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Metabolic syndrome in postmenopausal women is associated with lower erythrocyte PUFA/MUFA and n-3/n-6 ratio: A case-control study.
Muzsik, A, Jeleń, HH, Chmurzynska, A
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102155
Abstract
The aim of this study was to compare fatty acid (FA) intake and status in postmenopausal women with or without metabolic syndrome (MetS). 131 women were recruited to a case-control study in 2016-2018 in Poznań, Poland. Dietary intake, anthropometric and biochemical measurements, FA level in red blood cells (RBCs), and FADS1 (rs174546) and FADS2 (rs3834458) genotypes were determined. Compared to women without MetS, those with MetS had lower levels of EPA, n-3, EPA/α-linolenic acid (ALA), EPA/AA, DHA/AA, EPA+DHA/AA, PUFA/saturated FA, PUFA/monounsaturated FA, and n-3/n-6 ratios in RBCs. Participants with at least one minor allele of each polymorphism had lower levels of EPA, and EPA/AA, and a higher level of DHA/EPA in RBCs than did women with major alleles. MetS is associated with lower levels FAs that have a protective effect on cardiometabolic health. FADS1 and FADS2 polymorphisms are associated with unfavorable FA and status EPA/AA in RBC contributes to MetS.
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2.
Temporal sequence of the human RBCs' vesiculation observed in nano-scale with application of AFM and complementary techniques.
Kaczmarska, M, Grosicki, M, Bulat, K, Mardyla, M, Szczesny-Malysiak, E, Blat, A, Dybas, J, Sacha, T, Marzec, KM
Nanomedicine : nanotechnology, biology, and medicine. 2020;:102221
Abstract
Based on the multimodal characterization of human red blood cells (RBCs), the link between the storage-related sequence of the nanoscale changes in RBC membranes in the relation to their biochemical profile as well as mechanical and functional properties was presented. On the background of the accumulation of RBCs waste products, programmed cell death and impaired rheological properties, progressive alterations in the RBC membranes including changes in their height and diameter as well as the in situ characterization of RBC-derived microparticles (RMPs) on the RBCs surface were presented. The advantage of atomic force microscopy (AFM) in RMPs visualization, even at the very early stage of vesiculation, was shown based on the results revealed by other reference techniques. The nanoscale characterization of RMPs was correlated with a decrease in cholesterol and triglycerides levels in the RBC membranes, proving the link between the lipids leakage from RBCs and the process of vesiculation.
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3.
Ethyl glucuronide, a marker of alcohol consumption, correlates with metabolic markers of oxidant stress but not with hemolysis in stored red blood cells from healthy blood donors.
D'Alessandro, A, Fu, X, Reisz, JA, Stone, M, Kleinman, S, Zimring, JC, Busch, M, ,
Transfusion. 2020;(6):1183-1196
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Abstract
BACKGROUND Red blood cell (RBC) storage in the blood bank is associated with the progressive accumulation of oxidant stress. While the mature erythrocyte is well equipped to cope with such stress, recreative habits like alcohol consumption may further exacerbate the basal level of oxidant stress and contribute to the progress of the storage lesion. STUDY DESIGN AND METHODS RBC levels of ethyl glucuronide, a marker of alcohol consumption, were measured via ultra-high-pressure liquid chromatography coupled with high-resolution mass spectrometry. Analyses were performed on 599 samples from the recalled donor population at Storage Days 10, 23, and 42 (n = 250), as part of the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study. This cohort consisted of the 5th and 95th percentile of donors with extreme hemolytic propensity out of the original cohort of 13,403 subjects enrolled in the REDS-III RBC Omics study. Ehtyl glucuronide levels were thus correlated to global metabolomics and lipidomics analyses and RBC hemolytic propensity. RESULTS Ethyl glucuronide levels were positively associated with oxidant stress markers, including glutathione consumption and turnover, methionine oxidation, S-adenosylhomocysteine accumulation, purine oxidation, and transamination markers. Decreases in glycolysis and energy metabolism, the pentose phosphate pathway and ascorbate system were observed in those subjects with the highest levels of ethyl glucuronide, though hemolysis values were comparable between groups. CONCLUSION Though preliminary, this study is suggestive that markers of alcohol consumption are associated with increases in oxidant stress and decreases in energy metabolism with no significant impact on hemolytic parameters in stored RBCs from healthy donor volunteers.
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Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC®.
Hachem, M, Nacir, H, Picq, M, Belkouch, M, Bernoud-Hubac, N, Windust, A, Meiller, L, Sauvinet, V, Feugier, N, Lambert-Porcheron, S, et al
Nutrients. 2020;(1)
Abstract
AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.
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Total serum and intraerythrocyte magnesium concentrations in hemodialysis patients using different dialysate solutions.
Kusic, J, Markovic, R, Andjelkovic Apostolovic, M, Dragovic, G
Magnesium research. 2020;(2):28-36
Abstract
Beside routinely used 0.5 mmol/L dialysate-magnesium, higher dialysate-magnesium (1.0 mmol/L) was recently introduced. The aim of this study was to evaluate the impact of different dialysate-magnesium on serum and intraerythrocyte levels of magnesium (Mg) before and after dialysis. The study included 43 patients receiving chronic hemodialysis, divided into two groups based on dialysate-magnesium (0.5 or 1.0 mmol/L) used prior to study initiation and during 12 months of follow-up. Blood samples were taken at the mid-week dialysis; total serum Mg was measured colorimetrically and intraerythrocyte Mg by atomic absorption spectrophotometry. Hypermagnesiemia-associated complications were observed for 12 months. Total serum Mg was 1.14 ± 0.19 mmol/L before and 0.95 ± 0.16 mmol/L after dialysis in patients using lower dialysate-Mg (p < 0.001), whereas it was 1.47 ± 0.25 mmol/L before and 1.49 ± 0.18 mmol/L after dialysis in patients using higher dialysate-Mg (p = 0.926). Intraerythrocyte Mg was 1.98 ± 0.34 mmol/L before and 1.97 ± 0.28 mmol/L after dialysis in the lower dialysate-Mg group (p = 0.939), while it was 2.09 ± 0.37 mmol/L before and 2.19 ± 0.48 mmol/L after dialysis in the higher dialysate group (p = 0.067). After 12 months total serum Mg decreased in both the groups, remaining lower in 0.5 mmol/L dialysate-Mg group. No hypermagnesiemia-related symptoms occur during 12 months of follow-up in both the groups. In patients using lower dialysate-Mg total serum Mg remains within the reference range and shows postdialytic decline, while in higher dialysate-Mg group it exceeded reference range before and after dialysis without significant intradialytic change. The intraerythrocyte values remain within reference range with both dialysates used. No clinical signs and symptoms of hypermagnesiemia occur during longer administration of higher dialysate-magnesium despite high total serum Mg level.
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A new antigen SUMI carried on glycophorin A encoded by the GYPA*M with c.91A>C (p.Thr31Pro) belongs to the MNS blood group system.
Ito, S, Kaito, S, Miyazaki, T, Kikuchi, G, Isa, K, Tsuneyama, H, Kurita, R, Ogasawara, K, Uchikawa, M, Satake, M
Transfusion. 2020;(6):1287-1293
Abstract
BACKGROUND MNS is one of the highly polymorphic blood groups comprising many antigens generated by genomic recombination among the GYPA, GYPB, and GYPE genes as well as by single-nucleotide changes. We report a patient with red blood cell (RBC) antibody against an unknown low-frequency antigen, tentatively named SUMI, and investigated its carrier molecule and causal gene. STUDY DESIGN AND METHODS Standard serologic tests, including enzyme tests, were performed. Monoclonal anti-SUMI-producing cells (HIRO-305) were established by transformation and hybridization methods using lymphocytes from a donor having anti-SUMI. SUMI+ RBCs were examined by immunocomplex capture fluorescence analysis (ICFA) using HIRO-305 and murine monoclonal antibodies against RBC membrane proteins carrying blood group antigens. Genomic DNA was extracted from whole blood, and the GYPA gene was analyzed by polymerase chain reactions and Sanger sequencing. RESULTS Serologic screening revealed that 23 of the 541,522 individuals (0.0042%) were SUMI+, whereas 1351 of the 10,392 individuals (13.0%) had alloanti-SUMI. SUMI antigen was sensitive to ficin, trypsin, pronase, and neuraminidase, but resistant to α-chymotrypsin and sulfydryl-reducing agents. ICFA revealed that the SUMI antigen was carried on glycophorin A (GPA). According to Sanger sequencing and cloning, the SUMI+ individuals had a GYPA*M allele with c.91A>C (p.Thr31Pro), which may abolish the O-glycan attachment site. CONCLUSIONS The new low-frequency antigen SUMI is carried on GPA encoded by the GYPA*M allele with c.91A>C (p.Thr31Pro). Neuraminidase sensitivity suggests that glycophorin around Pro31 are involved in the SUMI determinant.
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High Variability in Erythrocyte, Plasma and Whole Blood EPA and DHA Levels in Response to Supplementation.
Sparkes, C, Sinclair, AJ, Gibson, RA, Else, PL, Meyer, BJ
Nutrients. 2020;(4)
Abstract
(1) Aim: the aim of this secondary analysis was to report the variability in response to n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation in erythrocytes, plasma and whole blood of a previously published dose response study. (2) Methods: a randomized, double-blind, placebo-controlled trial of parallel design was conducted, whereby pre-menopausal women were randomly assigned to consume 0, 0.35, 0.7 or 1 g/day of supplemental eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Fasted blood samples were taken at baseline and after eight weeks intervention. Erythrocyte, plasma and whole blood fatty acids were extracted using the method of Lepage and Roy and analysed using gas chromatography. (3) Results: There were significant increases in EPA plus DHA levels in the 0.7 g and 1 g dose groups, with the highest increase with the 1 g dose notably: in erythrocytes (from 5.69% to 7.59%), plasma (from 2.94% to 5.48%) and in whole blood (from 3.81% to 6.03%). There was high variability in response to the supplement in erythrocytes, plasma and whole blood across the different doses. (4) Conclusion: there is high individual variability in n-3 LCPUFA levels in response to n-3 LCPUFA supplementation, which should be taken into account in clinical trials using n-3 LCPUFA supplements.
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Stored RBC metabolism as a function of caffeine levels.
D'Alessandro, A, Fu, X, Reisz, JA, Kanias, T, Page, GP, Stone, M, Kleinman, S, Zimring, JC, Busch, M, ,
Transfusion. 2020;(6):1197-1211
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Abstract
BACKGROUND Coffee consumption is extremely common in the United States. Coffee is rich with caffeine, a psychoactive, purinergic antagonist of adenosine receptors, which regulate red blood cell energy and redox metabolism. Since red blood cell (purine) metabolism is a critical component to the red cell storage lesion, here we set out to investigate whether caffeine levels correlated with alterations of energy and redox metabolism in stored red blood cells. STUDY DESIGN AND METHODS We measured the levels of caffeine and its main metabolites in 599 samples from the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study via ultra-high-pressure-liquid chromatography coupled to high-resolution mass spectrometry and correlated them to global metabolomic and lipidomic analyses of RBCs stored for 10, 23, and 42 days. RESULTS Caffeine levels positively correlated with increased levels of the main red cell antioxidant, glutathione, and its metabolic intermediates in glutathione-dependent detoxification pathways of oxidized lipids and sugar aldehydes. Caffeine levels were positively correlated with transamination products and substrates, tryptophan, and indole metabolites. Expectedly, since caffeine and its metabolites belong to the family of xanthine purines, all xanthine metabolites were significantly increased in the subjects with the highest levels of caffeine. However, high-energy phosphate compounds ATP and DPG were not affected by caffeine levels, despite decreases in glucose oxidation products-both via glycolysis and the pentose phosphate pathway. CONCLUSION Though preliminary, this study is suggestive of a beneficial correlation between the caffeine levels and improved antioxidant capacity of stored red cells.
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Effect of fasting status and other pre-analytical variables on quantitation of long-chain fatty acids in red blood cells.
Lozier, BK, Kim, RN, Zuromski, LM, Kish-Trier, E, De Biase, I, Yuzyuk, T
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102211
Abstract
Long-chain fatty acids (LCFAs), including omega-3 and omega-6 fatty acids, play essential roles in health maintenance and outcomes. Insufficient intake or the inability to absorb LCFAs from the diet can cause a number of health problems. Evaluation of fatty acid profiles in plasma, serum or red blood cells (RBCs) is routinely used to monitor patients at risk of developing deficiency. Quantitation of LCFAs in RBCs offers advantages over serum/plasma due to low intra-individual variability. Fatty acid composition in RBCs also reflects long-term dietary intake, providing additional information about the patient's nutritional status. However, the literature does not currently address the impact of pre-analytical factors (conditions of RBC collection, sample handling and short-term storage) on LCFA measurements. This study evaluated the effect of several anticoagulants, interferents, different storage conditions and fasting status on quantitation of the twenty-one most abundant LCFAs in RBCs by gas chromatography negative chemical ionization-mass spectrometry (GCNCI-MS). LCFA results were assessed quantitatively (nmol/mL) or as a percent of total. Most common tube types (containing citrate, sodium heparin or EDTA) were all appropriate for blood collection. Whole blood and lysed RBCs were stable at least 24 h at room temperature and up to 7 days refrigerated. Lysed RBCs were also stable for up to three freeze/thaw cycles. The presence of icterus or lipemia did not affect results. LCFAs concentrations in RBCs did not change ~4 h after high-fat intake when the lipid concentration in circulation reaches a peak, while plasma levels of most fatty acids increased up to 40% in response. In summary, RBCs are a reliable sample type for LCFA quantitation in the clinical laboratory. In contrast to plasma or serum, RBCs isolated from non-fasting, hemolyzed or lipemic whole blood specimens are all acceptable for testing. Therefore, RBCs might be a preferable sample type for evaluation of nutritional status of young pediatric patients and in patients with conditions associated with hemolytic anemia or hyperlipidemia.
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Hypoxic storage of red blood cells improves metabolism and post-transfusion recovery.
DʼAlessandro, A, Yoshida, T, Nestheide, S, Nemkov, T, Stocker, S, Stefanoni, D, Mohmoud, F, Rugg, N, Dunham, A, Cancelas, JA
Transfusion. 2020;(4):786-798
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Abstract
BACKGROUND Blood transfusion is a lifesaving intervention for millions of recipients worldwide every year. Storing blood makes this possible but also promotes a series of alterations to the metabolism of the stored erythrocyte. It is unclear whether the metabolic storage lesion is correlated with clinically relevant outcomes and whether strategies aimed at improving the metabolic quality of stored units, such as hypoxic storage, ultimately improve performance in the transfused recipient. STUDY DESIGN AND METHODS Twelve healthy donor volunteers were recruited in a two-arm cross-sectional study, in which each subject donated 2 units to be stored under standard (normoxic) or hypoxic conditions (Hemanext technology). End-of-storage measurements of hemolysis and autologous posttransfusion recovery (PTR) were correlated to metabolomics measurements at Days 0, 21, and 42. RESULTS Hypoxic red blood cells (RBCs) showed superior PTR and comparable hemolysis to donor-paired standard units. Hypoxic storage improved energy and redox metabolism (glycolysis and 2,3-diphosphoglycerate), improved glutathione and methionine homeostasis, decreased purine oxidation and membrane lipid remodeling (free fatty acid levels, unsaturation and hydroxylation, acyl-carnitines). Intra- and extracellular metabolites in these pathways (including some dietary purines) showed significant correlations with PTR and hemolysis, though the degree of correlation was influenced by sulfur dioxide (SO2 ) levels. CONCLUSION Hypoxic storage improves energy and redox metabolism of stored RBCs, which results in improved posttransfusion recoveries in healthy autologous recipients-a Food and Drug Administration gold standard of stored blood quality. In addition, we identified candidate metabolic predictors of PTR for RBCs stored under standard and hypoxic conditions.