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Sample records for plasma reduced folates

  1. Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation.

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    Bosy-Westphal, A; Holzapfel, A; Czech, N; Müller, M J

    2001-01-01

    Adverse effects of high vitamin B(6) intake include peripheral neuropathy. Recent studies focussing on the reduction of plasma homocysteine as a risk factor for vascular disease showed that vitamin B(6) reduces plasma folate levels. The significance of this finding is unclear. We therefore analyzed plasma folate and basal homocysteine levels as well as the response to an oral methionine loading test in 8 healthy individuals before and after a controlled supplementation with oral doses of 25 mg pyridoxine for 10 days. Plasma pyridoxal phosphate increased from 40.6 +/- 13.6 to 426.8 +/- 200.3 nmol/l (p < 0.001), whereas plasma folate decreased from 6.3 +/- 1.6 to 4.6 +/-1.5 ng/ml (p < 0.01), respectively. Plasma vitamin B(12) and basal homocysteine levels remained unchanged (234.0 +/- 27.8 vs. 217.1 +/- 50.4 pg/ml and 10.9 +/- 4.8 vs. 10.1 +/- 3.6 micromol/l). There was no significant effect of vitamin B(6) supplementation on the area under methionine and homocysteine concentration versus time curve. Significant correlations were found between pre- and post-supplement levels of folate as well as PLP levels (r = 0.73, p < 0.05; r = 0.75, p < 0.05). These data suggest that a dose of 25 mg vitamin B(6) supplemented for 10 days reduces plasma folate but did not affect basal and postprandial homocysteine levels suggesting (1) a normal cellular availability of folate or (2) a compensation of impaired homocysteine remethylation by increased transsulfuration.

  2. Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 danish women

    DEFF Research Database (Denmark)

    Milman, N; Byg, KE; Hvas, Anne-Mette

    2006-01-01

    OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study, performed in 1995-1996, comprised 404 healthy pregnant Danish Caucasian women residential in Copenhagen County. Women taking folic acid tablets or vitamin B12...... injections were not included. Dietary multivitamin supplements containing folic acid 100 microg or vitamin B12 1 microg, taken by 34%, were discontinued at inclusion. Participants had normal renal function. Folate status [erythrocyte (Ery-) folate, plasma (P-) folate, P-homocysteine] was measured at 18, 32....../L increased during pregnancy from 0.7% to 19.0% postpartum (P pregnancy from 0.5% to 17...

  3. Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 danish women

    DEFF Research Database (Denmark)

    Milman, N; Byg, KE; Hvas, Anne-Mette;

    2006-01-01

    OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study, performed in 1995-1996, comprised 404 healthy pregnant Danish Caucasian women residential in Copenhagen County. Women taking folic acid tablets or vitamin B12...... status (defined as P-folate homocysteine >13 micromol/L) was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39 wk of gestation and 8 wk postpartum, respectively. CONCLUSION: Low folate status occurs among Danish pregnant women, especially in late pregnancy and postpartum during lactation. Despite...... injections were not included. Dietary multivitamin supplements containing folic acid 100 microg or vitamin B12 1 microg, taken by 34%, were discontinued at inclusion. Participants had normal renal function. Folate status [erythrocyte (Ery-) folate, plasma (P-) folate, P-homocysteine] was measured at 18, 32...

  4. The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis.

    Science.gov (United States)

    Ifergan, Ilan; Jansen, Gerrit; Assaraf, Yehuda G

    2008-07-25

    The reduced folate carrier (RFC), a bidirectional anion transporter, is the major uptake route of reduced folates essential for a spectrum of biochemical reactions and thus cellular proliferation. However, here we show that ectopic overexpression of the RFC, but not of folate receptor alpha, a high affinity unidirectional folate uptake route serving here as a negative control, resulted in an approximately 15-fold decline in cellular viability in medium lacking folates but not in folate-containing medium. Moreover to explore possible mechanisms of adaptation to folate deficiency in various cell lines that express the endogenous RFC, we first determined the gene expression status of the following genes: (a) RFC, (b) ATP-driven folate exporters (i.e. MRP1, MRP5, and breast cancer resistance protein), and (c) folylpoly-gamma-glutamate synthetase and gamma-glutamate hydrolase (GGH), enzymes catalyzing folate polyglutamylation and hydrolysis, respectively. Upon 3-7 days of folate deprivation, semiquantitative reverse transcription-PCR analysis revealed a specific approximately 2.5-fold decrease in RFC mRNA levels in both breast cancer and T-cell leukemia cell lines that was accompanied by a consistent fall in methotrexate influx, serving here as an RFC transport activity assay. Likewise a 2.4-fold decrease in GGH mRNA levels and approximately 19% decreased GGH activity was documented for folate-deprived breast cancer cells. These results along with those of a novel mathematical biomodeling devised here suggest that upon severe short term (i.e. up to 7 days) folate deprivation RFC transport activity becomes detrimental as RFC, but not ATP-driven folate exporters, efficiently extrudes folate monoglutamates out of cells. Hence down-regulation of RFC and GGH may serve as a novel adaptive response to severe folate deficiency.

  5. Xenopus reduced folate carrier regulates neural crest development epigenetically.

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    Jiejing Li

    Full Text Available Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

  6. Reduced levels of folate transporters (PCFT and RFC) in membrane lipid rafts result in colonic folate malabsorption in chronic alcoholism.

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    Wani, Nissar Ahmad; Kaur, Jyotdeep

    2011-03-01

    We studied the effect of chronic ethanol ingestion on folate transport across the colonic apical membranes (CAM) in rats. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20%) solution orally for 3 months and folate transport was studied in the isolated colon apical membrane vesicles. The folate transport was found to be carrier mediated, saturable, with pH optima at 5.0. Chronic ethanol ingestion reduced the folate transport across the CAM by decreasing the affinity of transporters (high Km) for the substrate and by decreasing the number of transporter molecules (low Vmax) on the colon luminal surface. The decreased transport activity at the CAM was associated with down-regulation of the proton-coupled folate transporter (PCFT) and the reduced folate carrier (RFC) which resulted in decreased PCFT and RFC protein levels in the colon of rats fed alcohol chronically. Moreover, the PCFT and the RFC were found to be distributed in detergent insoluble fraction of the CAM in rats. Floatation experiments on Optiprep density gradients demonstrated the association of the PCFT and the RFC protein with lipid rafts (LR). Chronic alcoholism decreased the PCFT and the RFC protein levels in the CAM LR in accordance with the decreased synthesis. Hence, we propose that downregulation in the expression of the PCFT and the RFC in colon results in reduced levels of these transporters in colon apical membrane LR as a mechanism of folate malabsorption during chronic alcoholism.

  7. Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

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    Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

    2015-01-01

    Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

  8. Betaine and folate status as cooperative determinants of plasma homocysteine in humans.

    NARCIS (Netherlands)

    Holm, P.I.; Ueland, P.M.; Vollset, S.E.; Midttun, O.; Blom, H.J.; Keijzer, M.B.; Heijer, M. den

    2005-01-01

    OBJECTIVE: Two published studies have demonstrated that betaine in the circulation is a determinant of plasma total homocysteine, but none had sufficient power to investigate the possible effect modification by folate status. METHODS AND RESULTS: We measured homocysteine, betaine, folate, vitamin B(

  9. Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells

    DEFF Research Database (Denmark)

    Baslund, B; Gregers, J; Nielsen, Claus Henrik

    2008-01-01

    To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells.......To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells....

  10. Reduced folate carrier: biochemistry and molecular biology of the normal and methotrexate-resistant cell.

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    Bosson, Geoffrey

    2003-01-01

    The cytotoxic drug methotrexate uses the reduced folate carrier for transport into the cell, where it inhibits key enzymes in nucleotide biosynthesis. Resistance to methotrexate can be achieved by altering the genetic code of the reduced folate carrier gene and thus change the structure and function of the protein. Our understanding of RFC structure and function is based on the information gained from studying the uptake of folates and antifolates in living cells and the application of molecular techniques to determine gene expression and genetic mutations. The aim of this essay is to explain the structure and function of the reduced folate carrier, review the molecular biology of the reduced folate carrier gene and the mutations and polymorphisms that can result in methotrexate resistance.

  11. Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma.

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    Cui, Lian-Hua; Quan, Zhen-Yu; Piao, Jin-Mei; Zhang, Ting-Ting; Jiang, Meng-Hui; Shin, Min-Ho; Choi, Jin-Su

    2016-06-30

    Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients' clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15-0.60), 0.33 (0.17-0.65), and 0.19 (0.09-0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02-3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

  12. Folate bioavailability.

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    McNulty, Helene; Pentieva, Kristina

    2004-11-01

    The achievement of optimal folate status to prevent neural-tube defects, and possibly other diseases, is hindered by the well-recognised incomplete bioavailability of the natural folates found in foods compared with the synthetic vitamin, folic acid. Folate bioavailability from different foods is considered to be dependent on a number of factors, including the food matrix, the intestinal deconjugation of polyglutamyl folates, the instability of certain labile folates during digestion and the presence of certain dietary constituents that may enhance folate stability during digestion. There is conflicting evidence as to whether the extent of conjugation of polyglutamyl folate (in the absence of specific inhibitors of deconjugation in certain foods) is a limiting factor in folate bioavailability. Estimates of the extent of lower bioavailability of food folates compared with folic acid (relative bioavailability) show great variation, ranging anywhere between 10 and 98%, depending on the methodological approach used. The lack of accurate data on folate bioavailability from natural food sources is of particular concern in those countries in which there is no mandatory folic acid fortification, and therefore a greater reliance on natural food folates as a means to optimise status. Apart from the incomplete bioavailability of food folates, the poor stability of folates in foods (particularly green vegetables) under typical conditions of cooking can substantially reduce the amount of vitamin ingested and thereby be an additional factor limiting the ability of food folates to enhance folate status. A recent workshop convened by the Food Standards Agency concluded that gaining a better understanding of folate bioavailability in representative human diets is a high priority for future research.

  13. Post-transcriptional regulation of the human reduced folate carrier as a novel adaptive mechanism in response to folate excess or deficiency

    OpenAIRE

    Hou, Zhanjun; Orr, Steve; Matherly, Larry H.

    2014-01-01

    The RFC (reduced folate carrier) is the principal mechanism by which folates and clinically used antifolates are delivered to mammalian cells. hRFC (human RFC) is subject to complex transcriptional controls and exists as homo-oligomer. To explore the post-transcriptional regulation of hRFC by exogenous folates, hRFC-null HeLa cells were stably transfected with hRFC under control of a constitutive promoter. hRFC transcripts and the total membrane protein increased with increasing LCV [(6R,S)5-...

  14. High Dietary Folate in Mice Alters Immune Response and Reduces Survival after Malarial Infection.

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    Danielle N Meadows

    Full Text Available Malaria is a significant global health issue, with nearly 200 million cases in 2013 alone. Parasites obtain folate from the host or synthesize it de novo. Folate consumption has increased in many populations, prompting concerns regarding potential deleterious consequences of higher intake. The impact of high dietary folate on the host's immune function and response to malaria has not been examined. Our goal was to determine whether high dietary folate would affect response to malarial infection in a murine model of cerebral malaria. Mice were fed control diets (CD, recommended folate level for rodents or folic acid-supplemented diets (FASD, 10x recommended level for 5 weeks before infection with Plasmodium berghei ANKA. Survival, parasitemia, numbers of immune cells and other infection parameters were assessed. FASD mice had reduced survival (p<0.01, Cox proportional hazards and higher parasitemia (p< 0.01, joint model of parasitemia and survival compared with CD mice. FASD mice had lower numbers of splenocytes, total T cells, and lower numbers of specific T and NK cell sub-populations, compared with CD mice (p<0.05, linear mixed effects. Increased brain TNFα immunoreactive protein (p<0.01, t-test and increased liver Abca1 mRNA (p<0.01, t-test, a modulator of TNFα, were observed in FASD mice; these variables correlated positively (rs = 0.63, p = 0.01. Bcl-xl/Bak mRNA was increased in liver of FASD mice (p<0.01, t-test, suggesting reduced apoptotic potential. We conclude that high dietary folate increases parasite replication, disturbs the immune response and reduces resistance to malaria in mice. These findings have relevance for malaria-endemic regions, when considering anti-folate anti-malarials, food fortification or vitamin supplementation programs.

  15. Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins.

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    Noiriel, Alexandre; Naponelli, Valeria; Gregory, Jesse F; Hanson, Andrew D

    2007-03-01

    Dihydropterins are intermediates of folate synthesis and products of folate breakdown that are readily oxidized to their aromatic forms. In trypanosomatid parasites, reduction of such oxidized pterins is crucial for pterin and folate salvage. We therefore sought evidence for this reaction in plants. Three lines of evidence indicated its absence. First, when pterin-6-aldehyde or 6-hydroxymethylpterin was supplied to Arabidopsis (Arabidopsis thaliana), pea (Pisum sativum), or tomato (Lycopersicon esculentum) tissues, no reduction of the pterin ring was seen after 15 h, although reduction and oxidation of the side chain of pterin-6-aldehyde were readily detected. Second, no label was incorporated into folates when 6-[(3)H]hydroxymethylpterin was fed to cultured Arabidopsis plantlets for 7 d, whereas [(3)H]folate synthesis from p-[(3)H]aminobenzoate was extensive. Third, no NAD(P)H-dependent pterin ring reduction was found in tissue extracts. Genetic evidence showed a similar situation in Escherichia coli: a GTP cyclohydrolase I (folE) mutant, deficient in pterin synthesis, was rescued by dihydropterins but not by the corresponding oxidized forms. Expression of a trypanosomatid pterin reductase (PTR1) enabled rescue of the mutant by oxidized pterins, establishing that E. coli can take up oxidized pterins but cannot reduce them. Similarly, a GTP cyclohydrolase I (fol2) mutant of yeast (Saccharomyces cerevisiae) was rescued by dihydropterins but not by most oxidized pterins, 6-hydroxymethylpterin being an exception. These results show that the capacity to reduce oxidized pterins is not ubiquitous in folate-synthesizing organisms. If it is lacking, folate precursors or breakdown products that become oxidized will permanently exit the metabolically active pterin pool.

  16. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, I.B.; Worm, J.; Ralfkiaer, E.

    2008-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, we...

  17. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, Ingelise Bjerring; Worm, Jesper; Ralfkiaer, Elisabeth

    2007-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, we...

  18. Determinants of folate and vitamin B12 plasma levels in the French E3N-EPIC cohort.

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    de Batlle, Jordi; Matejcic, Marco; Chajes, Veronique; Moreno-Macias, Hortensia; Amadou, Amina; Slimani, Nadia; Cox, David G; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Romieu, Isabelle

    2016-12-21

    Impaired B vitamin status has been identified as a risk factor for major chronic diseases. This study aims at examining the determinants of plasma folate and vitamin B12 concentrations, considering lifestyle factors and MTHFR polymorphisms. A total of 988 women aged 40-65 years from the French E3N cohort were investigated. Intakes of folate and vitamin B12 were assessed using food frequency questionnaires, and plasma concentrations were measured by microbiological assay. Dietary scores were computed to summarize folate and vitamin B12 dietary sources. MTHFR-C677T and MTHFR-A1298C were determined by Kaspar assay. Pearson's partial correlation coefficients and multivariable linear regression models were used to assess correlations between main determinants and plasma folate and vitamin B12 levels. The partial correlation coefficient between dietary intakes and plasma folate was 0.19 (p value vitamin B12. Dietary scores were the main determinant of B vitamin plasma concentrations with a percent change per unit increase of 12.64% (p value vitamin B12. Homozygous (T/T) or heterozygous (C/T) women for MTHFR-C677T had lower plasma folate concentrations [C/T: -6.48% (p value = 0.038) and T/T: -15.89% (p value vitamin plasma concentration include: smoking status for folate, and age and hormone replacement therapy for vitamin B12. We confirmed previous findings on the role of diet as main determinant of folate and vitamin B12 plasma concentrations. However, the impact of genetic polymorphisms and lifestyle factors on plasma B vitamin concentrations should not be neglected.

  19. High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: Results from the SEARCH Database

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    Daniel M. Moreira

    2013-06-01

    Full Text Available Introduction To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH database. Materials and Methods Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed and time to biochemical recurrence were performed with Cox proportional hazards. Results The median preoperative folate level was 11.6ng/mL (reference = 1.5-20.0ng/mL. Folate levels were significantly lower among African-American men than Caucasians (P = 0.003. In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001 and lower preoperative PSA (P = 0.003. In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95%CI = 0.37-1.03, P = 0.064. After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95%CI = 0.20-0.89, P = 0.023. Conclusion In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement, these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence.

  20. A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations

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    2005-04-01

    Full Text Available Background & Aims: At least 500 μg of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 μg of folate or with one 500 μg capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p

  1. A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations.

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    Pintó, Xavier; Vilaseca, M Antonia; Balcells, Susana; Artuch, Rafael; Corbella, Emili; Meco, José F; Vila, Ramon; Pujol, Ramon; Grinberg, Daniel

    2005-01-01

    Background & Aims: At least 500 mug of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 mug of folate or with one 500 mug capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (pfoods decreased tHcy by 8.6% (95% CI: -15.9 to -1.2) and synthetic folic acid capsules by 8% (95% CI: -13.3 to -2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease.

  2. Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study

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    Wernimont Susan M

    2011-11-01

    Full Text Available Abstract Background Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. Methods 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. Results Using a nominal P ≤ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. Conclusions No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val, is predictive of cardiovascular disease biomarkers.

  3. Plasma Homocysteine, Vitamin B12 and Folate Levels in Multiple System Atrophy: A Case-Control Study.

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    Shuyu Zhang

    Full Text Available Multiple system atrophy (MSA is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine.This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression.The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05. After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01-1.13, p < 0.05 for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls.Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA.

  4. Folate: a key to optimizing health and reducing disease risk in the elderly.

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    Rampersaud, Gail C; Kauwell, Gail P A; Bailey, Lynn B

    2003-02-01

    Inadequate folate status is associated with an increased risk for chronic diseases that may have a negative impact on the health of the aging population. Folate, a water-soluble vitamin, includes naturally occurring food folate and synthetic folic acid in supplements and fortified foods. Inadequate folate status may result in hyperhomocysteinemia, a significant risk factor for atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects and increased risk for cognitive dysfunction. Folate status may be negatively influenced by inadequate intake, genetic polymorphisms and interactions with various drugs. In the US, folic acid is now added to enriched grain products and continues to be included in the majority of ready-to-eat breakfast cereals. Recent data indicate that the folate status in the US population has improved significantly, presumably due to the effects of fortification. Folic acid (not food folate) intake in excess of the Tolerable Upper Intake Level may mask the diagnosis of a vitamin B(12) deficiency, which is more prevalent in the elderly than younger individuals. When folic acid supplements are recommended, a multivitamin that includes vitamin B(12) should also be advised. To safely and effectively increase folate intake in the elderly, naturally occurring folate-rich food sources should be promoted. Folate-rich foods include orange juice, dark green leafy vegetables, asparagus, strawberries and legumes. These foods are also excellent sources of other health-promoting nutrients associated with chronic disease risk reduction.

  5. Relationship between dietary folate intake and plasma monocyte chemoattractant protein-1 and interleukin-8 in heart failure patients.

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    Chung, Hye Kyung; Kim, Oh Yoen; Lee, Hyeran; Do, Hyun Joo; Kim, Young Soon; Oh, Jaewon; Kang, Seok-Min; Shin, Min-Jeong

    2011-07-01

    This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = -0.30, pmonocyte chemoattractant protein-1 significantly correlated with dietary folate intake (r = -0.31, pmonocyte chemoattractant protein-1 (pmonocyte chemoattractant protein-1 and interleukin-8 which indicates dietary folate may have a potentially beneficial role in the prevention and treatment of heart failure.

  6. Identification of dynein light chain road block-1 as a novel interaction partner with the human reduced folate carrier.

    Science.gov (United States)

    Ashokkumar, Balasubramaniem; Nabokina, Svetlana M; Ma, Thomas Y; Said, Hamid M

    2009-09-01

    The reduced folate carrier (RFC) is a major folate transport system in mammalian cells. RFC is highly expressed in the intestine and believed to play a role in folate absorption. Studies from our laboratory and others have characterized different aspects of the intestinal folate absorption process, but little is known about possible existence of accessory protein(s) that interacts with RFC and influences its physiology and/or cell biology. We investigated this issue by employing a bacterial two-hybrid system to screen a BacterioMatch II human intestinal cDNA library using the large intracellular loop between transmembrane domains 6 and 7 of the human RFC (hRFC) as bait. Our screening has resulted in the identification of dynein light chain road block-1 (DYNLRB1) as an interacting partner with hRFC. Existence of a direct protein-protein interaction between hRFC and DYNLRB1 was confirmed by in vitro pull-down assay and in vivo mammalian two-hybrid luciferase assay and coimmunoprecipitation analysis. Furthermore, confocal imaging of live human intestinal epithelial HuTu-80 cells demonstrated colocalization of DYNLRB1 with hRFC. Coexpression of DYNLRB1 with hRFC led to a significant (P < 0.05) increase in folate uptake. On the other hand, inhibiting the endogenous DYNLRB1 with gene-specific small interfering RNA or pharmacologically with a specific inhibitor (vanadate) led to a significant (P < 0.05) decrease in folate uptake. This study demonstrates for the first time the identification of DYNLRB1 as an interacting protein partner with hRFC. Furthermore, DYNLRB1 appears to influence the function and cell biology of hRFC.

  7. Human Folate Bioavailability

    Directory of Open Access Journals (Sweden)

    Cornelia M. Witthoft

    2011-04-01

    Full Text Available The vitamin folate is recognized as beneficial health-wise in the prevention of neural tube defects, anemia, cardiovascular diseases, poor cognitive performance, and some forms of cancer. However, suboptimal dietary folate intake has been reported in a number of countries. Several national health authorities have therefore introduced mandatory food fortification with synthetic folic acid, which is considered a convenient fortificant, being cost-efficient in production, more stable than natural food folate, and superior in terms of bioavailability and bioefficacy. Other countries have decided against fortification due to the ambiguous role of synthetic folic acid regarding promotion of subclinical cancers and other adverse health effects. This paper reviews recent studies on folate bioavailability after intervention with folate from food. Our conclusions were that limited folate bioavailability data are available for vegetables, fruits, cereal products, and fortified foods, and that it is difficult to evaluate the bioavailability of food folate or whether intervention with food folate improves folate status. We recommend revising the classical approach of using folic acid as a reference dose for estimating the plasma kinetics and relative bioavailability of food folate.

  8. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population.

    Science.gov (United States)

    Ibiebele, Torukiri I; Hughes, Maria Celia; Pandeya, Nirmala; Zhao, Zhen; Montgomery, Grant; Hayward, Nick; Green, Adèle C; Whiteman, David C; Webb, Penelope M

    2011-02-01

    Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

  9. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the substantiation of a health claim related to increasing maternal folate status by supplemental folate intake and reduced risk of neural tube defects pursuant to Article 14 of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    an opinion on the scientific substantiation of a health claim related to increasing maternal folate status by supplemental folate intake and reduced risk of neural tube defects. The Panel considers that the food constituent, supplemental folate, which is the subject of the claim, is sufficiently...... characterised. Increasing maternal folate status by supplemental folate intake is a beneficial physiological effect in the context of reducing the risk of neural tube defects. In weighing the evidence, the Panel took into account that the association between low maternal folate intakes and an increased risk...... of neural tube defects is well established, and that a recent systematic review showed an effect of maternal folic acid intakes on the risk of neural tube defects. The Panel concludes that a cause and effect relationship has been established between increasing maternal folate status by supplemental folate...

  10. Methionine synthase A2756G and reduced folate carrier1 A80G ...

    African Journals Online (AJOL)

    Maha Moustafa

    2015-10-09

    Oct 9, 2015 ... folate carrier (RFC1) A80G gene polymorphisms on the maternal risk for DS. Patients: This study ..... To our knowledge, studies concerning the frequency of .... acid efficiency increases chromosomal instability, chromosome 21.

  11. Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier

    Directory of Open Access Journals (Sweden)

    Kheradpour Albert

    2008-05-01

    Full Text Available Abstract Background Methotrexate (MTX uptake is mediated by the reduced folate carrier (RFC. Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied. Methods In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8, including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines. Results A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, p Conclusion This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription.

  12. Higher maternal plasma folate but not vitamin B-12 concentrations during pregnancy are associated with better cognitive function scores in 9-10 year old children in South-India1-3

    OpenAIRE

    Sargoor R Veena; Ghattu V Krishnaveni; Srinivasan, Krishnamachari; Wills, Andrew K.; Muthayya, Sumithra; Anura V Kurpad; Yajnik, Chittaranjan S.; Fall, Caroline HD

    2010-01-01

    Folate and vitamin B-12 (B-12) are essential for normal brain development. Few studies have examined the relationship of maternal folate and B-12 status during pregnancy to offspring cognitive function. To test the hypothesis that lower maternal plasma folate and B-12 concentrations and higher plasma homocysteine concentrations during pregnancy, are associated with poorer neurodevelopment, cognitive function was assessed during 2007-2008 among 536 children (aged 9-10 y) from the Mysore Parthe...

  13. Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression

    DEFF Research Database (Denmark)

    Assies, Johanna; Mocking, Roel J T; Lok, Anja

    2015-01-01

    controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA...... between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters...

  14. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  15. Interactions between plasma concentrations of folate and markers of vitamin B12 status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

    NARCIS (Netherlands)

    Doets, E.L.; Ueland, P.M.; Tell, G.S.; Vollset, S.E.; Nygard, O.K.; Veer, van 't P.; Groot, de C.P.G.M.; Nurk, E.; Refsum, H.; Smith, A.D.; Eussen, S.J.P.M.

    2014-01-01

    A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 mark

  16. Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study

    Science.gov (United States)

    Mendonça, Nuno; Mathers, John C.; Adamson, Ashley J.; Martin-Ruiz, Carmen; Seal, Chris J.; Jagger, Carol; Hill, Tom R.

    2016-01-01

    Very old adults are at increased risk of folate and vitamin B12 deficiencies due to reduced food intake and gastrointestinal absorption. The main aim was to determine the association between folate and vitamin B12 intake from total diets and food groups, and status. Folate or vitamin B12 intakes (2 × 24 h multiple pass recalls) and red blood cell (RBC) folate or plasma vitamin B12 (chemiluminescence immunoassays) concentrations were available at baseline for 731 participants aged 85 from the Newcastle 85+ Study (North-East England). Generalized additive and binary logistic models estimated the associations between folate and vitamin B12 intakes from total diets and food groups, and RBC folate and plasma B12. Folate intake from total diets and cereal and cereal products was strongly associated with RBC folate (p < 0.001). Total vitamin B12 intake was weakly associated with plasma vitamin B12 (p = 0.054) but those with higher intakes from total diets or meat and meat products were less likely to have deficient status. Women homozygous for the FUT2 G allele had higher concentrations of plasma vitamin B12. Cereals and cereal products are a very important source of folate in the very old. Higher intakes of folate and vitamin B12 lower the risk of “inadequate” status. PMID:27690091

  17. Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study.

    Science.gov (United States)

    Mendonça, Nuno; Mathers, John C; Adamson, Ashley J; Martin-Ruiz, Carmen; Seal, Chris J; Jagger, Carol; Hill, Tom R

    2016-09-28

    Very old adults are at increased risk of folate and vitamin B12 deficiencies due to reduced food intake and gastrointestinal absorption. The main aim was to determine the association between folate and vitamin B12 intake from total diets and food groups, and status. Folate or vitamin B12 intakes (2 × 24 h multiple pass recalls) and red blood cell (RBC) folate or plasma vitamin B12 (chemiluminescence immunoassays) concentrations were available at baseline for 731 participants aged 85 from the Newcastle 85+ Study (North-East England). Generalized additive and binary logistic models estimated the associations between folate and vitamin B12 intakes from total diets and food groups, and RBC folate and plasma B12. Folate intake from total diets and cereal and cereal products was strongly associated with RBC folate (p B12 intake was weakly associated with plasma vitamin B12 (p = 0.054) but those with higher intakes from total diets or meat and meat products were less likely to have deficient status. Women homozygous for the FUT2 G allele had higher concentrations of plasma vitamin B12. Cereals and cereal products are a very important source of folate in the very old. Higher intakes of folate and vitamin B12 lower the risk of "inadequate" status.

  18. Total plasma homocysteine, folate, and vitamin b12 status in healthy Iranian adults: the Tehran homocysteine survey (2003–2004/a cross – sectional population based study

    Directory of Open Access Journals (Sweden)

    Bandarian Fatemeh

    2006-02-01

    Full Text Available Abstract Background Elevated plasma total homocysteine is an independent risk factor for cardiovascular disease and a sensitive marker of the inadequate vitamin B12 and folate insufficiency. Folate and vitamin B12 have a protective effect on cardiovascular disease. This population based study was conducted to evaluate the plasma total homocysteine, folate, and vitamin B12 in healthy Iranian individuals. Methods This study was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region of Tehran University has been designed and conducted based on the methodology of MONICA/WHO Project. A total of 1214 people aged 25–64 years, were recruited and assessed regarding demographic characteristics, homocysteine, folate, and vitamin B12 levels with interview, questionnaires, examination and blood sampling. Blood samples were gathered and analyzed according to standard methods. Results The variables were assessed in 1214 participants including 428 men (35.3% and 786 women (64.7%. Age-adjusted prevalence of hyperhomocysteinemia (Hcy≥15 μmol/L was 73.1% in men and 41.07% in women (P Conclusion These results revealed that the prevalence of hyperhomocysteinemia, low folate and vitamin B12 levels are considerably higher than other communities. Implementation of preventive interventions such as food fortification with folic acid is necessary.

  19. Plasma homocysteine in adolescents depends on the interaction between methylenetetrahydrofolate reductase genotype, lipids and folate: a seroepidemiological study

    Directory of Open Access Journals (Sweden)

    Gil Ángel

    2009-10-01

    Full Text Available Abstract Background Many publications link high homocysteine levels to cardiovascular disease. In Spain there is little information on the prevalence of hyperhomocysteinaemia and associated vitamin factors among the general population, and less still among children. Cardiovascular risk factors in the childhood population may be related to the appearance of cardiovascular disease at adult age. The aim of this study is to establish a definition of hyperhomocysteinaemia in adolescents and to analyze the influence of vitamin and metabolic factors in homocysteine levels in this population group. Methods Descriptive, cross-sectional epidemiological study to estimate serum homocysteine, vitamin B12 and folate levels, as well as plasma total, HDL- and LDL- cholesterol in a schoolgoing population aged 13 to 17 years in Madrid, Spain. Spearman correlation analysis was performed to ascertain quantitative comparison, Pearson's χ2 test (frequency Results Based on the classic values for definition of hyperhomocysteinaemia in adults, prevalence of hyperhomocysteinaemia in the study population was: 1.26% for 15 μmol/L; and 2.52% for 12 μmol/L. Deficits in HDL cholesterol and serum folate levels yielded adjusted Odds Ratios (OR for hyperhomocysteinemia of 2.786, 95% CI (1.089-7.126, and 5.140, 95% CI (2.347-11.256 respectively. Mutation of the methylenetetrahydrofolate reductase (MTHFR C677T genotype also raises the risk of hyperhomocysteinaemia (CC→CT: OR = 2.362; 95% CI (1.107-5.042 CC→TT: OR = 6.124, 95% CI (2.301-16.303 Conclusion A good definition of hyperhomocysteinaemia in adolescents is the 90th percentile, equivalent to 8.23 μmol/L. Risk factors for hyperhomocysteinaemia are cHDL and folate deficiency, and the MTHFR C677T mutant genotype. No significant effect could be assessed for vitamin B12. Coexistence of all three factors increases the risk of suffering from hyperhomocysteinaemia 87-fold.

  20. Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study.

    Science.gov (United States)

    Cabo, Rona; Hernes, Sigrunn; Slettan, Audun; Haugen, Margaretha; Ye, Shu; Blomhoff, Rune; Mansoor, M Azam

    2015-05-01

    Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

  1. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    Directory of Open Access Journals (Sweden)

    Vegard Lysne

    2015-06-01

    Full Text Available The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP, with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

  2. Modification of pLL/DNA complexes with a multivalent hydrophilic polymer permits folate-mediated targeting in vitro and prolonged plasma circulation in vivo.

    Science.gov (United States)

    Ward, Christopher M; Pechar, Michal; Oupicky, David; Ulbrich, Karel; Seymour, Leonard W

    2002-01-01

    Gene delivery vectors based on poly(L-lysine) and DNA (pLL/DNA complexes) have limited use for targeted systemic application in vivo since they bind cells and proteins non-specifically. In this study we have attempted to form folate-targeted vectors with extended systemic circulation by surface modification of pLL/DNA complexes with hydrophilic polymers. pLL/DNA complexes were stabilised by surface modification with a multivalent reactive polymer based on alternating segments of poly(ethylene glycol) and tripeptides bearing reactive ester groups. Folate moieties were incorporated into the vectors either by direct attachment of folate to the polymer or via intermediate poly(ethylene glycol) spacers of 800 and 3400 Da. Polymer-coated complexes show similar morphology to uncoated complexes, their zeta potential is decreased towards zero, serum protein binding is inhibited and aqueous solubility is substantially increased. Intravenous (i.v.) administration to mice of coated complexes produced extended systemic circulation, with up to 2000-fold more DNA measured in the bloodstream after 30 min compared with simple pLL/DNA complexes. In further contrast to simple pLL/DNA complexes, coated complexes do not bind blood cells in vivo. Folate receptor targeting is shown to mediate targeted association with HeLa cells in vitro, leading to increased transgene expression. We demonstrate for the first time that DNA uptake via the folate receptor is dependent on pEG spacer length, with the transgene expression relatively independent of the level of internalised DNA. We show increased systemic circulation, decreased blood cell and protein binding, and folate-targeted transgene expression using pLL/DNA complexes surface-modified with a novel multireactive hydrophilic polymer. This work provides the basis for the development of plasma-circulating targeted vectors for in vivo applications. Copyright 2002 John Wiley & Sons, Ltd.

  3. Folate Production by Probiotic Bacteria

    Directory of Open Access Journals (Sweden)

    Stefano Raimondi

    2011-01-01

    Full Text Available Probiotic bacteria, mostly belonging to the genera Lactobacillus and Bifidobacterium, confer a number of health benefits to the host, including vitamin production. With the aim to produce folate-enriched fermented products and/or develop probiotic supplements that accomplish folate biosynthesis in vivo within the colon, bifidobacteria and lactobacilli have been extensively studied for their capability to produce this vitamin. On the basis of physiological studies and genome analysis, wild-type lactobacilli cannot synthesize folate, generally require it for growth, and provide a negative contribution to folate levels in fermented dairy products. Lactobacillus plantarum constitutes an exception among lactobacilli, since it is capable of folate production in presence of para-aminobenzoic acid (pABA and deserves to be used in animal trials to validate its ability to produce the vitamin in vivo. On the other hand, several folate-producing strains have been selected within the genus Bifidobacterium, with a great variability in the extent of vitamin released in the medium. Most of them belong to the species B. adolescentis and B. pseudocatenulatum, but few folate producing strains are found in the other species as well. Rats fed a probiotic formulation of folate-producing bifidobacteria exhibited increased plasma folate level, confirming that the vitamin is produced in vivo and absorbed. In a human trial, the same supplement raised folate concentration in feces. The use of folate-producing probiotic strains can be regarded as a new perspective in the specific use of probiotics. They could more efficiently confer protection against inflammation and cancer, both exerting the beneficial effects of probiotics and preventing the folate deficiency that is associated with premalignant changes in the colonic epithelia.

  4. Salicylic acid-induced elicitation of folates in coriander (Coriandrum sativum L.) improves bioaccessibility and reduces pro-oxidant status.

    Science.gov (United States)

    Puthusseri, Bijesh; Divya, Peethambaran; Lokesh, Veeresh; Neelwarne, Bhagyalakshmi

    2013-01-15

    Foliage of Coriandrum sativum is a rich source of natural folates amenable for enhancement through salicylic acid-mediated elicitation, thereby holding a great promise for natural-mode alleviation of this vitamin (B(9)) deficiency. In the present study we report salicylic acid-mediated differential elicitation of different forms of folates - 5-methyltetrahydrofolate, 5-formyltetrahydrofolate and 10-formyltetrahydrofolate - their stabilities during microwave-drying and bioaccessibilities from fresh and dried foliage. The first two compounds nearly doubled and the third increased sixfold post-elicitation, with all three showing concomitant increase in bioaccessibilities. Although a slight decrease in bioaccessibility was observed in dried foliage, over twofold increase of each form of folate upon elicitation would deliver much higher levels of natural folates from this traditional culinary foliage, which is widely used in many cuisines. Elicitor-mediated folate enhancement also imparted reduction of oxidative status and the enhancement of antioxidant enzyme activities in coriander foliage.

  5. A U-shaped association between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition

    Science.gov (United States)

    Chuang, Shu-Chun; Stolzenberg-Solomon, Rachael; Ueland, Per Magne; Vollset, Stein Emil; Middtun, Øivind; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Morois, Sophie; Clavel-Chapelon, Franςoise; Teucher, Brigit; Kaaks, Rudolf; Weikert, Cornelia; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Naska, Androniki; Jenab, Mazda; Slimani, Nadia; Romieu, Isabelle; Michaud, Dominique S.; Palli, Domenico; Sabina, Sieri; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Skeie, Guri; Duell, Eric J.; Rodriguez, Laudina; Molina-Montes, Esther; Huerta, José Marí; Larrañaga, Nerea; Gurrea, Aurelio Barricarte; Johansen, Dorthe; Manjer, Jonas; Ye, Weimin; Sund, Malin; Peeters, Petra HM; Jeumink, Suzanne; Wareham, Nicholas; Khaw, Kay-Tee; Crowe, Francesca; Riboli, Elio; Bueno-de-Mesquita, Bas; Vineis, Paolo

    2012-01-01

    Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5′-phosphate, riboflavin, and flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992–2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/−1y), date (+/−1y) and time (+/−3h) at blood collection, and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk The ORs for plasma folate ≤5, 5–10, 10–15 (reference), 15–20, and >20 nmol/L were 1.6 (95% CI=0.7–3.5), 1.4 (0.9–2.1), 1.0 (reference), 0.8 (0.5–1.2), and 1.3 (0.9–2.0), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.2 95% CI=1.0–1.4) but not in women (OR=0.9, 95% CI=0.8–1.1; p for heterogeneity<0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation. PMID:21411310

  6. Experimental maternal and neonatal folate status relationships in nonhuman primates.

    Science.gov (United States)

    Blocker, D E; Ausman, L M; Meadows, C A; Thenen, S W

    1989-07-01

    The influence of maternal dietary folic acid intake on folate status was studied in Cebus albifrons monkeys by feeding 10 or 250 micrograms/100 kcal dietary folic acid during pregnancy and 4 wk postpartum. Maternal, infant, and nonpregnant hematologic indices; blood and liver folate concentrations; and urinary formiminoglutamic acid excretion all varied with dietary folate intake and pregnancy status as did milk folate concentration in lactating dams. Maternal folate status, determined by plasma, red blood cell, and milk folate concentrations, as well as urinary formiminoglutamic acid excretion, all were correlated significantly with liver folate concentrations in neonates (r = 0.740, r = 0.919, r = 0.936, and r = -0.851, respectively). Results in these primates showed that neonatal folate status was related significantly to the dietary folate intake and folate status of the mother during pregnancy and lactation.

  7. Plasma Levels of Folates, Riboflavin, Vitamin B6, and Ascorbate in Severely Disturbed Children.

    Science.gov (United States)

    Sankar, D. V. Siva

    1979-01-01

    The plasma levels of folic acid, ascorbic acid, pyridoxine, and riboflavin were studied in 125 severely emotionally disturbed children (ages 5-16 years) to determine whether they had overt vitamin deficiencies. (Author/DLS)

  8. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate status.

    Science.gov (United States)

    Katre, Prachi; Bhat, Dattatray; Lubree, Himangi; Otiv, Suhas; Joshi, Suyog; Joglekar, Charudatta; Rush, Elaine; Yajnik, Chittaranjan

    2010-01-01

    Maternal vitamin B12 deficiency and hyperhomocysteinemia predict poor pregnancy outcome, foetal adiposity and insulin resistance. In India amongst practicing clinicians and policy makers there is little appreciation of widespread vitamin B12 deficiency. We investigated 163 (86 rural, 77 urban) pregnant women attending antenatal clinics in a rural health centre and a referral hospital in the city of Pune, at 17, 28, and 34 weeks gestation for vitamin supplements, and circulating concentrations of vitamin B12, folate, and total homocysteine. At enrolment 80% rural and 65% urban women had low vitamin B12 but only two rural women had low folate concentrations. During pregnancy 85% rural and 95% of urban women received folic acid; 12% rural and 84% urban women also received vitamin B12. In women receiving no supplementation (n=17) plasma vitamin B12 and folate did not change from 17 to 34 weeks gestation, but homocysteine increased (pHomocysteine concentrations at 34 weeks gestation in women receiving only folic acid (n=71, mean 8.4 (95% CI 7.8, 9.1) micromol/L) were comparable to the unsupplemented group (9.7 (7.3, 12.7), p=0.15), but women who received a total dose of >1000 microg of vitamin B12 up to 34 weeks (n=42, all with folic acid) had lower concentrations (6.7 (6.0, 7.4), phomocysteine concentration. In vitamin B12 insufficient, folate replete pregnant women, vitamin B12 supplementation is associated with a reduction of plasma total homocysteine concentration in late pregnancy.

  9. Folate Intake and Markers of Folate Status in Women of Reproductive Age, Pregnant and Lactating Women: A Meta-Analysis

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    Cristiana Berti

    2012-01-01

    Full Text Available Background. Pregnant and breastfeeding women are at risk for folate deficiency. Folate supplementation has been shown to be associated with enhanced markers of folate status. However, dose-response analyses for adult women are still lacking. Objective. To assess the dose-response relationship between total folate intake (folic acid plus dietary folate and markers of folate status (plasma/serum folate, red blood cell folate, and plasma homocysteine; to evaluate potential differences between women in childbearing age, pregnant and lactating women. Methods. Electronic literature searches were carried out on three databases until February 2010. The overall pooled regression coefficient (β and SE(β were calculated using meta-analysis on a double-log scale. Results. The majority of data was based on nonpregnant, nonlactating women in childbearingage. The pooled estimate of the relationship between folate intake and serum/plasma folate was 0.56 (95% CI = 0.40–0.72, P<0.00001; that is, the doubling of folate intake increases the folate level in serum/plasma by 47%. For red blood cell folate, the pooled-effect estimate was 0.30 (95% CI = 0.22–0.38, P<0.00001, that is, +23% for doubling intake. For plasma-homocysteine it was –0.10 (95% = –0.17 to –0.04, P=0.001, that is, –7% for doubling the intake. Associations tended to be weaker in pregnant and lactating women. Conclusion. Significant relationships between folate intake and serum/plasma folate, red blood cell folate, and plasma homocysteine were quantified. This dose-response methodology may be applied for setting requirements for women in childbearing age, as well as for pregnant and lactating women.

  10. EE-drospirenone-levomefolate calcium versus EE-drospirenone + folic acid: folate status during 24 weeks of treatment and over 20 weeks following treatment cessation

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    Diefenbach K

    2013-04-01

    Full Text Available Konstanze Diefenbach,1 Dietmar Trummer,1 Frank Ebert,1 Michael Lissy,2 Manuela Koch,2 Beate Rohde,1 Hartmut Blode3 1Bayer HealthCare Pharmaceuticals, Berlin, Germany; 2Nuvisan GmbH, Neu-Ulm, Germany; 3Bayer HealthCare Pharmaceuticals Global R&D Center, Beijing, People's Republic of China Background: Adequate folate supplementation in the periconceptional phase is recommended to reduce the risk of neural tube defects. Oral contraceptives may provide a reasonable delivery vehicle for folate supplementation before conception in women of childbearing potential. This study aimed to demonstrate that a fixed-dose combination of an oral contraceptive and levomefolate calcium leads to sustainable improvements in folate status compared with an oral contraceptive + folic acid. Methods: This was a double-blind, randomized, parallel-group study in which 172 healthy women aged 18–40 years received ethinylestradiol (EE-drospirenone-levomefolate calcium or EE-drospirenone + folic acid for 24 weeks (invasion phase, and EE-drospirenone for an additional 20 weeks (folate elimination phase. The main objective of the invasion phase was to examine the area under the folate concentration time-curve for plasma and red blood cell (RBC folate, while the main objective of the elimination phase was to determine the duration of time for which RBC folate concentration remained ≥ 906 nmol/L after cessation of EE-drospirenone-levomefolate calcium. Results: Mean concentration-time curves for plasma folate, RBC folate, and homocysteine were comparable between treatment groups during both study phases. During the invasion phase, plasma and RBC folate concentrations increased and approached steady-state after about 8 weeks (plasma or 24 weeks (RBC. After cessation of treatment with levomefolate calcium, folate concentrations decreased slowly. The median time to RBC folate concentrations falling below 906 nmol/L was 10 weeks (95% confidence interval 8–12 weeks after cessation

  11. [Folic acid reduces the risk of neural tube defects: awareness and folate intake among pregnant women in 2006].

    Science.gov (United States)

    Kondo, Atsuo; Shimosuga, Yoichi; Oguchi, Hidenori; Shibata, Kanemitsu; Kurauchi, Osamu; Ichiko, Satoshi; Inoue, Hiromi; Tada, Katsuhiko; Yamada, Manshou; Kaseki, Nariaki; Narita, Osamu; Kusanishi, Hiroshi; Yamada, Yoshitaka; Yamamoto, Shin-Ichi; Ooura, Kuniaki; Takemura, Masahiko; Watanabe, Takanori; Ishihara, Osamu; Takeda, Akihiro; Watanabe, Junichiro; Wakita, Katsuji; Itoh, Kunihiko; Katoh, Sentoyo; Koyama, Masayasu; Oota, Shunji; Ninomiya, Keiu; Matsuzawa, Katsuji; Hujishima, Yoshiko; Ishida, Shoutarou; Okai, Ikuyo; Hayakawa, Chisa; Gotoh, Tohru

    2008-08-01

    Folic acid plays an important role in proliferating cells and tissues of the fetus. A randomized control trial demonstrated in 1991 that 4 mg of folic acid supplements successfully prevented 72% of recurrence of neural tube defects (NTDs) in women who had had afflicted pregnancy. In 2000, the Japanese Government recommended women of childbearing age to take 400 microgram of folate supplements per day from 4 weeks prior to and 12 weeks after conception. A questionnaire study was performed in pregnant women by post on their awareness of the role folic acid plays, their life style, and folate intake by dietary consumption. Thirty-five percent of 1,251 pregnant women were aware of the important role of folic acid in the critical stage of fetal development and 31% actually took the supplement. Information on folic acid was obtained through mass media in 47% of the women, through the internet in 17%, through healthcare providers in 13% and so forth. The food record analysis revealed that the dietary intake of folic acid averaged 341 microg/day that was 60 microg less than what was recommended by the Government and that 33 of 86 women took the supplement. Overall, a half of pregnant women are required to take 400 microg folate supplement per day. It is to be stressed that primary prevention of NTDs by periconceptional intake of folic acid is a major public health opportunity and that prevention is more important than cure in the management of NTDs.

  12. Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2R, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults.

    Science.gov (United States)

    Using linear regression models, we studied the main and two-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma homocysteine normalized by red blood cell...

  13. Cognitive Impairment in Folate-Deficient Rats Corresponds to Depleted Brain Phosphatidylcholine and Is Prevented by Dietary Methionine without Lowering Plasma Homocysteine12

    OpenAIRE

    Troen, Aron M.; Chao, Wei-Hsun; Crivello, Natalia A.; D'Anci, Kristen E.; Shukitt-Hale, Barbara; Don E Smith; Selhub, Jacob; Rosenberg, Irwin H

    2008-01-01

    Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for...

  14. Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression: Implications for co-morbidity with cardiovascular disease.

    Science.gov (United States)

    Assies, Johanna; Mocking, Roel J T; Lok, Anja; Koeter, Maarten W J; Bockting, Claudi L H; Visser, Ieke; Pouwer, François; Ruhé, Henricus G; Schene, Aart H

    2015-10-30

    Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD.

  15. Plasma gelsolin is reduced in trauma patients

    DEFF Research Database (Denmark)

    Dahl, B; Schiødt, F V; Ott, P

    1999-01-01

    in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase...... after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20......-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P

  16. Plasma gelsolin is reduced in trauma patients

    DEFF Research Database (Denmark)

    Dahl, B; Schiødt, F V; Ott, P

    1999-01-01

    in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase...... after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20......-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P

  17. Endocytosis of GPI-linked membrane folate receptor-alpha.

    Science.gov (United States)

    Rijnboutt, S; Jansen, G; Posthuma, G; Hynes, J B; Schornagel, J H; Strous, G J

    1996-01-01

    GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36-38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae.

  18. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity

    Energy Technology Data Exchange (ETDEWEB)

    Fenech, Michael, E-mail: michael.fenech@csiro.au [CSIRO Food and Nutritional Sciences, PO Box 10041 Adelaide BC, SA 5000 (Australia)

    2012-05-01

    Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100 nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700 nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300 pmol/L and plasma homocysteine is less than 7.5 {mu}mol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400 {mu}g/day) and vitamin B12 (i.e. >2 {mu}g/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences.

  19. Folate and homocysteine levels in pregnancy.

    Science.gov (United States)

    Megahed, M A; Taher, I M

    2004-01-01

    This study aims to determine serum folate and plasma homocysteine levels in healthy pregnant women following a live birth and compare them with healthy non-pregnant women. Fifty healthy gravid multiparous women are included in the study and 25 normal non-pregnant female subjects act as controls (group I). The pregnant women are divided into two groups according to interpregnancy interval: group II (six months or less); group III (18-24 months). Venous blood samples are analysed for red blood cell folate and homocysteine, vitamin B12, serum folate and albumin, and serum aminotransferases (ALT and AST). There was a significant decrease in red cell folate and serum folate in group II compared to the control group (Phomocysteine and serum albumin showed significant decreases in both groups II and III compared to the control group. (Phomocysteine and serum albumin in the three studied groups. (r=0.42, Phomocysteine in the three studied groups. (r=-0.48, Ppregnant females with short interpregnancy intervals are more likely to develop folate deficiency. Educational strategies are required to increase folate awareness among women to promote the benefits of folic acid supplementation. Mandatory folate fortification of foods should be defined and monitored.

  20. Reduced-folate carrier (RFC is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart

    Directory of Open Access Journals (Sweden)

    Prasad Puttur

    2003-07-01

    Full Text Available Abstract Background Folate is essential for cellular proliferation and tissue regeneration. As mammalian cells cannot synthesize folates de novo, tightly regulated cellular uptake processes have evolved to sustain sufficient levels of intracellular tetrahydrofolate cofactors to support biosynthesis of purines, pyrimidines, and some amino acids (serine, methionine. Though reduced-folate carrier (RFC is one of the major proteins mediating folate transport, knowledge of the developmental expression of RFC is lacking. We utilized in situ hybridization and immunolocalization to determine the developmental distribution of RFC message and protein, respectively. Results In the mouse, RFC transcripts and protein are expressed in the E10.0 placenta and yolk sac. In the E9.0 to E11.5 mouse embryo RFC is widely detectable, with intense signal localized to cell populations in the neural tube, craniofacial region, limb buds and heart. During early development, RFC is expressed throughout the eye, but by E12.5, RFC protein becomes localized to the retinal pigment epithelium (RPE. Conclusions Clinical studies show a statistical decrease in the number of neural tube defects, craniofacial abnormalities, cardiovascular defects and limb abnormalities detected in offspring of female patients given supplementary folate during pregnancy. The mechanism, however, by which folate supplementation ameliorates the occurrence of developmental defects is unclear. The present work demonstrates that RFC is present in placenta and yolk sac and provides the first evidence that it is expressed in the neural tube, craniofacial region, limb buds and heart during organogenesis. These findings suggest that rapidly dividing cells in the developing neural tube, craniofacial region, limb buds and heart may be particularly susceptible to folate deficiency.

  1. Influence of folic acid-fortified foods on folate status in a folate depletion-repletion rat model.

    Science.gov (United States)

    O'Leary, K; Sheehy, P J

    2001-04-01

    An increasing number of foods fortified with varying levels of folic acid are appearing in the market place, targeted either at the general population or at specific consumer groups. Although it is assumed that the folate in these products should be highly bioavailable, there is a need to carry out studies to ascertain that this is, in fact, the case. The present study investigated the ability of selected folic acid-fortified foods (targeted at different types of consumer) to increase the folate status of folate-deficient rats. Forty-two weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1 % succinyl sulfathiazole (w/w) for 28 d. Following depletion, seven rats were randomly assigned to each of five repletion diets containing folic acid, Complan, Slim Fast, Opti-Fuel2 or Cola Coa calculated to provide 200 microg folate/kg of each diet. Calculations were based on folate information from the product labels. After a further 28 d, plasma, liver and kidney folate concentrations were determined by microbiological assay. Plasma homocysteine was measured by HPLC as a functional indicator of folate status. The folate content of the foods was measured by tri-enzyme extraction followed by microbiological assay. Our analyses suggest that there may be considerable inaccuracies on the part of the manufacturers in relation to the folate declarations on the product labels. Despite this, the four foods evaluated were highly effective in elevating plasma, liver and kidney folate and lowering plasma homocysteine concentrations in rats. These results lend support to the policy of food fortification with folic acid as a means of raising the folate status of the population, and in particular to the fortification of specific foods which may target areas of the population where increased folate status is most needed.

  2. Folate-deficiency anemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  3. How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study

    Directory of Open Access Journals (Sweden)

    Sherwood Kelly L

    2007-10-01

    Full Text Available Abstract Background In 1998, mandatory folic acid fortification of white flour and select cereal grain products was implemented in Canada with the intention to increase dietary folate intakes of reproducing women. Folic acid fortification has produced a dramatic increase in blood folate concentrations among reproductive age women, and a reduction in neural tube defect (NTD-affected pregnancies. In response to improved blood folate concentrations, many health care professionals are asking whether a folic acid supplement is necessary for NTD prevention among women with high blood folate values, and how reliably high RBC folate concentrations predict folate intakes shown in randomized controlled trials to be protective against NTDs. The objective of this study was to determine how predictive blood folate concentrations and folate intakes are of each other in a sample of well-educated lactating Canadian women exposed to high levels of synthetic folate. Methods The relationship between blood folate concentrations and dietary folate intakes, determined by weighed food records, were assessed in a sample of predominantly university-educated lactating women (32 ± 4 yr at 4-(n = 53 and 16-wk postpartum (n = 55. Results Median blood folate concentrations of all participants were well above plasma and RBC folate cut-off levels indicative of deficiency (6.7 and 317 nmol/L, respectively and all, except for 2 subjects, were above the cut-off for NTD-risk reduction (>906 nmol/L. Only modest associations existed between total folate intakes and plasma (r = 0.46, P P nd quartile of intake did not differ from that of women consuming >410 μg/d (3rd and 4th quartile. Conclusion Folate intakes, estimated by food composition tables, and blood folate concentrations are not predictive of each other in Canadian lactating women exposed to high levels of folate. Synthetic intakes > 151–410 μg/d in these women produced little additional benefit in terms of maximizing

  4. Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status

    NARCIS (Netherlands)

    Smulders, Y.M.; Smith, D.E.C.; Kok, R.M.; Teerlink, T.; Gellekink, H.; Vaes, W.H.J.; Stehouwer, C.D.A.; Jakobs, C.

    2007-01-01

    Background: Red blood cells (RBCs) represent a storage pool for folate. In contrast to plasma, RBC folate can appear in different biochemical isoforms. So far, only the methylenetetrahydrofolate reductase (MTHFR) 677 TT genotype has been identified as a determinant of RBC folate vitamer

  5. A comparison of folate status in women of child-bearing age in Korea and in the United States

    Directory of Open Access Journals (Sweden)

    Hyun T

    2012-07-01

    Full Text Available Taisun Hyun,1 Suguna Badiga,2 Han Byul Jang,1 Young-Hee Han,1 Chandrika J Piyathilake21Department of Food and Nutrition, Chungbuk National University, Cheongju, Korea; 2Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USABackground: Even though several studies have demonstrated that periconceptional supplementation with folic acid (FA reduces the occurrence of neural tube defects, FA fortification has been a topic of intense debate due to the possible adverse effects of higher folate status on several health conditions. Several countries, including Korea, have been indecisive as to whether fortification is warranted or not. It is therefore helpful for these countries to compare folate concentrations in their populations with populations exposed to mandatory FA fortification.Purpose: To evaluate the differences in the distribution of circulating concentrations of folate in Korea and the United States (US at different time points.Methods: The Korean study populations consisted of women of child-bearing age recruited in 1999 and in 2009. The US study populations consisted of women of child-bearing age recruited in the post FA fortification era (2005 and 2009. Plasma and red blood cell (RBC folate concentrations were measured using the Lactobacillus casei microbiological assay.Results: The percentage of US women with neural tube defect-protective levels of RBC folate was significantly higher compared to Korean women in 1999 and 2009. However, in 2009, when FA supplements became readily available for Koreans, 50% of Korean women in the study achieved the neural tube defect-protective level of RBC folate; 11% of them demonstrating supraphysiologic concentrations of plasma folate. Even though FA fortification in the US resulted in more than 80of women achieving >400 ng/mL of RBC folate by 2009, nearly 50% also demonstrated having supraphysiologic concentrations of plasma folate, which prompted some researchers to

  6. Dietary folate and folate vitamers and the risk of pancreatic cancer in the Netherlands cohort study

    NARCIS (Netherlands)

    Keszei, A.P.; Verhage, B.A.J.; Heinen, M.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between di

  7. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

    Science.gov (United States)

    Cario, Holger; Smith, Desirée E C; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-02-11

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Folate and Cancer

    Directory of Open Access Journals (Sweden)

    Luciana Yuki Tomita PhD

    2016-07-01

    Full Text Available Folate plays a central role in DNA synthesis and methylation, which are essential for DNA integrity maintenance and gene expression. Folate deficiency may lead to the incorporation of uracil into DNA and chromosome breaks, increasing the risk of cancer. However, conflicting evidence has been observed depending on the type of epidemiological study, dietary or circulating folate, and the type of cancer. New concern has arisen after a mandatory folic acid (FA fortification program adopted for the prevention of neural tube defects in the United States, which suggested an increase in the incidence of colorectal cancer. In the present article, folate status and cancer are under review, and a discussion of the challenge of assessing folate status through food intake, supplement use, FA fortification programs, circulating folate, and the interaction of diet and the polymorphism of the enzyme involved in folate metabolism will be presented.

  9. Assessing the Association between Natural Food Folate Intake and Blood Folate Concentrations: A Systematic Review and Bayesian Meta-Analysis of Trials and Observational Studies

    Directory of Open Access Journals (Sweden)

    Claire M. Marchetta

    2015-04-01

    Full Text Available Folate is found naturally in foods or as synthetic folic acid in dietary supplements and fortified foods. Adequate periconceptional folic acid intake can prevent neural tube defects. Folate intake impacts blood folate concentration; however, the dose-response between natural food folate and blood folate concentrations has not been well described. We estimated this association among healthy females. A systematic literature review identified studies (1 1992–3 2014 with both natural food folate intake alone and blood folate concentration among females aged 12–49 years. Bayesian methods were used to estimate regression model parameters describing the association between natural food folate intake and subsequent blood folate concentration. Seven controlled trials and 29 observational studies met the inclusion criteria. For the six studies using microbiologic assay (MA included in the meta-analysis, we estimate that a 6% (95% Credible Interval (CrI: 4%, 9% increase in red blood cell (RBC folate concentration and a 7% (95% CrI: 1%, 12% increase in serum/plasma folate concentration can occur for every 10% increase in natural food folate intake. Using modeled results, we estimate that a natural food folate intake of ≥450 μg dietary folate equivalents (DFE/day could achieve the lower bound of an RBC folate concentration (~1050 nmol/L associated with the lowest risk of a neural tube defect. Natural food folate intake affects blood folate concentration and adequate intakes could help women achieve a RBC folate concentration associated with a risk of 6 neural tube defects/10,000 live births.

  10. Folate Deficiency Is Prevalent in Women of Childbearing Age in Belize and Is Negatively Affected by Coexisting Vitamin B-12 Deficiency: Belize National Micronutrient Survey 2011.

    Science.gov (United States)

    Rosenthal, Jorge; Largaespada, Natalia; Bailey, Lynn B; Cannon, Michael; Alverson, C J; Ortiz, Dayrin; Kauwell, Gail Pa; Sniezek, Joe; Figueroa, Ramon; Daly, Robyn; Allen, Peter

    2017-06-01

    Background: Folate deficiency, vitamin B-12 deficiency, and anemia can have adverse effects on birth outcomes. Also, low vitamin B-12 reduces the formation of metabolically active folate.Objectives: We sought to establish the baseline prevalence of and factors associated with folate deficiency and insufficiency, vitamin B-12 deficiency, and anemia among women of childbearing age (WCBA) in Belize.Methods: In 2011, a national probability-based survey was completed among Belizean nonpregnant WCBA aged 15-49 y. Blood samples for determination of hemoglobin, folate (RBC and serum), and vitamin B-12 (plasma) and sociodemographic and health information were collected from 937 women. RBC and serum folate concentrations were measured by microbiologic assay (MBA). Folate status was defined based on both the WHO-recommended radioproteinbinding assay and the assay adjusted for the MBA.Results: The national prevalence estimates for folate deficiency in WCBA, based on serum and RBC folate concentrations by using the assay-matched cutoffs, were 11.0% (95% CI: 8.6%, 14.0%) and 35.1% (95% CI: 31.3%, 39.2%), respectively. By using the assay-matched compared with the WHO-recommended cutoffs, a substantially higher prevalence of folate deficiency was observed based on serum (6.9% absolute difference) and RBC folate (28.9% absolute difference) concentrations. The prevalence for RBC folate insufficiency was 48.9% (95% CI: 44.8%, 53.1%). Prevalence estimates for vitamin B-12 deficiency and marginal deficiency and anemia were 17.2% (95% CI: 14.2%, 20.6%), 33.2% (95% CI: 29.6%, 37.1%), and 22.7% (95% CI: 19.5%, 26.2%), respectively. The adjusted geometric means of the RBC folate concentration increased significantly (P-trend vitamin B-12 status relative to WCBA who were vitamin B-12 deficient.Conclusions: In Belize, the prevalence of folate and vitamin B-12 deficiencies continues to be a public health concern among WCBA. Furthermore, low folate status co-occurred with low vitamin B-12

  11. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  12. DECREASED LEVELS OF FOLATE RECEPTOR-β AND REDUCED NUMBERS OF FETAL MACROPHAGES (HOFBAUER CELLS) IN PLACENTAS FROM PREGNANCIES WITH SEVERE PREECLAMPSIA (PE)*

    Science.gov (United States)

    Tang, Zhonghua; Buhimschi, Irina A.; Buhimschi, Catalin S.; Tadesse, Serkalem; Norwitz, Errol; Niven-Fairchild, Tracy; Huang, Se-Te J; Guller, Seth

    2013-01-01

    Problem Preeclampsia (PE), a pregnancy complication of unknown etiology, is a major cause of maternal and fetal mortality and morbidity. Previous studies have described placental genes which are up-regulated in expression in PE, but few studies have addressed placental gene suppression in this syndrome. Method of Study Gene profiling and quantitative reverse transcription PCR (qRTPCR) analyses were used to identify genes down-regulated in placentas from women with severe preterm PE compared to gestational age-matched normotensive controls with spontaneous preterm birth (sPTB). Western blotting and immunohistochemistry were used to evaluate levels and patterns of cell type-specific protein expression in PE and sPTB group placentas. Results Levels of macrophage marker [folate receptor (FR)-β, CD163, and CD68] mRNA and FR-β protein were significantly down-regulated in PE group placentas compared to the sPTB group. Numbers of Hofbauer cells (HBCs, fetal macrophages) and FR-β protein in these cells were reduced in PE group placentas. Conclusion Severe PE is associated with decreased placental expression of FR-β and a reduction in the number of HBCs. Reduced placental macrophage function is likely to play a key role in the pathophysiology of PE. PMID:23480364

  13. Reducing Plasma Perturbations with Segmented Metal Shielding on Electrostatic Probes

    Energy Technology Data Exchange (ETDEWEB)

    Staack, D.; Raitses, Y.; Fisch N.J.

    2002-10-02

    Electrostatic probes are widely used to measure spatial plasma parameters in the quasi-neutral plasma created in Hall thrusters and similar E x B electric discharge devices. Significant perturbations of the plasma, induced by such probes, can mask the actual physics involved in operation of these devices. In an attempt to reduce these perturbations in Hall thrusters, the perturbations were examined by varying the component material, penetration distance, and residence time of various probe designs. This study leads us to a conclusion that secondary electron emission from insulator ceramic tubes of the probe can affect local changes of the plasma parameters causing plasma perturbations. A probe design, which consists of a segmented metal shielding of the probe insulator, is suggested to reduce these perturbations. This new probe design can be useful for plasma applications in which the electron temperature is sufficient to produce secondary electron emission by interaction of plasma electrons with dielectric materials.

  14. The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis.

    Science.gov (United States)

    Coppedè, Fabio; Lorenzoni, Valentina; Migliore, Lucia

    2013-07-05

    A common polymorphism (c.80A>G) in the gene coding for the reduced folate carrier (SLC19A1, commonly known as RFC-1) has been associated with maternal risk of the birth of a child with Down Syndrome (DS), but results are controversial. We searched major online databases to identify available case-control studies, and performed a meta-analysis to summarize the data concerning this association. Nine independent case-control studies were identified for a total of 930 DS mothers (MDS) and 1240 control mothers. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using both fixed and random effects models. An increase in the risk of having a birth with DS was observed for carriers of the homozygous GG genotype (OR 1.27, 95% CI 1.04-1.57; p = 0.02, fixed effects model), even after removal from the meta-analysis of published data with deviations from Hardy-Weinberg equilibrium (HWE) in controls (OR 1.26, 95% CI 1.02-1.55; p = 0.03, fixed effects model). Moreover, the pooled OR under the fixed effects model showed an increase in the maternal risk for the G allele (OR 1.14, 95% CI 1.01-1.30; p = 0.03). Present results suggest that the maternal RFC-1 80A>G polymorphism might be associated with an increased risk of having a birth with DS, particularly among carriers of the GG genotype.

  15. Genetic associations with plasma B12, B6, and folate levels in an ischemic stroke population from the Vitamin Intervention for Stroke Prevention (VISP trial

    Directory of Open Access Journals (Sweden)

    Keith L Keene

    2014-08-01

    Full Text Available B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP trial, a clinical trial designed to determine whether the daily intake of high dose folic acid, vitamins B6 and B12 reduce recurrent cerebral infarction. Extensive quality control (QC measures resulted in a total of 737,081 SNPs for analysis. Genome-wide association analyses for baseline quantitative measures of folate, Vitamins B12 and B6 were completed using linear regression approaches, implemented in PLINK. Six associations met or exceeded genome wide significance (P≤5x10-08. For baseline Vitamin B12, the strongest association was observed with a non-synonymous SNP (nsSNP located in the CUBN gene (P=1.76×10-13. Two additional CUBN intronic SNPs demonstrated strong associations with B12 (P= 2.92×10-10 and 4.11×10-10, while a second nsSNP, located in the TCN1 gene, also reached genome-wide significance (P= 5.148×10-11. For baseline measures of Vitamin B6, we identified genome-wide significant associations for SNPs at the ALPL locus (rs1697421; P= 7.06×10-10 and rs1780316; P= 2.25×10-08. In addition to the six genome-wide significant associations, nine SNPs (two for Vitamin B6, six for Vitamin B12, and one for folate measures provided suggestive evidence for association (P≤10-07. Our GWAS study has identified six genome-wide significant associations, nine suggestive associations, and successfully replicated five of 16 SNPs previously reported to be associated with measures of B vitamins. The six genome-wide significant associations are located in gene regions that have shown previous associations with measures of B vitamins, however four of the nine suggestive associations represent novel finding and warrant further investigation in

  16. Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

    Science.gov (United States)

    Iglesia, I; Huybrechts, I; González-Gross, M; Mouratidou, T; Santabárbara, J; Chajès, V; González-Gil, E M; Park, J Y; Bel-Serrat, S; Cuenca-García, M; Castillo, M; Kersting, M; Widhalm, K; De Henauw, S; Sjöström, M; Gottrand, F; Molnár, D; Manios, Y; Kafatos, A; Ferrari, M; Stehle, P; Marcos, A; Sánchez-Muniz, F J; Moreno, L A

    2017-01-01

    This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

  17. The Reduced Folate Carrier (RFC-1 80A>G Polymorphism and Maternal Risk of Having a Child with Down Syndrome: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lucia Migliore

    2013-07-01

    Full Text Available A common polymorphism (c.80A>G in the gene coding for the reduced folate carrier (SLC19A1, commonly known as RFC-1 has been associated with maternal risk of the birth of a child with Down Syndrome (DS, but results are controversial. We searched major online databases to identify available case-control studies, and performed a meta-analysis to summarize the data concerning this association. Nine independent case-control studies were identified for a total of 930 DS mothers (MDS and 1240 control mothers. Odds ratios (OR and 95% confidence intervals (CI were calculated using both fixed and random effects models. An increase in the risk of having a birth with DS was observed for carriers of the homozygous GG genotype (OR 1.27, 95% CI 1.04–1.57; p = 0.02, fixed effects model, even after removal from the meta-analysis of published data with deviations from Hardy-Weinberg equilibrium (HWE in controls (OR 1.26, 95% CI 1.02–1.55; p = 0.03, fixed effects model. Moreover, the pooled OR under the fixed effects model showed an increase in the maternal risk for the G allele (OR 1.14, 95% CI 1.01–1.30; p = 0.03. Present results suggest that the maternal RFC-1 80A>G polymorphism might be associated with an increased risk of having a birth with DS, particularly among carriers of the GG genotype.

  18. Sex Differences in mRNA Expression of Reduced Folate Carrier-1, Folypolyformyl Glutamate Synthase, and γ-Glutamyl Hydrolase in a Healthy Japanese Population.

    Science.gov (United States)

    Hashiguchi, Masayuki; Tanaka, Takanori; Shimizu, Mikiko; Tsuru, Tomomi; Chiyoda, Takeshi; Miyawaki, Kumika; Irie, Shin; Takeuchi, Osamu; Hakamata, Jun; Mochizuki, Mayumi

    2016-12-01

    Sex differences in the prevalence of autoimmune diseases such as rheumatoid arthritis (RA) are well known, but little is known about those differences in relation to therapeutic response. Reduced folate carrier-1 (RFC-1), folypolyformyl glutamate synthase (FPGS), and γ-glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. This study investigated the sex differences in mRNA expression of RFC-1, FPGS, and GGH in 190 unrelated healthy Japanese people. The genotypes and mRNA expression were determined using the real-time PCR method. Significant differences between men and women were observed in RFC-1, FPGS, and GGH mRNA expression. The mRNA expression of FPGS and GGH was greater in women than that in men, but the expression of RFC-1 was less in the former than the latter. In stratified analysis by genotype, significant differences in sex-specific mRNA expression were observed in G/G of FPGS, C/C of GGH 452, and C/C of GGH -401. All showed greater mRNA expression in women than in men. In the 5 single-nucleotide polymorphisms RFC-1 80G>A, RFC-1 -43T>C, FPGS 1994G>A, GGH 452C>T, and GGH -401C>T examined, the FPGS 1994 G/G (1.46-fold), GGH 452 C/C (2.16-fold), and GGH -401 C/C (2.68-fold) genotypes showed significantly higher mRNA expression in women than in men. Healthy Japanese adults in this study showed sex-specific differences in mRNA expression that differed among RFC-1, FPGS, and GGH. Therefore, the relationship between genetic polymorphisms and mRNA expression including sex differences might contribute to the variation in the efficacy/toxicity of MTX in patients with RA.

  19. Reduced folate carrier-1 80G > A gene polymorphism is not associated with methotrexate treatment response in South Indian Tamils with rheumatoid arthritis.

    Science.gov (United States)

    Muralidharan, Niveditha; Mariaselvam, Christina Mary; Mithun, C B; Negi, Vir Singh

    2016-04-01

    Methotrexate (MTX) is the most commonly used disease-modifying drug to treat rheumatoid arthritis (RA). Although there are no reliable molecular markers to predict the treatment response and adverse effects to MTX therapy, the polymorphisms in genes coding for MTX metabolizing enzymes and transporters may play a crucial role. The reduced folate carrier-1 (RFC-1) is a bidirectional anion exchanger which transports MTX and folinic acid. It is reported to influence MTX treatment response and adverse effects in some ethnic populations but not in others. It is also associated with susceptibility to various diseases including systemic lupus erythematosus (SLE). The present study was aimed at investigating the role of RFC-1 80G > A gene polymorphism in association with disease susceptibility, MTX treatment response and the MTX-induced adverse events in the South Indian Tamil patients with rheumatoid arthritis. The RFC-1 80G > A gene polymorphism was investigated in 327 patients with RA and in 322 healthy controls by PCR-RFLP method. It was found that the heterozygous RFC-1 80 GA genotype was associated with protection against RA [p = 0.02, odds ratio (OR) 0.69, 95 % confidence interval (CI) 0.50-0.95]. However, it was not found to be associated with MTX treatment response. The RFC-1 G allele frequency was higher in patients with adverse effects, but the difference was not statistically significant (p = 0.08, OR 1.44, 95 % CI 0.97-2.13). RFC-1 80G > A gene polymorphism confers protection for RA. However, it is not associated with MTX treatment response and MTX-induced adverse effects in South Indian Tamil patients with RA.

  20. Folate deficiency and an abnormal lymphocyte deoxyuridine suppression test in monkeys.

    Science.gov (United States)

    Thenen, S W; Hwang, S M; Blocker, D E; Meadows, C A

    1991-01-01

    Cebus albifrons were fed folate-deficient diets in order to assess folate status at the cellular level with the deoxyuridine suppression test. Plasma and red blood cell folates were significantly lower at 2 months, compared to control values. Hematologic signs of megaloblastic anemia occurred after 6 months, with significantly lower hematocrit, hemoglobin and red blood cell number values and increased polymorphonuclear leukocyte lobe counts. Urinary formiminoglutamic acid excretion also was elevated significantly. Whole blood lymphocyte cultures exhibited abnormal deoxyuridine suppression of [3H]-thymidine incorporation into DNA with folate deficiency. Thus this deoxyuridine suppression test can be used in isolated whole blood lymphocytes of these nonhuman primates to document folate deficiency.

  1. Development of a New Folate-Derived Ga-68-Based PET Imaging Agent.

    Science.gov (United States)

    Brand, Christian; Longo, Valerie A; Groaning, Mike; Weber, Wolfgang A; Reiner, Thomas

    2017-02-13

    The folate receptor (FR) has emerged as an interesting diagnostic and therapeutic drug target with many potential applications in oncologic and inflammatory disorders. It was therefore the aim of this study to develop a folate-derived Ga-68-based positron emission tomography (PET) imaging tracer that is straightforward to radiolabel and could be broadly used in clinical studies. We validated its target binding affinity and specificity and compared it to [(99m)Tc]EC20, the folate single-photon emission computed tomography (SPECT) imaging tracer that has been most extensively studied clinically so far. The new folic acid-derived PET imaging agent is linked via a polyethyleneglycol linker to the chelator 1,4,7-triazacyclononane-1,4,7-trisacetic acid (NOTA). This new compound, NOTA-folate, was labeled with gallium-68. We tested the probe's stability in human plasma and its selectivity in vitro, using the FR-positive KB cell line as well as the FR-negative A549 cell line. The pharmacokinetic profile of [(68)Ga]NOTA-folate was evaluated in FR-positive KB mouse xenografts. Following intravenous injection of [(68)Ga]NOTA-folate (383 ± 53 μCi), PET/computed tomography (CT) imaging studies as well as biodistribution studies were performed using KB tumor-bearing mice (n = 3). In vitro as well as in vivo studies were performed in parallel with the SPECT imaging tracer [(99m)Tc]EC20. In comparison to [(99m)Tc]EC20 (radiochemical yield (RCY) = 82.0 ± 2.9 %, 91.8 ± 2.0 % purity), similar radiochemical yield (87.2 ± 6.9 %) and radiochemical purity (95.6 ± 1.8 %) could be achieved for [(68)Ga]NOTA-folate. For both tracers, we observed high affinity for FR-positive cells in vitro and high plasma stability. In PET/CT and biodistribution studies, [(68)Ga]NOTA-folate appeared to display slightly superior in vivo performance in comparison to [(99m)Tc]EC20. In detail, (68)Ga-NOTA-folate showed very good tumor uptake and retention (6.6 ± 1.1 %ID/g), relatively

  2. Human folate metabolism using 14C-accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, A. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Arjomand, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Duecker, S. R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Johnson, H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schneider, P. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zulim, R. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bucholz, B. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vogel, J. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    1999-03-25

    Folate is a water soluble vitamin required for optimal health, growth and development. It occurs naturally in various states of oxidation of the pteridine ring and with varying lengths to its glutamate chain. Folates function as one-carbon donors through methyl transferase catalyzed reactions. Low-folate diets, especially by those with suboptimal methyltransferase activity, are associated with increased risk of neural tube birth defects in children, hyperhomocysteinemic heart disease, and cancer in adults. Rapidly dividing (neoplastic) cells have a high folate need for DNA synthesis. Chemical analogs of folate (antifolates) that interfere with folate metabolism are used as therapeutic agents in cancer treatment. Although much is known about folate chemistry, metabolism of this vitamin in vivo in humans is not well understood. Since folate levels in blood and tissues are very low and methods to measure them are inadequate, the few previous studies that have examined folate metabolism used large doses of radiolabeled folic acid in patients with Hodgkin's disease and cancer (Butterworth et al. 1969, Krumdieck et al. 1978). A subsequent protocol using deuterated folic acid was also insufficiently sensitive to trace a physiologic folate dose (Stites et al. 1997). Accelerator mass spectrometry (AMS) is an emerging bioanalytical tool that overcomes the limitations of traditional mass spectrometry and of decay counting of long lived radioisotopes (Vogel et al. 1995). AMS can detect attomolar concentrations of 14 C in milligram-sized samples enabling in vivo radiotracer studies in healthy humans. We used AMS to study the metabolism of a physiologic 80 nmol oral dose of 14 C-folic acid (1/6 US RDA) by measuring the 14 C-folate levels in serial plasma, urine and feces samples taken over a 150-day period after dosing a healthy adult volunteer.

  3. The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Vollset, S.E.; Igland, J.; Jenab, M.; Fredriksen, A.; Meyer, K.; Eussen, S.; Gjessing, H.K.; Ueland, P.M.; Pera, G.; Sala, N.; Agudo, A.; Capella, G.; Giudice, G. Del; Palli, D.; Boeing, H.; Weikert, C.; Bueno-De-Mesquita, H.B.; Carneiro, F.; Pala, V.; Vineis, P.; Tumino, R.; Panico, S.; Berglund, G.; Manjer, J.; Stenling, R.; Hallmans, G.; Martinez, C.; Dorronsoro, M.; Barricarte, A.; Navarro, C.; Quiros, J.R.; Allen, N.; Key, T.J.; Bingham, S.; Linseisen, J.; Kaaks, R.; Overvad, K.; Tjonneland, A.; Buchner, F.L.; Peeters, P.H.; Numans, M.E.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Trichopoulou, A.; Lund, E.; Slimani, N.; Ferrari, P.; Riboli, E.; Gonzalez, C.A.

    2007-01-01

    Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospec

  4. The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Vollset, Stein Emil; Igland, Jannicke; Jenab, Mazda; Fredriksen, Ase; Meyer, Klaus; Eussen, Simone; Gjessing, Hakon K.; Ueland, Per Magne; Pera, Guillem; Sala, Nuria; Agudo, Antonio; Capella, Gabriel; Del Giudice, Giuseppe; Palli, Domenico; Boeing, Heiner; Weikert, Cornelia; Bueno-de-Mesquita, H. Bas; Carneiro, Fatima; Pala, Valeria; Vineis, Paolo; Tumino, Rosario; Panico, Salvatore; Berglund, Goran; Manjer, Jonas; Stenling, Roger; Hallmans, Goran; Martinez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Navarro, Carmen; Quiros, Jose R.; Allen, Naomi; Key, Timothy J.; Bingham, Sheila; Linseisen, Jakob; Kaaks, Rudolf; Overvad, Kim; Tjonneland, Anne; Buchner, Frederike L.; Peeters, Petra H. M.; Numans, Mattijs E.; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Lund, Eiliv; Slimani, Nadia; Ferrari, Pietro; Riboli, Elio; Gonzalez, Carlos A.

    2007-01-01

    Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospec

  5. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    Science.gov (United States)

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-06

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  6. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice.

    Science.gov (United States)

    Li, Yanli; Gao, Rufei; Liu, Xueqing; Chen, Xuemei; Liao, Xinggui; Geng, Yanqing; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2015-08-04

    The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

  7. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice

    Directory of Open Access Journals (Sweden)

    Yanli Li

    2015-08-01

    Full Text Available The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34 immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA, placental growth factor (PLGF, and VEGF receptor 2 (VEGFR2 were also tested. Serum levels of homocysteine (Hcy, follicle stimulating hormone (FSH, luteinizing hormone (LH, prolactin (PRL, progesterone (P4, and estradiol (E2 were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR and estrogen receptor α (ERα were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

  8. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice

    Science.gov (United States)

    Li, Yanli; Gao, Rufei; Liu, Xueqing; Chen, Xuemei; Liao, Xinggui; Geng, Yanqing; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2015-01-01

    The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone. PMID:26247969

  9. Modulation of folate production in lactic acid bacteria

    NARCIS (Netherlands)

    Wegkamp, H.B.A.

    2008-01-01

    Food fortification has proven to be very useful in reducing health problems associated with mal-intake of essential nutrients, such as the B-vitamin folate. Folate is used as one-carbon donor/acceptor in several biochemical processes like synthesis of DNA, RNA and some amino acids. Sufficient intake

  10. Physiological responses to folate overproduction in Lactobacillus plantarum WCFS1

    NARCIS (Netherlands)

    Wegkamp, A.; Mars, A.E.; Faijes, M.; Molenaar, D.; Vos, de R.C.H.; Klaus, M.J.; Hanson, A.D.; Vos, de W.M.; Smid, E.J.

    2010-01-01

    Background Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells. Results Metabolite formatio

  11. Physiological responses to folate overproduction in Lactobacillus plantarum WCFS1

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    de Vos Ric CH

    2010-12-01

    Full Text Available Abstract Background Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells. Results Metabolite formation and gene expression were determined in a folate-overproducing- and wild-type strain. Differential metabolomics analysis of intracellular metabolite pools indicated that the pool sizes of 18 metabolites differed significantly between these strains. The gene expression profile was determined for both strains in pH-regulated chemostat culture and batch culture. Apart from the expected overexpression of the 6 genes of the folate gene cluster, no other genes were found to be differentially expressed both in continuous and batch cultures. The discrepancy between the low transcriptome and metabolome response and the 25% growth rate reduction of the folate overproducing strain was further investigated. Folate production per se could be ruled out as a contributing factor, since in the absence of folate production the growth rate of the overproducer was also reduced by 25%. The higher metabolic costs for DNA and RNA biosynthesis in the folate overproducing strain were also ruled out. However, it was demonstrated that folate-specific mRNAs and proteins constitute 8% and 4% of the total mRNA and protein pool, respectively. Conclusion Folate overproduction leads to very little change in metabolite levels or overall transcript profile, while at the same time the growth rate is reduced drastically. This shows that Lactobacillus plantarum WCFS1 is unable to respond to this growth rate reduction, most likely because the growth-related transcripts and proteins are diluted by the enormous amount of gratuitous folate-related transcripts and proteins.

  12. How do we reduce plasma transfusion in Rhode Island?

    Science.gov (United States)

    Nixon, Christian P; Tavares, Maria F; Sweeney, Joseph D

    2017-08-01

    Plasma transfusions are given to patients with coagulopathy, either prophylactically, before an invasive procedure; or therapeutically, in the presence of active bleeding; and as an exchange fluid in therapeutic plasma exchange for disorders such as thrombotic thrombocytopenic purpura. There is consensus that many prophylactic plasma transfusions are non-efficacious, and the misdiagnosis of thrombotic thrombocytopenic purpura results in unnecessary therapeutic plasma exchange. Beginning in 2001, programs to reduce plasma transfusion in the three major teaching hospitals in Rhode Island were initiated. The programs evolved through the establishment of guidelines, education for key prescribers of plasma, screening of plasma prescriptions, and engagement of individual prescribing physicians for out-of-guidelines prescriptions with modification or cancellation. Establishment of an in-house ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1, motif 13) assay in 2013 was used to prevent therapeutic plasma exchange in patients with non-thrombotic thrombocytopenic purpura microangiopathy. Transfusion service data were gathered at the hospital level regarding blood component use, hospital data for discharges, inpatient mortality, and mean case-mix index, and, at the state level, for units of plasma shipped from the community blood center to in-state hospitals. Between 2006 and 2016, a reduction in plasma use from 11,805 to 2677 units (a 77% decrease) was observed in the three hospitals and was mirrored in the state as a whole. This decline was not associated with any increase in red blood cell transfusion. Inpatient mortality either declined or was unchanged. An active program focused on education and interdiction can achieve a large decrease in plasma transfusions without evidence of patient harm. © 2017 AABB.

  13. The mathematical theory of reduced MHD models for fusion plasmas

    OpenAIRE

    Guillard, Hervé

    2015-01-01

    The derivation of reduced MHD models for fusion plasma is here formulated as a special instance of the general theory of singular limit of hyperbolic system of PDEs with large operator. This formulation allows to use the general results of this theory and to prove rigorously that reduced MHD models are valid approximations of the full MHD equations. In particular, it is proven that the solutions of the full MHD system converge to the solutions of an appropriate reduced model.

  14. A Cross-Sectional Study of Dietary and Genetic Predictors of Blood Folate Levels in Healthy Young Adults

    Directory of Open Access Journals (Sweden)

    Daniel Cummings

    2017-09-01

    Full Text Available Since 1998, the U.S. has mandated folic acid (FA fortification of certain grain products to reduce the risk of neural tube defects. Folate intake and red blood cell (RBC folate concentrations increased substantially post-intervention, although recent studies raise concerns about the level of ongoing benefit. This study investigated blood folate level determinants in healthy young adults, including intake of naturally occurring food folate, synthetic FA, and the interaction of naturally occurring food folate with a common missense variant in the FOLH1 gene thought to affect absorption. Participants (n = 265 completed the Diet History Questionnaire II, RBC folate testing, and were genotyped for the 484T>C FOLH1 variant. Men reported significantly greater intake of all folate sources except for supplemental FA, but RBC folate levels did not significantly differ by sex. Synthetic FA was a stronger predictor of RBC folate than naturally occurring food folate. In the largest racial group, synthetic FA and the interaction of FOLH1 genotype with naturally occurring food folate significantly predicted RBC folate, with the overall model accounting for 13.8% of the variance in RBC folate levels. Blood folate levels rely on a complex interaction of natural and synthetic folate intake as well as FOLH1 genotype.

  15. Fish oil -- how does it reduce plasma triglycerides?

    Science.gov (United States)

    Shearer, Gregory C; Savinova, Olga V; Harris, William S

    2012-05-01

    Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle β-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

  16. Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link.

    Science.gov (United States)

    Rogers, Eugene J

    2008-09-01

    The inverse association between maternal folate status and incidence of infants born with neural tube defects (NTD's) was recognized over twenty years ago and led the US health agencies in the early 1990s to recommend that women of childbearing age consume 400 microg of folic acid each day. The FDA followed by mandating that certain foods be fortified with folic acid and this has resulted in a significant enhancement of maternal folate status to levels that are often difficult to otherwise achieve naturally. At least one study indicates that this has decreased the incidence of NTD's. However, this same time period directly coincides with what many feel is the apparent beginning and continuous increase in the prevalence of Autism and related Autism Spectrum Disorders (ASD's) in the US. Are these similar time frames of changes in maternal folate status and possible Autism prevalence a random event or has improved maternal (and fetal) folate status during pregnancy played a role? It is not only plausible but highly likely. A particular polymorphic form to a key enzyme required to activate folate for methylation in neurodevelopment, 5-methylenetetrahydrofolate reductase (MTHFR), demonstrates reduced activity under low or normal folate levels but normal activity under conditions of higher folate nutritional status. A consequence of the presence of the polymorphic form of this enzyme during normal or reduced folate status are higher plasma homocysteine levels than noncarriers and the combination of these factors have been shown in several studies to result in an increase rate of miscarriage via thrombotic events. However, the incidence of hyperhomocysteinemia in the presence of the polymorphism is reduced under the common condition of enhanced folate status and thereby masks the latent adverse effects of the presence of this enzyme form during pregnancy. Of great importance is that this polymorphism, although common in the normal population, is found in significantly

  17. HELP LDL apheresis reduces plasma pentraxin 3 in familial hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Michela Zanetti

    Full Text Available BACKGROUND: Pentraxin 3 (PTX3, a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3. METHODS: Plasma lipids, PTX3, and CRP were measured in 19 patients with FH undergoing chronic HELP LDL apheresis before and after treatment and in 20 control subjects. In the patients assessment of inflammation and oxidative stress markers included also plasma TNFα, fibrinogen and TBARS. RESULTS: At baseline, FH patients had higher (p = 0.0002 plasma PTX3 than matched control subjects. In FH PTX3 correlated positively (p≤0.05 with age, gender and CRP and negatively (p = 0.01 with HELP LDL apheresis vintage. The latter association was confirmed after correction for age, gender and CRP. HELP LDL apheresis acutely reduced (p≤0.04 plasma PTX3, CRP, fibrinogen, TBARS and lipids, but not TNFα. No association was observed between mean decrease in PTX3 and in LDL cholesterol. PTX3 paralleled lipids, oxidative stress and inflammation markers in time-course study. CONCLUSION: FH is associated with increased plasma PTX3, which is acutely reduced by HELP LDL apheresis independently of LDL cholesterol, as reflected by the lack of association between change in PTX3 and in LDL levels. These results, together with the finding of a negative relationship between PTX3 and duration of treatment suggest that HELP LDL apheresis may influence both acutely and chronically cardiovascular outcomes in FH by modulating PTX3.

  18. Potential role of folate in pre-eclampsia.

    Science.gov (United States)

    Singh, Mansi Dass; Thomas, Philip; Owens, Julie; Hague, William; Fenech, Michael

    2015-10-01

    Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre-eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre-eclampsia.

  19. LINE-1 DNA methylation is inversely correlated with cord plasma homocysteine in man: a preliminary study.

    Science.gov (United States)

    Fryer, Anthony A; Nafee, Tamer M; Ismail, Khaled M K; Carroll, William D; Emes, Richard D; Farrell, William E

    2009-08-16

    Folic acid supplementation during pregnancy has known beneficial effects. It reduces risk of neural tube defects and low birth weight. Folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. However, most data on the effects of folate on the epigenome is derived from animal or in vitro models. We examined the relationship between cord blood methylation and maternal folic acid intake, cord blood folate and homocysteine using data from 24 pregnant women. Genome-wide methylation was determined by the level of methylation of LINE-1 repeats using Pyrosequencing. We show that cord plasma homocysteine (p = 0.001, r = -0.688), but not serum folate or maternal folic acid intake, is inverse correlated with LINE-1 methylation. This remained significant after correction for potential confounders (p = 0.004). These data indicate that levels of folate-associated intermediates in cord blood during late pregnancy have significant consequences for the fetal epigenome.

  20. Methylenetetrahydrofolate Reductase Activity and Folate Metabolism

    Directory of Open Access Journals (Sweden)

    Nursen Keser

    2014-04-01

    Full Text Available Folate is a vital B vitamin which is easily water-soluble. It is a natural source which is found in the herbal and animal foods. Folate has important duties in the human metabolism, one of them is the adjustment of the level of plasma homocysteine. Reduction in MTHFR (methylenetetrahydrofolate reductase,which is in charge of the metabolism of homocysteine activity affects the level of homocysteine. Therefore MTHFR is an important enzyme in folate metabolism. Some of the mutations occurring in the MTHFR gene is a risk factor for various diseases and may be caused the hyperhomocysteinemia or the homocystinuria, and they also may lead to metabolic problems. MTHFR is effective in the important pathways such as DNA synthesis, methylation reactions and synthesis of RNA. C677T and A1298C are the most commonly occurring polymorphisms in the gene of MTHFR. The frequency of these polymorphisms show differences in the populations. MTHFR, folate distribution, metabolism of homocysteine and S-adenosylmethionine, by the MTHFR methylation the genetic defects have the potential of affecting the risk of disease in the negative or positive way.

  1. Microarray analysis of E9.5 reduced folate carrier (RFC1; Slc19a1 knockout embryos reveals altered expression of genes in the cubilin-megalin multiligand endocytic receptor complex

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    Bauer Linda K

    2008-04-01

    Full Text Available Abstract Background The reduced folate carrier (RFC1 is an integral membrane protein and facilitative anion exchanger that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. Adequate maternal-fetal transport of folate is necessary for normal embryogenesis. Targeted inactivation of the murine RFC1 gene results in post-implantation embryolethality, but daily folic acid supplementation of pregnant dams prolongs survival of homozygous embryos until mid-gestation. At E10.5 RFC1-/- embryos are developmentally delayed relative to wildtype littermates, have multiple malformations, including neural tube defects, and die due to failure of chorioallantoic fusion. The mesoderm is sparse and disorganized, and there is a marked absence of erythrocytes in yolk sac blood islands. The identification of alterations in gene expression and signaling pathways involved in the observed dysmorphology following inactivation of RFC1-mediated folate transport are the focus of this investigation. Results Affymetrix microarray analysis of the relative gene expression profiles in whole E9.5 RFC1-/- vs. RFC1+/+ embryos identified 200 known genes that were differentially expressed. Major ontology groups included transcription factors (13.04%, and genes involved in transport functions (ion, lipid, carbohydrate (11.37%. Genes that code for receptors, ligands and interacting proteins in the cubilin-megalin multiligand endocytic receptor complex accounted for 9.36% of the total, followed closely by several genes involved in hematopoiesis (8.03%. The most highly significant gene network identified by Ingenuity™ Pathway analysis included 12 genes in the cubilin-megalin multiligand endocytic receptor complex. Altered expression of these genes was validated by quantitative RT-PCR, and immunohistochemical analysis demonstrated that megalin protein expression disappeared from the visceral yolk sac of RFC1-/- embryos, while cubilin protein was widely misexpressed

  2. Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children.

    Science.gov (United States)

    Ambroszkiewicz, J; Klemarczyk, W; Chełchowska, M; Gajewska, J; Laskowska-Klita, T

    2006-01-01

    The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

  3. Bioavailability and bioefficacy of folate and folic acid in man

    NARCIS (Netherlands)

    Brouwer, I.A.; Dusseldorp, van M.; West, C.E.; Steegers-Theunissen, R.P.M.

    2001-01-01

    Folic acid is important because supplementation around the time of conception has been proven to lower the risk of having offspring with a neural-tube defect. Furthermore, both dietary folate and folic acid decrease plasma total homocysteine concentrations. Elevated plasma homocysteine concentration

  4. Disruption of the folate pathway in zebrafish causes developmental defects

    Directory of Open Access Journals (Sweden)

    Lee Marina S

    2012-04-01

    Full Text Available Abstract Background Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development. Results We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX, a potent inhibitor of dihydrofolate reductase (Dhfr an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles. Conclusions Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development.

  5. A technique to reduce plasma armature formation voltage

    Energy Technology Data Exchange (ETDEWEB)

    Jamison, K.A. (Science Applications International Corp., Shalimar, FL (US)); Littrell, D.M. (Air Force Armament Lab., Eglin AFB, FL (United States))

    1991-01-01

    The initiation of a plasma armature by foil vaporization in a railgun is often accompanied by a large, fast, voltage transient appearing on both the breech and muzzle of the gun. For a railgun driven by an inductor/opening switch power supply, this voltage transient becomes a concern during current commutation from the switch to the railgun. To lessen the requirements on the opening switch, techniques must be found to reduce the armature formation voltage. This paper presents the experimental results from railgun firings at AFATL's Electromagnetic Launcher Basic Research Facility (Site A-15, Eglin Air Force Base, Florida) using different shapes of initiation foils. These foils have been designed to vaporize into a plasma armature with reduced transient voltages. A design criteria was developed to ensure that all portions of the foil vaporize at slightly different times.

  6. Gluten-Free Products Are Insufficient Source of Folate and Vitamin B12 for Coeliac Patients

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    Irena Colić Barić

    2011-01-01

    Full Text Available The gluten-free diet, the only treatment in coeliac disease, can be nutritionally unbalanced and deficient in several nutrients. Gluten-free products contain much lower levels of B vitamins, especially lower folate concentrations than their gluten-containing counterparts. Folate intake is considered as a major dietary determinant of plasma homocysteine concentration in healthy population. Elevated homocysteine is an independent risk factor for cardiovascular disease and has been associated with osteoporotic fractures, which are an increased risk factor in coeliac disease. The aim of this study is to determine dietary folate intake and plasma homocysteine concentration as metabolic markers of suboptimal intake of folate and B12 in Croatian coeliac patients living on a gluten-free diet. Subjects were 52 coeliac patients (83 % female, age 35±13 adhering to a gluten-free diet. Blood samples were analyzed for plasma homocysteine, serum and red blood cell folate and serum B12. Quantitative food frequency questionnaire was used to measure dietary folate intake. Mean dietary folate intake was 206 mg of dietary folate equivalents (DFE, which was far below the national recommendation of 400 µg of DFE (or 200 μg of folic acid. Mean homocysteine was (9±2 μmol/L (range from 5.42 to 13.90 μmol/L, while elevated homocysteine concentrations (>10 μmol/L were found in 34 % of subjects. In conclusion, coeliac patients adhering to gluten-free diet included in this study showed low folate intake and suboptimal folate and vitamin B12 status, possibly due to low folate content in gluten-free products. Therefore, folate fortification or enrichment of gluten-free products could be beneficial for coeliac patients and it would be of great interest for the food industry.

  7. Folate and neural tube defects: The role of supplements and food fortification.

    Science.gov (United States)

    Ami, Noam; Bernstein, Mark; Boucher, François; Rieder, Michael; Parker, Louise

    2016-04-01

    Periconceptional folic acid significantly reduces the risk of neural tube defects. It is difficult to achieve optimal levels of folate by diet alone, even with fortification of flour, especially because flour consumption in Canada is slightly decreasing. Intermittent concerns have been raised concerning possible deleterious effects of folate supplementation, including the masking of symptoms of vitamin B12 deficiency and an association with cancer, especially colorectal cancer. Both concerns have been disproved. The Canadian Paediatric Society endorses the following steps to enhance folate intake in women of child-bearing age: encouraging the consumption of folate-rich foods such as leafy vegetables, increasing the level of folate food fortification, taking a supplement containing folate and B12, and providing free folate supplementation to disadvantaged women of child-bearing age. These recommendations are consistent with those of the Society of Obstetricians and Gynaecologists of Canada.

  8. Folate status and socio-demographic predictors of folate status, among a national cohort of women aged 26-36 in Australia, 2004-2006.

    Science.gov (United States)

    Gall, Seana; Seal, Judy; Taylor, Roscoe; Dwyer, Terry; Venn, Alison

    2012-10-01

    To describe serum folate status and the socio-demographic correlates of serum folate status in a national sample of women aged 26-36 years in Australia, 2004-2006. Stored serum samples from 1,046 women, collected as part of the Childhood Determinants of Adult Health study, were analysed for serum folate. Median (IQR) serum folate was 27.1 nmol/L (18.8-35.0 nmol/L) with only 7.0% of samples below 11 nmol/L. Serum folate was positively associated with supplement use, educational level, occupational status and urban dwelling. In this population-based sample, most women had folate levels in the normal range with few having low serum folate. Those of lower socioeconomic position or with poorer health behaviours had lower folate levels, though most were still within the normal range. In the absence of comprehensive national survey data on the folate status of women of child-bearing age, these data provide a valuable baseline for evaluating the impact of mandatory folic acid fortification in Australia, which commenced in 2009. It is likely that mandatory fortification of the food supply with folic acid will reduce the disparities in folate status between socioeconomic groups and in people with poorer health behaviours. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

  9. Effect of dietary folic acid supplementation on egg folate content and the performance and folate status of two strains of laying hens.

    Science.gov (United States)

    Hebert, K; House, J D; Guenter, W

    2005-10-01

    Enrichment of eggs with folate is possible when dietary folic acid levels are increased. However, development of optimal strategies for the production of folate-enriched eggs requires knowledge as to differences due to strain of bird and a greater understanding of the factors limiting egg folate deposition. To this end, a study was designed to determine the response of two leghorn strains that differ in production performance. Hyline W36 and W98 hens (n = 6 per diet) received a barley-based ration containing 0, 2, 4, 8, 16, 32, 64, or 128 mg/kg of crystalline folic acid for 21 d. Response criteria included production parameters, measures of blood folate status, and egg folate content. Significant (P folic acid through a reduction in plasma homocysteine concentrations, suggesting that this strain has a higher requirement for folate than the W36 strain. Overall, egg folate content is maximized when crystalline folic acid is supplemented to the diet at 2 mg/kg or higher. Higher levels of egg folate are not achieved due to the saturation of the precursor pool for egg folate deposition.

  10. Folate and vitamin B12 status in Latin America and the Caribbean: An update

    Science.gov (United States)

    Background: The current magnitude of folate and vitamin B12 deficiency in Latin America and the Caribbean is uncertain. Objective: To summarize data on plasma or serum vitamin B12 and folate concentrations in Latin America and the Caribbean reported since 1990, a period that covers the era before an...

  11. Dietary folate and APC mutations in sporadic colorectal cancer.

    Science.gov (United States)

    de Vogel, Stefan; van Engeland, Manon; Lüchtenborg, Margreet; de Bruïne, Adriaan P; Roemen, Guido M J M; Lentjes, Marjolein H F M; Goldbohm, R Alexandra; van den Brandt, Piet A; de Goeij, Anton F P M; Weijenberg, Matty P

    2006-12-01

    Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.

  12. Epigenetic alterations in folate transport genes in placental tissue from fetuses with neural tube defects and in leukocytes from subjects with hyperhomocysteinemia

    Science.gov (United States)

    Farkas, Sanja A.; Böttiger, Anna K.; Isaksson, Helena S.; Finnell, Richard H.; Ren, Aiguo; Nilsson, Torbjörn K.; Nilsson, Torbjörn K.

    2013-01-01

    The objectives of this study were to identify tissue-specific differentially methylated regions (T-DMR’s) in the folate transport genes in placental tissue compared with leukocytes, and from placental tissues obtained from normal infants or with neural tube defects (NTDs). Using pyrosequencing, we developed methylation assays for the CpG islands (CGIs) and the CGI shore regions of the folate receptor α (FOLR1), proton-coupled folate transporter (PCFT) and reduced folate carrier 1 (RFC1) genes. The T-DMRs differed in location for each gene and the difference in methylation ranged between 2 and 54%. A higher T-DMR methylated fraction was associated with a lower mRNA level of the FOLR1 and RFC1 genes. Methylation fractions differed according to RFC1 80G > A genotype in the NTD cases and in leukocytes from subjects with high total plasma homocysteine (tHcy). There were no differences in methylated fraction of folate transporter genes between NTD cases and controls. We suggest that T-DMRs participate in the regulation of expression of the FOLR1 and RFC1 genes, that the RFC1 80G > A polymorphism exerts a gene-nutrition interaction on DNA methylation in the RFC1 gene, and that this interaction appears to be most prominent in NTD-affected births and in subjects with high tHcy concentrations. PMID:23417011

  13. Exploring the folate pathway in Plasmodium falciparum.

    Science.gov (United States)

    Hyde, John E

    2005-06-01

    As in centuries past, the main weapon against human malaria infections continues to be intervention with drugs, despite the widespread and increasing frequency of parasite populations that are resistant to one or more of the available compounds. This is a particular problem with the lethal species of parasite, Plasmodium falciparum, which claims some two million lives per year as well as causing enormous social and economic problems. Amongst the antimalarial drugs currently in clinical use, the antifolates have the best defined molecular targets, namely the enzymes dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), which function in the folate metabolic pathway. The products of this pathway, reduced folate cofactors, are essential for DNA synthesis and the metabolism of certain amino acids. Moreover, their formation and interconversions involve a number of other enzymes that have not as yet been exploited as drug targets. Antifolates are of major importance as they currently represent the only inexpensive regime for combating chloroquine-resistant malaria, and are now first-line drugs in a number of African countries. Aspects of our understanding of this pathway and antifolate drug resistance are reviewed here, with a particular emphasis on approaches to analysing the details of, and balance between, folate biosynthesis by the parasite and salvage of pre-formed folate from exogenous sources.

  14. Vitamin B12 and Folate Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Vitamin B12 and Folate Share this page: Was this ... as: Cobalamin; Folic Acid; RBC Folate Formal name: Vitamin B12; Folate Related tests: Complete Blood Count , Methylmalonic ...

  15. Preparation and Preliminary Biological Evaluation of {sup 177}Lu-DOTA folate as Potential Folate Receptor Targeting Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kang-Hyuk; Hong, Young-Don; Pyun, Mi-Sun; Lee, So-Young; Felipe, Fenelope; Yoon, Sun-Ha; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-10-15

    Folic Acid (FA) and FA derivatives are overexpressed on several tumor cells. The cell-membrane folic acid receptors are known to be responsible for the cellular accumulation of FA and FA analogs, such as methotrexate and folic acid. Folate has been characterized to have high affinity for the folate-receptor positive cells and tissues and considered to be useful as diagnostic imaging and therapeutic agent. In 1940s, Folate analogue, aminopterin, was first used for treatment of leukemia and recently, many folate derivatives were tried for cancer-treatment agent as well as visualization of folate receptor. Many researchers tried to conjugate folic acid with macromolecules or low molecular weight chelators through its alpha or gamma carboxylate. However, despite the reduced binding affinity, FAs are still recognized by the folate receptor. Therefore, we focused to develop folate-based radiopharmaceutical that has the potential to be used as a therapeutic agent. We report here the synthesis and the radiolabeling of {sup 177}Lu-DOTA as well as the biodistribution data of our developed compound.

  16. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

    Energy Technology Data Exchange (ETDEWEB)

    Tryndyak, Volodymyr P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Latendresse, John R. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Montgomery, Beverly [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Ross, Sharon A. [Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892 (United States); Beland, Frederick A. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

    2012-07-01

    MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of

  17. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    Science.gov (United States)

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients.

  18. Folates for reduction of risk of neural tube defects: using oral contraceptives as a source of folate

    OpenAIRE

    Nelson AL

    2011-01-01

    Anita L Nelson Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, CA, USA Abstract: The evidence that folates reduce the risk of neural tube defects (NTDs) is so compelling that supplementation has been recommended by every relevant authority. The Cochrane Database of Systematic Reviews has determined that folate supplementation should be rated as a Grade 1 recommendation. United States Preventive Health Services Task Force, the US Food ...

  19. Plasma antioxidant capacity is reduced in Asperger syndrome.

    Science.gov (United States)

    Parellada, Mara; Moreno, Carmen; Mac-Dowell, Karina; Leza, Juan Carlos; Giraldez, Marisa; Bailón, Concepción; Castro, Carmen; Miranda-Azpiazu, Patricia; Fraguas, David; Arango, Celso

    2012-03-01

    Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The role of folate metabolism in orofacial development and clefting.

    Science.gov (United States)

    Wahl, Stacey E; Kennedy, Allyson E; Wyatt, Brent H; Moore, Alexander D; Pridgen, Deborah E; Cherry, Amanda M; Mavila, Catherine B; Dickinson, Amanda J G

    2015-09-01

    Folate deficiency has been associated with numerous diseases and birth defects including orofacial defects. However, whether folate has a role in the face during early orofacial development has been unclear. The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Such defects are accompanied by a severe reduction in the muscle and cartilage jaw elements without significant change in neural crest pattern or global levels of methylation. We propose that the orofacial defects associated with DHFR deficient function are the result of decreased cell proliferation and increased cell death via DNA damage. In particular, localized apoptosis may also be depleting the cells of the face that express crucial genes for the differentiation of the jaw structures. Folate supplementation is widely known to reduce human risk for orofacial clefts. In the present study, we show that activating folate metabolism can reduce median oral clefts in the primary palate by increasing cell survival. Moreover, we demonstrate that a minor decrease in DHFR function exacerbates median facial clefts caused by RAR inhibition. This work suggests that folate deficiencies could be a major contributing factor to multifactorial orofacial defects.

  1. Association between folate intake, serum folate levels and the risk of lung cancer: a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    DAI Wei-min; YANG Bo; CHU Xiang-yang; WANG Yu-qi; ZHAO Ming; CHEN Li; ZHANG Guo-qing

    2013-01-01

    Background Folate plays a critical role in nucleotide synthesis and DNA methylation,and was considered to be associated with anti-carcinogenesis.Results from studies that concern the relationship between the folate intake or serum folate levels and lung cancer risk showed no consistency,which requires our further comprehensive metaanalysis.Methods Systematic literature search was conducted to identify the relevant studies (published prior to February 2013)according to standard protocol.Estimated effects were calculated under both random-effects and fixed-effects models.Heterogeneity between studies and publication bias were also evaluated.Results A total of 4390 cases and 6138 controls from 6 case-control studies revealed a significant overall inverse association between folate intake and lung cancer risk (OR =0.74,95% Cl =0.65-0.84,P< 0.001).Summary of 1438 cases and 2582 controls from 4 case-control studies and 44 cases out of a cohort of 1988 participants suggested a marginal association without significance (OR =0.78,95% Cl =0.60-1.02,P =0.075) between high serum folate levels and less lung cancer susceptibility; however,subgroup analysis about population-based case-control studies showed that high serum folate levels significantly associated with the reduced lung cancer risk (OR =0.76,95% Cl =0.58-1.00,P =0.048).Conclusion Higher folate intake can be a protective factor against lung cancer risk,and higher serum folate level is probably associated with reduced lung cancer risk in marginal manner,though more studies are warranted to confirm these associations.

  2. LRP2 mediates folate uptake in the developing neural tube.

    Science.gov (United States)

    Kur, Esther; Mecklenburg, Nora; Cabrera, Robert M; Willnow, Thomas E; Hammes, Annette

    2014-05-15

    The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for the delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole-embryo cultures showed that LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared with control littermates. Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure.

  3. Some nutritional effects of folate-binding protein in bovine milk on the bioavailability of folate to rats

    Energy Technology Data Exchange (ETDEWEB)

    Tani, M.; Iwai, K.

    1984-04-01

    The excretions of folate compounds into both the urine and bile were investigated in rats after the administration of pteroylglutamic acid (PteGlu) with or without the folate-binding protein (FBP) prepared from bovine milk. When the sample solution, containing either free or bound (/sup 3/H)PteGlu (i.e., bound to the FBP from milk), was delivered to rats intragastrically via oral intubation, the amounts of (/sup 3/H)PteGlu excreted into the feces did not change. On the other hand, the urinary excretion of /sup 3/H-labeled folate compounds, especially (/sup 3/H)5-methyltetrahydrofolic acid (5-CH/sub 3/-H/sub 4/PteGlu), after the administration of bound (/sup 3/H)PteGlu was significantly lower (P less than 0.01) than that after the administration of free (/sup 3/H)PteGlu. The urinary excretion of (/sup 3/H)5-CH/sub 3/-H/sub 4/PteGlu was directly proportional to the initial amount of free (/sup 3/H)PteGlu administered. The similar effect of FBP was also observed when the biliary excretion of /sup 3/H-labeled folate compounds was investigated in situ. Furthermore, the incorporation of (/sup 3/H)PteGlu into folate-requiring intestinal microorganisms was considerably reduced when it was bound to FBP. These results suggest that milk FBP has some nutritional effects on the bioavailability of folate in vivo.

  4. Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases.

    Science.gov (United States)

    Kao, Tseng-Ting; Chu, Chia-Yi; Lee, Gang-Hui; Hsiao, Tsun-Hsien; Cheng, Nai-Wei; Chang, Nan-Shan; Chen, Bing-Hung; Fu, Tzu-Fun

    2014-11-01

    Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.

  5. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India.

    Science.gov (United States)

    Yajnik, Chittaranjan S; Lubree, Himangi G; Thuse, Nileema V; Ramdas, Lalita V; Deshpande, Swapna S; Deshpande, Vaishali U; Deshpande, Jyoti A; Uradey, Bhagyashree S; Ganpule, Anjali A; Naik, Sadanand S; Joshi, Niranjan P; Farrant, Hannah; Refsum, Helga

    2007-01-01

    People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p homocysteine (tHcy) concentrations.

  6. Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.

    Science.gov (United States)

    Choi, Jeong-hwa; Yates, Zoe; Martin, Charlotte; Boyd, Lyndell; Ng, Xiaowei; Skinner, Virginia; Wai, Ron; Veysey, Martin; Lucock, Mark

    2015-01-01

    Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

  7. Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays.

    Science.gov (United States)

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2015-01-01

    Different sources of folate may have different bioavailability and hence may impact the standard definition of folate equivalents. In order to examine this, a short term human study was undertaken to evaluate the relative native folate bioavailabilities from spinach, Camembert cheese and wheat germs compared to pteroylmonoglutamic acid as the reference dose. The study had a single-centre, randomised, four-treatment, four-period, four-sequence, cross-over design, i.e. the four (food) items to be tested (referred to as treatments) were administered in sequences according to the Latin square, so that each experimental treatment occurred only once within each sequence and once within each study period. Each of the 24 subjects received the four experimental items separated by a 14-day equilibrium phase and received a pteroylmonoglutamic acid supplement for 14 days before the first testing and between the testings for saturation of body pools. Folates in test foods, plasma and urine samples were determined by stable isotope dilution assays, and in urine and plasma, the concentrations of 5-methyltetrahydrofolate were evaluated. Standard non-compartmental methods were applied to determine the biokinetic parameters C(max), t(max) and AUC from baseline corrected 5-methyltetrahydrofolate concentrations within the interval from 0 to 12 hours. The variability of AUC and C(max) was moderate for spinach and oral solution of pteroylmonoglutamic acid but high for Camembert cheese and very high for wheat germs. The median t(max) was lowest for spinach, though t(max) showed a high variability among all treatments. When comparing the ratio estimates of AUC and C(max) for the different test foods, highest bioavailability was found for spinach followed by that for wheat germs and Camembert cheese. The results underline the dependence of folate bioavailability on the type of food ingested. Therefore, the general assumption of 50% bioavailability as the rationale behind the definition of

  8. Folates: Chemistry, analysis, occurrence, biofortification and bioavailability.

    Science.gov (United States)

    Saini, Ramesh Kumar; Nile, Shivraj Hariram; Keum, Young-Soo

    2016-11-01

    Folates (Vitamin B9) include both naturally occurring folates and synthetic folic acid used in fortified foods and dietary supplements. Folate deficiency causes severe abnormalities in one-carbon metabolism can result chronic diseases and developmental disorders, including neural tube defects. Mammalian cells cannot synthesize folates de novo; therefore, diet and dietary supplements are the only way to attain daily folate requirements. In the last decade, significant advancements have been made to enhance the folate content of rice, tomato, common bean and lettuce by using genetic engineering approaches. Strategies have been developed to improve the stability of folate pool in plants. Folate deglutamylation through food processing and thermal treatment has the potential to enhance the bioavailability of folate. This review highlights the recent developments in biosynthesis, composition, bioavailability, enhanced production by elicitation and metabolic engineering, and methods of analysis of folate in food. Additionally, future perspectives in this context are identified. Detailed knowledge of folate biosynthesis, degradation and salvage are the prime requirements to efficiently engineer the plants for the enhancement of overall folate content. Similarly, consumption of a folate-rich diet with enhanced bioavailability is the best way to maintain optimum folate levels in the body. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Update on cobalamin, folate, and homocysteine.

    Science.gov (United States)

    Carmel, Ralph; Green, Ralph; Rosenblatt, David S; Watkins, David

    2003-01-01

    is a risk factor for vascular and thrombotic disease. In Section II, Dr. Green notes that the interactions of metabolism and clinical risk are not well understood and a causative relationship remains unproven despite new reports that lowering homocysteine levels may reduce vascular complications. Genetic and acquired influences may interact in important ways that are still being sorted out. The use of vitamins, especially folate, often reduces homocysteine levels but also carries potential disadvantages and even risks. Folate fortification of the diet and supplement use have also markedly reduced the frequency of folate deficiency, and cobalamin deficiency is now the more common deficiency state, especially among the elderly. Although genetic disorders are rare, they illuminate important metabolic mechanisms and pose diagnostic challenges, especially when clinical presentation occurs later in life. In Section III, Drs. Rosenblatt and Watkins use selected disorders to illustrate the subject. Imerslund-Gräsbeck syndrome, a hereditary disorder of cobalamin absorption at the ileal level, demonstrates genetic heterogeneity. Finnish patients show mutation of the gene for cubilin, the multiligand receptor for intrinsic factor. Surprisingly, Norwegian and other patients have been found recently to have mutations of the AMN (amnionless) gene, mutations that are lethal in mice at the embryonic stage. Two disorders of cobalamin metabolism, cblG and cblE, are now known to arise from mutations of the methionine synthase and methionine synthase reductase genes, respectively. These disorders feature megaloblastic anemia and neurologic manifestations. The folate disorder selected for illustration, methylenetetrahydrofolate reductase (MTHFR) deficiency, paradoxically causes neurological problems but no megaloblastic anemia. This rare deficiency is the most common inborn error of folate metabolism. It is distinct from the very common MTHFR gene polymorphisms, mutations that cause

  10. (64)Cu- and (68)Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate.

    Science.gov (United States)

    Farkas, Renáta; Siwowska, Klaudia; Ametamey, Simon M; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2016-06-06

    A number of folate-based radioconjugates have been synthesized and evaluated for nuclear imaging purposes of folate receptor (FR)-positive tumors and potential therapeutic application. A common shortcoming of radiofolates is, however, a significant accumulation of radioactivity in the kidneys. This situation has been faced by modifying the folate conjugate with an albumin-binding entity to increase the circulation time of the radiofolate, which led to significantly improved tumor-to-kidney ratios. The aim of this study was to develop an albumin-binding folate conjugate with a NODAGA-chelator (rf42) for labeling with (64)Cu and (68)Ga, allowing application for PET imaging. The folate conjugate rf42 was synthesized in 8 steps, with an overall yield of 5%. Radiolabeling with (64)Cu and (68)Ga was carried out at room temperature within 10 min resulting in (64)Cu-rf42 and (68)Ga-rf42 with >95% radiochemical purity. (64)Cu-rf42 and (68)Ga-rf42 were stable (>95% intact) in phosphate-buffered saline over more than 4 half-lives of the corresponding radionuclide. In vitro, the plasma protein-bound fraction of (64)Cu-rf42 and (68)Ga-rf42 was determined to be >96%. Cell experiments proved FR-specific uptake of both radiofolates, as it was reduced to 68)Ga-rf42 was found in KB tumors of mice (14.52 ± 0.99% IA/g and 11.92 ± 1.68% IA/g, respectively) at 4 h after injection. The tumor-to-kidney ratios were in the range of 0.43-0.55 over the first 4 h of investigation. At later time points (up to 72 h p.i. of (64)Cu-rf42) the tumor-to-kidney ratio increased to 0.73. High-quality PET/CT images were obtained 2 h after injection of (64)Cu-rf42 and (68)Ga-rf42, respectively, allowing distinct visualization of tumors and kidneys. Comparison of PET/CT images obtained with (64)Cu-rf42 and a (64)Cu-labeled DOTA-folate conjugate (cm10) clearly proved the superiority of NODAGA for stable coordination of (64)Cu. (64)Cu-cm10 showed high liver uptake, most probably as a consequence of

  11. Folates for reduction of risk of neural tube defects: using oral contraceptives as a source of folate

    Directory of Open Access Journals (Sweden)

    Nelson AL

    2011-11-01

    Full Text Available Anita L Nelson Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, CA, USA Abstract: The evidence that folates reduce the risk of neural tube defects (NTDs is so compelling that supplementation has been recommended by every relevant authority. The Cochrane Database of Systematic Reviews has determined that folate supplementation should be rated as a Grade 1 recommendation. United States Preventive Health Services Task Force, the US Food and Drug Administration (FDA, and the Centers for Disease Control and Prevention (CDC have all produced clear guidelines for such supplementation. Unfortunately, despite food fortification and targeted public health campaigns promoting folic acid supplementation, periconceptional utilization of folic acid supplements has decreased in the US in recent years. Worldwide, over 300,000 newborns are affected with NTDs every year. NTDs account for 10% of all neonatal mortality. This article will review the risk factors for NTDs and the evidence supporting folate supplementation. It will also describe the remaining problems and outline current ideas to solve them. Finally, new evidence of the effectiveness of adding metafolin to drospirenone-containing oral contraceptives in raising serum and red blood cell folate levels, the rationale for making such an addition, and an estimate of the magnitude of the contribution use of such pills might have on reducing NTDs will be discussed. Keywords: neural tube defects, folate, metafolin, oral contraceptives

  12. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of ...

    African Journals Online (AJOL)

    olayemitoyin

    Plasma ADA in DSTB patients before and 6 months of chemotherapy were not significantly different compared MDR TB patients. ... Also, ADA deficiency has a direct effect on the lungs, .... showed that the patients were sputum smear negative.

  13. Transformation of folate-consuming Lactobacillus gasseri into a folate producer

    NARCIS (Netherlands)

    Wegkamp, H.B.A.; Starrenburg, M.; Vos, de W.M.; Hugenholtz, J.; Sybesma, W.F.H.

    2004-01-01

    Five genes essential for folate biosynthesis in Lactococcus lactis were cloned on a broad-host-range lactococcal vector and were transferred to the folate auxotroph Lactobacillus gasseri. As a result L. gasseri changed from a folate consumer to a folate producer. This principle can be used to increa

  14. Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children

    OpenAIRE

    2013-01-01

    Aims/hypothesis In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points. Methods We measured plasma vitamin B12, folate...

  15. Mild folate deficiency induces genetic and epigenetic instability and phenotype changes in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Matsui Sei-Ichi

    2010-01-01

    Full Text Available Abstract Background Folate (vitamin B9 is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate (dTMP and s-adenosylmethionine (AdoMet. The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance, but still unclear. We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis, which is prominent in prostate cells. We, therefore, hypothesized that prostate cells might be highly susceptible to genetic, epigenetic and phenotypic changes consequent to folate restriction. Results We studied the consequences of long-term, mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate (TRAMP model, recapitulating different stages of prostate cancer; benign, transformed and metastatic. High-performance liquid chromatography analysis demonstrated that mild folate depletion (100 nM sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines. Random oligonucleotide-primed synthesis (ROPS revealed a significant increase in uracil misincorporation and DNA single strand breaks, while spectral karyotype analysis (SKY identified five novel chromosomal rearrangements in cells grown with mild folate depletion. Using global approaches, we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine, indicating a broad effect of folate depletion on epigenetic regulation. These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion. Conclusions This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with

  16. Mild folate deficiency induces genetic and epigenetic instability and phenotype changes in prostate cancer cells

    Science.gov (United States)

    2010-01-01

    Background Folate (vitamin B9) is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate (dTMP) and s-adenosylmethionine (AdoMet). The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance, but still unclear. We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis, which is prominent in prostate cells. We, therefore, hypothesized that prostate cells might be highly susceptible to genetic, epigenetic and phenotypic changes consequent to folate restriction. Results We studied the consequences of long-term, mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate (TRAMP) model, recapitulating different stages of prostate cancer; benign, transformed and metastatic. High-performance liquid chromatography analysis demonstrated that mild folate depletion (100 nM) sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines. Random oligonucleotide-primed synthesis (ROPS) revealed a significant increase in uracil misincorporation and DNA single strand breaks, while spectral karyotype analysis (SKY) identified five novel chromosomal rearrangements in cells grown with mild folate depletion. Using global approaches, we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine, indicating a broad effect of folate depletion on epigenetic regulation. These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion. Conclusions This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with supraphysiological

  17. Causes of vitamin B12 and folate deficiency.

    Science.gov (United States)

    Allen, Lindsay H

    2008-06-01

    This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.

  18. Plasma immersion ion implantation for reducing metal ion release

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, C.; Garcia, J. A.; Maendl, S.; Pereiro, R.; Fernandez, B.; Rodriguez, R. J. [Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain); Leibniz-Institut fuer Oberflaechenmodifizierung, 04318 Leipzig (Germany); Universidad de Oviedo, Departamento Quimica Fisica y Analitica (Spain); Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain)

    2012-11-06

    Plasma immersion ion implantation of Nitrogen and Oxygen on CoCrMo alloys was carried out to improve the tribological and corrosion behaviors of these biomedical alloys. In order to optimize the implantation results we were carried experiments at different temperatures. Tribocorrosion tests in bovine serum were used to measure Co, Cr and Mo releasing by using Inductively Coupled Plasma Mass Spectrometry analysis after tests. Also, X-ray Diffraction analysis were employed in order to explain any obtained difference in wear rate and corrosion tests. Wear tests reveals important decreases in rate of more than one order of magnitude for the best treatment. Moreover decreases in metal release were found for all the implanted samples, preserving the same corrosion resistance of the unimplanted samples. Finally this paper gathers an analysis, in terms of implantation parameters and achieved properties for industrial implementation of these treatments.

  19. Genetic associations with plasma B12, B6, and folate levels in an ischemic stroke population from the Vitamin Intervention for Stroke Prevention (VISP) trial

    OpenAIRE

    Keene, Keith L; Wei-Min eChen; Fang eChen; Stephen Richardson Williams; Elkhatib, Stacey D.; Fang-Chi eHsu; Mychaleckyj, Josyf C; Doheny, Kimberley F.; Pugh, Elizabeth W.; Hua eLing; Cathy C Laurie; Stephanie M Gogarten; Madden, Ebony B.; Worrall, Bradford B.; Sale, Michele M.

    2014-01-01

    B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high dose folic acid, vitamins B6 and B12 reduce recurrent cerebral infarction. Extensive quality control (QC) measures re...

  20. Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial

    OpenAIRE

    Keene, Keith L; Chen, Wei-Min; Chen, Fang; Stephen R Williams; Elkhatib, Stacey D.; Hsu, Fang-Chi; Mychaleckyj, Josyf C; Doheny, Kimberly F.; Pugh, Elizabeth W.; Ling, Hua; Cathy C Laurie; Stephanie M Gogarten; Madden, Ebony B.; Worrall, Bradford B.; Sale, Michele M.

    2014-01-01

    Background: B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high-dose folic acid, vitamins B6, and B12 reduce recurrent cerebral infarction. Methods: Extensive quality...

  1. Reduced description of light impurities in hydrogen coronal plasmas

    Directory of Open Access Journals (Sweden)

    D. Kh. Morozov

    2000-01-01

    Full Text Available Se aplica la teor a de impurezas radiativas a plasmas de reactores termonu- cleares, as como a nubes interestelares e intergal acticas, atm osferas estelares y prominencias solares. Las impurezas radiativas son capaces de cambiar la din amica del plasma. Permiten la aparici on de nuevos tipos de equilibrio, de ondas lineales y no-lineales y cambian signi cativamente los criterios de estabilidad. Para una de- scripci on completa de las impurezas, uno necesita un gran conjunto de ecuaciones que describan a cada uno de los estados de ionizaci on. Se muestra que es posible describir impurezas ligeras, con exactitud aceptable, con s olo dos o tres estados representativos de ionizaci on. Se muestra que la descripci on de cinco estados puede reducirse a uno de tres estados de ionizaci on. Se propone un modelo reducido para impurezas ligeras o para impurezas pesadas altamente ionizadas en plasmas coro- nales. Esto permite obtener soluciones anal ticas en muchos casos, reduciendo los tiempos de c omputo. Se deriva un conjunto de ecuaciones simples para determinar la din amica de la distribuci on de impurezas en los diferentes estados de ionizaci on.

  2. The Folate-Vitamin B12 Interaction, Low Hemoglobin, and the Mortality Risk from Alzheimer's Disease.

    Science.gov (United States)

    Min, Jin-Young; Min, Kyoung-Bok

    2016-03-21

    Abnormal hemoglobin levels are a risk factor for Alzheimer's disease (AD). Although the mechanism underlying these associations is elusive, inadequate micronutrients, particularly folate and vitamin B12, may increase the risk for anemia, cognitive impairment, and AD. In this study, we investigated whether the nutritional status of folate and vitamin B12 is involved in the association between low hemoglobin levels and the risk of AD mortality. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (1999-2006) Linked Mortality File. A total of 4,688 participants aged ≥60 years with available baseline data were included in this study. We categorized three groups based on the quartiles of folate and vitamin B12 as follows: Group I (low folate and vitamin B12); Group II (high folate and low vitamin B12 or low folate and high vitamin B12); and Group III (high folate and vitamin B12). Of 4,688 participants, 49 subjects died due to AD. After adjusting for age, sex, ethnicity, education, smoking history, body mass index, the presence of diabetes or hypertension, and dietary intake of iron, significant increases in the AD mortality were observed in Quartile1 for hemoglobin (HR: 8.4, 95% CI: 1.4-50.8), and the overall risk of AD mortality was significantly reduced with increases in the quartile of hemoglobin (p for trend = 0.0200), in subjects with low levels of both folate and vitamin B12 at baseline. This association did not exist in subjects with at least one high level of folate and vitamin B12. Our finding shows the relationship between folate and vitamin B12 levels with respect to the association between hemoglobin levels and AD mortality.

  3. Folate biofortification in food plants

    NARCIS (Netherlands)

    S. Bekaert; S. Storozhenko; P. Mehrshahi; M.J. Bennett; W. Lambert; J.F. Gregory III; K. Schubert; J. Hugenholtz; D. van der Straeten; A.D. Hanson

    2008-01-01

    Folate deficiency is a global health problem affecting many people in the developing and developed world. Current interventions (industrial food fortification and supplementation by folic acid pills) are effective if they can be used but might not be possible in less developed countries. Recent adva

  4. The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei*

    Science.gov (United States)

    Dewar, Simon; Sienkiewicz, Natasha; Ong, Han B.; Wall, Richard J.; Horn, David

    2016-01-01

    The aim of this study was to identify and characterize mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. In conjunction with drug susceptibility and folate transport studies, RNAi knockdown was used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterized in whole cells. RNA interference target sequencing experiments identified a tandem array of genes encoding a folate transporter family, TbFT1–3, as major contributors to antifolate drug uptake. RNAi knockdown of TbFT1–3 substantially reduced folate transport into trypanosomes and reduced the parasite's susceptibly to the classical antifolates methotrexate and raltitrexed. In contrast, knockdown of TbFT1–3 increased susceptibly to the non-classical antifolates pyrimethamine and nolatrexed. Both folate and methotrexate transport were inhibited by classical antifolates but not by non-classical antifolates or biopterin. Thus, TbFT1–3 mediates the uptake of folate and classical antifolates in trypanosomes, and TbFT1–3 loss-of-function is a mechanism of antifolate drug resistance. PMID:27703008

  5. Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice.

    Science.gov (United States)

    Nogueira, Eugénia; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, Ana; Almeida, Catarina R; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J L; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M; Gomes, Andreia C; Preto, Ana; Bismuth, Georges; Cavaco-Paulo, Artur

    2015-12-01

    Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.

  6. Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC.

    Science.gov (United States)

    Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2016-08-26

    Folate deficiency in fetal life is strongly associated with structural malformations and linked to intrauterine growth restriction. In addition, limited availability of methyl donors, such as folate, during pregnancy may result in abnormal gene methylation patterns and contribute to developmental programming. The fetus is dependent on placental transfer of folate, however the molecular mechanisms regulating placental folate transport are unknown. We used cultured primary human trophoblast cells to test the hypothesis that mechanistic target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake. Folate uptake stimulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of FR-α and RFC transporter isoforms without affecting global protein expression. Inhibition of the ubiquitin ligase Nedd4-2 had no effect on folate transport. In conclusion, we report for the first time that mTORC1/C2 are positive regulators of cellular folate uptake by modulating the cell surface abundance of specific transporter isoforms. We propose that regulation of placental folate transport by mTOR signaling provide a direct link between placental function, gene methylation and fetal programming.

  7. Folate in oats and its milling fractions.

    Science.gov (United States)

    Edelmann, Minnamari; Kariluoto, Susanna; Nyström, Laura; Piironen, Vieno

    2012-12-01

    Total folate content in oat varieties from three harvesting years (2006-2008), and in oats milling fractions, was determined using microbiological assay. Furthermore, folate vitamer distribution in milling fractions were examined with the UPLC method, which was taken in use and validated. The total folate content of the cultivars varied moderately within each year. The average content in the 2008 samples was 685ng/gdm. The UPLC method proved fast and sensitive for determining seven folate monoglutamates in cereal samples. Folate content in fractions, which are normally discarded, such as flour from oat cutting and flaking, were 1.5- to 2.5-fold higher than in native grain. The main folate vitamers found in the oat fractions were 5-CH(3)-H(4)folate, 5-HCO-H(4)folate, and 5,10-CH(+)-H(4)folate. The UPLC results more closely matched the microbiological results compared to those that are usually achieved with HPLC methods. This study illustrates that oats and, especially, by-products of milling are good sources of folate.

  8. Multicusp type machine for electron cyclotron resonance plasma with reduced dimensions

    Science.gov (United States)

    Amemiya, H.; Maeda, M.

    1996-03-01

    Plasmas are created in a cusp type magnetic trap using electron cyclotron resonance heating. The magnetic field is generated with permanent magnets forming a 12-pole, whereby the polarity at the ends of the rods has been reversed in order to obtain end plugs and to improve the plasma confinement. In this way, the plasma volume could be reduced such that the cross section was close to or smaller than the cutoff width of a circular waveguide. This increases the microwave power absorbed and gives a high plasma density even above the cutoff value.

  9. Multicusp type machine for electron cyclotron resonance plasma with reduced dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Amemiya, H.; Maeda, M. [The Institute of Physical and Chemical Research (RIKEN), Hirosawa 2-1, Wako-shi, Saitama-Pref., 351-01 (Japan)

    1996-03-01

    Plasmas are created in a cusp type magnetic trap using electron cyclotron resonance heating. The magnetic field is generated with permanent magnets forming a 12-pole, whereby the polarity at the ends of the rods has been reversed in order to obtain end plugs and to improve the plasma confinement. In this way, the plasma volume could be reduced such that the cross section was close to or smaller than the cutoff width of a circular waveguide. This increases the microwave power absorbed and gives a high plasma density even above the cutoff value. {copyright} {ital 1996 American Institute of Physics.}

  10. MEMBRANE-TRANSPORT OF METHOTREXATE IN A SQUAMOUS CARCINOMA CELL-LINE ADAPTED TO LOW FOLATE CONCENTRATIONS

    NARCIS (Netherlands)

    van der Laan, B.F.A.M.; Jansen, G; VANGESTEL, JA; SCHORNAGEL, JH; HORDIJK, GJ

    1991-01-01

    Membrane transport characteristics of the folate analogue methotrexate (MTX) were studied in a human squamous carcinoma cell line of the head and neck (HNSCC) adapted to grow in tissue culture media with nanomolar reduced folate concentrations (SCC-11B-LF), as compared to SCC-11B cells grown in stan

  11. Homocysteine, folate and pregnancy outcomes.

    Science.gov (United States)

    Kim, M W; Hong, S-C; Choi, J S; Han, J-Y; Oh, M-J; Kim, H J; Nava-Ocampo, A; Koren, G

    2012-08-01

    The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8-14.6) μmol/ml, p homocysteine concentration with pre-eclampsia.

  12. A Milk-Free Diet Downregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome

    Science.gov (United States)

    Ramaekers, Vincent T.; Sequeira, Jeffrey M.; Blau, Nenad; Quadros, Edward V.

    2008-01-01

    In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a…

  13. Dietary folate and folate vitamers and the risk of prostate cancer in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Verhage, B.A.J.; Cremers, P.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2012-01-01

    Purpose: The aim of the present study was to examine the association between intake of folate, and specific folate vitamers, and the risk of advanced and total prostate cancer. Methods: The association between dietary folate and prostate cancer risk was evaluated in The Netherlands Cohort Study (NLC

  14. A Milk-Free Diet Downregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome

    Science.gov (United States)

    Ramaekers, Vincent T.; Sequeira, Jeffrey M.; Blau, Nenad; Quadros, Edward V.

    2008-01-01

    In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a…

  15. Validation of Folate-Enriched Eggs as a Functional Food for Improving Folate Intake in Consumers.

    Science.gov (United States)

    Altic, Leslie; McNulty, Helene; Hoey, Leane; McAnena, Liadhan; Pentieva, Kristina

    2016-11-30

    Functional foods enriched with folate may be beneficial as a means of optimizing folate status in consumers. We recently developed novel eggs enriched with folate through folic acid supplementation of the hen's feed, but their potential to influence consumer folate status is unknown because the natural folate forms incorporated into the eggs may not necessarily be retained during storage and cooking. This study aimed to determine the stability of natural folates in folate-enriched eggs under typical conditions of storage and cooking. Total folate was determined by microbiological assay following tri-enzyme treatment in folate-enriched eggs and un-enriched (barn and free-range) on the day they were laid, after storage (up to 27 days) and after using four typical cooking methods (boiling, poaching, frying, scrambling) for different durations. On the day of laying, the folate content of enriched eggs was found to be significantly higher than that of un-enriched barn or free-range eggs (mean ± SD; 123.2 ± 12.4 vs. 41.2 ± 2.8 vs. 65.6 ± 18.5 µg/100 g; p functional foods with enriched folate content. Further studies will confirm their effectiveness in optimizing the biomarker folate status of consumers.

  16. Cobalamin and folate status in 6 to 35 months old children presenting with acute diarrhea in Bhaktapur, Nepal.

    Directory of Open Access Journals (Sweden)

    Manjeswori Ulak

    Full Text Available BACKGROUND: Cobalamin and folate are essential micronutrients and are important in DNA and RNA synthesis, cell proliferation, growth, hematopoiesis, and cognitive function. However, data on cobalamin and folate status are lacking particularly from young children residing in low and middle income countries. OBJECTIVE: To measure cobalamin and folate status and identifies their predictors among 6 to 35 months old children presenting with acute diarrhea. DESIGN: This was a cross-sectional study in 823 children presenting with acute diarrhea. We measured plasma cobalamin, folate, methylmalonic acid and total homocysteine who sought treatment for acute diarrhea between June 1998 and August 2000. RESULTS: The mean (SD plasma concentrations of cobalamin, folate, total homocysteine and methylmalonic acid were 206 (124 pmol/L, 55 (32 nmol/L, 11.4 (5.6 µmol/L and 0.79 (1.2 µmol/L, respectively. The prevalence of low plasma cobalamin (10 µmol/L and elevated methylmalonic acid (>0.28 µmol/L were 73% and 52%, respectively. In the regression analyses, the plasma cobalamin concentration was positively associated with age, and introduction of animal or formula milk. CONCLUSIONS: Our study indicated that poor cobalamin status was common particularly among breastfed children. Folate deficiency was virtually none existent. Possible consequences of cobalamin deficiency in young children need to be explored.

  17. Folate inadequacy in the diet of pregnant women

    OpenAIRE

    2014-01-01

    OBJECTIVE: To estimate food and dietary folate inadequacies in the diets of adult pregnant women. METHODS: A prospective study was conducted with 103 healthy pregnant adult users of the Public Health Care System of Ribeirão Preto, São Paulo, Brazil. The present study included the 82 women with complete food intake data during pregnancy, which were collected by three 24-hour dietary recalls. Food folate (folate naturally present in foods) and dietary folate (food folate plus folate from f...

  18. Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase.

    Science.gov (United States)

    Kronenberg, Golo; Harms, Christoph; Sobol, Robert W; Cardozo-Pelaez, Fernando; Linhart, Heinz; Winter, Benjamin; Balkaya, Mustafa; Gertz, Karen; Gay, Shanna B; Cox, David; Eckart, Sarah; Ahmadi, Michael; Juckel, Georg; Kempermann, Gerd; Hellweg, Rainer; Sohr, Reinhard; Hörtnagl, Heide; Wilson, Samuel H; Jaenisch, Rudolf; Endres, Matthias

    2008-07-09

    Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/- hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency.

  19. Folate and fiber in the prevention of colorectal cancer:Between shadows and the light

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer deaths throughout the world. Endoscopy has its functional and finan-cial limitations; therefore,chemoprevention might be crucial in reducing the incidence of CRC. Although a number of studies have demonstrated the potential chemopreventive effects of folate (or folic acid),many challenges still remain. The relationship between fo-late intake and CRC risk is a complex association that might depend on many factors including ge...

  20. Socio-demographic and lifestyle factors associated with folate status among non-supplement-consuming Canadian women of childbearing age.

    Science.gov (United States)

    Shi, Yipu; De Groh, Margaret; MacFarlane, Amanda J

    2014-05-09

    Mandatory folic acid fortification was implemented in Canada in 1998 to reduce the risk of neural tube defects (NTD). Our objective was to assess the relationship between socio-demographic factors and folate status in non-supplement-consuming Canadian women of childbearing age. Data on demographic factors, lifestyle factors, physical measures and red blood cell (RBC) folate concentration were collected from 1,008 non-supplement-consuming women aged 15-49 years in the Canadian Health Measures Survey (2007-2009). RBC folate ³906 nmol/L was used as a cut-off for optimal folate status for protection from NTD. Approximately 75% of non-supplement consuming women had an RBC folate concentration ³906 nmol/L. Young age (15-19 years), White ethnicity, less than secondary education, lowest income adequacy, smoking and high body mass index were associated with a higher prevalence of lower folate status. After adjustment, only young age (adjusted odds ratio [OR] 1.99-95% confidence interval [CI]: 1.25-3.18) was associated with lower folate status. Less than secondary education (adjusted OR 5.66, 95% CI: 1.10-29.04) and lowest income adequacy (adjusted OR 4.77, 95% CI: 1.06-21.49) were associated with lower folate status in women aged 15-24 and 25-49 years, respectively. Many risk factors for lower folate status identified before food fortification was implemented were not associated with folate status in our representative sample of non-supplement-consuming Canadian women. However, younger women, women aged 15-24 with less than secondary education and women aged 25-49 with low income adequacy remain at risk of lower folate status, supporting the continued promotion of folic acid supplement use to women of childbearing age.

  1. Folate supplementation in people with sickle cell disease

    Science.gov (United States)

    Dixit, Ruchita; Nettem, Sowmya; Madan, Simerjit S; Soe, Htoo Htoo Kyaw; Abas, Adinegara BL; Vance, Leah D; Stover, Patrick J

    2017-01-01

    Background Sickle cell disease is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with sickle cell disease, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with sickle cell disease, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating sickle cell disease. Objectives To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with sickle cell disease. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries. Date of last search: 07 December 2015. Selection criteria Randomised, placebo-controlled trials of folate supplementation for sickle cell disease. Data collection and analysis Four review authors assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. We used the standard Cochrane-defined methodological procedures. Main results One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double

  2. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

    Science.gov (United States)

    Matejcic, M; de Batlle, J; Ricci, C; Biessy, C; Perrier, F; Huybrechts, I; Weiderpass, E; Boutron-Ruault, M C; Cadeau, C; His, M; Cox, D G; Boeing, H; Fortner, R T; Kaaks, R; Lagiou, P; Trichopoulou, A; Benetou, V; Tumino, R; Panico, S; Sieri, S; Palli, D; Ricceri, F; Bueno-de-Mesquita, H B As; Skeie, G; Amiano, P; Sánchez, M J; Chirlaque, M D; Barricarte, A; Quirós, J R; Buckland, G; van Gils, C H; Peeters, P H; Key, T J; Riboli, E; Gylling, B; Zeleniuch-Jacquotte, A; Gunter, M J; Romieu, I; Chajès, V

    2017-03-15

    Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

  3. High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus.

    Science.gov (United States)

    Lai, Jun S; Pang, Wei Wei; Cai, Shirong; Lee, Yung Seng; Chan, Jerry K Y; Shek, Lynette P C; Yap, Fabian K P; Tan, Kok Hian; Godfrey, Keith M; van Dam, Rob M; Chong, Yap Seng; Chong, Mary F F

    2017-03-24

    B-vitamins and homocysteine may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the cross-sectional associations of plasma folate, vitamins B6, B12, and homocysteine concentrations with GDM and glycemia in a sample of multi-ethnic Asian pregnant women. Plasma concentrations of folate, vitamins B6, B12, homocysteine and glucose were measured at 26-weeks' gestation in 913 pregnant women. GDM was diagnosed using the 1999 World Health Organization criteria. Associations were examined with linear or logistic regression, adjusted for confounders and stratified by ethnicity. Higher plasma folate was associated with higher 2-h glucose and higher odds of GDM [0.15 (0.02, 0.23) per 1-SD increment in folate, OR 1.29 (1.00, 1.60)], mainly among Indian mothers. Higher plasma vitamin B12 and homocysteine were associated with lower fasting and 2-h glucose, and lower odds of GDM [-0.04 (-0.07, -0.01) per 1-SD increment in B12 and -0.09 (-0.18, -0.003) respectively, OR: 0.81 (0.68, 0.97); -0.05 (-0.08, -0.02) per 1-SD increment in homocysteine and -0.12 (-0.21, -0.02) respectively, OR: 0.76 (0.62, 0.92)]. The highest odds of GDM were observed among women with combined vitamin B12 insufficiency and high folate concentration [OR: 1.97 (1.05, 3.68)]. An association between higher vitamin B6 and higher 2-h glucose shifted towards null adjusting for other B-vitamins. Higher maternal folate coupled with vitamin B12 insufficiency was associated with higher GDM risk. This finding has potential implications for antenatal supplement recommendations but will require confirmation in future studies. Copyright © 2017. Published by Elsevier Ltd.

  4. Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases.

    Science.gov (United States)

    Stamp, Lisa K; Roberts, Rebecca L

    2011-10-01

    Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis and is frequently used in the management of other forms of inflammatory arthritis. It is currently challenging to predict which patients will achieve adequate disease control and which patients will develop adverse effects while taking MTX. As an analog of dihydrofolic acid, MTX enters cells through the reduced folate carrier-1 protein, and is polyglutamated. MTX polyglutamates inhibit key enzymes in the folate pathway to produce an anti-inflammatory effect. It has been suggested that genetic polymorphisms in the folate pathway may influence intracellular folate and MTX polyglutamates pools, and thus MTX response. However, studies to identify genetic predictors have yielded inconclusive results. Nonreplication across studies has been attributed to insufficient statistical power as well as pharmacological and clinical confounders. Prospective studies, standardizing the definitions of response and toxicity, and application of genome-wide approaches may advance the search for genetic predictors of MTX response.

  5. Folate supplementation in patients with psoriasis treated with methotrexate – effect on safety and efficacy

    Directory of Open Access Journals (Sweden)

    Magdalena Żychowska

    2014-10-01

    Full Text Available Methotrexate (MTX is commonly used in dermatology, mainly in patients with psoriasis and psoriatic arthritis. Gastrointestinal disorders, mouth ulcerations, malaise, hair loss, hepatic dysfunction and bone marrow suppression are the most common adverse effects of MTX therapy. The occurrence of side effects is suggested to be the main reason for discontinuation of the therapy. Supplementation with folates seems to be a good strategy in limiting adverse effects; however, excessive doses may decrease the efficacy of MTX therapy. Currently, there are no consistent recommendations for folate supplementation in psoriatic patients. An extensive PubMed search (1960 – March 2014 revealed only a few studies, with one randomized controlled trial concerning the impact of folate supplementation in patients with psoriasis. These studies support the protective effect of folate supplementation and suggest that folic acid may reduce gastrointestinal disturbances. Further research, including randomized controlled trials, should be performed.

  6. Bioavailability of folate from fortified milk products

    NARCIS (Netherlands)

    Verwei, M.

    2004-01-01

    The gap between actual intake and recommended intake of folate could be bridged by the consumption of fortified food products. Milk is considered as a potential food matrix for folate fortification in countries (such as theFolate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

    Aging is associated with increased risk of cardiovascular and neurodegenerative disorders and an increase in their risk factors, such as decreased concentrations of folate and increased concentrations of homocysteine. The association of folate and homocysteine with age-related disease and, most impo

  7. Rho GTPases RhoA and Rac1 mediate effects of dietary folate on metastatic potential of A549 cancer cells through the control of cofilin phosphorylation.

    Science.gov (United States)

    Oleinik, Natalia V; Helke, Kristi L; Kistner-Griffin, Emily; Krupenko, Natalia I; Krupenko, Sergey A

    2014-09-19

    Folate, an important nutrient in the human diet, has been implicated in cancer, but its role in metastasis is not established. We have shown previously that the withdrawal of medium folate leads to the inhibition of migration and invasion of A549 lung carcinoma cells. Here we have demonstrated that medium folate regulates the function of Rho GTPases by enabling their carboxyl methylation and translocation to plasma membrane. Conversely, the lack of folate leads to the retention of these proteins in endoplasmic reticulum. Folate also promoted the switch from inactive (GDP-bound) to active (GTP-bound) GTPases, resulting in the activation of downstream kinases p21-activated kinase and LIM kinase and phosphorylation of the actin-depolymerizing factor cofilin. We have further demonstrated that in A549 cells two GTPases, RhoA and Rac1, but not Cdc42, are immediate sensors of folate status: the siRNA silencing of RhoA or Rac1 blocked effects of folate on cofilin phosphorylation and cellular migration and invasion. The finding that folate modulates metastatic potential of cancer cells was confirmed in an animal model of lung cancer using tail vein injection of A549 cells in SCID mice. A folate-rich diet enhanced lung colonization and distant metastasis to lymph nodes and decreased overall survival (35 versus 63 days for mice on a folate-restricted diet). High folate also promoted epithelial-mesenchymal transition in cancer cells and experimental mouse tumors. Our study provides experimental evidence for a mechanism of metastasis promotion by dietary folate and highlights the interaction between nutrients and metastasis-related signaling.

  8. Folate deficiency and neurological disorders in adults.

    Science.gov (United States)

    Botez, M I

    1976-01-01

    The restless legs syndrome could represent a folate responsive disorder in both patients with acquired-folate deficiency and those with familial symptomatology. Patients with acquired folate-deficiency could be divided into two subgroups. (i) those with minor neurological signs (restless legs syndrome, vibration sense impairment and tactile hypoesthesia in both legs with diminished ankle jerks and a prolonged or assymetrical Achilles-reflex time) and (ii) those with major neurological signs (subacute combined degeneration with or without neuropathies). In some of these patients the classical triad of the malabsorption syndrome is replaced by another triad, constipation, abnormal jejunal biopsy and abnormal d-xylose absorption. A low folic serum acid level could induce minor neuropsychiatric symptoms while an additional low CSF folate could induce major neurological symptoms in spite of the presence of a normal erythrocyte folate level and in the absence of frank anemia. Possible further studies are described.

  9. Surface Modification of Fine Particle by Plasma Grafting in a Circulating Fluidized Bed Reactor under Reduced Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sounghee [Woosuk University, Jinchon (Korea, Republic of)

    2015-10-15

    A plasma surface modification of powders has been carried out in a circulating fluidized bed reactor under reduced pressure. Polystyrene (PS) particles treated by plasma are grafted with polyethylene glycol (PEG) on the surface. The virgin, plasma-treated and grafted powders were characterized by DPPH method, FTIR, SEM and contact angle meter. The plasma-treated PS powders have well formed peroxide on the surface, By PEG grafting polymerization, PEG is well grafted and dispersed on the surface of the plasma-treated PS powders. The PEG-g-PS particle was successfully synthesized using the plasma circulating fluidized bed reactor under reduced pressure.

  10. Validation of Folate-Enriched Eggs as a Functional Food for Improving Folate Intake in Consumers

    Directory of Open Access Journals (Sweden)

    Leslie Altic

    2016-11-01

    Full Text Available Functional foods enriched with folate may be beneficial as a means of optimizing folate status in consumers. We recently developed novel eggs enriched with folate through folic acid supplementation of the hen’s feed, but their potential to influence consumer folate status is unknown because the natural folate forms incorporated into the eggs may not necessarily be retained during storage and cooking. This study aimed to determine the stability of natural folates in folate-enriched eggs under typical conditions of storage and cooking. Total folate was determined by microbiological assay following tri-enzyme treatment in folate-enriched eggs and un-enriched (barn and free-range on the day they were laid, after storage (up to 27 days and after using four typical cooking methods (boiling, poaching, frying, scrambling for different durations. On the day of laying, the folate content of enriched eggs was found to be significantly higher than that of un-enriched barn or free-range eggs (mean ± SD; 123.2 ± 12.4 vs. 41.2 ± 2.8 vs. 65.6 ± 18.5 µg/100 g; p < 0.001. Storage at refrigerator and room temperature for periods up to the Best Before date resulted in no significant losses to the folate content of folate-enriched eggs. Furthermore, folate in enriched eggs remained stable when cooked by four typical methods for periods up to the maximum cooking time (e.g., 135 ± 22.5, 133.9 ± 23.0 and 132.5 ± 35.1; p = 0.73, for raw, scrambled for 50 s and scrambled for 2 min, respectively. Thus, natural folates in folate-enriched eggs remain highly stable with little or no losses following storage and cooking. These findings are important because they demonstrate the feasibility of introducing folate-enriched eggs into the diet of consumers as functional foods with enriched folate content. Further studies will confirm their effectiveness in optimizing the biomarker folate status of consumers.

  11. The tunable plasma synthesis of Pt-reduced graphene oxide nanocomposites

    Directory of Open Access Journals (Sweden)

    Yulong Ma

    2017-06-01

    Full Text Available Herein, we have developed Pt-plasma reduced graphene oxide (Pt/P-rGO catalysts displaying high overpotentials for methanol oxidation reaction (MOR through facile and tunable plasma treatments. We provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. The analysis results showed that the Pt nanoparticles (NPs were successfully deposited on P-rGO. The deposition and uniformity of Pt NPs were influenced by tuning the discharge power of the plasma. The catalytic performance towards the methanol oxidation reaction is investigated. The Pt/P-rGO NPs composites under 100 W show the best electrocatalytic activity. These results were vital to the further application of graphene-based metal nanocomposites synthesized by plasma technology.

  12. Increased production of folate by metabolic engineering of Lactococcus lactis

    NARCIS (Netherlands)

    Sybesma, W.F.H.; Starrenburg, M.; Kleerebezem, M.; Mierau, I.; Vos, de W.M.; Hugenholtz, J.

    2003-01-01

    The dairy starter bacterium Lactococcus lactis is able to synthesize folate and accumulates large amounts of folate, predominantly in the polyglutamyl form. Only small amounts of the produced folate are released in the extracellular medium. Five genes involved in folate biosynthesis were identified

  13. Quantifying folate bioavailability: a critical appraisal of methods

    NARCIS (Netherlands)

    Boonstra, A.; Verhoef, P.; West, C.E.

    2004-01-01

    Purpose of review Dietary reference intakes for folate rely on a good estimate of folate bioavailability from the general diet. In this review, current methods for quantifying the bioavailability of dietary folate and specific folate vitamers in humans are reviewed. Emphasis is on isotopic labeling

  14. Thrombolytic therapy reduces red blood cell aggregation in plasma without affecting intrinsic aggregability.

    Science.gov (United States)

    Ben-Ami, R; Sheinman, G; Yedgar, S; Eldor, A; Roth, A; Berliner, A S; Barshtein, G

    2002-03-15

    Red blood cell (RBC) aggregation may contribute to occlusion of the coronary microcirculation during myocardial infarction. We studied the effect of thrombolytic therapy on RBC aggregation in patients with acute myocardial infarction (AMI). Compared with patients with myocardial infarction who did not receive thrombolytic therapy, those treated with systemic thrombolysis exhibited significantly reduced RBC aggregation, reduced plasma fibrinogen levels and increased plasma D-dimer levels. Using measurement of RBC aggregation in a standardized dextran-500 solution, reduction in RBC aggregation after thrombolysis was shown to be plasma dependent. Thrombolytic therapy had no direct effect on intrinsic RBC aggregability in patients with AMI. We conclude that thrombolytic therapy has rheologic consequences that may contribute to its overall efficacy. Inhibition of RBC aggregation by thrombolytic therapy may result from the degradation of fibrinogen, a key factor in the formation of RBC aggregates, and from the generation of fibrinogen degradation products capable of disaggregating RBCs.

  15. Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Joshua T Emmerson

    2016-07-01

    Full Text Available Context Folates are B-vitamins that cannot be generated de novo and are therefore obtained from the diet. In the brain, these vitamins are involved in nucleotide synthesis, DNA repair, lipid metabolism, methylation and neurotransmitter synthesis. It is well established that adequate levels of maternal folates are required for closure of the neural tube within the first month of pregnancy, however, it is not clear whether maternal folates are needed throughout pregnancy for brain development and whether they influence offspring neurological function after birth. The aim of this review is to outline current literature from epidemiological and animal model studies that shows maternal supplementation of folates throughout pregnancy does indeed affect offspring neurological function after birth. Evidence Acquisition A Medline search was performed using the following mesh terms, maternal-fetal exchange, folic acid, offspring neurologic manifestations, methylenetetrahydrofolate reductase (MTHFR, embryology, and behavior. Results The studies described in the present review have reported that maternal deficiencies in folates during pregnancy result in changes in behavior as well as in blood and brain tissue in offspring, including altered methylation, including reduced levels of the global methyl donor S-adenosylmethionine (SAM, and increased levels of oxidative stress. Conclusions The data summarized here outlines the importance of adequate levels of folates throughout pregnancy to facilitate appropriate neurological development of offspring after birth.

  16. Plasma-induced high efficient synthesis of boron doped reduced graphene oxide for supercapacitors

    DEFF Research Database (Denmark)

    Li, Shaobo; Wang, Zhaofeng; Jiang, Hanmei

    2016-01-01

    In this work, we presented a novel route to synthesize boron doped reduced graphene oxide (rGO) by using the dielectric barrier discharge (DBD) plasma technology under ambient conditions. The doping of boron (1.4 at%) led to a significant improvement in the capacitance of rGO and supercapacitors...

  17. Niacin reduces plasma CETP levels by diminishing liver macrophage content in CETP transgenic mice

    NARCIS (Netherlands)

    Li, Z.; Wang, Y.; Sluis, R.J. van der; Hoorn, J.W.A. van der; Princen, H.M.G.; Eck, M. van; Berkel, T.J.C. van; Rensen, P.C.N.; Hoekstra, M.

    2012-01-01

    The anti-dyslipidemic drug niacin has recently been shown to reduce the hepatic expression and plasma levels of CETP. Since liver macrophages contribute to hepatic CETP expression, we investigated the role of macrophages in the CETP-lowering effect of niacin in mice. In vitro studies showed that nia

  18. High thermoelectric performance of reduced lanthanide molybdenum oxides densified by spark plasma sintering

    DEFF Research Database (Denmark)

    Xu, Jianxiao Jackie; Sonne, Monica; Yanangiya, Shun-ichi

    2010-01-01

    Four highly reduced molybdenum oxides LnMo8O14 (Ln = La, Ce, Nd and Sm) containing bicapped Mo8 clusters were synthesized via solid state reaction followed by spark plasma sintering. The thermoelectric properties were investigated, and NdMo8O14 exhibits the best performance with the maximum power...

  19. Arc Root Motions in an Argon-Hydrogen Direct-Current Plasma Torch at Reduced Pressure

    Institute of Scientific and Technical Information of China (English)

    HUANG He-Ji; PAN Wen-Xia; WU Cheng-Kang

    2008-01-01

    Arc root motions in generating dc argon hydrogen plasma at reduced pressure are optically observed using a high-speed video camera. The time resolved angular position of the arc root attachment point is measured and analysed. The arc root movement is characterized as a chaotic and jumping motion along the circular direction on the anode surface.

  1. Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome.

    Directory of Open Access Journals (Sweden)

    Michelle K Y Siu

    Full Text Available Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα in carcinomas. The role of another folate transporter, reduced folate carrier (RFC, is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic and RFC (putative tumor suppressive in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients.

  2. Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome.

    Science.gov (United States)

    Siu, Michelle K Y; Kong, Daniel S H; Chan, Hoi Yan; Wong, Esther S Y; Ip, Philip P C; Jiang, LiLi; Ngan, Hextan Y S; Le, Xiao-Feng; Cheung, Annie N Y

    2012-01-01

    Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients.

  3. Resistive Reduced MHD Modeling of Multi-Edge-Localized-Mode Cycles in Tokamak X -Point Plasmas

    Science.gov (United States)

    Orain, F.; Bécoulet, M.; Huijsmans, G. T. A.; Dif-Pradalier, G.; Hoelzl, M.; Morales, J.; Garbet, X.; Nardon, E.; Pamela, S.; Passeron, C.; Latu, G.; Fil, A.; Cahyna, P.

    2015-01-01

    The full dynamics of a multi-edge-localized-mode (ELM) cycle is modeled for the first time in realistic tokamak X -point geometry with the nonlinear reduced MHD code jorek. The diamagnetic rotation is found to be instrumental to stabilize the plasma after an ELM crash and to model the cyclic reconstruction and collapse of the plasma pressure profile. ELM relaxations are cyclically initiated each time the pedestal gradient crosses a triggering threshold. Diamagnetic drifts are also found to yield a near-symmetric ELM power deposition on the inner and outer divertor target plates, consistent with experimental measurements.

  4. Maternal Risk for Down Syndrome Is Modulated by Genes Involved in Folate Metabolism

    Directory of Open Access Journals (Sweden)

    Bruna Lancia Zampieri

    2012-01-01

    Full Text Available Studies have shown that the maternal risk for Down syndrome (DS may be modulated by alterations in folate metabolism. The aim of this study was to evaluate the influence of 12 genetic polymorphisms involved in folate metabolism on maternal risk for DS. In addition, we evaluated the impact of these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an indicator of vitamin B12 status concentrations. The polymorphisms transcobalamin II (TCN2 c.776C>G, betaine-homocysteine S-methyltransferase (BHMT c.742A>G, methylenetetrahydrofolate reductase (NAD(PH (MTHFR c.677 C>T and the MTHFR 677C-1298A-1317T haplotype modulate DS risk. The polymorphisms MTHFR c.677C>T and solute carrier family 19 (folate transporter, member 1 (SLC19A1 c.80 A>G modulate folate concentrations, whereas the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR c.66A>G polymorphism affects the MMA concentration. These results are consistent with the modulation of the maternal risk for DS by these polymorphisms.

  5. Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis.

    Science.gov (United States)

    Rengarajan, Srinivas; Lee, Donna H; Oh, Young Taek; Delpire, Eric; Youn, Jang H; McDonough, Alicia A

    2014-05-01

    Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.

  6. Folate

    Science.gov (United States)

    ... and corn masa flour (used to make corn tortillas and tamales, for example). To find out whether ... Dietary Guidelines for Americans . Foods contain vitamins, minerals , dietary fiber and other substances that benefit health. In some ...

  7. Professor John Scott, folate and neural tube defects.

    Science.gov (United States)

    Hoffbrand, A Victor

    2014-02-01

    John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. © 2013 John Wiley & Sons Ltd.

  8. Folate Receptor Targeted Alpha-Therapy Using Terbium-149

    Directory of Open Access Journals (Sweden)

    Cristina Müller

    2014-03-01

    Full Text Available Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09 using folate receptor (FR-positive cancer cells in vitro and in tumor-bearing mice. 149Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified 149Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with 149Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A or with 149Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq. A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received 149Tb-cm09 (B: 30.5 d; C: 43 d compared to untreated controls (A: 21 d. Analysis of blood parameters revealed no signs of acute toxicity to the kidneys or liver in treated mice over the time of investigation. These results demonstrated the potential of folate-based α-radionuclide therapy in tumor-bearing mice.

  9. Pilot Study on Folate Bioavailability from A Camembert Cheese reveals contradictory findings to recent results from a Human Short-term study

    Directory of Open Access Journals (Sweden)

    Sabine eMönch

    2016-04-01

    Full Text Available Different dietary sources of folate have differing bioavailabilities which may affect their nutritional value. In order to examine if these differences also occur within the same food products, a short term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analysed by stable isotope dilution assays. The biokinetic parameters Cmax, tmax and AUC were determined in plasma within the interval of 0 to 12 hours. When comparing the ratio estimates of AUC and Cmax for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64% compared to a different brand in our previous investigation (8.8%. It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50 % bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

  10. Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study.

    Science.gov (United States)

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2016-01-01

    Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional "value." In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters C max, t max, and area under the curve (AUC) were determined in plasma within the interval of 0-12 h. When comparing the ratio estimates of AUC and C max for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

  11. Compliance with Iron-Folate Supplement and Associated Factors among Antenatal Care Attendant Mothers in Misha District, South Ethiopia: Community Based Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Abinet Arega Sadore

    2015-01-01

    Full Text Available Background. In Ethiopia, higher proportions of pregnant women are anemic. Despite the efforts to reduce iron deficiency anemia during pregnancy, only few women took an iron supplement as recommended. Thus, this study aimed to assess compliance with iron-folate supplement and associated factors among antenatal care attendant mothers in Misha district, South Ethiopia. Method. Community based cross-sectional study supported with in-depth interview was conducted from March 1 to March 30, 2015. The sample size was determined using single population proportion to 303. Simple random sampling technique was used to select the study participants. Bivariate and multivariable logistic regression analyses were employed to identify factors associated with compliance to iron-folate supplement. Results. The compliance rate was found to be 39.2%. Mothers knowledge of anemia (AOR = 4.451, 95% CI = (2.027,9.777, knowledge of iron-folate supplement (AOR = 3.509, 95% CI = (1.442,8.537, and counseling on iron-folate supplement (AOR = 4.093, 95% CI = (2.002,8.368 were significantly associated with compliance to iron-folate supplement. Conclusions. Compliance rate of iron-folate supplementation during pregnancy remains very low. This study showed that providing women with clear instructions about iron-folate tablet intake and educating them on the health benefits of the iron-folate tablets can increase compliance with iron-folate supplementation.

  12. Folate deficiency increases mtDNA and D-1 mtDNA deletion in aged brain of mice lacking uracil-DNA glycosylase.

    Science.gov (United States)

    Kronenberg, Golo; Gertz, Karen; Overall, Rupert W; Harms, Christoph; Klein, Jeanette; Page, Melissa M; Stuart, Jeffrey A; Endres, Matthias

    2011-04-01

    Strong epidemiological and experimental evidence links folate deficiency and resultant hyperhomocysteinemia with cognitive decline and neurodegeneration. Here, we tested the hypothesis that uracil misincorporation contributes to mitochondrial pathology in aged brain following folate deprivation. In a 2 × 2 design, 14-month-old mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls were subjected to a folate-deficient versus a regular diet for six weeks. Folate-deficient feeding significantly enhanced mtDNA content and overall abundance of the D-1 mtDNA deletion in brain of Ung-/-, but not of wild-type mice. Independent of folate status, the frequency of the D-1 mtDNA deletion in mtDNA was significantly increased in Ung-/- mice. The rate of mitochondrial biogenesis as assessed at six weeks of the experimental diet by mRNA expression levels of transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and of mitochondrial transcription factor A (Tfam) was not affected by either Ung-/- genotype or short-term folate deficiency. Similarly, citrate synthase (CS) activity in the brain did not differ across experimental groups. By contrast, independent of genotype, lactate dehydrogenase (LDH) activity was significantly reduced in folate-deficient animals. Our results suggest that impaired uracil excision repair causes an increase in mitochondrial mutagenesis in aged brain along with a compensatory increase in mtDNA content in response to low folate status. Folate deficiency may contribute to neurodegeneration via mtDNA damage.

  13. Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.

    Science.gov (United States)

    Jia, Xiaoming; Chen, Yanfeng; Zidichouski, Jeffrey; Zhang, Junzeng; Sun, Changhao; Wang, Yanwen

    2008-11-01

    The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100mgkg(-1)bodyweightd(-1)), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p=0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p=0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p=0.0002) and non-HDL-C by 59% (peffect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p=0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects.

  14. Plasma osmolality predicts mortality in patients with heart failure with reduced ejection fraction.

    Science.gov (United States)

    Kaya, HakkI; Yücel, Oğuzhan; Ege, Meltem Refiker; Zorlu, Ali; Yücel, Hasan; Güneş, Hakan; Ekmekçi, Ahmet; Yılmaz, Mehmet Birhan

    2017-01-01

    Heart failure (HF) is a fatal disease. Plasma osmolality with individual impacts of sodium, blood urea nitrogen (BUN), and glucose has not been studied prognostically in patients with HF. This study aims to investigate the impact of serum osmolality on clinical endpoints in HF patients. A total of 509 patients (383 males, 126 females) with HF with reduced ejection fraction in three HF centres were retrospectively analysed between January 2007 and December 2013. Follow-up data were completed for 496 patients. Plasma osmolality was calculated as (2 × Na) + (BUN/2.8) + (Glucose/18). Quartiles of plasma osmolality were produced, and the possible relationship between plasma osmolality and cardiovascular mortality was investigated. The mean follow-up was 25 ± 22 months. The mean age was 56.5 ± 17.3 years with a mean EF of 26 ± 8%. The mean levels of plasma osmolality were as follows in the quartiles: 1st % = 280 ± 6, 2nd % = 288 ± 1, 3rd % = 293 ± 2 (95% confidence interval [CI] 292.72-293.3), and 4th % = 301 ± 5 mOsm/kg. The EF and B-type natriuretic peptide levels were similar in the four quartiles. Univariate and multivariate analyses in the Cox proportional hazard model revealed a significantly higher rate of mortality in the patients with hypo-osmolality. The Kaplan-Meier plot showed graded mortality curves with the 1st quartile having the worst prognosis, followed by the 4th quartile and the 2nd quartile, while the 3rd quartile was shown to have the best prognosis. Our study results suggest that normal plasma osmolality is between 275 and 295 mOsm/kg. However, being close to the upper limit of normal range (292-293 mOsm/kg) seems to be the optimal plasma osmolality level in terms of cardiovascular prognosis in patients with HF.

  15. Genetics Home Reference: hereditary folate malabsorption

    Science.gov (United States)

    ... individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number ... Deficiency Encyclopedia: Folate-Deficiency Anemia Encyclopedia: Malabsorption Encyclopedia: Megaloblastic Anemia (image) Health Topic: Anemia Health Topic: Folic Acid ...

  16. Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cellsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Baslund, B.; Gregers, J.; Nielsen, Claus Henrik

    2008-01-01

    OBJECTIVE: To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells. METHODS: Mononuclear cells were isolated from peripheral blood of healthy persons. Real-time PCR was used to detect the RFC80 variants. FITC-labelled MTX was added...... to cells stimulated with Candida albicans or tetanus toxoid, and the uptake of MTX was measured by flow cytometry. A FITC-conjugated monoclonal antibody against RFC was used to detect the cellular RFC expression. RESULTS: Antigen-stimulated CD4+ T cells and B cells from individuals with the GG variant (n...... = 9) exhibited lower uptake of MTX than individuals expressing the AA variant (n = 8), or the GA variant (n = 8). No difference could be demonstrated between the three groups with respect to the expression of RFC by CD4+ T cells and B cells, and CD4+ T cells from individuals homozygous for the G...

  17. High incidence of reduced plasma HDL cholesterol in diabetic patients treated with rosiglitazone and fibrate.

    Science.gov (United States)

    Keidar, Shlomo; Guttmann, Hadassa; Stam, Tamar; Fishman, Ilana; Shapira, Chen

    2007-11-01

    A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

  18. Red blood cell folate levels in pregnant women with a history of mood disorders: a case series

    Science.gov (United States)

    Yaremco, Elyse; Inglis, Angela; Innis, Sheila M.; Hippman, Catriona; Carrion, Prescilla; Lamers, Yvonne; Honer, William G.; Austin, Jehannine

    2014-01-01

    Objective Maternal folate supplementation reduces offspring risk for neural tube defects (NTDs) and other congenital abnormalities. Maternal red blood cell (RBC) folate concentrations of >906nmol/L have been associated with the lowest risk of having an NTD affected pregnancy. Mood disorders (e.g. depression, bipolar disorder) are common among women and can be associated with folate deficiency. Thus, pregnant women with histories of mood disorders may be prone to RBC folate levels insufficient to provide optimal protection against NTDs. While previous studies have assessed RBC folate concentrations in pregnant women from the general population, none have looked specifically at a group of pregnant women who have a history of a mood disorder. Methods We collected data about RBC folate concentrations and folic acid supplement intake during early pregnancy (906nmol/L, despite all participants reporting current daily use of folic acid supplements. Data regarding offspring were available for 22 women: birthweights ranged from 2296g to 4819g, and congenital abnormalities were identified in two (hypoplastic left heart, annular pancreas). Conclusion Data from this exploratory case series suggest a need for future larger scale controlled studies investigating RBC folate concentrations in early pregnancy and offspring outcomes among women with and without histories of mood disorders. PMID:23760977

  19. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels.

  20. Plasma-induced highly efficient synthesis of boron doped reduced graphene oxide for supercapacitors.

    Science.gov (United States)

    Li, Shaobo; Wang, Zhaofeng; Jiang, Hanmei; Zhang, Limei; Ren, Jingzheng; Zheng, Mingtao; Dong, Lichun; Sun, Luyi

    2016-09-21

    In this work, we presented a novel route to synthesize boron doped reduced graphene oxide (rGO) by using the dielectric barrier discharge (DBD) plasma technology under ambient conditions. The doping of boron (1.4 at%) led to a significant improvement in the capacitance of rGO and supercapacitors based on the as-synthesized B-rGO exhibited an outstanding specific capacitance.

  1. Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark

    DEFF Research Database (Denmark)

    Tjønneland, A; Christensen, J.; Olsen, A.

    2006-01-01

    There is consistent evidence that alcohol increases the risk of breast cancer. It has been suggested that the increased risk associated with alcohol intake may be reduced by adequate intake of folate. Since many women consume alcohol, detection of a risk-reducing mechanism would have major public...

  2. Losartan reduces oxidative damage to renal DNA and conserves plasma antioxidant capacity in diabetic rats.

    Science.gov (United States)

    Lodovici, Maura; Bigagli, Elisabetta; Tarantini, Francesca; Di Serio, Claudia; Raimondi, Laura

    2015-11-01

    Increased reactive oxygen species (ROS) levels produced by hyperglycemia and angiotensin-II (AT-II) are considered among the pathogenic factors in the malignant transformation of diabetic renal cells. We aimed to investigate the potential role of AT-II in the increased cancer risk seen in diabetes; measuring oxidative damage to renal DNA and protective antioxidant defenses, including adiponectin (Adp) and plasma antioxidant capacity by the Ferric Reducing Ability of Plasma (FRAP) method. In the kidney of streptozotocin (STZ)-induced (55 mg/kg) diabetic rats either treated or not treated for 3 weeks with losartan, an AT-II type 1 receptor antagonist (20 mg/kg/day); we measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels, as an index of oxidative DNA damage, circulating Adp and FRAP. Diabetic rats showed significantly higher 8-oxodGuo levels in renal DNA (8.48 ± 0.98 × 10(-6) dG, mean ± SEM n = 11) than normoglycemic ones (1.18 ± 0.04 × 10(-6) dG, mean ± SEM, n=7) and lower plasma Adp and FRAP levels in comparison to normoglycemics. The treatment of diabetic rats with losartan significantly (P Losartan treatment preserves FRAP levels, reduces DNA oxidative injury and thus the carcinogenesis risk. Furthermore, our results indicate that Adp plasma levels are a further marker of oxidative injury to the kidney and confirm that it is an important part of the plasma antioxidant defense.

  3. Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study.

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

    2009-05-01

    Full Text Available BACKGROUND: Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. METHODS AND FINDINGS: In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08-0.61, p = 0.004 and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24-0.83, p = 0.010. Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11-0.90, p = 0.031 and 0.53, 0.28-0.99, p = 0.046, respectively. Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth

  4. Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

    Science.gov (United States)

    Bukowski, Radek; Malone, Fergal D.; Porter, Flint T.; Nyberg, David A.; Comstock, Christine H.; Hankins, Gary D. V.; Eddleman, Keith; Gross, Susan J.; Dugoff, Lorraine; Craigo, Sabrina D.; Timor-Tritsch, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; D'Alton, Mary E.

    2009-01-01

    Background Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. Methods and Findings In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08–0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24–0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11–0.90, p = 0.031 and 0.53, 0.28–0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm

  5. Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Guérard, Melanie, E-mail: melanie.guerard@roche.com; Zeller, Andreas; Festag, Matthias; Schubert, Christine; Singer, Thomas; Müller, Lutz

    2014-09-15

    The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the

  6. Long-term consumption of a raw food diet is associated with favorable serum LDL cholesterol and triglycerides but also with elevated plasma homocysteine and low serum HDL cholesterol in humans

    National Research Council Canada - National Science Library

    Koebnick, Corinna; Garcia, Ada L; Dagnelie, Pieter C; Strassner, Carola; Lindemans, Jan; Katz, Norbert; Leitzmann, Claus; Hoffmann, Ingrid

    2005-01-01

    ...) on serum lipids and plasma vitamin B-12, folate, and total homocysteine (tHcy). In a cross-sectional study, the lipid, folate, vitamin B-12, and tHcy status of 201 adherents to a raw food diet...

  7. Long-Term Consumption of a Raw Food Diet Is Associated with Favorable Serum LDL Cholesterol and Triglycerides but Also with Elevated Plasma Homocysteine and Low Serum HDL Cholesterol in Humans1,2

    National Research Council Canada - National Science Library

    Corinna Koebnick; Ada L Garcia; Pieter C Dagnelie; Carola Strassner

    2005-01-01

    ...) on serum lipids and plasma vitamin B-12, folate, and total homocysteine (tHcy). In a cross-sectional study, the lipid, folate, vitamin B-12, and tHcy status of 201 adherents to a raw food diet...

  8. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

    Science.gov (United States)

    Misaka, S; Yatabe, J; Müller, F; Takano, K; Kawabe, K; Glaeser, H; Yatabe, M S; Onoue, S; Werba, J P; Watanabe, H; Yamada, S; Fromm, M F; Kimura, J

    2014-04-01

    This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

  9. A cleaning method for reduced graphene oxide by inductively coupled plasma

    Science.gov (United States)

    Shen, Yan; Zhou, Peng; Zhang, David Wei

    2016-10-01

    In this work, we make reduced graphene oxide (rGO) solution via chemical way and use it to fabricate Field-effect transistor (FET) channel by spin coating for investigating the performance of grapheme-based devices. An inductively coupled plasma (ICP) with very low plasma density is applied to etch the surface of rGO. It has been confirmed that residues and contaminations can be removed through etching and proper etching parameters can lead to better electrical properties more like the pristine graphene without creating defects. Considering the application of graphene added to silicon-based electronic devices, such a cleaning method can be used due to its advantages of being a low-temperature, large-area, high-throughput, and Si-compatible process.

  10. Assessment of pyridoxine and folate intake in migraine patients

    Directory of Open Access Journals (Sweden)

    Omid Sadeghi

    2016-01-01

    Conclusion: Migraine patients had lower dietary intake of folate, compared with non-migraine group subjects. There was no significant association between folate and pyridoxine intake with the frequency of migraine attacks. Further studies are needed to confirm our findings.

  11. DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas.

    Science.gov (United States)

    Xue, Geng; Lu, Chao-Jing; Pan, Shu-Jun; Zhang, Yin-Ling; Miao, Hui; Shan, Shi; Zhu, Xiao-Ting; Zhang, Yi

    2017-08-01

    Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo. Then, the correlation analysis between folate level, DNA methylation alteration in promoter and expression of CBS was carried out in vitro and vivo. Further, the methylation patterns of CBS promoter in plasma cfDNA were detected and statistically correlated with pathological parameters and clinical outcome. Our study showed that DNA hypomethylation in CBS promoter, induced by folate deficiency, would lead to up-regulation of CBS both in vitro and vivo. Patients with cfDNA hypomethylation of CBS promoter in plasma were correlated with high tumor stage and poor clinical outcome. In addition, cfDNA hypomethylation of CBS promoter in plasma was shown to be an independent prognostic factor for recurrence and cancer-related death in CRC. Our results indicated that DNA hypomethylation of CBS promoter induced by folate deficiency could serve as a potential noninvasive circulating biomarker and may be helpful in developing more effective prognostic markers for CRC.

  12. Folate receptors and neural tube closure.

    Science.gov (United States)

    Saitsu, Hirotomo

    2017-02-28

    Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.

  13. Folates in plants: research advances and progress in crop biofortification

    Science.gov (United States)

    Gorelova, Vera; Ambach, Lars; Rébeillé, Fabrice; Stove, Christophe; Van Der Straeten, Dominique

    2017-03-01

    Folates, also known as B9 vitamins, serve as donors and acceptors in one-carbon (C1) transfer reactions. The latter are involved in synthesis of many important biomolecules, such as amino acids, nucleic acids and vitamin B5. Folates also play a central role in the methyl cycle that provides one-carbon groups for methylation reactions. The important functions fulfilled by folates make them essential in all living organisms. Plants, being able to synthesize folates de novo, serve as an excellent dietary source of folates for animals that lack the respective biosynthetic pathway. Unfortunately, the most important staple crops such as rice, potato and maize are rather poor sources of folates. Insufficient folate consumption is known to cause severe developmental disorders in humans. Two approaches are employed to fight folate deficiency: pharmacological supplementation in the form of folate pills and biofortification of staple crops. As the former approach is considered rather costly for the major part of the world population, biofortification of staple crops is viewed as a decent alternative in the struggle against folate deficiency. Therefore strategies, challenges and recent progress of folate enhancement in plants will be addressed in this review. Apart from the ever-growing need for the enhancement of nutritional quality of crops, the world population faces climate change catastrophes or environmental stresses, such as elevated temperatures, drought, salinity that severely affect growth and productivity of crops. Due to immense diversity of their biochemical functions, folates take part in virtually every aspect of plant physiology. Any disturbance to the plant folate metabolism leads to severe growth inhibition and, as a consequence, to a lower productivity. Whereas today’s knowledge of folate biochemistry can be considered very profound, evidence on the physiological roles of folates in plants only starts to emerge. In the current review we will discuss the

  14. Quarantine versus pathogen-reduced plasma-coagulation factor content and rotational thromboelastometry coagulation.

    Science.gov (United States)

    Theusinger, Oliver M; Goslings, David; Studt, Jan-Dirk; Brand-Staufer, Brigitte; Seifert, Burkhardt; Spahn, Donat R; Frey, Beat M

    2017-03-01

    Different types of fresh-frozen plasma (FFP) exist, and the concentrations of plasma proteins vary between individuals and blood groups. Furthermore, processing may also influence the content. Quarantine-stored plasma (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept) technology (piFFP) were analyzed regarding procoagulant and anticoagulant hemostasis proteins, including endogenous thrombin (thrombin-generation) potential (ETP). Thirty-five samples of each type of FFP were analyzed using only male Blood Group O donors. FFP units were stored frozen for comparable periods of time before plasma protein content was assessed. Once the units were thawed, all tests were completed within 4 hours. The results are presented as means ± standard deviations or as median (minimum; maximum) and were compared using independent-sample t tests (significance, p < 0.01). Significantly higher concentrations of adintegrin-like and metalloprotease with thrombospondin type-13 motifs (ADAMTS13), fibrinogen, Factor (F)V, FVIII, FXIII, protein S, protein S activity, antithrombin, microvesicle (<900 nm), and α2 antiplasmin were observed in qFFP. The variability of factors was significantly lower in piFFP. Tissue factor (TF) at 1 picomolar (pM) exhibited significantly longer lag time, a lower peak, lower ETP, and a lower velocity index in qFFP compared with piFFP. In TF at 5 pM, significant differences in lag time (longer in qFFP), velocity index (lower in qFFP), and peak (lower in qFFP) were observed. Rotational thromboelastometry revealed a significantly longer (p = 0.002) clot-formation time with intrinsic thromboelastometry for piFFP and a significantly shorter clotting time (p = 0.004) with thromboelastometry fibrinogen testing for piFFP. Pathogen reduction reduces procoagulant and anticoagulant coagulation factors as well as variability. A thrombin-generation assay showed no reduced ETP and no supraphysiological thrombin generation. None of the

  15. Some More Comments on 'Folate Deficiency in Chronic Pancreatitis'

    Directory of Open Access Journals (Sweden)

    Conrad Wagner

    2010-11-01

    Full Text Available GNMT: glycine N-methyltransferase; SAH: Sadenosylhomocysteine; SAM: S-adenosylmethionine Dear Sir, The comprehensive review by Braganza and Dormandy on micronutrient therapy for chronic pancreatitis included emphasis on the role of methyl group and thiol metabolism [1]. I am writing to expand on the comments expressed in the letter by Rajesh et al. [2] and the reply by Dr. Braganza [3] in the July issue of JOP. Journal of the Pancreas (Online. These have served to highlight the results reported by Girish et al. in which they suggest that a deficiency of methyl groups may be a factor in the development of pancreatitis [4]. In their letter, Rajesh et al. cite our paper showing that pancreatic secretion in rats is compromised in folate deficiency [2]. There is a close relationship between folate and methyl group metabolism. Folate is required for the de novo synthesis of methyl groups. The ratio of Sadenosylmethionine (SAM to S-adenosylhomocysteine (SAH is regulated by the enzyme glycine Nmethyltransferase (GNMT under the control of a specific form of folate [5]. GNMT is very abundant in the exocrine cells of the pancreas [6] and in a subsequent publication we showed that SAM plays an important role in the secretory process from pancreatic exocrine cells [7]. In that paper we provided evidence that SAM might be needed for carboxymethylation of G proteins that are needed in the process of exocytosis. It should also be noted that the process of exocytosis involves the fusion and regeneration of membranes that are generated in the Golgi and the rough endoplasmic reticulum [8]. Tissues that are actively involved in exocrine secretion may then have an increased requirement for synthesis of phosphatidylcholine, an important component of the plasma membrane. There are two pathways that are used for the synthesis of phosphatidylcholine. The major pathway in most tissues utilizes preformed choline reacting with cytidine triphosphate to eventually form

  16. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate.

    Science.gov (United States)

    Klee, G G

    2000-08-01

    Vitamin B(12) and folate are two vitamins that have interdependent roles in nucleic acid synthesis. Deficiencies of either vitamin can cause megaloblastic anemia; however, inappropriate treatment of B(12) deficiency with folate can cause irreversible nerve degeneration. Inadequate folate nutrition during early pregnancy can cause neural tube defects in the developing fetus. In addition, folate and vitamin B(12) deficiency and the compensatory increase in homocysteine are a significant risk factor for cardiovascular disease. Laboratory support for the diagnosis and management of these multiple clinical entities is controversial and somewhat problematic. Automated ligand binding measurements of vitamin B(12) and folate are easiest to perform and widely used. Unfortunately, these tests are not the most sensitive indicators of disease. Measurement of red cell folate is less dependent on dietary fluctuations, but these measurements may not be reliable. Homocysteine and methylmalonic acid are better metabolic indicators of deficiencies at the tissue level. There are no "gold standards" for the diagnosis of these disorders, and controversy exists regarding the best diagnostic approach. Healthcare strategies that consider the impact of laboratory tests on the overall costs and quality of care should consider the advantages of including methylmalonic acid and homocysteine in the early evaluation of patients with suspected deficiencies of vitamin B(12) and folate.

  17. Association between Alcohol Consumption, Folate Intake, and Risk of Pancreatic Cancer: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Winta Yellow

    2017-05-01

    Full Text Available Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3% of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls in a largely white population (>96%. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day. Our study showed dietary folate intake had a modest effect size, but was significantly inversely associated with pancreatic cancer (odds ratio (OR = 0.99, p < 0.0001. The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

  18. A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

    NARCIS (Netherlands)

    R.J.W. Meesters (Roland); R. Cornelissen (Robin); R.J. van Klaveren (Rob); R. de Jonge (Robert); E. den Boer (Ethan); J. Lindemans (Jan); T.M. Luider (Theo)

    2010-01-01

    textabstractAn analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry. Patient plasma samples spiked with

  19. Aberrant folate status in schizophrenic patients: what is the evidence?

    NARCIS (Netherlands)

    Muntjewerff, J.W.; Blom, H.J.

    2005-01-01

    A vast amount of case reports, open studies and, to a lesser extent, case-control studies have been published on the topic of psychopathology and folate deficiency. These studies reported a high incidence of serum folate deficiency in patients with various psychiatric disorders. Folate deficiency se

  20. Natural variation in folate levels among tomato (Solanum lycopersicum) accessions.

    Science.gov (United States)

    Upadhyaya, Pallawi; Tyagi, Kamal; Sarma, Supriya; Tamboli, Vajir; Sreelakshmi, Yellamaraju; Sharma, Rameshwar

    2017-02-15

    Folate content was estimated in tomato (Solanum lycopersicum) accessions using microbiological assay (MA) and by LC-MS. The MA revealed that in red-ripe fruits folate levels ranged from 4 to 60μg/100g fresh weight. The LC-MS estimation of red-ripe fruits detected three folate forms, 5-CH3-THF, 5-CHO-THF, 5,10-CH(+)THF and folate levels ranged from 14 to 46μg/100g fresh weight. In mature green and red ripe fruit, 5-CH3-THF was the most abundant folate form. Comparison of LC-MS with MA revealed that MA inaccurately estimates folate levels. The accumulation of folate forms and their distribution varied among accessions. The single nucleotide polymorphism was examined in the key genes of the folate pathway to understand its linkage with folate levels. Despite the significant variation in folate levels among tomato accessions, little polymorphism was found in folate biosynthesis genes. Our results indicate that variation in folate level is governed by a more complex regulation at cellular homeostasis level. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Folate Metabolism and the Risk of Down Syndrome

    Science.gov (United States)

    Patterson, David

    2008-01-01

    Folate is an important vitamin that contributes to cell division and growth and is therefore of particular importance during infancy and pregnancy. Folate deficiency has been associated with slowed growth, anaemia, weight loss, digestive disorders and some behavioural issues. Adequate folate intake around the time of conception and early pregnancy…

  2. Reduced Brillouin scattering from multiline CO2 laser interaction with a plasma

    Science.gov (United States)

    Giles, R.; Fedosejevs, R.; Offenberger, A. A.

    1982-08-01

    Experimental verification of reduced stimulated Brillouin scattering (SBS) is reported for multiline CO2 laser radiation interacting with high-density plasma. For long-pulse (40-nsec) irradiation SBS was observed to decrease from 15% to a negligible level when the spectrum of the incident laser pulse was changed from 1 to 2 or more well-separated frequencies. Results for both long- and short-pulse multiline laser conditions are in general accord with the expected behavior for varying Δωγ0, where Δω is the frequency separation and γ0 is the homogeneous growth rate.

  3. Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia.

    Science.gov (United States)

    Cortés-Puch, Irene; Wang, Dong; Sun, Junfeng; Solomon, Steven B; Remy, Kenneth E; Fernandez, Melinda; Feng, Jing; Kanias, Tamir; Bellavia, Landon; Sinchar, Derek; Perlegas, Andreas; Solomon, Michael A; Kelley, Walter E; Popovsky, Mark A; Gladwin, Mark T; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles

    2014-02-27

    In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

  4. Neuronal injury: folate to the rescue?

    Science.gov (United States)

    Kronenberg, Golo; Endres, Matthias

    2010-05-01

    Strong epidemiological evidence indicates that derangement of single-carbon metabolism has detrimental effects for proper CNS functioning. Conversely, a role for folate supplementation in the treatment and prevention of neurodegenerative and neuropsychiatric disorders remains to be established. In this issue of the JCI, in an elegant series of experiments in rodents, Iskandar and colleagues demonstrate a crucial role of folate in the regeneration of afferent spinal neurons after injury. Probing sequential steps in folate metabolism, from cellular entry to DNA methylation, the authors show that axonal regeneration relies upon the integrity of DNA methylation pathways. These findings provide the first demonstration of an epigenetic mechanism contributing to neurorepair and suggest that manipulation of the methylation milieu may offer promising new therapeutic avenues to promote regeneration.

  5. Polyphenols from Berries of Aronia melanocarpa Reduce the Plasma Lipid Peroxidation Induced by Ziprasidone

    Directory of Open Access Journals (Sweden)

    Anna Dietrich-Muszalska

    2014-01-01

    Full Text Available Background. Oxidative stress in schizophrenia may be caused partially by the treatment of patients with antipsychotics. The aim of the study was to establish the effects of polyphenol compounds derived from berries of Aronia melanocarpa (Aronox on the plasma lipid peroxidation induced by ziprasidone in vitro. Methods. Lipid peroxidation was measured by the level of thiobarbituric acid reactive species (TBARS. The samples of plasma from healthy subjects were incubated with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml alone and with Aronox (5 ug/ml; 50 ug/ml. Results. We observed a statistically significant increase of TBARS level after incubation of plasma with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml (after 24 h incubation: P=7.0 × 10−4, P=1.6 × 10−3, and P=2.7 × 10−3, resp. and Aronox lipid peroxidation caused by ziprasidone was significantly reduced. After 24-hour incubation of plasma with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml in the presence of 50 ug/ml Aronox, the level of TBARS was significantly decreased: P=6.5 × 10−8, P=7.0 × 10−6, and P=3.0 × 10−5, respectively. Conclusion. Aronox causes a distinct reduction of lipid peroxidation induced by ziprasidone.

  6. Generation and analysis of plasmas with centrally reduced helicity in full-tungsten ASDEX upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Bock, Alexander

    2016-03-01

    The most promising concepts for harnessing nuclear fusion are toroidal devices like tokamaks, where a plasma is confined by helically twisted magnetic field lines. To provide the twisting of the field lines, a tokamak relies on a toroidal current in the plasma, which is largely generated by a transformer. As such, conventional tokamaks are limited to pulsed operation. Moreover, this current makes tokamak plasmas prone to numerous confinement degrading magnetohydrodynamic (MHD) instabilities that can emerge at locations where the field line helicity q takes on rational values like 1/1, 3/2 or 2/1, i.e. sawteeth or neoclassical tearing modes (NTMs). This thesis presents studies of plasmas with centrally elevated q-profiles created by external electron-cyclotron and neutral beam current drive (ECCD/NBCD) under steady-state conditions in the full-tungsten tokamak ASDEX Upgrade. Without the usually monotonic q-profile, instabilities of low helicity disappear, thereby improving the plasma stability. Furthermore, elevating q increases the amount of so-called (toroidal) bootstrap current, which the plasma drives by itself in the presence of pressure gradients, thereby reducing the reliance on the transformer. In the best case, an advanced tokamak (AT) could thus run in steady state. Additionally, an elevated and thus flat/slightly reversed q-profile is thought to improve confinement by impeding turbulent transport. Reconstruction of the tailored q-profile is accomplished with the new integrated data equilibrium (IDE) code and information from a key diagnostic that is based on the Motional Stark Effect (MSE). During the course of this work it was discovered that the MSE diagnostic suffers from interference from polarised background light. A prototype mitigation system was successfully tested. Also, non-linearities in the diagnostic's optical relay system were found and a calibration scheme devised to take them into account. Both the conventional approach of AT

  7. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism.

    NARCIS (Netherlands)

    Steinfeld, R.; Grapp, M.; Kraetzner, R.; Dreha-Kulaczewski, S.; Helms, G.; Dechent, P.; Wevers, R.A.; Grosso, S.; Gartner, J.

    2009-01-01

    Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited brain-specifi

  8. Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

    Science.gov (United States)

    Iglesia, Iris; Mouratidou, Theodora; González-Gross, Marcela; Novakovic, Romana; Breidenassel, Christina; Jiménez-Pavón, David; Huybrechts, Inge; De Henauw, Stefaan; Geelen, Anouk; Gottrand, Frédéric; Kafatos, Anthony; Mistura, Lorenza; de Heredia, Fátima Pérez; Widhalm, Kurt; Manios, Yanis; Molnar, Denes; Stehle, Peter; Gurinovic, Mirjana; Cavelaars, Adrienne E J M; Van't Veer, Pieter; Moreno, Luis A

    2014-03-01

    Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Vitamin intakes were obtained from two 24-hour recalls in 2253 participants (47% males). Vitamin B biomarkers were assessed in a subsample of 977 participants (46% males). Socioeconomic factors were assessed by questionnaire, and 1-way analysis of covariance and linear regression analysis were applied. For males and females, mean intakes of folate were 211.19 and 177.18 μg/d, and for vitamin B12, 5.98 and 4.54 μg/d, respectively. Levels of plasma folate, red blood cell folate, serum B12, and holotranscobalamin were 18.74, 807.19, 330.64, and 63.04 nmol/L in males, respectively, and 19.13, 770.16, 377.9, and 65.63 nmol/L in females, respectively. Lower folate intakes were associated with several SEFs, including maternal and paternal education in both sexes. Regarding folate biomarkers, lower plasma folate intakes were associated with single/shared care in males and with lower paternal occupation in females. Lower vitamin B12 intakes were associated with almost all the studied SEFs, except paternal occupation in both sexes. In females, when considering vitamin B12 biomarkers, lower plasma vitamin B12 was associated with lower maternal education and occupation, and lower holotranscobalamin was associated with lower maternal education and lower paternal occupation. In conclusion, from the set of socioeconomic determinants studied in a sample of European adolescents, maternal education and paternal occupation were more consistently associated with folate and vitamin B12 intakes and biomarkers concentrations.

  9. Circulating Unmetabolized Folic Acid: Relationship to Folate Status and Effect of Supplementation

    OpenAIRE

    Carolyn Tam; Deborah O'Connor; Gideon Koren

    2012-01-01

    There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects. In this paper, we examined the folic acid status of women of reproductive age in relation to dietary intake and the effect of folic acid supplementation (1.1 mg or 5 mg). Plasma unmetabolized folic acid was not significantly correlated with folate intake estimated by food frequency questionnaire or...

  10. Folate status of gut microbiome affects Caenorhabditis elegans lifespan

    Directory of Open Access Journals (Sweden)

    Nguyen Theresa PT

    2012-07-01

    Full Text Available Abstract In a paper in BMC Biology Virk et al. show that Caenorhabditis elegans lifespan is extended in response to a diet of folate-deficient Escherichia coli. The deficiencies in folate biosynthesis were due to an aroD mutation, or treatment of E. coli with sulfa drugs, which are mimics of the folate precursor para-aminobenzoic acid. This study suggests that pharmacological manipulation of the gut microbiome folate status may be a viable approach to slow animal aging, and raises questions about folate supplementation. See research article http://www.http://www.biomedcentral.com/1741-7007/10/67

  11. Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Feigelson, Heather Spencer; Jonas, Carolyn R; Robertson, Andreas S; McCullough, Marjorie L; Thun, Michael J; Calle, Eugenia E

    2003-02-01

    Recent studies suggest that the increased risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake. We examined this question among 66,561 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. A total of 1,303 incident cases had accrued during the first 5 years of follow-up. Cox proportional hazards models and stratified analysis were used to examine the relationship between alcohol, dietary and total folate intake, multivitamin use, dietary methionine, and breast cancer. We observed an increasing risk of breast cancer with increasing alcohol consumption (P for trend = 0.01). In the highest category of consumption (15 or more grams of ethanol/day), the risk of breast cancer was 1.26 (95% confidence interval, 1.04-1.53) compared with nonusers. We observed this association with higher alcohol consumption for in situ, localized, and regional disease. We found no association between risk of breast cancer and dietary folate, total folate, multivitamin use, or methionine intake. Furthermore, we found no evidence of an interaction between levels of dietary folate (P for interaction = 0.10) or total folate (P for interaction = 0.61) and alcohol. Nor did we find evidence of an interaction between alcohol consumption and recent or long-term multivitamin use (P for interaction = 0.27). Our results are consistent with a positive association with alcohol but do not support an association with folate or methionine intake or an interaction between folate and alcohol intake on risk of breast cancer.

  12. Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

    Science.gov (United States)

    Kishimoto, Kenji; Kobayashi, Ryoji; Sano, Hirozumi; Suzuki, Daisuke; Maruoka, Hayato; Yasuda, Kazue; Chida, Natsuko; Yamada, Masafumi; Kobayashi, Kunihiko

    2014-07-01

    Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency.

  13. Folates in Asian noodles: III. Fortification, impact of processing, and enhancement of folate intakes.

    Science.gov (United States)

    Bui, Lan T T; Small, Darryl M

    2007-06-01

    Asian noodles, a widely consumed staple food, were evaluated as potential vehicles for fortification with folic acid. Samples of white salted, yellow alkaline, and instant noodles, prepared under controlled laboratory conditions, were fortified and folates were measured at each stage of processing using a microbiological assay. Although the 3 styles showed differing patterns of retention, overall losses were slightly more than 40% and were similar for all styles. White salted and yellow alkaline noodles showed no significant decrease in total folate content during production. In contrast, significant losses occurred for instant noodles during steaming and deep-frying of the noodle strands. In all cases, substantial losses occurred during subsequent cooking of the dried noodles. Fortification at a rate of 50% of the reference value per serving resulted in retention of folate at levels corresponding to 30% following cooking, whereas unfortified noodles contributed less than 4% per serving. It is concluded that fortifying Asian noodles provides an effective means for enhancing folate intake.

  14. Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age.

    Science.gov (United States)

    Borradale, D; Isenring, E; Hacker, E; Kimlin, M G

    2014-02-05

    In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18-47years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500μg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of 600 Joules per day had significantly higher depletion of serum folate (p=0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B=-0.49; t=-3.75; p=solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

  15. 还原型叶酸载体基因多态性与急性白血病易感性的相关性%Association of single nucleotide polymorphism of reduced folate carrier gene with susceptibility to acute leukemia

    Institute of Scientific and Technical Information of China (English)

    赵玮; 岳丽杰; 陈小文

    2011-01-01

    目的 研究还原型叶酸载体(reduced folate carrier,RFC)80G/A单核苷酸多态性(single nucleotide polymorphism,SNP)与急性白血病(acute leukemia,AL)之间的关联性.方法 采用逆转录-聚合酶链反应-变性梯度凝胶电泳(reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis,RT-PCR-DGGE)结合DNA直接测序,对98例AL患儿和135名正常儿童进行RFC第80位点SNP筛查.结果 在AL组和正常儿童组中发现RFC 80 GA基因型的例数分别为53和52,AA基因型例数分别为24和30,两组A等位基因频率分别为0.515和0.415.应用x2分析发现RFC 80G/A与AL存在交互作用.结论 确定了中国儿童RFC 80G/A的等位基因频率,并初步认为RFC 80G/A与AL发生存在一定的相关性.%Objective To investigate the allele and genotype frequencies of reduced folate carrier gene (RFC) 80G/A polymorphism in Chinese patients with acute leukemia (AL) and healthy control children,and to provide clue for association between the single nucleotide polymorphism (SNP) of RFC and the occurrence of AL. Methods Bone marrow samples from 98 childhood patients with AL and peripheral blood samples from 135 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for the polymorphisms in RFC 80G/A by reverse transcriptase-polymerase chain reactiondenaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing. Results The A allele frequencies of the AL patients and control children were 0. 515 and 0. 415, respectively (P<0. 05). Chisquare test confirmed a statistical significance of the association between RFC80 G/A and AL. Conclusion RFC 80AA or GA genotype may contribute to increasing the susceptibility to AL.

  16. Enhancement of the folate content in Egyptian pita bread

    Directory of Open Access Journals (Sweden)

    Cornelia M. Witthöft

    2012-04-01

    Full Text Available Introduction: Egypt has a high incidence of neural tube defects related to folate deficiency. One major food source for folate is pita (baladi bread, which is consumed daily. Bioprocessing (e.g. germination has been reported to increase the folate content in cereals. The aim was to produce pita bread with increased folate content using germinated wheat flour (GWF.Methods: Prior to milling the effects of germination and drying conditions on folate content in wheat grains were studied. Pita bread was baked from wheat flour substituted with different levels of GWF. The folate content in dough and bread and rheological properties of dough were determined.Results: Germination of wheat grains resulted in, depending on temperature, 3- to 4-fold higher folate content with a maximum of 61 µg/100 g DM (dry matter. The folate content in both flour and bread increased 1.5 to 4-fold depending on the level of flour replacement with GWF. Pita bread baked with 50% sieved GWF was acceptable with respect to colour and layer separation, and had a folate content of 50 µg/100 g DM compared with 30 µg/100 g DM in conventional pita bread (0% GWF.Conclusion: Using 50% GWF, pita bread with increased folate content, acceptable for the Egyptian consumer, was produced. Consumption of this bread would increase the average daily folate intake by 75 µg.

  17. The role of polymorphisms in genes of folate metabolism and hyperhomocysteinemia in realization of missed abortion in the Ist trimester

    Directory of Open Access Journals (Sweden)

    Alija Aimbetova

    2011-04-01

    Full Text Available The article explores mechanisms of non-developing the Ist trimester pregnancy on the basis of studying frequency of polymorphic alleles in folate metabolism genes MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, homocysteine level, platelet and plasma haemostasis sections.Polymorphism in MTHFR, MTRR, and MTR genes of folate metabolism causes hyperhomocysteinemia and thrombophilic changes. In conditions of genetically accustomed thrombophilic changes the desynchronization of fibrinolysis and fibrin formation processes during implantation occurs that leads to poor trophoblast invasion and its inadequacy, which in turn causes miscarriage due to non-developing pregnancy in the Ist trimester.

  18. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Lorenza Mistura

    2013-05-01

    Full Text Available To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF, 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002, 19.4% (p < 0.001 and 21.9% (p < 0.001, as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid. After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.

  19. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

    Science.gov (United States)

    Zappacosta, Bruno; Mastroiacovo, Pierpaolo; Persichilli, Silvia; Pounis, George; Ruggeri, Stefania; Minucci, Angelo; Carnovale, Emilia; Andria, Generoso; Ricci, Roberta; Scala, Iris; Genovese, Orazio; Turrini, Aida; Mistura, Lorenza; Giardina, Bruno; Iacoviello, Licia

    2013-01-01

    Background/Objectives: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations. PMID:23698160

  20. Improved performance of bipolar charge plasma transistor by reducing the horizontal electric field

    Science.gov (United States)

    Bramhane, Lokesh Kumar; Singh, Jawar

    2017-04-01

    In this paper, we have proposed a modified lateral bipolar charge plasma transistor (BCPT). The appropriate work function engineering is used to induce the electron-hole concentrations under different regions. The reduced work function difference and absence of oxide layer (tox) in the proposed lateral BCPT reduce the horizontal electric field (EX) at the emitter. Also, reduced work function difference at base metal contact decreases the electric field at base-emitter and base-collector junctions. 2-D TCAD simulations of the proposed device reveal that there are evenly spaced output characteristic curves, improved cut-off frequency and breakdown voltage. The reduction in horizontal electric field about one-fourth compared to the conventional lateral BCPT results in realistic current gain (β) and reduced on-set voltage makes proposed device suitable for low power applications. The proposed device exhibits improved cut-off frequency (fT = 7.5 GHz) compared to the lateral BCPT (3.7 GHz) and improved current gain (37.67) and same cut-off frequency (= 7.5 GHz) compared to the conventional BJT (β = 26.5 &fT = 7.5 GHz).

  1. Dietary Intake of Folate, but not Vitamin B(2) or B (12), Is Associated with Increased Bone Mineral Density 5 Years after the Menopause

    DEFF Research Database (Denmark)

    Rejnmark, L; Vestergaard, P; Hermann, A P

    2008-01-01

    Folate, vitamin B(2) (riboflavin), and vitamin B(12 )may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on ...

  2. Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition.

    Science.gov (United States)

    Wibowo, Ardian S; Singh, Mirage; Reeder, Kristen M; Carter, Joshua J; Kovach, Alexander R; Meng, Wuyi; Ratnam, Manohar; Zhang, Faming; Dann, Charles E

    2013-09-17

    Antifolates, folate analogs that inhibit vitamin B9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.

  3. Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification.

    Science.gov (United States)

    Johansson, I; Van Guelpen, B; Hultdin, J; Johansson, M; Hallmans, G; Stattin, P

    2010-08-01

    B vitamins have been implicated in major chronic diseases but results have been inconsistent. This study evaluated the accuracy of dietary intakes of folate, vitamin B12, riboflavin and vitamin B6 as measured by the Northern Sweden Food Frequency Questionnaire (FFQ) against repeated 24-h recalls (24HR) and plasma levels, taking into consideration the MTHFR 677C>T polymorphism. B vitamin intakes assessed by a semi-quantitative FFQ designed to measure the intake over the previous year were compared with those from 10 24HR, as well as to plasma levels of folate and vitamin B12, in randomly selected men (n=96) and women (n=99) aged 30-60 years. FFQ-based B-vitamin intakes were also compared with plasma levels of B-vitamins and with MTHFR 677C4T genotype in 878 men, aged 40-61 years. Intakes of vitamins B12 and riboflavin were similar, whereas folate and B6 intakes were 16-27% higher, as estimated by FFQ versus 24HR. Spearman correlation coefficients between the two methods ranged from 0.31 to 0.63 (all Pvitamin B12. Intakes estimated by FFQ were correlated with plasma levels, but coefficients were lower (range: 0.13-0.33), particularly for vitamin B12 in men (0.15-0.18). Folate intake was not correlated with plasma levels in subjects with the MTHFR 677 T/T genotype. The validity of the Northern Sweden FFQ for assessing B vitamin intake is similar to that of many other FFQs used in large-scale studies. The FFQ is suitable for ranking individuals by intake of folate, riboflavin, vitamin B6 and to a lesser extent vitamin B12.

  4. Iron and Folate-Deficiency Anaemias.

    Science.gov (United States)

    Hercberg, Serge

    1990-01-01

    Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

  5. Folate, vitamin B12 and human health

    Science.gov (United States)

    During the past decade the role of folate and vitamin B12 in human nutrition have been under constant re-examination. Basic knowledge on the metabolism and interactions between these essential nutrients has expanded and multiple complexities have been unraveled. These micronutrients have shared func...

  6. Haematological implications of folate food fortification

    African Journals Online (AJOL)

    Reports of folate-deficient megaloblastic anaemia in pregnant and lactating women in ..... in the world subsisting on various combinations of vegetarian diets, with low B12 contents .... of animal protein in low-income groups. There is no greater ...

  7. Dietary folate: Bioavailability studies in humans

    NARCIS (Netherlands)

    Melse, A.

    2003-01-01

    Keywords:Folate; Folic acid; Dietaryfolateintake;Folatebioavailability;Polyglutamylfolic acid;Homocysteine; GCPII 1561C>T polymorphism; Stable isotopes

  8. Iron and Folate-Deficiency Anaemias.

    Science.gov (United States)

    Hercberg, Serge

    1990-01-01

    Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

  9. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Science.gov (United States)

    Debrah, Alexander Yaw; Mand, Sabine; Specht, Sabine; Marfo-Debrekyei, Yeboah; Batsa, Linda; Pfarr, Kenneth; Larbi, John; Lawson, Bernard; Taylor, Mark; Adjei, Ohene; Hoerauf, Achim

    2006-09-01

    Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of

  10. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Alexander Yaw Debrah

    2006-09-01

    Full Text Available Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS, dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(sVEGFR-3]. Lymphedema patients were additionally monitored for stage (grade of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with

  11. Statistical Analysis of Reducing Biochemical Oxygen Demand (BOD) on Industrial Rubber Wastewater using Dielectric Barrier Discharge Plasma

    Science.gov (United States)

    Syakur, Abdul; Zaman, Badrus; Yunita Nurmaliakasih, Dias

    2017-04-01

    Dielectric Barrier Discharge plasma (DBD) is one of type non-thermal plasma (non-equilibrium plasma) or can be referred to as cold plasma. In this research, DBD plasma be utilized to reduce organic compounds like Biochemichal oxygen demand in the wastewater rubber processing. In the environment field DBD plasma has been used as a treatment for reducing air pollutants such as gas COx, NOx and HC. In addition DBD plasma have been developed to processed wastewater as an alternative technology in wastewater treatment. DBD plasma appears when the electrode is given a high voltage so that, it will form electric field in the area of the electrodes which allows the ionization and the presence of high-energy electrons in the area. The presence of these electrons will ionize molecules of H2O into active species such as OH•, H• and H2O2. The active species that can oxidize into CO2 and H2O so, BOD that can be degraded. In this research for wastewater treatment used high voltage are 10kV, 11kV, 12kV and 13kV and variations of processing time for 5, 10, 15, 20, and 25 (minutes). By increasing the voltage and extend the contact time then the speed variation of electrons to ionize the greater and more active species to be formed to degrade the pollutants to the maximum. This research used quantitative analysis with statistical analysis using SPSS software.

  12. Transformation of light paraffins in a microwave-induced plasma-based reactor at reduced pressure

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Manuel; Jimenez-Sanchidrian, Cesar; Romero-Salguero, Francisco Jose [Department of Organic Chemistry, Faculty of Sciences, University of Cordoba, Campus de Rabanales, Marie Curie Building, Ctra. Nnal. IV, km 396, 14071 Cordoba (Spain); del Carmen Garcia, Maria [Department of Applied Physics, Polytechnic School, University of Cordoba, Campus de Rabanales, Albert Einstein Building, Ctra. Nnal. IV, km 396, 14071 Cordoba (Spain)

    2010-05-15

    In this work, the effects of the plasma chemistry of an argon microwave (2.45 GHz) discharge at reduced pressure on the conversion of three different alkanes (n-pentane, n-hexane and n-heptane) have been studied. Optical emission spectroscopy has been used for identifying the species generated in the plasma and for estimating its gas temperature. Gas chromatography, mass spectrometry, X-ray diffraction and FTIR spectroscopy have been employed for identifying and analyzing all the compounds present as reaction products. Microwave power and hydrocarbon flow rate have been found critically to affect both conversion and selectivity. The main gas products have been hydrogen and ethylene. At low powers (100-150 W) the conversion to hydrogen has been quite selective. However, at high powers (>300 W) or slow hydrocarbon flow rate ethylene has resulted to be the major product. In most cases, an important fraction of a carbon deposit has been obtained which has been characterized as an amorphous hydrogenated carbon film. Some plausible mechanisms explaining the formation of the main reaction products have been discussed. (author)

  13. The use of cold plasma technology to reduce carryover in screening assays.

    Science.gov (United States)

    Akhlaq, Mohammed; Rosethorne, Elizabeth M; Sattikar, Afrah; Kent, Toby C

    2013-08-01

    The accurate transfer of biological reagents represents a fundamental step in the drug screening process, and the elimination of carryover is critical for the generation of accurate measurements of biological activity. The introduction of automated liquid robotics into screening laboratories has transformed the drug screening process, enabling accurate and reproducible transfer of liquids to become a high-throughput activity, but has also introduced a new challenge for drug discoverers: to establish screening workflows that limit analyte carryover for the generation of high-quality screening data. The widespread use of pipetting tips on automated liquid handlers often necessitates the use of optimized wash protocols for removing contaminants and frequently requires the use and disposal of large quantities of organic solvents. Furthermore, many chemical and biological reagents are recalcitrant to removal from pipetting tips by treatment with organic solvents. The use of cold atmospheric plasma technology provides an alternative approach for removal of contaminants and offers many advantages over traditional decontamination protocols commonly used during biological screening. This report describes the evaluation of a cold plasma tip-cleaning system for reducing carryover in a range of biological screening assays requiring the transfer of low molecular weight compound, nucleic acid, and bacterial liquid transfers. The validation of this technology for biological screening assays is presented, and the impact of this technology for screening workflows is discussed.

  14. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    Science.gov (United States)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  15. Nutritional Intake and Status of Cobalamin and Folate among Non-Pregnant Women of Reproductive Age in Bhaktapur, Nepal

    Directory of Open Access Journals (Sweden)

    Ram K. Chandyo

    2016-06-01

    Full Text Available Cobalamin and folate are especially important for women of childbearing age due to their ubiquitous role in fetal growth and development. Population-based data on cobalamin and folate status are lacking from Nepal, where diets are mostly vegetarian. The objectives of the study were to investigate cobalamin and folate intake and status, and to explore associations with socio-demographics, anthropometrics, anemia, and dietary habits. Following a random selection of geographical clusters, we collected blood samples from 500 non-pregnant women and 24-h dietary recalls and food frequency questionnaires from a subsample of 379 women. Twenty percent of the women did not consume any food containing cobalamin during the days recalled, and in 72% nutritional cobalamin intake was <1 μg/day. Eighty-four percent of the women had cobalamin intake lower than the estimated average requirement (EAR (<2 μg/day. In contrast, only 12% of the women had a folate intake less than 100 μg per day, whereas 62% had intake between 100 and 320 μg. Low plasma cobalamin (<150 pmol/L was found in 42% of the women, most of whom (88% also had elevated levels of methylmalonic acid. Our results indicated a high prevalence of nutritional cobalamin deficiency, while folate deficiency was uncommon.

  16. Criterion for reducible hydrodynamic equations of baryon-rich quark-gluon plasma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Besides the state equation there exists another cubic algebraic equation about μf in the form of μ3f + Pμf + q = 0, which relates parameters, temperature T, chemical potential μf, and net quark number nff (flavor f) for a baryon-rich quark-gluon plasma (QGP). A criterion may be acquired simply according to Cardan formula of the solution of the above equation, which gives naturally a condition: if n 《 27rT3/3/ , one may approximately use the conservation of specific entropy, and then the set of hydrodynamic equation of baryon-rich QGP may be reduced to the sct of hydrodynamic equation for baryon-free QGP.

  17. A reduced model for relativistic electron beam transport in solids and dense plasmas

    Science.gov (United States)

    Touati, M.; Feugeas, J.-L.; Nicolaï, Ph; Santos, J. J.; Gremillet, L.; Tikhonchuk, V. T.

    2014-07-01

    A hybrid reduced model for relativistic electron beam transport based on the angular moments of the relativistic kinetic equation with a special closure is presented. It takes into account collective effects with the self-generated electromagnetic fields as well as collisional effects with the slowing down of the relativistic electrons by plasmons, bound and free electrons and their angular scattering on both ions and electrons. This model allows for fast computations of relativistic electron beam transport while describing their energy distribution evolution. Despite the loss of information concerning the angular distribution of the electron beam, the model reproduces analytical estimates in the academic case of a monodirectional and monoenergetic electron beam propagating through a warm and dense plasma and hybrid particle-in-cell simulation results in a realistic laser-generated electron beam transport case.

  18. Kinetic simulations and reduced modeling of longitudinal sideband instabilities in non-linear electron plasma waves

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, S. [Centre de Recherches en Physique des Plasmas, Association Euratom-Confédération Suisse, Ecole Polytechnique Fédérale de Lausanne, Lausanne, (Switzerland); Berger, R. L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Cohen, B. I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hausammann, L. [Centre de Recherches en Physique des Plasmas, Association Euratom-Confédération Suisse, Ecole Polytechnique Fédérale de Lausanne, Lausanne, (Switzerland); Valeo, E. J. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)

    2014-10-01

    Kinetic Vlasov simulations of one-dimensional finite amplitude Electron Plasma Waves are performed in a multi-wavelength long system. A systematic study of the most unstable linear sideband mode, in particular its growth rate γ and quasi- wavenumber δk, is carried out by scanning the amplitude and wavenumber of the initial wave. Simulation results are successfully compared against numerical and analytical solutions to the reduced model by Kruer et al. [Phys. Rev. Lett. 23, 838 (1969)] for the Trapped Particle Instability (TPI). A model recently suggested by Dodin et al. [Phys. Rev. Lett. 110, 215006 (2013)], which in addition to the TPI accounts for the so-called Negative Mass Instability because of a more detailed representation of the trapped particle dynamics, is also studied and compared with simulations.

  19. Construction of reduced transport model by gyro-kinetic simulation with kinetic electrons in helical plasmas

    Science.gov (United States)

    Toda, S.; Nakata, M.; Nunami, M.; Ishizawa, A.; Watanabe, T.-H.; Sugama, H.

    2016-10-01

    A reduced model of the turbulent ion heat diffusivity is proposed by the gyrokinetic simulation code (GKV-X) with the adiabatic electrons for the high-Ti Large Helical Device discharge. The plasma parameter region of the short poloidal wavelength is studied, where the ion temperature gradient mode becomes unstable. The ion heat diffusivity by the nonlinear simulation with the kinetic electrons is found to be several times larger than the simulation results using the adiabatic electrons in the radial region 0.46 ion energy flux. The model of the turbulent diffusivity is derived as the function of the squared electrostatic potential fluctuation and the squared zonal flow potential. Next, the squared electrostatic potential fluctuation is approximated with the mixing length estimate. The squared zonal flow potential fluctuation is shown as the linear zonal flow response function. The reduced model of the turbulent diffusivity is derived as the function of the physical parameters by the linear GKV-X simulation with the kinetic electrons. This reduced model is applied to the transport code with the same procedure as.

  20. A Reduced-order NLTE Kinetic Model for Radiating Plasmas of Outer Envelopes of Stellar Atmospheres

    Science.gov (United States)

    Munafò, Alessandro; Mansour, Nagi N.; Panesi, Marco

    2017-04-01

    The present work proposes a self-consistent reduced-order NLTE kinetic model for radiating plasmas found in the outer layers of stellar atmospheres. A detailed collisional-radiative kinetic mechanism is constructed by leveraging the most up-to-date set of ab initio and experimental data available in the literature. This constitutes the starting point for the derivation of a reduced-order model, obtained by lumping the bound energy states into groups. In order to determine the needed thermo-physical group properties, uniform and Maxwell–Boltzmann energy distributions are used to reconstruct the energy population of each group. Finally, the reduced set of governing equations for the material gas and the radiation field is obtained based on the moment method. Applications consider the steady flow across a shock wave in partially ionized hydrogen. The results clearly demonstrate that adopting a Maxwell–Boltzmann grouping allows, on the one hand, for a substantial reduction of the number of unknowns and, on the other, to maintain accuracy for both gas and radiation quantities. Also, it is observed that, when neglecting line radiation, the use of two groups already leads to a very accurate resolution of the photo-ionization precursor, internal relaxation, and radiative cooling regions. The inclusion of line radiation requires adopting just one additional group to account for optically thin losses in the α, β, and γ lines of the Balmer and Paschen series. This trend has been observed for a wide range of shock wave velocities.

  1. Validation of a food frequency questionnaire to assess folate intake of Dutch elderly people

    NARCIS (Netherlands)

    Rest, van de O.; Durga, J.; Verhoef, P.; Boonstra, A.; Brants, H.A.M.

    2007-01-01

    Folate is required for 1-carbon metabolism and deficiency in folate leads to megaloblastic anemia. Low levels of folate have been associated with increased risk of vascular disease. To investigate whether RDA of folate are met, habitual folate intake needs to be assessed reliably. We developed a FFQ

  2. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

    2003-08-28

    Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75{+-}1.55 {mu}m versus after supplementation: 70.25{+-}1.31 {mu}m; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels.

  3. Folate inadequacy in the diet of pregnant women

    Directory of Open Access Journals (Sweden)

    Lívia de Castro Crivellenti

    2014-06-01

    Full Text Available OBJECTIVE: To estimate food and dietary folate inadequacies in the diets of adult pregnant women. METHODS: A prospective study was conducted with 103 healthy pregnant adult users of the Public Health Care System of Ribeirão Preto, São Paulo, Brazil. The present study included the 82 women with complete food intake data during pregnancy, which were collected by three 24-hour dietary recalls. Food folate (folate naturally present in foods and dietary folate (food folate plus folate from fortified wheat flour and cornmeal inadequacies were determined, using the Estimated Average Requirement as cutoff. RESULTS: The diets of 100% and 94% of the pregnant women were inadequate in food folate and dietary folate, respectively. However, fortified foods increased the medium availability of the nutrient by 87%. CONCLUSION: The large number of pregnant women consuming low-folate diets was alarming. Nationwide population studies are needed to confirm the hypothesized high prevalence of low-folate diets among pregnant women.

  4. Folate Receptor Targeted Alpha-Therapy Using Terbium-149

    CERN Document Server

    Müller, Cristina; Haller, Stephanie; Dorrer, Holger; Köster, Ulli; Johnston, Karl; Zhernosekov, Konstantin; Türler, Andreas; Schibli, Roger

    2014-01-01

    Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09) using folate receptor (FR)-positive cancer cells in vitro and in tumor-bearing mice. 149Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified 149Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with 149Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A) or with 149Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq). A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received 149Tb-cm09 (B: 30.5 d; C: 43 d) compared to untreated controls (A: 21 d). Analysis of blood parameters rev...

  5. The status of vitamin B12 and folate among Chinese women: a population-based cross-sectional study in northwest China.

    Science.gov (United States)

    Dang, Shaonong; Yan, Hong; Zeng, Lingxia; Wang, Quanli; Li, Qiang; Xiao, Shengbin; Fan, Xiaojing

    2014-01-01

    To assess the status of the vitamin B12 and folate of Chinese women living in northwest China. A population-based cross-sectional study was conducted in 2008 among Chinese women aged 10-49 years living in Shaanxi province of northwest China. A stratified multistage random sampling method was adopted to obtain a sample of 1170 women. The women were interviewed for collection of their background information and their plasma vitamin B12 and folate were measured with the immunoassay method. The status of both vitamins was evaluated and the prevalence of deficiency was estimated. The median value of the women was 214.5 pg/mL for vitamin B12 and 4.6 ng/mL for folate. The urban women had a significantly higher vitamin B12 (254.1 vs. 195.9 pg/mL) but lower folate (4.4 vs. 4.7 ng/mL) than rural women. Total prevalence of deficiency was 45.5% (95% CI: 42.6% ∼ 48.4%) for vitamin B12 and 14.7% (95% CI: 12.6% ∼ 16.8%) for folate. About 36% of women presented vitamin B12 deficiency alone, 5.2% belonged to folate deficiency alone and 9.5% was combined deficiency in both vitamins. More than 25% of the women were in marginal vitamin B12 status (200-299 pg/mL) and 60% in marginal status of folate (3-6 ng/mL). About 75.2% of rural women with folate deficiency were deficient in vitamin B12 and 46% for urban women. Quantile regression model found decreasing coefficient of folate status across 73 different quantiles of vitamin B12, which indicated that the women with folate deficiency had lower vitamin B12 significantly compared with those with no deficiency. The deficiency of vitamin B12 and folate is still prevalent among the Chinese women in northwest China. Vitamin B12 deficiency could be more serious and the improvement of poor vitamin B12 status should be invoked when practicing the supplementation of folate against the neural tube defects in northwest China.

  6. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance.

    NARCIS (Netherlands)

    Veldman, B.A.J.; Vervoort, G.M.M.; Blom, H.J.; Smits, P.

    2005-01-01

    INTRODUCTION: Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function.

  7. The Technology of Non-thermal Plasma Assisted NH3-SCR Reduce Marine Diesel Emission and Aldehydes Byproducts Formation

    Directory of Open Access Journals (Sweden)

    Lei Jiang

    2013-12-01

    Full Text Available This study describes briefly various after-treatment technologies in marine diesel engines and application difficulties of DPF and SCR are included. An experiment has been conducted using non-thermal plasma generated by Dielectric Barrier Discharge (DBD process assisted NH3-SCR catalyst to reduce the nitrogen oxides (NOx from diesel engine exhaust. The formation mechanism of byproducts-type such as HCHO and CH3CHO in the non-thermal plasma assisted NH3-SCR hybrid system.

  8. Central alpha-activation by clonidine reduces plasma level of beta-endorphin in patients with essential hypertension.

    Science.gov (United States)

    Yasunari, K; Kanayama, Y; Kohno, M; Murakawa, K; Kawarabayashi, T; Takeda, T; Kotsugai, N; Sato, K

    1985-10-21

    Whether peripheral beta-endorphin contributes to the antihypertensive action of clonidine was examined by measuring plasma levels of beta-endorphin-like immunoreactivity (beta EpLI) after acute administration of clonidine in patients with essential hypertension. Administration of clonidine (0.225 mg) in one dose significantly lowered blood pressure, decreased heart rate and reduced the plasma level of beta EpLI and ACTH, while the placebo had no effect on blood pressure, heart rate or plasma level of beta EpLI suggesting that peripheral beta-endorphin does not play a major role in the antihypertensive action of acute clonidine administration.

  9. A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2015-07-01

    Full Text Available Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein, or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %, for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2. Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2 was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

  10. Bactericidal active ingredient in cryopreserved plasma-treated water with the reduced-pH method for plasma disinfection

    Science.gov (United States)

    Kitano, Katsuhisa; Ikawa, Satoshi; Nakashima, Yoichi; Tani, Atsushi; Yokoyama, Takashi; Ohshima, Tomoko

    2016-09-01

    For the plasma disinfection of human body, plasma sterilization in liquid is crucial. We found that the plasma-treated water (PTW) has strong bactericidal activity under low pH condition. Physicochemical properties of PTW is discussed based on chemical kinetics. Lower temperature brings longer half-life and the bactericidal activity of PTW can be kept by cryopreservation. High performance PTW, corresponding to the disinfection power of 22 log reduction (B. subtilis spore), can be obtained by special plasma system equipped with cooling device. This is equivalent to 65% H2O2, 14% sodium hypochlorite and 0.33% peracetic acid, which are deadly poison for human. But, it is deactivated soon at higher temperature (4 sec. at body temperature), and toxicity to human body seems low. For dental application, PTW was effective on infected models of human extracted tooth. Although PTW has many chemical components, respective chemical components in PTW were isolated by ion chromatography. In addition to peaks of H2O2, NO2- and NO3-, a specific peak was detected. and only this fraction had bactericidal activity. Purified active ingredient of PTW is the precursor of HOO, and further details will be discussed in the presentation. MEXT (15H03583, 23340176, 25108505). NCCE (23-A-15).

  11. Ex-ante evaluation of biotechnology innovations: the case of folate biofortified rice in China.

    Science.gov (United States)

    De Steur, Hans; Blancquaert, Dieter; Gellynck, Xavier; Lambert, Willy; Van Der Straeten, Dominique

    2012-12-01

    In order to valorize novel biotechnology innovations, there is a need to evaluate ex-ante their market potential. A case in point is biofortification, i.e. the enhancement of the micronutrient content of staple crops through conventional or genetic breeding techniques. In a recent article in Nature Biotechnology, for example, De Steur et al. (2010) demonstrated the large potential consumer health benefits of folate biofortified rice as a means to reduce folate deficiency and Neural-Tube Defects. By focusing on a Chinese high-risk region of Neural-Tube Defects, the current study defines the potential cost-effectiveness of this genetically modified crop where the need to improve folate intake levels is highest. Building on the Disability-Adjusted Life Years (DALY) approach, both the potential health impacts and costs of its implementation are measured and benchmarked against similar innovations. The results show that this transgenic crop could be a highly cost-effective product innovation (US$ 120.34 - US$ 40.1 per DALY saved) to alleviate the large health burden of folate deficiency and reduce the prevalence of neural-tube birth defects. When compared with other biofortified crops and target regions, folate biofortified rice in China has a relatively high health impact and moderate cost-effectiveness. This research further supports the need for, and importance of ex-ante evaluation studies in order to adequately market and, thus, valorize biotechnology innovations. Although the cost-effectiveness analysis enables to illustrate the market potential of innovative agricultural biotechnology research, further research is required to address policy issues on transgenic biofortification, such as biosafety regulatory requirements.

  12. Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yu-Lun Li

    2014-03-01

    Full Text Available This study reports on the cellular uptake of folate tethered micelles using a branched skeleton of poly(ethylene glycol and poly(ε-caprolactone. The chemical structures of the copolymers were characterized by proton nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. Doxorubicin (DOX was utilized as an anticancer drug. The highest drug loading efficiencies of DOX in the folate decorated micelle (DMCF and folate-free micelle (DMC were found to be 88.5% and 88.2%, respectively, depending on the segment length of the poly(ε-caprolactone in the copolymers. A comparison of fluorescent microscopic images of the endocytosis pathway in two cell lines, human breast cancer cells (MCF-7 and human oral cavity carcinoma cells (KB, revealed that the micelles were engulfed by KB and MCF-7 cells following in vitro incubation for one hour. Flow cytometric analysis revealed that free folic acid can inhibit the uptake of DOX by 48%–57% and 26%–39% in KB cells and MCF-7 cells, respectively. These results prove that KB cells are relatively sensitive to folate-tethered micelles. Upon administering methyl-β-cyclodextrin, an inhibitor of the caveolae-mediated endocytosis pathway, the uptake of DOX by KB cells was reduced by 69% and that by MCF-7 cells was reduced by 56%. This finding suggests that DMCF enters cells via multiple pathways, thus implying that the folate receptor is not the only target of tumor therapeutics.

  13. Cryptophane-Folate Biosensor for 129Xe NMR

    Science.gov (United States)

    2014-12-01

    9), 775−782. (51) Wang, S., and Low, P. S. (1998) Folate-mediated targeting of antineoplastic drugs , imaging agents, and nucleic acids to cancer...implications in targeted therapy. Adv. Drug Delivery Rev. 56, 1067−1084. (47) Sudimack, J., and Lee, R. J. (2000) Targeted drug delivery via the folate...receptor. Adv. Drug Delivery Rev. 41 (2), 147−162. (48) Hilgenbrink, A. R., and Low, P. S. (2005) Folate receptor- mediated drug targeting: from

  14. Child's homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status.

    Science.gov (United States)

    Lubree, H G; Katre, P A; Joshi, S M; Bhat, D S; Deshmukh, U S; Memane, N S; Otiv, S R; Rush, E C; Yajnik, C S

    2012-02-01

    Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std β 0.201, R 2 7.7%), current consumption of cow's milk (std β 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std β -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 μm) and predicted by lower pregnancy vitamin B12 (std β -0.206, R 2 4.1%), lack of vitamin supplementation (std β -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std β 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

  15. Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes

    Science.gov (United States)

    van der Zwaluw, Nikita L.; Brouwer-Brolsma, Elske M.; van de Rest, Ondine; van Wijngaarden, Janneke P.; In ’t Veld, Paulette H.; Kourie, Daniella I.; Swart, Karin M. A.; Enneman, Anke W.; van Dijk, Suzanne C.; van der Velde, Nathalie; Kessels, Roy P. C.; Smeets, Paul A. M.; Kok, Frans J.; Dhonukshe-Rutten, Rosalie A. M.; de Groot, Lisette C. P. G. M.

    2016-01-01

    Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = −0.91, 95% CI −1.85–0.03; p = 0.06) and between serum folate and TBV (β = −0.20, 95% CI −0.38, −0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058–1069 mL) than the non-supplemented group (1072, 95% CI 1067–1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health. PMID:28029114

  16. Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

    Science.gov (United States)

    van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; van de Rest, Ondine; van Wijngaarden, Janneke P; In 't Veld, Paulette H; Kourie, Daniella I; Swart, Karin M A; Enneman, Anke W; van Dijk, Suzanne C; van der Velde, Nathalie; Kessels, Roy P C; Smeets, Paul A M; Kok, Frans J; Dhonukshe-Rutten, Rosalie A M; de Groot, Lisette C P G M

    2016-12-24

    We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T₁-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03). Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.

  17. Folate, vitamin B12, and vitamin B6 status of a group of high socioeconomic status women in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.

    Science.gov (United States)

    Fayyaz, Faiqa; Wang, Flora; Jacobs, René L; O'Connor, Deborah L; Bell, Rhonda C; Field, Catherine J

    2014-12-01

    Folic acid supplementation and food fortification policies have improved folate status in North American women of child bearing age. Recent studies have reported the possible inadequacy of vitamin B12 and B6 in the etiology of neural tube defects in folate-fortified populations. The aims of this study were to describe folate status and its relationship to supplementation and to assess vitamin B12 and B6 status in a cohort of pregnant women. Supplement intake data were collected in each trimester from the first cohort (n = 599) of the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Red blood cell folate (RBCF) and plasma folate, holotranscobalamin, and pyridoxal 5-phosphate were measured. Overt folate deficiency was rare (3%) but 24% of women in their first trimester had suboptimal RBCF concentration (1360 nmol·L(-1)) was observed in approximately half of the women during each pregnancy trimester. Vitamin B12 and B6 deficiencies were rare (pregnancy and over half the women had abnormally high RBCF, suggesting that supplementation during pregnancy is not appropriate in a cohort of women considered to be healthy and a low risk for nutritional deficiencies.

  18. The effects of folate intake on DNA and single-carbon pathway metabolism in the fruit fly Drosophila melanogaster compared to mammals.

    Science.gov (United States)

    Blatch, Sydella A; Stabler, Sally P; Harrison, Jon F

    2015-11-01

    Mechanisms of vitamin function in non-mammals are poorly understood, despite being essential for development. Folate and cobalamin are B-vitamin cofactors with overlapping roles in transferring various single-carbon units. In mammals, one or both is needed for nucleotide synthesis, DNA methylation, amino acid conversions and other reactions. However, there has been little investigation of the response to folate or cobalamin in insects. Here, we manipulated folate intake and potentially cobalamin levels in the fruit fly Drosophila melanogaster with chemically-defined diets, an antibiotic to reduce bacterially-derived vitamins, and the folate-interfering pharmaceutical methotrexate, to see if single-carbon metabolites and DNA synthesis rates would be affected. We found that similar to mammals with low folate intake, fruit fly larvae had significantly slower growth and DNA synthesis rates. But changes to single carbon-metabolites did not mirror that of mammals with abnormal folate or given MTX. Five of the nine metabolites measured were not significantly affected (methionine, serine, glycine, methylglycine, and dimethylglycine) and three (cystathionine, methylgycine, and methylmalonic acid) were only decreased in larvae consuming methotrexate. Metabolites expected to be elevated if flies used cobalamin from microbial symbionts were not affected by dietary sulfaquinoxaline. Our data support the role of folate in nucleotide synthesis in D. melanogaster and that microbial symbionts provide functioning folates. We could not confirm how folate intake affects single carbon pathway metabolites, nor whether Drososphila use microbially-derived cobalamin. Further work should explore which cofactors are used in fruit flies in these important and potentially novel pathways.

  19. The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake.

    Science.gov (United States)

    Ozaki, Mari; Molloy, Anne M; Mills, James L; Fan, Ruzong; Wang, Yifan; Gibney, Eileen R; Shane, Barry; Brody, Lawrence C; Parle-McDermott, Anne

    2015-10-01

    Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions, and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting. In this study, we evaluated whether the DHFR 19 bp deletion/insertion polymorphism affects circulating folate biomarkers in, to our knowledge, the largest cohort to address this question to date. Healthy young Irish individuals (n = 2507) between 19 and 36 y of age were recruited between February 2003 and February 2004. Folic acid intake from supplements and fortified foods was assessed with the use of a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate, and plasma total homocysteine (tHcy) were measured. Data were analyzed with the use of linear regression models. Folic acid intake was positively associated with serum (P folic acid intake (>326 μg folic acid/d; P = 0.96). A nonsignificant trend toward lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0-51 μg/d). In this cohort of healthy young individuals, the DHFR 19 bp deletion allele did not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect from this polymorphism on blood folate concentrations. © 2015 American Society for Nutrition.

  20. Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Cangemi, Claudia; Henriksen, J E

    2015-01-01

    whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous...... treatment (P=0.009), but increased after placebo (P=0.017). Baseline plasma fibulin-1 correlated with BP and estimated glomerular filtration rate. Increased levels of plasma fibulin-1 (P=0.004) were observed in diabetic participants reporting erectile dysfunction as compared with participants who did not....... Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling....

  1. The association between atopy and factors influencing folate metabolism: is low folate status causally related to the development of atopy?

    DEFF Research Database (Denmark)

    Husemoen, LL; Toft, U.; Fenger, Mogens

    2006-01-01

    BACKGROUND: Deficiency of folate has been associated with several disorders characterized by enhanced activation of the cellular immune system (non-allergic th1 type immune response). Whether folate status is also associated with atopic disease (allergic th2 type immune response) is unknown. We a.......12, 95% CI 0.98-1.29). CONCLUSIONS: The results suggest that an impaired folate metabolism may be causally related to the development of atopy....

  2. Salt stress reduces kernel number of corn by inhibiting plasma membrane H(+)-ATPase activity.

    Science.gov (United States)

    Jung, Stephan; Hütsch, Birgit W; Schubert, Sven

    2017-04-01

    Salt stress affects yield formation of corn (Zea mays L.) at various physiological levels resulting in an overall grain yield decrease. In this study we investigated how salt stress affects kernel development of two corn cultivars (cvs. Pioneer 3906 and Fabregas) at and shortly after pollination. In an earlier study, we found an accumulation of hexoses in the kernel tissue. Therefore, it was hypothesized that hexose uptake into developing endosperm and embryo might be inhibited. Hexoses are transported into the developing endosperm by carriers localized in the plasma membrane (PM). The transport is driven by the pH gradient which is built up by the PM H(+)-ATPase. It was investigated whether the PM H(+)-ATPase activity in developing corn kernels was inhibited by salt stress, which would cause a lower pH gradient resulting in impaired hexose import and finally in kernel abortion. Corn grown under control and salt stress conditions was harvested 0 and 2 days after pollination (DAP). Under salt stress sucrose and hexose concentrations in kernel tissue were higher 0 and 2 DAP. Kernel PM H(+)-ATPase activity was not affected at 0 DAP, but it was reduced at 2 DAP. This is in agreement with the finding, that kernel growth and thus kernel setting was not affected in the salt stress treatment at pollination, but it was reduced 2 days later. It is concluded that inhibition of PM H(+)-ATPase under salt stress impaired the energization of hexose transporters into the cells, resulting in lower kernel growth and finally in kernel abortion.

  3. Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2013-11-01

    Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

  4. Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha.

    Science.gov (United States)

    Hansen, Mariann F; Greibe, Eva; Skovbjerg, Signe; Rohde, Sarah; Kristensen, Anders C M; Jensen, Trine R; Stentoft, Charlotte; Kjær, Karina H; Kronborg, Camilla S; Martensen, Pia M

    2015-07-01

    The signal transducer and activator of transcription 3 (STAT3) is a well-described pro-oncogene found constitutively activated in several cancer types. Folates are B vitamins that, when taken up by cells through the Reduced Folate Carrier (RFC), are essential for normal cell growth and replication. Many cancer cells overexpress a glycophosphatidylinositol (GPI)-anchored Folate Receptor α (FRα). The function of FRα in cancer cells is still poorly described, and it has been suggested that transport of folate is not its primary function in these cells. We show here that folic acid and folinic acid can activate STAT3 through FRα in a Janus Kinase (JAK)-dependent manner, and we demonstrate that gp130 functions as a transducing receptor for this signalling. Moreover, folic acid can promote dose dependent cell proliferation in FRα-positive HeLa cells, but not in FRα-negative HEK293 cells. After folic acid treatment of HeLa cells, up-regulation of the STAT3 responsive genes Cyclin A2 and Vascular Endothelial Growth Factor (VEGF) were verified by qRT-PCR. The identification of this FRα-STAT3 signal transduction pathway activated by folic and folinic acid contributes to the understanding of the involvement of folic acid in preventing neural tube defects as well as in tumour growth. Previously, the role of folates in these diseases has been attributed to their roles as one-carbon unit donors following endocytosis into the cell. Our finding that folic acid can activate STAT3 via FRα adds complexity to the established roles of B9 vitamins in cancer and neural tube defects.

  5. 母亲还原叶酸载体1基因80G/A多态性与子女唐氏综合症易感性关系的meta分析%Correlation between maternal reduced folate carrier 1 gene 80G/A polymorphism and offspring down syndrome susceptibility: A meta-Analysis

    Institute of Scientific and Technical Information of China (English)

    何大莉; 曾照芳

    2013-01-01

    目的:探讨母亲还原叶酸载体1(RFC1)基因80G/A多态性与子女唐氏综合症(DS)易感性的相关性.方法:计算机检索PubMed、MEDLINE 、Web of Science、CNKI、CBM数据库,收集从建库至2012年9月间关于母亲RFC1基因80G/A多态性与子女DS易感性相关性的病例对照研究,对符合纳入标准的文献进行Meta分析.结果:共纳入7个研究,包括病例625例,对照767例.Meta分析结果显示:母亲RFC1基因80G/A多态性与子女DS易感性的相关性在各比较模型中差异无统计学意义[A Vs.G:OR=0.85,95%CI(0.73,1.00);AA Vs.GG:OR=0.73,95%CI(0.53,0.99);AA Vs.AG+ GG:OR=0.82,95%CI(0.63,1.06);AA+ AG Vs.GG:OR=0.81,95%CI(0.64,1.03)].基于人种的亚组分析结果显示,两者相关性无统计学意义.结论:目前的研究结果显示,母亲RFC1基因80G/A多态性与子女DS易感性无明显相关性.%Objective:To evaluate the correlation between maternal reduced folate carrier 1 (RFCl)gene 80G/A polymorphism and offspring Down syndrome susceptibility.Methods: We searched PubMed,MEDL!NE,Web of Science, CNKK CBM database and collected all the publications about the correlation between maternal reduced folate carrier 1 gene 80G/A polymorphism and offspring Down syndrome susceptibility. Results: A total of 7 studies involving 625 mothers who had children affected by DS and 767 controls mothers who had no miscarriages or children affected by genetic disorders in their life. The results of meta - analyses showed no significant difference was found in the correlation between maternal RFC1 80G/A polymorphism and offspring Down syndrome susceptibility( A Vs. G: OR = 0.85,95%CI(0.73,1.00); AAVs.GG: OR = 0.73,95%CI(0.53,0.99); AA Vs. AG+GG: OR = 0.82,95%CI(0.63,1.06); AA+AGVs. GG: OR = 0.81,95%CI(0.64,1.03) ]. In the subgroup analyses on ethnicity, no significant correlation was found. Conclusion:The present meta - analysis suggests that the correlation between maternal RFC1 80G/A polymorphism and

  6. 叶酸代谢相关基因的多态性与唐氏综合征的关系%Relationship between genetic polymorphisms of folate metabolism, plasma homocysteine levels and risk of Down syndrome

    Institute of Scientific and Technical Information of China (English)

    王文; 刘福民; 严晓南; 陈红

    2009-01-01

    Objective To investigate whether genetic polymorphisrns of methylenetetrahydrofolate reductase (MTHFR) contribute to the risk of Down syndrome(DS). Methods Altogether, 100 Chinese mothers who had given birth to DS babies (study group) and 100 matched mothers (control) were chosen and all were Han nationality. Genotypes of MTHFR 677 and MTHFR 1298 were determined by PCR-RFLP and MGB-Taqman resl-time PCR. The concentration of plasma homocysteine (HCY) was measured by chemilumineaence. Results The mutations of one or both alleles of MTHFR 677 and MTHFR 1298 were associated with a 2. 37-fold(95%CI: 1.19~3.05) and 1.97-fold(95%CI: 1.04~3.75) increase in the risk of having a child with DS. Combination of MTHFR 677CT and 1298AC/CC genotype had a 5. 62-fold increased risk of having a child with DS(95%Ch 1.86~17.03) and the combination of MTHFR 677TT and MTHFR 1298AC/CC genotype was significantly associated with an increased risk of DS(OR=11.84, 95%CI: 1.39~100.62). The mean plasma HCY concentration was significantly higher in the study group than that of control [(9.04±3.85) μmol/L vs (6.53±2. 06) μmol/L, P0.05). Higher HCY level was found in the genotype-pairs of MTHFR 677CT/TT and 1298AC/CC (P0.05).同时存在MTHFR 677CT/TT和1298AC/CC基因组合可使血浆HCY水平增高(P<0.05).结论 HCY/叶酸代谢相关基因的多态与汉族妇女生育DS患儿的风险相关,且可能存在基因的协同作用.

  7. Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Plomgaard, Peter; de Vries, Rindert; Dahlback, Bjorn; Nielsen, Lars B.

    2009-01-01

    Background: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (MetS) subjects

  8. Autism and Folate-dependent One-carbon Metabolism: Serendipity and Critical Branch-point Decisions in Science.

    Science.gov (United States)

    James, S Jill

    2013-11-01

    Folate-dependent one-carbon metabolism is present in every cell of the body. It represents a central systems biology hub that reverberates into countless other pathways with more specialized roles in specialized cell types throughout the body. I have spent 25 years of research on this core biochemical pathway with several unanticipated iterations that led me from Down syndrome to congenital heart defects to leukemia and finally to autism about 12 years ago. Figure 1 provides an overview of the three interdependent pathways involved in folate-dependent methionine "transmethylation" and "transsulfuration." Methionine is necessary for the synthesis of S-adenosylmethionine (SAM), the major methyl donor for all cellular methylation reactions. It is also the major precursor for cysteine, the rate-limiting amino acid for glutathione synthesis linking transmethylation and transsulfuration pathways. Methionine levels can be negatively affected by genetic and environmental factors that reduce folate availability and/or oxidative inhibition of the methionine synthase enzyme. Because these three metabolic pathways are mutually interdependent, genetic or environmental perturbation of folate or methionine metabolism will indirectly impact glutathione synthesis, and conversely, alterations in glutathione synthesis will alter flux through pathways of folate and methionine metabolism. This interdependency translates into broader impact on essential cellular functions.

  9. [Serum folate and homocysteine concentrations in women smoking during pregnancy and in umbilical cord blood of newborns].

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Lewandowski, Leszek; Gajewska, Joanna; Laskowska-Klita, Teresa

    2007-01-01

    In metabolism of homocysteine several enzymes and vitamin cofactors are involves. Genetic abnormalities in these enzymes or nutritional deficiency vitamins, especially of folate may lead to hyperhomocysteinemia, a known risk factor for some pregnancy complications. High maternal homocysteine and low folate levels correlate with low birth weight. Maternal smoking affected significantly total homocysteine concentration in infants. Studies in this area are still scarce and report on limited number of patients. The aim of our study was to assess serum folate and total homocysteine (tHcy) concentrations in smoking pregnant women and in their newborn infants as compared with nonsmoking. The study consisted of 57 pregnant women, who qualified into two groups: smoking (n=28) and nonsmoking (n=29). The serum concentrations of folate were determined by electrochemiluninescent method and tHcy by fluorescence polarization immunoassay. We shown, that serum homocysteine concentrations were significantly higher in smoking as compared with nonsmoking pregnant women (phomocysteine and folate showed a significant positive correlation's with these parameters in newborns. Average birth weight infants born to smoking mother was significantly lower than nonsmoking cigarettes (phomocysteine levels in serum of mothers and their infants. Smoking exposure is also associate with reduced birth weight.

  10. Folate Protects Hepatocytes of Hyperhomocysteinemia Mice from Apoptosis via Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-activated Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Yang, Anning; Sun, Yue; Mao, Caiyan; Yang, Songhao; Huang, Min; Deng, Mei; Ding, Ning; Yang, Xiaoling; Zhang, Minghao; Jin, Shaoju; Jiang, Yideng; Huang, Ying

    2017-02-23

    Folate deficiency is a known risk factor for liver injury; however, the underlying mechanism remains unclear. In this study, we employed a high homocysteine-induced liver injury model of Apolipoprotein E-deficient (ApoE(-/-) ) mice fed high-methionine diet and found that high homocysteine induced endoplasmic reticulum (ER) stress and liver cell apoptosis by downregulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression; observations that were attenuated with supplementation of dietary folate. The regulation on CFTR expression was mediated by CFTR promoter methylation and trimethylation of lysine 27 on histone H3 (H3K27me3). Mechanistically, folate inhibited homocysteine-induced CFTR promoter methylation and H3K27me3, which resulted in upregulation of CFTR expression, and reduced ER stress and liver cell apoptosis. Further study showed that folate inhibited the expression of DNA methyltransferase 1 and enhancer of zeste homolog 2, downregulated the cellular concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and upregulated the SAM/SAH ratio, leading to the inhibition of Hcy-induced DNA hypermethylation and H3K27me3 in CFTR promoter. In conclusion, our results provide insight into the protective role of folate in homocysteine-induced ER stress and liver cell apoptosis through the regulation of CFTR expression. This article is protected by copyright. All rights reserved.

  11. Targeting of pegylated liposomal mitomycin-C prodrug to the folate receptor of cancer cells: Intracellular activation and enhanced cytotoxicity.

    Science.gov (United States)

    Patil, Yogita; Amitay, Yasmine; Ohana, Patricia; Shmeeda, Hilary; Gabizon, Alberto

    2016-03-10

    Mitomycin C (MMC) is a powerful anti-bacterial, anti-fungal and anti-tumor antibiotic, often active against multidrug resistant cells. Despite a broad spectrum of antitumor activity, MMC clinical use is relatively limited due to its fast clearance and dose-limiting toxicity. To exploit the potential antitumor activity of MMC and reduce its toxicity we have previously developed a formulation of pegylated liposomes with a lipophilic prodrug of MMC (PL-MLP), activated by endogenous reducing agents which are abundant in the tumor cell environment in the form of different thiols. PL-MLP has minimal in vitro cytotoxicity unless reducing agents are added to the cell culture to activate the prodrug. In the present study, we hypothesized that targeting PL-MLP via folate receptors will facilitate intracellular activation of prodrug and enhance cytotoxic activity without added reducing agents. We grafted a lipophilic folate conjugate (folate-PEG(5000)-DSPE) to formulate folate targeted liposomes (FT-PL-MLP) and examined in vitro cell uptake and cytotoxic activity in cancer cell lines with high folate receptors (HiFR). 3H-cholesterol-hexadecyl ether (3H-Chol)-radiolabeled liposomes were prepared to study liposome-cell binding in parallel to cellular uptake of prodrug MLP. 3H-Chol and MLP cell uptake levels were 4-fold and 9-fold greater in KB HiFR cells when FT-PL-MLP is compared to non-targeted PL-MLP liposomes. The cytotoxic activity of FT-PL-MLP liposomes was significantly increased up to ~5-fold compared with PL-MLP liposomes in all tested HiFR expressing cell lines. The enhanced uptake and intracytoplasmic liposome delivery was confirmed by confocal fluorescence studies with Rhodamine-labeled liposomes. In vivo, no significant differences in pharmacokinetics and biodistribution were observed when PL-MLP was compared to FT-PL-MLP by the intravenous route. However, when liposomes were directly injected into the peritoneal cavity of mice with malignant ascites of J6456 Hi

  12. Quantitative flux analysis reveals folate-dependent NADPH production

    Science.gov (United States)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  13. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  14. Comparison of the effect of homocysteine in the reduced form, its thiolactone and protein homocysteinylation on hemostatic properties of plasma.

    Science.gov (United States)

    Malinowska, Joanna; Nowak, Paweł; Olas, Beata

    2011-03-01

    Mechanisms involved in the relationship between hyperhomocysteinemia and hemostatic process are still unclear. In the literature there are few papers describing studies on the effects of homocysteine (Hcys) on proteins that participate in blood coagulation and fibrinolysis in human. The aim of our study was to establish and compare the influence of a reduced form of Hcys (at final doses of 0.01 - 1 mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 0.1 - 1 μM) on the clot formation (using whole human plasma and purified fibrinogen) and the fibrin lysis. Moreover, the aim of our study was to explain the effect of plasma protein modifications (S- and N-homocysteinylation) on selected parameters of hemostasis. We observed that HTL, like its precursor, a reduced form of Hcys stimulated polymerization of fibrinogen, but this process was not dose-dependent. In the presence of HTL (at the lowest tested concentration - 0.1μM) the increase was about 55%. Our present results also demonstrated that Hcys in the reduced form (0.01 - 1 mM) and HTL at lower doses than Hcys (0.1 - 1 μM) reduced the fibrin lysis in whole human plasma. Our results reported that HTL, like the reduced form of Hcys (at concentrations corresponding to concentrations in plasma during hyperhomocysteinemia) induced modifications of hemostatic plasma proteins, and the consequence of these modifications may be alteration in protein structure associated with changes of hemostatic functions.

  15. Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum.

    Science.gov (United States)

    Nickell, Justin; Salvatore, Michael F; Pomerleau, Francois; Apparsundaram, Subbu; Gerhardt, Greg A

    2007-11-01

    Extracellular L-glutamate poses a severe excitotoxic threat to neurons and glia when unregulated, therefore low synaptic levels of this neurotransmitter must be maintained via a rapid and robust transport system. A recent study from our laboratory showed a reduced glutamate uptake rate in the striatum of the aged Fischer 344 (F344) rat, yet the mechanism underlying this phenomenon is unknown. The current study utilized in vivo electrochemical recordings, immunoblotting and biotinylation in young (6 months), late-middle aged (18 months) and aged (24 months) F344 rats to elucidate the potential role that glutamate transporters (GLT-1, GLAST, and EAAC1) may play in this mechanism. Here we show that the time necessary to clear glutamate from the late-middle aged and aged striatum is significantly prolonged in comparison to the young striatum. In addition, an analysis of various sub-regions of the striatum revealed a marked dorsoventral gradient in terms of glutamate clearance times in the aged striatum, a phenomenon which was not present in the striatum of the animals of the remaining age groups. We also found that the decreased glutamate clearance time observed in the late-middle aged and aged rats is not due to a decrease in the production of total transporter protein among these three transporters. Rather, a significant reduction in the amount of GLAST expressed on the plasma membrane surface in the aged animals (approximately 55% when compared to young rats) may contribute to this phenomenon. These age-related alterations in extracellular l-glutamate regulation may be key contributors to the increased susceptibility of the aged brain to excitotoxic insults such as stroke and hypoxia.

  16. Nutrigenetics in cancer research--folate metabolism and colorectal cancer.

    Science.gov (United States)

    Ulrich, Cornelia M

    2005-11-01

    The B vitamin folate is essential for one-carbon transfer reactions, including those related to the methylation of DNA or other substrates and nucleotide synthesis. Epidemiologic and experimental studies implicate low-folate intakes in elevated risk of colorectal neoplasia and suggest that biologic mechanisms underlying this relation include disturbances in DNA methylation patterns or adverse effects on DNA synthesis and repair. With the completion of the Human Genome Project, a vast amount of data on inherited genetic variability has become available. This genetic information can be used in studies of molecular epidemiology to provide information on multiple aspects of folate metabolism. First, studies linking polymorphisms in folate metabolism to an altered risk of cancer provide evidence for a causal link between this pathway and colorectal carcinogenesis. Second, studies on genetic characteristics can help clarify whether certain individuals may benefit from higher or lower intakes of folate or nutrients relevant to folate metabolism. Third, studies on genetic polymorphisms can generate hypotheses regarding possible biologic mechanisms that connect this pathway to carcinogenesis. Last, genetic variability in folate metabolism may predict survival after a cancer diagnosis, possibly via pharmacogenetic effects. To solve the puzzle of the folate-cancer relation, a transdisciplinary approach is needed that integrates knowledge from epidemiology, clinical studies, experimental nutrition, and mathematical modeling. This review illustrates knowledge that can be gained from molecular epidemiology in the context of nutrigenetics, and the questions that this approach can answer or raise.

  17. Intake of dietary folate vitamers and risk of colorectal carcinoma

    NARCIS (Netherlands)

    Konings, E.J.M.; Goldbohm, R.A.; Brants, H.A.M.; Saris, W.H.M.; Brandt, P.A. van den

    2002-01-01

    BACKGROUND. Several studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk. METHODS. The aim of the current study wa

  18. Metabolic engineering of folate production in lactic acid bacteria

    NARCIS (Netherlands)

    Sybesma, W.F.H.

    2003-01-01

    Folate is an essential compound in the human diet. Folate deficiency occurs frequently among certain population groups even in highly developed countries and may increase the risks for several diseases like neural tube defects, cardiovascular diseases and certain forms of cancer. The dairy starter b

  19. Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

    DEFF Research Database (Denmark)

    Dullaart, Robin P F; Plomgaard, Peter; de Vries, Rindert

    2009-01-01

    BACKGROUND: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (Met......S) subjects, and determined whether intima media thickness (IMT) is associated with apoM. METHODS: In 19 non-diabetic subjects with and 60 non-diabetic subjects without MetS (NCEP, ATP III criteria), the relationships of plasma apoM with obesity, glucose, insulin, lipids and adipokines, as well as with IMT...

  20. Enhancement of liquid treatment efficiency by microwave plasma under flow-induced reduced pressure

    Science.gov (United States)

    Ito, Michiko; Takahashi, Tomohiro; Takitou, Sho; Takashima, Seigo; Nomura, Norio; Kitagawa, Tominori; Toyoda, Hirotaka

    2017-02-01

    A new microwave plasma device system for in-line solution treatment is developed. In this system, the Venturi effect for pressure reduction is utilized for stable and effective plasma production. The decomposition of phenol solution is tested to verify the efficiency of an in-line plasma treatment system, and such a treatment system is confirmed to have a higher decomposition efficiency than our previously developed batch-type treatment system. Increases in phenol decomposition speed and decomposition energy efficiency with increasing solution flow rate are observed, which suggests the suppression of OH radical recombination and the utilization of OH radicals under flowing solution conditions.

  1. Resistive reduced MHD modeling of multi-edge-localized-mode cycles in Tokamak X-point plasmas.

    Science.gov (United States)

    Orain, F; Bécoulet, M; Huijsmans, G T A; Dif-Pradalier, G; Hoelzl, M; Morales, J; Garbet, X; Nardon, E; Pamela, S; Passeron, C; Latu, G; Fil, A; Cahyna, P

    2015-01-23

    The full dynamics of a multi-edge-localized-mode (ELM) cycle is modeled for the first time in realistic tokamak X-point geometry with the nonlinear reduced MHD code jorek. The diamagnetic rotation is found to be instrumental to stabilize the plasma after an ELM crash and to model the cyclic reconstruction and collapse of the plasma pressure profile. ELM relaxations are cyclically initiated each time the pedestal gradient crosses a triggering threshold. Diamagnetic drifts are also found to yield a near-symmetric ELM power deposition on the inner and outer divertor target plates, consistent with experimental measurements.

  2. Caffeine ingestion after rapid weight loss in judo athletes reduces perceived effort and increases plasma lactate concentration without improving performance.

    Science.gov (United States)

    Lopes-Silva, Joao P; Felippe, Leandro J C; Silva-Cavalcante, Marcos D; Bertuzzi, Romulo; Lima-Silva, Adriano E

    2014-07-22

    The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this "loading period", subjects ingested a capsule containing either caffeine (6 mg·kg-1) or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (-3.9% ± 1.6% and -4.0% ± 2.3% from control, respectively, p caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

  3. Brief Report: Are Autistic-Behaviors in Children Related to Prenatal Vitamin Use and Maternal Whole Blood Folate Concentrations?

    Science.gov (United States)

    Braun, Joseph M.; Froehlich, Tanya; Kalkbrenner, Amy; Pfeiffer, Christine M.; Fazili, Zia; Yolton, Kimberly; Lanphear, Bruce P.

    2014-01-01

    Prenatal multivitamin/folic acid supplement use may reduce the risk of autism spectrum disorders. We investigated whether 2nd trimester prenatal vitamin use and maternal whole blood folate (WBF) concentrations were associated with Social Responsiveness Scale (SRS) scores at 4-5 years of age in a prospective cohort of 209 mother-child pairs. After…

  4. Brief Report: Are Autistic-Behaviors in Children Related to Prenatal Vitamin Use and Maternal Whole Blood Folate Concentrations?

    Science.gov (United States)

    Braun, Joseph M.; Froehlich, Tanya; Kalkbrenner, Amy; Pfeiffer, Christine M.; Fazili, Zia; Yolton, Kimberly; Lanphear, Bruce P.

    2014-01-01

    Prenatal multivitamin/folic acid supplement use may reduce the risk of autism spectrum disorders. We investigated whether 2nd trimester prenatal vitamin use and maternal whole blood folate (WBF) concentrations were associated with Social Responsiveness Scale (SRS) scores at 4-5 years of age in a prospective cohort of 209 mother-child pairs. After…

  5. Do dietary patterns in older men influence change in homocysteine through folate fortification? The Normative Aging Study

    Science.gov (United States)

    In 1996, the Food and Drug Administration issued a regulation requiring all enriched grain products to be fortified with folic acid to reduce the risk of neural-tube defects, but it remains unclear how this fortification has affected folate and homocysteine status in subgroups of the population with...

  6. Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.

    Science.gov (United States)

    O'Donnell, James S; McKinnon, Thomas A J; Crawley, James T B; Lane, David A; Laffan, Michael A

    2005-09-15

    ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.

  7. Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

    LENUS (Irish Health Repository)

    Walsh, Sarah K

    2012-01-31

    Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

  8. Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol.

    Science.gov (United States)

    Dietrich-Muszalska, Anna; Olas, Beata; Kontek, Bogdan; Rabe-Jabłońska, Jolanta

    2011-07-01

    Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to establish the effects of beta-d-glucan, polysaccharide derived from the yeast cell walls of species such as Saccharomyces cerevisiae, and the antipsychotics (the first generation antipsychotic (FGA) - haloperidol and the second generation antipsychotic (SGA) - amisulpride) action on plasma lipid peroxidation in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with haloperidol or amisulpride in the presence of beta-glucan (4 μg/ml). The action of beta-d-glucan was also compared with the properties of a well characterized commercial monomeric polyphenol - resveratrol (3,4',5-trihydroxystilbene, the final concentration - 4 μg/ml). The two-way analysis variance showed that the differences in TBARS levels were depended on the type of tested drugs (p=7.9 × 10(-6)). We observed a statistically increase of the level of biomarker of lipid peroxidation such as TBARS after 1 and 24h incubation of plasma with haloperidol compared to the control samples (p0.05). We showed that in the presence of beta-glucan, lipid peroxidation in plasma samples treated with haloperidol was significantly decreased. Moreover, we did not observe the synergistic action of beta-glucan and amisulpride on the inhibition of plasma lipid peroxidation. However, the beta-d-glucan was found to be more effective antioxidant, than the solution of pure resveratrol. The presented results indicate that beta-glucan seems to have distinctly protective effects against the impairment of plasma lipid molecules induced by haloperidol.

  9. [Reducing centers on the surface of Escherichia coli bacteria and their role in copper-induced plasma membrane permeability].

    Science.gov (United States)

    Lebedev, V S; Veselovskiĭ, A V; Deĭnega, E Iu; Fedorov, Iu I

    2000-01-01

    The reducing properties of Escherichia coli and their role in the induction of nonselective cationic permeability of plasma membrane by the action of Cu2+ ions were studied. The ability of cells to reduce exogenous dithiopyridine was shown to be maximal in freshly collected culture and to decrease upon starvation or exhaustion of bacteria by dinitrophenol, in the presence of other oxidants of cell thiols in the medium, and after the disturbance of the barrier properties of membrane by tetrachloracetic acid or butanol. The alkylation of cell thiols accessible for N-ethyl maleimide completely disrupted the reducing activity of bacteria. These data are consistent with the conception that the reduction of dithiopyridine and Cu2+ ions by bacteria occurs on the thiol-containing centers of the cell surface, which are continuously reduced by the transfer of cell reducing equivalents from the inner to the outer surface of plasma membrane. The analysis of data on the effect of external oxidizing and reducing agents on the copper-induced plasmolysis of bacteria showed that the induction of membrane permeability by the action of copper can occur upon interaction with critical targets on the surface of Cu+ ions formed in the periplasmic space in the reaction of Cu2+ ions with reducing centers.

  10. In vivo imaging of folate receptor positive tumor xenografts using novel 68Ga-NODAGA-folate conjugates.

    Science.gov (United States)

    Fani, Melpomeni; Tamma, Maria-Luisa; Nicolas, Guillaume P; Lasri, Elisabeth; Medina, Christelle; Raynal, Isabelle; Port, Marc; Weber, Wolfgang A; Maecke, Helmut R

    2012-05-07

    The overexpression of the folate receptor (FR) in a variety of malignant tumors, along with its limited expression in healthy tissues, makes it an attractive tumor-specific molecular target. Noninvasive imaging of FR using radiolabeled folate derivatives is therefore highly desirable. Given the advantages of positron emission tomography (PET) and the convenience of (68)Ga production, the aim of our study was to develop a new (68)Ga-folate-based radiotracer for clinical application. The chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) was conjugated to folic acid and to 5,8-dideazafolic acid using 1,2-diaminoethane as a spacer, resulting in two novel conjugates, namely, P3246 and P3238, respectively. Both conjugates were labeled with (68/67)Ga. In vitro internalization, efflux, and saturation binding studies were performed using the FR-positive KB cell line. Biodistribution and small-animal PET imaging studies were performed in nude mice bearing subcutaneous KB xenografts. Both conjugates were labeled with (68)Ga at room temperature within 10 min in labeling yields >95% and specific activity ~30 GBq/μmol. The K(d) values of (68/67)Ga-P3246 (5.61 ± 0.96 nM) and (68/67)Ga-P3238 (7.21 ± 2.46 nM) showed high affinity for the FR. (68/67)Ga-P3246 showed higher cell-associated uptake in vitro than (68/67)Ga-P3238 (approximately 72 and 60% at 4 h, respectively, P 68)Ga-P3246 and (68)Ga-P3238 (16.56 ± 3.67 and 10.95 ± 2.12% IA/g, respectively, P > 0.05) and remained at about the same level up to 4 h. Radioactivity also accumulated in the FR-positive organs, such as kidneys (91.52 ± 21.05 and 62.26 ± 14.32% IA/g, respectively, 1 h pi) and salivary glands (9.05 ± 2.03 and 10.39 ± 1.19% IA/g, respectively, 1 h pi). The specificity of the radiotracers for the FR was confirmed by blocking experiments where tumor uptake was reduced by more than 85%, while the uptake in the kidneys and the salivary glands was reduced by more than 90%. Reduction of

  11. Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.

    Science.gov (United States)

    Zhang, Li; Yuan, Yongsheng; Tong, Qing; Jiang, Siming; Xu, Qinrong; Ding, Jian; Zhang, Lian; Zhang, Rui; Zhang, Kezhong

    2016-01-01

    This study aimed to evaluate the level of taurine in plasma, and its association with the severity of motor and non-motor symptoms (NMS) and chronic levodopa treatment in Parkinson's disease (PD). Plasma taurine level was measured in treated PD (tPD), untreated PD (ntPD) and control groups. Motor symptoms and NMS were assessed using the Unified Parkinson's Disease Rating Scale, the short form of the McGill Pain Questionnaire, the Hamilton Depression Scale, the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms and the Pittsburgh Sleep Quality Index. Longtime exposure to levodopa was indicated by its approximate cumulative dosage. The plasma taurine levels of PD patients were decreased when compared with controls and negatively associated with motor severity but not NMS. Moreover, tPD patients exhibited lower levels of plasma taurine than ntPD patients. Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD. After controlling for potential confounders, the association between taurine and levodopa remained significant. Our study supports that taurine may play important roles in the pathophysiology of PD and the disturbances caused by chronic levodopa administration.

  12. Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women.

    Science.gov (United States)

    Matsubara, Tomoko; Miyaki, Asako; Akazawa, Nobuhiko; Choi, Youngju; Ra, Song-Gyu; Tanahashi, Koichiro; Kumagai, Hiroshi; Oikawa, Satoshi; Maeda, Seiji

    2014-02-01

    The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and β-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50-76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50-76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the cross-sectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the β-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the β-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.

  13. Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren

    Science.gov (United States)

    Tapaninen, Tuija; Neuvonen, Pertti J; Niemi, Mikko

    2011-01-01

    AIM The aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren. METHODS In a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h. RESULTS Orange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%, P juice correlated with aliskiren AUC during the water phase (r = 0.98, P juice and apple juice phases, respectively, than during the water phase (P juice and apple juice greatly reduce the plasma concentrations and renin-inhibiting effect of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided. PMID:21204914

  14. Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives.

    Science.gov (United States)

    Ozbek, Zeynep; Kucukali, Cem Ismail; Ozkok, Elif; Orhan, Nurcan; Aydin, Makbule; Kilic, Gamze; Sazci, Ali; Kara, Ihsan

    2008-07-01

    We investigated the effect of polymorphic variants of c.1298A>C (Glu429Ala) and c.677C>T (Ala222Val) in methylenetetrahydrofolate (MTHFR) gene on the total homocysteine (tHcy), folate and B12 levels in patients with bipolar disorder, first-degree relatives of patients, and controls. The c.677C>T and c.1298A>C polymorphisms in MTHFR were determined by polymerase chain reaction-restriction fragment length polymorphism in 197 bipolar patients, 278 relatives and 238 controls. tHcy and folate and vitamin B12 levels were measured by Fluorescence Polarization Immunoassay and Electrochemiluminescence, respectively. The tHcy was significantly increased in patients and relatives. In contrast, folate and B12 were significantly lower in patients and relatives. Gender was not considered as a significant determinant in the multivariate analysis. Genotypes of c.1298A>C and c.677C>T were correlated with tHcy, folate and B12. Patients and relatives carrying TT and/or AA and AC genotypes had elevated tHcy and reduced folate and B12 levels. High tHcy but low folate and vitamin B12 levels may be a risk factor for development of bipolar disorder.

  15. A low-glycemic-index diet reduces plasma PAI-1 activity in overweight women

    DEFF Research Database (Denmark)

    Jensen, Lotte

    to decrease during weight loss. However, the beneficial effects of healthy diets on PAI-1 levels may not solely depend on weight loss, but other factors may also play a role. For example better glycemic control has been observed in diabetic patients after a low glycemic index (GI) diet compared to a high GI......Introduction An elevated level of plasminogen activator inhibitor-1 (PAI-1) in plasma is a core feature of the metabolic syndrome. Plasma PAI-1 is elevated in obesity and might be responsible for some of the secondary effects of obesity as diabetes and cardiovascular diseases. PAI-1 has been shown...... diet. Still, the relevance of GI in preventing the metabolic syndrome is controversial. Objectives The main purpose of the present study was to investigate the effect of 10 weeks intake of a low glycemic index vs. a high glycemic index high-carbohydrate, low fat ad libitum diet on plasma PAI-1 activity...

  16. Folate targeted polymeric 'green' nanotherapy for cancer

    Science.gov (United States)

    Narayanan, Sreeja; Binulal, N. S.; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

    2010-07-01

    The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)—'NanoGSE'—was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ~ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ~ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

  17. Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Melissa N Barber

    Full Text Available BACKGROUND: Obesity and type 2 diabetes (T2DM are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM. METHODOLOGY/PRINCIPAL FINDINGS: Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD-induced reduction in lysophosphatidylcholine (LPC levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients. CONCLUSION: Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.

  18. Folate receptor targeted liposomes encapsulating anti-cancer drugs.

    Science.gov (United States)

    Chaudhury, Anumita; Das, Surajit

    2015-01-01

    Among all available lipid based nanoparticulate systems, the success of liposomal drug delivery system is evident by the number of liposomal products available in the market or under advanced stages of preclinical and clinical trials. Liposome has the ability to deliver chemotherapeutic agents to the targeted tissues or even inside the cancerous cells by enhanced intracellular penetration or improved tumour targeting. In the last decade, folate receptor mediated tumour targeting has emerged as an attractive alternative method of active targeting of cancer cells through liposomes due to its numerous advantages over other targeting methods. Folate receptors, also known as folate binding proteins, allow the binding and internalization of folate or folic acid into the cells by a method called folate receptor mediated endocytosis. They have restricted presence in normal cells and are mostly expressed during malignant transformation. In this review article, folate receptor targeting capability of liposomes has been described. This review article has focussed on the different cancer drugs which have been encapsulated in folate receptor targeted liposomes and their in vitro as well as in vivo efficacies in several tumour models.

  19. Effects of industrial processing on folate content in green vegetables.

    Science.gov (United States)

    Delchier, Nicolas; Ringling, Christiane; Le Grandois, Julie; Aoudé-Werner, Dalal; Galland, Rachel; Georgé, Stéphane; Rychlik, Michael; Renard, Catherine M G C

    2013-08-15

    Folates are described to be sensitive to different physical parameters such as heat, light, pH and leaching. Most studies on folates degradation during processing or cooking treatments were carried out on model solutions or vegetables only with thermal treatments. Our aim was to identify which steps were involved in folates loss in industrial processing chains, and which mechanisms were underlying these losses. For this, the folates contents were monitored along an industrial canning chain of green beans and along an industrial freezing chain of spinach. Folates contents decreased significantly by 25% during the washing step for spinach in the freezing process, and by 30% in the green beans canning process after sterilisation, with 20% of the initial amount being transferred into the covering liquid. The main mechanism involved in folate loss during both canning green beans and freezing spinach was leaching. Limiting the contact between vegetables and water or using steaming seems to be an adequate measure to limit folates losses during processing.

  20. Rice folate enhancement through metabolic engineering has an impact on rice seed metabolism, but does not affect the expression of the endogenous folate biosynthesis genes.

    Science.gov (United States)

    Blancquaert, Dieter; Van Daele, Jeroen; Storozhenko, Sergei; Stove, Christophe; Lambert, Willy; Van Der Straeten, Dominique

    2013-11-01

    Folates are key-players in one-carbon metabolism in all organisms. However, only micro-organisms and plants are able to synthesize folates de novo and humans rely entirely on their diet as a sole folate source. As a consequence, folate deficiency is a global problem. Although different strategies are currently implemented to fight folate deficiency, up until now, all of them have their own drawbacks. As an alternative and complementary means to those classical strategies, folate biofortification of rice by metabolic engineering was successfully achieved a couple of years ago. To gain more insight into folate biosynthesis regulation and the effect of folate enhancement on general rice seed metabolism, a transcriptomic study was conducted in developing transgenic rice seeds, overexpressing 2 genes of the folate biosynthetic pathway. Upon folate enhancement, the expression of 235 genes was significantly altered. Here, we show that rice folate biofortification has an important effect on folate dependent, seed developmental and plant stress response/defense processes, but does not affect the expression of the endogenous folate biosynthesis genes.

  1. Natural variation of folate content and composition in spinach (Spinacia oleracea) germplasm.

    Science.gov (United States)

    Shohag, M J I; Wei, Yan-yan; Yu, Ning; Zhang, Jie; Wang, Kai; Patring, Johan; He, Zhen-li; Yang, Xiao-e

    2011-12-14

    Breeding to increase folate levels in edible parts of plants, termed folate biofortification, is an economical approach to fight against folate deficiency in humans, especially in the developing world. Germplasm with elevated folates are a useful genetic source for both breeding and direct use. Spinach is one of the well-know vegetables that contains a relatively high amount of folate. Currently, little is known about how much folate, and their composition varies in different spinach accessions. The aim of this study was to investigate natural variation in the folate content and composition of spinach genotypes grown under controlled environmental conditions. The folate content and composition in 67 spinach accessions were collected from the United States Department of Agriculture (USDA) and Asian Vegetable Research and Development Center (AVRDC) germplasm collections according to their origin, grown under control conditions to screen for natural diversity. Folates were extracted by a monoenzyme treatment and analyzed by a validated liquid chromatography (LC) method. The total folate content ranged from 54.1 to 173.2 μg/100 g of fresh weight, with 3.2-fold variation, and was accession-dependent. Four spinach accessions (PI 499372, NSL 6095, PI 261787, and TOT7337-B) have been identified as enriched folate content over 150 μg/100 g of fresh weight. The folate forms found were H(4)-folate, 5-CH(3)-H(4)-folate, and 5-HCO-H(4)-folate, and 10-CHO-folic acid also varied among different accessions and was responsible for variation in the total folate content. The major folate vitamer was represented by 5-CH(3)-H(4)-folate, which on average accounted for up to 52% of the total folate pool. The large variation in the total folate content and composition in diverse spinach accessions demonstrates the great genetic potential of diverse genotypes to be exploited by plant breeders.

  2. Caffeine Ingestion after Rapid Weight Loss in Judo Athletes Reduces Perceived Effort and Increases Plasma Lactate Concentration without Improving Performance

    Science.gov (United States)

    Lopes-Silva, Joao P.; Felippe, Leandro J. C.; Silva-Cavalcante, Marcos D.; Bertuzzi, Romulo; Lima-Silva, Adriano E.

    2014-01-01

    The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this “loading period”, subjects ingested a capsule containing either caffeine (6 mg·kg−1) or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (−3.9% ± 1.6% and −4.0% ± 2.3% from control, respectively, p judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate. PMID:25054553

  3. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

    2001-01-01

    We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

  4. Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine

    Science.gov (United States)

    Phenylbutyrate (PB) has been used as an alternative pathway to excrete nitrogen in urea cycle disorder patients for the last 20 years. PB, after oxidation to phenylacetate, is conjugated with glutamine and excreted in the urine. A reduction in the plasma concentration of branched amino acids (BCAA) ...

  5. Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

    NARCIS (Netherlands)

    Goekoop, J. G.; de Winter, R. F. P.; Wolterbeek, R.; Spinhoven, P.; Zitman, F. G.; Wiegant, V. M.

    2009-01-01

    The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of d

  6. Plasma graft of poly(ethylene glycol) methyl ether methacrylate (PEGMA) on RGP lens surface for reducing protein adsorption

    Science.gov (United States)

    Shiheng, Yin; Li, Ren; Yingjun, Wang

    2017-01-01

    Poly(ethylene glycol) methyl ether methacrylate (PEGMA) was grafted on fluorosilicone acrylate rigid gas permissible contact lens surface by means of argon plasma induced polymerization to improve surface hydrophilicity and reduce protein adsorption. The surface properties were characterized by contact angle measurement, x-ray photoelectron spectroscopy (XPS) and atomic force microscopy respectively. The surface protein adsorption was evaluated by lysozyme solution immersion and XPS analysis. The results indicated that a thin layer of PEGMA was successfully grafted. The surface hydrophilicity was bettered and surface free energy increased. The lysozyme adsorption on the lens surface was reduced greatly. The study was supported by National Natural Science Foundation of China (No. 51273072).

  7. Red cell or serum folate: what to do in clinical practice?

    Science.gov (United States)

    Farrell, Christopher-John L; Kirsch, Susanne H; Herrmann, Markus

    2013-03-01

    Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate.

  8. Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

    Science.gov (United States)

    Chen, Fei; Shao, Kejing; Zhu, Bao; Jiang, Mengjun

    2016-05-15

    A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides.

  9. Caffeine Ingestion after Rapid Weight Loss in Judo Athletes Reduces Perceived Effort and Increases Plasma Lactate Concentration without Improving Performance

    Directory of Open Access Journals (Sweden)

    Joao P. Lopes-Silva

    2014-07-01

    Full Text Available The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this “loading period”, subjects ingested a capsule containing either caffeine (6 mg·kg−1 or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (−3.9% ± 1.6% and −4.0% ± 2.3% from control, respectively, p < 0.05. At three hours after weigh-in, body weight had increased with both treatments but remained below the control (−3.0% ± 1.3% and −2.7% ± 2.2%. There were no significant differences in the number of throws between the control, caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p < 0.05. In conclusion, caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

  10. Preparation and characterization of folate-poly(ethylene glycol)-grafted-trimethylchitosan for intracellular transport of protein through folate receptor-mediated endocytosis.

    Science.gov (United States)

    Zheng, Yu; Song, Xiangrong; Darby, Michael; Liang, Yufeng; He, Ling; Cai, Zheng; Chen, Qiuhong; Bi, Yueqi; Yang, Xiaojuan; Xu, Jiapeng; Li, Yuanbo; Sun, Yiyi; Lee, Robert J; Hou, Shixiang

    2010-01-01

    To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins to specific tumor cells, folate-poly(ethylene glycol)-grafted-trimethylchitosan (folate-PEG-g-TMC) was synthesized. Nano-scaled spherical polyelectrolyte complexes between the folate-PEG-g-TMC and fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) were prepared under suitable weight ratio of copolymer to FITC-BSA by ionic interaction between the positively charged copolymers and the negatively charged FITC-BSA. Intracellular uptake of FITC-BSA was specifically enhanced in SKOV3 cells (folate receptor over-expressing cell line) through folate receptor-mediated endocytosis compared with A549 cells (folate receptor deficient cell line). Folate-PEG-g-TMC shows promise for intracellular transport of negatively charged therapeutic proteins into folate receptor over-expressing tumor cells.

  11. Clovamide-rich extract from Trifolium pallidum reduces oxidative stress-induced damage to blood platelets and plasma.

    Science.gov (United States)

    Kolodziejczyk, Joanna; Olas, Beata; Wachowicz, Barbara; Szajwaj, Barbara; Stochmal, Anna; Oleszek, Wieslaw

    2011-09-01

    Numerous plants (including clovers) have been widely used in folk medicine for the treatment of different disorders. This in vitro study was designed to examine the antioxidative effects of the clovamide-rich fraction, obtained from aerial parts of Trifolium pallidum, in the protection of blood platelets and plasma against the nitrative and oxidative damage, caused by peroxynitrite (ONOO(-)). Carbonyl groups and 3-nitrotyrosine in blood platelet and plasma proteins were determined by ELISA tests. Thiol groups level was estimated by using 5,5'-dithio-bis(2-nitro-benzoic acid, DTNB). Plasma lipid peroxidation was measured spectrophotometrically as the production of thiobarbituric acid reactive substances. The results from our work indicate that clovamide-rich T. pallidum extract may reveal the protective properties in the prevention against oxidative stress. The presence of clovamide-rich T. pallidum extract (12.5-100 μg/ml) partly inhibited ONOO(-)-mediated protein carbonylation and nitration. All the used concentrations of T. pallidum extract reduced lipid peroxidation in plasma. The antioxidative action of the tested extract in the protection of blood platelet lipids was less effective; the extract at the lowest final concentration (12.5 μg/ml) had no protective effect against lipid peroxidation. The present results indicate that the extract from T. pallidum is likely to be a source of compounds with the antioxidative properties, useful in the prevention against the oxidative stress-related diseases.

  12. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2013-01-01

    Full Text Available Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs coated with oleic acid (OA were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR spectroscopy, thermogravimetric analysis (TGA, transmission electron microscopy (TEM, and vibrating sample magnetometer (VSM. The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD and differential scanning calorimetry (DSC methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES. Bovine serum albumin (BSA was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug.

  13. The role of methionine in the intracellular accumulation and function of folates

    Energy Technology Data Exchange (ETDEWEB)

    Scott, J.M.; McKenna, B.; McGing, P.; Molloy, A.; Dinn, J.; Weir, D.G.

    1983-01-01

    It is suggested that mammalian cells have evolved to respond to methionine deficiency since in such circumstances vital methylation reactions are put at risk, due to decreased levels of S-adenosyl-methionine. Decreased cellular homocysteine, as a result of decreased methionine, would also restrict cell division by decreased conversion of plasma 5-CH3-H/sub 4/PteGlu into intracellular polyglutamates. Cobalamin deficiency, either nutritional or due to exposure to the Co(I)cobalamin inactivating agent nitrous oxide, prevents the demethylation of 5-CH3-H/sub 4/PteGlu, which even in the presence of adequate amounts of homocysteine and methionine prevents rapidly proliferating cells from converting enough of the plasma 5-CH3-H/sub 4/ PteGlu into folylpolyglutamate forms to permit normal DNA biosynthesis and cell replication. This, together with the trapping of the cellular folate cofactors in the 5-CH3-H/sub 4/PteGlu form, results in megaloblastic changes occurring in tissues such as the marrow. The vital role of the methylation reactions was demonstrated by exposing monkeys to nitrous oxide which inactivated their methionine synthetase. The resultant ataxia and severe demyelination was prevented and diminished by methionine supplementation. When methionine synthetase was similarly inactivated in mice it was shown that while 5-CH3-H/sub 4/PteGlu enters mammalian cells, it is not converted into a polyglutamyl form and subsequently leaves the cell unmetabolised. In similar experiments in rats methionine was found to have only a small effect in restoring folylpolyglutamate biosynthesis. It was found that a decrease in the deoxythymidine salvage pathway by methionine has led others to the mistaken conclusion that methionine has an 'anti-folate' effect in bone marrow, i.e. that it decreases folate availability for thymidylate synthetase.

  14. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schieferstein, Hanno

    2013-07-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new {sup 18}F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed {sup 18}F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable {sup 18}F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for {sup 18}F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2]{sup +}/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were

  15. Reduced entropic model for studies of multidimensional nonlocal transport in high-energy-density plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Del Sorbo, D.; Feugeas, J.-L.; Nicolaï, Ph.; Olazabal-Loumé, M.; Dubroca, B.; Guisset, S.; Touati, M.; Tikhonchuk, V. [Centre Lasers Intenses et Applications, Université de Bordeaux-CNRS-CEA, UMR 5107, F-33405 Talence (France)

    2015-08-15

    Hydrodynamic simulations of high-energy-density plasmas require a detailed description of energy fluxes. For low and intermediate atomic number materials, the leading mechanism is the electron transport, which may be a nonlocal phenomenon requiring a kinetic modeling. In this paper, we present and test the results of a nonlocal model based on the first angular moments of a simplified Fokker-Planck equation. This multidimensional model is closed thanks to an entropic relation (the Boltzman H-theorem). It provides a better description of the electron distribution function, thus enabling studies of small scale kinetic effects within the hydrodynamic framework. Examples of instabilities of electron plasma and ion-acoustic waves, driven by the heat flux, are presented and compared with the classical formula.

  16. Reduced entropic model for studies of multidimensional nonlocal transport in high-energy-density plasmas

    Science.gov (United States)

    Del Sorbo, D.; Feugeas, J.-L.; Nicolaï, Ph.; Olazabal-Loumé, M.; Dubroca, B.; Guisset, S.; Touati, M.; Tikhonchuk, V.

    2015-08-01

    Hydrodynamic simulations of high-energy-density plasmas require a detailed description of energy fluxes. For low and intermediate atomic number materials, the leading mechanism is the electron transport, which may be a nonlocal phenomenon requiring a kinetic modeling. In this paper, we present and test the results of a nonlocal model based on the first angular moments of a simplified Fokker-Planck equation. This multidimensional model is closed thanks to an entropic relation (the Boltzman H-theorem). It provides a better description of the electron distribution function, thus enabling studies of small scale kinetic effects within the hydrodynamic framework. Examples of instabilities of electron plasma and ion-acoustic waves, driven by the heat flux, are presented and compared with the classical formula.

  17. Hippophae rhamnoides L. Fruits Reduce the Oxidative Stress in Human Blood Platelets and Plasma.

    Science.gov (United States)

    Olas, Beata; Kontek, Bogdan; Malinowska, Paulina; Żuchowski, Jerzy; Stochmal, Anna

    2016-01-01

    Effects of the phenolic fraction from Hippophae rhamnoides fruits on the production of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and the generation of superoxide anion (O2 (-∙)) in human blood platelets (resting platelets and platelets stimulated by a strong physiological agonist, thrombin) were studied in vitro. We also examined antioxidant properties of this fraction against human plasma lipid peroxidation and protein carbonylation induced by a strong biological oxidant, hydrogen peroxide (H2O2) or H2O2/Fe (a donor of hydroxyl radicals). The tested fraction of H. rhamnoides (0.5- 50 µg/mL; the incubation time: 15 and 60 min) inhibited lipid peroxidation induced by H2O2 or H2O2/Fe. The H. rhamnoides phenolic fraction inhibited not only plasma lipid peroxidation, but also plasma protein carbonylation stimulated by H2O2 or H2O2/Fe. Moreover, the level of O2 (-∙) in platelets significantly decreased. In comparative experiments, the H. rhamnoides fraction was a more effective antioxidant than aronia extract or grape seed extract (at the highest tested concentration, 50 µg/mL). The obtained results suggest that H. rhamnoides fruits may be a new, promising source of natural compounds with antioxidant and antiplatelet activity beneficial not only for healthy people, but also for those with oxidative stress-associated diseases.

  18. Hippophae rhamnoides L. Fruits Reduce the Oxidative Stress in Human Blood Platelets and Plasma

    Directory of Open Access Journals (Sweden)

    Beata Olas

    2016-01-01

    Full Text Available Effects of the phenolic fraction from Hippophae rhamnoides fruits on the production of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation and the generation of superoxide anion (O2-∙ in human blood platelets (resting platelets and platelets stimulated by a strong physiological agonist, thrombin were studied in vitro. We also examined antioxidant properties of this fraction against human plasma lipid peroxidation and protein carbonylation induced by a strong biological oxidant, hydrogen peroxide (H2O2 or H2O2/Fe (a donor of hydroxyl radicals. The tested fraction of H. rhamnoides (0.5– 50 µg/mL; the incubation time: 15 and 60 min inhibited lipid peroxidation induced by H2O2 or H2O2/Fe. The H. rhamnoides phenolic fraction inhibited not only plasma lipid peroxidation, but also plasma protein carbonylation stimulated by H2O2 or H2O2/Fe. Moreover, the level of O2-∙ in platelets significantly decreased. In comparative experiments, the H. rhamnoides fraction was a more effective antioxidant than aronia extract or grape seed extract (at the highest tested concentration, 50 µg/mL. The obtained results suggest that H. rhamnoides fruits may be a new, promising source of natural compounds with antioxidant and antiplatelet activity beneficial not only for healthy people, but also for those with oxidative stress-associated diseases.

  19. ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

    Directory of Open Access Journals (Sweden)

    Kexiu Song

    2014-01-01

    Full Text Available HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

  20. A Candidate Gene Study of Folate-Associated One Carbon Metabolism Genes and Colorectal Cancer Risk

    Science.gov (United States)

    Levine, A. Joan; Figueiredo, Jane C.; Lee, Won; Conti, David V.; Kennedy, Kathleen; Duggan, David J; Poynter, Jenny N.; Campbell, Peter T.; Newcomb, Polly; Martinez, Maria Elena; Hopper, John L.; Le Marchand, Loic; Baron, John A.; Limburg, Paul J.; Ulrich, Cornelia M.; Haile, Robert W.

    2010-01-01

    Background Folate-associated one carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer. Methods This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry (C-CFR). We used a comprehensive tagSNP approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B12 metabolism. Genotyping was performed using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. MSI status was determined using standard techniques and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or co-dominant model. Results In the log additive model, two linked (r2=0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in CRC risk after correction for multiple testing (OR=0.87; 95% CI=0.71 – 0.94; P=0.029 and OR=0.87 95% CI=0.71 – 0.95, P=0.034 for rs1677693 and rs1643659 respectively. These two linked (r2=0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced CRC risk only among individuals not using multivitamin supplements. Conclusions Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect CRC risk except in non multivitamin users. Impact This study suggests that multivitamin supplement use may modify the association between folate pathway genes and CRC risk in a post folic acid supplemented population. PMID:20615890

  1. Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Deborah A. Kennedy

    2012-01-01

    Full Text Available Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (MTHFR polymorphisms and risk of colorectal cancer (CRC and examine whether the risk is modified by level of folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms “folic acid,” “folate,” “colorectal cancer,” “methylenetetrahydrofolate reductase,” “MTHFR.” Observational studies were included which (1 assessed the risk of CRC for each polymorphism and/or (2 had defined levels of folate intake for each polymorphism and assessed the risk of CRC. Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the 677CT versus CC genotype was 1.02 (95% CI 0.95–1.10 and for 677TT versus CC was 0.88 (95% CI 0.80–0.96 both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56–0.89 and the 677TT genotype 0.63 (95% CI 0.41–0.97. Conclusion. These results suggest that the 677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for both MTHFR 677 CC and TT genotypes.

  2. Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders.

    Science.gov (United States)

    Schaevitz, Laura R; Picker, Jonathan D; Rana, Jasmine; Kolodny, Nancy H; Shane, Barry; Berger-Sweeney, Joanne E; Coyle, Joseph T

    2012-06-01

    Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidase II (GCPII) and dietary folic acid deficiency. In addition to serving as a neuropeptidase, GCPII catalyzes the absorption of folate. GCPII and folate depletion interact within the one-carbon metabolic pathway and/or of modulate the glutamatergic system. Four groups of mice were tested: wild-type, GCPII hypomorphs, and wild-types and GCPII hypomorphs both fed a folate deficient diet. Due to sex differences in the prevalence of SZ and AD, both male and female mice were assessed on a number of behavioral tasks including locomotor activity, rotorod, social interaction, prepulse inhibition, and spatial memory. Wild-type mice of both sexes fed a folic acid deficient diet showed motor coordination impairments and cognitive deficits, while social interactions were decreased only in males. GCPII mutant mice of both sexes also exhibited reduced social propensities. In contrast, all folate-depleted GCPII hypomorphs performed similarly to untreated wild-type mice, suggesting that reduced GCPII expression and folate deficiency are mutually protective. Analyses of folate and neurometabolite levels associated with glutamatergic function suggest several potential mechanisms through which GCPII and folate may be interacting to create this protective effect.

  3. Dietary folate and APC mutations in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Engeland, M. van; Lüchtenborg, M.; Bruïne, A.P. de; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Goldbohm, R.A.; Brandt, P.A. van den; Goeij, A.F.P.M. de; Weijenberg, M.P.

    2006-01-01

    Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between

  4. Compliance with the consumption of iron and folate supplements by ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... supplements to all pregnant women to prevent anaemia as recommended by World ... women with folate and iron supplements and nutrition education. ... formulated as follows: (i) To determine the ..... Trends in antenatal care ...

  5. Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects%神经管畸形患儿还原叶酸载体基因和叶酸之间交互作用

    Institute of Scientific and Technical Information of China (English)

    裴丽君; 朱慧萍; 李智文; 张卫; 任爱国; 朱江辉; 李竹

    2005-01-01

    Objective To search the interaction between reduced folate carrier gene ( RFC1 A80G) polymorphism of children with neural tube defects (NTDs) and maternal periconceptional no supplementation of folic acid. The purpose is to provide the epidemiological evidence for finding genetic marker of NTDs. Methods RFC1 (A80G) genotype was detected using PCR-restricted fragment length polymorphism for the blood DNA of 104 trios with NTDs-affected child, and 100 control families with non-malformed control children. The authors investigated the gene-environment interactions between the offspring RFC1 genotype and maternal periconceptional folic acid supplementation through a case-control study. Results It was observed that the offspring with the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to those with the AA genotype (OR=2.56;95%CI=1.04-6.36) in this population under investigation. The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95%CI=2.86-21.75). Among the mothers who did not utilize folic acid supplements, the NTDs risk was 3.30 (95%CI=1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR=8.80, 95%CI=2.86-29.82), compared to "offspring with AA or GA genotype" and "maternal folic acid use", the interactive coefficient being 1.45. Conclusion The above findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in Chinese population, and there is a potential gene-nutrient interaction between offspring RFC1 GG genotype and maternal periconceptional intake of folic acid on the risk of NTDs. However,the sample size of this study was limited, a larger sample of population-based study is required to pursue the initial observation.%目的探讨神经管畸形(neural tube defects, NTDs)患儿还原叶酸载体基因(reduced

  6. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

    Science.gov (United States)

    Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

    2013-05-24

    Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

  7. Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice.

    Science.gov (United States)

    Bijland, Silvia; Pieterman, Elsbet J; Maas, Annemarie C E; van der Hoorn, José W A; van Erk, Marjan J; van Klinken, Jan B; Havekes, Louis M; van Dijk, Ko Willems; Princen, Hans M G; Rensen, Patrick C N

    2010-08-13

    The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (-38%) and TG (-60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles (-68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [(3)H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver.

  8. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration

    Science.gov (United States)

    Knuth, Nicolas D.; Shrivastava, Cara R.; Horowitz, Jeffrey F.

    2009-01-01

    The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. On three separate occasions, nine overweight subjects (body mass index = 30 ± 1 kg/m2; 5 men, 4 women) consumed 1) a control meal (∼800 kcal; 100 g of carbohydrate, 31 g of fat, and 30 g of protein), 2) a low-fat meal (∼530 kcal; 100 g of carbohydrate, 1 g of fat, and 30 g of protein), or 3) a low-fat meal plus lipid infusion [same meal as low-fat meal, but the total energy provided was the same as control (800 kcal), with the “missing” fat (∼30 g) provided via an intravenous lipid infusion]. All three meals contained [13C]glucose (3 mg/kg body wt) to assess the bioavailability of ingested glucose. During the 5-h period after each meal, we measured the recovery of [13C]glucose in plasma, plasma glucose, and insulin concentrations. We also measured plasma concentration of the gastrointestinal peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY3-36 (PYY3-36). The recovery of the ingested [13C]glucose in the hour after ingestion was greater (P < 0.05) after the low-fat than after the control meal [area under the curve (AUC): 1,206 ± 252 and 687 ± 161 μM·h, respectively]. However, removing dietary fat from the meal did not affect the plasma concentration of glucose or insulin. Importantly, [13C]glucose recovery was not different during the low-fat and lipid infusion trials (AUC: 1,206 ± 252 and 1,134 ± 247 μM·h, respectively), indicating that the accelerated delivery of exogenous glucose found after removing fat from the meal is due exclusively to the reduction of fat in the gastrointestinal tract. In parallel with these findings, the reduction in fat calories from the meal reduced plasma concentration of GIP, GLP-1, and PYY3-36. In summary, these data suggest that removing fat from the diet expedited exogenous glucose delivery into the systemic circulation

  9. Leptin reduces plasma ANP level via nitric oxide-dependent mechanism.

    Science.gov (United States)

    Yuan, Kuichang; Yu, Jiahua; Shah, Amin; Gao, Shan; Kim, Sun Young; Kim, Sung Zoo; Park, Byung-Hyun; Kim, Suhn Hee

    2010-04-01

    Leptin is a circulating adipocyte-derived hormone that influences blood pressure (BP) and metabolism. This study was designed to define the possible role of leptin in regulation of the atrial natriuretic peptide (ANP) system using acute and chronic experiments. Intravenous infusion of rat leptin (250 microg/kg injection plus 2 microg.kg(-1).min(-1) for 20 min) into Sprague-Dawley rats increased BP by 25 mmHg and decreased plasma level of ANP from 80.3 +/- 3.45 to 51.8 +/- 3.3 pg/ml. Reserpinization attenuated the rise in BP, but not the reduction of plasma ANP during leptin infusion. N(omega)-nitro-l-arginine methyl ester prevented the effects of leptin on the reduction of ANP level. In hyperleptinemic rats that received adenovirus containing rat leptin cDNA (AdCMV-leptin), BP increased during first 2 days and then recovered to control value. Plasma concentration of ANP and expression of ANP mRNA, but not of atrial ANP, in hyperleptinemic rats were lower than in the control groups on the first and second week after administration of AdCMV-leptin. These effects were not observed by the pretreatment with N(omega)-nitro-l-arginine methyl ester. No differences in renal function and ANP receptor density in the kidney were found between hyperleptinemic and control rats. Basal ANP secretion and isoproterenol-induced suppression of ANP secretion from isolated, perfused atria of hyperleptinemic rats were not different from those of other control groups. These data suggest that leptin inhibits ANP secretion indirectly through nitric oxide without changing basal or isoproterenol-induced ANP secretion.

  10. New Roles of Folate Receptor Alpha in Oncogenic Cell Signalling

    DEFF Research Database (Denmark)

    Hansen, Mariann Fagernæs

    I løbet af sine ph.d.-studier har Mariann Fagernæs Hansen undersøgt proteinet Folat Receptoren, der naturligt kan binde folinsyre. Folat Receptoren har betydning for cellevækst og er til stede på overfladen af mange kræftceller. I mange lande tilsættes folinsyre aktivt i f.eks. mel- og morgenmads...

  11. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Madsen, Lise; Hao, Qin

    2009-01-01

    Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins...... varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA...

  12. Deposition of LDH on plasma treated polylactic acid to reduce water permeability

    KAUST Repository

    Bugatti, Valeria

    2013-04-01

    A simple and scalable deposition process was developed to prepare polylactic acid (PLA) coatings with enhanced water barrier properties for food packaging applications. This method based on electrostatic interactions between the positively charged layers of layered double hydroxides (LDHs) modified with ionic liquids (ILs) and the negatively charged plasma treated polylactic acid leads to homogeneous, stable, and highly durable coatings. Deposition of the LDH coatings increases the surface hydrophobicity of the neat PLA, which results to a decrease in water permeability by about 35%. © 2013 Elsevier Inc.

  13. Antioxidative effect of folate-modified chitosan nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Subhankari; Prasad; Chakraborty; Santanu; Kar; Mahapatra; Sumanta; Kumar; Sahu; Panchanan; Pramanik; Somenath; Roy

    2011-01-01

    Objective:To evaluate the potency of carboxymethyl chitosan-2,2’ ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) on tissue injury,antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice.Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2,2’ ethylenedioxy bis-ethylamine.Animals were divided into four groups,i.e.,control,nicotine(1 mg/kg bw/day),CMC-EDBE-FA(1 mg/kg bw/day) and nicotine(1 mg/kg bw/day) and CMC-EDBE-FA(1 mg/kg bw/day) for 7 days.Levels of lipid peroxidation, oxidized glutathione level,antioxidant enzyme status and DNA damage were observed and compared.Results:The significantly increase of lipid peroxidation,oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group;those were significantly reduced in CMC-EDBE-FA supplemented group.Moreover,significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA.Only CMC-EDBE-FA treated groups showed no significant change as compared with control group;rather than it repairs the tissue damage of nicotine treated group.Conclusions:These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.

  14. Antioxidative effect of folate-modified chitosan nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Subhankari Prasad Chakraborty; Santanu Kar Mahapatra; Sumanta Kumar Sahu; Panchanan Pramanik; Somenath Roy

    2011-01-01

    Objective: To evaluate the potency of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) on tissue injury, antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice. Methods:CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. Animals were divided into four groups, i.e., control, nicotine (1 mg/kg bw/day), CMC-EDBE-FA (1 mg/kg bw/day) and nicotine (1 mg/kg bw/day) and CMC-EDBE-FA (1 mg/kg bw/day) for 7 days. Levels of lipid peroxidation, oxidized glutathione level, antioxidant enzyme status and DNA damage were observed and compared. Results: The significantly increase of lipid peroxidation, oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group; those were significantly reduced in CMC-EDBE-FA supplemented group. Moreover, significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA. Only CMC-EDBE-FA treated groups showed no significant change as compared with control group; rather than it repairs the tissue damage of nicotine treated group. Conclusions: These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.

  15. Plasma homocysteine levels in female patients with eating disorders.

    NARCIS (Netherlands)

    Levine, J.; Gur, E.; Loewenthal, R.; Vishne, T.; Dwolatzky, T.; Beijnum, I.M. van; Sela, B.A.; Vered, I.; Yosef, G.; Stein, D.

    2007-01-01

    OBJECTIVE: To examine plasma homocysteine, vitamin B(12), and folate levels in females with restricting and bingeing/purging eating disorders (EDs). METHOD: Adolescent and adult female patients were compared to appropriate control groups with regard to plasma homocysteine levels. RESULTS: The plasma

  16. [Folates and fetal programming: role of epigenetics and epigenomics].

    Science.gov (United States)

    Guéant, Jean-Louis; Daval, Jean-Luc; Vert, Paul; Nicolas, Jean-Pierre

    2012-12-01

    Folates are needed for synthesis of methionine, the precursor of S-adenosyl methionine (SAM). They play therefore a key role in nutrition and epigenomics by fluxing monocarbons towards synthesis or methylation of DNA and RNA, and methylation of gene transregulators, respectively. The deficiency produces intrauterine growth retardation and birth dejects. Folate deficiency deregulates epigenomic mechanisms related to fetal programming through decreased cellular availability of SAM. Epigenetic mechanisms of folate deficiency are illustrated by inheritance of coat colour of agouti mice model and altered expression of Igf2/H19 imprinting genes. Dietary exposure to fumonisin FB1 acts synergistically with folate deficiency on alterations of heterochromatin assembly. Deficiency in folate and vitamin B12 produces impaired fatty acid oxidation in liver and heart through imbalanced methylation and acetylation of PGC1-alpha and decreased expression of SIRT1, and long-lasting cognitive disabilities through impaired hippocampal cell proliferation, differentiation and plasticity and atrophy of hippocampal CA1. Deciphering these mechanisms will help understand the discordances between experimental models and population studies on folate supplementation.

  17. Present and future of folate biofortification of crop plants.

    Science.gov (United States)

    Blancquaert, Dieter; De Steur, Hans; Gellynck, Xavier; Van Der Straeten, Dominique

    2014-03-01

    Improving nutritional health is one of the major socio-economic challenges of the 21st century, especially with the continuously growing and ageing world population. Folate deficiency is an important and underestimated problem of micronutrient malnutrition affecting billions of people worldwide. More and more countries are adapting policies to fight folate deficiency, mostly by fortifying foods with folic acid. However, there is growing concern about this practice, calling for alternative or complementary strategies. In addition, fortification programmes are often inaccessible to remote and poor populations where folate deficiency is most prevalent. Enhancing folate content in staple crops by metabolic engineering is a promising, cost-effective strategy to eradicate folate malnutrition worldwide. Over the last decade, major progress has been made in this field. Nevertheless, engineering strategies have thus far been implemented on a handful of plant species only and need to be transferred to highly consumed staple crops to maximally reach target populations. Moreover, successful engineering strategies appear to be species-dependent, hence the need to adapt them in order to biofortify different staple crops with folate.

  18. Intake of Mung Bean Protein Isolate Reduces Plasma Triglyceride Level in Rats

    Directory of Open Access Journals (Sweden)

    Nobuhiko Tachibana

    2013-09-01

    Full Text Available ABSTRACTBackground: Mung bean is well known as a starch source, but the physiological effects of mung bean protein have received little attention. In this study, we isolated mung bean protein from de-starched mung bean solutions, and investigated its influence on lipid metabolism. Objective: The aim of this study is to clarify the influence of the lipid metabolism by consumption of mung bean protein isolate (MPIMethods: Diets containing either mung bean protein isolate (MPI or casein were fed to normal rats for 28 days.Results: Both groups ate the same amount of food, but the plasma triglyceride level, relative liver weight and liver lipid contents (cholesterol and triglyceride pool in the MPI group were significantly lower than in the casein group. In the MPI group, the expression of sterol regulatory-element binding factor 1 (SREBF1 mRNA in the liver was significantly different when compared with the casein group. The significantly lower levels of insulin and free fatty acids in the MPI-fed rats may be due to the regulation of genes related to lipid metabolism in the liver.Conclusions: These results suggest that MPI may improve the plasma lipid profile by normalizing insulin sensitivity.Keywords: mung bean, Vigna radiata L., 8S globulin, triglyceride, β-conglycinin, 7S globulin, insulin sensitivity, SREBF1

  19. Development of reduced fat minced meats using inulin and bovine plasma proteins as fat replacers.

    Science.gov (United States)

    Rodriguez Furlán, Laura T; Padilla, Antonio Pérez; Campderrós, Mercedes E

    2014-02-01

    This work deals with the effect of the addition of inulin and bovine plasma proteins as fat replacers, on the quality of minced meat. The proteins are obtained by ultrafiltration and freeze-drying. The following determinations were carried out: chemical composition, sensorial analysis (color, flavor, taste and consistency), emulsion stability and instrumental texture analysis of samples. The resulting formulations were compared with full-fat minced meat, as control. The results showed an increase of protein contents after fat replacement, while a fat reduction of 20-35% produced light products enriched with proteins and inulin as the functional ingredient. No change was observed in color, flavor, or taste among the samples. However, the sensory analysis showed that the combination of plasma protein (2.5%w/w) and inulin (2%w/w) had the best acceptability with respect to consistency, and had a lower fat drain from the emulsion. Texture profile analysis revealed that this formulation assimilated the control texture properties, being that this result is required for adequate consumer acceptance.

  20. Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

    National Research Council Canada - National Science Library

    Castaño, Erika; Caviedes, Lorena; Hirsch, Sandra; Llanos, Miguel; Iñiguez, Germán; Ronco, Ana María

    2017-01-01

    ... (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns...

  1. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

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    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  2. Development of new folate-based PET radiotracers: preclinical evaluation of {sup 68}Ga-DOTA-folate conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); University Hospital Freiburg, Clinic for Nuclear Medicine, Freiburg (Germany); Wang, Xuejuan [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Nicolas, Guillaume [University Hospital Basel, Department of Nuclear Medicine, Basel (Switzerland); Medina, Christelle; Raynal, Isabelle; Port, Marc [Guerbet, Research Department, Aulnay-sous-Bois (France)

    2011-01-15

    A number of {sup 111}In- and {sup 99m}Tc-folate-based tracers have been evaluated as diagnostic agents for imaging folate receptor (FR)-positive tumours. A {sup 68}Ga-folate-based radiopharmaceutical would be of great interest, combining the advantages of PET technology and the availability of {sup 68}Ga from a generator. The aim of the study was to develop a new {sup 68}Ga-folate-based PET radiotracer. Two new DOTA-folate conjugates, named P3026 and P1254, were synthesized using the 1,2-diaminoethane and 3-{l_brace}2-[2-(3-amino-propoxy)-ethoxy]-ethoxy{r_brace}-propylamine as a spacer, respectively. Both conjugates were labelled with {sup 67/68}Ga. Binding affinity, internalization and externalization studies were performed using the FR-positive KB cell line. Biodistribution and PET/CT imaging studies were performed in nude mice, on a folate-deficient diet, bearing KB and HT1080 (FR-negative) tumours, concurrently. The new radiotracers were evaluated comparatively to the reference molecule {sup 111}In-DTPA-folate ({sup 111}In-P3139). The K{sub d} values of {sup 67/68}Ga-P3026 (4.65 {+-} 0.82 nM) and {sup 67/68}Ga-P1254 (4.27 {+-} 0.42 nM) showed high affinity for the FR. The internalization rate followed the order {sup 67/68}Ga-P3026 >{sup 67/68}Ga-P1254 >{sup 111}In-P3139, while almost double cellular retention was found for {sup 67/68}Ga-P3026 and {sup 67/68}Ga-P1254, compared to {sup 111}In-P3139. The biodistribution data of {sup 67/68}Ga-DOTA-folates showed high and receptor-mediated uptake on the FR-positive tumours and kidneys, with no significant differences compared to {sup 111}In-P3139. PET/CT images, performed with {sup 68}Ga-P3026, showed high uptake in the kidneys and clear visualization of the FR-positive tumours. The DOTA-folate conjugates can be efficiently labelled with {sup 68}Ga in labelling yields and specific activities which allow clinical application. The characteristics of the {sup 67/68}Ga-DOTA-folates are comparable to {sup 111}In-DTPA-folate

  3. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

    Directory of Open Access Journals (Sweden)

    Xie M

    2013-07-01

    Full Text Available M Xie, H Zhang, Y Xu, T Liu, S Chen, J Wang, T ZhangDepartment of Otorhinolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of ChinaAbstract: Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36 of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24. Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.Keywords: nasopharyngeal carcinoma, laryngeal carcinoma, folate receptor, molecular targeting, cisplatin, nanomedicine

  4. An unusual role of folate in the self-assembly of heparin-folate conjugates into nanoparticles

    Science.gov (United States)

    Wang, Jianquan; Ma, Daoshuang; Lu, Qian; Wu, Shaoxiong; Lee, Gee Young; Lane, Lucas A.; Li, Bin; Quan, Li; Wang, Yiqing; Nie, Shuming

    2015-09-01

    Tumor targeting agents including antibodies, peptides, and small molecules, are often used to improve the delivery efficiency of nanoparticles. Despite numerous studies investigating the abilities of targeting agents to increase the accumulation of nanosized therapeutics within diseased tissues, little attention has been focused on how these ligands can affect the self-assembly of the nanoparticle's modified polymer constituents upon chemical conjugation. Here we present an actively tumor targeted nanoparticle constructed via the self-assembly of a folate modified heparin. Folate conjugation unexpectedly allowed the self-assembly of heparin, where a majority of the folate molecules (>80%) resided inside the core of the nanoparticle. The folate-heparin nanoparticles could also physically encapsulate lipophilic fluorescent dyes, enabling the use of the constructs as activatable fluorescent probes for targeted in vivo tumor imaging.Tumor targeting agents including antibodies, peptides, and small molecules, are often used to improve the delivery efficiency of nanoparticles. Despite numerous studies investigating the abilities of targeting agents to increase the accumulation of nanosized therapeutics within diseased tissues, little attention has been focused on how these ligands can affect the self-assembly of the nanoparticle's modified polymer constituents upon chemical conjugation. Here we present an actively tumor targeted nanoparticle constructed via the self-assembly of a folate modified heparin. Folate conjugation unexpectedly allowed the self-assembly of heparin, where a majority of the folate molecules (>80%) resided inside the core of the nanoparticle. The folate-heparin nanoparticles could also physically encapsulate lipophilic fluorescent dyes, enabling the use of the constructs as activatable fluorescent probes for targeted in vivo tumor imaging. Electronic supplementary information (ESI) available: NMR spectra and fluorescent images of HF-488 with cancer

  5. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  6. Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?

    NARCIS (Netherlands)

    van Rooij, IALM; Vermeij-Keers, C; Kluijtmans, LAJ; Ocke, MC; Zielhuis, GA; Goorhuis-Brouwer, SM; van der Biezen, JJ; Kuijpers-Jagtman, AM; Steegers-Theunissen, RPM

    2003-01-01

    Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effec

  7. The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor$

    Institute of Scientific and Technical Information of China (English)

    Pei Zhang a; Yu-Qiang Gou b; Xia Gao a; Rui-Bin Bai a; Wen-Xia Chen a; Bo-Lu Sun a; Fang-Di Hu a; n; Wang-Hong Zhao c

    2016-01-01

    An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α), electron transfer number (n) and electrode reaction standard rate constant (ks) were 0.53, 2 and 3.4 s?1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70 ? 10 ? 7 ? 1.25 ? 10 ? 5 M with the detection limit (s/n ¼ 3) of 1.84 ? 10 ? 8 M. The assay was success-fully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2), area under curve (AUC), and plasma clearance (CL) were calculated to be 3.345 7 0.647 min, 5750 7 656.0 mg min/mL, and 5.891 7 0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10μL and had no complicated sample pretreatment (without deproteinization), which was simple, eco-friendly, and time-and cost-efficient for rutin pharmacokinetic studies.

  8. A water-soluble extract of chicken reduced plasma triacylglycerols, but showed no anti-atherosclerotic activity in apoE−/− mice

    Directory of Open Access Journals (Sweden)

    Rita Vik

    2015-08-01

    Conclusion: Chicken protein displayed a slight potential to increase mitochondrial fatty acid oxidation and reduce plasma TAG. However, CP did not affect plasma cholesterol levels, inflammation status or atherosclerotic development in apoE−/− mice. Based on these results, dietary intervention with CP does not have sufficient capacity to influence atherosclerotic development in apoE−/− mice.

  9. Oil pollution increases plasma antioxidants but reduces coloration in a seabird.

    Science.gov (United States)

    Pérez, Cristóbal; Lores, Marta; Velando, Alberto

    2010-08-01

    It has been suggested that condition-dependent signals may be a useful measure of environmental quality. In this study, we tested the hypothesis that oil pollution enhances oxidative stress and impairs expression of a carotenoid-based signal in a wild population of the yellow-legged gull (Larus michahellis). During the courtship period, a group of gulls were fed a supplementary diet containing heavy fuel oil from the Prestige oil spill and were compared with control gulls fed a similar supplementary diet without fuel oil. Blood levels of polycyclic aromatic hydrocarbons, the most toxic components of crude oils, were higher (30%) in the Prestige oil-fed gulls than in the control gulls. Plasma concentrations of vitamin E and carotenoids were also significantly higher in the Prestige oil-fed gulls (31 and 27%, respectively). Although, the plasma levels of lipid peroxidation markers were higher (13%) in gulls fed with Prestige oil than in the control gulls, these differences were not significant, possibly because of the small number of gulls analyzed. The red bill spot was significantly smaller (16%) in the oil-fed gulls than in the control individuals. This study provides the first experimental evidence that a carotenoid-based signal in a free-living seabird is affected by exposure to oil pollution and is hence indicative of environmental quality. Since the yellow-legged gull belongs to a complex of species widely distributed throughout the northern hemisphere, the method described may constitute a useful tool for evaluating sub-lethal effects of oil spills in seabirds.

  10. Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle.

    Science.gov (United States)

    Watt, Matthew J; Holmes, Anna G; Steinberg, Gregory R; Mesa, Jose L; Kemp, Bruce E; Febbraio, Mark A

    2004-07-01

    Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O(2) uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased (P HSL) activity (CON: 13.9 +/- 2.5, NA: 9.1 +/- 3.0 nmol.min(-1).mg protein(-1)). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 +/- 0.8; NA, 6.3 +/- 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 +/- 0.07; 180 min: 0.17 +/- 0.04 nmol.min(-1).mg protein(-1)). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)alpha1 activity was not affected by exercise or NA, whereas AMPKalpha2 activity was increased (P < 0.05) from rest during exercise in NA and was greater (P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.

  11. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy

    NARCIS (Netherlands)

    Velzing-Aarts, Francien V; Holm, Pål I; Fokkema, M Rebecca; van der Dijs, Fey P; Ueland, Per M; Muskiet, Frits A

    2005-01-01

    Background: Plasma concentrations of total homocysteine (tHcy) decrease during pregnancy. This reduction has been investigated in relation to folate status, but no study has addressed the possible role of betaine and its precursor choline. Objective: We investigated the courses of plasma choline and

  12. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    John S. Parks

    2013-07-01

    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  13. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    Science.gov (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  14. Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel 18F-Folate Radiotracer

    Directory of Open Access Journals (Sweden)

    Adrienne Müller

    2014-03-01

    Full Text Available Folate receptor β (FR-β is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cellular debris to define the likelihood of plaque inflammation and eventually rupture. In this study, we determined the presence of FR-β-expressing macrophages in atherosclerotic lesions by the use of a fluorine-18-labeled folate-based radiotracer. Human endarterectomized specimens were used to measure gene expression levels of FR-β and CD68. Increased FR-β and CD68 levels were found in atherosclerotic plaques compared to normal artery walls by quantitative real-time polymerase chain reaction. Western blotting and immunohistochemistry demonstrated prominent FR-β protein levels in plaques. FR- β-positive cells colocalized with activated macrophages (CD68 in plaque tissue. Carotid sections incubated with 3′-aza-2′- [18F]fluorofolic acid displayed increased accumulation in atherosclerotic plaques through in vitro autoradiography. Specific binding of the radiotracer correlated with FR-β-expressing macrophages. These results demonstrate high FR-β expression in atherosclerotic lesions of human carotid tissue correlating with CD68-positive macrophages. Areas of high 3′-aza-2′-[18F]fluorofolic acid binding within the lesions represented FR-β-expressing macrophages. Selectively targeting FR-β-positive macrophages through folate-based radiopharmaceuticals may be useful for noninvasive imaging of plaque inflammation.

  15. Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris.

    Science.gov (United States)

    Gavin, James P; Myers, Stephen D; Willems, Mark E T

    2016-07-01

    Eccentric exercise can result in muscle damage and interleukin-6 (IL-6) secretion. Glycogen availability is a potent stimulator of IL-6 secretion. We examined effects of eccentric exercise in a low-glycogen state on neuromuscular function and plasma IL-6 secretion. Twelve active men (23 ± 4 yr, 179 ± 5 cm, 77 ± 10 kg, means ± SD) completed two downhill treadmill runs (gradient, -12%, 5 × 8 min; speed, 12.1 ± 1.1 km/h) with normal (NG) and reduced muscle glycogen (RG) in randomized order and at least 6 wk apart. Muscle glycogen was reduced using an established cycling protocol until exhaustion and dietary manipulation the evening before the morning run. Physiological responses were measured up to 48 h after the downhill runs. During recovery, force deficits of musculus quadriceps femoris by maximal isometric contractions were similar. Changes in low-frequency fatigue were larger with RG. Voluntary activation and plasma IL-6 levels were similar in recovery between conditions. It is concluded that unaccustomed, damaging eccentric exercise with low muscle glycogen of the m. quadriceps femoris 1) exacerbated low-frequency fatigue but 2) had no additional effect on IL-6 secretion. Neuromuscular impairment after eccentric exercise with low muscle glycogen appears to have a greater peripheral component in early recovery.

  16. Prospects in folate receptor-targeted radionuclide therapy

    Directory of Open Access Journals (Sweden)

    Cristina eMüller

    2013-09-01

    Full Text Available Targeted radionuclide therapy is based on systemic application of particle-emitting radiopharmaceuticals which are directed towards a specific tumor-associated target. Accumulation of the radiopharmaceutical in targeted cancer cells results in high doses of absorbed radiation energy whereas toxicity to non-targeted healthy tissue is limited. This strategy has found widespread application in the palliative treatment of neuroendocrine tumors using somatostatin-based radiopeptides. The folate receptor (FR has been identified as a target associated with a variety of frequent tumor types (e.g. ovarian, lung, brain, renal and colorectal cancer. In healthy organs and tissue FR-expression is restricted to only a few sites such as for instance the kidneys. This demonstrates why FR-targeting is an attractive strategy for the development of new therapy concepts. Due to its high FR-binding affinity (KD < 10-9 M the vitamin folic acid has emerged as an almost ideal targeting agent. Therefore, a variety of folic acid radioconjugates for nuclear imaging have been developed. However, in spite of the large number of cancer patients who could benefit of a folate-based radionuclide therapy, a therapeutic concept with folate radioconjugates has not yet been envisaged for clinical application. The reason is the generally high accumulation of folate radioconjugates in the kidneys where emission of particle-radiation may result in damage to the renal tissue. Therefore, the design of more sophisticated folate radioconjugates providing improved tissue distribution profiles are needed.This review article summarizes recent developments with regard to a therapeutic application of folate radioconjugates. A new construct of a folate radioconjugate and an application protocol which makes use of a pharmacological interaction allowed the first preclinical therapy experiments with radiofolates. These results raise hope for future application of such new concepts also in the

  17. Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

    Science.gov (United States)

    Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

    2016-09-01

    The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

  18. Multiscale Gyrokinetics for Rotating Tokamak Plasmas II: Reduced Models for Electron Dynamics

    CERN Document Server

    Abel, I G

    2012-01-01

    In this paper, we extend the multiscale approch developed in [Abel et. al., Rep. Prog. Phys., in press] by exploiting the scale separation between ions and the electrons. The gyrokinetic equation is expanded in powers of the electron to ion mass ratio, which provides a rigorous method for deriving the reduced electron model. We prove that ion-scale electromagnetic turbulence cannot change the magnetic topology, and argue that to lowest order the magnetic field lies on fluctuating flux surfaces. These flux surfaces are used to construct magnetic coordinates, and in these coordinates a closed system of equations for the electron response to ion-scale turbulence is derived. All fast electron timescales have been eliminated from these equations. We also use these magnetic surfaces to construct transport equations for electrons and for electron heat in terms of the reduced electron model.

  19. Prebiotics, Prosynbiotics and Synbiotics: Can They Reduce Plasma Oxidative Stress Parameters? A Systematic Review.

    Science.gov (United States)

    Salehi-Abargouei, Amin; Ghiasvand, Reza; Hariri, Mitra

    2017-01-03

    This study assessed the effectiveness of presybiotics, prosybiotics and synbiotics on reducing serum oxidative stress parameters. PubMed/Medline, Ovid, Google Scholar, ISI Web of Science and SCOPUS were searched up to September 2016. English language randomized clinical trials reporting the effect of presybiotics, prosybiotics or synbiotic interventions on serum oxidative stress parameters in human adults were included. Twenty-one randomized clinical trials met the inclusion criteria for systematic review. Two studies investigated prebiotics, four studies synbiotics and fifteen studies probiotics. According to our systematic review, prebiotic could decrease malondialdehyde and increase superoxidative dismutase, but evidence is not enough. In comparison with fructo-oligosaccharide, inulin is much more useful for oxidative stress reduction. Using probiotics with dairy products could reduce oxidative stress significantly, but probiotic in form of supplementation did not have any effect on oxidative stress. There is limited but supportive evidence that presybiotics, prosybiotics and synbiotics are effective for reducing oxidative stress parameters. Further randomized clinical trials with longer duration of intervention especially on population with increased oxidative stress are needed to provide more definitive results before any recommendation for clinical use of these interventions.

  20. Biocompatibility of folate-modified chitosan nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Subhankari Prasad Chakraborty; Sumanta Kumar Sahu; Panchanan Pramanik; Somenath Roy

    2012-01-01

    Objective: To evaluate the acute toxicity of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity. Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. In vivo acute toxicity, in vitro cyto-toxicity and antimicrobial activity of CMC-EDBE-FA nanoparticle were determined. Results: Vancomycin exhibited the antibacterial activity against vancomycin sensitive Staphylococcus aureus, but CMC-EDBE-FA nanoparticle did not give any antibacterial activity as evidenced by minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), disc agar diffusion (DAD) and killing kinetic assay. Further, the CMC-EDBE-FA nanoparticle showed no signs of in vivo acute toxicity up to a dose level of 1000 mg/kg p.o., and as well as in vitro cyto-toxicity up to 250 μg/mL. Conclusions: These findings suggest that CMC-EDBE-FA nanoparticle is expected to be safe for biomedical applications.

  1. Leukocyte-Reduced Platelet-Rich Plasma Treatment of Basal Thumb Arthritis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Markus Loibl

    2016-01-01

    Full Text Available A positive effect of intra-articular platelet-rich plasma (PRP injection has been discussed for osteoarthritic joint conditions in the last years. The purpose of this study was to evaluate PRP injection into the trapeziometacarpal (TMC joint. We report about ten patients with TMC joint osteoarthritis (OA that were treated with 2 intra-articular PRP injections 4 weeks apart. PRP was produced using the Double Syringe System (Arthrex Inc., Naples, Florida, USA. A total volume of 1.47±0.25 mL PRP was injected at the first injection and 1.5±0.41 mL at the second injection, depending on the volume capacity of the joint. Patients were evaluated using VAS, strength measures, and the Mayo Wrist score and DASH score after 3 and 6 months. VAS significantly decreased from 6.2±1.6 to 5.4±2.2 at six-month follow-up (P<0.05. The DASH score was unaffected; however, the Mayo Wrist score significantly improved from 46.5±18.6 to 67.5±19.0 at six-month follow-up (P=0.05. Grip was unaffected, whereas pinch declined from 6.02±2.99 to 3.96±1.77 at six-month follow-up (P<0.05. We did not observe adverse events after the injection of PRP, except one occurrence of a palmar wrist ganglion, which resolved without treatment. PRP injection for symptomatic TMC OA is a reasonable therapeutic option in early stages TMC OA and can be performed with little to no morbidity.

  2. Controlled release of folic acid through liquid-crystalline folate nanoparticles.

    Science.gov (United States)

    Misra, Rahul; Katyal, Henna; Mohanty, Sanat

    2014-11-01

    The present study explores folate nanoparticles as nano-carriers for controlled drug delivery. Cross-linked nanoparticles of liquid crystalline folates are composed of ordered stacks. This paper shows that the folate nanoparticles can be made with less than 5% loss in folate ions. In addition, this study shows that folate nanoparticles can disintegrate in a controlled fashion resulting in controlled release of the folate ions. Release can be controlled by the size of nanoparticles, the extent of cross-linking and the choice of cross-linking cation. The effect of different factors like agitation, pH, and temperature on folate release was also studied. Studies were also carried out to show the effect of release medium and role of ions in the release medium on disruption of folate assembly.

  3. Enhancing the natural folate level in wine using bioengineering and stabilization strategies.

    Science.gov (United States)

    Liu, Yazheng; Walkey, Christopher J; Green, Timothy J; van Vuuren, Hennie J J; Kitts, David D

    2016-03-01

    Folate deficiency is linked to many diseases, some of which may have higher probability in individuals with alcohol-induced alterations in one-carbon metabolism. Our study shows that folate content in commercial wine is not related to white or red varieties, but associated with the yeast that is used to produce the wine. The stability of folate in these wines, once opened for consumption, did not correlate with total phenolic or sulfite content. In addition, we employed yeast bioengineering to fortify wine with folate. We confirmed by overexpression that FOL2 was the key gene encoding the rate-limiting step of folate biosynthesis in wine yeast. In this study, we also show that overexpression of other folate biosynthesis genes, including ABZ1, ABZ2, DFR1, FOL1 and FOL3, had no effect on folate levels in wine. Ensuring stability of the increased natural folate in all wines was achieved by the addition of ascorbate.

  4. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B/sub 12/: report of a preliminary randomized, double-blind intervention trial

    Energy Technology Data Exchange (ETDEWEB)

    Heimburger, D.C.; Alexander, C.B.; Birch, R.; Butterworth, C.E. Jr.; Bailey, W.C.; Krumdieck, C.L.

    1988-03-11

    To test whether changes in folate and vitamin B/sub 12/ nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, the authors conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 ..mu..g of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B/sub 12/. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B/sub 12/ used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B/sub 12/ by smokers.

  5. Differences in folate-protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5-methyltetrahydrofolate

    Energy Technology Data Exchange (ETDEWEB)

    Luka, Zigmund; Pakhomova, Svetlana; Loukachevitch, Lioudmila V; Newcomer, Marcia E; Wagner, Conrad [Vanderbilt; (LSU)

    2012-06-27

    Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S-adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5-methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate-GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme.

  6. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1.

  7. Plasma HDL reduces nonesterified fatty acid hydroperoxides originating from oxidized LDL: a mechanism for its antioxidant ability.

    Science.gov (United States)

    Kotosai, Mari; Shimada, Sachiko; Kanda, Mai; Matsuda, Namiko; Sekido, Keiko; Shimizu, Yoshibumi; Tokumura, Akira; Nakamura, Toshiyuki; Murota, Kaeko; Kawai, Yoshichika; Terao, Junji

    2013-06-01

    The antioxidant property of plasma high-density lipoprotein (HDL) is thought to be involved in potential anti-atherogenic effects but the exact mechanism is not known. We aimed to reveal the contribution of HDL on the elimination of lipid hydroperoxides (LOOH) derived from oxidized low-density lipoprotein (LDL). Oxidized LDL prepared by copper ion-induced oxidation contained nonesterified fatty acid hydroperoxides (FFA-OOH) and lysophosphatidylcholine (lysoPtdCho), in addition to cholesteryl ester hydroperoxides (CE-OOH) and phosphatidylcholine hydroperoxides (PtdCho-OOH). A platelet-activating factor-acetylhydrolase (PAF-AH) inhibitor suppressed formation of FFA-OOH and lysoPtdCho in oxidized LDL. Among LOOH species, FFA-OOH was preferentially reduced by incubating oxidized LDL with HDL. HDL exhibited selective FFA-OOH reducing ability if it was mixed with a liposomal solution containing FFA-OOH, CE-OOH and PtdCho-OOH. Two-electron reduction of the hydroperoxy group to the hydroxy group was confirmed by the formation of 13-hydroxyoctadecadienoic acid from 13-hydroperoxyoctadecadienoic acid in HPLC analyses. This reducing effect was also found in apolipoprotein A-1 (apoA-1). FFA-OOH released from PtdCho-OOH due to PAF-AH activity in oxidized LDL undergo two-electron reduction by the reducing ability of apoA1 in HDL. This preferential reduction of FFA-OOH may participate in the mechanism of the antioxidant property of HDL.

  8. Aspects of Weak Interactions between Folate and Glycine Betaine.

    Science.gov (United States)

    Bhojane, Purva P; Duff, Michael R; Bafna, Khushboo; Rimmer, Gabriella P; Agarwal, Pratul K; Howell, Elizabeth E

    2016-11-15

    Folate, or vitamin B9, is an important compound in one-carbon metabolism. Previous studies have found weaker binding of dihydrofolate to dihydrofolate reductase in the presence of osmolytes. In other words, osmolytes are more difficult to remove from the dihydrofolate solvation shell than water; this shifts the equilibrium toward the free ligand and protein species. This study uses vapor-pressure osmometry to explore the interaction of folate with the model osmolyte, glycine betaine. This method yields a preferential interaction potential (μ23/RT value). This value is concentration-dependent as folate dimerizes. The μ23/RT value also tracks the deprotonation of folate's N3-O4 keto-enol group, yielding a pKa of 8.1. To determine which folate atoms interact most strongly with betaine, the interaction of heterocyclic aromatic compounds (as well as other small molecules) with betaine was monitored. Using an accessible surface area approach coupled with osmometry measurements, deconvolution of the μ23/RT values into α values for atom types was achieved. This allows prediction of μ23/RT values for larger molecules such as folate. Molecular dynamics simulations of folate show a variety of structures from extended to L-shaped. These conformers possess μ23/RT values from -0.18 to 0.09 m(-1), where a negative value indicates a preference for solvation by betaine and a positive value indicates a preference for water. This range of values is consistent with values observed in osmometry and solubility experiments. As the average predicted folate μ23/RT value is near zero, this indicates folate interacts almost equally well with betaine and water. Specifically, the glutamate tail prefers to interact with water, while the aromatic rings prefer betaine. In general, the more protonated species in our small molecule survey interact better with betaine as they provide a source of hydrogens (betaine is not a hydrogen bond donor). Upon deprotonation of the small molecule, the

  9. Reduced anesthetic requirements, diminished brain plasma membrane Ca(2+)-ATPase pumping, and enhanced brain synaptic plasma membrane phospholipid methylation in diabetic rats: effects of insulin.

    Science.gov (United States)

    Janicki, P K; Horn, J L; Singh, G; Janson, V E; Franks, W T; Franks, J J

    1995-01-01

    We have recently reported that streptozocin (STZ)-induced diabetes in rats was associated with i) reduced Ca2+ pumping by rat brain synaptic plasma membrane Ca(2+)-ATPase (PMCA) and ii) a substantial reduction in the partial pressures of halothane and xenon required to prevent movement in response to stimulation (minimum effective dose or MED). MED for both agents correlated well with the degree of hemoglobin glycation and with PMCA activity. We now report that MEDs for isoflurane, enflurane, and desflurane were also substantially reduced in STZ-diabetic rats, compared with placebo-injected controls. In addition, we examined the effect of insulin treatment, begun 2 weeks after induction of diabetes and continued for 3 more weeks, on isoflurane MED and on brain synaptic PMCA and phospholipid-N-methyltransferase I (PLMT I), another enzyme altered by inhalation anesthetics (IA). Partial treatment of diabetes, as indicated by decreased glycated hemoglobin (GHb) compared to untreated diabetic rats, was associated with an isoflurane MED of 1.05 vol%, intermediate between a control mean of 1.57 vol% and an untreated diabetic mean of 0.82 vol% (p SPM from diabetic rats did not differ from control values, but PMCA pumping in SPM from the D-M was reduced to about 85% of control levels. Good correlation (r = 0.89, p < 0.01) was found between isoflurane MED and GHb in all treatment groups. These findings provide further evidence for an important role for PMCA in IA action. They also suggest that anesthetic effects on the calcium pump at specific anatomic sites may be of major importance in producing anesthesia.

  10. Reducing elevated plasma LDL cholesterol: the central role of the LDL receptor.

    Science.gov (United States)

    Vincent, J

    2014-07-01

    Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and reduction of elevated LDL-C reduces mortality in patients at risk. This benefit has evolved from the use of statins and knowledge of the LDL receptor (LDLR). The most potent drugs used for dyslipidemias act by mechanisms that involve this receptor. Advances in molecular genetics and understanding of the regulation of this receptor have revealed several pharmacological targets that are being explored to develop more targeted therapies for dyslipidemias.

  11. Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women.

    OpenAIRE

    Lajous, Martin; Romieu, Isabelle; Sabia, Séverine; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise

    2006-01-01

    International audience; OBJECTIVE: Adequate folate intake may be important for breast cancer prevention. Its protective effect may be influenced by factors associated with folate metabolism. We sought to evaluate folate intake in relation to breast cancer risk and examine whether the relation is affected by alcohol and intake of vitamin B(2) and B(12). METHODS: A prospective cohort analysis of folate intake was conducted among 62,739 postmenopausal women in the French E3N cohort who had compl...

  12. The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor

    Directory of Open Access Journals (Sweden)

    Pei Zhang

    2016-04-01

    Full Text Available An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO film coated on a glassy carbon electrode (GCE was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α, electron transfer number (n and electrode reaction standard rate constant (ks were 0.53, 2 and 3.4 s−1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70×10−7−1.25×10−5 M with the detection limit (s/n=3 of 1.84×10−8 M. The assay was successfully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2, area under curve (AUC, and plasma clearance (CL were calculated to be 3.345±0.647 min, 5750±656.0 µg min/mL, and 5.891±0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization, which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.

  13. Vitamin B12, folate, homocysteine and urinary methylmalonic acid levels in infants.

    Science.gov (United States)

    Karademir, F; Suleymanoglu, S; Ersen, A; Aydinoz, S; Gultepe, M; Meral, C; Ozkaya, H; Gocmen, I

    2007-01-01

    Serum vitamin B12 and folate, and their functional markers, plasma homocysteine and urinary methylmalonate (uMMA) were measured in 204 healthy, term infants at birth, and at 2 and 6 months. Compared with infants receiving formula food, those fed mother's milk had lower vitamin B12 and folate at 2 and 6 months. In infants receiving mother's milk, vitamin B12 levels were similar at birth (238 pg/ml) and 2 months (243 pg/ml), whereas with formula milk the level was significantly higher at 2 months (558 pg/ml) than at birth (257 pg/ml). Vitamin B12 was negatively correlated with homocysteine at birth and 6 months. The level of uMMA (mmol/mol creatinine) was higher at 2 (mother's milk, 25.5; formula, 23.97) and 6 months (19.77; 15) than at birth (11.97; 10.88), and was not correlated with vitamin B12 levels. Homocysteine may be a reliable marker of vitamin B12 status in neonates and infants; however, uMMA is not suitable as a marker of vitamin B12 status.

  14. Tumor targeting using {sup 67}Ga-DOTA-Bz-folate - investigations of methods to improve the tissue distribution of radiofolates

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina, E-mail: cristina.mueller@psi.ch [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Vlahov, Iontcho R.; Santhapuram, Hari Krishna R.; Leamon, Christopher P. [Endocyte Inc., West Lafayette, IN 47906 (United States); Schibli, Roger [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich (Switzerland)

    2011-07-15

    Introduction: Use of folic acid radioconjugates for folate receptor (FR) targeting is a promising strategy for imaging purposes as well as for potential therapy of cancer and inflammatory diseases due to the frequent FR overexpression found on cancer cells and activated macrophages. Herein, we report on preclinical results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [{sup 67}Ga]-gallium. Methods: DOTA-Bz-EDA-folate was prepared by conjugation of ethylenediamine-({gamma})-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling was carried out with {sup 67}GaCl{sub 3} according to standard procedures. Biodistribution studies of the tracer were performed in mice bearing FR-positive KB tumor xenografts. The effects on radiofolate biodistribution with coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as well as different routes of administration were likewise investigated. Supportive imaging studies were performed using a small-animal single photon emission computed tomography (SPECT)/CT scanner. Results: {sup 67}Ga-DOTA-Bz-EDA-folate showed a high and specific accumulation in tumors (6.30%{+-}0.75% ID/g, 1 h pi and 6.08%{+-}0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted tissues was negligible, but significant accumulation was found in FR-positive kidneys, which resulted in unfavorably low tumor-to-kidney ratios (<0.1). Coadministered amino acids or diuretics did not effectively reduce renal accumulation; in contrast, predosed pemetrexed did significantly reduce kidney uptake (<29% of control values). The SPECT/CT studies confirmed the excellent tumor-to-background contrast of {sup 67}Ga-radiofolate and the favorable reduction in kidney uptake (with improved imaging quality) resulting from pemetrexed administration. Conclusion: Conventional methods to reduce kidney uptake of radiofolates fail. However, the novel {sup 67}Ga-radiolabeled DOTA-Bz-EDA-folate can effectively be used to image FR

  15. Determination of folate concentrations in diverse potato germplasm using a trienzyme extraction and microbiological assay

    Science.gov (United States)

    We determined total folate concentrations of potato tubers from 67 cultivars, advanced breeding lines, or wild species. Folates were extracted by a tri-enzyme treatment and analyzed by using a Lactobacillus rhamnosus microbiological assay. Folate concentrations varied from 521 ± 96 to 1373 ± 230 ng/...

  16. Supplementation with engineered Lactococcus lactis improves the folate status in deficient rats

    NARCIS (Netherlands)

    LeBlanc, J.G.; Sybesma, W.F.H.; Starrenburg, M.; Sesma, F.; Vos, de W.M.; Giori, de G.S.; Hugenholtz, J.

    2010-01-01

    Objective: The aim of this study was to establish the bioavailability of different folates produced by engineered Lactococcus lactis strains using a rodent depletion-repletion bioassay. Methods: Rats were fed a folate-deficient diet, which produces a reversible subclinical folate deficiency,

  17. Exploring folate diversity in wild and primitive potatoes for modern crop improvement

    Science.gov (United States)

    Malnutrition is one of the world’s largest health concerns. Folate (a.k.a. vitamin B9) is essential in the human diet and without adequate folate intake several serious health concerns such as congenital birth defects and an increased risk of stroke and heart disease can occur. Most people’s folate ...

  18. Folate metabolism in the human colon: cellular responses identified through in vitro studies

    NARCIS (Netherlands)

    Pellis, E.P.M.

    2006-01-01

    Low folate intake influences the risk of not only neural tube defects and vascular diseases, but also colorectal tumours. Folate forms have different roles in the one-carbon metabolism. This includes DNA synthesis and methylation reactions. Folate is present as 5'-methyltetrahydrofolate (MTHF) in

  19. Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults

    DEFF Research Database (Denmark)

    Thuesen, B H; Husemoen, L L N; Ovesen, L

    2010-01-01

    Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency...

  20. Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma

    Science.gov (United States)

    Kim, Jinsik; Chae, Myung-Sic; Lee, Sung Min; Jeong, Dahye; Lee, Byung Chul; Lee, Jeong Hoon; Kim, Youngsoo; Chang, Suk Tai; Hwang, Kyo Seon

    2016-08-01

    Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer’s disease and its plasma concentration is in the pg mL-1 range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL-1. Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.

  1. Detergent activation of the binding protein in the folate radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, S.I.; Holm, J.; Lyngbye, J.

    1982-01-01

    A minor cow's whey protein associated with ..beta..-lactoglobulin is used as binding protein in the competitive radioassay for serum and erythrocyte folate. Seeking to optimize the assay, we tested the performance of binder solutions of increasing purity. The folate binding protein was isolated from cow's whey by means of CM-Sepharose CL-6B cation-exchange chromatography, and further purified on a methotrexate-AH-Sepharose 4B affinity matrix. In contrast to ..beta..-lactoglobulin, the purified protein did not bind folate unless the detergents cetyltrimethylammonium (10 mmol/Ll) or Triton X-100 (1 g/L) were present. Such detergent activation was not needed in the presence of serum. There seems to be a striking analogy between these phenomena and the well-known reactivation of certain purified membrane-derived enzymes by surfactants (lipids/detergents).

  2. Projection on Proper elements for code control: Verification, numerical convergence, and reduced models. Application to plasma turbulence simulations

    Science.gov (United States)

    Cartier-Michaud, T.; Ghendrih, P.; Sarazin, Y.; Abiteboul, J.; Bufferand, H.; Dif-Pradalier, G.; Garbet, X.; Grandgirard, V.; Latu, G.; Norscini, C.; Passeron, C.; Tamain, P.

    2016-02-01

    The Projection on Proper elements (PoPe) is a novel method of code control dedicated to (1) checking the correct implementation of models, (2) determining the convergence of numerical methods, and (3) characterizing the residual errors of any given solution at very low cost. The basic idea is to establish a bijection between a simulation and a set of equations that generate it. Recovering equations is direct and relies on a statistical measure of the weight of the various operators. This method can be used in any number of dimensions and any regime, including chaotic ones. This method also provides a procedure to design reduced models and quantify its ratio of cost to benefit. PoPe is applied to a kinetic and a fluid code of plasma turbulence.

  3. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

    1999-01-01

    OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore...... sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We infused GLP-1 (2.4 pmol.kg-1.min-1) or saline subcutaneously for 48 h in randomized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed....... CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure....

  4. Rapid atmospheric pressure plasma jet processed reduced graphene oxide counter electrodes for dye-sensitized solar cells.

    Science.gov (United States)

    Liu, Hsiao-Wei; Liang, Sheng-Ping; Wu, Ting-Jui; Chang, Haoming; Kao, Peng-Kai; Hsu, Cheng-Che; Chen, Jian-Zhang; Chou, Pi-Tai; Cheng, I-Chun

    2014-09-10

    In this work, we present the use of reduced graphene oxide (rGO) as the counter electrode materials in dye-sensitized solar cells (DSSCs). rGO was first deposited on a fluorine-doped tin oxide glass substrate by screen-printing, followed by post-treatment to remove excessive organic additives. We investigated the effect of atmospheric pressure plasma jet (APPJ) treatment on the DSSC performance. A power conversion efficiency of 5.19% was reached when DSSCs with an rGO counter electrode were treated by APPJs in the ambient air for a few seconds. For comparison, it requires a conventional calcination process at 400 °C for 15 min to obtain comparable efficiency. Scanning electron micrographs show that the APPJ treatment modifies the rGO structure, which may reduce its conductivity in part but simultaneously greatly enhances its catalytic activity. Combined with the rapid removal of organic additives by the highly reactive APPJ, DSSCs with APPJ-treated rGO counter electrode show comparable efficiencies to furnace-calcined rGO counter electrodes with greatly reduced process time. This ultrashort process time renders an estimated energy consumption per unit area of 1.1 kJ/cm(2), which is only one-third of that consumed in a conventional furnace calcination process. This new methodology thus saves energy, cost, and time, which is greatly beneficial to future mass production.

  5. Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion.

    Directory of Open Access Journals (Sweden)

    Karine Bibeau

    Full Text Available Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days, rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2, apoptotic enzyme (Caspase -3 and -9 and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.

  6. Evidence for two different nitrate-reducing activities at the plasma membrane in roots of Zea mays L.

    Science.gov (United States)

    de Marco, A; Jia, C; Fischer-Sehliebs, E; Varanini, Z; Lüttge, U

    1994-01-01

    Plasma-membrane (PM) vesicles isolated from 6-d-old corn roots by sucrose gradient centrifugation or two-phase partitioning showed an NADH-dependent nitrate reductase (NR) activity averaging at 40 nmol per milligram PM protein per hour. This membrane-associated NR activity could not be removed from two-phase partitioned PM vesicles by salt washing, osmotic shock treatment, sonication, or freeze-thawing to reverse vesicle sidedness. Therefore, it could not be attributed to contamination of membrane vesicles by the soluble, cytosolic NR. Plasma-membrane vesicles reduced NO~ in the presence of the electron donors NADH or NADPH at an activity ratio of 2.2. The NADH- and NADPH-dependent NR activities of outside-out oriented PM vesicles differed in their sensitivity toward the detergent Brij 58,leading to a latency of 65% or 29% using NADH or NADPH as electron donor, respectively. The activities of NO 3 reduction in the presence of saturating concentrations of NADH and NADPH were additive. Furthermore,both activities were characterized by a different pH dependence with a pH optimum of 7.5 for the NADH-dependent activity and of 6.8 for the NADPH-dependent activity. The membrane-associated NAD(P)H-dependent NR activities responded to different nitrogen nutrition of plants in a manner different from the soluble forms of the enzyme. The data confirm the existence of a corn PM NR and suggest that there may be two different NO₃-reducing enzymes located at the PM of corn roots.

  7. Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

    Science.gov (United States)

    Colomina, Jose M.; Cavallé-Busquets, Pere; Fernàndez-Roig, Sílvia; Solé-Navais, Pol; Fernandez-Ballart, Joan D.; Ballesteros, Mónica; Ueland, Per M.; Meyer, Klaus; Murphy, Michelle M.

    2016-01-01

    The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from −0.11 [0.06], p = 0.055 to −0.23 [0.06], p < 0.001). Conclusion: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele. PMID:27735840

  8. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: A pooled analysis of 8 prospective studies

    NARCIS (Netherlands)

    Cho, E.; Hunter, D.J.; Spiegelman, D.; Albanes, D.; Beeson, W.L.; Brandt, P.A. van den; Colditz, G.A.; Feskanich, D.; Folsom, A.R.; Fraser, G.E.; Freudenheim, J.L.; Giovannucci, E.; Goldbohm, R.A.; Graham, S.; Miller, A.B.; Rohan, T.E.; Sellers, T.A.; Virtamo, J.; Willett, W.C.; Smith-Warner, S.A.

    2006-01-01

    Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency

  9. Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study

    NARCIS (Netherlands)

    J.C.J. Steenweg-de Graaff (Jolien); S.J. Roza (Sabine); A.N. Walstra (Alette N.); H. El Marroun (Hanan); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent W. V.); A. Hofman (Albert); F.C. Verhulst (Frank); H.W. Tiemeier (Henning); T.J.H. White (Tonya)

    2015-01-01

    textabstractPurpose: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid su

  10. Hyperhomocysteinemia in healthy young men and elderly men with normal serum folate concentration is not associated with poor vascular reactivity or oxidative stress.

    Science.gov (United States)

    Hirsch, Sandra; Ronco, Ana María; Vasquez, Marcela; de la Maza, María Pía; Garrido, Argelia; Barrera, Gladys; Gattas, Vivien; Glasinovic, Andrea; Leiva, Laura; Bunout, Daniel

    2004-07-01

    The mechanism by which homocysteine (Hcy) causes endothelial dysfunction is probably mediated by oxidative stress. The aim of this study was to evaluate the effect of oxidative stress on endothelial function in young and elderly hyperhomocysteinemic (HHcy) men. A total of 35 HHcy (Hcy > 15 micro mol/L), young (n = 15; 20-40 y) and elderly men (n = 20; > 65 y) and 33 normohomocysteinemic (NHcy; controls) young (n = 14) and elderly (n = 19) men (Hcy < 13 micro mol/L), without classic cardiovascular risk factors were recruited. Serum Hcy, folate, and vitamin B-12, whole-blood glutathione, plasma total antioxidants status, TBARS, and 8-F(2alpha) isoprostanes were determined. Noninvasive ultrasound measurements of endothelium-dependent (EDVR) and -independent dilatation (EIVR) were performed. EDVR, EIVR, and markers of oxidative stress did not differ among the groups. Folate concentrations were higher in elderly than in young men (P < 0.001), independent of Hcy concentrations. Vitamin B-12 concentrations were lower in HHcy than in NHcy elderly men (P < 0.045). EDVR was correlated with folate concentrations in young men (r = 0.40, P = 0.04) and negatively with BMI in elderly men (r = -0.52, P = 0.002). In the present study, HHcy with normal serum folate concentrations was not associated with poor EDVR or oxidative stress in healthy young and elderly men.

  11. Relative bioavailability of folate from the traditional food plant Moringa oleifera L. as evaluated in a rat model.

    Science.gov (United States)

    Saini, R K; Manoj, P; Shetty, N P; Srinivasan, K; Giridhar, P

    2016-01-01

    Moringa oleifera is an affordable and rich source of dietary folate. Quantification of folate by HPLC showed that 5-formyl-5,6,7,8-tetrahydrofolic acid (502.1 μg/100 g DW) and 5,6,7,8-tetrahydrofolic acid (223.9 μg/100 g DW) as the most dominant forms of folate in M. oleifera leaves. The bioavailability of folate and the effects of folate depletion and repletion on biochemical and molecular markers of folate status were investigated in Wistar rats. Folate deficiency was induced by keeping the animals on a folate deficient diet with 1 % succinyl sulfathiazole (w/w). After the depletion period, animals were repleted with different levels of folic acid and M. oleifera leaves as a source of folate. Feeding the animals on a folate deficient diet for 7 weeks caused a significant (3.4-fold) decrease in serum folate content, compared to non-depleted control animals. Relative bioavailability of folate from dehydrated leaves of M. oleifera was 81.9 %. During folate depletion and repletion, no significant changes in liver glycine N-methyl transferase and 5-methyltetrahydrofolate-homocysteine methyltransferase expression were recorded. In RDA calculations, only 50 % of natural folate is assumed to be bioavailable. Therefore, the bioavailability of folate from Moringa is much higher, suggesting that M. oleifera based food can be used as a significant source of folate.

  12. Increased chromosome fragility as a consequence of blood folate levels, smoking status, and coffee consumption

    Energy Technology Data Exchange (ETDEWEB)

    Chen, A.T.L.; Reidy, J.A.; Annest, J.L.; Welty, T.K.; Zhou, H. (Centers for Disease Control, Atlanta, GA (USA))

    1989-01-01

    Chromosome fragility in 96 h, low-folate cultures was found to be associated with smoking status, coffee consumption, and blood folate level. The higher proportion of cells with chromosome aberrations in cigarette smokers was attributable to lower red cell folate levels in smokers compared with nonsmokers. There was a positive linear relationship between the average cups of coffee consumed per day and the proportion of cells with aberrations. This association was independent of the effects of smoking and red cell folate level. These data suggest that smoking history, coffee consumption, and red cell folate level are important considerations for the design and interpretation of fragile site studies in cancer cytogenetics.

  13. Effects and safety of periconceptional folate supplementation for preventing birth defects

    Science.gov (United States)

    Maria De-Regil, Luz; Fernández-Gaxiola, Ana C; Dowswell, Therese; Peña-Rosas, Juan Pablo

    2014-01-01

    Background It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. Objectives This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies. Selection criteria We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. Data collection and analysis We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy. Main results Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95

  14. Highly reduced current collapse in AlGaN/GaN high-electron-mobility transistors by combined application of oxygen plasma treatment and field plate structures

    Science.gov (United States)

    Asubar, Joel T.; Yoshida, Satoshi; Tokuda, Hirokuni; Kuzuhara, Masaaki

    2016-04-01

    We report on the highly reduced current collapse in AlGaN/GaN high-electron-mobility transistors (HEMTs) by combined application of pre-passivation oxygen (O2) plasma treatment and gate field plate (FP) structures schemes. Four different devices were fabricated in this work: (1) conventional HEMT as reference device, (2) field-plated HEMT, (3) O2 plasma-treated HEMT, (4) both field-plated and O2 plasma-treated HEMT. Analysis of dependence of normalized dynamic R on (NDR) on gate pulse on-time (t on) revealed that gate-FP reduces the emission time constant (τ i ) of trapped electrons while O2-plasma treatment decreases the density of traps. For all measurement conditions, the device with both FP and O2 plasma treatment exhibited the least NDR compared to devices with either FP or O2 plasma treatment only, demonstrating for the first time the compatibility of both O2 plasma treatment and FP schemes in mitigating current collapse.

  15. Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye;

    2017-01-01

    Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim o......)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.......Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim...... of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG(®) [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid...

  16. Folate, vitamin B12 and Homocysteine status in the post-folic acid fortification era in different subgroups of the Brazilian population attended to at a public health care center.

    Science.gov (United States)

    Barnabé, Aline; Aléssio, Ana Cláudia Morandi; Bittar, Luis Fernando; de Moraes Mazetto, Bruna; Bicudo, Angélica M; de Paula, Erich V; Höehr, Nelci Fenalti; Annichino-Bizzacchi, Joyce M

    2015-02-19

    Folate and vitamin B12 are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. Low levels of these vitamins have been associated with high concentrations of homocysteine (Hcy) and can lead to health complications. Several genetic polymorphisms affect the metabolism of these vitamins. The aims of this study were to assess folate, vitamin B12 and homocysteine status in distinct Brazilian individuals after the initiation of folic acid fortification by Brazilian authorities and to investigate the effects of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms on folate, vitamin B12 and Hcy levels in these populations. A total of 719 individuals including the elderly, children, as well as pregnant and lactating women were recruited from our health care center. Folate, vitamin B12 and Hcy levels were measured by conventional methods. Genotype analyses of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms were performed by PCR-RFLP. The overall prevalence of folate and vitamin B12 deficiencies were 0.3% and 4.9%, respectively. Folate deficiency was observed only in the elderly (0.4%) and pregnant women (0.3%), whereas vitamin B12 deficiency was observed mainly in pregnant women (7.9%) and the elderly (4.2%). Plasma Hcy concentrations were significantly higher in the elderly (33.6%). Pregnant women carrying the MTHFR 677TT genotype showed lower serum folate levels (p = 0.042) and higher Hcy levels (p = 0.003). RFC1 A80G and GCPII C1561T polymorphisms did not affect folate and Hcy levels in the study group. After a multivariate analysis, Hcy levels were predicted by variables such as folate, vitamin B12, gender, age and RFC1 A80G polymorphism, according to the groups studied. Our results suggest that folate deficiency is practically nonexistent in the post-folic acid fortification era in the subgroups evaluated. However, screening for vitamin B12 deficiency may be particularly relevant in our

  17. A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications

    Energy Technology Data Exchange (ETDEWEB)

    Mansoori, G. Ali, E-mail: mansoori@uic.edu; Brandenburg, Kenneth S. [Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan St. (MC 063), Chicago, IL 60607 (United States); Shakeri-Zadeh, Ali [Department of Medical Physics, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2010-11-18

    We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy.

  18. Folate and MMA predict cognitive impairment in elderly stroke survivors: A cross sectional study.

    Science.gov (United States)

    Pascoe, Michaela C; Linden, Thomas

    2016-09-30

    Elderly stroke survivors are at risk of malnutrition and long-term cognitive impairment. Vitamin B-related metabolites, folate and methylmalonic acid, have been implicated in cognitive function. We conducted a study exploring the relationship between blood folate, methylmalonic acid and post-stroke cognitive impairment. This is a cross sectional study of elderly Swedish patients (n=149) 20 months post-stroke, assessed using the Mini Mental State Examination, serum blood levels of methylmalonic acid and red blood cell levels of folate. Linear modeling indicated that low levels of blood folate and elevated methylmalonic acid significantly contributed to cognitive impairment in stroke survivors. Half of the stroke survivors were shown to have folate deficiency at 20 months after stroke. Folate deficiency is common long term after stroke and both low folate and elevated methylmalonic acid appear to be associated with long term cognitive impairment, in elderly Swedish stroke survivors.

  19. Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts.

    Science.gov (United States)

    Chevrier, Cécile; Perret, Claire; Bahuau, Michel; Zhu, Huiping; Nelva, Agnès; Herman, Christine; Francannet, Christine; Robert-Gnansia, Elisabeth; Finnell, Richard H; Cordier, Sylvaine

    2007-02-01

    The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

  20. Updated folate data in the Dutch Food Composition Database and implications for intake estimates.

    Science.gov (United States)

    Westenbrink, Susanne; Jansen-van der Vliet, Martine; van Rossum, Caroline

    2012-01-01

    Nutrient values are influenced by the analytical method used. Food folate measured by high performance liquid chromatography (HPLC) or by microbiological assay (MA) yield different results, with in general higher results from MA than from HPLC. This leads to the question of how to deal with different analytical methods in compiling standardised and internationally comparable food composition databases? A recent inventory on folate in European food composition databases indicated that currently MA is more widely used than HPCL. Since older Dutch values are produced by HPLC and newer values by MA, analytical methods and procedures for compiling folate data in the Dutch Food Composition Database (NEVO) were reconsidered and folate values were updated. This article describes the impact of this revision of folate values in the NEVO database as well as the expected impact on the folate intake assessment in the Dutch National Food Consumption Survey (DNFCS). The folate values were revised by replacing HPLC with MA values from recent Dutch analyses. Previously MA folate values taken from foreign food composition tables had been recalculated to the HPLC level, assuming a 27% lower value from HPLC analyses. These recalculated values were replaced by the original MA values. Dutch HPLC and MA values were compared to each other. Folate intake was assessed for a subgroup within the DNFCS to estimate the impact of the update. In the updated NEVO database nearly all folate values were produced by MA or derived from MA values which resulted in an average increase of 24%. The median habitual folate intake in young children was increased by 11-15% using the updated folate values. The current approach for folate in NEVO resulted in more transparency in data production and documentation and higher comparability among European databases. Results of food consumption surveys are expected to show higher folate intakes when using the updated values.

  1. Updated folate data in the Dutch Food Composition Database and implications for intake estimates

    Directory of Open Access Journals (Sweden)

    Susanne Westenbrink

    2012-04-01

    Full Text Available Background and objective: Nutrient values are influenced by the analytical method used. Food folate measured by high performance liquid chromatography (HPLC or by microbiological assay (MA yield different results, with in general higher results from MA than from HPLC. This leads to the question of how to deal with different analytical methods in compiling standardised and internationally comparable food composition databases? A recent inventory on folate in European food composition databases indicated that currently MA is more widely used than HPCL. Since older Dutch values are produced by HPLC and newer values by MA, analytical methods and procedures for compiling folate data in the Dutch Food Composition Database (NEVO were reconsidered and folate values were updated. This article describes the impact of this revision of folate values in the NEVO database as well as the expected impact on the folate intake assessment in the Dutch National Food Consumption Survey (DNFCS. Design: The folate values were revised by replacing HPLC with MA values from recent Dutch analyses. Previously MA folate values taken from foreign food composition tables had been recalculated to the HPLC level, assuming a 27% lower value from HPLC analyses. These recalculated values were replaced by the original MA values. Dutch HPLC and MA values were compared to each other. Folate intake was assessed for a subgroup within the DNFCS to estimate the impact of the update. Results: In the updated NEVO database nearly all folate values were produced by MA or derived from MA values which resulted in an average increase of 24%. The median habitual folate intake in young children was increased by 11–15% using the updated folate values. Conclusion: The current approach for folate in NEVO resulted in more transparency in data production and documentation and higher comparability among European databases. Results of food consumption surveys are expected to show higher folate intakes

  2. Association of anaemia with micronutrient (iron, folate and Vitamin ...

    African Journals Online (AJOL)

    Objective: Anaemia is the major cause of morbidity and mortality in paediatric age with much aetiology ... Analysis was done using SPSS version 13.0. ... Key words: Anaemia, frequency, association, iron, folate, vitamin B12, under-five children ...

  3. Research goals for folate and related B vitamin in Europe

    NARCIS (Netherlands)

    Finglas, P.M.; Meer, K. de; Molloy, A.; Verhoef, P.; Pietrzik, K.; Powers, H.J.; Straeten, D. van der; Jägerstad, M.; Varela-Moreiras, G.; Vliet, T. van; Havenaar, R.; Buttriss, J.; Wright, A.J.A.

    2006-01-01

    In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, f

  4. Quantification of Niacin and Folate Contents in Peanuts

    Science.gov (United States)

    Peanuts (Arachis hypogaea L.) are known to be sources of several important B-vitamins, including niacin and folate. Recent research has shown that therapeutic doses of niacin are beneficial for vascular health; therefore, determination of the concentrations found in current varieties in production ...

  5. Causes of Vitamin B12 and Folate Deficiency

    Science.gov (United States)

    This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetar...

  6. Research goals for folate and related B vitamin in Europe

    NARCIS (Netherlands)

    Finglas, P.M.; Meer, de K.; Molloy, A.; Verhoef, P.; Pietrzik, K.; Powers, H.J.; Straeten, van der D.; Jagerstad, M.; Varela-Moreiras, G.; Vliet, van T.; Havenaar, R.; Buttriss, J.

    2006-01-01

    In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements,

  7. Hyperhomocysteinemia in ulcerative colitis is related to folate levels

    Institute of Scientific and Technical Information of China (English)

    Petros Zezos; Georgia Papaioannou; Nikolaos Nikolaidis; Themistoclis Vasiliadis; Olga Giouleme; Nikolaos Evgenidis

    2005-01-01

    AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were gathered.RESULTS: Median serum Hcys levels in UC patients were similar to those in controls (12.26 μmol/L vs 12.32 μmol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125;95% CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2 = 0.4; P<0.001).CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.

  8. Influence of maternal folate status on human fetal growth parameters

    NARCIS (Netherlands)

    van Uitert, Evelyne M.; Steegers-Theunissen, Regine P. M.

    2013-01-01

    Worldwide periconceptional folic acid supplement use is recommended to prevent neural tube defects. This also stimulated research on maternal folate status in association with fetal growth, an important predictor of perinatal and future development and health. We provide an overview of literature on

  9. Oxidative-stress-mediated teratogenesis and the role of folate

    NARCIS (Netherlands)

    Tran, Y.H.; Bergman, J.; Bakker, M.; Groen, H.; Wilffert, B.

    2016-01-01

    Background: Oxidative stress (OS) is one of the underlying teratogenic mechanisms of medical drugs. Folate is indirectly involved in OS because of its role in the methylation steps in the detoxification of xenobiotics and in the repair of OS-induced DNA damage. Our study was to explore the associati

  10. Folate deficiency in women of reproductive age in nine ...

    African Journals Online (AJOL)

    2009-10-13

    Oct 13, 2009 ... be from 50% to 82%.5,6 Fortification of grains with folic acid has ... In logistic regression analysis, only low plant food diets (p = 0.001) and iron deficiency ..... enhance our ability to distinguish folate deficiency from vitamin B12.

  11. DNA methylation and folate metabolism in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Shun Shi Zhu; Shu Dong Xiao; Zhi Ping Chen; Yao Shi; Jing Yuan Fang; Rong Rong Li; Joel B Masor

    2000-01-01

    AIM To investigate DNA methylation status in gastric cancer and its relationship with folate metabolism.METHODS Serum before operation, the gastric mucosa from the lesion, and the surrounding area inpatients with gastric cancer and the remote normal-appearing mucosa of the resected stomach were collectedrespectively. The serum folate, mucosal tissue folate, S-adenosylmethionine ( SAM ), S-adenosylhomocysteine (SAH), and the DNA methylation levels were determined.RESULTS The tissue folate was significantly lower than that in ulcers, especially in the surrounding andnormal mucosa (0.38±0.13, 0.50±0.17 vs 0.53±0.50, 0.79±0.82ng/mg protein, P < 0.01), and itdecreased gradually in the lesion areas. The DNA methylation status showed similar decreasing trend incancers compared with the methylation increasing trend in ulcers. The SAM level ascended in the lesion areaswith a higher. concentration in cancer mueosa (63.5±43.0 vs 25.9±11.9nmol/g tissue, P < 0.01 ). Theaccumulation of SAH in the surrounding and normal mucosa of cancers was observed (17.3±24.6, 15.5±8.6vs 14.6±4.2, 10.0±1.9nmol/g tissue, P < 0.05 - 0.01). There were significantly negative correlationsbetween tissue folate and the SAM and SAH levels in the three areas.CONCLUSION Patients with gastric cancer have the regional folate deficiency in the stomach mucosa,although the serum folate level remains normal. This disturbs the local SAM and SAH metabolism withaccumulation of SAH and DNA hypomethylation which has been known as an important molecularmechanism for carcinogenesis. Folic acid can modulate DNA methylation status by its effect in one-carbongroup metabolism and thus affect the process of the carcinogenesis. Therefore, this may be an access for theprevention of gastric cancer.

  12. 去冷沉淀血浆的质量分析%Analysis of quality of cryoprecipitate-reduced plasma

    Institute of Scientific and Technical Information of China (English)

    马莉; 周静宇; 黎美君; 李长清; 孙盼; 林方昭; 刁戈; 李剑平; 张红抑; 刘建强; 张心声; 柏则蓉

    2013-01-01

    Objective To compare the levels of coagulation factors, fibrinogen (Fib) and Von Willebrand factor cleaving protease, a disintegrin-like and metalloprotease with thrombospondin-1 repeats 13 (ADAMTS13), in cryoprecipitate-re-duced plasma (CRP). Methods CRP was prepared with the fresh frozen plasma (FFP) from 140 donors. The coagula-tion-promoting activities of FⅡ, FⅣ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ in FFP and CRP were determined by one-stage Biggers method, while the activities of Fib and Von Willebrand factor antigen (vWF : Ag) by immune turbidimetry. The activity and antigen contents of ADAMTS13 in FFP and CRP were determined by fluorescence resonance energy transfer (FRET) assay. Results As compared with those in FFP, the levels of FⅧ : C, FⅤ : C, FⅦ : C, FⅨ : C, FⅩ : C, FⅪ : C, Fib, vWF : Ag decreased significantly (P 0. 05). Conclusion CRP may be used for treatment of thrombotic thrombocytopenic purpura (TTP) instead of CRP, while is unsuitable for complementary treatment of FⅧ, Fib and vWF deficiency.%目的 比较去冷沉淀血浆(Cryoprecipitate-reduced plasma,CRP)中系列凝血因子、纤维蛋白原(Fibrinogen,Fib)和血管性血友病因子裂解蛋白酶(A disintegrin-like and metalloprotease with thrombospondin-1 repeats 13,ADAMTS-13)水平的变化.方法 用140人份新鲜冰冻血浆(Fresh frozen plasma,FFP)制备CRP,采用Biggers一期法测定FFP和CRP中FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FX、FⅪ、FⅫ的促凝活性;免疫比浊法测定Fib和血管性血友病因子抗原因子活动度(vWF:Ag)水平;荧光共振能量转移法(Fluorescence resonance energy transfer,FRET)测定70人份FFP和CRP中的ADAMTS13活性及抗原含量.结果 与FFP比较,CRP中FⅧ:C、FⅤ:C、FⅦ:C、FⅨ:C、FX:C、FⅪ:C、Fib、vWF:Ag水平均明显下降,且差异均有统计学意义(P<0.05或<0.001);FⅡ:C、FⅫ:C、ADAMTS13抗原含量和活性差异均无统计学意义(P>0.05).结论 CRP可代替FFP用于血栓

  13. Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia.

    Directory of Open Access Journals (Sweden)

    J Pedro Fernández-Murray

    2016-01-01

    Full Text Available Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia.

  14. Laying hens can convert high doses of folic acid added to the feed into natural folates in eggs providing a novel source of food folate.

    Science.gov (United States)

    Hoey, Leane; McNulty, Helene; McCann, Elizabeth M E; McCracken, Kelvin J; Scott, John M; Marc, Barbara Blaznik; Molloy, Anne M; Graham, Ciaren; Pentieva, Kristina

    2009-01-01

    There are few good sources of natural food folates apart from green leafy vegetables and these may have a limited potential to increase folate status because of substantial losses that can occur during cooking. Fortified foods can overcome this but are controversial because of safety concerns regarding chronic exposure to high-dose folic acid (FA; the synthetic form). The aim of the present study was to develop eggs with an enriched natural folate content and minimal unmetabolised FA. Forty-eight, 30-week-old laying hens were randomised to receive the basal feed (formulated to provide 1 mg folate/kg feed) to which had been added one of the following FA levels (0, 2, 4, 8, 16, 32 mg/kg feed). Total folate was measured in eggs collected throughout the 12-week study period and the FA content estimated at 12 weeks. Results showed that the maximal egg folate content was achieved by adding 16 mg FA/kg feed. At this optimal dose, the total folate content per egg was 75 microg (compared with 32 microg in a regular egg) of which FA represented at most 10%, a level which would probably be converted into natural folates by humans after ingestion. The results demonstrate that it is possible to use synthetic FA at high doses to produce novel animal foods enriched with natural folates in a cost-efficient process. Such foods may be particularly relevant to European populations without access to FA fortification and therefore dependent on natural food folate sources for the primary prevention of folate-related disease.

  15. Enhancing pterin and para-aminobenzoate content is not sufficient to successfully biofortify potato tubers and Arabidopsis thaliana plants with folate

    NARCIS (Netherlands)

    Blancquaert, D.; Storozhenko, S.; Daele, W.; Stove, C.; Visser, R.G.F.; Lambert, W.; Straeten, van der D.

    2013-01-01

    Folates are important cofactors in one-carbon metabolism in all living organisms. Since only plants and micro- organisms are capable of biosynthesizing folates, humans depend entirely on their diet as a folate source. Given the low folate content of several staple crop products, folate deficiency af

  16. Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

    Science.gov (United States)

    Russo, G T; Giandalia, A; Romeo, E L; Scarcella, C; Gambadoro, N; Zingale, R; Forte, F; Perdichizzi, G; Alibrandi, A; Cucinotta, D

    2016-03-01

    Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P vitamin B12 level reduction, but not with DPN.

  17. Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells.

    Directory of Open Access Journals (Sweden)

    John C Panetta

    Full Text Available Methotrexate (MTX is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL. The accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG, in ALL cells is an important determinant of its antileukemic effects. We studied 194 of 356 patients enrolled on St. Jude Total XV protocol for newly diagnosed ALL with the goal of characterizing the intracellular pharmacokinetics of MTXPG in leukemia cells; relating these pharmacokinetics to ALL lineage, ploidy and molecular subtype; and using a folate pathway model to simulate optimal treatment strategies. Serial MTX concentrations were measured in plasma and intracellular MTXPG concentrations were measured in circulating leukemia cells. A pharmacokinetic model was developed which accounted for the plasma disposition of MTX along with the transport and metabolism of MTXPG. In addition, a folate pathway model was adapted to simulate the effects of treatment strategies on the inhibition of de novo purine synthesis (DNPS. The intracellular MTXPG pharmacokinetic model parameters differed significantly by lineage, ploidy, and molecular subtypes of ALL. Folylpolyglutamate synthetase (FPGS activity was higher in B vs T lineage ALL (p<0.005, MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03, MTX influx and FPGS activity were lower in the t(12;21 (ETV6-RUNX1 subtype (p<0.05, and the ratio of FPGS to γ-glutamyl hydrolase (GGH activity was lower in the t(1;19 (TCF3-PBX1 subtype (p<0.03 than other genetic subtypes. In addition, the folate pathway model showed differential inhibition of DNPS relative to MTXPG accumulation, MTX dose, and schedule. This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy.

  18. Susceptibility to virus-cell fusion at the plasma membrane is reduced through expression of HIV gp41 cytoplasmic domains.

    Science.gov (United States)

    Malinowsky, Katharina; Luksza, Julia; Dittmar, Matthias T

    2008-06-20

    The cytoplasmic tail of the HIV transmembrane protein plays an important role in viral infection. In this study we analyzed the role of retroviral cytoplasmic tails in modulating the cytoskeleton and interfering with virus-cell fusion. HeLaP4 cells expressing different HIV cytoplasmic tail constructs showed reduced acetylated tubulin levels whereas the cytoplasmic tail of MLV did not alter microtubule stability indicating a unique function for the lentiviral cytoplasmic tail. The effect on tubulin is mediated through the membrane proximal region of the HIV cytoplasmic tail and was independent of membrane localization. Site-directed mutagenesis identified three motifs in the HIV-2 cytoplasmic tail required to effect the reduction in acetylated tubulin. Both the YxxPhi domain and amino acids 21 to 45 of the HIV-2 cytoplasmic tail need to be present to change the level of acetylated tubulin in transfected cells. T-cells stably expressing one HIV-2 cytoplasmic tail derived construct showed also a reduction in acetylated tubulin thus confirming the importance of this effect not only for HeLaP4 and 293T cells. Challenge experiments using transiently transfected HeLaP4 cells and T cells stably expressing an HIV cytoplasmic tail construct revealed both reduced virus-cell fusion and replication of HIV-1(NL4.3) compared to control cells. In the virus-cell fusion assay only virions pseudotyped with either HIV or MLV envelopes showed reduced fusion efficiency, whereas VSV-G pseudotyped virions where not affected by the expression of HIV derived cytoplasmic tail constructs, indicating that fusion at the plasma but not endosomal membrane is affected. Overexpression of human histone-deacetylase 6 (HDAC6) and constitutively active RhoA resulted in a reduction of acetylated tubulin and reduced virus-cell fusion as significant as that observed following expression of HIV cytoplasmic tail constructs. Inhibition of HDAC6 showed a strong increase in acetylated tubulin and increase of

  19. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate1, 2, 3, 4

    Science.gov (United States)

    Lakoff, Alanna; Fazili, Zia; Aufreiter, Susanne; Pfeiffer, Christine M; Connolly, Bairbie; Gregory, Jesse F; Pencharz, Paul B; O’Connor, Deborah L

    2016-01-01

    Background Folate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [13C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome. Objective We determined whether and how much of a physiologic dose of [13C5]5-formyltetrahydrofolate delivered in a pH-sensitive enteric caplet to an intact colonic microbiome is absorbed. Design Healthy adults ingested a specially designed pH-sensitive acrylic copolymer–coated barium sulfate caplet that contained 855 nmol (400 μg) [13C5]5-formyltetrahydrofolate. After a washout period ≥4 wk, subjects received an intravenous injection of the same compound (214 nmol). Serially collected blood samples before and after each test dose were analyzed by using a microbiological assay and liquid chromatography–tandem mass spectrometry. Results Caplet disintegration in the colon was observed by fluoroscopic imaging for 6 subjects with a mean (±SD) complete disintegration time of 284 ± 155 min. The mean (±SEM) rate of appearance of [13C5]5-methyltetrahydrofolate in plasma was 0.33 ± 0.09 (caplet) and 5.8 ± 1.2 (intravenous) nmol/h. Likely because of the significant time in the colon, the mean apparent absorption across the colon was 46%. Conclusions Folate is absorbed across the colon in humans with an undisturbed microbiome. This finding and previous observations of the size of the colonic depot of folate and its potential for manipulation by diet (eg, dietary fiber, oligosaccharides, and probiotics) suggest that an individual’s dietary folate requirement may differ depending on the consumption of dietary constituents that affect the size and composition of

  20. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate.

    Science.gov (United States)

    Lakoff, Alanna; Fazili, Zia; Aufreiter, Susanne; Pfeiffer, Christine M; Connolly, Bairbie; Gregory, Jesse F; Pencharz, Paul B; O'Connor, Deborah L

    2014-11-01

    Folate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [(13)C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome. We determined whether and how much of a physiologic dose of [(13)C5]5-formyltetrahydrofolate delivered in a pH-sensitive enteric caplet to an intact colonic microbiome is absorbed. Healthy adults ingested a specially designed pH-sensitive acrylic copolymer-coated barium sulfate caplet that contained 855 nmol (400 μg) [(13)C5]5-formyltetrahydrofolate. After a washout period ≥ 4 wk, subjects received an intravenous injection of the same compound (214 nmol). Serially collected blood samples before and after each test dose were analyzed by using a microbiological assay and liquid chromatography-tandem mass spectrometry. Caplet disintegration in the colon was observed by fluoroscopic imaging for 6 subjects with a mean (± SD) complete disintegration time of 284 ± 155 min. The mean (± SEM) rate of appearance of [(13)C5]5-methyltetrahydrofolate in plasma was 0.33 ± 0.09 (caplet) and 5.8 ± 1.2 (intravenous) nmol/h. Likely because of the significant time in the colon, the mean apparent absorption across the colon was 46%. Folate is absorbed across the colon in humans with an undisturbed microbiome. This finding and previous observations of the size of the colonic depot of folate and its potential for manipulation by diet (eg, dietary fiber, oligosaccharides, and probiotics) suggest that an individual's dietary folate requirement may differ depending on the consumption of dietary constituents that affect the size and composition of their gastrointestinal microbiota. In

  1. Innovative Plasma Disinfection Technique with the Reduced-pH Method and the Plasma-Treated Water (PTW) -Safety and Powerful Disinfection with Cryopreserved PTW-

    Science.gov (United States)

    Kitano, Katsuhisa; Ikawa, Satoshi; Nakashima, Yoichi; Tani, Atsushi; Yokoyama, Takashi; Ohshima, Tomoko

    2015-09-01

    Among the applications of the plasma disinfection to human body, plasma sterilization in liquid is crucial. We found that the plasma-treated water (PTW) has strong bactericidal activity under low pH condition and the half-lives of its activity depend on temperature. Lower temperature brings longer half-life and the bactericidal activity of PTW can be kept by cryopreservation. These physicochemical properties were in accordance with Arrhenius equation both in liquid and solid states. From the experimental results of ESR (Electron Spin Resonance) measurement of O2-in liquid against PTW with spin trapping method, half-lives of PTW were also in accordance with Arrhenius equation. It suggests that high concentration PTW as integrated value can be achieved by cooling of plasma apparatus. Pure PTW has disinfection power of 22 log reduction (B. subtilis). This corresponds to 65% H2O2, 14% hypochlorous acid and 0.33% peracetic acid, which are deadly poison for human. On the other hand, PTW is deactivated soon at body temperature. This indicates that toxicity to human body seems to be low. PTW, which is a sort of indirect plasma exposure, with pH and temperature controls could be applied for safety and powerful disinfection. MEXT (15H03583, 23340176, 25108505). NCCE (23-A-15).

  2. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis.

    Science.gov (United States)

    Pan, Yun; Liu, Ya; Guo, Haizhuo; Jabir, Majid Sakhi; Liu, Xuanchen; Cui, Weiwei; Li, Dong

    2017-04-13

    Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn's disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

  3. A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting.

    Science.gov (United States)

    Lohade, Atul A; Jain, Rajesh R; Iyer, Krishna; Roy, Sushant K; Shimpi, Hemant H; Pawar, Yogita; Rajan, M G R; Menon, Mala D

    2016-12-01

    Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.

  4. Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients

    NARCIS (Netherlands)

    J.W. van der Heijden; R. Oerlemans; B.A.C. Dijkmans; H. Qi; C.J. van der Laken; W.F. Lems; A.L. Jackman; M.C. Kraan; P.P. Tak; M. Ratnam; G. Jansen

    2009-01-01

    OBJECTIVE: To determine the expression of folate receptor beta (FRbeta) in synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid arthritis (RA) patients and to identify novel folate antagonists that are more selective in the targeting and internalization of FRbeta than methotrexat

  5. Folate receptor-β imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque

    NARCIS (Netherlands)

    Jager, Nynke A.; Westra, Johanna; Golestani, Reza; van Dam, Gooitzen M.; Low, Philip S.; Tio, Rene A.; Slart, Riemer H. J. A.; Boersma, Hendrikus; Bijl, Marc; Zeebregts, Clark J.

    2014-01-01

    UNLABELLED: In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the pr

  6. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Rinder, Christiane; Beige, Joachim;

    2004-01-01

    Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure.......Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure....

  7. Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol

    Science.gov (United States)

    The plasma LDL-cholesterol-lowering effect of plant sterols (PS) appears to be independent of background diet, but definitive proof is lacking. The effect of background diet on plasma concentrations of PS has not been reported. We determined the effects of manipulating dietary contents of PS and f...

  8. Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans.

    Science.gov (United States)

    Fryer, Anthony A; Emes, Richard D; Ismail, Khaled M K; Haworth, Kim E; Mein, Charles; Carroll, William D; Farrell, William E

    2011-01-01

    Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.

  9. Status of Vitamin B12 and Folate among the Urban Adult Population in South India.

    Science.gov (United States)

    Sivaprasad, M; Shalini, T; Balakrishna, N; Sudarshan, M; Lopamudra, P; Suryanarayana, P; Arlappa, N; Ravikumar, B P; Radhika, M S; Reddy, G Bhanuprakash

    2016-01-01

    Deficiency of vitamin B12 (B12) and folate (FA) leads to a wide spectrum of disorders that affect all age groups. However, reports on B12 and FA status in healthy adults in India are limited. Hence, we determined the plasma levels and dietary intake of B12 and FA in the adult population. We conducted a community-based cross-sectional study in an urban setup among 630 apparently healthy adults distributed into 3 age groups: 21-40, 41-60 and >60 years. Plasma concentrations of B12 and FA were analyzed by radio immunoassay and dietary intake by 24-hour recall method. The overall prevalence of FA deficiency was 12%, but there was no significant difference in plasma FA concentrations among the groups. While the overall prevalence of B12 deficiency was 35%, it was significantly higher in the 21-40 (44%) and 41-60 age groups (40%) when compared with the >60 group (30%). B12 deficiency was higher in vegetarians (54%) compared to those consuming mixed diet (31%), and the reverse was the case with FA. However, the dietary intakes of FA and B12 were not significantly different among the groups. These results indicate a higher prevalence of B12 deficiency in apparently healthy adults in an urban setup. © 2015 S. Karger AG, Basel.

  10. Effect of maternal and post weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult Apc+/Min and wild type mice.

    Directory of Open Access Journals (Sweden)

    Jill Ann Mckay

    2011-05-01

    Full Text Available Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g. DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC pathogenesis, we hypothesised low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine (SI of wild type (WT and Apc+/Min mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57Bl6/J mice were fed low or normal folate diets from mating with Apc+/Min males to the end of lactation. A sub set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in 4 treatment groups of Apc+/Min and WT mice. p53 was more methylated in weaning and adult WT compared with Apc+/Min mice (p>0.001. Igf2 and Apc were hypermethylated in adult Apc+/Mi n compared with WT mice (p=0.004 & p=0.012 respectively. Low maternal folate reduced p53 methylation in adults (p=0.04. Low post-weaning folate increased Apc methylation in Apc+/Min mice only (p=0.008 for interaction. These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc+/Min mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalised nutrition.

  11. Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome

    Science.gov (United States)

    Mohanty, Pankaj K.; Kapoor, Seema; Dubey, Anand P.; Pandey, Sanjeev; Shah, Renuka; Nayak, Hemant K.; Polipalli, Sunil K.

    2012-01-01

    AIMS AND OBJECTIVE: Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome. DESIGN: This was a case–control study. MATERIAL AND METHODS Fifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene. RESULTS: The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535. CONCLUSION: Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of

  12. No relation between folate and homocysteine levels and depression in early pregnant women.

    Science.gov (United States)

    Watanabe, Hiroko; Suganuma, Nobuhiko; Hayashi, Ayako; Hirowatari, Yumiko; Hirowatari, Tsuneharu; Ohsawa, Masami

    2010-12-01

    The objective in this study was to evaluate the association between folate and homocysteine (Hcy) levels and depressive symptoms in early pregnancy. A cross-sectional study was conducted with 86 pregnant women in the first trimester. A Japanese version of the Center for Epidemiologic Studies Depression (CES-D) scale was used to screen for depression. Non-fasting blood samples were collected from the women to measure folate and Hcy levels. Fifty-three (61.6%) women scored at or above a clinical cut-off of 16, and were classified with depression. In logistic regression analyses, no significant associations were observed between the incidence of depression in the first trimester and elevated Hcy and deficiencies of serum folate, folate intake, vitamin B6 intake and vitamin B12 intake. Folate and Hcy concentrations, and folate consumption, may not be protective against depression in early pregnancy.

  13. Concentrations of blood folate in Brazilian studies prior to and after fortification of wheat and cornmeal (maize flour) with folic acid: a review.

    Science.gov (United States)

    Britto, Jéssica Carrilho; Cançado, Rodolfo; Guerra-Shinohara, Elvira Maria

    2014-01-01

    In July 2004, the Brazilian Ministry of Health through the National Health Surveillance Agency made the fortification of wheat flour and cornmeal (maize flour) with iron and folic acid mandatory, with the intention of reducing the rate of diseases such as neural tube defects. The aim of the study was to investigate the impact of the folic acid fortified wheat flour and cornmeal on serum and red blood cell folate levels and on the reduction of neural tube defects in different Brazilian studies. In order to compare folate concentrations in the Brazilian population prior to and following the implementation of mandatory fortification of wheat and cornmeal, studies that involved blood draws between January 1997 and May 2004 (pre-fortification period), and from June 2004 to the present (post-fortification period) were chosen. The data search included PubMed and Scopus databases as well as the Brazilian Digital Library of Theses and Dissertations. The following keywords were employed for the query: folate, folic acid, fortification, Brazil, healthy population, the elderly, children and pregnant women. A total of 47 Brazilian studies were selected; 26 from the pre-fortification period and 22 after the fortification implementation. The studies were classified according to the cohort investigated (pregnant women, children, adolescents, adults and the elderly). After the implementation of flour fortification with folic acid in Brazil, serum folate concentrations increased in healthy populations (57% in children and adolescents and 174% in adults), and the incidence of neural tube defects dropped. Folic acid fortification of wheat flour and cornmeal increased the blood folate concentrations and reduced the incidence of neural tube defects. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  14. Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

    OpenAIRE

    2016-01-01

    Context Folates are B-vitamins that cannot be generated de novo and are therefore obtained from the diet. In the brain, these vitamins are involved in nucleotide synthesis, DNA repair, lipid metabolism, methylation and neurotransmitter synthesis. It is well established that adequate levels of maternal folates are required for closure of the neural tube within the first month of pregnancy, however, it is not clear whether maternal folates are needed throughout pregnancy for brain ...

  15. Exploring Folate Diversity in Wild and Primitive Potatoes for Modern Crop Improvement

    OpenAIRE

    Robinson,Bruce; Sathuvalli, Vidyasagar; Bamberg, John; Goyer, Aymeric

    2015-01-01

    Malnutrition is one of the world’s largest health concerns. Folate (also known as vitamin B9) is essential in the human diet, and without adequate folate intake, several serious health concerns, such as congenital birth defects and an increased risk of stroke and heart disease, can occur. Most people’s folate intake remains sub-optimal, even in countries that have a folic acid food fortification program in place. Staple crops, such as potatoes, represent an appropriate organism for biofortifi...

  16. Effects of yeasts and bacteria on the levels of folates in rye sourdoughs.

    Science.gov (United States)

    Kariluoto, Susanna; Aittamaa, Marja; Korhola, Matti; Salovaara, Hannu; Vahteristo, Liisa; Piironen, Vieno

    2006-02-01

    Fermentation of rye dough is often accompanied with an increase in folate content. In this study, three sourdough yeasts, Candida milleri CBS 8195, Saccharomyces cerevisiae TS 146, and Torulaspora delbrueckii TS 207; a control, baker's yeast S. cerevisiae ALKO 743; and four Lactobacillus spp., L. acidophilus TSB 262, L. brevis TSB 307, L. plantarum TSB 304, and L. sanfranciscensis TSB 299 originally isolated from rye sourdough were examined for their abilities to produce or consume folates. The microorganisms were grown in yeast extract-peptone-d-glucose medium as well as in small-scale fermentations that modelled the sourdough fermentation step used in rye baking. Total folate contents were determined using Lactobacillus rhamnosus (ATCC 7469) as the growth indicator organism. The microorganisms studied did not excrete folates into the media in significant amounts. Yeasts increased the folate contents of sterilised rye flour-water mixtures from 6.5 microg/100 g to between 15 and 23 microg/100 g after 19-h fermentation, whereas lactic acid bacteria decreased it to between 2.9 and 4.2 microg/100 g. Strains of Lactobacillus bulgaricus, L. casei, L. curvatus, L. fermentum, L. helveticus, Pediococcus spp., and Streptococcus thermophilus that were also tested gave folate contents after fermentation that varied between 2 and 10.4 microg/100 g. Although the four Lactobacillus spp. from sourdough consumed folates their effect on folate contents in co-cultivations was minimal. It was concluded that the increase of folate content during fermentation was mainly due to folate synthesis by yeasts. Fermentation of non-sterilised flour-water mixtures as such resulted in three-fold increases in the folate contents. Two folate producing bacteria were isolated from the non-sterilised flour and identified as Enterobacter cowanii and Pantoea agglomerans.

  17. A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era.

    Directory of Open Access Journals (Sweden)

    Suguna Badiga

    Full Text Available Studies in populations unexposed to folic acid (FA fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+. However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1 The association between MTHFR C677T polymorphism and risk of CIN 2+; 2 The modifying effects of plasma folate concentrations on this association; and 3 The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s, in peripheral blood mononuclear cell (PBMC DNA, a documented biomarker of CIN risk.The study included 457 US women diagnosed with either CIN 2+ (cases or ≤ CIN 1 (non-cases. Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN.The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030. Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017.This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation.

  18. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients

    National Research Council Canada - National Science Library

    Ando, M; Sanaka, T; Nihei, H

    1999-01-01

    .... Remnant lipoproteins are atherogenic and are frequently observed in uremic plasma. LDL from uremic patients has been shown to be susceptible to in vitro peroxidation, suggesting that oxidized LDL (ox-LDL...

  19. Lipids rich in phosphatidylethanolamine from natural gas-utilizing bacteria reduce plasma cholesterol and classes of phospholipids

    DEFF Research Database (Denmark)

    Müller, H.; Hellgren, Lars; Olsen, E.;

    2004-01-01

    We compared the effects of three different high-lipid diets on plasma lipoproteins and phospholipids in mink (Mustela vison). The 18 mink studied were fed one of the three diets during a 25-d period in a parallel group design. The compared diets had 0, 17, and 67% extracted lipids from natural gas...... phospholipids, lysoPC, and PI were lowered significantly compared with the mink fed a SB-diet. Plasma total cholesterol was correlated with total phospholipids as well as with PC (R = 0.8, P ... was observed in the 67LNGB-fed mink compared with the SB-fed mink. We conclude that phospholipids from the 67LNGB-diet decreased plasma lipoprotein levels, the LDL-HDL cholesterol ratio, and plasma phospholipid levels, especially lysoPC and PC, compared with the highly unsaturated soybean oil. Our findings...

  20. Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

    LENUS (Irish Health Repository)

    2011-09-01

    To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet.

  1. [Folate and folic acid intake estimation and food enrichment requirements].

    Science.gov (United States)

    Olivares Martínez, Ana Belén; Ros Berruezo, Gaspar; Bernal Cava, M José; Martínez Graciá, Carmen; Periago Castón, M Jesús

    2005-03-01

    The term "folate" is a generic way to name the different forms derived from folic acid, one of the B vitamins (specifically B9 vitamin). They are essential in the metabolism when they act as cofactors in the transfer reactions of one carbon. However, only plants and microorganisms are able to synthesize them de novo, in such a way that both animals and human beings have to intake them through their diet. Folic acid is widely spread in nature, mainly in vegetables, liver ans cereals. However, nowadays, the lack of folates in the diet is one of the most common nutritional deficiencies in the world, and it has serious consequences on human health. There is evidence that even in developed countries folate intake is usually low; and even, is some cases, below optima levels. The authorities in several countries have adapted different norms related to folic acid, fortifying staple food such as dairy products or cereals, mandatory (U.S.A., Canada or Chile) or voluntary (most of the European countries).

  2. Epigenetic synergies between biotin and folate in the regulation of pro-inflammatory cytokines and repeats.

    Science.gov (United States)

    Xue, J; Zempleni, J

    2013-11-01

    The protein biotin ligase, holocarboxylase synthetase (HLCS), is a chromatin protein that interacts physically with the DNA methyltransferase DNMT1, the methylated cytosine-binding protein MeCP2 and the histone H3 K9-methyltransferase EHMT1, all of which participate in folate-dependent gene repression. Here we tested the hypothesis that biotin and folate synergize in the repression of pro-inflammatory cytokines and long-terminal repeats (LTRs), mediated by interactions between HLCS and other chromatin proteins. Biotin and folate supplementation could compensate for each other's deficiency in the repression of LTRs in Jurkat and U937 cells. For example, when biotin-deficient Jurkat cells were supplemented with folate, the expression of LTRs decreased by >70%. Epigenetic synergies were more complex in the regulation of cytokines compared with LTRs. For example, the abundance of TNF-α was 100% greater in folate- and biotin-supplemented U937 cells compared with biotin-deficient and folate-supplemented cells. The NF-κB inhibitor curcumin abrogated the effects of folate and biotin in cytokine regulation, suggesting that transcription factor signalling adds an extra layer of complexity to the regulation of cytokine genes by epigenetic phenomena. We conclude that biotin and folate synergize in the repression of LTRs and that these interactions are probably mediated by HLCS-dependent epigenetic mechanisms. In contrast, synergies between biotin and folate in the regulation of cytokines need to be interpreted in the context of transcription factor signalling.

  3. Vitamin B12 and folate levels in long-term vegans.

    Science.gov (United States)

    Bar-Sella, P; Rakover, Y; Ratner, D

    1990-06-01

    Serum vitamin B12, serum folate and red blood cell (RBC) folate levels were examined among 36 strict vegans of 5-35 years' duration. Vitamin B12 levels among the vegans were generally lower than in a control population. Most of the vegans had vitamin B12 values less than 200 pg/ml. RBC folate levels were normal but serum folate levels among the vegans were higher than among the controls. None of the vegans had any hematologic evidence of vitamin B12 deficiency, however four of them had neurologic complaints. Long-standing vegans should be monitored for vitamin B12 levels.

  4. MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum.

    Science.gov (United States)

    Rijpma, Sanna R; van der Velden, Maarten; Bilos, Albert; Jansen, Robert S; Mahakena, Sunny; Russel, Frans G M; Sauerwein, Robert W; van de Wetering, Koen; Koenderink, Jan B

    2016-02-01

    Multidrug resistance-associated proteins (MRP) of Plasmodium falciparum have been associated with altered drug sensitivity. Knowledge on MRP substrate specificity is indispensible for the characterization of resistance mechanisms and identifying its physiological roles. An untargeted metabolomics approach detected decreased folate concentrations in red blood cells infected with schizont stage parasites lacking expression of MRP1. Furthermore, a tenfold decrease in sensitivity toward the folate analog methotrexate was detected for parasites lacking MRP1. PfMRP1 is involved in the export of folate from parasites into red blood cells and is therefore a relevant factor for efficient malaria treatment through the folate pathway.

  5. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  6. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    2007-04-01

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  7. Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655.

    Science.gov (United States)

    Chandrasekar Rajendran, S C; Chamlagain, B; Kariluoto, S; Piironen, V; Saris, P E J

    2017-06-01

    Lactococcus lactis N8 and Saccharomyces boulardii SAA655 were investigated for their ability to synthesize B-vitamins (riboflavin and folate) and their functional role as microbial starters in idli fermentation. In this study, ultra-high performance liquid chromatography and microbiological assay were used to determine the total riboflavin and folate content respectively. Increased levels of folate were evident in both L. lactis N8 and S. boulardii SAA655 cultivated medium. Enhanced riboflavin levels were found only in S. boulardii SAA655 grown medium, whereas decreased riboflavin level was found in L. lactis N8 cultivated medium. To evaluate the functional role of microbial starter strains, L. lactis N8 and S. boulardii SAA655 were incorporated individually and in combination into idli batter, composed of wet grounded rice and black gram. For the experiments, naturally fermented idli batter was considered as control. The results indicated that natural idli fermentation did not enhance the riboflavin level and depleted folate levels by half. In comparison with control, L. lactis N8 and S. boulardii SAA655 incorporated idli batter (individually and in combination) increased riboflavin and folate levels by 40-90%. Apart from compensating the folate loss caused by natural fermentation, S. boulardii SAA655 fermented idli batter individually and in combination with L. lactis N8 also showed the highest leavening character. Moreover, the microbial starter incorporation did not significantly influence the pH of idli batter. Incorporation of L. lactis N8 and S. boulardii SAA655 can evidently enhance the functional and technological characteristics of idli batter. UN General Assembly declared 2016 the International Year of pulses emphasizing the importance of legumes as staple food. Furthermore, this is the first experimental report of in situ biofortifcation of riboflavin and folate using microbes in pulse based fermented staple food. The current study suggests possible

  8. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: decreased CIMT, reduced plasma lipid levels, and decreased blood pressure

    Directory of Open Access Journals (Sweden)

    Yacov Fogelman

    2016-04-01

    Full Text Available Background: Ethanolic extract of licorice root has been shown to reduce low-density lipoprotein (LDL oxidation in atherosclerotic mice and in both hypercholesterolemic and normal lipidemic humans. Objective: This study examined the effect of licorice-root extract on carotid intima-media thickness (CIMT in individuals with hypercholesterolemia. Design: Individuals with hypercholesterolemia (total cholesterol ≥6.18 mmol/L [240 mg/dL] and without significant stenosis were randomly allocated to two groups: an experimental group that consumed 0.2 g/day of ethanolic extract of licorice root for 12 months, and a control group that received a placebo. Results: Of 110 eligible participants, 94 (41–80 years old completed the study. A significant CIMT decrease from 0.92±0.25 mm to 0.84±0.21 mm was observed in the experimental group compared with an increase from 0.85±0.17 mm to 0.88±0.19 mm in the control group. Mean plasma total cholesterol levels and LDL cholesterol decreased, at the range baseline to 1 year, from 284±32 mg/dl to 262±25 mg/dl and from 183±8.5 mg/dl to 174±9.1 mg/dl, respectively, for the experimental group (p<0.001 and from 291±35 to 289±31 mg/dl and from 177.6±10.7 to 179.3±9.6 (p=0.08, respectively, for the control group. Mean high-density lipoprotein (HDL did not change significantly in either group. In the experimental group, systolic blood pressure decreased from 138±12 mmHg to 125±13 mmHg after 1 year (p=0.01 and increased from 136±15 mmHg to 137±13 mmHg in the control group. Diastolic blood pressure decreased from 92±9 mmHg to 84±10 mmHg (p=0.01 in the experimental group and increased from 89±11 mmHg to 90±8 mmHg in the control group. Conclusion: Following 1 year of licorice consumption, mean CIMT, total cholesterol, LDL levels, and blood pressure were decreased. This suggests that licorice may attenuate the development of atherosclerosis and of related cardiovascular diseases.

  9. 去冷沉淀血浆与普通血浆临床应用价值的比较%Contrast of Clinical Value between Plasma Cryoprecipitate Reduced and Ordinary Frozen Plasma

    Institute of Scientific and Technical Information of China (English)

    庄文; 陈镇奇; 林昂; 黄蓝生; 张延玮

    2009-01-01

    目的 探讨去冷沉淀血浆中部分有效成分的实际含量,为临床选择不同血浆输注提供实验室依据.方法 采集23袋(200 ml/袋)ACD-B血液保存液保存的血液,4 h内分离制备新鲜冰冻血浆,各袋均留2份标本;1份同新鲜冰冻血浆一起置-35℃保存,于第3天速融后检测总蛋白、白蛋白、纤维蛋白原、凝血因子Ⅴ、Ⅷ、Ⅹ含量;1份置4℃保存21 d后检测总蛋白、白蛋白、纤维蛋白原、凝血因子Ⅴ、Ⅷ、Ⅹ含量;新鲜冰冻血浆于第3天取出制备冷沉淀,留取去冷沉淀血浆标本1份检测总蛋白、白蛋白、纤维蛋白原、凝血因子Ⅴ、Ⅷ、Ⅹ含量.结果 去冷沉淀血浆中的血浆蛋白和凝血因子均低于普通血浆(P<0.001).结论 去冷沉淀血浆的使用价值有局限性,不能与普通血浆等同使用.%Objective To know about some of the actual amount of active ingredient in plasma cryoprecipitate reduced, so as to provide experimental evidence for different selection of plasma infusion.Method To collect 23 bags of whole blood(ACD-B,200 ml),and to separate and prepare fresh frozen plasma in 4 hours. Two samples were taken from each bag,one saved with the fresh frozen plasma in refrigerator of -35℃, thawed and checked total protein,albumin,fibrinogen, factor Ⅴ,factor Ⅷ, factor Ⅹ after3 days;the other one saved in refrigerator of 4℃, thawed and checked total protein,albumin,fibrinogen,factor Ⅴ,factor Ⅷ, factor Ⅹ after 21 days. The fresh frozen plasma separated and prepared of cryoprecipitate after 3 days,took samples of the plasma cryoprecipitate reduced to check total protein,albumin,fibrinogen,factor Ⅴ,factor Ⅷ,factor Ⅹ. Results Plasma proteins and coagulation factors in plasma cryoprecipitate reduced were lower than ordinary plasma(P<0.001). Conclusions The value of plasma cryoprecipitate reduced has limitations, can not be used equated with the ordinary plasma.

  10. Molecular mechanism of plasma sterilization in solution with the reduced pH method: importance of permeation of HOO radicals into the cell membrane

    Science.gov (United States)

    Takai, Eisuke; Ikawa, Satoshi; Kitano, Katsuhisa; Kuwabara, Junpei; Shiraki, Kentaro

    2013-07-01

    Sterilization of certain infected areas of the human body surface is necessary for dental and surgical therapies. Because the blood is filled with body fluid, sterilization in solution is essential. In vitro solution sterilization has been successively carried out using a combination of low-temperature atmospheric-pressure plasma and the reduced pH method, where the solution is sufficiently acidic. Here, we show the molecular mechanism of such plasma sterilization in solution based on microbiology. Three kinds of bacteria were inactivated by plasma treatment under various pH conditions. The theoretical and experimental models revealed that the sterilization was characterized by the concentration of hydroperoxy radicals (HOO·), which were dependent on the pH value. Bacterial inactivation rates were proportional to the HOO· concentrations calculated by the theoretical model. To evaluate the penetration of radicals into the cell membrane, a bacterial model using dye-included micelles was used. Decolouration rates of the model were also in proportion with the calculated HOO· concentrations. These results indicate that the key species for plasma sterilization were hydroperoxy radicals. More importantly, the high permeation of hydroperoxy radicals into the cell membrane plays a key role for efficient bactericidal inactivation using the reduced pH method.

  11. C-13 NMR spectroscopy of plasma reduces interference of hypertriglyceridemia in the H-1 NMR detection of malignancy; Application in patients with breast lesions

    Energy Technology Data Exchange (ETDEWEB)

    Fossell, E.T.; Hall, F.M. (Beth Israel Hospital and Harvard Medical School, Charles E. Dana Research Institute, Boston (USA). Department of Radiology); McDonagh, J. (Beth Israel Hospital and Harvard Medical School, Charles E. Dana Research Institute, Boston (USA). Department of Pathology)

    1991-05-01

    The authors have previously described the application of water-suppressed proton nuclear magnetic resonance (H-1 NMR) spectroscopy of plasma for detection of malignancy. Subsequently, hypertriglyceridemia has been identified as a source of false positive results. Here is described a confirmatory, adjunctive technique -analysis of the carbon-13 (C-13) NMR spectrum of plasma- which also identifies the presence of malignancy but is not sensitive to the plasma triglyceride level. Blinded plasma samples from 480 normal donors and 208 patients scheduled for breast biopsy were analyzed by water-suppressed H-1 and C-13 NMR spectroscopy. Triglyceride levels were also measured. Among the normal donors, there were 38 individuals with hypertriglyceridemia of whom 18 had results consistent with malignancy by H-1 NMR spectroscopy. However, the C-13 technique reduced the apparent H-1 false positive rate from 7.0 to 0.6 percent. Similarly, in the breast biopsy cohort, C-13 reduced the false positive rate from 2.8 to 0.9 percent. Furthermore, the accuracy of the combined H-1/C-13 test in this blinded study was greater than 96 percent in 208 patients studied. (author). 27 refs.; 5 figs.; 4 tabs.

  12. Development of glucose biosensors based on plasma polymerization-assisted nanocomposites of polyaniline, tin oxide, and three-dimensional reduced graphene oxide

    Science.gov (United States)

    Wu, Shide; Su, Fangfang; Dong, Xiaodong; Ma, Chuang; Pang, Long; Peng, Donglai; Wang, Minghua; He, Linghao; Zhang, Zhihong

    2017-04-01

    A biosensor based on the plasma polyaniline (pPANI)-modified tin oxide and 3D reduced graphene oxide (SnO2@3D-rGO) nanocomposite was fabricated to detect glucose. The SnO2@3D-rGO nanocomposite was synthesized by simultaneously reducing 3D graphene oxide (3D-GO) and translating SnCl4 into SnO2, followed by pPANI modification. The content of amino groups in the SnO2@3D-rGO@pPANI nanocomposites depended on the plasma input powers used in plasma deposition. The SnO2@3D-rGO nanocomposite was important in the electrochemical biosensor to detect glucose. The fabricated biosensor exhibited a much higher sensitivity than that formed from individual components, namely, SnO2@3D-rGO and pPANI. This biosensor demonstrated a low detection limit of 0.047 ng mL-1 (0.26 nM) (S/N = 3) within the concentration range of 0.1 ng mL-1 to 5 μg mL-1. The selectivity, stability, and practicality of the SnO2@3D-rGO@pPANI-based biosensor were observed. In conclusion, the plasma surface-modified nanocomposite is a promising candidate as biosensor for glucose detection and biological diagnosis.

  13. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  14. Reducing Dietary Cation-Anion Difference on Acid-Base Balance, Plasma Minerals Level and Anti-Oxidative Stress of Female Goats

    Institute of Scientific and Technical Information of China (English)

    WU Wen-xuan; YANG Yi; ZHANG Ji-kun; LI Sheng-li

    2013-01-01

    Reducing dietary cation-anion difference (DCAD) has been proved an effective way to prevent milk fever in dairy cows. Based on the similar physiological gastro-intestinal tract anatomy and metabolic process between female goats and dairy cows, this study was conducted to evaluate the effects of varying DCAD on fluid acid-base status, plasma minerals concentration and anti-oxidative stress capacity of female goats. Urinary pH, plasma Ca, P and Mg;and anti-oxidative stress indices of total superoxide dismutase (T-SOD), hydrogen peroxide (H2O2), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were determined to evaluate the effect. Forty-eight Guizhou black female goats ((15±1.9) mon of old, (22.3±3.75) kg of BW) were randomly allocated to 4 blocks of 12 goats each and were fed 1 of 4 diets differed in DCAD level (calculated as Na+K-Cl-S, mEq kg-1 DM). Levels of DCAD were preliminarily designed to be control (+150 mEq kg-1 DM, CON), high DCAD (+300 mEq kg-1 DM, HD), low DCAD (0 mEq kg-1 DM, LD) and negative DCAD (-150 mEq kg-1 DM, ND), respectively. A commercial anionic salts (Animate) and sodium bicarbonate (NaHCO3) were supplemented to reduce and increase DCAD level, respectively. There was no difference in dry matter intake for 4 groups of goats. Urine pH was aggressively decreased (P0.05) plasma Mg level. There was no significant (P>0.05) difference in plasma GSH-Px activity and H2O2, but anionic salts supplementation in LD and ND significantly increased (P<0.05) plasma T-SOD activity and tended to reduce MDA (P<0.1) over HD and CON. Results from this study indicated that reducing DCAD could decrease urine pH and increase plasma Ca concentration of female goats. Additionally, reducing DCAD was helpful to enhance anti-oxidative stress capability of female goats.

  15. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Nielsen, I. L. F.; Rasmussen, S.E.; Mortensen, Alicja;

    2005-01-01

    Anthocyanin-rich beverages have shown beneficial effects on coronary heart disease in epidemiological and intervention studies. In the present study, we investigated the effect of black currant anthocyanins on atherosclerosis. Watanabe Heritable Hyperlipidemic rabbits (n = 61) were fed either...... a purified anthocyanin fraction front black currants, a black currant juice, probucol or control diet for 16 weeks. Purified anthocyanins significantly increased plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Intake of black currant juice had no effect on total plasma cholesterol......, but lowered very-low-density lipoprotein (VLDL) cholesterol significantly. There were no significant effects of either purified anthocyanins or black currant juice on aortic cholesterol or development of atherosclerosis after 16 weeks. Probucol had no effect on plasma cholesterol but significantly lowered...

  16. Leukocyte-Reduced Platelet-Rich Plasma Alters Protein Expression of Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Loibl, Markus; Lang, Siegmund; Hanke, Alexander; Herrmann, Marietta; Huber, Michaela; Brockhoff, Gero; Klein, Silvan; Nerlich, Michael; Angele, Peter; Prantl, Lukas; Gehmert, Sebastian

    2016-08-01

    Application of platelet-rich plasma and stem cells has become important in regenerative medicine. Recent literature supports the use of platelet-rich plasma as a cell culture media supplement to stimulate proliferation of adipose tissue-derived mesenchymal stem cells. The underlying mechanism of proliferation stimulation by platelet-rich plasma has not been investigated so far. Adipose tissue-derived mesenchymal stem cells were cultured in α-minimal essential medium supplemented with platelet-rich plasma or fetal calf serum. Cell proliferation was assessed with cell cycle kinetics using flow cytometric analyses after 48 hours. Differences in proteome expression of the adipose tissue-derived mesenchymal stem cells were analyzed using a reverse-phase protein array to quantify 214 proteins. Complementary Ingenuity Pathways Analysis and gene set enrichment analysis were performed using protein data, and confirmed by Western blot analysis. A higher percentage of adipose tissue-derived mesenchymal stem cells in the S phase in the presence of platelet-rich plasma advocates the proliferation stimulation. Ingenuity Pathways Analysis and gene set enrichment analysis confirm the involvement of the selected proteins in the process of cell growth and proliferation. Ingenuity Pathways Analysis revealed a participation in the top-ranked canonical pathways PI3K/AKT, PTEN, ILK, and IGF-1. Gene set enrichment analysis identified the authors' protein set as being part of significantly regulated protein sets with the focus on cell cycle, metabolism, and the Kyoto Encyclopedia of Genes and Genomes transforming growth factor-β signaling pathway. The present study provides evidence that platelet-rich plasma stimulates proliferation and induces a unique change in the proteomic profile of adipose tissue-derived mesenchymal stem cells. The interpretation of altered expression of regulatory proteins represents a step forward toward achieving good manufacturing practice-compliant criteria

  17. Metabolic engineering of folate and its precursors in Mexican common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Ramírez Rivera, Naty G; García-Salinas, Carolina; Aragão, Francisco J L; Díaz de la Garza, Rocío Isabel

    2016-10-01

    Folate (vitamin B9) deficiency causes several health problems globally. However, folate biofortification of major staple crops is one alternative that can be used to improve vitamin intakes in populations at risk. We increased the folate levels in common bean by engineering the pteridine branch required for their biosynthesis. GTP cyclohydrolase I from Arabidopsis (AtGchI) was stably introduced into three common bean Pinto cultivars by particle bombardment. Seed-specific overexpression of AtGCHI caused significant increases of up to 150-fold in biosynthetic pteridines in the transformed lines. The pteridine boost enhanced folate levels in raw desiccated seeds by up to threefold (325 μg in a 100 g portion), which would represent 81% of the adult recommended daily allowance. Unexpectedly, the engineering also triggered a general increase in PABA levels, the other folate precursor. This was not observed in previous engineering studies and was probably caused by a feedforward mechanism that remains to be elucidated. Results from this work also show that common bean grains accumulate considerable amounts of oxidized pteridines that might represent products of folate degradation in desiccating seeds. Our study uncovers a probable different regulation of folate homoeostasis in these legume grains than that observed in other engineering works. Legumes are good sources of folates, and this work shows that they can be engineered to accumulate even greater amounts of folate that, when consumed, can improve folate status. Biofortification of common bean with folates and other micronutrients represents a promising strategy to improve the nutritional status of populations around the world. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.