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L-ornithine L-aspartate

Romila Mascarenhas, Hoang V Le, Kenneth D Clevenger, Helaina J Lehrer, Dagmar Ringe, Neil L Kelleher, Richard B Silverman, Dali Liu
Potent mechanism-based inactivators can be rationally designed against PLP-dependent drug targets, such as ornithine aminotransferase (OAT) or γ-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity towards other PLP-dependent off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma (HCC) target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT...
August 17, 2017: Biochemistry
Milan Holeček
Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles...
September 2017: Nutrition
Sandeep Singh Sidhu, Barjesh Chander Sharma, Omesh Goyal, Harsh Kishore, Navpreet Kaur
High quality data on efficacy of L-Ornithine L-Aspartate (LOLA) in cirrhotics with bouts of overt hepatic encephalopathy (OHE) is missing. We aimed to evaluate the efficacy of intravenous LOLA in reversal of bouts of OHE in cirrhotics. In this prospective double-blind randomized placebo controlled trial conducted at two tertiary care institutes in India, 370 cirrhotics with bouts of OHE were screened. After exclusion, 193 (52.16%) patients were randomized to receive either intravenous infusions of LOLA (n=98), 30 grams daily or Placebo (n=95) for 5 days...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lusliany J Rondón, M C Farges, N Davin, B Sion, A M Privat, M P Vasson, A Eschalier, C Courteix
PURPOSE: Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes...
July 19, 2017: European Journal of Nutrition
Jakub Krijt, Jitka Sokolová, Pavel Ješina, Lenka Dvořáková, Martin Řeboun, Katarína Brennerová, Martin Mistrík, Jiří Zeman, Tomáš Honzík, Viktor Kožich
BACKGROUND: Liver enzymes are released from hepatocytes into circulation and their activity can be measured in the blood. We examined whether the plasma activity of the liver enzyme ornithine carbamoyltransferase, determined by a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay, could be utilized for the detection of OTC deficiency (OTCD), an X-linked inborn error of the urea cycle. METHODS: The plasma ornithine carbamoyltransferase (OTC) activity was assayed in the reverse reaction using isotopically labeled citrulline-d4 as a substrate and by determination of the product, ornithine-d4, by LC-MS/MS analysis...
July 26, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
Daniela Viramontes Hörner, Amanda Avery, Ruth Stow
Alterations in the levels of intestinal microbiota, endotoxemia, and inflammation are novel areas of interest in the pathogenesis of hepatic encephalopathy (HE). Probiotics and symbiotics are a promising treatment option for HE due to possible beneficial effects in modulating gut microflora and might be better tolerated and more cost-effective than the traditional treatment with lactulose, rifaximin or L-ornithine-L-aspartate. A systematic search of the electronic databases PubMed, ISI Web of Science, EMBASE, and Cochrane Library was conducted for randomized controlled clinical trials in adult patients with cirrhosis, evaluating the effect of probiotics and symbiotics in changes on intestinal microflora, reduction of endotoxemia, inflammation, and ammonia, reversal of minimal hepatic encephalopathy (MHE), prevention of overt hepatic encephalopathy (OHE), and improvement of quality of life...
April 2017: Journal of Clinical Gastroenterology
R Hugh Dunstan, Diane L Sparkes, Benjamin J Dascombe, Margaret M Macdonald, Craig A Evans, Christopher J Stevens, Marcus J Crompton, Johan Gottfries, Jesse Franks, Grace Murphy, Ryan Wood, Timothy K Roberts
Sweat contains amino acids and electrolytes derived from plasma and athletes can lose 1-2L of sweat per hour during exercise. Sweat may also contain contributions of amino acids as well as urea, sodium and potassium from the natural moisturizing factors (NMF) produced in the stratum corneum. In preliminary experiments, one participant was tested on three separate occasions to compare sweat composition with surface water washings from the same area of skin to assess contributions from NMF. Two participants performed a 40 minute self-paced cycle session with sweat collected from cleansed skin at regular intervals to assess the contributions to the sweat load from NMF over the period of exercise...
2016: PloS One
Angela Maria Amorini, Giacomo Lazzarino, Valentina Di Pietro, Stefano Signoretti, Giuseppe Lazzarino, Antonio Belli, Barbara Tavazzi
In this study, concentrations of free amino acids (FAA) and amino group containing compounds (AGCC) following graded diffuse traumatic brain injury (mild TBI, mTBI; severe TBI, sTBI) were evaluated. After 6, 12, 24, 48 and 120 hr aspartate (Asp), glutamate (Glu), asparagine (Asn), serine (Ser), glutamine (Gln), histidine (His), glycine (Gly), threonine (Thr), citrulline (Cit), arginine (Arg), alanine (Ala), taurine (Tau), γ-aminobutyrate (GABA), tyrosine (Tyr), S-adenosylhomocysteine (SAH), l-cystathionine (l-Cystat), valine (Val), methionine (Met), tryptophane (Trp), phenylalanine (Phe), isoleucine (Ile), leucine (Leu), ornithine (Orn), lysine (Lys), plus N-acetylaspartate (NAA) were determined in whole brain extracts (n = 6 rats at each time for both TBI levels)...
March 2017: Journal of Cellular and Molecular Medicine
Annick Bertrand, Marie Bipfubusa, Catherine Dhont, François-P Chalifour, Pascal Drouin, Chantal J Beauchamp
Specific amino acids have protective functions in plants under stress conditions. This study assessed the effects of rhizobial strains on the amino acid composition in alfalfa under salt stress. Two alfalfa cultivars (Medicago sativa L. cv Apica and salt-tolerant cv Halo) in association with two Sinorhizobium meliloti strains with contrasting growth under salt stress (strain A2 and salt-tolerant strain Rm1521) were exposed to different levels of NaCl (0, 20, 40, 80 or 160 mM NaCl) under controlled conditions...
November 2016: Plant Physiology and Biochemistry: PPB
Vijay P B Grover, Mark J W McPhail, Marzena Wylezinska-Arridge, Mary M E Crossey, Julie A Fitzpatrick, Louise Southern, Brian K Saxby, Nicola A Cook, I Jane Cox, Adam D Waldman, Novraj S Dhanjal, Aluel Bak-Bol, Roger Williams, Marsha Y Morgan, Simon D Taylor-Robinson
The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences...
February 2017: Metabolic Brain Disease
Asunción Cremades, Jesús Del Rio-Garcia, Ana Lambertos, Carlos López-Garcia, Rafael Peñafiel
The administration of l-arginine hydrochloride has been used for testing pituitary secretion in humans, and as an experimental model for induction of acute pancreatitis in rats and mice. Whereas in the first case, the administration of the amino acid is associated with hiperkalemia, in the model of acute pancreatitis no data are available on possible changes in potassium homeostasis. The present study shows that the acute administration to mice of l-arginine hydrochloride or other cationic amino acids almost duplicate plasma potassium levels...
2016: SpringerPlus
Claude Bachmann, Alexander Kainz, Elisabeth Haschke-Becher
OBJECTIVE: Quantifying pre-analytical effects of postprandial sampling delay and daily protein intake on plasma amino acid concentrations in healthy infants fed formula with low protein content (1.8-1.9 g/100 kcal). Intake of formula with higher protein content bears a risk for later obesity (Kirchberg, J Clin Endocrinol Metab 100(1):149-158, 2015). Formulas containing less than 1.8 g protein might be adequate but not safe (Fomon, J Pediatr Gastroenterol Nutr 28:495-501, 1999). With on-demand feeding reproducible controls of indispensible amino acid concentration cannot be made at trough level...
2017: JIMD Reports
Susan E Waisbren, Andrea L Gropman, Mark L Batshaw
The Urea Cycle Disorders Consortium (UCDC) has conducted, beginning in 2006, a longitudinal study (LS) of eight enzyme deficiencies/transporter defects associated with the urea cycle. These include N-acetylglutamate synthase deficiency (NAGSD); Carbamyl phosphate synthetase 1 deficiency (CPS1D); Ornithine transcarbamylase deficiency (OTCD); Argininosuccinate synthetase deficiency (ASSD) (Citrullinemia); Argininosuccinate lyase deficiency (ASLD) (Argininosuccinic aciduria); Arginase deficiency (ARGD, Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome (or mitochondrial ornithine transporter 1 deficiency [ORNT1D]); and Citrullinemia type II (mitochondrial aspartate/glutamate carrier deficiency [CITRIN])...
July 2016: Journal of Inherited Metabolic Disease
Maria Garrido, Jelena Skorucak, Daniela Raduazzo, Matteo Turco, Giuseppe Spinelli, Paolo Angeli, Piero Amodio, Peter Achermann, Sara Montagnese
UNLABELLED: Hyperammonaemia/mild hepatic encephalopathy (HE) can be simulated by the oral administration of a so-called amino acid challenge (AAC). This study sought to assess the effects of the AAC alone and in combination with either ammonia-lowering [L-ornithine-L-aspartate (LOLA)] or vigilance-enhancing medication (caffeine). Six patients with cirrhosis (5 males; 61.3 ± 9.2 years; 5 Child A, 1 Child B) and six healthy volunteers (5 males; 49.8 ± 10.6 years) were studied between 08:00 and 19:00 on Monday of three consecutive weeks...
August 2016: Metabolic Brain Disease
Heidi L Dalton, Cecilia K Blomstedt, Alan D Neale, Ros Gleadow, Kathleen D DeBoer, John D Hamill
Transgenic plants of Nicotiana tabacum L. homozygous for an RNAi construct designed to silence ornithine decarboxylase (ODC) had significantly lower concentrations of nicotine and nornicotine, but significantly higher concentrations of anatabine, compared with vector-only controls. Silencing of ODC also led to significantly reduced concentrations of polyamines (putrescine, spermidine and spermine), tyramine and phenolamides (caffeoylputrescine and dicaffeoylspermidine) with concomitant increases in concentrations of amino acids ornithine, arginine, aspartate, glutamate and glutamine...
May 2016: Journal of Experimental Botany
Jin-Ok Ahn, Qiang Li, Young-Heun Lee, Sei-Myoung Han, Cheol-Yong Hwang, Hwa-Young Youn, Jin-Young Chung
Seventeen dogs were treated with L-ornithin-L-aspartate (LOLA; experimental group). Three dogs were treated with lactulose recognized therapy (control group). Following LOLA administration, 15 dogs experienced a significant decrease in ammonia level (p < 0.05) and showed clinical signs of improvement. However, there were no clinical signs of improvement in two dogs, even though the ammonia level decreased. Conversely, the clinical signs of the control group also improved and the ammonia level decreased, although these changes were not significant (p > 0...
September 30, 2016: Journal of Veterinary Science
H M Durgun, A Ozhasenekler, R Dursun, M K Basarali, G Turkcu, M Orak, M Ustundag, C Guloglu
OBJECTIVE: Ethyl alcohol is a substance that is widely used worldwide and known to exert toxic effects on liver. In this study, we aimed to examine the effect of L-ornithine L-aspartate (LOLA) on the toxicity of a single dose of ethyl alcohol in rats. SUBJECTS AND METHOD: We used 32 randomly selected male Sprague-Dawley rats weighing 200-250 g. The rats were grouped into four groups with each group containing eight rats: Group 1: the control group, Group 2: the ethyl alcohol group, Group 3: the LOLA group and Group 4: the ethyl alcohol+LOLA group...
June 2015: West Indian Medical Journal
Karl-Uwe Petersen
Hepatic encephalopathy is a result of insufficient liver function, with grave consequences for the patients. It is primarily caused by disturbed hepatic elimination of the neurotoxin, ammonia (NH3). Aside from dietetic measures, treatment rests on drugs designed to reduce the NH3 burden. The primary options, lactulose and the practically unabsorbable antibiotic rifaximin are suitable to decrease the bacterial NH3 generation in the intestine. Other antibiotics like neomycin at best have a place in acute treatment...
May 2015: Medizinische Monatsschrift Für Pharmazeuten
Phillip K Henderson, Jorge L Herrera
Hepatic encephalopathy exists along a continuum from abnormal neuropsychiatric testing in the absence of clinical findings to varying degrees of detectable clinical findings. The International Society for Hepatic Encephalopathy and Nitrogen Metabolism has endorsed the term "covert" to encompass minimal hepatic encephalopathy and grade I overt hepatic encephalopathy. Covert hepatic encephalopathy has been associated with poor quality of life, decreased employment, increased falls, and increased traffic accidents that significantly impact quality of life and health care expenditures...
August 2015: Clinics in Liver Disease
Kavish R Patidar, Jasmohan S Bajaj
Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative...
November 2015: Clinical Gastroenterology and Hepatology
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