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isotopic tracer method

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https://www.readbyqxmd.com/read/29233262/medicinal-chemistry-strategies-for-pet-tracer-discovery
#1
REVIEW
José Ignacio Andrés, Mark Schmidt
The detection of gamma rays, resulting from decay of positron emitting isotopes, allows exquisitely sensitive detection of probes radiolabeled with such isotopes. These probes can be designed for high affinity binding to specific molecular targets and be used as tools in the early development of drugs, particularly for neuropsychiatric disorders. Availability of novel tracers requires dedicated resources and selection assays. Many of the selection assays are similar to those used for discovery of clinical compounds, although the distribution and clearance of target specific radioligands requires different in vitro and in vivo methods and new derivatives...
November 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29224090/men-are-from-mars-women-are-from-venus-sex-differences-in-insulin-action-and-secretion
#2
Ananda Basu, Simmi Dube, Rita Basu
Sex difference plays a substantial role in the regulation of glucose metabolism in healthy glucose-tolerant humans. The factors which may contribute to the sex-related differences in glucose metabolism include differences in lifestyle (diet and exercise), sex hormones, and body composition. Several epidemiological and observational studies have noted that impaired glucose tolerance is more common in women than men. Some of these studies have attributed this to differences in body composition, while others have attributed impaired insulin sensitivity as a cause of impaired glucose tolerance in women...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29212434/stable-isotope-pharmacokinetic-studies-provide-insight-into-effects-of-age-sex-and-weight-on-levothyroxine-metabolism
#3
Islam Younis, Mariam A Ahmed, Kenneth D Burman, Offie P Soldin, Jacqueline Jonklaas
Background We wished to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex. Methods A pharmacokinetic study was performed after administration of a tracer dose of carbon-13- labeled LT4 (13C-LT4). The study was conducted at an academic medical center. Adults of any age being treated with levothyroxine for hypothyroidism were enrolled in the study. A single dose of 13C- LT4 was administered. Eighteen serial plasma samples were collected. One sample was obtained before the 13C- LT4 dose and the majority of the remaining samples were collected over the 120-hour period post-dosing...
December 6, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29200272/stable-isotope-resolved-analysis-with-quantitative-dissolution-dynamic-nuclear-polarization
#4
Mathilde Hauge Lerche, Demet Yigit, Anne Birk Frahm, Jan Henrik Ardenkjær-Larsen, Ronja Maja Malinowski, Pernille Rose Jensen
Metabolite profiles and their isotopomer distributions can be studied non-invasively in complex mixtures with NMR. The advent of dissolution Dynamic Nuclear Polarization (dDNP) and isotope enrichment add sensitivity and resolution to such met-abolic studies. Metabolic pathways and networks can be mapped and quantified if protocols that control and exploit the ex situ sig-nal enhancement are created. We present a sample preparation method, including cell incubation, extraction and signal enhance-ment, to facilitate reproducible and quantitative dDNP (qdDNP) NMR-based isotope tracer analysis...
December 4, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29159966/interrogating-marine-virus-host-interactions-and-elemental-transfer-with-boncat-and-nanosims-based-methods
#5
Alexis L Pasulka, Kimberlee Thamatrakoln, Sebastian H Kopf, Yunbin Guan, Bonnie Poulos, Annie Moradian, Michael J Sweredoski, Sonja Hess, Mathew B Sullivan, Kay D Bidle, Victoria J Orphan
While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses...
November 21, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/29158483/noninvasive-liquid-diet-delivery-of-stable-isotopes-into-mouse-models-for-deep-metabolic-network-tracing
#6
Ramon C Sun, Teresa W-M Fan, Pan Deng, Richard M Higashi, Andrew N Lane, Anh-Thu Le, Timothy L Scott, Qiushi Sun, Marc O Warmoes, Ye Yang
Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of (13)C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive (13)C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of (13)C6-glucose feeding...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149751/massive-arrival-of-desalinated-seawater-in-a-regional-urban-water-cycle-a-multi-isotope-study-b-s-o-h
#7
W Kloppmann, Ido Negev, Joseph Guttman, Orly Goren, Ittai Gavrieli, Catherine Guerrot, Christine Flehoc, Marie Pettenati, Avihu Burg
"Man-made" or unconventional freshwater, like desalinated seawater or reclaimed effluents, is increasingly introduced into regional water cycles in arid or semi-arid countries. We show that the breakthrough of reverse osmosis-derived freshwater in the largely engineered water cycle of the greater Tel Aviv region (Dan Region) has profoundly changed previous isotope fingerprints. This new component can be traced throughout the system, from the drinking water supply, through sewage, treated effluents, and artificially recharged groundwater at the largest Soil-Aquifer Treatment system in the Middle East (Shafdan) collecting all the Dan region sewage...
November 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29131928/n-and-o-isotope-%C3%AE-15-n-%C3%AE-%C3%AE-15-n-%C3%AE-%C3%AE-18-o-%C3%AE-17-o-analyses-of-dissolved-no3-and-no2-by-the-cd-azide-reduction-method-and-n2-o-laser-spectrometry
#8
Leonard I Wassenaar, Cedric Douence, Mark Altabet, Pradeep Aggarwal
RATIONALE: The nitrogen and oxygen (δ(15) N, δ(18) O, δ(17) O) isotopic compositions of NO3(-) and NO2(-) are important tracers of nutrient dynamics in soil, rain, groundwater and the oceans. The Cd-azide method was used to convert NO3 or NO2 to N2 O for N and triple-O isotopic analyses by N2 O-laser spectrometry. A protocol for laser-based headspace isotope analyses was compared with isotope-ratio mass spectrometry. Lasers provide the ability to directly measure (17) O anomalies which can help discern atmospheric N sources...
November 13, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29054406/a-novel-puromycin-decorporation-method-to-quantify-skeletal-muscle-protein-breakdown-a-proof-of-concept-study
#9
Hannah Crossland, Kenneth Smith, Philip J Atherton, Daniel J Wilkinson
The precise roles that the major proteolytic pathways play in the regulation of skeletal muscle mass remain incompletely understood, in part due to technical limitations associated with current techniques used to quantify muscle protein breakdown (MPB). We aimed to develop a method to assess MPB in cells, based on loss of puromycin labelling of translated polypeptide chains. Following an initial 24 h incubation period with puromycin (1 μM), loss of puromycin labelling from murine C2C12 myotubes was assessed over 48 h, both in the presence or absence of protein synthesis inhibitor cycloheximide (CHX)...
October 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29039106/improved-ultrafiltration-method-to-measure-drug-release-from-nanomedicines-utilizing-a-stable-isotope-tracer
#10
Sarah L Skoczen, Stephan T Stern
An important step in the early development of a nanomedicine formulation is the evaluation of stability and drug release in biological matrices. Additionally, the measurement of encapsulated and unencapsulated nanomedicine drug fractions is important for the determination of bioequivalence (pharmacokinetic equivalence) of generic nanomedicines. Unfortunately, current methods to measure drug release in plasma are limited, and all have fundamental disadvantages including non-equilibrium conditions and process-induced artifacts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29035267/coastal-ocean-and-shelf-sea-biogeochemical-cycling-of-trace-elements-and-isotopes-lessons-learned-from-geotraces
#11
REVIEW
Matthew A Charette, Phoebe J Lam, Maeve C Lohan, Eun Young Kwon, Vanessa Hatje, Catherine Jeandel, Alan M Shiller, Gregory A Cutter, Alex Thomas, Philip W Boyd, William B Homoky, Angela Milne, Helmuth Thomas, Per S Andersson, Don Porcelli, Takahiro Tanaka, Walter Geibert, Frank Dehairs, Jordi Garcia-Orellana
Continental shelves and shelf seas play a central role in the global carbon cycle. However, their importance with respect to trace element and isotope (TEI) inputs to ocean basins is less well understood. Here, we present major findings on shelf TEI biogeochemistry from the GEOTRACES programme as well as a proof of concept for a new method to estimate shelf TEI fluxes. The case studies focus on advances in our understanding of TEI cycling in the Arctic, transformations within a major river estuary (Amazon), shelf sediment micronutrient fluxes and basin-scale estimates of submarine groundwater discharge...
November 28, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/29027346/application-of-stable-isotope-labelling-techniques-for-the-detection-of-active-diazotrophs
#12
Roey Angel, Christopher Panhölzl, Raphael Gabriel, Craig Herbold, Wolfgang Wanek, Andreas Richter, Stephanie A Eichorst, Dagmar Woebken
Investigating active participants in the fixation of dinitrogen gas is vital as N is often a limiting factor for primary production. Biological nitrogen fixation (BNF) is performed by a diverse guild of bacteria and archaea (diazotrophs), which can be free-living or symbionts. Free-living diazotrophs are widely distributed in the environment, yet our knowledge about their identity and ecophysiology is still limited. A major challenge in investigating this guild is inferring activity from genetic data as this process is highly regulated...
October 13, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28983702/measurement-of-the-15-n-14-n-ratio-of-phenylalanine-in-fermentation-matrix-by-isotope-ratio-mass-spectrometry
#13
Shiwei Zhang, Qiding Zhong, Daobing Wang, Zhanbin Huang, Guohui Li
OBJECTIVES: To determine the origin of (15)N-labeled phenylalanine in microbial metabolic flux analysis using (15)N as a tracer, a method for measuring phenylalanine δ(15)N using HPLC coupled with elemental analysis-isotope ratio mass spectrometry (EA-IRMS) was developed. RESULTS: The original source of the (15)N-labeled phenylalanine was determined using this new method that consists of three steps: optimization of the HPLC conditions, evaluation of the isotope fractionation effects, and evaluation of the effect of pre-processing on the phenylalanine nitrogen stable isotope...
October 5, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28983132/modeling-the-isotopic-evolution-of-snowpack-and-snowmelt-testing-a-spatially-distributed-parsimonious-approach
#14
Pertti Ala-Aho, Doerthe Tetzlaff, James P McNamara, Hjalmar Laudon, Patrick Kormos, Chris Soulsby
Use of stable water isotopes has become increasingly popular in quantifying water flow paths and travel times in hydrological systems using tracer-aided modeling. In snow-influenced catchments, snowmelt produces a traceable isotopic signal, which differs from original snowfall isotopic composition because of isotopic fractionation in the snowpack. These fractionation processes in snow are relatively well understood, but representing their spatiotemporal variability in tracer-aided studies remains a challenge...
July 2017: Water Resources Research
https://www.readbyqxmd.com/read/28982052/radionuclides-as-natural-tracers-of-the-interaction-between-groundwater-and-surface-water-in-the-river-andarax-spain
#15
Francisco Navarro-Martinez, Alejandro Salas Garcia, Francisco Sánchez-Martos, Antonio Baeza Espasa, Luis Molina Sánchez, Antonio Rodríguez Perulero
The identification of specific aquifers that supply water to river systems is fundamental to understanding the dynamics of the rivers' hydrochemistry, particularly in arid and semiarid environments where river flow may be discontinuous. There are multiple methods to identify the source of river water. In this study of the River Andarax, in the Southeast of Spain, an analysis of natural tracers (physico-chemical parameters, uranium, radium and radon) in surface water and groundwater indicates that chemical parameters and uranium clearly identify the areas where there is groundwater-surface water interaction...
October 2, 2017: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/28972298/oxygen-isotope-analysis-of-levoglucosan-a-tracer-of-wood-burning-in-experimental-and-ambient-aerosol-samples
#16
J Blees, M Saurer, R T W Siegwolf, V Ulevicius, A S H Prevôt, J Dommen, M M Lehmann
RATIONALE: Levoglucosan is formed from cellulose during biomass burning. It is therefore often used as a specific tracer to quantify the contribution of wood burning to the aerosol loading. The stable oxygen isotope composition (δ(18) O value) of biomass is determined by the water cycle and varies regionally, and hence the δ(18) O value of levoglucosan could help to identify source regions of organic aerosols. METHODS: After solvent extraction of the organic fraction and concentration steps, a recently developed methylation derivatisation technique was applied on experimental (i...
October 3, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28960906/hplc-ms-ms-a-potential-method-to-track-the-in-vivo-degradation-of-zein-based-biomaterial
#17
Hua-Jie Wang, Shunji Kato, Yue Zhang, Kiyotaka Nakagawa, Teruo Miyazawa, Jin-Ye Wang
Given the inadequacies of existing clinic tracking strategies, such as isotopic tracer techniques, one of the major thrusts in protein-based tissue engineering substitutes prior to use in clinic is to develop a safe technique that can effectively track their degradation in vivo. Keeping in view the possible application of a natural polymer, zein as a novel bone substitute, with the advantages of good bio-compatibility, bio-degradability and outstanding mechanical properties, we attempted here to construct a HPLC-MS/MS method to track the in vivo degradation of zein porous scaffold...
September 29, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28938478/roux-en-y-gastric-bypass-surgery-has-unique-effects-on-postprandial-fgf21-but-not-fgf19-secretion
#18
COMPARATIVE STUDY
Lydia-Ann L S Harris, Gordon I Smith, Bettina Mittendorfer, J Christopher Eagon, Adewole L Okunade, Bruce W Patterson, Samuel Klein
Context: Fibroblast growth factor (FGF)19 and FGF21 are secreted by the intestine and liver in response to macronutrient intake. Intestinal resection and reconstruction via bariatric surgery may alter their regulation. Objective: We tested the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery, but not matched weight loss induced by laparoscopic adjustable gastric banding (LAGB), increases postprandial plasma FGF19 and FGF21 concentrations...
October 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28931590/leucine-transamination-is-lower-in-middle-aged-compared-with-younger-adults
#19
Paolo Tessari
Background: Insulin and age affect leucine (and protein) kinetics in vivo. However, to our knowledge, leucine transamination and the effects of insulin have not been studied in participants of different ages.Objective: The aims of the study were to measure whole-body leucine deamination to α-ketoisocaproate (KIC) and KIC reamination to leucine in middle-aged and younger healthy adults, both in the postabsorptive state and after hyperinsulinemia.Methods: Younger (mean ± SE age: 26 ± 2 y) and middle-aged (54 ± 3 y) healthy men and women were enrolled...
September 20, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28921623/one-step-synthesis-of-18-f-cabozantinib-for-use-in-positron-emission-tomography-imaging-of-c-met
#20
Vegard Torp Lien, Jo Klaveness, Dag Erlend Olberg
Cabozantinib is an FDA approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c-Met. Non-invasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. Based on cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor...
September 18, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
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