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https://www.readbyqxmd.com/read/29457994/uric-acid-and-allopurinol-aggravate-absence-epileptic-activity-in-wistar-albino-glaxo-rijswijk-rats
#1
Renáta Krisztina Lakatos, Árpád Dobolyi, Zsolt Kovács
Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete...
February 16, 2018: Brain Research
https://www.readbyqxmd.com/read/29454961/first-line-anti-tuberculosis-drugs-induce-hepatotoxicity-a-novel-mechanism-based-on-a-urinary-metabolomics-platform
#2
Jun Cao, Yijun Mi, Cuilin Shi, Yicong Bian, Chenrong Huang, Zhijian Ye, Linsheng Liu, Liyan Miao
Tuberculosis (TB) has become a global public health and social threat. As clinical first-line drugs, rifampicin and isoniazid used in combination with pyrazinamide and ethambutol (the HRZE regimen) usually induce hepatotoxicity. However, the mechanisms underlying this phenomenon remain unclear, and studying the metabolic impact of co-treating TB patients with the HRZE regimen can provide new hepatotoxicity evidence. In this study, urine metabolites from TB patients were profiled using a high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) platform...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29425801/analytical-and-clinical-validation-of-an-lc-ms-ms-method-to-measure-thiopurine-s-methyltransferase-activity-by-quantifying-d3-6-mmp
#3
Jing Ma, Christiaan W Sies, Linda S Pike
BACKGROUND: Identification of patients with thiopurine S-methyltransferase (TPMT) deficiency prior to thiopurine drug therapy has become routine clinical practice worldwide. To measure TPMT activity, traditional radiochemical assays have been replaced by chromatographic methods. METHOD: Inspired by the increasing number of isotope labelled sources that may be of benefit for the TPMT assay, a new LC-MS/MS method for TPMT activity was developed and validated. Isotope labelled d3-S-adenosyl-l-methionine (d3-SAM) was selected for the enzymatic methylation of mercaptopurine during sample incubation; d3-6-methylmercaptopurine (d3-6-MMP) with d2-2, 8-hypoxanthine as the internal standard was quantified to ascertain individual TPMT activity...
February 6, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29420256/nicotinamide-phosphoribosyltransferase-deficiency-potentiates-the-anti-proliferative-activity-of-methotrexate-through-enhanced-depletion-of-intracellular-atp
#4
Rakesh K Singh, Leon van Haandel, Daniel P Heruth, Shui Q Ye, J Steven Leeder, Mara L Becker, Ryan S Funk
Lower plasma nicotinamide phosphoribosyltransferase (NAMPT) levels are associated with improved response to methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). Cell-based studies confirmed that reduced cellular NAMPT activity potentiates the pharmacologic activity of MTX, however the mechanism of this interaction has yet to be defined. Therefore, in this study we investigate the mechanism of enhanced pharmacologic activity of MTX in NAMPT-deficient A549 cells. The siRNA-based silencing of NAMPT expression resulted in a greater than three-fold increase in the sensitivity to MTX (p<0...
February 2, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29416770/hprt1-activity-loss-is-associated-with-resistance-to-thiopurine-in-all
#5
Fan Yang, Houshun Fang, Dan Wang, Yao Chen, Yonggong Zhai, Bin-Bing S Zhou, Hui Li
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro, we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414865/development-of-an-effective-6-methylpurine-counterselection-marker-for-genetic-manipulation-in-thermococcus-barophilus
#6
Tiphaine Birien, Axel Thiel, Ghislaine Henneke, Didier Flament, Yann Moalic, Mohamed Jebbar
A gene disruption system for Thermococcus barophilus was developed using simvastatin (HMG-CoA reductase encoding gene) for positive selection and 5-Fluoroorotic acid (5-FOA), a pyrF gene for negative selection. Multiple gene mutants were constructed with this system, which offers the possibility of complementation in trans, but produces many false positives (<80%). To significantly reduce the rate of false positives, we used another counterselective marker, 6-methylpurine (6-MP), a toxic analog of adenine developed in Thermococcus kodakarensis, consistently correlated with the TK0664 gene (encoding a hypoxanthine-guanine phosphoribosyl-transferase)...
February 7, 2018: Genes
https://www.readbyqxmd.com/read/29413003/effects-of-chitosan-oligosaccharides-on-microbiota-composition-of-silver-carp-hypophthalmichthys-molitrix-determined-by-culture-dependent-and-independent-methods-during-chilled-storage
#7
Shiliang Jia, Xiaochang Liu, Zhan Huang, Yan Li, Longteng Zhang, Yongkang Luo
This study evaluated the effects of chitosan oligosaccharides (COS) on the changes in quality and microbiota of silver carp fillets stored at 4 °C. During storage, 1% (w/v) COS treated samples maintained good quality, as evidenced by retarding sensory deterioration, inhibiting microbial growth, attenuating the production of total volatile basic nitrogen, putrescine, cadaverine and hypoxanthine, and delaying degradation of inosine monophosphate and hypoxanthine ribonucleotide. Meanwhile, variability in the predominant microbiota in different samples was investigated by culture-dependent and -independent methods...
March 2, 2018: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29406992/disturbed-purine-nucleotide-metabolism-in-chronic-kidney-disease-is-a-risk-factor-for-cognitive-impairment
#8
Muhammed Khairujjaman Mazumder, Banashree Chetia Phukan, Aradhana Bhattacharjee, Anupom Borah
Chronic kidney disease (CKD) is an increasing global health burden. Disturbance in purine metabolism pathway and a higher level of serum uric acid, called hyperuricemia, is a risk factor of CKD, and it has been linked to increased prevalence and progression of the disease. In a recent study, it has been demonstrated that purine nucleotides and uric acid alter the activity of acetylcholinesterase (AChE). Thus, we hypothesize that adenine, hypoxanthine, xanthine, 2,8-dihydroxyadenine and uric acid may potentially interfere with the activity of AChE...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29385571/the-solute-transport-profile-of-two-aza-guanine-transporters-from-the-honey-bee-pathogen-paenibacillus-larvae
#9
Candace R Alexander, Douglas W Dingman, Neil P Schultes, George S Mourad
Two nucleobase transporters encoded in the genome of the Honey bee bacterial pathogen Paenibacillus larvae belong to the azaguanine-like transporters and are referred to as PlAzg1 and PlAzg2. PlAzg1 & 2 display significant amino acid sequence similarity, share predicted secondary structures and functional sequence motifs with two Escherichia coli nucleobase cation symporter 2 (NCS2) members; adenine permease (EcAdeP) and guanine-hypoxanthine permease EcGhxP. However, similarity does not define function. Heterologous complementation and functional analysis using nucleobase transporter deficient Saccharomyces cerevisiae strains revealed that PlAzg1 transports, adenine, hypoxanthine, xanthine and uracil, while PlAzg2 transports adenine, guanine, hypoxanthine, xanthine, cytosine and uracil...
January 29, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29378713/enhanced-ex-vivo-plasmodium-vivax-intraerythrocytic-enrichment-and-maturation-for-rapid-and-sensitive-parasite-growth-assays
#10
Gabriel W Rangel, Martha A Clark, Usheer Kanjee, Caeul Lim, Kathryn Shaw-Saliba, Maria José Menezes, Anjali Mascarenhas, Laura Chery, Edwin Gomes, Pradipsinh K Rathod, Marcelo U Ferreira, Manoj T Duraisingh
Plasmodium vivax chloroquine resistance has been documented in nearly every region endemic for this malaria-causing parasite. Unfortunately, P. vivax resistance surveillance and drug discovery is challenging due to low parasitemias of patient isolates, and poor parasite survival through ex vivo maturation, that reduce the sensitivity and scalability of current P. vivax antimalarial assays. Using cryopreserved patient isolates from Brazil and fresh patient isolates from India, we established a robust enrichment method for P...
January 29, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29371963/genome-wide-analysis-of-the-human-malaria-parasite-plasmodium-falciparum-transcription-factor-pfnf-yb-shows-interaction-with-a-ccaat-motif
#11
Wânia Rezende Lima, David Correa Martins, Kleber Simônio Parreira, Pedro Scarpelli, Miriam Santos de Moraes, Pantelis Topalis, Ronaldo Fumio Hashimoto, Célia R S Garcia
Little is known about transcription factor regulation during the Plasmodium falciparum intraerythrocytic cycle. In order to elucidate the role of the P. falciparum (Pf)NF-YB transcription factor we searched for target genes in the entire genome. PfNF-YB mRNA is highly expressed in late trophozoite and schizont stages relative to the ring stage. In order to determine the candidate genes bound by PfNF-YB a ChIP-on-chip assay was carried out and 297 genes were identified. Ninety nine percent of PfNF-YB binding was to putative promoter regions of protein coding genes of which only 16% comprise proteins of known function...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29371154/trypanosoma-brucei-bloodstream-forms-express-highly-specific-and-separate-transporters-for-adenine-and-hypoxanthine-evidence-for-a-new-protozoan-purine-transporter-family
#12
Gustavo D Campagnaro, Khalid J Alzahrani, Jane C Munday, Harry P De Koning
The transport of nucleobases and nucleosides in protozoan parasites is known to be performed by Equilibrative Nucleoside Transporter (ENT) family members, including the extensively studied P1 and P2 nucleoside transporters of T. brucei bloodstream forms. Studies with P2 knockout parasites suggested the existence of as yet uncharacterised purine transport mechanisms in these cells. Here, we deleted several ENT genes, in addition to P2, including an array comprising three genes encoding for high-affinity broad-selectivity nucleobase transporters - the longest multi-gene locus deletion in T...
January 22, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29363833/purine-related-metabolites-and-their-converting-enzymes-are-altered-in-frontal-parietal-and-temporal-cortex-at-early-stages-of-alzheimer-s-disease-pathology
#13
Patricia Alonso-Andrés, José Luis Albasanz, Isidro Ferrer, Mairena Martín
Adenosine, hypoxanthine, xanthine, guanosine, and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA), and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine, and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine, and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered...
January 24, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29340645/a-plasma-metabolomic-signature-involving-purine-metabolism-in-human-optic-atrophy-1-opa1-related-disorders
#14
Cinzia Bocca, Judith Kouassi Nzoughet, Stéphanie Leruez, Patrizia Amati-Bonneau, Marc Ferré, Mariame-Selma Kane, Charlotte Veyrat-Durebex, Juan Manuel Chao de la Barca, Arnaud Chevrollier, Chadi Homedan, Christophe Verny, Dan Miléa, Vincent Procaccio, Gilles Simard, Dominique Bonneau, Guy Lenaers, Pascal Reynier
Purpose: Dominant optic atrophy (DOA; MIM [Mendelian Inheritance in Man] 165500), resulting in retinal ganglion cell degeneration, is mainly caused by mutations in the optic atrophy 1 (OPA1) gene, which encodes a dynamin guanosine triphosphate (GTP)ase involved in mitochondrial membrane processing. This work aimed at determining whether plasma from OPA1 pathogenic variant carriers displays a specific metabolic signature. Methods: We applied a nontargeted clinical metabolomics pipeline based on ultra-high-pressure liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) allowing the exploration of 500 polar metabolites in plasma...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29329872/development-and-validation-of-a-hilic-uv-method-for-the-determination-of-nucleotides-in-fish-samples
#15
Maria Logotheti, Konstantina Theochari, Marios Kostakis, Ioannis N Pasias, Nikolaos S Thomaidis
The aim of this work was the development of a simple, novel and accurate method for the determination of adenosine triphosphate (ATP) and its first five catabolites: adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine (Ino) and hypoxanthine (Hx), in fish tissue, based on hydrophilic interaction liquid chromatography (HILIC). For this purpose, a stationary phase for polar and hydrophilic compounds (ZIC-pHILIC) was used. The effect of different chromatographic parameters and the molecular mechanism based on the van't Hoff plot were examined...
May 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29324308/antacids-side-effect-hyperuricaemia-could-be-alleviated-by-long-term-aerobic-exercise-via-accelerating-atp-turnover-rate
#16
Shu Yuan, Zhong-Wei Zhang, Zi-Lin Li
Hyperuricemia is the term for an abnormally high serum uric acid level. Many factors contribute to hyperuricemia, however no definite correlation between proton pump inhibitors (PPIs) and hyperuricemia has been reported before. Physical exercise also decreases serum uric acid levels. However, the detailed biochemical-regulatory mechanisms remain unknown. Here we found that adenylate deaminase activities are much higher in hyperuricemia patients than in the healthy people. Therefore, the patients have higher levels of adenosine metabolites hypoxanthine and uric acid...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29310655/methylene-blue-induced-morphological-deformations-in-plasmodium-falciparum-gametocytes-implications-for-transmission-blocking
#17
Ishan Wadi, C Radhakrishna Pillai, Anupkumar R Anvikar, Abhinav Sinha, Mahendra Nath, Neena Valecha
BACKGROUND: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients...
January 8, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29306799/purine-salvage-in-plants
#18
REVIEW
Hiroshi Ashihara, Claudio Stasolla, Tatsuhito Fujimura, Alan Crozier
Purine bases and nucleosides are produced by turnover of nucleotides and nucleic acids as well as from some cellular metabolic pathways. Adenosine released from the S-adenosyl-L-methionine cycle is linked to many methyltransferase reactions, such as the biosynthesis of caffeine and glycine betaine. Adenine is produced by the methionine cycles, which is related to other biosynthesis pathways, such those for the production of ethylene, nicotianamine and polyamines. These purine compounds are recycled for nucleotide biosynthesis by so-called "salvage pathways"...
January 4, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29305058/altered-gastrointestinal-motility-in-an-animal-model-of-lesch-nyhan-disease
#19
Maria G Zizzo, Monica Frinchi, Domenico Nuzzo, Hyder A Jinnah, Giuseppa Mudò, Daniele F Condorelli, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio, Flavia Mulè, Natale Belluardo, Rosa Serio
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon...
December 20, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/29233758/l-donovani-xprt-molecular-characterization-and-evaluation-of-inhibitors
#20
Bhumi Patel, Dhaval Patel, Krupali Parmar, Rupal Chauhan, Desh Deepak Singh, Anju Pappachan
Among all PRT enzymes of purine salvage pathway in Leishmania, XPRT (Xanthine phosphoribosyl transferase) is unique in its substrate specificity and their non-existence in human. It is an interesting protein not only for drug designing but also to understand the molecular determinants of its substrate specificity. Analysis of the 3D model of L. donovani XPRT (Ld-XPRT) revealed that Ile 209, Glu 215 and Tyr 208 may be responsible for the altered substrate specificity of Ld-XPRT. Comparisons with it's nearest homologue in humans, revealed significant differences between the two...
December 9, 2017: Biochimica et Biophysica Acta
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