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European Journal of Nutrition Jun 2023Choline deficiency leads to pathologies particularly of the liver, brain and lung. Adequate supply is important for preterm infants and patients with cystic fibrosis. We... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Choline deficiency leads to pathologies particularly of the liver, brain and lung. Adequate supply is important for preterm infants and patients with cystic fibrosis. We analysed the assimilation of four different enterally administered deuterium-labelled (D9-) choline supplements in adults.
METHODS
Prospective randomised cross-over study (11/2020-1/2022) in six healthy men, receiving four single doses of 2.7 mg/kg D9-choline equivalent each in the form of D9-choline chloride, D9-phosphorylcholine, D9-alpha-glycerophosphocholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-glycero-3-phosphoryl-choline (D9-POPC), in randomised order 6 weeks apart. Plasma was obtained at baseline (t = - 0.1 h) and at 0.5 h to 7d after intake. Concentrations of D9-choline and its D9-labelled metabolites were analysed by tandem mass spectrometry. Results are shown as median and interquartile range.
RESULTS
Maximum D9-choline and D9-betaine concentrations were reached latest after D9-POPC administration versus other components. D9-POPC and D9-phosphorylcholine resulted in lower D9-trimethylamine (D9-TMAO) formation. The AUCs (0-7d) of plasma D9-PC concentration showed highest values after administration of D9-POPC. D9-POPC appeared in plasma after fatty acid remodelling, predominantly as D9-1-palmitoyl-2-linoleyl-PC (D9-PLPC), confirming cleavage to 1-palmitoyl-lyso-D9-PC and re-acylation with linoleic acid as the most prominent alimentary unsaturated fatty acid.
CONCLUSION
There was a delayed increase in plasma D9-choline and D9-betaine after D9-POPC administration, with no differences in AUC over time. D9-POPC resulted in a higher AUC of D9-PC and virtually absent D9-TMAO levels. D9-POPC is remodelled according to enterocytic fatty acid availability. D9-POPC seems best suited as choline supplement to increase plasma PC concentrations, with PC as a carrier of choline and targeted fatty acid supply as required by organs. This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498, 22.01.2020.
STUDY REGISTRATION
This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498.
Topics: Adult; Humans; Infant; Infant, Newborn; Male; Betaine; Choline; Cross-Over Studies; Deuterium; Fatty Acids; Infant, Premature; Phosphatidylcholines; Phosphorylcholine; Prospective Studies
PubMed: 36840817
DOI: 10.1007/s00394-023-03121-z -
Children (Basel, Switzerland) Oct 2022Low and high birth weight (BW) are associated with obesity later in life; however, this association has not been extensively studied in African countries. This study...
Low and high birth weight (BW) are associated with obesity later in life; however, this association has not been extensively studied in African countries. This study determines the association between BW and body composition derived from deuterium oxide (D2O) dilution in 6- to 8-year-old South African children (n = 91; 40 boys, 51 girls). BW was recorded retrospectively from the children’s Road-to-Health cards. Weight and height were measured using standard procedures, and D2O dilution was used to determine total body water and, subsequently, to determine body fat. Fatness was classified using the McCarthy centiles, set at 2nd, 85th, and 95th (underfat, overfat and obese). BW correlated with body composition measures, such as body weight (r = 0.23, p = 0.03), height (r = 0.33, p < 0.001), and fat free mass (FFM; r = 0.27, p = 0.01). When multiple regression analysis was employed, BW significantly and positively associated with FFM (β = 0.24, p = 0.013; 95% CI: 0.032; 0.441) and fat mass (β = 0.21, p = 0.02, 95%CI: 0.001; 0.412) in girls and boys combined. A total of 13% of the children had a low BW, with 21% being overweight and 17% obese. More girls than boys were overweight and obese. Intervention strategies that promote healthy uterine growth for optimal BW are needed in order to curb the global obesity pandemic.
PubMed: 36291533
DOI: 10.3390/children9101597 -
European Journal of Sport Science Sep 2016Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great... (Review)
Review
Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.
Topics: Exercise; Humans; Hypertrophy; Muscle, Skeletal; Resistance Training
PubMed: 26289597
DOI: 10.1080/17461391.2015.1073362 -
Advanced Science (Weinheim,... Aug 2023Gas-solid reactions are important for many redox processes that underpin the energy and sustainability transition. The specific case of hydrogen-based iron oxide...
Gas-solid reactions are important for many redox processes that underpin the energy and sustainability transition. The specific case of hydrogen-based iron oxide reduction is the foundation to render the global steel industry fossil-free, an essential target as iron production is the largest single industrial emitter of carbon dioxide. This perception of gas-solid reactions has not only been limited by the availability of state-of-the-art techniques which can delve into the structure and chemistry of reacted solids, but one continues to miss an important reaction partner that defines the thermodynamics and kinetics of gas phase reactions: the gas molecules. In this investigation, cryogenic-atom probe tomography is used to study the quasi in situ evolution of iron oxide in the solid and gas phases of the direct reduction of iron oxide by deuterium gas at 700°C. So far several unknown atomic-scale characteristics are observed, including, D accumulation at the reaction interface; formation of a core (wüstite)-shell (iron) structure; inbound diffusion of D through the iron layer and partitioning of D among phases and defects; outbound diffusion of oxygen through the wüstite and/or through the iron to the next free available inner/outer surface; and the internal formation of heavy nano-water droplets at nano-pores.
PubMed: 37290039
DOI: 10.1002/advs.202300626 -
Molecules (Basel, Switzerland) Aug 2022Visible light-sensitized oxidation of micropollutants (MPs) in the presence of meso-tetrakis(4-sulfonatophenyl)porphyrin photosensitizers was studied. In order to...
Visible light-sensitized oxidation of micropollutants (MPs) in the presence of meso-tetrakis(4-sulfonatophenyl)porphyrin photosensitizers was studied. In order to explore the role of type I (ROS generation) or type II (singlet oxygen) photooxidation, radical scavengers were used to obtain insight into the mechanism of photodegradation. It was revealed that singlet oxygen is the main ROS taking part in TPPS- sensitized photooxidation of micropollutants. The interaction of MPs with O in deuterium oxide (DO) was investigated by measuring the phosphorescence lifetime of O. The rate constant (kq) for the total (physical and chemical) quenching of O by MPs was determined in a DO buffer (pD 7, 9 and 10.8). The rate constants of singlet oxygen quenching and reaction with MPs were determined, and the rate constant of excited TPPS quenching by MPs was also estimated.
Topics: Kinetics; Oxidation-Reduction; Oxygen; Porphyrins; Reactive Oxygen Species; Singlet Oxygen
PubMed: 36014499
DOI: 10.3390/molecules27165260 -
Molecules (Basel, Switzerland) Sep 2022The structure and function of biological macromolecules change due to intermolecular deuterium bond formation or deuterium substitution with environmental DO. In this...
The structure and function of biological macromolecules change due to intermolecular deuterium bond formation or deuterium substitution with environmental DO. In this study, surface-enhanced Raman spectroscopy (SERS) was used to detect interaction sites between DO and ssDNA and their action mechanisms. SERS peaks of ssDNA changed with increasing DO proportions, and the site of action mainly involved A and G bases, whose number strengthened the interaction between sequences and DO and hence the SERS peak intensities. Fixing the number of A and G bases prevented changes in their positions from significantly altering the map. We also identified the interaction between ssDNA sequences that easily formed a G-quadruplex structure and DO. The amplitude of the SERS peak intensity change reflected the ssDNA structural stability and number of active sites. These findings are highly significant for exploring genetic exchanges and mutations and could be used to determine the stability and structural changes of biological macromolecules.
Topics: DNA, Single-Stranded; Deuterium; Deuterium Oxide; G-Quadruplexes; Spectrum Analysis, Raman
PubMed: 36144761
DOI: 10.3390/molecules27186023 -
Journal of Cachexia, Sarcopenia and... Feb 2021Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of...
BACKGROUND
Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of translational capacity in muscle atrophy and regrowth from disuse is largely unknown. Therefore, we investigated the effect of muscle disuse and reloading on translational capacity in middle-aged men (Study 1) and in rats (Study 2).
METHODS
In Study 1, 28 male participants (age 50.03 ± 3.54 years) underwent 2 weeks of knee immobilization followed by 2 weeks of ambulatory recovery and a further 2 weeks of resistance training. Muscle biopsies were obtained for measurement of total RNA and pre-ribosomal (r)RNA expression, and vastus lateralis cross-sectional area (CSA) was determined via peripheral quantitative computed tomography. In Study 2, male rats underwent hindlimb suspension (HS) for either 24 h (HS 24 h, n = 4) or 7 days (HS 7d, n = 5), HS for 7 days followed by 7 days of reloading (Rel, n = 5) or remained as ambulatory weight bearing (WB, n = 5) controls. Rats received deuterium oxide throughout the study to determine RNA synthesis and degradation, and mTORC1 signalling pathway was assessed.
RESULTS
Two weeks of immobilization reduced total RNA concentration (20%) and CSA (4%) in men (both P ≤ 0.05). Ambulatory recovery restored total RNA concentration to baseline levels and partially restored muscle CSA. Total RNA concentration and 47S pre-rRNA expression increased above basal levels after resistance training (P ≤ 0.05). In rats, RNA synthesis was 30% lower while degradation was ~400% higher in HS 7d in soleus and plantaris muscles compared with WB (P ≤ 0.05). mTORC1 signalling was lower in HS compared with WB as was 47S pre-rRNA (P ≤ 0.05). With reloading, the aforementioned parameters were restored to WB levels while RNA degradation was suppressed (P ≤ 0.05).
CONCLUSIONS
Changes in RNA concentration following muscle disuse and reloading were associated with changes in ribosome biogenesis and degradation, indicating that both processes are important determinants of translational capacity. The pre-clinical data help explain the reduced translational capacity after muscle immobilization in humans and demonstrate that ribosome biogenesis and degradation might be valuable therapeutic targets to maintain muscle mass during disuse.
Topics: Animals; Hindlimb Suspension; Male; Muscle, Skeletal; Muscular Atrophy; Protein Biosynthesis; Rats; Ribosomes
PubMed: 33231914
DOI: 10.1002/jcsm.12636 -
Chemical & Pharmaceutical Bulletin 2020The high-order functions of molecular capture and chiral recognition of tea gallated catechins (-)-epigallocatechin-3-O-gallate (EGCg) in water were investigated. A... (Review)
Review
The high-order functions of molecular capture and chiral recognition of tea gallated catechins (-)-epigallocatechin-3-O-gallate (EGCg) in water were investigated. A solution of equimolar amounts of a variety of heterocyclic compounds and EGCg in water afforded adhesive precipitates containing the heterocyclic compounds and EGCg at a molar ratio of 1 : 1, based on the integrated value of NMR proton signals. The molecular capture abilities of a variety of heterocyclic compounds using EGCg from the aqueous solutions were evaluated with the ratios of the heterocyclic compounds included in the precipitates of EGCg complex to the total heterocyclic compounds used. In the H-NMR spectrum of a solution containing cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), and EGCg in a DO solution, a difference in the chemical shift of the H-NMR signal for some protons of the Pro residue was observed. Judging from the crystal structures of the 2 : 2 EGCg complexes of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift derived mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg.In the H-NMR spectrum of a solution containing the pharmaceuticals racemic (R,S)-propranolol, (R,S)-diprophylline, (R,S)-proxyphylline and EGCg in DO, splitting of the H-NMR signals of the pharmaceuticals was observed. It was suggested that the pharmaceuticals formed diastereomers of EGCg complexes, as a result chirality of the pharmaceuticals was recognized by EGCg in the DO solution.
Topics: Catechin; Deuterium Oxide; Drug Development; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Stereoisomerism
PubMed: 33268646
DOI: 10.1248/cpb.c20-00197 -
Theranostics 2021Endovascular intervention plays an important role in the treatment of various diseases, in which MRI-guidance can potentially improve precision. However, the clinical...
Endovascular intervention plays an important role in the treatment of various diseases, in which MRI-guidance can potentially improve precision. However, the clinical applications of currently available contrast media, including Gadolinium-based contrast agents and superparamagnetic iron oxide particles (SPIO), are hindered by safety concerns. In the present study, we sought to develop DO as a novel contrast agent for guiding endovascular neurointervention. Animal studies were approved by institutional ACUC and conducted using an 11.7 T Bruker Biospec system and a 3T Siemens Trio clinical scanner for rodent and canine imaging, respectively. The locally selective blood brain barrier opening (BBBO) in rat brains was obtained by intraarterial (IA) injection of mannitol. The dynamic T* EPI MRI sequence was used to study the trans-catheter perfusion territory by IA administered SPIO before mannitol administration, whereas a dynamic T FLASH sequence was used to acquire Gd contrast-enhanced MRI for assessing BBBO after injection of mannitol. The contrast generated by DO assessed by either EPI or FLASH methods was compared with the corresponding results assessed by SPIO or Gd. The utility of DO MRI was also demonstrated to guide drug delivery to glioma in a mouse model. Finally, the clinical utility of DO-MRI was demonstrated in a canine model. Our study has shown that the contrast generated by DO can be used to precisely delineate trans-catheter perfusion territory in both small and large animals. The perfusion territories determined by DO-MRI show moderate correlation with those by SPIO-MRI (Spearman coefficient r = 0.5234, P < 0.001). Moreover, our results show that the perfusion territory determined by DO-MRI can successfully predict the areas with BBBO after mannitol treatment similar to that assessed by Gd-MRI (Spearman coefficient r = 0.6923, P < 0.001). Using DO-MRI as imaging guidance, the optimal infusion rate in the mouse brain was determined to be 150 µL/min to maximize the delivery efficacy to the tumor without serious off-target delivery to the brain parenchyma. The enhanced drug delivery of antibodies to the brain tumor was confirmed by fluorescence imaging. Our study demonstrated that DO can be used as a negative MRI contrast medium to guide endovascular neurointervention. The established DO -MRI method is safe and quantitative, without the concern of contrast accumulation. These qualities make it an attempting approach for a variety of endovascular procedures.
Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Carotid Artery, Internal; Catheterization; Computer Systems; Contrast Media; Deuterium Oxide; Dogs; Drug Delivery Systems; Endovascular Procedures; Female; Ferric Compounds; Glioma; Infusions, Intra-Arterial; Injections, Intra-Arterial; Magnetic Resonance Imaging; Male; Mannitol; Mice; Mice, Inbred C57BL; Neuroimaging; Phantoms, Imaging; Rats; Rats, Sprague-Dawley; Surgery, Computer-Assisted; Tissue Distribution
PubMed: 33995656
DOI: 10.7150/thno.55953 -
Journal of the American Society For... Jul 2022Antimicrobial resistance is a serious challenge facing human and veterinary health. Current methods of detecting resistance are limited in turn-around time or universal...
Antimicrobial resistance is a serious challenge facing human and veterinary health. Current methods of detecting resistance are limited in turn-around time or universal detection. In this work, a new antimicrobial susceptibility test is developed and validated, which utilizes deuterium labeling of membrane lipids to track the growth of bacterial cells. We hypothesize that deuterium uptake and subsequent labeling of lipids can be detected using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Additionally, bacteria growth is performed on the MALDI target, minimizing sample preparation materials and time. When two strains are grown in the presence of deuterium oxide, labeling can be detected in as little as 30 min to 2 h. The labeling efficiency, or the ratio of labeled to unlabeled lipid peaks, provides information about the growth rate of bacteria. This growth ratio can differentiate between resistant and susceptible strains of bacteria as a resistant strain will maintain ∼50% labeling efficiency between untreated and treated cultures. In comparison, a susceptible strain will see a decrease in fractional abundance of deuterium from ∼50% in the untreated to ∼10% in the treated. This approach is applied to measure the minimum inhibitory concentration (MIC) of the resistant and susceptible strains from on-target microdroplet culture in a range of antibiotic concentrations. The first antibiotic concentration with a significant decrease in fractional abundance of deuterium correlates well with a traditionally obtained MIC using broth dilution, indicating the clinical relevance of the results.
Topics: Anti-Bacterial Agents; Bacteria; Deuterium; Drug Resistance, Bacterial; Escherichia coli; Humans; Lipids; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35623100
DOI: 10.1021/jasms.2c00056