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https://www.readbyqxmd.com/read/29135898/acute-illness-protocol-for-urea-cycle-disorders
#1
Lance H Rodan, Saud H Aldubayan, Gerard T Berry, Harvey L Levy
Inborn errors of metabolism (IEMs) are genetic disorders that disrupt enzyme activity, cellular transport, or energy production. They are individually rare but collectively have an incidence of 1:1000. Most patients with IEMs are followed up by a physician with expertise in biochemical genetics (metabolism), but may present outside this setting. Because IEMs can present acutely with life-threatening crises that require specific interventions, it is critical for the emergency physician, internist, and critical care physician as well as the biochemical geneticist to have information on the initial assessment and management of patients with these disorders...
November 14, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/29133058/design-and-synthesis-of-thienopyrimidine-urea-derivatives-with-potential-cytotoxic-and-pro-apoptotic-activity-against-breast-cancer-cell-line-mcf-7
#2
Eman F Abdelhaleem, Mohammed K Abdelhameid, Asmaa E Kassab, Manal M Kandeel
A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC50 = 9...
October 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29121091/effects-of-four-different-antihypertensive-drugs-on-plasma-metabolomic-profiles-in-patients-with-essential-hypertension
#3
Timo P Hiltunen, Jenni M Rimpelä, Robert P Mohney, Steven M Stirdivant, Kimmo K Kontula
OBJECTIVE: In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. METHODS: Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/29119048/elucidating-immunometabolic-targets-in-glioblastoma
#4
REVIEW
Pooja Agarwal, Michael J Pajor, David M Anson, Maheedhara R Guda, Collin M Labak, Andrew J Tsung, Kiran K Velpula
Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29109428/serial-omics-of-p53-brca1-mouse-breast-tumor-and-normal-mammary-gland
#5
Susanne B Breitkopf, Mateus De Oliveira Taveira, Min Yuan, Gerburg M Wulf, John M Asara
This study demonstrates a liquid-liquid extraction for the sequential tandem mass spectrometry (LC-MS/MS) analysis of non-polar lipids, polar metabolites, proteins and phosphorylation sites from a single piece of tissue. Extraction of 10 mg BRCA-/-, p53-/- breast tumor tissue or normal mammary gland tissue with methyl-tert-butyl ether (MTBE) results in three phases: an upper non-polar phase containing 1,382 lipids, a lower polar phase with 805 metabolites and a precipitated protein pellet with 4,792 proteins with 1,072 phosphorylation sites...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107336/citrulline-in-health-and-disease-review-on-human-studies
#6
REVIEW
Cinzia Papadia, Sylwia Osowska, Luc Cynober, Alastair Forbes
The amino acid L-citrulline (CIT) is safely used from the neonatal period onwards in those with urea cycle defects and carbamyl phosphate synthetase or ornithine transcarbamylase deficiencies, but several lines of enquiry indicate that it might have a much wider therapeutic role. When protein intake is low and there is a catabolic state, endogenous arginine (ARG) synthesis cannot fully be met and its supplementation can prove challenging, particularly in patients with critical and multisystem illness. Supplementary CIT could constitute a safer but still focused means of delivering ARG to endothelial and immune cells as CIT is efficiently recycled into these cells and as kidneys can convert CIT into ARG...
October 16, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29100030/plasma-biomarker-discovery-for-early-chronic-kidney-disease-diagnosis-based-on-chemometric-approaches-using-lc-qtof-targeted-metabolomics-data
#7
S Benito, A Sánchez-Ortega, N Unceta, J J Jansen, G Postma, F Andrade, L Aldámiz-Echevarria, L M C Buydens, M A Goicolea, R J Barrio
Chronic kidney disease (CKD) is a progressive pathological condition in which renal function deteriorates in time. The first diagnosis of CKD is often carried out in general care attention by general practitioners by means of serum creatinine (CNN) levels. However, it lacks sensitivity and thus, there is a need for new robust biomarkers to allow the detection of kidney damage particularly in early stages. Multivariate data analysis of plasma concentrations obtained from LC-QTOF targeted metabolomics method may reveal metabolites suspicious of being either up-regulated or down-regulated from urea cycle, arginine methylation and arginine-creatine metabolic pathways in CKD pediatrics and controls...
October 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29098735/glucose-and-lipid-metabolism-disorders-in-the-chickens-with-dexamethasone-induced-oxidative-stress
#8
Z-P Lv, Y-Z Peng, B-B Zhang, H Fan, D Liu, Y-M Guo
The purpose of this study was to investigate the effects of long-term treatment with dexamethasone (DEX) on the antioxidation and nutrition metabolism in broiler chickens. Broilers were placed on a high-nutrient diet for 41 days, and half were given orally DEX-supplemented water at 20 mg/L every other day from 19 to 41 days of age. DEX treatment downregulated superoxide dismutase activity as well as the mRNA expression of CuZn-superoxide dismutase and glutathione peroxidase with a decrease in GSH/GSSG ratio and an increase in malondialdehyde level in the liver of broilers...
November 3, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/29083113/hydroxyethyl-starch-and-kidney-function-a-retrospective-study-in-patients-undergoing-therapeutic-plasma-exchange
#9
Muthuchellappan Radhakrishnan, Akshay Batra, Sundar Periyavan, Mariamma Philip, Vivek Anand
PURPOSE: Hydroxyethyl starch (HES) and albumin are used as replacement fluids during therapeutic plasma exchange (TPE). HES solutions are no longer recommended in critically ill patients due to its effect on kidneys and coagulation. In this retrospective study, we tried to look at the association between cumulative HES administration and kidney function in patients undergoing TPE. METHODS: Transfusion medicine department register was scrutinized to identify adult patients who had completed at least 5 cycles of TPE during the period June 2014-May 2015...
October 30, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/29075921/conduction-mechanism-and-improved-endurance-in-hfo2-based-rram-with-nitridation-treatment
#10
Fang-Yuan Yuan, Ning Deng, Chih-Cheng Shih, Yi-Ting Tseng, Ting-Chang Chang, Kuan-Chang Chang, Ming-Hui Wang, Wen-Chung Chen, Hao-Xuan Zheng, Huaqiang Wu, He Qian, Simon M Sze
A nitridation treatment technology with a urea/ammonia complex nitrogen source improved resistive switching property in HfO2-based resistive random access memory (RRAM). The nitridation treatment produced a high performance and reliable device which results in superior endurance (more than 10(9) cycles) and a self-compliance effect. Thus, the current conduction mechanism changed due to defect passivation by nitrogen atoms in the HfO2 thin film. At a high resistance state (HRS), it transferred to Schottky emission from Poole-Frenkel in HfO2-based RRAM...
October 26, 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29075241/in-vivo-isotopic-labeling-of-symbiotic-bacteria-involved-in-cellulose-degradation-and-nitrogen-recycling-within-the-gut-of-the-forest-cockchafer-melolontha-hippocastani
#11
Pol Alonso-Pernas, Stefan Bartram, Erika M Arias-Cordero, Alexey L Novoselov, Lorena Halty-deLeon, Yongqi Shao, Wilhelm Boland
The guts of insects harbor symbiotic bacterial communities. However, due to their complexity, it is challenging to relate a specific symbiotic phylotype to its corresponding function. In the present study, we focused on the forest cockchafer (Melolontha hippocastani), a phytophagous insect with a dual life cycle, consisting of a root-feeding larval stage and a leaf-feeding adult stage. By combining in vivo stable isotope probing (SIP) with (13)C cellulose and (15)N urea as trophic links, with Illumina MiSeq (Illumina-SIP), we unraveled bacterial networks processing recalcitrant dietary components and recycling nitrogenous waste...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29071700/-treatment-of-encephalopathy-by-means-of-valproic-acid-with-carglumic-acid-two-case-reports-and-a-review-of-the-literature
#12
J J Nava-Mateos, P Roiz-Rey, J Diaz Alvarez-Mediavilla, D Cebrian-Novella, V Gomez-Del Olmo, L Ceberio-Hualde
INTRODUCTION: Valproic acid (VPA) is a drug mainly used to treat epilepsy. Hyperammonaemic encephalopathy due to VPA is a rare but serious complication. The mechanism by which VPA influences the increase in ammonia consists in blocking the urea cycle, thereby inhibiting N-acetylglutamate synthase and diminishing acetyl coenzyme A. Generally, the treatment employed has been to withdraw VPA and to administer arginine, carnitine, antibiotics, glucose and protein restriction. Previous experience with carglumic acid is limited to reports of isolated cases of paediatric patients...
November 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/29056417/regulation-of-glutamate-dehydrogenase-gdh-in-response-to-whole-body-freezing-in-wood-frog-liver-linked-to-differential-acetylation-and-adp-ribosylation
#13
Stuart R Green, Kenneth B Storey
Glutamate dehydrogenase (GDH) represents a critical enzyme catalyzing the reaction spanning amino acid catabolism, the Krebs cycle, and urea production in the wood frog. GDH breaks down glutamate and NAD(+) to generate α-ketoglutaric acid (α-KG), NADH and ammonium that can be metabolized to form urea. Purification of GDH from control and frozen male wood frog livers was performed using a two-step column chromatography procedure with a cation exchange column and a GTP-agarose affinity column. Analysis of kinetic parameters of the purified GDH showed several notable differences between the control and stress...
October 19, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29055942/interaction-of-excitatory-amino-acid-transporters-1-3-eaat1-eaat2-eaat3-with-n-carbamoylglutamate-and-n-acetylglutamate
#14
Birgitta C Burckhardt, Gerhard Burckhardt
BACKGROUND/AIMS: Inborn deficiency of the N-acetylglutamate synthase (NAGS) impairs the urea cycle and causes neurotoxic hyperammonemia. Oral administration of N-carbamoylglutamate (NCG), a synthetic analog of N-acetylglutamate (NAG), successfully decreases plasma ammonia levels in the affected children. Due to structural similarities to glutamate, NCG may be absorbed in the intestine and taken up into the liver by excitatory amino acid transporters (EAATs). METHODS: Using Xenopus laevis oocytes expressing either human EAAT1, 2, or 3, or human sodium-dependent dicarboxylate transporter 3 (NaDC3), transport-associated currents of NAG, NCG, and related dicarboxylates were assayed...
October 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29054078/subacute-oral-toxicity-assessment-of-benalaxyl-in-mice-based-on-metabolomics-methods
#15
Xinru Wang, Dezhen Wang, Zhiqiang Zhou, Wentao Zhu
In this study, the metabolic responses of mice after 30 days of exposure to benalaxyl were assessed using NMR-based untargeted metabolomics and LC-MS-based targeted profiling of 20 amino acids. Urinary (1)H NMR analyses revealed alterations in energy metabolism, lipid metabolism, vitamin B metabolism, the urea cycle and amino acid metabolism, and targeted analyses indicated that the serum levels of asparagine, histidine, lysine and aspartic acid were significantly altered. Additionally, significant oxidative stress was observed in the liver and kidney, although no apparent histopathological injury was observed...
October 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/29042138/managing-the-excessive-proliferation-of-glycogen-accumulating-organisms-in-industrial-activated-sludge-by-nitrogen-supplementation-a-fish-nanosims-approach
#16
Cristobal A Onetto, Kathryn L Eales, Paul Guagliardo, Matt R Kilburn, Joanna M Gambetta, Paul R Grbin
Defluviicoccus vanus-related glycogen accumulating organisms (GAO) regularly proliferate in industrial wastewater treatment plants handling high carbon but nitrogen deficient wastes. When GAO dominate, they are associated with poor performance, characterised by slow settling biomass and turbid effluents. Although their ecophysiology has been studied thoroughly in domestic waste treatment plants, little attention has been paid to them in aerobic industrial systems. In this study, the effect of nitrogen addition on GAO carbon metabolism was investigated during an 8h cycle...
October 2, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/29037871/moringa-oleifera-seed-lectin-inhibits-ehrlich-ascites-carcinoma-cell-growth-by-inducing-apoptosis-through-the-regulation-of-bak-and-nf-%C3%AE%C2%BAb-gene-expression
#17
A K M Asaduzzaman, Imtiaj Hasan, Aninda Chakrabortty, Sadnima Zaman, Shaikh Shohidul Islam, Fazle Rabbi Shakil Ahmed, K M Ahsanul Kabir, Md Nurujjaman, Md Belal Uddin, Mohammad Taufiq Alam, Ranajit Kumar Shaha, Syed Rashel Kabir
A Moringa oleifera seed lectin (MOSL) was purified by using chitin column with the molecular mass of 17±1kDa. The lectin agglutinated mouse, cow and human erythrocytes and the hemagglutination activity was inhibited by methyl-α-d-mannopyranoside, methyl-β-d-galactopyranoside, lactose and glucose. The lectin exhibited 100% hemagglutination activity at the pH range from 8.0 to 9.0 and temperature range from 30 to 60°C. Additionally, the lectin gradually lost its activity in the presence of urea but the activity abolish completely when treated with EDTA...
October 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29034505/in-vivo-characterization-of-the-downfield-part-of-1-h-mr-spectra-of-human-brain-at-9-4-t-magnetization-exchange-with-water-and-relation-to-conventionally-determined-metabolite-content
#18
Nicole D Fichtner, Ioannis-Angelos Giapitzakis, Nikolai Avdievich, Ralf Mekle, Daniel Zaldivar, Anke Henning, Roland Kreis
PURPOSE: To perform exchange-rate measurements on the in vivo human brain downfield spectrum (5-10 ppm) at 9.4 T and to compare the variation in concentrations of the downfield resonances and of known upfield metabolites to determine potential peak labels. METHODS: Non-water-suppressed metabolite cycling was used in combination with an inversion transfer technique in two brain locations in healthy volunteers to measure the exchange rates and T1 values of exchanging peaks...
October 16, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29031835/metabolomic-analysis-of-oxidative-stress-superoxide-dismutase-mutation-and-paraquat-induced-stress-in-drosophila-melanogaster
#19
Marney L Doran, Jose M Knee, Nan Wang, Teresa Z Rzezniczak, Tony L Parkes, Liang Li, Thomas J S Merritt
Oxidative stress results in substantial biochemical and physiological perturbations in essentially all organisms. To determine the broad metabolic effects of oxidative stress, we have quantified the response in Drosophila melanogaster to both genetically and environmentally derived oxidative stress. Flies were challenged with loss of Superoxide dismutase activity or chronic or acute exposure to the oxidizing chemical paraquat. Metabolic changes were then quantified using a recently developed chemical isotope labeling (CIL) liquid chromatography - mass spectrometry (LC-MS) platform that targets the carboxylic acid and amine/phenol submetabolomes with high metabolic coverage...
October 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29030642/saline-is-as-effective-as-nitrogen-scavengers-for-treatment-of-hyperammonemia
#20
G van Straten, M G M de Sain-van der Velden, I M van Geijlswijk, R P Favier, S J Mesu, N E Holwerda-Loof, M van der Ham, H Fieten, J Rothuizen, B Spee, N M Verhoeven-Duif
Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I)...
October 13, 2017: Scientific Reports
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