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1.
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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Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding.
Stevens, J, Wyatt, C, Brown, P, Patel, D, Grujic, D, Freedman, SD
Journal of pediatric gastroenterology and nutrition. 2018;(4):527-532
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Abstract
OBJECTIVES Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, enteral nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability, and improvement of fatty acid (FA) status in red blood cell (RBC) membranes, a marker of long-term FA absorption, with an in-line digestive cartridge (RELiZORB) that hydrolyzes fat in enteral formula. METHODS Patients with CF receiving EN participated in a multicenter, 90-day open-label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of docosahexaenoic acid (DHA)+ eicosapentaenoic acid (EPA). Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study. RESULTS A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω-6/ω-3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events. CONCLUSIONS RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Because improvement in omega-3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long-term therapeutic benefits in patients with CF.
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Docosahexaenoic acid levels in erythrocytes and their association with the University Selection Test Outcomes in Chile.
Valenzuela, R, Barrera, C, Orellana, Y, Almagià, A, Arancibia, V, Larraín, C, Silva, C, Billeke, P, Zamorano, F, Martínez, V, et al
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:25-30
Abstract
The aim of this study was to quantitate the relative impact of DHA and AA levels in erythrocytes, anthropometric parameters and socio-economic status of school-age children, of both genders, graduated from high school in Chile, on the scholastic achievement in the University Selection Test (Prueba de Selección Universitaria, PSU) both language scholastic achievement (LSA) and mathematics scholastic achievement (MSA). A representative sample of 671 school-age young graduated from high school in 2013, 550 and 548 of them took the PSU for LSA and MSA, respectively. Only school-age young with high (n = 91) and low (n = 69) SA in both tests were considered. A total of 122 school-age children agreed to participate in the study and were divided as follows: Group 1: high PSU outcome (n = 70; males n = 48) and Group 2: low PSU outcome (n = 52; males n = 23). Data were analyzed by means of SAS software. Independently of gender, DHA, socio-economic status and head circumference-for-age Z-score were the most relevant parameters explaining both LSA (R2 = 0.650; p < 0.0001) and MSA outcomes (R2 = 0.700; p < 0.0001). These results can be useful for nutrition, health and education planning, in order to protect children starting from an early age and thus increase their school outcomes.
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Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5-3 Years.
Akkermans, MD, Uijterschout, L, Vloemans, J, Teunisse, PP, Hudig, F, Bubbers, S, Verbruggen, S, Veldhorst, M, de Leeuw, TG, van Goudoever, JB, et al
Pediatric hematology and oncology. 2015;(8):624-32
Abstract
Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5-3 years. ID was defined as serum ferritin (SF) <12 μg/L in the absence of infection (C-reactive protein [CRP] <5 mg/L) and IDA as hemoglobin <110 g/L combined with ID. RDW (%) and the platelet count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2-6.3) to be iron deficient, compared with anemic children with a RDW <14.3%. The platelet count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children.
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Association of low baseline levels of erythrocyte folate with treatment nonresponse at three months in rheumatoid arthritis patients receiving methotrexate.
de Rotte, MC, de Jong, PH, Pluijm, SM, Calasan, MB, Barendregt, PJ, van Zeben, D, van der Lubbe, PA, de Sonnaville, PB, Lindemans, J, Hazes, JM, et al
Arthritis and rheumatism. 2013;(11):2803-13
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Abstract
OBJECTIVE To investigate whether baseline concentrations of one-carbon metabolism biomarkers are associated with treatment nonresponse and adverse events in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). METHODS A prospective derivation cohort (n = 285) and validation cohort (n = 102) of RA patients receiving MTX were studied. Concentrations of plasma homocysteine, serum vitamin B12 , serum folate, erythrocyte vitamin B6 , and erythrocyte folate were determined at baseline and after 3 months of treatment. Nonresponse after 3 months was assessed using the Disease Activity Score in 28 joints (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Adverse events at 3 months were assessed using biochemical parameters and health status questionnaires. Analyses were corrected for baseline DAS28, age, sex, MTX dose, comedications, and presence of the methylenetetrahydrofolate reductase 677TT genotype. RESULTS In the derivation cohort, the mean DAS28 scores at baseline and 3 months were 4.94 and 3.12, respectively, and 78% of patients experienced adverse events. This was similar between the 2 cohorts, despite a lower MTX dose in the validation cohort. Patients with lower levels of erythrocyte folate at baseline had a higher DAS28 at 3 months in both the derivation cohort (β = -0.15, P = 0.037) and the validation cohort (β = -0.20, P = 0.048). In line with these results, lower baseline erythrocyte folate levels were linearly associated with a 3-month DAS28 of >3.2 in both cohorts (derivation cohort, P = 0.049; validation cohort, P = 0.021) and with nonresponse according to the EULAR criteria (derivation cohort, P = 0.066; validation cohort, P = 0.027). None of the other biomarkers (levels at baseline or changes over 3 months) were associated with the DAS28 or treatment nonresponse. Baseline levels of the biomarkers and changes in levels after 3 months were not associated with incidence of adverse events. CONCLUSION A low baseline concentration of erythrocyte folate is associated with high disease activity and nonresponse at 3 months after the start of MTX treatment and could be used in prediction models for MTX outcome. None of the investigated one-carbon metabolism biomarkers were associated with incidence of adverse events at 3 months.
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Preventing enterocyte damage by maintenance of mean arterial pressure during major nonabdominal surgery in children.
Thuijls, G, Derikx, JP, de Kruijf, M, van Waardenburg, DA, van Bijnen, AA, Ambergen, T, van Rhijn, LW, Willigers, HM, Buurman, WA
Shock (Augusta, Ga.). 2012;(1):22-7
Abstract
Loss of the gut barrier, which is related to hypotension and gastrointestinal hypoperfusion during surgery, has been implicated as a critical event in postoperative complications development. This study aims at preventing gut barrier loss by maintenance of mean arterial pressure (MAP) in patients undergoing major nonabdominal surgery. In 20 previously included children undergoing spinal fusion surgery, the critical MAP value, which should be maintained to prevent enterocyte damage, was determined. In the following 12 children, MAP was kept above the critical value during surgery. Gut mucosal barrier loss was assessed by plasma intestinal fatty acid-binding proteins levels, a marker for enterocyte damage. Gastrointestinal perfusion was measured by gastric tonometry. First, we determined that the MAP should be maintained greater than 60 mmHg to prevent enterocyte damage. Next, maintenance of the MAP above this critical value during surgery resulted in adequate intestinal perfusion and preservation of enterocyte integrity, represented by intestinal fatty acid-binding protein levels within the reference range. This study shows that maintenance of the MAP at greater than 60 mmHg is associated with adequate intestinal perfusion and reduced enterocyte loss in children undergoing major nonabdominal surgery. These data stress the importance and benefits of good circulatory management during major surgery.
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The impact of different intensities of regular donor plasmapheresis on humoral and cellular immunity, red cell and iron metabolism, and cardiovascular risk markers.
Tran-Mi, B, Storch, H, Seidel, K, Schulzki, T, Haubelt, H, Anders, C, Nagel, D, Siegler, KE, Vogt, A, Seiler, D, et al
Vox sanguinis. 2004;(3):189-97
Abstract
BACKGROUND AND OBJECTIVES Major studies are still lacking on the impact of differing intensities of long-term donor plasmapheresis, not only on total serum protein, albumin and immunoglobulin G (IgG), but also on humoral and cellular immunity, red cell and iron metabolism, and biochemical cardiovascular risk markers. MATERIALS AND METHODS Three groups of donors, comprising 483 individuals undergoing differing intensities of long-term serial plasmapheresis, were entered into a cross-sectional study. A fourth control group consisted of 100 non-donors. In addition to measuring total protein, albumin and IgG levels, we determined parameters of humoral and cellular immunity, red cell and iron metabolism and recognized biochemical cardiovascular risk factors. RESULTS The median annual net amount of plasma donated by the three donor groups was 37, 16 and 10 l, respectively (P < 0.0001). Donors had significantly lower total serum protein, albumin and IgG levels than non-donors (P < 0.0001), but the intensity of plasmapheresis had no influence on those parameters. Like non-donors, all plasma donors had normal humoral and cellular immunity. No increased rates of iron store depletion were observed in the three groups of plasma donors. Plasma donors were not at increased cardiovascular risk. CONCLUSIONS Regular donor plasmapheresis of up to 45 l of plasma per year appears to be as safe as more moderate plasmapheresis programmes, with respect to the parameters analysed in this study. Individuals donating under these conditions did not develop impaired humoral and cellular immunity, iron store depletion, or increased cardiovascular risk with regard to established biochemical risk markers. Prospective studies are required to determine more exactly than in retrospective analyses the reasons why donors withdraw from plasmapheresis programmes.