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Kynurenic acid

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https://www.readbyqxmd.com/read/28735520/gemst-a-taylor-made-combination-that-reverts-neuroanatomical-changes-in-stroke
#1
Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas
In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO2-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers...
May 25, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733707/angiotensin-ii-type-1-receptor-blockers-inhibit-kat-ii-activity-in-the-brain-its-possible-clinical-applications
#2
Izabela Zakrocka, Katarzyna M Targowska-Duda, Artur Wnorowski, Tomasz Kocki, Krzysztof Jóźwiak, Waldemar A Turski
Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms...
July 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28731451/novel-blood-based-biomarkers-of-cognition-stress-and-physical-or-cognitive-training-in-older-adults-at-risk-of-dementia-preliminary-evidence-for-a-role-of-bdnf-irisin-and-the-kynurenine-pathway
#3
Olivia C Küster, Daria Laptinskaya, Patrick Fissler, Cathrin Schnack, Martina Zügel, Verena Nold, Franka Thurm, Sina Pleiner, Alexander Karabatsiakis, Björn von Einem, Patrick Weydt, Andre Liesener, Andreas Borta, Alexander Woll, Bastian Hengerer, Iris-Tatjana Kolassa, Christine A F von Arnim
 Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28729445/preferential-disruption-of-prefrontal-gabaergic-function-by-nanomolar-concentrations-of-the-%C3%AE-7nach-negative-modulator-kynurenic-acid
#4
Eden Flores-Barrera, Daniel R Thomases, Daryn K Cass, Ajay Bhandari, Robert Schwarcz, John P Bruno, Kuei Y Tseng
Increased concentrations of kynurenic acid (KYNA) in the prefrontal cortex (PFC) are thought to contribute to the development of cognitive deficits observed in schizophrenia. Although this view is consistent with pre-clinical studies showing a negative impact of prefrontal KYNA elevation on executive function, the mechanism underlying such a disruption remains unclear. Here we measured changes in local field potential responses to ventral hippocampal stimulation in vivo, and conducted whole-cell patch-clamp recordings in brain slices to reveal how nanomolar concentrations of KYNA alter synaptic transmission in the PFC of male adult rats...
July 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28726741/magnolol-a-natural-polyphenol-attenuates-dextran-sulfate-sodium-induced-colitis-in-mice
#5
Ling Zhao, Hai-Tao Xiao, Huai-Xue Mu, Tao Huang, Ze-Si Lin, Linda L D Zhong, Guang-Zhi Zeng, Bao-Min Fan, Cheng-Yuan Lin, Zhao-Xiang Bian
Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity...
July 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28712413/sleep-disturbance-and-kynurenine-metabolism-in-depression
#6
Hyong Jin Cho, Jonathan Savitz, Robert Dantzer, T Kent Teague, Wayne C Drevets, Michael R Irwin
OBJECTIVE: Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28710517/urinary-profiling-of-tryptophan-and-its-related-metabolites-in-patients-with-metabolic-syndrome-by-liquid-chromatography-electrospray-ionization-mass-spectrometry
#7
Ji Sun Oh, Hong Seong Seo, Kyoung Heon Kim, Heesoo Pyo, Bong Chul Chung, Jeongae Lee
Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity...
July 14, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#8
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain IL-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28707585/migraine-neurogenic-inflammation-drug-development-pharmacochemical-aspects
#9
Melinda Lukács, János Tajti, Ferenc Fülöp, József Toldi, Lars Edvinsson, László Vécsei
BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28706436/the-presence-of-kynurenine-aminotransferases-in-the-human-cornea-evidence-from-bioinformatics-analysis-of-gene-expression-and-immunohistochemical-staining
#10
Anna Matysik-Woźniak, Anselm Jünemann, Waldemar A Turski, Artur Wnorowski, Krzysztof Jóźwiak, Roman Paduch, Etsuo Okuno, Joanna Moneta-Wielgoś, Tomasz Chorągiewicz, Ryszard Maciejewski, Robert Rejdak
PURPOSE: Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), a compound of significant biological activity. The aim of this study is to investigate the presence and distribution of KAT immunoreactivity in the healthy human cornea. METHODS: Data on gene expression in human eye structures were extracted from public microarray experiments using Genevestigator software. Immunohistochemistry was conducted using polyclonal antibodies against KAT I, II, and III on sections of eight enucleated eyes from patients with choroidal melanoma...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28705908/importance-of-kynurenine-in-pulmonary-hypertension
#11
Bence M Nagy, Chandran Nagaraj, Andreas Meinitzer, Neha Sharma, Rita Papp, Vasile Foris, Bahil Ghanim, Grazyna Kwapiszewska, Gabor Kovacs, Walter Klepetko, Thomas R Pieber, Harald Mangge, Horst Olschewski, Andrea Oslchewski
The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hyper-tension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to in-vestigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine and kynurenic-acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls and 20 patients with chronic lung disease or meta-bolic syndrome without-PH. Laser-dissected pulmonary arteries from IPAH and control lungs were tested for the expression of IDO, the rate-limiting enzyme for the conversion from tryptophan to kynurenine...
July 13, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28690204/depressive-anxiety-and-hypomanic-symptoms-in-schizophrenia-may-be-driven-by-tryptophan-catabolite-trycat-patterning-of-iga-and-igm-responses-directed-to-trycats
#12
Buranee Kanchanatawan, Sunee Sirivichayakul, André F Carvalho, George Anderson, Piotr Galecki, Michael Maes
The aim of this study was to delineate the associations between the tryptophan catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH-kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls. The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of Schizophrenia (PANSS) were measured...
July 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28680298/high-fat-diet-and-voluntary-chronic-aerobic-exercise-recover-altered-levels-of-aging-related-tryptophan-metabolites-along-the-kynurenine-pathway
#13
Keon-Joo Lee, Keun-Hwa Jung, Joo-Youn Cho, Soon-Tae Lee, Hwa Suk Kim, Jun Hwa Shim, Sang Kun Lee, Manho Kim, Kon Chu
Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28666226/comprehensive-analysis-of-the-tryptophan-metabolome-in-urine-of-patients-with-acute-intermittent-porphyria
#14
Alex Gomez-Gomez, Josep Marcos, Paula Aguilera, Jordi To-Figueras, Oscar J Pozo
BACKGROUND: Acute intermittent porphyria (AIP) is a rare metabolic disorder due to a deficiency of porphobilinogen deaminase, the third enzyme of the heme biosynthetic pathway. This low enzymatic activity may predispose to the appearance of acute neurological attacks. Seminal studies suggested that AIP was associated with changes in tryptophan homeostasis with inconclusive results. Therefore, the aim of this study was to analyze the urinary metabolome of AIP patients focusing on tryptophan metabolism using state-of-the-art technology...
June 19, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28659861/the-effect-of-systemic-nitroglycerin-administration-on-the-kynurenine-pathway-in-the-rat
#15
Gábor Nagy-Grócz, Klaudia F Laborc, Gábor Veres, Attila Bajtai, Zsuzsanna Bohár, Dénes Zádori, Annamária Fejes-Szabó, Eleonóra Spekker, László Vécsei, Árpád Párdutz
The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28628213/changes-in-kynurenine-pathway-metabolism-in-parkinson-patients-with-l-dopa-induced-dyskinesia
#16
Jesper F Havelund, Andreas D Andersen, Michael Binzer, Morten Blaabjerg, Niels H H Heegaard, Egon Stenager, Nils J Faergeman, Jan Bert Gramsbergen
L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28560624/urinary-metabolomic-profiling-in-rats-exposed-to-dietary-di-2-ethylhexyl-phthalate-dehp-using-ultra-performance-liquid-chromatography-quadrupole-time-of-flight-tandem-mass-spectrometry-uplc-q-tof-ms
#17
Xinwen Dong, Yunbo Zhang, Jin Dong, Yue Zhao, Jipeng Guo, Zhanju Wang, Mingqi Liu, Xiaolin Na, Cheng Wang
Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS)...
May 30, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28551532/effects-of-tryptophan-kynurenine-and-kynurenic-acid-exerted-on-human-reconstructed-corneal-epithelium-in-vitro
#18
Anna Matysik-Woźniak, Roman Paduch, Waldemar A Turski, Ryszard Maciejewski, Anselm G Jünemann, Robert Rejdak
BACKGROUND: Tryptophan metabolites formed along kynurenine pathway may affect cell proliferation and tissue function. This pathway presents potential sites for drug discovery. Tryptophan and its metabolites kynurenine and kynurenic acid may be involved in the physiology and pathology of the ocular surface. The purpose of this work is to investigate the effect exerted by tryptophan, kynurenine and kynurenic acid upon corneal epithelium. METHODS: A SkinEthic™ HCE human reconstructed corneal epithelium model was used...
February 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28546077/systemic-administration-of-l-kynurenine-sulfate-induces-cerebral-hypoperfusion-transients-in-adult-c57bl-6-mice
#19
Dániel Péter Varga, Ákos Menyhárt, Tamás Puskás, Ferenc Bari, Eszter Farkas, Zsolt Kis, László Vécsei, József Toldi, Levente Gellért
The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission. Recently, l-KYN or one of its derivatives were attributed a direct role in the regulation of the systemic circulation. l-KYN dilates arterial blood vessels during sepsis in rats, while it increases cerebral blood flow (CBF) in awake rabbits...
May 22, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28527020/changes-in-serum-levels-of-kynurenine-metabolites-in-paediatric-patients-affected-by-adhd
#20
Melania Evangelisti, Pietro De Rossi, Jole Rabasco, Renato Donfrancesco, Luana Lionetto, Matilde Capi, Gabriele Sani, Maurizio Simmaco, Ferdinando Nicoletti, Maria Pia Villa
This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
May 19, 2017: European Child & Adolescent Psychiatry
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