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Kynurenate

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https://www.readbyqxmd.com/read/28628213/changes-in-kynurenine-pathway-metabolism-in-parkinson-patients-with-l-dopa-induced-dyskinesia
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28486923/kynurenic-acid-and-neuroprotective-activity-of-the-ketogenic-diet-in-the-eye
#6
Tomasz Żarnowski, Maria Tulidowicz-Bielak, Iwona Żarnowska, Krystyna Mitosek-Szewczyk, Artur Wnorowski, Krzysztof Jóźwiak, Maciej Gasior, Waldemar A Turski
There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD...
May 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28482311/tryptophan-breakdown-and-cognition-in-bipolar-disorder
#7
Martina Platzer, Nina Dalkner, Frederike T Fellendorf, Armin Birner, Susanne A Bengesser, Robert Queissner, Nora Kainzbauer, René Pilz, Simone Herzog-Eberhard, Carlo Hamm, Christa Hörmanseder, Alexander Maget, Philipp Rauch, Harald Mangge, Dietmar Fuchs, Sieglinde Zelzer, Gregor Schütze, Natalie Moll, Markus J Schwarz, Rodrigo B Mansur, Roger S McIntyre, Eva Z Reininghaus
INTRODUCTION: It has been demonstrated that bipolar disorder (BD) is often accompanied by cognitive deficits across all subdomains including verbal memory, attention and executive functioning. Cognitive deficits are observed both during episodes of mania or depression, as well as during the euthymic phase. It has been proposed that chronic immune-mediated inflammation in the central nervous system results in alterations in neural structures that subserve cognitive function. Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity...
April 27, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28469469/tryptophan-metabolism-in-patients-with-chronic-kidney-disease-secondary-to-type-2-diabetes-relationship-to-inflammatory-markers
#8
Subrata Debnath, Chakradhar Velagapudi, Laney Redus, Farook Thameem, Balakuntalam Kasinath, Claudia E Hura, Carlos Lorenzo, Hanna E Abboud, Jason C O'Connor
OBJECTIVE: Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. METHODS: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28469467/interactions-of-tryptophan-and-its-catabolites-with-melatonin-and-the-alpha-7-nicotinic-receptor-in-central-nervous-system-and-psychiatric-disorders-role-of-the-aryl-hydrocarbon-receptor-and-direct-mitochondria-regulation
#9
REVIEW
George Anderson, Michael Maes
Recent work indicates an intimate interaction of the tryptophan catabolite (TRYCAT) pathways with the melatonergic pathways, primarily via TRYCAT pathway induction taking tryptophan away from the production of serotonin, which is a necessary precursor for the melatonergic pathways. The alpha 7 nicotinic receptor may be significantly modulated by this interaction, given its inactivation by the TRYCAT, kynurenic acid, and its induction by melatonin. Similarly, the aryl hydrocarbon receptor is activated by both kynurenic acid and kynurenine, leading to CYP1A2 and melatonin metabolism, whereas melatonin may act to inhibit the aryl hydrocarbon receptor...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28463241/serum-kynurenic-acid-is-reduced-in-affective-psychosis
#10
B E Wurfel, W C Drevets, S A Bliss, J R McMillin, H Suzuki, B N Ford, H M Morris, T K Teague, R Dantzer, J B Savitz
A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative N-methyl-d-aspartate (NMDA) receptor agonist...
May 2, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28452488/metabolomics-study-of-the-effects-of-inflammation-hypoxia-and-high-glucose-on-isolated-human-pancreatic-islets
#11
Marta Garcia-Contreras, Alejandro Tamayo-Garcia, Kirk L Pappan, Gregory A Michelotti, Cherie L Stabler, Camillo Ricordi, Peter Buchwald
The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation...
May 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28442354/the-influence-of-stress-on-neuroinflammation-and-alterations-in-brain-structure-and-function-in-major-depressive-disorder
#12
REVIEW
Yong-Ku Kim, Eunsoo Won
Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid...
June 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28431630/kynurenic-acid-and-its-analogue-can-alter-the-opioid-receptor-g-protein-signaling-after-acute-treatment-via-nmda-receptor-in-rat-cortex-and-striatum
#13
Reza Samavati, Ferenc Zádor, Edina Szűcs, Bernadett Tuka, Diána Martos, Gábor Veres, Róbert Gáspár, István M Mándity, Ferenc Fülöp, László Vécsei, Sándor Benyhe, Anna Borsodi
Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28426698/extensive-alterations-of-blood-metabolites-in-pediatric-cerebral-malaria
#14
Sanchit Gupta, Karl Seydel, Miguel A Miranda-Roman, Catherine M Feintuch, Alex Saidi, Ryung S Kim, Gretchen L Birbeck, Terrie Taylor, Johanna P Daily
Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy...
2017: PloS One
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#15
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28408830/twelve-week-physical-exercise-does-not-have-a-long-lasting-effect-on-kynurenines-in-plasma-of-depressed-patients
#16
Vincent Millischer, Sophie Erhardt, Örjan Ekblom, Yvonne Forsell, Catharina Lavebratt
BACKGROUND: Physical exercise has well-characterized positive effects on depressive symptoms. The underlying biologic mechanisms are, however, far from established. A recently discovered mechanism has linked the enhanced conversion of kynurenine to kynurenic acid (KYNA) to an increased resilience toward stress-induced depression in mice. The aim of this study was to translate these findings to humans. MATERIALS AND METHODS: Kynurenine and KYNA levels were measured by high-performance liquid chromatography in plasma samples from 117 patients affected by mild-to-moderate depression before and within a week after a 12-week training period at three different intensities...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28403801/iga-igm-responses-to-gram-negative-bacteria-are-not-associated-with-perinatal-depression-but-with-physio-somatic-symptoms-and-activation-of-the-tryptophan-catabolite-pathway-at-the-end-of-term-and-postnatal-anxiety
#17
Chutima Roomruangwong, Buranee Kanchanatawan, Sunee Sirivichayakul, George Anderson, André F Carvalho, Sebastien Duleu, Michel Geffard, Michael Maes
Evidence has implicated the translocation of commensal Gram-negative bacteria (Gram-B) due to leaky gut in the pathophysiology of depression and physio-somatic symptoms (e.g. fatigue, pain, irritable bowel syndrome, malaise, etc.). In addition, the leaky gut may contribute to immune-inflammatory activation and oxidative stress. This study investigated whether bacterial translocation is associated with perinatal depression and anxiety scores and with prenatal physio-somatic symptoms and immune-inflammatory biomarkers, including the tryptophan catabolite (TRYCAT) pathway...
April 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28364692/the-effect-of-three-angiotensin-converting-enzyme-inhibitors-on-kynurenic-acid-production-in-rat-kidney-in-vitro
#18
Izabela Zakrocka, Tomasz Kocki, Waldemar A Turski
BACKGROUND: The renin-angiotensin system (RAS) is commonly known to regulate blood pressure, water and electrolyte homeostasis, however it also exerts paracrine and autocrine actions on the kidney. Angiotensin-converting enzyme inhibitors (ACE-Is), alongside their hypotensive properties, have been shown to decrease kidney function decline in animal models of nephropathy. Glutamate (GLU) is the main stimulatory neurotransmitter in the central nervous system, however its importance in the periphery should also be considered...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28338954/meta-analysis-of-cerebrospinal-fluid-cytokine-and-tryptophan-catabolite-alterations-in-psychiatric-patients-comparisons-between-schizophrenia-bipolar-disorder-and-depression
#19
Alexandre K Wang, Brian J Miller
INTRODUCTION: Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders. METHODS: Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies...
March 17, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28337634/topical-dura-mater-application-of-cfa-induces-enhanced-expression-of-c-fos-and-glutamate-in-rat-trigeminal-nucleus-caudalis-attenuated-by-kyna-derivate-szr72
#20
M Lukács, K Warfvinge, J Tajti, F Fülöp, J Toldi, L Vécsei, L Edvinsson
BACKGROUND: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72...
December 2017: Journal of Headache and Pain
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