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Magnetic Resonance in Medicine Apr 2023To characterize the ( H) deuterium MR signal measured from human brain at 7T in participants loading with D O to ˜1.5% enrichment over a six-week period.
PURPOSE
To characterize the ( H) deuterium MR signal measured from human brain at 7T in participants loading with D O to ˜1.5% enrichment over a six-week period.
METHODS
H spectroscopy and imaging measurements were used to track the time-course of H enrichment within the brain during the initial eight-hour loading period in two participants. Multi-echo gradient echo (MEGE) images were acquired at a range of TR values from four participants during the steady-state loading period and used for mapping H T and T relaxation times. Co-registration to higher resolution H images allowed T and T relaxation times of deuterium in HDO in cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) to be estimated.
RESULTS
H concentrations measured during the eight-hour loading were consistent with values estimated from cumulative D O dose and body mass. Signal changes measured from three different regions of the brain during loading showed similar time-courses. After summing over echoes, gradient echo brain images acquired in 7.5 minutes with a voxel volume of 0.36 ml showed an SNR of ˜16 in subjects loaded to 1.5%. T -values for deuterium in HDO were significantly shorter than corresponding values for H in H O, while T values were similar. H relaxation times in CSF were significantly longer than in GM or WM.
CONCLUSION
Deuterium MR Measurements at 7T were used to track the increase in concentration of H in brain during heavy water loading. H T and T relaxation times from water in GM, WM, and CSF are reported.
Topics: Humans; Deuterium; Magnetic Resonance Imaging; Brain; Gray Matter; Brain Mapping
PubMed: 36426762
DOI: 10.1002/mrm.29539 -
Journal of the American Chemical Society Aug 2020The United States is in the midst of an unprecedented epidemic of opioid substance use disorder, and while pharmacotherapies including opioid agonists and antagonists...
The United States is in the midst of an unprecedented epidemic of opioid substance use disorder, and while pharmacotherapies including opioid agonists and antagonists have shown success, they can be inadequate and frequently result in high recidivism. With these challenges facing opioid use disorder treatments immunopharmacotherapy is being explored as an alternative therapy option and is based upon antibody-opioid sequestering to block brain entry. Development of a heroin vaccine has become a major research focal point; however, producing an efficient vaccine against heroin has been particularly challenging because of the need to generate not only a potent immune response but one against heroin and its multiple psychoactive molecules. In this study, we explored the consequence of regioselective deuteration of a heroin hapten and its impact upon the immune response against heroin and its psychoactive metabolites. Deuterium (H) and cognate protium heroin (H) haptens were compared head to head in an inclusive vaccine study. Strikingly the H vaccine granted greater efficacy in blunting heroin analgesia in murine behavioral models compared to the H vaccine. Binding studies confirmed that the H vaccine elicited both greater quantities and equivalent or higher affinity antibodies toward heroin and 6-AM. Blood-brain biodistribution experiments corroborated these affinity tests. These findings suggest that regioselective hapten deuteration could be useful for the resurrection of previous drug of abuse vaccines that have met limited success in the past.
Topics: Deuterium; Haptens; Heroin; Molecular Conformation; Vaccines
PubMed: 32700530
DOI: 10.1021/jacs.0c05219 -
Radiology Feb 2020
Topics: Deuterium; Glycolysis; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neoplasms
PubMed: 31825290
DOI: 10.1148/radiol.2019192024 -
Journal of Mass Spectrometry : JMS Feb 2022Stable isotope tracing can be safely used for metabolic studies in animals and humans. The endogenous biosynthesis of lipids (lipogenesis) is a key process throughout...
Stable isotope tracing can be safely used for metabolic studies in animals and humans. The endogenous biosynthesis of lipids (lipogenesis) is a key process throughout the entire life but especially during brain and lung growth. Adequate synthesis of pulmonary surfactant lipids is indispensable for life. With this study, we report the use of deuterium-depleted water (DDW), suitable for human consumption, as metabolic precursor for lipogenesis. We studied 13 adult rabbits for 5 days. Four rabbits drank tap water (TW) and served as controls; in four animals, DDW was substituted to drinking water, whereas five drank deuterium-enriched water (DEW). After 5 days, a blood sample and a bronchoalveolar lavage (BAL) sample were collected. The H/ H (δ H) of BAL palmitic acid (PA) desaturated phosphatidylcholine (DSPC), the major phospholipid of pulmonary surfactant, and of plasma water was determined by high-resolution mass spectrometry. We found that the δ H values of DDW, DEW and TW were -984 ± 2‰, +757 ± 2‰ and -58 ± 1‰, respectively. After 5 days, plasma water values were -467 ± 87‰, +377 ± 56‰ and -53 ± 6‰, and BAL DSPC-PA was -401 ± 27‰, -96 ± 38‰ and -249 ± 9‰ in the DDW, DEW and TW, respectively. With this preliminary study, we demonstrated the feasibility of using DDW to label pulmonary surfactant lipids. This novel approach can be used in animals and in humans, and we speculate that it could be associated with more favourable study compliance than DEW in human studies.
Topics: Animals; Deuterium; Drinking Water; Phosphatidylcholines; Phospholipids; Pulmonary Surfactants; Rabbits
PubMed: 35060656
DOI: 10.1002/jms.4808 -
PeerJ 2023Hydrogen sulfide (HS), as an endogenous gas signaling molecule, plays an important role in plant growth regulation and resistance to abiotic stress. This study aims to...
Hydrogen sulfide (HS), as an endogenous gas signaling molecule, plays an important role in plant growth regulation and resistance to abiotic stress. This study aims to investigate the mechanism of exogenous HS on the growth and development of seedlings under salt stress and to determine the optimal concentration for foliar application. To investigate the regulatory effects of exogenous HS (donor sodium hydrosulfide, NaHS) at concentrations ranging from 0 to 1 mM on reactive oxygen species (ROS), antioxidant system, and osmoregulation in seedlings under 300 mM NaCl stress. The growth of seedlings was inhibited by salt stress, which resulted in a decrease in the leaf relative water content (LRWC), specific leaf area (SLA), and soluble sugar content in leaves, elevated activity levels of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT); and accumulated superoxide anion (O), proline, malondialdehyde (MDA), and soluble protein content in leaves; and increased L-cysteine desulfhydrase (LCD) activity and endogenous HS content. This indicated that a high level of ROS was produced in the leaves of seedlings and seriously affected the growth and development of seedlings. The exogenous application of different concentrations of NaHS reduced the content of O , proline and MDA, increased the activity of antioxidant enzymes and the content of osmoregulators (soluble sugars and soluble proteins), while the LCD enzyme activity and the content of endogenous HS were further increased with the continuous application of exogenous HS. The inhibitory effects of salt stress on the growth rate of plant height and ground diameter, the LRWC, biomass, and SLA were effectively alleviated. A comprehensive analysis showed that the LRWC, POD, and proline could be used as the main indicators to evaluate the alleviating effect of exogenous HS on seedlings under salt stress. The optimal concentration of exogenous HS for seedlings under salt stress was 0.025 mM. This study provides an important theoretical foundation for understanding the salt tolerance mechanism of and for cultivating high-quality germplasm resources.
Topics: Salt Tolerance; Hydrogen Sulfide; Reactive Oxygen Species; Seedlings; Antioxidants; Salt Stress; Peroxidase; Peroxidases; Coloring Agents; Deuterium
PubMed: 37641597
DOI: 10.7717/peerj.15881 -
Structure (London, England : 1993) Sep 2021In this issue of Structure, Gadjos et al. (2021b) determine the structure of a bacterial lectin in complex with L-fucose by neutron diffraction of both perdeuterated...
In this issue of Structure, Gadjos et al. (2021b) determine the structure of a bacterial lectin in complex with L-fucose by neutron diffraction of both perdeuterated protein and carbohydrate ligand. The structure provides insight into lectin-ligand interactions, opening avenues for drug design targeting bacterial lectins for intervention in infectious disease.
Topics: Deuterium; Fucose; Glycomics; Lectins; Ligands
PubMed: 34478636
DOI: 10.1016/j.str.2021.08.004 -
Clinical Nutrition ESPEN Aug 2021Body composition in childhood is not only a marker of the prevalence of obesity, but it can also be used to assess associated metabolic complications. Bioelectrical...
BACKGROUND AND AIMS
Body composition in childhood is not only a marker of the prevalence of obesity, but it can also be used to assess associated metabolic complications. Bioelectrical impedance analysis (BIA) shows promise as an easy to use, rapid, and non-invasive tool to evaluate body composition. The objectives of this study were to: (a) develop BIA prediction equations to estimate total body water (TBW) and fat-free mass (FFM) in European children and early adolescents and to validate the analysis with the deuterium dilution as the reference technique and (b) compare our results with previously published paediatric BIA equations.
METHODS
The cohort included 266 healthy children and adolescents between 7 and 14 years of age, 46% girls, in five European countries: Bosnia and Herzegovina, Latvia, Montenegro, North Macedonia, and Portugal. TBW and FFM were the target variables in the developed regression models. For model development, the dataset was randomly split into training and test sets, in 70:30 ratio, respectively. Model tuning was performed with 10-fold cross-validation that confirmed the unbiased estimate of its performance. The final regression models were retrained on the whole dataset.
RESULTS
Cross-validated regression models were developed using resistance index, weight, and sex as the optimal predictors. The new prediction equations explained 87% variability in both TBW and FFM. Limits of agreement between BIA and reference values, were within ±17% of the mean, (-3.4, 3.7) and (-4.5, 4.8) kg for TBW and FFM, respectively. BIA FFM and TBW estimates were within one standard deviation for approximately 83% of the children. BIA prediction equations underestimated TBW and FFM by 0.2 kg and 0.1 kg respectively with no proportional bias and comparable accuracy among different BMI-for-age subgroups. Comparison with predictive equations from published studies revealed varying discrepancy rates with the deuterium dilution measurements, with only two being equivalent to the equations developed in this study.
CONCLUSIONS
The small difference between deuterium dilution and BIA measurements validated by Bland-Altman analysis, supports the application of BIA for epidemiological studies in European children using the developed equations.
Topics: Adolescent; Body Composition; Child; Deuterium; Electric Impedance; Female; Humans; Indicator Dilution Techniques; Male; Obesity
PubMed: 34330497
DOI: 10.1016/j.clnesp.2021.05.001 -
Radiation Protection Dosimetry Sep 2022Tritium is released into the ocean from nuclear facilities located at coastal areas. In addition, tritiated water is decided to be released into the ocean from the...
Tritium is released into the ocean from nuclear facilities located at coastal areas. In addition, tritiated water is decided to be released into the ocean from the Fukushima Dai-ichi Nuclear Power Plant. Although released tritium concentration would be strictly controlled, impact of tritium on the marine products is major concern for the public. In this study, deuterium transfers from seawater into seaweed (ulva) and abalone were measured. In addition, organically bound deuterium (OBD) transfer from ulva into abalone was measured. OBD concentrations in ulva were saturated in 2 weeks and those in abalone were saturated in 6 months. Ulva and abalone were exposed to seawater containing 0.2% (mol-D/mol-H) deuterium. Maximum OBD concentrations in ulva were ~0.1% (mol-D/mol-H) and those in abalone muscle were ~0.035% (mol-D/mol-H). Numerical deuterium transfer model was constructed. Obtained numerical model well represented the OBD-enriched ulva feeding experiment.
Topics: Cesium Radioisotopes; Deuterium; Food Chain; Fukushima Nuclear Accident; Japan; Radiation Monitoring; Seawater; Tritium; Water Pollutants, Radioactive
PubMed: 36083768
DOI: 10.1093/rpd/ncac072 -
Nature Communications Jun 2021Despite the well-established chemical processes for C-D bond formation, the toolbox of enzymatic methodologies for deuterium incorporation has remained underdeveloped....
Despite the well-established chemical processes for C-D bond formation, the toolbox of enzymatic methodologies for deuterium incorporation has remained underdeveloped. Here we describe a photodecarboxylase from Chlorella variabilis NC64A (CvFAP)-catalyzed approach for the decarboxylative deuteration of various carboxylic acids by employing DO as a cheap and readily available deuterium source. Divergent protein engineering of WT-CvFAP is implemented using Focused Rational Iterative Site-specific Mutagenesis (FRISM) as a strategy for expanding the substrate scope. Using specific mutants, several series of substrates including different chain length acids, racemic substrates as well as bulky cyclic acids are successfully converted into the deuterated products (>40 examples). In many cases WT-CvFAP fails completely. This approach also enables the enantiocomplementary kinetic resolution of racemic acids to afford chiral deuterated products, which can hardly be accomplished by existing methods. MD simulations explain the results of improved catalytic activity and stereoselectivity of WT CvFAP and mutants.
Topics: Carboxy-Lyases; Carboxylic Acids; Catalysis; Chlorella; Decarboxylation; Deuterium; Deuterium Oxide; Molecular Docking Simulation; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Engineering; Recombinant Proteins; Substrate Specificity
PubMed: 34172745
DOI: 10.1038/s41467-021-24259-6 -
Medical Physics Oct 2022In proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic...
BACKGROUND
In proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions.
PURPOSE
A novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU-accelerated proton MC dose calculation and take full advantage of the computing power of GPU.
METHODS
Neutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous-slowing-down-approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient-specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared.
RESULTS
Integrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D-3D gamma passing rates with a criterion of 2%/2 mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D-3D gamma passing rates with 2%/2 mm/10% between dose distributions from VPMC and MCsquare were 98.56 ± 1.09% in patient geometries. The 2D-3D gamma analysis with 3%/2 mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91 ± 0.88%. VPMC calculation was highly efficient and took 2.84 ± 2.44 s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries.
CONCLUSION
VPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation.
Topics: Deuterium; Humans; Monte Carlo Method; Proton Therapy; Protons; Water
PubMed: 35960865
DOI: 10.1002/mp.15913