hyperammonemia

Summary

Summary: Metabolic disorder characterized by elevated level of ammonia in blood.

Top Publications

  1. ncbi Mechanisms of hyperammonemia
    Claude Bachmann
    Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland
    Clin Chem Lab Med 40:653-62. 2002
  2. ncbi Hyperammonemia in the ICU
    Alison S Clay
    Department of Surgery and Medicine, Duke University Medical Center, Box 2945, Durham, NC 27710, USA
    Chest 132:1368-78. 2007
  3. ncbi N-carbamylglutamate in emergency management of hyperammonemia in neonatal acute onset propionic and methylmalonic aciduria
    Luca Filippi
    Neonatal Intensive Care Unit, Department of Critical Care Medicine, A Meyer University Children s Hospital, IT 50134 Florence, Italy
    Neonatology 97:286-90. 2010
  4. ncbi Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure
    Flemming Tofteng
    Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    J Cereb Blood Flow Metab 26:21-7. 2006
  5. ncbi Hyperammonemia-induced toxicity for the developing central nervous system
    Laurène Cagnon
    Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CI 02 33, Avenue Pierre Decker 2, CH 1011 Lausanne, Switzerland
    Brain Res Rev 56:183-97. 2007
  6. pmc Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes
    Marshall L Summar
    Vanderbilt University Medical Center, Nashville, TN, USA
    Acta Paediatr 97:1420-5. 2008
  7. ncbi Effect of morin on the levels of circulatory liver markers and redox status in experimental chronic hyperammonaemic rats
    S Subash
    Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
    Singapore Med J 49:650-5. 2008
  8. pmc Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients
    Shu jie Chen
    Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
    World J Gastroenterol 14:1914-8. 2008
  9. pmc Alterations of blood brain barrier function in hyperammonemia: an overview
    Marta Skowronska
    Departament of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02 106 Warszawa, Pawinskiego 5, Poland
    Neurotox Res 21:236-44. 2012
  10. ncbi Hyperammonemia increases the expression and activity of the glutamine/arginine transporter y+ LAT2 in rat cerebral cortex: implications for the nitric oxide/cGMP pathway
    Magdalena Zielinska
    Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 Str, 02 106 Warsaw, Poland
    Neurochem Int 58:190-5. 2011

Detail Information

Publications274 found, 100 shown here

  1. ncbi Mechanisms of hyperammonemia
    Claude Bachmann
    Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland
    Clin Chem Lab Med 40:653-62. 2002
    b>Hyperammonemia is mainly found in hepatic encephalopathy and in genetic defects of the urea cycle or other pathways of the intermediary metabolism...
  2. ncbi Hyperammonemia in the ICU
    Alison S Clay
    Department of Surgery and Medicine, Duke University Medical Center, Box 2945, Durham, NC 27710, USA
    Chest 132:1368-78. 2007
    ..When hyperammonemia is not thought to be the result of liver failure, treatment for an occult disorder of metabolism must begin ..
  3. ncbi N-carbamylglutamate in emergency management of hyperammonemia in neonatal acute onset propionic and methylmalonic aciduria
    Luca Filippi
    Neonatal Intensive Care Unit, Department of Critical Care Medicine, A Meyer University Children s Hospital, IT 50134 Florence, Italy
    Neonatology 97:286-90. 2010
    In propionic aciduria and methylmalonic aciduria, hyperammonemia as a symptom of metabolic decompensation is one of the major clinical problems...
  4. ncbi Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure
    Flemming Tofteng
    Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    J Cereb Blood Flow Metab 26:21-7. 2006
    ..prospective study of patients with fulminant hepatic failure (FHF), we tested the hypothesis that arterial hyperammonemia results in cerebral accumulation of the osmotic active amino acids glutamine and alanine, processes that were ..
  5. ncbi Hyperammonemia-induced toxicity for the developing central nervous system
    Laurène Cagnon
    Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CI 02 33, Avenue Pierre Decker 2, CH 1011 Lausanne, Switzerland
    Brain Res Rev 56:183-97. 2007
    In pediatric patients, hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle deficiencies or organic acidemias...
  6. pmc Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes
    Marshall L Summar
    Vanderbilt University Medical Center, Nashville, TN, USA
    Acta Paediatr 97:1420-5. 2008
    ..A large longitudinal interventional study of patients with a urea cycle disorder (UCD) in hyperammonaemic crisis was undertaken to amass a significant body of data on their presenting symptoms and survival...
  7. ncbi Effect of morin on the levels of circulatory liver markers and redox status in experimental chronic hyperammonaemic rats
    S Subash
    Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
    Singapore Med J 49:650-5. 2008
    ..Our aim was to investigate the effect of morin on circulatory liver markers, lipid peroxidation and antioxidant status in ammonium chloride (AC)-induced hyperammonaemic rats...
  8. pmc Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients
    Shu jie Chen
    Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
    World J Gastroenterol 14:1914-8. 2008
    ..To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients...
  9. pmc Alterations of blood brain barrier function in hyperammonemia: an overview
    Marta Skowronska
    Departament of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02 106 Warszawa, Pawinskiego 5, Poland
    Neurotox Res 21:236-44. 2012
    Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute--(ALF) or chronic liver failure...
  10. ncbi Hyperammonemia increases the expression and activity of the glutamine/arginine transporter y+ LAT2 in rat cerebral cortex: implications for the nitric oxide/cGMP pathway
    Magdalena Zielinska
    Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 Str, 02 106 Warsaw, Poland
    Neurochem Int 58:190-5. 2011
    The pathogenesis of hepatic encephalopathy (HE) is associated with hyperammonemia (HA) and subsequent exposure of the brain to excess of ammonia...
  11. ncbi Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy
    Regina Rodrigo
    Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Valencia, Spain
    Gastroenterology 139:675-84. 2010
    b>Hyperammonemia and inflammation cooperate to induce neurological alterations in hepatic encephalopathy...
  12. ncbi HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation
    S Fecarotta
    Department of Pediatrics, Federico II University, Via S Pansini 5, 80131 Naples, Italy
    J Inherit Metab Dis 29:186-9. 2006
    ..The diagnosis of HHH syndrome should be considered in patients with fulminant hepatitis-like presentations. Early identification and treatment of these patients can be life-saving and can avoid liver transplantation...
  13. ncbi Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome
    B Y Hsu
    Division of Endocrinology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Pediatr 138:383-9. 2001
    OBJECTIVE: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for ..
  14. ncbi Neurological aspects of hyperinsulinism-hyperammonaemia syndrome
    Nadia Bahi-Buisson
    Department of Paediatric Neurology and Metabolic Diseases, Necker Children s Hospital, Paris V University, Paris, France
    Dev Med Child Neurol 50:945-9. 2008
    ..Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy...
  15. ncbi Transient hyperammonemia due to L-asparaginase therapy in children with acute lymphoblastic leukemia or non-Hodgkin lymphoma
    C Jörck
    Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
    Pediatr Hematol Oncol 28:3-9. 2011
    ..non-Hodgkin lymphoma (NHL) in childhood includes intravenous therapy with asparaginase (Asp), which may cause hyperammonemia. In this study, all patients receiving asparaginase therapy at the Hospital for Children and Adolescents of ..
  16. ncbi Pathogenesis and diagnosis of hepatic encephalopathy
    Mark J W McPhail
    Hepatology Section, Department of Medicine, 10th Floor QEQM Wing, St Mary s Hospital Campus, Imperial College London, South Wharf Street, London W2 1NY, UK
    Expert Rev Gastroenterol Hepatol 4:365-78. 2010
    ..b>Hyperammonemia and subsequent cell swelling is a key pathophysiological abnormality, but this aspect alone is insufficient to ..
  17. ncbi Nitric oxide in hepatic encephalopathy and hyperammonemia
    Vemuganti L Raghavendra Rao
    Department of Neurological Surgery and Cardiovascular Research Center, University of Wisconsin Madison, H4 334 CSC, 600 Highland Avenue, Madison, WI 53792, USA
    Neurochem Int 41:161-70. 2002
    ..b>Hyperammonemia associated with liver dysfunction results in increased NO, which may lead to learning and memory impairments ..
  18. ncbi Direct exposure to ammonia and hyperammonemia increase the extracellular accumulation and degradation of astroglia-derived glutathione in the rat prefrontal cortex
    Wojciech Hilgier
    Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
    Toxicol Sci 117:163-8. 2010
    ..GSH in the microdialysates was significantly elevated in rats with simple hyperammonemia (HA) or hepatic encephalopathy (HE) (three ip administrations of ammonium acetate or thioacetamide, ..
  19. ncbi Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia
    K V Rao
    Laboratory of Neuropathology, Veterans Administration Medical Center, University of Miami School of Medicine, Florida, USA
    Metab Brain Dis 16:67-78. 2001
    ..Altered mitochondrial metabolism appears to be an important mechanism responsible for the cerebral abnormalities associated with HE and other hyperammonemic states...
  20. ncbi Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum
    Nisrin ElMlili
    Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Valencia, Spain
    J Neurochem 112:1005-14. 2010
    ..of the glutamate--nitric oxide (NO)--cGMP pathway is responsible for some cognitive alterations in rats with hyperammonemia and hepatic encephalopathy...
  21. ncbi Acute hyperammonemia activates branched-chain amino acid catabolism and decreases their extracellular concentrations: different sensitivity of red and white muscle
    Milan Holecek
    Department of Physiology, Medical Faculty in Hradec Kralove, Charles University in Prague, Simkova 870, 500 38, Hradec Kralove, Czech Republic
    Amino Acids 40:575-84. 2011
    b>Hyperammonemia is considered to be the main cause of decreased levels of the branched-chain amino acids (BCAA), valine, leucine, and isoleucine, in liver cirrhosis...
  22. ncbi Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations
    Johannes Haberle
    University Children s Hospital Zurich, Division of Metabolism, Zurich, Switzerland
    Hum Mutat 32:579-89. 2011
    Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease...
  23. ncbi Acetyl-L-carnitine in hepatic encephalopathy
    Michele Malaguarnera
    International Ph D Program in Neuropharmacology, University of Catania, Catania, Italy
    Metab Brain Dis 28:193-9. 2013
    ..The aim of this review was to provide an explanation on the possible toxic effects of ammonia in HE and evaluate the potential clinical benefits of ALC...
  24. ncbi Hyperammonemia causes protein oxidation and enhanced proteasomal activity in response to mitochondria-mediated oxidative stress in rat primary astrocytes
    Rebecca Widmer
    Research Institute of Environmental Medicine at the Heinrich Heine University, Dusseldorf, Germany
    Arch Biochem Biophys 464:1-11. 2007
    b>Hyperammonemia, as a consequence of severe liver failure, is strongly associated with the neurological syndrome hepatic encephalopathy (HE) whereby excessive ammonia is metabolized by astrocytes, followed by cell and brain swelling in ..
  25. ncbi Hyperammonemia inhibits the natriuretic peptide receptor 2 (NPR-2)-mediated cyclic GMP synthesis in the astrocytic compartment of rat cerebral cortex slices
    Magdalena Zielinska
    Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02 106 Warsaw, Poland
    Neurotoxicology 28:1260-3. 2007
    The decrease of cyclic GMP (cGMP) level in the brain, contributing to cognitive and memory deficit in hyperammonemia (HA), has been attributed to the interference of ammonia with the NMDA/nitric oxide/soluble guanylate cyclase (GC)/cGMP ..
  26. ncbi The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure
    Peter Nissen Bjerring
    Department of Hepatology, Rigshospitalet, Copenhagen, Denmark
    J Hepatol 57:774-9. 2012
    ..This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA), an extracorporeal liver support system, on cerebral amino acids and lactate to pyruvate ratio...
  27. ncbi Alternative pathway therapy for urea cycle disorders: twenty years later
    M L Batshaw
    Children's National Medical Center, Washington, DC 20010, USA
    J Pediatr 138:S46-54; discussion S54-5. 2001
    ..Finally, it must be acknowledged that alternative pathway therapy has limited effectiveness in preventing hyperammonemia and must be combined with effective dietary management...
  28. ncbi Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation
    Claude Bachmann
    Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne, Switzerland
    Eur J Pediatr 162:410-6. 2003
    ....
  29. ncbi Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis
    Debbie L Shawcross
    Liver Failure Group, Institute of Hepatology, University College London Medical School, 69 75, Chenies Mews, London WC1E 6HX, UK
    J Hepatol 40:247-54. 2004
    ..We tested the hypothesis that SIRS mediators, such as nitric oxide and proinflammatory cytokines, may exacerbate the neuropsychological effects of hyperammonemia in cirrhosis.
  30. pmc Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyperammonemia in rats
    H Tanigami
    Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, 600 North Wolfe Street Blalock 1404, Baltimore, MD 21287 4961, USA
    Neuroscience 131:437-49. 2005
    ..b>Hyperammonemia increased the number of swollen astrocytes in cortex and MSO reduced this increase to control values...
  31. ncbi Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome
    Jason R Treberg
    Department of Biochemistry, Memorial University of Newfoundland, St John s, Newfoundland, Canada
    Am J Physiol Endocrinol Metab 298:E1219-25. 2010
    The hyperinsulism/hyperammonemia (HI/HA) syndrome is caused by glutamate dehydrogenase (GDH) gain-of-function mutations that reduce the inhibition by GTP, consequently increasing the activity of GDH in vivo...
  32. ncbi The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema
    Peter Nissen Bjerring
    Dept Hepatology, section A 2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
    Metab Brain Dis 24:5-14. 2009
    ..This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress, inflammation and regulation of cerebral blood ..
  33. pmc Neurological implications of urea cycle disorders
    A L Gropman
    Department of Neurology, Children s National Medical Center and the George Washington University of the Health Sciences, 111 Michigan Avenue, N W, Washington, DC 20010, USA
    J Inherit Metab Dis 30:865-79. 2007
    ..Thus, both strategies are intriguing areas for potential investigation in human urea cycle disorders...
  34. pmc Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage
    Volodymyr I Pidoplichko
    Department of Neuroscience, Menninger Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 103:11376-80. 2006
    ..The ammonium sensitivity suggests a role for ASIC1s in hepatic encephalopathy, cirrhosis, and other neuronal disorders that are associated with hyperammonemia.
  35. ncbi Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
    S Salvi
    Department of Neurosciences, Pathology, and Radiology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
    Neurology 57:911-4. 2001
    The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome...
  36. ncbi Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene
    Katharina Engel
    Universitatsklinikum Munster, Klinik und Poliklinik für Kinder und Jugendmedizin, Munster, Germany
    Hum Mutat 30:300-7. 2009
    ..of ASS1 shows various clinical manifestations encompassing severely affected patients with fatal neonatal hyperammonemia as well as asymptomatic individuals with only a biochemical phenotype...
  37. ncbi Long-term management of patients with urea cycle disorders
    G T Berry
    Division of Human Genetics and Molecular Biology, Department of Pediatrics, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Pennsylvania 19104-4399, USA
    J Pediatr 138:S56-60; discussion S60-1. 2001
    ....
  38. ncbi Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency
    Peter Gessler
    Klinikum, Klinik fur Kinder und Jugendliche, 78461 Konstanz, Germany
    Eur J Pediatr 169:197-9. 2010
    N-Acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder, which may present in the neonatal period with severe hyperammonemia and marked neurological impairment.
  39. ncbi Urea cycle disorders
    J V Leonard
    Biochemistry, Endocrine and Metabolic Unit, Institute of Child Health, London, UK
    Semin Neonatol 7:27-35. 2002
    ..Severe hyperammonaemia is usually associated with irreversible neurological damage, particularly if levels have been above 800 micromol/l for >24 hours, and the option of withdrawing treatment should be discussed with the family...
  40. ncbi Current concepts in the pathogenesis of urea cycle disorders
    Olivier Braissant
    Inborn Errors of Metabolism, Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CI 02 33, Lausanne, Switzerland
    Mol Genet Metab 100:S3-S12. 2010
    The common feature of urea cycle diseases (UCD) is a defect in ammonium elimination in liver, leading to hyperammonemia. This excess of circulating ammonium eventually reaches the central nervous system, where the main toxic effects of ..
  41. ncbi Urea cycle disorders: clinical presentation outside the newborn period
    Wendy Smith
    Maine Pediatric Specialty Group, Portland, ME 04102, USA
    Crit Care Clin 21:S9-17. 2005
    ..Treatment with dietary protein restriction and medications may be challenging in children...
  42. ncbi The hyperinsulinism/hyperammonemia syndrome
    Andrew A Palladino
    The Children s Hospital of Philadelphia, Division of Endocrinology and Diabetes, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA
    Rev Endocr Metab Disord 11:171-8. 2010
    The hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common form of congenital hyperinsulinism (HI)...
  43. pmc Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?
    Virginie Levrat
    Centre de référence Maladies Héréditaires du Métabolisme, Service de Pediatrie, Hopital Edouard Herriot, Lyon, France
    Orphanet J Rare Dis 3:2. 2008
    b>Hyperammonemia in patients with methylmalonic aciduria (MMA) and propionic aciduria (PA) is caused by accumulation of propionyl-CoA which decreases the synthesis of N-acetyl-glutamate, the natural activator of carbamyl phosphate ..
  44. ncbi Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism
    Charles A Stanley
    Division of Endocrinology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Mol Genet Metab 81:S45-51. 2004
    The second most common form of congenital hyperinsulinism, the hyperinsulinism/hyperammonemia syndrome (HI/HA), is associated with dominantly expressed missense mutations of the mitochondrial matrix enzyme, glutamate dehydrogenase (GDH)...
  45. ncbi Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome
    José A Camacho
    Department of Pediatrics, Division of Human Genetics, University of California, Irvine, CA 92697 3940, USA
    Pediatr Res 60:423-9. 2006
    We studied two related families (HHH013 and HHH015) with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a disorder of the urea cycle and ornithine degradation pathway, who have the same novel ornithine transporter (..
  46. pmc Brain alanine formation as an ammonia-scavenging pathway during hyperammonemia: effects of glutamine synthetase inhibition in rats and astrocyte-neuron co-cultures
    Sherry Dadsetan
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    J Cereb Blood Flow Metab 33:1235-41. 2013
    b>Hyperammonemia is a major etiological toxic factor in the development of hepatic encephalopathy...
  47. ncbi Ornithine transcarbamylase deficiency: a urea cycle defect
    Neil Gordon
    Wilmslow, UK
    Eur J Paediatr Neurol 7:115-21. 2003
    ..Liver transplant can be considered when symptoms are life-threatening, although there may be severe complications.Gene replacement therapy is the hope of the future...
  48. pmc Arginase I deficiency: severe infantile presentation with hyperammonemia: more common than reported?
    Shailly Jain-Ghai
    Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G1X8
    Mol Genet Metab 104:107-11. 2011
    Enzyme defects of the urea cycle typically present with significant hyperammonemia and its associated toxicity, in the first few months of life...
  49. ncbi Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder
    José A Camacho
    Department of Pediatrics, University of Oklahoma Health Sciences Center, 975 N E 10th Street, Biomedical Research Center, Room BRC 256, Oklahoma City, OK 73104, USA
    Mol Genet Metab 79:257-71. 2003
    ..characterized the mitochondrial ornithine transporter (ORNT1), the gene defective in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a urea cycle disorder...
  50. ncbi Hyperammonemia in idiopathic epileptic seizure
    Kensuke Nakamura
    Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo 113 8655, Japan Electronic address
    Am J Emerg Med 31:1486-9. 2013
    It is known that patients with convulsion often present hyperammonemia. The elevation of ammonia levels in convulsion is considered to occur along with extensive muscle contractions, but the details remain unclear...
  51. ncbi Moderate grade hyperammonemia activates lactate dehydrogenase-4 and 6-phosphofructo-2-kinase to support increased lactate turnover in the brain slices
    Aditi Mehrotra
    Department of Zoology, Banaras Hindu University, Varanasi, India
    Mol Cell Biochem 381:157-61. 2013
    ..The low grade hyperammonemia (HA) is a common condition in the patients with chronic hepatic encephalopathy (HE); however, biochemistry of ..
  52. ncbi Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy
    Vicente Felipo
    Laboratory of Neurobiology Centro de Investigación Príncipe Felipe, Valencia, Spain
    Metab Brain Dis 27:51-8. 2012
    To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE)...
  53. ncbi Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved
    Regina Rodrigo
    Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Fundación de la Comunidad Valenciana Centro de Investigacion Principe Felipe, Valencia, Spain
    Neurochem Int 48:472-7. 2006
    ..b>Hyperammonemia and liver failure result in altered glutamatergic neurotransmission, which contributes to hepatic ..
  54. ncbi Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum
    Santosh Singh
    Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, India
    Neurochem Res 33:103-13. 2008
    ..Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated ..
  55. pmc Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis
    Jia Qiu
    Departments of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Am J Physiol Endocrinol Metab 303:E983-93. 2012
    b>Hyperammonemia and sarcopenia (loss of skeletal muscle) are consistent abnormalities in cirrhosis and portosystemic shunting...
  56. ncbi Hyperammonemia due to valproic acid in the psychiatric setting
    Russell B Carr
    Northern Virginia Mental Health Institute, Falls Church, Virginia, USA
    Am J Psychiatry 164:1020-7. 2007
  57. ncbi Interorgan metabolism of ornithine phenylacetate (OP)--a novel strategy for treatment of hyperammonemia
    Sherry Dadsetan
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
    Biochem Pharmacol 85:115-23. 2013
    Combined administration of ornithine and phenylacetate (OP) is proposed as a novel treatment of hyperammonemia and hepatic encephalopathy...
  58. ncbi Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis
    Rodrigo Jover
    Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain
    Hepatology 43:1257-66. 2006
    ..In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances...
  59. ncbi Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice
    Juan C Marini
    Molecular and Human Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
    J Nutr 136:1834-8. 2006
    ..An unbalanced amino acid mixture, however, resulted in reduced ureagenesis and hyperammonemia. To study the effect of ornithine supplementation [316 micromol/(kg...
  60. pmc Enzymatic analysis of α-ketoglutaramate--a biomarker for hyperammonemia
    Lenka Halámková
    Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY 13699, USA
    Talanta 100:7-11. 2012
    ..The present study is the first step toward the development of a clinically useful probe for KGM analysis in biological fluids...
  61. ncbi [Study of correlation between Helicobacter pylori infection and hyperammonemia and hepatic encephalopathy in cirrhotic patients]
    Cun she Yang
    Department of Digestive Medicine, Central Hospital of Xianyang, Xianyang 712000, Shannxi, China
    Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 19:422-4. 2007
    ....
  62. ncbi Investigation of the oxidative effect of chronic hyperammonemia on the kidney and the possible protective effect of allopurinol
    Onur Elmas
    Gulhane Military Medical Academy, Ankara, Turkey
    Ren Fail 33:61-5. 2011
    Although there have been many studies on this topic, the molecular mechanism of the toxic effects of hyperammonemia on cells has not yet been fully explained...
  63. ncbi Interorgan ammonia metabolism in liver failure: the basis of current and future therapies
    Gavin Wright
    UCL Institute of Hepatology, Division of Medicine, University College London, London, UK
    Liver Int 31:163-75. 2011
    ..Better understanding of these alternative pathways are leading to the development of new therapeutic approaches...
  64. ncbi Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan
    Abdulrazaq A H Sokoro
    Department of Pathology, Diagnostic Services of Manitoba and University of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada
    J Inherit Metab Dis 33:S275-81. 2010
    ..human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition...
  65. ncbi Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis
    Alessia Bersagliere
    Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
    Hepatology 55:869-78. 2012
    In patients with cirrhosis, hyperammonemia and hepatic encephalopathy are common after gastrointestinal bleeding and can be simulated by an amino acid challenge (AAC), or the administration of a mixture of amino acids mimicking the ..
  66. ncbi The human and mouse SLC25A29 mitochondrial transporters rescue the deficient ornithine metabolism in fibroblasts of patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome
    José A Camacho
    Department of Pediatrics, University of California Irvine, Irvine, CA 92697, USA
    Pediatr Res 66:35-41. 2009
    The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle (UCD) and ornithine degradation pathway caused by mutations in the mitochondrial ornithine transporter (ORNT1)...
  67. ncbi [Vegetable protein diets with or without non-absorbable antibiotics for the treatment of chronic portal systemic encephalopathy]
    M Uribe
    , , , Tlalpan, ,
    Rev Invest Clin 42:120-6. 1990
    ..At the beginning of treatment vegetable protein diet should be administered and only in case of failure, antibiotics are to be indicated...
  68. ncbi RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia
    Freimut Schliess
    Heinrich Heine Universitat Dusseldorf, Klinik fur Gastroenterologie, Hepatologie, und Infektiologie, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Metab Brain Dis 24:119-34. 2009
    ..RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic encephalopathy...
  69. ncbi Hyperammonemia following intravenous valproate loading
    Jennifer L DeWolfe
    University of Alabama at Birmingham Epilepsy Center, Department of Neurology, 1719 6th Avenue South, CIRC 312, Birmingham, AL 35294 0021, United States
    Epilepsy Res 85:65-71. 2009
    Valproic acid (VPA) has been associated with hyperammonemia with and without encephalopathy. We report the frequent but transient nature of hyperammonemia following intravenous (IV) administration of loading doses of VPA.
  70. ncbi Dual mechanism of brain damage induced in vivo by the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
    Carolina Maso Viegas
    Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, UFRGS, Porto Alegre, RS, Brazil
    Brain Res 1369:235-44. 2011
    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by a defect in the mitochondrial ornithine transporter, leading to accumulation of ornithine (Orn), homocitrulline (Hcit) and ..
  71. ncbi Effects of hyperammonemia and liver failure on glutamatergic neurotransmission
    Pilar Monfort
    Department of Neurobiology, Instituto de Investigaciones Citologicas, FVIB, Valencia, Spain
    Metab Brain Dis 17:237-50. 2002
    ..There are studies in the literature reporting alterations in all these steps in hyperammonemia and/or hepatic failure. Glutamatergic neurotransmission modulates important cerebral processes...
  72. ncbi Heliox use in the treatment of acute hyperammonemia
    J Barr
    Pediatric Intensive Care Unit, Assaf Harofeh Medical Center, Zerifin, Israel
    J Child Neurol 16:456-8. 2001
    The objective of this study was to evaluate a new method for the treatment of acute hyperammonemia with a helium-oxygen mixture (heliox). We conducted a prospective, randomized, controlled study of male Sprague-Dawley rats...
  73. ncbi Inborn errors of metabolism: an update on epidemiology and on neonatal-onset hyperammonemia
    F Deodato
    Divisions of Metabolism, Ospedale Pediatrico Bambino Gesu, Scientific Institute IRCCS, Rome, Italy
    Acta Paediatr Suppl 93:18-21. 2004
    ..Other relevant issues of our investigations focused on creating protocols of treatment for neonatal IEM, and on the development of new methods for the biochemical diagnosis...
  74. ncbi The molecular basis of ornithine transcarbamylase deficiency
    M Tuchman
    Children s Research Institute, Children s National Medical Center, Washington, DC 20010 2970, USA
    Eur J Pediatr 159:S196-8. 2000
    ..OTC deficiency is an X-linked disorder that causes hyperammonemia leading to brain damage, mental retardation and death...
  75. ncbi Unregulated insulin secretion by pancreatic beta cells in hyperinsulinism/hyperammonemia syndrome: role of glutamate dehydrogenase, ATP-sensitive potassium channel, and nonselective cation channel
    Mie Kawajiri
    Deparment of Pediatrics, Osaka City University Graduate School of Medicien, Osaka, Japan
    Pediatr Res 59:359-64. 2006
    The hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by "gain of function" of glutamate dehydrogenase (GDH)...
  76. ncbi Evidence for oxidative/nitrosative stress in the pathogenesis of hepatic encephalopathy
    Chantal Bemeur
    Neuroscience Research Unit, Hôpital Saint Luc CHUM University of Montreal, Montreal, QC, Canada
    Metab Brain Dis 25:3-9. 2010
    ..However, evidence from studies in HE patients is limited. This review summarizes this evidence for a role of oxidative/nitrosative stress in relation to ammonia toxicity and to the pathogenesis of HE...
  77. ncbi Management of ornithine transcarbamylase deficiency in pregnancy
    Hector Mendez-Figueroa
    Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Perinatol 27:775-84. 2010
    ..A comprehensive plan for patients who develop hyperammonemia is recommended.
  78. ncbi Environmental heat stress, hyperammonemia and nucleotide metabolism during intermittent exercise
    Magni Mohr
    Institute of Exercise and Sport Sciences, Department of Human Physiology, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen Ø, Denmark
    Eur J Appl Physiol 97:89-95. 2006
    ....
  79. ncbi Proceedings of a consensus conference for the management of patients with urea cycle disorders
    M Summar
    Division of Medical Genetics, Vanderbilt University, Nashville, Tennessee, USA
    J Pediatr 138:S6-10. 2001
    ..On the other hand, there are many issues on which the panel agreed. In many instances the availability of reliable information on the respective topics determined whether consensus could be reached...
  80. pmc Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized (1)H and (15)N NMR spectroscopy
    Cristina Cudalbu
    Laboratory for Functional and Metabolic Imaging, Center for Biomedical Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    J Cereb Blood Flow Metab 32:696-708. 2012
    ..033±0.001 μmol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification.
  81. ncbi Continuous hemofiltration in the control of neonatal hyperammonemia: a 10-year experience
    Claire Westrope
    Department of Paediatric Intensive Care Medicine, Birmingham Children s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
    Pediatr Nephrol 25:1725-30. 2010
    ..review of the utilization of continuous veno-venous hemofiltration (CVVH) for the treatment of neonatal hyperammonemia, 14 patients were identified with hyperammonemia due to either a urea cycle defect or an organic acidemia...
  82. ncbi Hereditary urea cycle diseases in Finland
    Päivi Keskinen
    Department of Pediatrics, Tampere University Hospital, Tampere, Finland
    Acta Paediatr 97:1412-9. 2008
    ..To estimate the incidence of urea cycle diseases (UCDs) in Finland and determine the course of the various disorders as well as the outcome...
  83. pmc Vaccines are not associated with metabolic events in children with urea cycle disorders
    Thomas M Morgan
    Department of Pediatrics Division of Genetics and Genomic Medicine, Vanderbilt University School of Medicine, DD 2205 Medical Center North, Nashville, TN 37232 2578, USA
    Pediatrics 127:e1147-53. 2011
    ..Patients with UCDs are subject to hyperammonemic episodes (HAEs) after infection, fever, or other stressors...
  84. ncbi Sequential activation of soluble guanylate cyclase, protein kinase G and cGMP-degrading phosphodiesterase is necessary for proper induction of long-term potentiation in CA1 of hippocampus. Alterations in hyperammonemia
    Pilar Monfort
    Laboratory of Neurobiology, Instituto de Investigaciones Citologicas, Fundación Valenciana de Investigaciones Biomédicas FVIB, Amadeo de Saboya 4, 46010 Valencia, Spain
    Neurochem Int 45:895-901. 2004
    ..b>Hyperammonemia is the main responsible for the neurological alterations found in liver disease and hepatic encephalopathy, ..
  85. ncbi Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency
    Hironori Nagasaka
    Division of Metabolism, Chiba Children s Hospital, Chiba 266 0007, Japan
    Eur J Pediatr 165:618-24. 2006
    ..In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored...
  86. ncbi Cognitive outcome in urea cycle disorders
    Andrea L Gropman
    Children s Research Institute, Children s National Medical Center, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC 20010 2916, USA
    Mol Genet Metab 81:S58-62. 2004
    ..Such methods of investigation may serve as a model for studying the relationship between genes, biochemical markers, brain function, and behavior in other metabolic diseases...
  87. ncbi Remittent hyperammonemia in congenital portosystemic shunt
    Giovanni Battista Ferrero
    Department of Pediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy
    Eur J Pediatr 169:369-72. 2010
    ..We report the case of three boys with neuropsychological symptoms associated with mild fasting hyperammonemia. An oral protein load allowed the detection of a detoxication defect due to PSS related to PDV...
  88. ncbi Hyperammonemia and encephalopathy in patients with multiple myeloma
    Giampaolo Talamo
    Am J Hematol 82:414-5. 2007
  89. ncbi Seven novel mutations in the ORNT1 gene (SLC25A15) in patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome
    S Salvi
    Molecular Medicine, IRCCS Bambino Gesù, Rome Italy
    Hum Mutat 18:460. 2001
    Eight unrelated Italian patients with the hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome were analyzed for mutations in the ORNT1 gene. Seven novel mutations were identified (Q89X, G27R, G190D, R275Q, c.861insG, c...
  90. ncbi Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy
    F Barrueto
    Pitt County Memorial Hospital, Brody School of Medicine, East Carolina University, Greenville, NC, USA
    Acad Emerg Med 8:999-1001. 2001
    ..His coma and hyperammonemia were attributed to his chronic valproate therapy...
  91. ncbi Hyperammonemia increases GABAergic tone in the cerebellum but decreases it in the rat cortex
    Omar Cauli
    Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Valencia, Spain
    Gastroenterology 136:1359-67, e1-2. 2009
    ..It has been proposed that hyperammonemia-induced increases in gamma-aminobutyric acid "(GABAergic) tone" contribute to the pathogenesis of hepatic ..
  92. ncbi Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis
    Zuhair N Al-Hassnan
    Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
    J Neurol Sci 264:187-94. 2008
    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by mutations in ORNT1 gene that encodes a mitochondrial ornithine transporter...
  93. ncbi Hypothermia in acute liver failure
    Rajiv Jalan
    Liver Failure Group, Institute of Hepatology, London, United Kingdom
    Metab Brain Dis 19:215-21. 2004
    ..The present review explores the experimental and clinical data to define the role of hypothermia as a treatment modality for increased intracranial pressure in patients with acute liver failure...
  94. ncbi Clinical practice: the management of hyperammonemia
    Johannes Haberle
    Kinderspital Zurich, Division of Metabolism, University Children s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Eur J Pediatr 170:21-34. 2011
    b>Hyperammonemia is a life-threatening condition which can affect patients at any age. Elevations of ammonia in plasma indicate its increased production and/or decreased detoxification...
  95. ncbi New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA
    Cátia C P Aires
    Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    J Hepatol 55:426-34. 2011
    b>Hyperammonemia is a frequent side-effect of valproic acid (VPA) therapy, which points to an imbalance between ammoniagenesis and ammonia disposal via the urea cycle...
  96. ncbi A case of hyperinsulinism/hyperammonaemia syndrome with reduced carbamoyl-phosphate synthetase-1 activity in liver: a pitfall in enzymatic diagnosis for hyperammonaemia
    K Ihara
    Department of Pediatrics, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
    J Inherit Metab Dis 28:681-7. 2005
    ....
  97. ncbi Alternative-pathway therapy for hyperammonemia
    Vivian E Shih
    N Engl J Med 356:2321-2. 2007
  98. ncbi Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver
    D Kini
    Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
    Indian J Gastroenterol 20:237-40. 2001
    ..CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function...
  99. ncbi Hyperammonemia in the pediatric emergency care setting
    Nermeen M Galal
    Emergency Department, Cairo University Specialized Pediatric Hospital, Cairo University, Cairo, Egypt
    Pediatr Emerg Care 26:888-91. 2010
    b>Hyperammonemia is encountered frequently in acutely ill children presenting for emergency care with altered levels of consciousness (ALOC). Ammonia production, metabolism, and excretion are affected by different variables...
  100. ncbi Hyperammonemia in review: pathophysiology, diagnosis, and treatment
    Ari Auron
    Blank Memorial Hospital for Children, Des Moines, IA 50309, USA
    Pediatr Nephrol 27:207-22. 2012
    ..A variety of environmental causes and medications may also lead to ammonia toxicity. Hyperammonemia refers to a clinical condition associated with elevated ammonia levels manifested by a variety of symptoms and ..
  101. ncbi Transient hyperammonemia due to urea cycle enzyme deficiency in Irish wolfhounds
    M M J M Zandvliet
    Department of Clinical Sciences of Companion Animal Medicine, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
    J Vet Intern Med 21:215-8. 2007
    ..frequently have a congenital portosystemic shunt, but a considerable proportion of the 6- to 8-wk-old pups has hyperammonemia in the absence of portosystemic shunting...

Research Grants62

  1. Genotype Analysis for Diagnosis of Urea Cycle Disorders
    Steven Dobrowolski; Fiscal Year: 2007
    ..b>Hyperammonemia is the primary phenotype of urea cycle defects but differentiating individual gene deficiencies within the ..
  2. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..of protein, while severely affected human patients require severe protein restriction to prevent lethal hyperammonemia. Mice (and rats) are particularly poor models for studying liver fibrosis and cirrhosis, common features of ..
  3. REGULATION OF 15N UREA ISOTOPOMERS PRODUCTION
    Itzhak Nissim; Fiscal Year: 2013
    Impaired urea synthesis and consequent hyperammonemia (HA) are common occurrences in disorders of congenital defects of the urea cycle and of fatty acid oxidation (FAO), nonalcoholic fatty liver disease (NAFLD) and/or "Metabolic Syndrome"..
  4. REGULATION OF 15N UREA ISOTOPOMERS PRODUCTION
    Itzhak Nissim; Fiscal Year: 2009
    Impaired urea synthesis and consequent hyperammonemia may occur secondary to inborn errors of the urea cycle, treatment with certain drugs or faulty hepatic fatty acid oxidation (FAO), fatty liver or "Metabolic Syndrome" (MS)...
  5. Pathophysiology and Gene Replacement Strategies for Arginase Deficiency
    Gerald S Lipshutz; Fiscal Year: 2013
    ..clinically by progressive mental impairment, spasticity, growth retardation, and periodic episodes of hyperammonemia. This proposal is two-fold: 1) to develop gene-based correction of arginase deficiency with viral vectors and ..
  6. Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders
    Juan Marini; Fiscal Year: 2013
    ..The reduction in the hepatic capacity to detoxify ammonia in Urea Cycle Disorders (UCD) patients results in hyperammonemia that causes irritability, lethargy, cerebral edema, seizures and coma that can lead to death...
  7. Rare Diseases Clinical Research Consortia (RDCRC) for the RDCR Network
    Mark L Batshaw; Fiscal Year: 2013
    ..lyase (AL) deficiency (Argininosuccinic aciduria);Arginase (ARG) deficiency (Argininemia);Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome;and Citrullinemia type II...
  8. N-acetylglutamate Synthase: Structure, Function &Defects
    Mendel Tuchman; Fiscal Year: 2012
    ..The deficiency of NAG in inherited NAGS deficiency, organic acidemias and valproate treatment causes hyperammonemia that frequently leads to brain damage, developmental disabilities and death...
  9. Gene Therapy for Urea Cycle Disorders
    James M Wilson; Fiscal Year: 2013
    ..before considering clinical trials in those with severe OTCD who present with life-threatening episodes of hyperammonemia as neonates...
  10. METHAMPHETAMINE TOXICITY AND CORTICOSTRIATAL GLUTAMATE
    Bryan K Yamamoto; Fiscal Year: 2013
    ..The key mediator of HE is hyperammonemia. Ammonia (NH3) causes neuronal damage through mechanisms strikingly similar to excitotoxicity and oxidative ..
  11. Intestinal Epithelia Ammonium Transport
    Roger T Worrell; Fiscal Year: 2012
    ..poorly understood, this despite the well known impact of portal vein NH4+ concentration in the development of hyperammonemia in liver disease...
  12. Mechanisms of Malnutrition in Cirrhosis with Portosystemic Shunting
    Srinivasan Dasarathy; Fiscal Year: 2013
    ..b>Hyperammonemia is a consistent abnormality in cirrhosis and PSS due to impaired hepatic detoxification of ammonia...
  13. Planning a Multicenter Cooling Trial for Hyperammonemic Metabolic Crises
    DAVID LLOYD WESSEL; Fiscal Year: 2013
    ..conduct of a randomized clinical trial of therapeutic hypothermia as adjunct therapy in young children with hyperammonemia associated encephalopathy resulting from urea cycle disorders (UCDs) or organic acidemias (OAs)...
  14. Urea Cycle Disorders Satellite Symposium: 11th International Meeting
    BRENDAN HL LEE; Fiscal Year: 2012
    ..Chronic and acute episodes of hyperammonemia in children with partial defects result in cognitive and neurological deficits...
  15. Neuroprotection from hyperammonemia: small molecule screen
    Mendel Tuchman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Hyperammonemia caused either by inborn errors of metabolism, liver failure or extreme catabolic stress can be life threatening and can cause severe brain damage resulting in intellectual and ..
  16. Urea Cycle Disorders Satellite Symposium to the 12th ICIEM
    Marshall L Summar; Fiscal Year: 2013
    ..Chronic and acute episodes of hyperammonemia in children with partial defects result in cognitive and neurological deficits...
  17. BACTERIAL UREASE IN THE CATHETERIZED URINARY TRACT
    HARRY MOBLEY; Fiscal Year: 1990
    ..bacilli isolated produced the enzyme urease which has been implicated in pyelonephritis, hepatic coma, hyperammonemia, complement inactivation, and kidney and bladder stone formation...
  18. Genotype Analysis for Diagnosis of Urea Cycle Disorders
    Steven Dobrowolski; Fiscal Year: 2005
    ..Unequivocal and rapid diagnosis of UCDs is difficult because hyperammonemia, the primary biochemical phenotype, is not specific to UCDs being observed in broad categories of metabolic ..
  19. CEREBROVASCULAR ALTERATIONS DURING HYPERAMMONEMIA
    Raymond Koehler; Fiscal Year: 2000
    b>Hyperammonemia with or without liver disease results in swollen astrocytes and large increases in brain glutamine levels. Ammonia is metabolized by an active glutamine synthetase pool localized in astrocytes...
  20. INBORN ERRORS--MOLECULAR ANALYSIS IN CULTURED CELLS
    Leon Rosenberg; Fiscal Year: 1990
    ..CS) deficiency; methylmalonic acidemia, due to methylmalonyl CoA mutase apoenzyme (MUT) deficiency; hyperammonemia, due to ornithine transcarbamylase (OTC) deficiency; and propionic acidemia, due to propionyl CoA carboxylase (..
  21. Beta Catenin Regulation of Skeletal Muscle Hypertrophy
    KARYN ANN ESSER; Fiscal Year: 2013
    ..This work has found that hyperammonemia caused by cirrhosis leads to sarcopenia as the result of increased myostatin expression and decreased protein ..
  22. MARINE AND FRESHWATER BIOMEDICAL SCIENCES CENTER
    Lora Fleming; Fiscal Year: 2006
    ..of development: Damselfish Neurofibromatosis, Cultured Human Schwann Cells, Aplysia Neurophysiology, Toadfish Hyperammonemia, Transgenic Fishes, Squirrelfish Zinc Metabolisin/Transport, Fish Immunology arid Sentinel Species...
  23. HEPATIC COMA--GLIAL BENZODIAZEPINE RECEPTORS & STEROIDS
    Michael Norenberg; Fiscal Year: 2000
    ..They further propose that the elevation of neurosteroids result from an upregulation of astrocytic PBR by the hyperammonemia associated with liver failure...
  24. HYPERAMMONEMIA AND CANCER ANOREXIA
    WILLIAM CHANCE; Fiscal Year: 1990
    ..These experiments should delineate specific causes of anorexia in cancer and suggest several therapeutic options...
  25. Extreme Ammonia Tolerance Mechanisms: A Model Vertebrate
    Patrick Walsh; Fiscal Year: 2004
    Hepatic Encephalopathy (HE), and resultant elevated blood and tissue ammonia concentrations (i.e., hyperammonemia, HA), has profound central nervous system (CNS) effects, and can have environmental causes...
  26. Cell Volume Regulation in Neurons and Glia
    FRANCISCO ALVAREZ LEEFMANS; Fiscal Year: 2006
    ..implications of this research stem from the fact that millimolar concentrations of NH3/NH4+ in arterial blood (hyperammonemia) are a key factor in producing brain edema characteristic of acute liver failure, a condition that may occur ..
  27. N-carbamylglutamate in the treatment of hyperammonemia
    Mendel Tuchman; Fiscal Year: 2013
    ..provided by applicant): The overall objective of this project is to determine whether treatment of acute hyperammonemia with N-carbamyl-L-glutamate (NCG) in propionic acidemia (PA), methylmalonic acidemia (MMA), carbamyl phosphate ..
  28. GENE THERAPY FOR ORNITHINE TRANSCARBAMYLASE DEFICIENCY
    Mark Batshaw; Fiscal Year: 1999
    ..on treatment of the acute hyperammonemic crisis by transient expression of OTC, and long-term prevention of hyperammonemia by stable correction of OTCD...
  29. UREA CYCLE ENZYMOPATHIES
    SAUL BRUSILOW; Fiscal Year: 1991
    ..The role of the intravenous dosage form of these drugs on the hyperammonemia of Reye's syndrome will also be evaluated...
  30. NEUROTRANSMITTERS, APPETITE & INBORN METABOLISM ERRORS
    Mark Batshaw; Fiscal Year: 1991
    ..errors of urea synthesis, and in epileptic patients receiving the anticonvulsant valproate which induces hyperammonemia will be studied...
  31. BACULOVIRAL VECTORS FOR UREA CYCLE DISORDERS
    Frederick Boyce; Fiscal Year: 2000
    ..Inborn errors of metabolism involving enzymes of the urea cycle may lead to hyperammonemia, coma, mental retardation, and sometimes death...
  32. STRUCTURE/FUNCTION OF CARBAMYL PHOSPHATE SYNTHETASE
    CAROL LUSTY; Fiscal Year: 2001
    ..Lesions in the human NH3-dependent enzyme either are lethal or lead to hyperammonemia, hepatic coma, and CNS damage. New directed enzyme therapies are continually being developed...
  33. BIOCHEMICAL APPROACH TO NMDA RECEPTORS & EXCITOTOXICITY
    David Lynch; Fiscal Year: 1999
    ..including hypoxic-ischemic damage, Huntington's disease, secondary damage from head trauma, glutaric acidemia, hyperammonemia and other central nervous system disorders...
  34. CEREBRAL GLUTAMATE CONTROL BY IN VIVO 15N MR
    Brian Ross; Fiscal Year: 1999
    ..Studies will also be performed under selected conditions which were chosen for possible clinical relevance: hyperammonemia, steroid therapy, and after inhibition of the glutarnate transporter by an antisense oligonucleotide.
  35. COMMON POLYMORPHISM EFFECTS ON UREA CYCLE FUNCTION
    Marshall Summar; Fiscal Year: 2001
    ..b>Hyperammonemia, however, is much more common and is associated with non-genetic conditions and environmental exposures...
  36. ISLET DYSREGULATION IN INFANTS
    Charles Stanley; Fiscal Year: 2008
    ..The results of this research will provide essential information for improving the diagnosis and treatment of HI children and for understanding the basis of insulin regulation in normal humans. ..
  37. MOLECULAR BASIS OF A NEW FORM OF HYPERINSULINISM
    CHARLES ALFRED STANLEY; Fiscal Year: 2010
    ..Previous years focused on the mechanisms of the hyperinsulinism / hyperammonemia syndrome associated with dominant, gain of function mutations of glutamate dehydrogenase (GDH)...
  38. International Medical Conference of Congenital Hyperinsulinism
    Charles Stanley; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  39. Ped Endocrine Career Development in Diabetes Research
    Charles Stanley; Fiscal Year: 2007
    ..The Program is strongly supported by access to a superb range of institutional resources, including the CHOP GCRC and the UPenn DERC. Request is made for 2 Appointee slots in this Program each year. ..
  40. Transcriptional Regulation of Craniofacial Skeletogenesis
    Brendan Lee; Fiscal Year: 2009
    ....
  41. TRANSCRIPTIONAL REGULATORS IN CHONDROGENESIS
    Brendan Lee; Fiscal Year: 2002
    ....
  42. Adenoviral hepatocyte gene therapy in Citrullinemia
    Brendan Lee; Fiscal Year: 2005
    ..This urea cycle disorder is characterized by severe neurologic morbidity associated with hyperammonemia which may present in both neonates, children, and adults...
  43. ENTERAL PRECURSORS FOR UREA SYNTHESIS IN HUMANS
    Brendan Lee; Fiscal Year: 2006
    ..In addition it is anticipated that the results will benef it other individuals who have compromised protein metabolism. ..
  44. In vivo function and tolerance to Factor VIII variants
    BRENDAN HL LEE; Fiscal Year: 2011
    ..abstract_text> ..
  45. Dysregulation of 3-prolyl-hydroxylation in Human Skeletal Dysplasias
    BRENDAN HL LEE; Fiscal Year: 2010
    ..e., the in vivo phenotypic and biochemical consequences of dysregulation of the 3-prolyl-hydroxylation machinery. ..
  46. GENETIC & ENVIRONMENTAL DETERMINANTS OF CRANIOFACIAL DIS
    Brendan Lee; Fiscal Year: 2005
    ..Together, these studies will identify genes important in pathogenesis of human malformation and elucidate their modes of action in both cell autonomous and cell non-autonomous models mechanisms of development. ..
  47. Pathophysiological Interpretations of Dynamic PET/CT of Molecular Liver Biology
    Susanne Keiding; Fiscal Year: 2010
    ..This will lead to improved diagnosis and treatment of the large groups of patients with liver disease and cancer in the liver. ..
  48. The molecular bases of inherited urea cycle disorders and ureagenesis regulation
    Mendel Tuchman; Fiscal Year: 2010
    ..The mouse and human N-acetylglutamate synthase (NAGS) genes were identified and cloned and mutations causing hyperammonemia were identified...
  49. MECHANISM OF GLUTATHIONE CONJUGATE DEPENDENT TOXICITY
    Arthur Cooper; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. AUTISM--A MODEL OF ANOMALOUS NEURAL SYSTEMS DEVELOPMENT
    Pauline Filipek; Fiscal Year: 2001
    ....
  51. FUNCTIONAL METABOLIC ACTIVITY IN GLIA IN VIVO
    Gerald Dienel; Fiscal Year: 2003
    ..abstract_text> ..
  52. Transcription Factors & Inflammatory Mediators in Stroke
    Raghu Vemuganti; Fiscal Year: 2007
    ..The ultimate goal is to define the role of SOCS-3/STAT-3 in post-ischemic cerebral inflammation. ..
  53. Arginine and Ovine Model for Fetal Growth Restriction
    Guoyao Wu; Fiscal Year: 2007
    ..This will ultimately promote favorable pregnancy outcomes while saving billions of healthcare dollars in the U.S. and worldwide. [unreadable] [unreadable] [unreadable]..
  54. Mechanisms of glutamate dehydrogenase allostery
    Thomas Smith; Fiscal Year: 2008
    ..regulation by our finding that mutations that affect GTP inhibition are the root cause of the hyperinsulinism/hyperammonemia (HI//HA) syndrome in children...
  55. Anaplerotic therapy in Propionic Acidemia
    Nicola Longo; Fiscal Year: 2008
    ..whether nutritional supplements capable of filling-up the citric acid cycle (anaplerotic therapy) can improve hyperammonemia, glutamine levels, and outcome in patients with propionic acidemia...
  56. Role of Egr-1 in post-stroke inflammation & brain damage
    Raghu Vemuganti; Fiscal Year: 2009
    ..The ultimate goal is to define the role of EgM and its regulators to develop therapies to control cerebral inflammation at the level of transcription. ..
  57. Towards a Vaccine for the Common Cold
    THOMAS JAMES SMITH; Fiscal Year: 2010
    ..If successful, the methods developed here will also yield a rapid way to identify potential, conserved, vaccine targets for other antigenically diverse viruses as well. ..
  58. NMR Studies of Brain Energetics & Hypoglycemia In Vivo
    Kevin Behar; Fiscal Year: 2009
    ....
  59. Parkinsons disease:visual dysfunction and hallucinations
    Suzanne Holroyd; Fiscal Year: 2005
    ..The results may also increase our understanding of visual hallucinations in other disorders. Conceivably, such knowledge could lead to strategies to prevent, minimize or treat such symptoms. ..
  60. STRUCTURAL STUDIES OF PROTEIN SUBUNITS
    Thomas Smith; Fiscal Year: 2004
    ..These studies have the potential of changing the way we view the early steps in the viral infection process and will allow us to develop tools that are applicable to other viral systems. ..
  61. FUNCTIONAL METABOLISM IN WORKING BRAIN
    Gerald Dienel; Fiscal Year: 2007
    ..abstract_text> ..
  62. MITOCHONDRIAL DNA ANALYSIS IN CYCLIC VOMITING SYNDROME
    Richard Boles; Fiscal Year: 2002
    ..An extensive amount of clinical and laboratory data will be collected in all patients, allowing for the comparison of CVS sufferers with and without mtDNA mutations. ..