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Kynurenine

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https://www.readbyqxmd.com/read/27907873/excellent-storage-stability-and-sensitive-detection-of-neurotoxin-quinolinic-acid
#1
Ranjana Singh, Sunayana Kashyap, Suveen Kumar, Shiju Abraham, Tejendra K Gupta, Arvind M Kayastha, Bansi D Malhotra, Preeti Suman Saxena, Anchal Srivastava, Ranjan K Singh
Quinolinic acid (QA) is a metabolite of tryptophan degradation obtained through kynurenine pathway, produced naturally in the mammalian brain as well as in the human cerebrospinal fluid. The presence of QA ~10-40µM is a clear indicator of many neurological disorders as well as deficiency of vitamin B6 in human being. In the present work; rapid, sensitive and cost-effective bio-electrodes were prepared to detect the trace amount of endogenous neurotoxin (QA). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies were carried out to measure the electrochemical response of the fabricated bio-electrodes as a function of QA concentrations...
November 23, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27907839/influence-of-picolinic-acid-on-seizure-susceptibility-in-mice
#2
Anna Cioczek-Czuczwar, Piotr Czuczwar, Waldemar Andrzej Turski, Jolanta Parada-Turska
BACKGROUND: The mechanism of drug resistance in epilepsy remains unknown. Picolinic acid (PIC) is an endogenous metabolite of the kynurenine pathway and a chelating agent added to dietary supplements. Both inhibitory and excitatory properties of PIC were reported. The aim of this study was to determine the influence of exogenously applied PIC upon the electroconvulsive threshold and the activity of chemical convulsants in eight models of epilepsy in mice. METHODS: All experiments were performed on adult male Swiss albino mice...
October 12, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27904735/urinary-metabolomics-of-young-italian-autistic-children-supports-abnormal-tryptophan-and-purine-metabolism
#3
Federica Gevi, Lello Zolla, Stefano Gabriele, Antonio M Persico
BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27904018/impact-of-plasma-kynurenine-level-on-functional-capacity-and-outcome-in-heart-failure%C3%A3-results-from-studies-investigating-co-morbidities-aggravating-heart-failure-sica-hf
#4
Masaaki Konishi, Nicole Ebner, Jochen Springer, Joerg C Schefold, Wolfram Doehner, Thomas Bernd Dschietzig, Stefan D Anker, Stephan von Haehling
BACKGROUND: Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.Methods and Results:Plasma kynurenine was assessed in 249 patients with HF (67±11 years, 21% women) and in 45 controls from the SICA-HF study...
November 30, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27889626/absence-of-kynurenine-3-monooxygenase-reduces-mortality-of-acute-viral-myocarditis-in-mice
#5
Hisako Kubo, Masato Hoshi, Akihiro Mouri, Chieko Tashita, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO(-/-) mice and KMO(+/+) mice...
November 23, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27886578/kynurenic-acid-and-psychotic-symptoms-and-personality-traits-in-twins-with-psychiatric-morbidity
#6
Magdalena E Kegel, Viktoria Johansson, Lennart Wetterberg, Maria Bhat, Lilly Schwieler, Tyrone D Cannon, Ina Schuppe-Koistinen, Göran Engberg, Mikael Landén, Christina M Hultman, Sophie Erhardt
Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins...
November 16, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27886064/probiotic-supplements-beneficially-affect-tryptophan-kynurenine-metabolism-and-reduce-the-incidence-of-upper-respiratory-tract-infections-in-trained-athletes-a-randomized-double-blinded-placebo-controlled-trial
#7
Barbara Strasser, Daniela Geiger, Markus Schauer, Johanna M Gostner, Hannes Gatterer, Martin Burtscher, Dietmar Fuchs
BACKGROUND: Prolonged intense exercise has been associated with transient suppression of immune function and an increased risk of infections. In this context, the catabolism of amino acid tryptophan via kynurenine may play an important role. The present study examined the effect of a probiotic supplement on the incidence of upper respiratory tract infections (URTI) and the metabolism of aromatic amino acids after exhaustive aerobic exercise in trained athletes during three months of winter training...
November 23, 2016: Nutrients
https://www.readbyqxmd.com/read/27876634/individual-and-interactive-sex-specific-effects-of-acute-restraint-and-systemic-ifn-%C3%AE-treatment-on-neurochemistry
#8
Darcy Litteljohn, Chris Rudyk, Sara Razmjou, Zach Dwyer, Shuaib Syed, Shawn Hayley
Compelling evidence supports the involvement of the pro-inflammatory cytokines, IL-6, IFN-α and TNF-α in depression and related stress-associated pathologies. A role has also been suggested for the Th1-type cytokine, IFN-γ, with most mechanistic accounts focusing on the cytokine's capacity to induce indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is surprisingly little evidence directly linking IFN-γ to alterations of brain regional monoamine activity and HPA axis functioning...
November 19, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27867514/hepatitis-c-virus-drives-the-pathogenesis-of-hepatocellular-carcinoma-from-immune-evasion-to-carcinogenesis
#9
Miriam Canavese, Danushka Wijesundara, Guy J Maddern, Branka Grubor-Bauk, Ehud Hauben
Persistent hepatitis C virus (HCV) infection is associated with high incidence of hepatocellular carcinoma (HCC), the most common primary malignancy of the liver with over half a million new cases diagnosed annually worldwide. The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and its activation by environmental chemicals and by its endogenous ligand kynurenine (Kyn) has been implicated in a variety of tumour-promoting processes such as transformation, tumorigenesis and in immunosuppression that enables tumour survival and growth...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27861556/antioxidant-properties-of-kynurenines-density-functional-theory-calculations
#10
Aleksandr V Zhuravlev, Gennady A Zakharov, Boris F Shchegolev, Elena V Savvateeva-Popova
Kynurenines, the main products of tryptophan catabolism, possess both prooxidant and anioxidant effects. Having multiple neuroactive properties, kynurenines are implicated in the development of neurological and cognitive disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Autoxidation of 3-hydroxykynurenine (3HOK) and its derivatives, 3-hydroxyanthranilic acid (3HAA) and xanthommatin (XAN), leads to the hyperproduction of reactive oxygen species (ROS) which damage cell structures. At the same time, 3HOK and 3HAA have been shown to be powerful ROS scavengers...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27860276/regulation-of-kynurenine-biosynthesis-during-influenza-virus-infection
#11
Lana Gaelings, Sandra Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B Lorey, Janne Tynell, Liesbeth Vande Ginste, Ronan Le Goffic, Matthew S Miller, Marika Kuisma, Varpu Marjomäki, Jef De Brabander, Sampsa Matikainen, Tuula A Nyman, Dennis Bamford, Xavier Saelens, Ilkka Julkunen, Henrik Paavilainen, Veijo Hukkanen, Vidya Velagapudi, Denis E Kainov
Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus-host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis...
November 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27859255/modulation-of-multidrug-resistance-associated-proteins-function-in-erythrocytes-in-glycerol-induced-acute-renal-failure-rats
#12
Aoi Matsushima, Keisuke Oda, Nobuhiro Mori, Teruo Murakami
OBJECTIVES: Evaluation of the function of multidrug resistance-associated proteins (MRPs) expressed in erythrocytes and screening of endogenous MRPs modulator(s) in glycerol-induced acute renal failure (ARF) rats. METHODS: Concentrations of 2,4-dinitrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, in erythrocytes after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, were determined in control and ARF rats. The screening of endogenous MRPs modulator(s) was performed using washed erythrocytes and inside-out erythrocyte membrane vesicles (IOVs) in vitro...
November 18, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27835640/mass-spectrometry-based-metabolomics-comparison-of-liver-grafts-from-donors-after-circulatory-death-dcd-and-donors-after-brain-death-dbd-used-in-human-orthotopic-liver-transplantation
#13
Olga Hrydziuszko, M Thamara P R Perera, Richard Laing, Jennifer Kirwan, Michael A Silva, Douglas A Richards, Nick Murphy, Darius F Mirza, Mark R Viant
Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2)...
2016: PloS One
https://www.readbyqxmd.com/read/27832762/tryptophan-metabolism-its-relation-to-inflammation-and-stress-markers-and-association-with-psychological-and-cognitive-functioning-tasmanian-chronic-kidney-disease-pilot-study
#14
Naama Karu, Charlotte McKercher, David S Nichols, Noel Davies, Robert A Shellie, Emily F Hilder, Matthew D Jose
BACKGROUND: Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning...
November 10, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27830572/inflammation-associated-co-morbidity-between-depression-and-cardiovascular-disease
#15
Angelos Halaris
Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27830380/recovery-of-pan-genotypic-and-genotype-specific-amino-acid-alterations-in-chronic-hepatitis-c-after-viral-clearance-transition-at-the-crossroad-of-metabolism-and-immunity
#16
Ming-Ling Chang, Mei-Ling Cheng, Su-Wei Chang, Hsiang-Yu Tang, Cheng-Tang Chiu, Chau-Ting Yeh, Ming-Shi Shiao
Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography-tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients...
November 10, 2016: Amino Acids
https://www.readbyqxmd.com/read/27828964/chronic-treatment-with-the-ido1-inhibitor-1-methyl-d-tryptophan-minimizes-the-behavioural-and-biochemical-abnormalities-induced-by-unpredictable-chronic-mild-stress-in-mice-comparison-with-fluoxetine
#17
Anthony Laugeray, Jean-Marie Launay, Jacques Callebert, Oguz Mutlu, Gilles J Guillemin, Catherine Belzung, Pascal R Barone
We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure-a validated model of stress-induced depression-results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine...
2016: PloS One
https://www.readbyqxmd.com/read/27819068/the-kynurenine-tryptophan-ratio-and-glioblastoma-patients-treated-with-hsppc-96-vaccine
#18
Alicia Lenzen, Lijie Zhai, Kristen L Lauing, Galina Gritsina, Erik Ladomersky, Matthew Genet, C David James, Orin Bloch, Derek A Wainwright
The discovery that immunotherapy is a clinically-relevant approach for the treatment of malignant tumors is revolutionizing patient care. In adults diagnosed with glioblastoma (GBM), an aggressive and incurable primary brain tumor, autologous HSPPC-96 vaccination provides a significant increase in overall survival. However, all GBM patients eventually succumb to their disease, providing rationale for discovering new methods that proactively identify individuals that will respond, optimally. Of the immunosuppressive mediators that contribute to the inhibition of productive tumor immunity, indoleamine 2,3 dioxygenase 1 (IDO1), a rate-limiting enzyme that catabolizes tryptophan (Trp) into kynurenine (Kyn), has been demonstrated to be expressed at elevated levels in patients with malignant glioma...
September 2016: Immunotherapy (Los Angeles, Calif.)
https://www.readbyqxmd.com/read/27818124/chrysin-promotes-attenuation-of-depressive-like-behavior-and-hippocampal-dysfunction-resulting-from-olfactory-bulbectomy-in-mice
#19
Carlos Borges Filho, Cristiano Ricardo Jesse, Franciele Donato, Lucian Del Fabbro, Marcelo Gomes de Gomes, André Tiago Rossito Goes, Leandro Cattelan Souza, Silvana Peterini Boeira
Chrysin is a natural flavonoid which is found in bee propolis, honey and various plants, and antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. In this work, we investigated the action of chrysin treatment (5 or 20 mg/kg) for 14 days in the depressant-like behavior and in the hippocampal dysfunction induced by olfactory bulbectomy (OB), an animal model of agitated depression. Results demonstrated that OB occasioned a depressant-like behavior in the splash test, open field test and forced swimming test...
November 3, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27815661/improved-radiosynthesis-and-biological-evaluations-of-l-and-d-1-18-f-fluoroethyl-tryptophan-for-pet-imaging-of-ido-mediated-kynurenine-pathway-of-tryptophan-metabolism
#20
Yangchun Xin, Hancheng Cai
PURPOSE: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (PET) could provide valuable information for noninvasive assessment of cancer immunotherapy response. In this work, radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan (1-L-[(18)F]FETrp) and its enantioisomer 1-D-[(18)F]FETrp were synthesized and evaluated for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism...
November 4, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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