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NMR and hepatic encephalopathy

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https://www.readbyqxmd.com/read/27638475/urinary-metabolic-profiling-by-1-h-nmr-spectroscopy-in-patients-with-cirrhosis-may-discriminate-overt-but-not-covert-hepatic-encephalopathy
#1
Mark J W McPhail, Sara Montagnese, Manuela Villanova, Hamza El Hadi, Piero Amodio, Mary M E Crossey, Roger Williams, I Jane Cox, Simon D Taylor-Robinson
To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance ((1)H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE (OHE, n = 21), covert HE (cHE, n = 7) or no HE (n = 17)...
September 17, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/26105442/pp120-hydatidiform-mole-as-a-cause-of-eclampsia-in-the-first-trimester-a-case-report
#2
S Ottanelli, S Simeone, C Serena, M P Rambaldi, A Villanucci, K Tavella, G Amunni, F Mecacci, G Mello
INTRODUCTION: The occurrence of preeclampsia before the 20th week of gestation is rare and it has been associated with hydatidiform molar pregnancy. OBJECTIVES: We describe a case of first trimester eclampsia which occurred in a patient with hydatidiform mole. METHODS: Case report. RESULTS: A 16-year-old woman came to emergency service for abdominal pain and vaginal bleeding. She had been suffering of vomiting after meals and complaining for abdominal mass for 2months, without consulting her physician...
July 2012: Pregnancy Hypertension
https://www.readbyqxmd.com/read/25735860/ammonia-metabolism-and-hyperammonemic-disorders
#3
REVIEW
Valerie Walker
Human adults produce around 1000 mmol of ammonia daily. Some is reutilized in biosynthesis. The remainder is waste and neurotoxic. Eventually most is excreted in urine as urea, together with ammonia used as a buffer. In extrahepatic tissues, ammonia is incorporated into nontoxic glutamine and released into blood. Large amounts are metabolized by the kidneys and small intestine. In the intestine, this yields ammonia, which is sequestered in portal blood and transported to the liver for ureagenesis, and citrulline, which is converted to arginine by the kidneys...
2014: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/25034052/pathophysiology-of-brain-dysfunction-in-hyperammonemic-syndromes-the-many-faces-of-glutamine
#4
REVIEW
Roger F Butterworth
Ineffective hepatic clearance of excess ammonia in the form of urea, as occurs in urea cycle enzymopathies (UCDs) and in liver failure, leads to increases in circulating and tissue concentrations of glutamine and a positive correlation between brain glutamine and the severity of neurological symptoms. Studies using 1H/13C Nuclear Magnetic Resonance (NMR) spectroscopy reveal increased de novo synthesis of glutamine in the brain in acute liver failure (ALF) but increases of synthesis rates per se do not correlate with either the severity of encephalopathy or brain edema...
September 2014: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/24512824/increased-brain-lactate-is-central-to-the-development-of-brain-edema-in-rats-with-chronic-liver-disease
#5
Cristina R Bosoi, Claudia Zwingmann, Helen Marin, Christian Parent-Robitaille, Jimmy Huynh, Mélanie Tremblay, Christopher F Rose
BACKGROUND & AIMS: The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis. METHODS: Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR)...
March 2014: Journal of Hepatology
https://www.readbyqxmd.com/read/22382077/pathogenesis-of-hepatic-encephalopathy-and-brain-edema-in-acute-liver-failure-role-of-glutamine-redefined
#6
REVIEW
Paul Desjardins, Ting Du, Wenlei Jiang, Liang Peng, Roger F Butterworth
Acute liver failure (ALF) is characterized neuropathologically by cytotoxic brain edema and biochemically by increased brain ammonia and its detoxification product, glutamine. The osmotic actions of increased glutamine synthesis in astrocytes are considered to be causally related to brain edema and its complications (intracranial hypertension, brain herniation) in ALF. However studies using multinuclear (1)H- and (13)C-NMR spectroscopy demonstrate that neither brain glutamine concentrations per se nor brain glutamine synthesis rates correlate with encephalopathy grade or the presence of brain edema in ALF...
June 2012: Neurochemistry International
https://www.readbyqxmd.com/read/20690770/serum-metabolic-signature-of-minimal-hepatic-encephalopathy-by-1-h-nuclear-magnetic-resonance
#7
Beatriz Jiménez, Carmina Montoliu, David A MacIntyre, Miguel A Serra, Abdallah Wassel, María Jover, Manuel Romero-Gomez, Jose M Rodrigo, Antonio Pineda-Lucena, Vicente Felipo
Minimal hepatic encephalopathy (MHE) reduces quality of life of cirrhotic patients, predicts overt hepatic encephalopathy, and is associated with poor prognosis. We hypothesized that MHE arises once metabolic alterations derived from the liver reach a particular threshold. Our aim was to assess whether metabolic profiling of serum samples by high-field (1)H-nuclear magnetic resonance spectroscopy ((1)H NMR) and subsequent multivariate analyses would be useful to characterize metabolic perturbations associated with MHE and to identify potential metabolic biomarkers...
October 1, 2010: Journal of Proteome Research
https://www.readbyqxmd.com/read/18637065/a-1h-nuclear-magnetic-resonance-based-metabonomic-approach-for-grading-hepatic-encephalopathy-and-monitoring-the-effects-of-therapeutic-hypothermia-in-rats
#8
Ignasi Barba, Nicolas Chatauret, David García-Dorado, Juan Córdoba
BACKGROUND: There are no good biomarkers for grading hepatic encephalopathy (HE) and monitoring the effectiveness of therapeutic measures. METHODS: We applied (1)H nuclear magnetic resonance (NMR)-based metabonomics of brain samples obtained from acute liver failure rats sacrificed after ligation of the hepatic artery (at 6 h, precoma and coma stages), sham-operated controls and mild hypothermia (35 degrees C) for 6 or 15 h as a therapeutic measure. RESULTS: Partial least square discriminant analysis established a classification model that scored the severity of encephalopathy...
September 2008: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/17823857/the-anaplerotic-flux-and-ammonia-detoxification-in-hepatic-encephalopathy
#9
REVIEW
Claudia Zwingmann
Metabolic alterations in the brain underly many of the mechanisms leading to acute and chronic Hepatic Encephalopathy (HE). Controversy exists about the role of glutamine accumulation as a causal factor in HE. Glutamine formation contributes to detoxify ammonia, whereby anaplerotic mechanisms in the astrocytes have to be sufficient to replenish Krebs cycle intermediates. The application of ex vivo high-resolution nuclear magnetic resonance (NMR) spectroscopy permits direct measurements of metabolites and different metabolic pathways...
December 2007: Metabolic Brain Disease
https://www.readbyqxmd.com/read/17722064/nuclear-magnetic-resonance-studies-of-energy-metabolism-and-glutamine-shunt-in-hepatic-encephalopathy-and-hyperammonemia
#10
REVIEW
Claudia Zwingmann
Hepatic encephalopathy (HE) in both acute and chronic liver failure is more likely a reversible functional disease rather than an irreversible pathological lesion of brain cells. Metabolic alterations underlie many of the mechanisms leading to HE. This paper summarizes in vivo and ex vivo (1)H-, (13)C-, and (15)N-nuclear magnetic resonance (NMR) spectroscopy data on patients and experimental models of HE. In vivo NMR spectroscopy provides a unique opportunity to study metabolic changes noninvasively in the brain in vivo, and to quantify various metabolites in localized brain areas, and ex vivo NMR permits the high-resolution measurement of metabolites and the identification of different metabolic pathways...
November 15, 2007: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/16374780/selectively-increased-expression-of-the-astrocytic-endothelial-glucose-transporter-protein-glut1-in-acute-liver-failure
#11
Mireille Bélanger, Paul Desjardins, Nicolas Chatauret, Roger F Butterworth
Acute liver failure (ALF) is consistently accompanied by alterations in brain energy metabolites and recent nuclear magnetic resonance (NMR) studies suggest disturbances in brain oxidative metabolism in experimental ALF. Glucose transport across the blood-brain barrier is essential to sustain brain energy metabolism and is accomplished by the facilitative glucose transporter GLUT1. To investigate alterations in brain glucose uptake in acute liver failure further, GLUT1 expression and [14C]-2-deoxy-D-glucose uptake were measured in the brains of rats with hepatic devascularization...
April 1, 2006: Glia
https://www.readbyqxmd.com/read/15916833/an-update-on-the-role-of-brain-glutamine-synthesis-and-its-relation-to-cell-specific-energy-metabolism-in-the-hyperammonemic-brain-further-studies-using-nmr-spectroscopy
#12
REVIEW
Claudia Zwingmann, Roger Butterworth
Ammonia is a neurotoxin that is implicated in the pathogenesis of hepatic encephalopathy due to acute and chronic liver failure. However, its relation to neurological damage and brain edema is poorly understood. During the last decades, it has been the prevailing hypothesis that an osmotic disturbance induced by the astrocytic accumulation of glutamine leads to brain edema. However, various findings are at variance with this hypothesis. The present review will discuss: (a) correlation of ammonia with encephalopathy and brain edema in HE; (b) glutamine synthesis and astrocyte swelling; (c) glutamine synthesis and the glutamine-cycle: relation to brain energy metabolism; (d) glutamine synthesis and the glutamate-glutamine cycle and its relation to anaplerotic activity; (e) evidence favouring the "glutamine hypothesis"; (f) evidence contradicting the "glutamine hypothesis"; (g) glutamine synthesis and osmoregulation; (h) glutamine synthesis in chronic liver failure; (i) impaired brain energy metabolism in acute liver failure (ALF) and its relation to astrocytic glutamine synthesis...
July 2005: Neurochemistry International
https://www.readbyqxmd.com/read/15908044/ammonia-toxicity-under-hyponatremic-conditions-in-astrocytes-de-novo-synthesis-of-amino-acids-for-the-osmoregulatory-response
#13
Claudia Zwingmann, Dieter Leibfritz
This study investigates how the metabolic activity and de novo synthesis of amino acids from glucose correlate with changes in intracellular organic osmolytes involved in astrocytic volume regulation during hyperammonemia and hyponatremia. Multinuclear (1H-, 31P-, 13C-) NMR spectra were recorded to quantify water-soluble metabolites, the cellular energy state, as well as the incorporation of [1-(13)C]glucose into amino acids of primary astrocyte cultures. Myo-inositol levels were strongly decreased already at 3h after treatment with NH4Cl; other intracellular osmolytes, such as hypotaurine and choline-containing compounds were also decreased, along with a concomitant increase of both the total concentration and the amount of newly synthesized glutamine, alanine, and glutathione...
July 2005: Neurochemistry International
https://www.readbyqxmd.com/read/14746928/selective-alterations-of-brain-osmolytes-in-acute-liver-failure-protective-effect-of-mild-hypothermia
#14
Claudia Zwingmann, Nicolas Chatauret, Christopher Rose, Dieter Leibfritz, Roger F Butterworth
The principal cause of mortality in patients with acute liver failure (ALF) is brain herniation resulting from intracranial hypertension caused by a progressive increase of brain water. In the present study, ex vivo high-resolution 1H-NMR spectroscopy was used to investigate the effects of ALF, with or without superimposed hypothermia, on brain organic osmolyte concentrations in relation to the severity of encephalopathy and brain edema in rats with ALF due to hepatic devascularization. In normothermic ALF rats, glutamine concentrations in frontal cortex increased more than fourfold at precoma stages, i...
February 27, 2004: Brain Research
https://www.readbyqxmd.com/read/12949727/effects-of-hypothermia-on-brain-glucose-metabolism-in-acute-liver-failure-a-h-c-nuclear-magnetic-resonance-study
#15
Nicolas Chatauret, Claudia Zwingmann, Christopher Rose, Dieter Leibfritz, Roger F Butterworth
BACKGROUND & AIMS: Mild hypothermia has a protective effect on brain edema and encephalopathy in both experimental and human acute liver failure. The goals of the present study were to examine the effects of mild hypothermia (35 degrees C) on brain metabolic pathways using combined (1)H and (13)C-Nuclear Magnetic Resonance (NMR) spectroscopy, a technique which allows the study not only of metabolite concentrations but also their de novo synthesis via cell-specific pathways in the brain...
September 2003: Gastroenterology
https://www.readbyqxmd.com/read/12620282/effects-of-ammonia-on-high-affinity-glutamate-uptake-and-glutamate-transporter-eaat3-expression-in-cultured-rat-cerebellar-granule-cells
#16
Helen Chan, Claudia Zwingmann, Marc Pannunzio, Roger F Butterworth
Increased levels of extracellular glutamate are a consistent feature of hepatic encephalopathy (HE) associated with liver failure and other hyperammonemic pathologies. Reduction of glutamate uptake has been described in ammonia-exposed cultured astrocytes, synaptosomes, and in animal models of hyperammonemia. In the present study, we examine the effects of pathophysiological concentrations of ammonia on D-aspartate (a non-metabolizable analog of glutamate) uptake by cultured rat cerebellar granule neurons. Exposure of these cells to ammonia resulted in time-dependent (24% reduction at 24h and 60% reduction at 5 days, P<0...
July 2003: Neurochemistry International
https://www.readbyqxmd.com/read/12540793/selective-increase-of-brain-lactate-synthesis-in-experimental-acute-liver-failure-results-of-a-h-c-nuclear-magnetic-resonance-study
#17
Claudia Zwingmann, Nicolas Chatauret, Dieter Leibfritz, Roger F Butterworth
Acute liver failure (ALF) results in alterations of energy metabolites and of glucose-derived amino acid neurotransmitters in brain. However, the dynamics of changes in glucose metabolism remain unclear. The present study was undertaken using (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy to determine the rates of incorporation of glucose into amino acids and lactate via cell-specific pathways in relation to the severity of encephalopathy and brain edema in rats with ALF because of hepatic devascularization...
February 2003: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/12357553/follow-up-by-one-and-two-dimensional-nmr-of-plasma-from-pigs-with-ischemia-induced-acute-liver-failure-treated-with-a-bioartificial-liver
#18
David Tréhout, Mireille Desille, Bich-Thuy Doan, Stephan Mahler, Benjamin Frémond, Yannick Mallédant, Jean-Pierre Campion, Jeanne Desbois, Jean-Claude Beloeil, Jacques de Certaines, Bruno Clément
Hepatic encephalopathy may occur following acute hepatic failure (AHF), which results in the release of toxic compounds from the injured liver. These compounds, which induce cerebral edema, are not well characterized, yet. The aim of this study was to evaluate the potential interest of NMR spectroscopy in the follow-up of different plasma compounds in pigs with ischemia-induced fulminant hepatic failure treated or not with a bioartificial liver (BAL), which has been previously shown to improve the neurological status of the animals...
October 2002: NMR in Biomedicine
https://www.readbyqxmd.com/read/12020614/in-vivo-13c-nmr-studies-of-compartmentalized-cerebral-carbohydrate-metabolism
#19
REVIEW
Rolf Gruetter
Localized 13C nuclear magnetic resonance (NMR) spectroscopy provides a unique window for studying cerebral carbohydrate metabolism through, e.g. the completely non-invasive measurement of cerebral glucose and glycogen metabolism. In addition, label incorporation into amino acid neurotransmitters such as glutamate (Glu), GABA and aspartate can be measured providing information on Krebs cycle flux and oxidative metabolism. Given the compartmentation of key enzymes such as pyruvate carboxylase and glutamine synthetase, the detection of label incorporation into glutamine indicated that neuronal and glial metabolism can be measured in vivo...
August 2002: Neurochemistry International
https://www.readbyqxmd.com/read/10873206/hyperammonemia-and-chronic-hepatic-encephalopathy-an-in-vivo-pmrs-study-of-the-rat-brain
#20
D Astore, C A Boicelli
The brain energy metabolism of rats affected by chronic hepatic encephalopathy due to portacaval shunting was monitored by in vivo 31P-nuclear magnetic resonance spectroscopy before and after ammonium acetate administration. With respect to healthy unoperated and to sham operated controls, portacaval shunting decreased the levels of the nuclear magnetic resonance (NMR) visible brain phosphocreatine and nucleoside phosphates, and the intracellular [free Mg(2+)]. Ammonium acetate induced a further decrease of the levels of the NMR detectable phosphocreatine and nucleoside triphosphates and of the [free Mg(2+)], while the PMR spectra of the brain of non-shunted rats did not show any significant change even after treatment with ammonium acetate...
July 2000: Magma
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