Changes in the Dimeric State of Neuronal Nitric Oxide Synthase
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
2016 Bill No. CS for SB 1528 Ì460300XÎ460300
Florida Senate - 2016 PROPOSED COMMITTEE SUBSTITUTE Bill No. CS for SB 1528 460300 Ì460300XÎ 576-03397-16 Proposed Committee Substitute by the Committee on Appropriations (Appropriations Subcommittee on Criminal and Civil Justice) 1 A bill to be entitled 2 An act relating to illicit drugs; amending s. 893.02, 3 F.S.; defining terms; deleting a definition; revising 4 definitions; amending s. 893.03, F.S.; providing that 5 class designation is a way to reference scheduled 6 controlled substances; adding, deleting, and revising 7 the list of Schedule I controlled substances; revising 8 the list of Schedule III anabolic steroids; amending 9 s. 893.033, F.S.; adding, deleting, and revising the 10 list of precursor and essential chemicals; amending s. 11 893.0356, F.S.; defining the term “substantially 12 similar”; deleting the term “potential for abuse”; 13 requiring that a controlled substance analog be 14 treated as the highest scheduled controlled substance 15 of which it is an analog; amending s. 893.13, F.S.; 16 creating a noncriminal penalty for selling, 17 manufacturing, or delivering, or possessing with 18 intent to sell, manufacture, or deliver any unlawful 19 controlled substance in, on, or near an assisted 20 living facility; creating a criminal penalty for a 21 person 18 years of age or older who delivers to a 22 person younger than 18 years of age any illegal 23 controlled substance, who uses or hires a person 24 younger than 18 years of age in the sale or delivery 25 of such substance, or who uses a person younger than 26 18 years of age to assist in avoiding detection for 27 specified violations; deleting a criminal penalty for Page 1 of 197 2/12/2016 8:29:32 AM Florida Senate - 2016 PROPOSED COMMITTEE SUBSTITUTE Bill No. -
(12) United States Patent (10) Patent No.: US 7.803,838 B2 Davis Et Al
USOO7803838B2 (12) United States Patent (10) Patent No.: US 7.803,838 B2 Davis et al. (45) Date of Patent: Sep. 28, 2010 (54) COMPOSITIONS COMPRISING NEBIVOLOL 2002fO169134 A1 11/2002 Davis 2002/0177586 A1 11/2002 Egan et al. (75) Inventors: Eric Davis, Morgantown, WV (US); 2002/0183305 A1 12/2002 Davis et al. John O'Donnell, Morgantown, WV 2002/0183317 A1 12/2002 Wagle et al. (US); Peter Bottini, Morgantown, WV 2002/0183365 A1 12/2002 Wagle et al. (US) 2002/0192203 A1 12, 2002 Cho 2003, OOO4194 A1 1, 2003 Gall (73) Assignee: Forest Laboratories Holdings Limited 2003, OO13699 A1 1/2003 Davis et al. (BM) 2003/0027820 A1 2, 2003 Gall (*) Notice: Subject to any disclaimer, the term of this 2003.0053981 A1 3/2003 Davis et al. patent is extended or adjusted under 35 2003, OO60489 A1 3/2003 Buckingham U.S.C. 154(b) by 455 days. 2003, OO69221 A1 4/2003 Kosoglou et al. 2003/0078190 A1* 4/2003 Weinberg ...................... 514f1 (21) Appl. No.: 11/141,235 2003/0078517 A1 4/2003 Kensey 2003/01 19428 A1 6/2003 Davis et al. (22) Filed: May 31, 2005 2003/01 19757 A1 6/2003 Davis 2003/01 19796 A1 6/2003 Strony (65) Prior Publication Data 2003.01.19808 A1 6/2003 LeBeaut et al. US 2005/027281.0 A1 Dec. 8, 2005 2003.01.19809 A1 6/2003 Davis 2003,0162824 A1 8, 2003 Krul Related U.S. Application Data 2003/0175344 A1 9, 2003 Waldet al. (60) Provisional application No. 60/577,423, filed on Jun. -
Tetrahydrobiopterin Loading Test in Hyperphenylalaninemia
003 1-399819113005-0435$03.00/0 PEDIATRIC RESEARCH Vol. 30, No. 5, 1991 Copyright 0 199 1 International Pediatric Research Foundation, Inc. Pr~ntc.d in U.S. A Tetrahydrobiopterin Loading Test in Hyperphenylalaninemia ALBERT0 PONZONE, ORNELLA GUARDAMAGNA, SILVIO FERRARIS, GIOVANNI B. FERRERO, IRMA DIANZANI, AND RICHARD G. H. COTTON InstiflifeofPediatric Clinic(A.P., O.G., S.F., G.B.F., I.D.], University of Torino, 10126 Torino, Italy and Olive Miller Laboratory [R.G.H.C.],Murdoch Institute, Royal Children's Hospital, Vicroria,Australia 3052 ABSTRACT. Some cases of primary hyperphenylalanine- PKU to describe some cases clinically unresponsive to a Phe- mia are not caused by the lack of phenylalanine hydroxyl- restricted diet and later shown to be due to BH4 deficiency ase, but by the lack of its cofactor tetrahydrobiopterin. ( 1-4). These patients are not clinically responsive to a phenylal- By analyzing all the essential components of the complex anine-restricted diet, but need specific substitution therapy. hydroxylation system of aromatic amino acids, it became appar- Thus, it became necessary to examine all newborns ent that a defect in the BH4 recycling enzyme DHPR (EC screened as positive with the Guthrie test for tetrahydro- 1.66.99.7) and two defects in BH4 synthetic pathway enzymes, biopterin deficiency. Methods based on urinary pterin or guanosine triphosphate cyclohydrolase I (EC 3.5.4.16) and 6- on specific enzyme activity measurements are limited in PPH4S, may lead to cofactor deficiency resulting in HPA and in their availability, and the simplest method, based on the impaired production of dopamine and serotonin (5-7). -
Coronary Microvascular Dysfunction in CAD: Consequences and Potential Therapeutic Applications
4 Coronary Microvascular Dysfunction in CAD: Consequences and Potential Therapeutic Applications Alan N. Beneze1, Jeffrey M. Gold4 and Betsy B. Dokken1,2,3 1University of Arizona College of Medicine 2University of Arizona Department of Medicine, Section of Endocrinology 3University of Arizona Sarver Heart Center 4Inpatient Physicians Consultants, Tucson, Arizona USA 1. Introduction Substantial research and clinical effort has been directed toward the understanding, identification and management of coronary artery disease (CAD). As a result, the processes of cholesterol accumulation and inflammation that lead to large vessel occlusions have been fully elucidated. In contrast to those with CAD, many patients have symptoms of angina and reductions in coronary flow reserve despite normal coronary angiography of the large epicardial arteries. In this situation the vessels that limit flow to myocardium are the more distal epicardial prearterioles and intramyocardial arterioles – vessels typically too small to be directly visualized by conventional coronary angiography. These vessels comprise the coronary microcirculation. Coronary microvascular dysfunction (CMVD), in contrast to CAD, continues to be poorly understood and difficult to manage. In addition, the presence of CMVD can be a confounding factor in the management of patients with CAD. 2. Anatomy and physiology of the coronary microcirculation The coronary arterial network is generally divided into three sequential morphological zones. The large epicardial coronary arteries decrease in diameter from 2-5 to 500 microns as they branch off of the aorta and travel distally along the epicardium. Distal to the large coronary arteries are epicardial pre-arterioles that decrease in diameter from 500 to 100 microns. Finally, the pre-arterioles give rise to intramyocardial arterioles that measure 100 microns or less in diameter. -
(12) United States Patent (10) Patent N0.: US 6,310,270 B1 Huang Et Al
US006310270B1 (12) United States Patent (10) Patent N0.: US 6,310,270 B1 Huang et al. (45) Date of Patent: Oct. 30, 2001 (54) ENDOTHELIAL NOS KNOCKOUT MICE Benrath, J. et al., “Substance P and nitric oxide mediate AND METHODS OF USE Wound healing of ultraviolet photodamaged rat skin: evi dence for an effect of nitric oxide on keratinocyte prolifera (75) Inventors: Paul L. Huang, Boston; Mark C. tion,” Nerosci. Letts. 200.'17—20 (Nov. 1995). Fishman, Newton Center; Michael A. Boeckxstaens, G.E. et al., “Evidence for nitric oxide as Moskowitz, Belmont, all of MA (US) mediator of non—adrenergic, non—cholinergic relaxations induced by ATP and GABA in the canine gut,” Br J. (73) Assignee: The General Hospital Corporation, Pharmacol. 102:434—438 (1991). Boston, MA (US) Bohme, G.A. et al., “Possible involvement of nitric oxide in ( * ) Notice: Subject to any disclaimer, the term of this long—term potentiation,” Eur J. Pharmacol. 199:379—381 patent is extended or adjusted under 35 (1991). U.S.C. 154(b) by 0 days. Booth, R.F.G. et al., “Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular (21) Appl. No.: 08/818,082 manipulation,” Atherosclerosis 76.'257—268 (1989). Bredt, D.S. et al., “Localization of nitric oxide synthase (22) Filed: Mar. 14, 1997 indicating a neural role for nitric oxide,” Nature Related US. Application Data 347:768—770. (60) Provisional application No. 60/027,362, ?led on Sep. 18, Bredt, D.S. and Snyder, S.H., “Isolation of nitric oxide 1996, and provisional application No. -
Nitric Oxide Synthase Inhibitors As Antidepressants
Pharmaceuticals 2010, 3, 273-299; doi:10.3390/ph3010273 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review Nitric Oxide Synthase Inhibitors as Antidepressants Gregers Wegener 1,* and Vallo Volke 2 1 Centre for Psychiatric Research, University of Aarhus, Skovagervej 2, DK-8240 Risskov, Denmark 2 Department of Physiology, University of Tartu, Ravila 19, EE-70111 Tartu, Estonia; E-Mail: [email protected] (V.V.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +4577893524; Fax: +4577893549. Received: 10 November 2009; in revised form: 7 January 2010 / Accepted: 19 January 2010 / Published: 20 January 2010 Abstract: Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression. Keywords: nitric oxide; antidepressants; psychiatry; depression; anxiety 1. Introduction Recent data from Denmark and Europe [1,2], indicate that brain disorders account for 12% of all direct costs in the Danish health system and 9% of the total drug consumption was used for treatment of brain diseases. -
7-Nitro Indazole, a Selective Neuronal Nitric Oxide Synthase Inhibitor in Vivo, Impairs Spatial Learning in The
Downloaded from learnmem.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH 7-Nitro Indazole, a Selective Neuronal Nitric Oxide Synthase Inhibitor in Vivo, Impairs Spatial Learning in the Rat Christian H61scher, 1'3 Liam McGlinchey, 1 Roger Anwyl, 2 and Michael J. Rowan ~Department of Pharmacology and Therapeutics and 2Department of Physiology Trinity College Dublin 2, Republic of Ireland Abstract Introduction Nitric oxide (NO) is an intercellular messen- Nitric oxide (NO) is an intercellular ger that plays a role in many physiological systems. messenger that has been suggested to have In the nervous system, NO acts as a neurotrans- a role in learning and memory formation. mitter (Amir 1992). The enzyme NO synthase Previous studies with nonselective NO (NOS) has been found in neurons (Bredt and Sny- synthase inhibitors have produced der 1992; Vincent and Kimura 1992), and endog- contradictory results in learning enous NO production occurs in neuronal cultures experiments. However, these drugs also (Ma et al. 1991). At least three isoforms of NOS produced blood pressure changes, as NO is have been identified. NOS isoform I is found in an endothelial-derived relaxing factor. A neurons, whereas isoform III has been purified novel NO synthase inhibitor, 7-nitro from endothelial cells (Schmidt et al. 1992). Both indazole (7-NI), as a dose (30 mg/kg i.p.) isoforms are Ca 2+ dependent (Moncada and shown previously to inhibit neuronal NO Palmer 1992). Isoform type II is inducible and synthase by 85% without affecting blood Ca 2+ independent. It is found in most tissues of pressure, produced amnesic effects both in the body (Kilbourn 1991; Nathan 1991). -
Example of How Amehsi Specification Indicators Can Be Mapped to Health
Example of how Amehsi Specification Indicators can be Mapped to Health Conditions and Health Statuses The information presented here may be covered by copyrights and patents Some of the Amehsi Factors which can be alleviated using Amehsi Specification Recommendations and Demise Oncology Leukemia Lymphoma HIV Information. This document may be protected by copyrights and patents Choline Deficiency or Circumstantial Choline Deficiency from upregulated Choline Kinase Pathway or Kennedy Pathway Factors Causal Causal Causal Causal Causal Homocysteine Required as Symptom, Correlated and Incipiently Causal, inhibits PEMT Required Causal Causal Causal S-Adenosyl Homocysteine Downregulat Required as Symptom, Correlated and Incipiently Causal, inhibits PEMT Required Causal ed PEMT Causal Trimethylamine-N-Oxide Causal, inhibits PEMT Causal Causal Causal Incipient Enabler Choline Kinase Upregulation Causal Required Required uNOS Required Required as both PEMT1 or PEMT2 since Diagnostic Assay sometimes does not report if one of these is inhibited while the other is not. PEMT produces a Monomethylethanolamine that Phosphatidylethanolamine deteriorates PCBs, Dioxins, Aryl Methyltransferase Downregulation Cyclic Hydrocarbons, Alkyl Halides, other Carcinogens and produces Serine Proteases that catabolize Amino acids to thier most basic structures, resulting in purified cellular environment and embryonic Causal cellular plasticity Required Required Required Inducible Nitric Oxide Synthase, Required, inhibits PEMT and upregulated Choline kinase, as well as -
Enos-Uncoupling in Age-Related Erectile Dysfunction
International Journal of Impotence Research (2011) 23, 43–48 & 2011 Macmillan Publishers Limited All rights reserved 0955-9930/11 www.nature.com/ijir ORIGINAL ARTICLE eNOS-uncoupling in age-related erectile dysfunction JM Johnson, TJ Bivalacqua, GA Lagoda, AL Burnett and B Musicki Department of Urology, The Johns Hopkins University, Baltimore, MD, USA Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS -
Effects of Nitric Oxide Synthase Inhibitors on Equine and Bovine Follicular Dynamics and Steroidogenesis
Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 2001 Effects of Nitric Oxide Synthase Inhibitors on Equine and Bovine Follicular Dynamics and Steroidogenesis. Carlos Roberto fontes Pinto Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Pinto, Carlos Roberto fontes, "Effects of Nitric Oxide Synthase Inhibitors on Equine and Bovine Follicular Dynamics and Steroidogenesis." (2001). LSU Historical Dissertations and Theses. 430. https://digitalcommons.lsu.edu/gradschool_disstheses/430 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. -
Cgmp Signaling and Vascular Smooth Muscle Cell Plasticity
Journal of Cardiovascular Development and Disease Review cGMP Signaling and Vascular Smooth Muscle Cell Plasticity Moritz Lehners †, Hyazinth Dobrowinski †, Susanne Feil and Robert Feil * ID Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, Germany; [email protected] (M.L.); [email protected] (H.D.); [email protected] (S.F.) * Correspondence: [email protected]; Tel.: +49-7071-2973350 † These authors contributed equally to this work. Received: 14 March 2018; Accepted: 16 April 2018; Published: 19 April 2018 Abstract: Cyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as atherosclerosis. Recent studies have shown that VSMCs contribute to the development of atherosclerotic plaques by clonal expansion and transdifferentiation to macrophage-like cells. VSMCs express a variety of cGMP generators and effectors, including NO-sensitive guanylyl cyclase (NO-GC) and cGMP-dependent protein kinase type I (cGKI), respectively. According to the traditional view, cGMP inhibits VSMC proliferation, but this concept has been challenged by recent findings supporting a stimulatory effect of the NO-cGMP-cGKI axis on VSMC growth. Here, we summarize the relevant studies with a focus on VSMC growth regulation by the NO-cGMP-cGKI pathway in cultured VSMCs and mouse models of atherosclerosis, restenosis, and angiogenesis. We discuss potential reasons for inconsistent results, such as the use of genetic versus pharmacological approaches and primary versus subcultured cells. We also explore how modern methods for cGMP imaging and cell tracking could help to improve our understanding of cGMP’s role in vascular plasticity. -
7-Nitro Inctazole, an Inhibitor of Neuronal Nitric Oxide Synthase, Attenuates Pilocarpine-Induced Seizures
CORE Metadata, citation and similar papers at core.ac.uk Provided by Erasmus University Digital Repository eJp ELSEVIER European Journal of Pharmacology287 (1995) 211-213 Short communication 7-Nitro inctazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures Redmer Van Leeuwen, Ren6 De Vries, Mihailo R. Dzoljic * Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, Netherlands Received 26 June 1995; revised 9 October 1995; accepted 13 October 1995 Abstract 7-Nitro indazole (25-100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS. Keywords: Epilepsy; Nitric oxide (NO); Nitric oxide (NO) synthase; 7-Nitro indazole; Pilocarpine; Seizure 1. Introduction nine), potentiated seizures induced in rats by various convulsant compounds, such as quinolinate (Haberny As a retrograde messenger, nitric oxide (NO) in- et al., 1992), kainic acid (Rondouin et al., 1993) and duces presynaptically the release of several neurotrans- bicuculline (Wang et al., 1994). These data indicated mitters, including the excitatory amino acid, L-gluta- that NO is an endogenous anticonvulsant substance. mate (Montague et al., 1994). This indicates that NO All NO synthase inhibitors used in these studies are deranges the neurotransmitter balance in the central alkyl esters of arginine and affect both neuronal NO nervous system (CNS) and affects neuronal excitability.