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https://www.readbyqxmd.com/read/28792876/nad-deficiency-congenital-malformations-and-niacin-supplementation
#1
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie
BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28754152/cerebrospinal-fluid-kynurenine-and-kynurenic-acid-concentrations-are-associated-with-coma-duration-and-long-term-neurocognitive-impairment-in-ugandan-children-with-cerebral-malaria
#2
Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert O Opoka, Paul Bangirana, Carl M Sellgren, Ronny Wickström, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy C John
BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed...
July 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28751584/kynurenines-tryptophan-s-metabolites-in-exercise-inflammation-and-mental-health
#3
REVIEW
Igor Cervenka, Leandro Z Agudelo, Jorge L Ruas
Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28740612/3-hydroxykynurenine-a-tryptophan-metabolite-generated-during-the-infection-is-active-against-trypanosoma-cruzi
#4
Carolina P Knubel, Constanza Insfran, Fernando F Martinez, Cintia Diaz Lujan, Ricardo E Fretes, Martin G Theumer, Laura Cervi, Claudia C Motran
The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28740260/richer-gut-microbiota-with-distinct-metabolic-profile-in-hiv-infected-elite-controllers
#5
Jan Vesterbacka, Javier Rivera, Kajsa Noyan, Mariona Parera, Ujjwal Neogi, Malu Calle, Roger Paredes, Anders Sönnerborg, Marc Noguera-Julian, Piotr Nowak
Gut microbiota dysbiosis features progressive HIV infection and is a potential target for intervention. Herein, we explored the microbiome of 16 elite controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative controls. We found that the number of observed genera and richness indices in fecal microbiota were significantly higher in EC versus naive. Genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were more abundant in EC, whereas Blautia and Anaerostipes were depleted...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738353/inflammation-effects-on-glutamate-as-a-pathway-to-neuroprogression-in-mood-disorders
#6
Ebrahim Haroon, Andrew H Miller
Neuroprogression is a term used to describe worsening psychopathology, poor treatment response, and declining cognitive and functional outcomes among patients with chronic mental disorders. Chronic inflammatory activation and glutamate-mediated excitotoxicity are two key etiological factors implicated in the development of neuroprogression. In this chapter, we hypothesize that the association between chronic inflammatory activation, neuroprogression, and glutamate dysregulation might be mediated by glial dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28738351/major-depression-as-a-neuroprogressive-prelude-to-dementia-what-is-the-evidence
#7
Brian E Leonard
Epidemiological studies implicate chronic depression as a predisposing factor for dementia in later life. However, the link is incompletely understood and controversial. The aim of this review is to consider some of the biological factors that contribute to neuroprogressive brain dysfunction in late life as a consequence of prolonged, low-grade inflammation in the course of depressive episodes. As chronic inflammation is known to precipitate increased apoptosis of neurons and astrocytes, this could be a contributing factor to brain dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28736331/microbial-regulation-of-hippocampal-mirna-expression-implications-for-transcription-of-kynurenine-pathway-enzymes
#8
Gerard M Moloney, Olivia F O'Leary, Eloisa Salvo-Romero, Lieve Desbonnet, Fergus Shanahan, Timothy G Dinan, Gerard Clarke, John F Cryan
Increasing evidence points to a functional role of the enteric microbiota in brain development, function and behaviour including the regulation of transcriptional activity in the hippocampus. Changes in CNS miRNA expression may reflect the colonisation status of the gut. Given the pivotal impact of miRNAs on gene expression, our study was based on the hypothesis that gene expression would also be altered in the germ-free state in the hippocampus. We measured miRNAs in the hippocampus of Germ free (GF), conventional (C) and Germ free colonised (exGF) Swiss Webster mice...
July 20, 2017: Behavioural Brain 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
#9
Olivia C Küster, Daria Laptinskaya, Patrick Fissler, Cathrin Schnack, Martina Zügel, Verena Nold, Franka Thurm, Sina Pleiner, Alexander Karabatsiakis, Björn von Einem, Patrick Weydt, André 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...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28723608/breastfeeding-and-the-gut-brain-axis-is-there-a-role-for-melatonin
#10
REVIEW
George Anderson, Cathy Vaillancourt, Michael Maes, Russel J Reiter
The benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system...
July 19, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28712531/the-role-of-tryptophan-metabolism-and-food-craving-in-the-relationship-between-obesity-and-bipolar-disorder
#11
N Dalkner, M Platzer, S A Bengesser, A Birner, F T Fellendorf, R Queissner, A Painold, H Mangge, D Fuchs, B Reininghaus, H P Kapfhammer, S J Holasek, E Z Reininghaus
BACKGROUND & AIMS: Individuals with bipolar disorder (BD) have a significantly increased risk of obesity-related conditions. The imbalance between food intake and energy expenditure is assumed to be a major risk factor for obesity in BD. This study analyzed food craving in relation to anthropometric, metabolic, and neurobiological parameters in a well-characterized cohort of euthymic individuals with BD. METHODS: One-hundred-thirty-five patients completed the Food-Craving Inventory assessing four categories of food craving (fat, fast-food, sweets and carbohydrate craving)...
July 4, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28712413/sleep-disturbance-and-kynurenine-metabolism-in-depression
#12
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/28688912/inhibition-of-the-kynurenine-pathway-protects-against-reactive-microglial-associated-reductions-in-the-complexity-of-primary-cortical-neurons
#13
Katherine O'Farrell, Eimear Fagan, Thomas J Connor, Andrew Harkin
Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP...
September 5, 2017: European Journal of Pharmacology
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
#14
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/28664173/dietary-amino-acid-intakes-associated-with-a-low-phenylalanine-diet-combined-with-amino-acid-medical-foods-and-glycomacropeptide-medical-foods-and-neuropsychological-outcomes-in-subjects-with-phenylketonuria
#15
Bridget M Stroup, Sangita G Murali, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy, Denise M Ney
This article provides original data on median dietary intake of 18 amino acids from amino acid medical foods, glycomacropeptide medical foods, and natural foods based on 3-day food records obtained from subjects with phenylketonuria who consumed low-phenylalanine diets in combination with amino acid medical foods and glycomacropeptide medical foods for 3 weeks each in a crossover design. The sample size of 30 subjects included 20 subjects with classical phenylketonuria and 10 with a milder or variant form of phenylketonuria...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28659861/the-effect-of-systemic-nitroglycerin-administration-on-the-kynurenine-pathway-in-the-rat
#16
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/28659716/aspects-of-tryptophan-and-nicotinamide-adenine-dinucleotide-in-immunity-a-new-twist-in-an-old-tale
#17
REVIEW
Hector Rodriguez Cetina Biefer, Anju Vasudevan, Abdallah Elkhal
Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28651456/phytochemical-treatments-target-kynurenine-pathway-induced-oxidative-stress
#18
K Parasram
OBJECTIVE: The objective of this paper was to link the phytochemical and metabolic research treating quinolinic acid induced oxidative stress in neurodegenerative disorders. METHODS: Quinolinic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, plays a role in the oxidative stress associated with many neurological disorders and is used to simulate disorders such as Parkinson's disease. RESULTS: In these models, phytochemicals have been shown to reduce striatal lesion size, reduce inflammation and prevent lipid peroxidation caused by quinolinic acid...
June 26, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#19
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
June 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28631232/activation-of-brain-indoleamine-2-3-dioxygenase-contributes-to-depressive-like-behavior-induced-by-an-intracerebroventricular-injection-of-streptozotocin-in-mice
#20
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Lucian Del Fabbro, André Tiago Rossito Goes, Franciele Donato, Silvana Peterini Boeira
There is a lack of information concerning the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. The elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In the present study, we reported that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, as measured by the increased duration of immobility in the tail suspension test and decreased sucrose intake in the sucrose preference test...
June 19, 2017: Neurochemical Research
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