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https://www.readbyqxmd.com/read/28214451/a-novel-lc-ms-ms-method-for-the-simultaneous-quantification-of-topiramate-and-its-main-metabolites-in-human-plasma
#1
Daniela Milosheska, Robert Roškar
The aim of the present report was to develop and validate simple, sensitive and reliable LC-MS/MS method for quantification of topiramate (TPM) and its main metabolites: 2,3-desisopropylidene TPM, 4,5-desisopropylidene TPM, 10-OH TPM and 9-OH TPM in human plasma samples. The most abundant metabolite 2,3-desisopropylidene TPM was isolated from patients urine, characterized and afterwards used as an authentic standard for method development and validation. Sample preparation method employs 100μL of plasma sample and liquid-liquid extraction with a mixture of ethyl acetate and diethyl ether as extraction solvent...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28214354/long-chain-unsaturated-fatty-acids-as-possible-important-metabolites-for-primary-angle-closure-glaucoma-based-on-targeted-metabolomic-analysis
#2
Shengzhong Rong, Yang Li, Yue Guan, Lili Zhu, Qiang Zhou, Mucong Gao, Hongzhi Pan, Lina Zou, Dong Chang
Primary angle-closure glaucoma (PACG) is a severe chronic neurodegenerative disease in Asia. Identification of important metabolites associated with PACG is crucial for early intervention and advancing knowledge of the disease mechanism. We applied gas chromatography-mass spectrometry (GC-MS) for targeted metabolomic analysis on serum samples from thirty-eight newly diagnosed PACG patients and forty-eight controls. Palmitoleic acid (PA), linoleic acid (LA), gamma-linolenic acid (GLA) and arachidonic acid (ARA) were identified as important metabolites associated with PACG...
February 18, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28214288/an-accelerator-mass-spectrometry-enabled-microtracer-study-to-evaluate-the-first-pass-effect-on-the-absorption-of-yh4808
#3
Anhye Kim, Byung-Yong Yu, Stephen R Dueker, Kwang-Hee Shin, Hwa Suk Kim, Hyungmi Ahn, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Howard Lee
(14) C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the non-radiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively...
February 18, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28214243/synthetic-metabolic-bypass-for-a-metabolic-toggle-switch-enhances-acetyl-coa-supply-for-isopropanol-production-by-escherichia-coli
#4
Yuki Soma, Taiki Yamaji, Fumio Matsuda, Taizo Hanai
Almost all synthetic pathways for biofuel production are designed to require endogenous metabolites in glycolysis, such as phosphoenolpyruvate, pyruvate, and acetyl-CoA. However, such metabolites are also required for bacterial cell growth. To reduce the metabolic imbalance between cell growth and target chemical production, we previously constructed a metabolic toggle switch (MTS) as a conditional flux redirection tool controlling metabolic flux of TCA cycle toward isopropanol production. This approach succeeded to improve the isopropanol production titer and yield while ensuring sufficient cell growth...
February 14, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28214148/muscle-characteristics-only-partially-explain-color-variations-in-fresh-hams
#5
K Stufft, J Elgin, B Patterson, S K Matarneh, R Preisser, H Shi, E M England, T L Scheffler, E W Mills, D E Gerrard
Fresh hams display significant lean color variation that persists through further processing and contributes to a less desirable cured product. In an attempt to understand the underlying cause of this color disparity, we evaluated the differences in muscle characteristics and energy metabolites across semimembranosus (SM) muscles differing in color variation. The L* (lightness) and a* (redness) values were highest and lowest (P<0.001), respectfully in the most caudal aspects of the muscle while the ultimate pH was the lowest (P<0...
December 24, 2016: Meat Science
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#6
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213944/separation-of-hydroxynorketamine-stereoisomers-using-capillary-electrophoresis-with-sulfated-%C3%AE-cyclodextrin-and-highly-sulfated-%C3%AE-cyclodextrin
#7
Friederike A Sandbaumhüter, Regula Theurillat, Wolfgang Thormann
The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed...
February 18, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#8
Kevin D Quinn, Michaela Schedel, Yasmeen Nkrumah-Elie, Anthony Joetham, Michael Armstrong, Charmion Cruickshank-Quinn, Richard Reisdorph, Erwin W Gelfand, Nichole Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213885/epigenetic-modifier-induced-enhancement-of-fumiquinazoline-c-production-in-aspergillus-fumigatus-ga-l7-an-endophytic-fungus-from-grewia-asiatica-l
#9
Ankita Magotra, Manjeet Kumar, Manoj Kushwaha, Praveen Awasthi, Chand Raina, Ajai Prakash Gupta, Bhahwal A Shah, Sumit G Gandhi, Asha Chaubey
Present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of Aspergillus fumigatus (GA-L7), an endophytic fungus isolated from Grewia asiatica L. Seven secondary metabolites were isolated from A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28213660/evidence-of-an-unidentified-extracellular-heat-stable-factor-produced-by-lysobacter-enzymogenes-oh11-that-degrade-fusarium-graminearum-ph1-hyphae
#10
Benard Omondi Odhiambo, Gaoge Xu, Guoliang Qian, Fengquan Liu
Lysobacter enzymogenes OH11 produces heat-stable antifungal factor (HSAF) and lytic enzymes possessing antifungal activity. This study bio-prospected for other potential antifungal factors besides those above. The cells and extracellular metabolites of L. enzymogenes OH11 and the mutants ΔchiA, ΔchiB, ΔchiC, Δclp, Δpks, and ΔpilA were examined for antifungal activity against Fusarium graminearum PH1, the causal agent of Fusarium head blight (FHB). Results evidenced that OH11 produces an unidentified extracellular heat-stable degrading metabolite (HSDM) that exhibit degrading activity on F...
February 17, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28213652/evaluating-stress-physiology-and-parasite-infection-parameters-in-the-translocation-of-critically-endangered-woylies-bettongia-penicillata
#11
Stephanie Hing, Amy S Northover, Edward J Narayan, Adrian F Wayne, Krista L Jones, Sarah Keatley, R C Andrew Thompson, Stephanie S Godfrey
Translocation can be stressful for wildlife. Stress may be important in fauna translocation because it has been suggested that it can exacerbate the impact of infectious disease on translocated wildlife. However, few studies explore this hypothesis by measuring stress physiology and infection indices in parallel during wildlife translocations. We analysed faecal cortisol metabolite (FCM) concentration and endoparasite parameters (nematodes, coccidians and haemoparasites) in a critically endangered marsupial, the woylie (Bettongia penicillata), 1-3 months prior to translocation, at translocation, and 6 months later...
February 17, 2017: EcoHealth
https://www.readbyqxmd.com/read/28213610/prebiotic-inulin-type-fructans-induce-specific-changes-in-the-human-gut-microbiota
#12
Doris Vandeputte, Gwen Falony, Sara Vieira-Silva, Jun Wang, Manuela Sailer, Stephan Theis, Kristin Verbeke, Jeroen Raes
OBJECTIVE: Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles...
February 17, 2017: Gut
https://www.readbyqxmd.com/read/28213543/functional-characterization-of-a-28-kb-catabolic-island-from-pseudomonas-sp-m1-involved-in-biotransformation-of-%C3%AE-myrcene-and-related-plant-derived-volatiles
#13
Pedro Soares-Castro, Pedro Montenegro-Silva, Hermann J Heipieper, Pedro M Santos
Pseudomonas sp. M1 is able to mineralize highly hydrophobic and recalcitrant compounds such as benzene, phenol and their methylated/halogenated derivatives, as well as the backbone of several monoterpenes. The ability to use such spectrum of compounds as sole carbon source is, most probably, associated with a genetic background evolved under different environmental constraints. The outstanding performance of M1 strain regarding β-myrcene catabolism was elucidated in this work, with focus on the biocatalytical potential of β-myrcene-associated core-code, comprised in a 28-kb genomic island (GI), predicted to be organized in 8 transcriptional units...
February 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28213532/susceptibility-and-pk-pd-relationships-of-staphylococcus-aureus-strains-from-ovine-and-caprine-with-clinical-mastitis-against-five-veterinary-fluoroquinolones
#14
J M Serrano-Rodríguez, C Cárceles-García, C M Cárceles-Rodríguez, M L Gabarda, J M Serrano-Caballero, E Fernández-Varón
Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic-pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values...
February 17, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28213524/g-protein-coupled-receptor-kinase-2-grk-2-regulates-serotonin-metabolism-through-the-monoamine-oxidase-amx-2-in-caenorhabditis-elegans
#15
Jianjun Wang, Jiansong Luo, Dipendra K Aryal, William C Wetzel, Richard Nass, Jeffrey L Benovic
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs) and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans. Our studies demonstrate that grk-2 loss-of-function strains are egg-laying defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213512/27-hydroxycholesterol-impairs-neuronal-glucose-uptake-through-an-irap-glut4-system-dysregulation
#16
Muhammad-Al-Mustafa Ismail, Laura Mateos, Silvia Maioli, Paula Merino-Serrais, Zeina Ali, Maria Lodeiro, Eric Westman, Eran Leitersdorf, Balázs Gulyás, Lars Olof-Wahlund, Bengt Winblad, Irina Savitcheva, Ingemar Björkhem, Angel Cedazo-Mínguez
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced (18)F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N)...
February 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28213335/transformation-products-of-clindamycin-in-moving-bed-biofilm-reactor-mbbr
#17
Gordon T H Ooi, Monica Escola Casas, Henrik R Andersen, Kai Bester
Clindamycin is widely prescribed for its ability to treat a number of common bacterial infections. Thus, clindamycin enters wastewater via human excretion or disposal of unused medication and widespread detection of pharmaceuticals in rivers proves the insufficiency of conventional wastewater treatment plants in removing clindamycin. Recently, it has been discovered that attached biofilm reactors, e.g., moving bed biofilm reactors (MBBRs) obtain a higher removal of pharmaceuticals than conventional sludge wastewater treatment plants...
February 2, 2017: Water Research
https://www.readbyqxmd.com/read/28213273/2-methoxyestradiol-protects-against-ischemia-reperfusion-injury-in-alcoholic-fatty-liver-by-enhancing-sirtuin-1-mediated-autophagy
#18
Hong-Ik Cho, Min-Jong Seo, Sun-Mee Lee
Alcoholic fatty liver (AFL) is susceptible to ischemia/reperfusion (I/R) injury, responding with inflammation and extensive hepatocellular damage. Autophagy maintains cellular homeostasis and regulates inflammation and lipid metabolism. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of estradiol, exhibits antioxidant and anti-inflammatory properties. This study examined the cytoprotective mechanisms of 2-ME2 on hepatic I/R in AFL, focusing on autophagy signaling. C57BL/6 mice were fed an ethanol diet (ED) to induce AFL, or a control diet (CD) for 6 weeks, and then subjected to 60 min of ischemia and 5 h of reperfusion...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213249/on-line-flow-injection-molecularly-imprinted-solid-phase-extraction-for-the-preconcentration-and-determination-of-1-hydroxypyrene-in-urine-samples
#19
Montserrat Serrano, Mónica Bartolomé, Juan Carlos Bravo, Gema Paniagua, Judith Gañan, Alejandrina Gallego-Picó, Rosa María Garcinuño
New analytical strategies tend to automation of sample pre-treatment and flow analysis techniques provided a number of enhanced analytical methods allowing high throughput. Flow techniques are usually faster, more robust and more flexible than their batch equivalents. In addition, flow methods use less sample and reagent amounts and reduce analytical costs and waste. A flow injection solid-phase extraction pre-concentration system using a molecularly imprinted polymer (MIP) packed micro-column was developed for the determination of 1-hydroxypyrene in human urine with fluorescence detection...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28213225/a-melamine-based-molecularly-imprinted-sensor-for-the-determination-of-8-hydroxydeoxyguanosine-in-human-urine
#20
Neeraj Kumar, Rosy, Rajendra N Goyal
A sensitive and facile molecular imprinted sensor has been fabricated using edge plane pyrolytic graphite (EPPG) for the determination of an important oxidative DNA damage product, 8-hydroxydeoxyguanosine (8-OHdG). The molecularly imprinted polymer film was fabricated by electropolymerization of melamine in the presence of 8-OHdG, on glutaraldehyde/poly 1,5-diaminonaphthalene modified EPPG. The imprinted sensor surface was characterized by using Field Emission Scanning Electron Microscopy, Electron Impedance Spectroscopy, Cyclic Voltammetry, Square Wave Voltammetry and UV-visible spectroscopy...
May 1, 2017: Talanta
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