.3 Patent Application Publication Jul. 8, 2010 Sheet 1 of 4 US 2010/0172909 A1 es O O C wa o c O V v (D 92 s. ON- I - o its 5 wn a 9 - Yee v O Y O ea 5 O O NY O CC o S O . v se C 9E k sw O S O queto E C (C C (s ma 5 CC O "a S s CC eAoouou uo WWOJO unoue uOSsedx. Patent Application Publication Jul. 8, 2010 Sheet 2 of 4 US 2010/0172909 A1 Patent Application Publication US 2010/0172909 A1 (6u/6u) enq Suen jounoue e6exee Patent Application Publication Jul. 8, 2010 Sheet 4 of 4 US 2010/0172909 A1 (%)x. ...paleisulupe xx.... --> semigoNH Alio 8883 & O 8.8d. i03 essex e^. i.e. ifid exee joinoue at a de e. US 2010/0172909 A1 Jul. 8, 2010 CEREBRAL EDEMIA SUPPRESSANT 181. Concerning the anti-HMGB1 antibody, it is only experi mentally demonstrated that certain anti-HMGB1 antibody TECHNICAL FIELD inhibits cell migration of HMGB1, and it is not experimen 0001. The present invention relates to a drug for suppress tally demonstrated at all that the anti-HMGB1 antibody is ing cerebral edema. useful for Suppressing edema. Cerebral edema is not described in the publication either. BACKGROUND ART DISCLOSURE OF THE INVENTION 0002 Cerebral edema is a condition characterized by an excess of watery fluid collected in the extracellular spaces of 0007 Under the above circumstance, the objective to be the brain, such as circumferences of brain cell and cerebral solved by the present invention is to provide a method for blood vessel. Cerebral edema needs aggressive medical treat effectively suppressing cerebral edema. ment, since cerebral edema increases pressure in the brain to 0008. The present inventors have continuously studied cause death. anti-HMGB1 antibody. As a result, the present inventors 0003 Cerebral edema is classified into vasogenic edema found out that the anti-HMGB1 antibody which specifically and cytotoxic edema. Vasogenic edema is caused by break binds to C-tail of HMGB1 can effectively suppress cerebral down of blood-brainbarrier due to cerebral contusion, intrac edema, resulting in completion of the present invention. erebral hemorrhage, cerebral tumor and the like, and by 0009. The method for suppressing cerebral edema accord excessive increase of vascular permeability, which leads leak ing to the present invention is characterized in comprising a age and accumulation of plasma component outside of brain step of administering an anti-HMGB1 monoclonal antibody cell. Cytotoxic edema is caused by increasing fluid compo recognizing 208EEEDDDDE215 as an HMGB1 epitope. nent in brain cell due to hypoxia, impaired metabolism and 0010. According to the present invention method, cerebral the like. It is said that the breakdown of the blood-brain edema can be effectively suppressed. In addition, it is con barrier is not observed for the case of cytotoxic edema. How sidered that a possibility generating a serious adverse side ever, it is difficult to clearly distinguish cytotoxic edema from effect is extremely low based on the relatively safe clinical vasogenic edema, since disease condition may transit from application of antibody drugs currently used Therefore, the vasogenic edema to cytotoxic edema. Therefore, it is very method for suppressing cerebral edema according to the important for Suppressing cerebral edemato inhibit the break present invention is extremely useful. down of the blood-brain barrier, that is, excessive increase of vascular permeability. 0004 As the therapeutic agent for cerebral edema, glyc BRIEF DESCRIPTION OF THE DRAWINGS erol, mannitol, diuretics, and the like are exemplified. How ever, a more effective therapeutic agent is required. 0011 FIG. 1 shows the effects of the anti-HMGB1 mono 0005 HMGB1, i.e. High Mobility Group box 1, is a pro clonal antibody which specifically binds to C-tail with neu tein in which 95% or more of amino acid sequence is equal tralizing the activity of HMGB1. FIG. 1(A) shows the levels from a rodent to a human. The HMGB1 is present in a normal of ICAM-1 expression on monocytes by addition of HMGB1, cell. However, the blood concentration thereof is increased by and FIG. 1 (B) shows the levels of ICAM-1 expression in case stimulation with LPS (liposaccharide) which is an endotoxin that the anti-HMGB1 monoclonal antibody is added simulta released in sepsis, one of systemic inflammatory response neously with addition of HMGB1. syndromes, leading to final tissue failure. Therefore, in the 0012 FIG. 2 shows the suppressing effects of administra technology described in Published Japanese Translation of tion of the anti-HMGB1 monoclonal antibody which specifi PCT International Publication No. 2003-520763, an HMG cally binds to C-tail on the increased permeability of brain antagonist is administered in order to treat a symptom having blood vessel. In non-ischemic group without load of cerebral a characteristic of activation of an inflammatory cytokine ischemia, leakage of Evans blue, i.e. dye, is not seen. On the cascade. However, there is neither description nor Suggestion other hand, in a control antibody-administered group to about not only cerebral edema but also general edema in the which cerebral ischemia was loaded and a control antibody publication. In addition, it is described in Published Japanese was administered, a considerable amount of leakage is Translation of PCT International Publication No. 2005 observed. In an anti-HMGB1 antibody-administered group to 512507 that the anti-HMGB1 antibody may treat a disease which the anti-HMGB1 monoclonal antibody of the present associated with an inflammatory cytokine cascade. However, invention was administered, such a leakage is clearly inhib the anti-HMGB1 antibody specifically binds to the box part ited. of HMGB1, and there is neither description nor suggestion 0013 FIG. 3 summarizes the quantitative comparison of about not only cerebral edema but also general edema in the the leakage of Evans blue into brain tissue between the con publication. trol antibody-administered group and the anti-HMGB1 anti 0006. In addition, it is described in Published Japanese body-administered group. It is found that the increased per Translation of PCT International Publication No. 2005 meability of brain blood vessels can be significantly inhibited 537253 that an HMGB1 antagonist such as anti-HMGB1 by administering the anti-HMGB1 monoclonal antibody. antibody is used for treating edema and the like. However, the 0014 FIG. 4 is a graph showing the relative amount of dye anti-HMGB1 antibody actually used in the publication is (Evans blue) which extravasated from microvasculature after antibodies which specifically bind to box or residues 166 to administration of saline, HMGB1 only, HMGB1+the anti US 2010/0172909 A1 Jul. 8, 2010 HMGB1 monoclonal antibody according to the present 0.2 to 2 mg/kg per dosage. However, the dose of the Suppres invention, or HMGB1+a monoclonal antibody binding to box sant should be suitably changed depending on patient's age, of HMGB1, to the dorsal skin of experimental rats. sex and severity of illness and the like. 0023. In the present invention method, the cerebral edema BEST MODE FOR CARRYING OUT THE Suppressant may be administered by intravenous injection. It INVENTION is at least experimentally demonstrated that the cerebral edema Suppressant according to the present invention can 0015. In the present invention method, the cerebral edema suppressant which contains the anti-HMGB1 monoclonal Suppress cerebral edema by intravenous injection, though it is antibody specifically binding to C-tail of HMGB1 as active unknown whether the Suppressant acts on brain blood vessel ingredients is administered. to inhibit the increased permeability or acts on brain cell 0016. The anti-HMGB1 monoclonal antibody according through the blood-brain barrier. to the present invention specifically binds to C-tail of 0024 Cerebral edema suppressant results from a number HMGB1 and neutralizes HMGB1, and inhibits the increased of causes. It is preferable to administer the cerebral edema permeability of brain blood vessel, to suppress cerebral Suppressant according to the present invention immediately edema. On the other hand, the antibody does not act on the after the cause of cerebral edema arises, since it becomes other parts of HMGB1 and other substances. Therefore, it is possible the Suppressant can prevent plasma proteins from considered that there is no or extremely little possibility of extravasating from brain blood vessel and can prevent the production of an adverse side effect.
Load more

Recommended publications
  • Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents
    Novel “Add-On” Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents Haojun Chen*1,2, Orit Jacobson*2, Gang Niu2, Ido D. Weiss3, Dale O. Kiesewetter2, Yi Liu2, Ying Ma2, Hua Wu1, and Xiaoyuan Chen2 1Department of Nuclear Medicine, Xiamen Cancer Hospital of the First Affiliated Hospital of Xiamen University, Xiamen, China; 2Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland; and 3Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland One of the major design considerations for a drug is its The goal of drug development is to achieve high activity and pharmacokinetics in the blood. A drug with a short half-life in specificity for a desired biologic target. However, many potential the blood is less available at a target organ. Such a limitation pharmaceuticals that meet these criteria fail as therapeutics because dictates treatment with either high doses or more frequent doses, of unfavorable pharmacokinetics, in particular, rapid blood clearance, both of which may increase the likelihood of undesirable side effects. To address the need for additional methods to improve which prevents the achievement of therapeutic concentrations. For the blood half-life of drugs and molecular imaging agents, we some drugs, the administration of large or frequently repeated doses developed an “add-on” molecule that contains 3 groups: a trun- is required to achieve and maintain therapeutic levels (1) but can, in cated Evans blue dye molecule that binds to albumin with a low turn, increase the probability of undesired side effects.
    [Show full text]
  • A Review of Dietary (Phyto)Nutrients for Glutathione Support
    nutrients Review A Review of Dietary (Phyto)Nutrients for Glutathione Support Deanna M. Minich 1,* and Benjamin I. Brown 2 1 Human Nutrition and Functional Medicine Graduate Program, University of Western States, 2900 NE 132nd Ave, Portland, OR 97230, USA 2 BCNH College of Nutrition and Health, 116–118 Finchley Road, London NW3 5HT, UK * Correspondence: [email protected] Received: 8 July 2019; Accepted: 23 August 2019; Published: 3 September 2019 Abstract: Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
    [Show full text]
  • L -Glutamic Acid (G1251)
    L-Glutamic acid Product Number G 1251 Store at Room Temperature Product Description Precautions and Disclaimer Molecular Formula: C5H9NO4 For Laboratory Use Only. Not for drug, household or Molecular Weight: 147.1 other uses. CAS Number: 56-86-0 pI: 3.081 Preparation Instructions 1 pKa: 2.10 (α-COOH), 9.47 (α-NH2), 4.07 (ϕ-COOH) This product is soluble in 1 M HCl (100 mg/ml), with 2 Specific Rotation: D +31.4 ° (6 N HCl, 22.4 °C) heat as needed, yielding a clear, colorless solution. Synonyms: (S)-2-aminoglutaric acid, (S)-2- The solubility in water at 25 °C has been reported to aminopentanedioic acid, 1-aminopropane-1,3- be 8.6 mg/ml.2 dicarboxylic acid, Glu2 Storage/Stability L-Glutamic acid is one of the two amino acids that Aqueous glutamic acid solutions will form contains a carboxylic acid group in its side chains. pyrrolidonecarboxylic acid slowly at room temperature Glutamic acid is commonly referred to as "glutamate", and more rapidly at 100 °C.9 because its carboxylic acid side chain will be deprotonated and thus negatively charged in its References anionic form at physiological pH. In amino acid 1. Molecular Biology LabFax, Brown, T. A., ed., BIOS metabolism, glutamate is formed from the transfer of Scientific Publishers Ltd. (Oxford, UK: 1991), p. amino groups from amino acids to α-ketoglutarate. It 29. thus acts as an intermediary between ammonia and 2. The Merck Index, 12th ed., Entry# 4477. the amino acids in vivo. Glutamate is converted to 3. Biochemistry, 3rd ed., Stryer, L., W.
    [Show full text]
  • Solutions to 7.012 Problem Set 1
    MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Solutions to 7.012 Problem Set 1 Question 1 Bob, a student taking 7.012, looks at a long-standing puddle outside his dorm window. Curious as to what was growing in the cloudy water, he takes a sample to his TA, Brad Student. He wanted to know whether the organisms in the sample were prokaryotic or eukaryotic. a) Give an example of a prokaryotic and a eukaryotic organism. Prokaryotic: Eukaryotic: All bacteria Yeast, fungi, any animial or plant b) Using a light microscope, how could he tell the difference between a prokaryotic organism and a eukaryotic one? The resolution of the light microscope would allow you to see if the cell had a true nucleus or organelles. A cell with a true nucleus and organelles would be eukaryotic. You could also determine size, but that may not be sufficient to establish whether a cell is prokaryotic or eukaryotic. c) What additional differences exist between prokaryotic and eukaryotic organisms? Any answer from above also fine here. In addition, prokaryotic and eukaryotic organisms differ at the DNA level. Eukaryotes have more complex genomes than prokaryotes do. Question 2 A new startup company hires you to help with their product development. Your task is to find a protein that interacts with a polysaccharide. a) You find a large protein that has a single binding site for the polysaccharide cellulose. Which amino acids might you expect to find in the binding pocket of the protein? What is the strongest type of interaction possible between these amino acids and the cellulose? Cellulose is a polymer of glucose and as such has many free hydroxyl groups.
    [Show full text]
  • An Investigation of D-Cycloserine As a Memory Enhancer NCT00842309 Marchmay 23, 15, 2016 2019 Sabine Wilhelm, Ph.D
    MayMarch 23, 2016 15, 2019 An investigation of D-cycloserine as a memory enhancer NCT00842309 MarchMay 23, 15, 2016 2019 Sabine Wilhelm, Ph.D. May 23, 2016 1. Background and Significance BDD is defined as a preoccupation with an imagined defect in appearance; if a slight physical anomaly is present, the concern is markedly excessive (American Psychiatric Association [APA], 1994). Preoccupations may focus on any body area but commonly involve the face or head, most often the skin, hair, or nose (Phillips et al., 1993). These preoccupations have an obsessional quality, in that they occur frequently and are usually difficult to resist or control (Phillips et al., 1998). Additionally, more than 90% of BDD patients perform repetitive, compulsive behaviors (Phillips et al., 1998), such as frequent mirror checking (Alliez & Robin, 1969), excessive grooming (Vallat et al., 1971), and skin picking (Phillips & Taub, 1995). Accordingly, a core component of Cognitive-Behavioral treatment for BDD is exposure and response prevention (ERP). Exposure and response prevention involves asking patients to gradually expose themselves to situations that make them anxious (e.g. talking to a stranger, going to a party) while refraining from engaging in any rituals (e.g. excessive grooming or camouflaging) or safety behaviors (e.g. avoiding eye contact). Rituals and safety behaviors are thought to maintain the fear response because they prevent the sufferer from staying in contact with the stimulus long enough for his or her anxiety to extinguish. By exposing the patient to the feared situation while preventing the rituals and safety behaviors, the patient’s anxiety is allowed to naturally extinguish and he is able to acquire a sense of safety in the presence of the feared stimulus.
    [Show full text]
  • Genefor the De Novo
    Agric. Biol. Chem., 47 (10), 2405~2408, 1983 2405 Rapid Paper B; these two proteins are collectively termed quinolinate synthetase, (2) Protein B converts Synthesis of Quinolinic Acid by aspartic acid to an intermediate capable of the EnzymePreparation of undergoing condensation with DHAP cata- Escherichia coli Which Contains lyzed by Protein A, (3) Proteins A and B are coded by nadA and nadB, respectively, and (4) a Plasmid Carrying the nad the quinolinate synthetase system is subjected Gene for the de novo to feedback inhibition as well as end product Synthesis of NAD repression. An outline of quinolinic acid syn- thesis is shown in Fig. 1. Intermediates of Masaaki Kuwahara, Mizuyo Yonehana, quinolinic acid synthesis, however, have not Tetsuhiro Kimura and Yutaka Ishida yet been isolated in pure forms except for butynedioic acid and its amination product2) Department of Food Science, KagawaUniversity, which are proposed to be intermediates. Our Miki-cho, Kagawa 761-07, Japan experiment aimed to elucidate the inter- Received March 17, 1983 mediary metabolism of the de novo pathway for NADsynthesis using recombinant DNA A plasmid, pNADHl, carrying the nad gene for the de techniques with an E. coli host-vector system. novo synthesis of NADwas constructed with pBR322 and chromosomal DNAof Escherichia coli. Cleavage by re- MATERIALS AND METHODS striction endonucleases showed that the plasmid contained a DNAinsert of 8.9 Kbp at the Hin&lll site ofpBR322. Strains. Escherichia coli C600 (F~, thr~, leu", thi ~, m~, The cell-free extract of a transformant of E. coli C600 r~, LacY) and HB101 carrying plasmid pBR322 were which contained the plasmid formed 5 times more quinol- provided by Prof.
    [Show full text]
  • Ibotenic Acid
    Ibotenic acid Catalog Number I2765 Storage at Room Temperature Product Description Preparation Instructions Molecular Formula: C5H6N2O4 This product is soluble in water (1 mg/ml) with Molecular Weight: 158.1 < 5 min. sonication, yielding a clear, colorless CAS Number: 2552-55-8 solution. Melting point: 151-152 °C1 Synonyms: α-amino-3-hydroxy-5-isoxazoleacetic Storage/Stability acid1 Store the product desiccated at –20 C and it remains active for at least 3 years. This product is the principal toxin found in many mushroom varieties. Cells metabolize this product to References another active derivative, muscimol. Both of these 1. The Merck Index, 11th ed., Entry# 4808. toxins act as excitatory amino acids by mimicking the 2. Collingridge, et al., Excitatory amino acid receptors natural transmitters, glutamic acid and aspartic acid, on in the vertebrate central nervous system. neurons in the central nervous system.2,3 These toxins Pharmacological Review, 40(2), 143 (1989). may also cause selective death of neurons sensitive to these excitatory amino acids.4,5 This product is a potent 3. Johnston, G. A., et al., Spinal interneuron excitation glutamate agonist, which has been used to potentiate by conformationally restricted analogues of L- anesthesia and to inhibit tremor and emesis. glutamic acid. Nature, 248(5451), 804-805 (1974). 4. Gallagher, M., et al., The amygdala central nucleus This product has also been used to suppress enzymatic and appetitive Pavlovian conditioning: lesions activities. When injected into rat brain, it was shown to impair one class of conditioned behavior. J. suppress choline acetyltransferase activity.6 Seven days after injection, enzyme levels had decreased 60%; Neurosci., 10(6), 1906-1911 (1990) after 3 months activity had returned to normal.
    [Show full text]
  • And L- Glutamic Acid (030802, 374350) Technical Document
    Gamma aminobutyric acid (GABA) and L- Glutamic Acid (030802, 374350) Technical Document Reason for Issuance: New Active Ingredient Date Issued: August 1998 EPA Publication Number: EPA 730-F-98-019 1. Description of the Chemical o Generic Name(s)of the Active Ingredient(s): Gamma aminobutyric Acid and L- Glutamic Acid o OPP Chemical Codes: 030802 and 374350 o Year of Initial Registration: 1998 o Pesticide Type: Biochemical plant growth regulator o U.S. and Foreign Producers: Auxein Corporation 2. Use Sites, Application Timing & Target Pests Application of AuxiGro WP, the end-use product containing GABA and L-Glutamic Acid, enhances plant growth. AuxiGro WP may be used on beans, cole crops, green peppers, lettuce, peanuts, potatoes, spinach, tomatoes, lawn and turfgrasses, and ornamentals. Methods of application include both foliar and drench treatments. 3. Science Findings A. Toxicololgy Mammalian toxicology data requirements have been submitted and adequately satisfy requirements to support the unconditional registration of AuxiGro WP. The data which were submitted for this product indicated: an acute oral study (Tox Category IV), an acute dermal study (Tox Category IV), an acute inhalation study (Tox Category IV), a primary dermal irritation study (Tox Category IV), a primary eye irritation study (Tox Category III), and a dermal sensitization study (non- sensitizer). Data waivers accepted include mutagenicity, immunotoxicity, and genotoxicity. B. Human Health Effects a. Acute and Chronic Dietary Risks for Sensitive Subpopulations, Particularly Infants and Children The two active ingredients of AuxiGro, L-Glutamic acid and gamma aminobutyric acid (GABA) are amino acids naturally present in plants and animals. Both compounds serve as brain neurotransmitters.
    [Show full text]
  • Differential Control of Steroidogenesis by Nitric Oxide and Its Adaptation with Hypoxia
    259 THEMATIC REVIEW eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia Charles A Ducsay and Dean A Myers1 Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA 1Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA (Correspondence should be addressed to C A Ducsay; Email: [email protected]) Abstract Nitric oxide (NO) plays a role in a wide range of physiological regulation of NO synthases in specific endocrine tissues processes. Aside from its widely studied function in the including ovaries, testes, and adrenal glands. The effects of regulation of vascular function, NO has been shown to hypoxia on generation of NO and subsequent effects on impact steroidogenesis in a number of different tissues. The steroid biosynthesis will also be examined. Finally, a potential goal of this review is to explore the effects of NO on steroid model for the interaction of hypoxia on NO synthesis and production and further, to discern its source(s) and steroid production is proposed. mechanism of action. Attention will be given to the Journal of Endocrinology (2011) 210, 259–269 Introduction NO and steroidogenesis The initial rate-limiting step in steroidogenesis involves Nitric oxide (NO) is a diatomic free-radical gas involved in a cholesterol transport to the inner mitochondrial membrane number of physiologic processes (Moncada & Palmer 1991, by steroidogenic acute regulatory protein (StAR) and its Moncada et al.1991) and is synthesized from L-arginine by a binding partner, peripheral benzodiazepine receptor.
    [Show full text]
  • NMDA Agonists Using ALZET Osmotic Pumps
    ALZET® Bibliography References on the Administration of NMDA Agonists Using ALZET Osmotic Pumps Aspartic Acid P7453: M. Domercq, et al. Excitotoxic oligodendrocyte death and axonal damage induced by glutamate transporter inhibition. Glia 2005;52(1):36-46 ALZET Comments: Oligonucleotide, antisense; oligonucleotide sense; kainate, dihydro-; aspartic acid, DL-threo-B-benzyloxy-; Saline, sterile; CSF/CNS (optic nerve); Rabbit; 1003D; 3 days; Controls received mp w/ vehicle, or contralateral nerves; antisense (glutamate transporters GLAST + GLT-1); animal info (adult, male, white New Zealand). P6888: J. Darman, et al. Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. Journal of Neuroscience 2004;24(34):7566-7575 ALZET Comments: Aspartic acid, dl-threo-B-hydroxy; spermine, 1-naphthyl acetyl; CSF/CNS (intrathecal, subarachnoid space); Rat; 1007D; 7 days; Controls received mp w/ saline; enzyme inhibitors (GLT-1, GluR2). P3908: A. Hirata, et al. AMPA receptor-mediated slow neuronal death in the rat spinal cord induced by long-term blockade of glutamate transporters with THA. Brain Research 1997;771(37-44 ALZET Comments: Aspartic acid, dl-threo-B-hydroxy; Glutamate, l-; CSF, artificial;; CSF/CNS (subarachnoid space, intrathecal); Rat; 2ML1; no duration posted; dose-response; cannula position verified. P0289: R. M. Mangano, et al. Chronic infusion of endogenous excitatory amino acids into rat striatum and hippocampus. Brain Res. Bull 1983;10(47-51 ALZET Comments: Aminobutyric acid, Y-; Aspartic acid, dl-threo-B-hydroxy; Aspartic acid, l-; Cysteine sulfinic acid; Glutamic acid, l-; Radio-isotopes; 3H tracer; Acetate; Saline; CSF/CNS (corpus striatum); CSF/CNS (hippocampus); Rat; 2002; 2 weeks; comparison of injec.
    [Show full text]
  • Amino Acid Transport Pathways in the Small Intestine of the Neonatal Rat
    Pediat. Res. 6: 713-719 (1972) Amino acid neonate intestine transport, amino acid Amino Acid Transport Pathways in the Small Intestine of the Neonatal Rat J. F. FITZGERALD1431, S. REISER, AND P. A. CHRISTIANSEN Departments of Pediatrics, Medicine, and Biochemistry, and Gastrointestinal Research Laboratory, Indiana University School of Medicine and Veterans Administration Hospital, Indianapolis, Indiana, USA Extract The activity of amino acid transport pathways in the small intestine of the 2-day-old rat was investigated. Transport was determined by measuring the uptake of 1 mM con- centrations of various amino acids by intestinal segments after a 5- or 10-min incuba- tion and it was expressed as intracellular accumulation. The neutral amino acid transport pathway was well developed with intracellular accumulation values for leucine, isoleucine, valine, methionine, tryptophan, phenyl- alanine, tyrosine, and alanine ranging from 3.9-5.6 mM/5 min. The intracellular accumulation of the hydroxy-containing neutral amino acids threonine (essential) and serine (nonessential) were 2.7 mM/5 min, a value significantly lower than those of the other neutral amino acids. The accumulation of histidine was also well below the level for the other neutral amino acids (1.9 mM/5 min). The basic amino acid transport pathway was also operational with accumulation values for lysine, arginine and ornithine ranging from 1.7-2.0 mM/5 min. Accumulation of the essential amino acid lysine was not statistically different from that of nonessential ornithine. Ac- cumulation of aspartic and glutamic acid was only 0.24-0.28 mM/5 min indicating a very low activity of the acidic amino acid transport pathway.
    [Show full text]
  • Occurrence of Agmatine Pathway for Putrescine Synthesis in Selenomonas Ruminatium
    Biosci. Biotechnol. Biochem., 72 (2), 445–455, 2008 Occurrence of Agmatine Pathway for Putrescine Synthesis in Selenomonas ruminatium Shaofu LIAO,1;* Phuntip POONPAIROJ,1;** Kyong-Cheol KO,1;*** Yumiko TAKATUSKA,1;**** y Yoshihiro YAMAGUCHI,1;***** Naoki ABE,1 Jun KANEKO,1 and Yoshiyuki KAMIO2; 1Laboratory of Applied Microbiology, Department of Microbial Biotechnology, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiyamachi, Aobaku, Sendai 981-8555, Japan 2Department of Human Health and Nutrition, Graduate School of Comprehensive Human Sciences, Shokei Gakuin University, 4-10-1 Yurigaoka, Natori 981-1295, Japan Received August 28, 2007; Accepted November 16, 2007; Online Publication, February 7, 2008 [doi:10.1271/bbb.70550] Selenomonas ruminantium synthesizes cadaverine and Polyamines such as putrescine, cadaverine, and putrescine from L-lysine and L-ornithine as the essential spermidine are essential constituents of peptidoglycan constituents of its peptidoglycan by a constitutive lysine/ and they play a significant role in the maintenance of the ornithine decarboxylase (LDC/ODC). S. ruminantium integrity of the cell envelope in Selenomonas ruminan- grew normally in the presence of the specific inhibitor tium, Veillonella parvulla, V. alcalescens, and Anaero- for LDC/ODC, DL- -difluoromethylornithine, when vibrio lipolytica.1–3) When S. ruminantium and two arginine was supplied in the medium. In this study, species of Veillonella are grown in a medium supple- we discovered the presence of arginine decarboxylase mented with putrescine or cadaverine, putrescine and (ADC), the key enzyme in agmatine pathway for cadaverine respectively link covalently to the -carbox- putrescine synthesis, in S. ruminantium. We purified yl group of the D-glutamic acid residue of the peptido- and characterized ADC and cloned its gene (adc) from glycan, which is catalyzed by diamine:lipid intermediate S.
    [Show full text]