Sample records for folic acid antagonists

  1. Synergistic Antimicrobial Activities of Folic Acid Antagonists and Nucleoside Analogs?

    PubMed Central

    Zander, Johannes; Besier, Silke; Ackermann, Hanns; Wichelhaus, Thomas A.

    2010-01-01

    The antimicrobial activities of folic acid antagonists are supposed to be antagonized by elevated extracellular thymidine concentrations in damaged host tissues. Therefore, this study was aimed at screening for nucleoside analogs that impair bacterial thymidine utilization and analyzing the combined antimicrobial activities of nucleoside analogs and folic acid antagonists in the presence of thymidine. Our screening results revealed that different nucleoside analogs, in particular halogenated derivatives of 2?-deoxyuridine, substantially impaired the bacterial utilization of extracellular thymidine in Staphylococcus aureus. Time-kill methods showed that 5-iodo-2?-deoxyuridine enhanced the extent of killing of trimethoprim-sulfamethoxazole (SXT) at 24 h against S. aureus in the presence of thymidine (200 ?g/liter). While SXT (40 mg/liter) alone did not kill bacteria in the presence of thymidine, its combination with the nucleoside analog at a concentration of 8 ?mol/liter showed a bactericidal effect. Moreover, 5-iodo-2?-deoxyuridine combined with SXT in the presence of thymidine showed a broad spectrum of activity against several Gram-positive and Gram-negative bacteria. In conclusion, these data provide evidence that the in vitro antimicrobial activity of SXT in the presence of thymidine can be significantly improved by combination with a nucleoside analog. PMID:20028816

  2. Neural Tube Defects in Relation to Use of Folic Acid Antagonists during Pregnancy

    Microsoft Academic Search

    Sonia Hernández-Díaz; Martha M. Werler; Alexander M. Walker; Allen A. Mitchell

    Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTDs). To determine whether periconceptional exposure to folic acid antagonists (FAAs) might therefore increase the risk of NTDs, the authors examined data from an ongoing case-control study of birth defects (1979-1998) in the United States and Canada. They compared data on 1,242 infants with NTDs (spina bifida, anencephaly, and

  3. Folic Acid

    MedlinePLUS

    ... lifelong disabilities. They may also need many surgeries. Anencephaly (an-en-SEF-uh-lee), which is when most or all of the brain does not develop. Babies with this problem die before or shortly after birth. The results of some studies suggest that folic acid might also help to prevent other types of ...

  4. Folic Acid

    MedlinePLUS Videos and Cool Tools

    ... register. I'm interested in: Pregnancy Baby growth & care Research Volunteer opportunities Advocacy in government For health ... acid During your pregnancy Your pregnant body Prenatal care Eating and nutrition Physical activity Emotional and life ...

  5. Folic acid (image)

    MedlinePLUS

    ... show that an increase in the mother's dietary folic acid before conception and during the first month of pregnancy reduces the risk of having a child with a neural tube defect. The recommendation is that women of childbearing years ...

  6. Folic Acid Recommendations Survey

    Microsoft Academic Search

    S. A. Pinkham; K. Cobb

    1999-01-01

    This study was designed to determine the current practices of women's health care providers with regard to folic acid knowledge and recommendations. Two-hundred-twenty obstetrician\\/gynecologists and certified nurse-midwives participated by completing questionnaires.A gap between the belief that folic acid reduces the risk of neural tube defects [NTDs] and the lack of widespread supplementation recommendations was revealed. Results showed that only 45%

  7. Folic acid and preconceptional care

    Microsoft Academic Search

    Nancy H Levine; Katherine Lyon Daniel; Joe Mulinare

    2001-01-01

    If all women capable of becoming pregnant consumed 400 ?g (0.4 mg) of the B vitamin folic acid daily before conception and during the first trimester, the annual number of neural-tube birth defect (NTD)–affected pregnancies in this country could be reduced by 50% to 70%. Despite this important relationship, most women are not aware that folic acid prevents NTDs, and

  8. Folic Acid Questions and Answers

    MedlinePLUS

    ... Multimedia & Tools Partners About Us Information For... Media Policy Makers Questions and Answers Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Q: Why can’t I wait until I’m pregnant—or planning to get pregnant to start taking folic acid? ...

  9. Getting folic acid nutrition right

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The two articles in this issue of the journal provide some definitive answers to questions relating to folic acid exposure and folate nutritional status of the US population in the post-fortification era, and, by implication, pose other questions. Most convincingly, these reports, which are based la...

  10. Photosensitized degradation of folic acid

    NASA Astrophysics Data System (ADS)

    Vorobei, A. V.; Vorobei, P. A.

    2011-09-01

    We demonstrate the key role of singlet oxygen in photodegradation of folic acid on exposure to UVA radiation and with photosensitizing treatment. We propose possible uses for photosensitized degradation of folates to enhance the efficacy of photodynamic therapy and for development of a high-sensitivity photochemical method for determining folates in biological systems.

  11. Is folic acid good for everyone?

    Microsoft Academic Search

    A David Smith; Young-in Kim; Helga Refsum

    ABSTRACT Fortification of food with folic acid to reduce the number,of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When forti- fication is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect preg- nancy that is prevented. Are

  12. Preconceptional folic acid supplement use in Lebanon

    Microsoft Academic Search

    H Tamim; G Harrison; M Atoui; G Mumtaz; F El-Kak; M Seoud; K Yunis

    2009-01-01

    Objective: The objective of the present study was to assess the prevalence and determinants of preconceptional folic acid supplement use among pregnant women in Lebanon. Design\\/setting\\/subjects: The study was a descriptive epidemiological study. Analysis was performed on 5280 deliveries admitted to twelve member hospitals of the National Collaborative Perinatal Neonatal Network during the period September 2003-January 2005. Information on folic

  13. Folic acid in general medicine and dermatology.

    PubMed

    Gisondi, Paolo; Fantuzzi, Francesca; Malerba, Mario; Girolomoni, Giampiero

    2007-01-01

    Folic acid is a vitamin B essential for the integrity and function of DNA. Relative deficiency of folic acid may occur in conditions such as pregnancy and hyperproliferative or chronic inflammatory disorders. Folic acid supplementation has been proven to be beneficial in the prevention of neural tube defects and in limiting methotrexate side effects, and may reduce the risk of colorectal cancer. Folate is a critical vitamin in determining plasma homocysteine levels, which in turn is a major risk factor for cardiovascular diseases. The results of large clinical trials with dietary supplementation of folic acid, vitamin B12 and vitamin B6 have shown that this homocysteine-lowering therapy is effective in the secondary prevention of non-fatal strokes, but had no effect in the prevention of fatal cardiovascular diseases. Hyperhomocysteinemia has also been reported in age-related neurological conditions with cognitive impairment (e.g. dementia), and psychiatric disorders such as depression. Elevated homocysteine levels are frequent in patients with chronic immune-mediated disorders including rheumatoid arthritis, systemic lupus erythematosus, chronic plaque psoriasis and psoriatic arthritis, which have in common a tendency to an accelerated atherosclerosis leading to increased deaths from cardiovascular events. Folic acid supplementation appears as a reasonable therapeutic option in patients affected by chronic inflammatory skin diseases, such as moderate to severe psoriasis; in particular, those with concomitant hyperhomocysteinemia, low plasma folate and additional cardiovascular risk factors. PMID:17538801

  14. Effect of folic acid on zinc absorption

    SciTech Connect

    Wada, L.; Keating, S.; King, J.C.; Stokstad, E.L.R.

    1986-03-05

    The effect of folic acid on zinc uptake was studied in the human and in the rat. The serum zinc response to a 25 mg oral dose or zinc was measured with and without a 10 mg dose of folic acid. Serum zinc levels were measured prior to the oral dose of zinc and at hourly intervals up to 4 hours after the dose. When zinc was given along, the increases in serum zinc from baseline at hours 1, 2, 3 and 4 were 92, 118, 92 and 66 ..mu..g/dl, respectively. When both zinc and folic acid were given, the increases in serum zinc at hours 1, 2, 3 and 4 were 100, 140, 110 and 75 ..mu..g/dl, respectively. When the increases in serum zinc were plotted against time, there was no significant difference between the areas under the two curves. The everted jejunal sac from the rat was used to study the effect of folate on zinc transport using 100 ..mu..M zinc in the mucosal buffer. The addition of folic acid at levels up to 10/sup -3/M had no significant effect on zinc transport to the serosal side solution or on uptake by the intestinal mucosa. This in vivo study with humans and in vitro study with rat intestine does not support a direct adverse effect of folic acid on zinc absorption.

  15. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow....

  16. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow....

  17. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow....

  18. Cost-effectiveness of periconceptional supplementation of folic acid

    Microsoft Academic Search

    M. J. Postma; J. Londeman; M. Veenstra; L. T. W. de Jong-van den Berg; H. E. K. de Walle

    2002-01-01

    Background: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns – such as spina bifida – and possibly other congenital malformations.Objective: To estimate cost effectiveness of periconceptional supplementation of folic acid using pharmaco-economic model calculation.Method: Probabilities for NTDs, risk reductions through periconceptional supplementation of folic acid and lifetime costs

  19. Original article Effects of intramuscular injections of folic acid

    E-print Network

    Paris-Sud XI, Université de

    Original article Effects of intramuscular injections of folic acid on serum folates, haematological each, were used to determine the effect of intramuscular injections of folic acid on serum folates containing 5 mg/ml folic acid, while in the other the animals were non-injected controls. The concen- tration

  20. Neural tube defects, folic acid and methylation.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J

    2013-09-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  1. Prevention of Birth Defects: Folic Acid

    Microsoft Academic Search

    Roger Williamson

    2001-01-01

    Neural tube defects (NTDs) comprise an important category contributing to infant mortality. While some NTDs may be due to identifiable inherited or specific environmental factors, most are multifactorial, with genetic and environmental factors contributing to their occurrence. Folic acid has been found to have a protective effect against the recurrence and occurrence of NTDs. In addition to natural dietary sources,

  2. Should folic acid fortification be mandatory? Yes

    Microsoft Academic Search

    Nicholas J Wald; Godfrey P Oakley

    2007-01-01

    The UK's Food Standards Agency recently recommended mandatory folic acid fortification of some foods. Nicholas Wald and Godfrey Oakley argue that it's a safe effective way of preventing spina bifida and anencephaly—but Richard Hubner and colleagues say that more research into the harms is needed

  3. Should folic acid fortification be mandatory? No

    Microsoft Academic Search

    Richard A Hubner; Richard D Houlston; Kenneth R Muir

    2007-01-01

    The UK's Food Standards Agency recently recommended mandatory folic acid fortification of some foods. Nicholas Wald and Godfrey Oakley argue that it's a safe effective way of preventing spina bifida and anencephaly—but Richard Hubner and colleagues say that more research into the harms is needed

  4. Folic acid and hexose absorption in sprue

    Microsoft Academic Search

    C. D. Gerson; N. Cohen; N. Brown; J. Lindenbaum; G. W. Hepner; H. D. Janowitz

    1974-01-01

    Using an intestinal perfusion technique, folic acid (PGA) and hexose absorption were studied in 9 patients with sprue. Folate malabsorption was only demonstrable during perfusion with glucose or galactose and saline, not with saline alone. Hexose absorption was diminished. The stimulation by sugar of PGA, water, and sodium transport, as seen in controls, was absent. 2 patients with untreated tropical

  5. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  6. Neural tube defects : Prevention by folic acid and other vitamins

    Microsoft Academic Search

    Andrew J. Copp; Nicholas D. E. Greene

    2000-01-01

    Folic acid has been demonstrated in clinical trials to reduce significantly the recurrence (and probably occurrence) of neural\\u000a tube defects (NTD). In the U.K., there has been no decline in prevalence of NTD since the publication of the findings with\\u000a folic acid. This article examines a series of questions relating to the action of folic acid, with emphasis on the

  7. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1295 Folic acid test system. (a)...

  8. Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: The Folic Acid Clinical Trial Study

    PubMed Central

    Champagne, Josee; Rennicks White, Ruth; Coyle, Doug; Fraser, William; Smith, Graeme; Fergusson, Dean; Walker, Mark C.

    2013-01-01

    Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 80/7 and 166/7 weeks of gestation are randomized in a 1?:?1 ratio to folic acid 4.0?mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159. PMID:24349782

  9. Fluorescence spectroscopic behaviour of folic acid

    NASA Astrophysics Data System (ADS)

    Tyagi, A.; Penzkofer, A.

    2010-02-01

    The fluorescence spectroscopic behaviour of folic acid (FA) in 4 M HCl (dominant bi-cationic form), 0.1 M HCl (bi-cationic and cationic form), citric acid-NaOH pH 6 buffer (neutral form), 0.1 M and 4 M KOH (anionic form), and trifluoroacetic acid is studied. The thermal stability is investigated. Absolute absorption cross-section spectra are determined and compared with fluorescence excitation spectra. Intrinsic fluorescence quantum distributions and fluorescence quantum yields are extracted from fluorescence spectra measurements. The temporal fluorescence decay after picosecond pulse excitation is studied. The fluorescence quenching mechanisms for the different ionic forms of FA are discussed: excited-state proton release for bi-cationic FA, photo-physical non-radiative relaxation for cationic FA, and photo-induced intra-molecular electron transfer for neutral and anionic FA. Aerobic FA in 4 M KOH at elevated temperature dehydrated to 9,10-dehydro-folic acid. Its photo-dynamics was governed by twisted intra-molecular charge transfer and photo-isomerisation.

  10. Folic Acid Consumption in Fars Province, Southern Iran

    Microsoft Academic Search

    Massumi SJ; Shenavar R. MSc

    Background: Spina bifida and anencephaly are among serious and fatal anomalies in infants that may lead to a 50-70% of reduction in incidence when folic acid is consumed before conception. Methods: In a cross sectional study, 2997 pregnant women were evaluated to determine the level of their knowledge and practice about using folic acid in Fars Province, southern Iran. Results:

  11. Chemiluminescence inhibition assay for folic acid using flow injection analysis.

    PubMed

    Song, Zhenghua; Wang, Lin

    2003-01-01

    A new flow injection method for the determination of folic acid is described. A fast oxidation reaction occurred when folic acid was mixed with potassium ferricyanide generating ferrocyanide which then inhibited the chemiluminescent reaction of ferricyanide and luminol in alkaline medium. The decrease of chemiluminescence intensity was correlated with the folic acid concentration in the range 0.1-21 microg/mL; the detection limit for the assay was 0.03 microg/mL (3sigma). A complete analysis of folic acid, including sampling and washing, could be performed within 2 min with a relative standard deviation of less than 4.0%. The proposed method has been applied successfully to the determination of folic acid in pharmaceutical preparations. PMID:12892416

  12. Avidity Mechanism of Dendrimer–Folic Acid Conjugates

    PubMed Central

    2015-01-01

    Multivalent conjugation of folic acid has been employed to target cells overexpressing folate receptors. Such polymer conjugates have been previously demonstrated to have high avidity to folate binding protein. However, the lack of a monovalent folic acid–polymer material has prevented a full binding analysis of these conjugates, as multivalent binding mechanisms and polymer-mass mechanisms are convoluted in samples with broad distributions of folic acid-to-dendrimer ratios. In this work, the synthesis of a monovalent folic acid–dendrimer conjugate allowed the elucidation of the mechanism for increased binding between the folic acid–polymer conjugate and a folate binding protein surface. The increased avidity is due to a folate-keyed interaction between the dendrimer and protein surfaces that fits into the general framework of slow-onset, tight-binding mechanisms of ligand/protein interactions. PMID:24725205

  13. Promotora de Salud: Promoting Folic Acid Use Among Hispanic Women

    PubMed Central

    deRosset, Leslie; Mullenix, Amy; Flores, Alina; Mattia-Dewey, Daniel; Mai, Cara T.

    2015-01-01

    Background The U.S. Public Health Service recommends that all women in the United States capable of becoming pregnant consume 400 ?g of folic acid daily to reduce their risk of having a pregnancy affected by a neural tube defect (NTD). However, disparities exist in the consumption of folic acid, with Hispanic women having lower rates of folic acid consumption than non-Hispanic white women. Methods A community-based feasibility study was designed to assess the utility of the promotora de salud model to promote consumption of multivitamins containing folic acid for the prevention of NTDs among Spanish-speaking Hispanic women in North Carolina. The study consisted of an educational intervention given by a promotora (a lay, community health worker), with data collection occurring at baseline and four months post-intervention to measure changes in knowledge and behavior. Overall, 52% (n = 303) of participants completed all components of the study. Results Self-reported daily multivitamin consumption increased from 24% at baseline to 71% four months post-intervention. During the same time frame, awareness of folic acid increased from 78% to 98% and knowledge of the role of folic acid in the prevention of birth defects increased from 82% to 92%. Conclusions The results of this study indicate that the promotora de salud model may be effective in reaching a subpopulation of women with the folic acid message. Additional studies with larger population sizes are warranted to validate these findings. PMID:24707879

  14. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1295 Folic acid test system. (a) Identification....

  15. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

    Microsoft Academic Search

    Kam S Woo; Ping Chook; Yvette I Lolin; John E Sanderson; Con Metreweli; David S Celermajer

    1999-01-01

    OBJECTIVESTo evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.BACKGROUNDHyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.METHODSAdults subjects were recruited from a community-based atherosclerosis

  16. Folic acid for the prevention of congenital anomalies

    Microsoft Academic Search

    J. Hall; F. Solehdin

    1998-01-01

    Paediatricians need to be aware of the broad implications that sufficient maternal folic acid intake has on the wellbeing\\u000a of the embryo and fetus. There is now strong evidence that adequate periconceptional maternal folic acid supplementation during\\u000a critical periods of organ formation is associated with reduction in both the occurrence and recurrence of neural tube defects,\\u000a congenital heart defects (particularly

  17. Chemiluminescence flow sensor for folic acid with immobilized reagents.

    PubMed

    Song, Z; Zhou, X

    2001-11-01

    A novel chemiluminescence (CL) sensor for folic acid combined flow-injection (FI) technology was presented in this paper. The analytical reagents involved in the CL reaction, including luminol and hexacyanoferrate(III), were both immobilized on an anion-exchange column in FI system. The CL signal produced by the reaction between luminol and hexacyanoferrate(III), which were eluted from the column through sodium phosphate injection, was decreased in the presence of folic acid. The CL emission was correlated with the folic acid concentration in the range from 0.01 to 15 microg ml(-1), and the detection limit was 3.5 ng ml(-1) folic acid (3sigma). At a flow rate of 2.0 ml min(-1), including sampling and washing, could be performed in 2 min with a relative standard deviation of < 2.5%. The flow sensor could be reused more than 300 times and has been applied to the analysis of folic acid in pharmaceutical preparations. and the recovery was from 97.4% to 100.4%. PMID:11765783

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

    PubMed Central

    Tam, Carolyn; O'Connor, Deborah; Koren, Gideon

    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 biomarkers. The proportion of women with detectable levels of unmetabolized folic acid increased from 65% to 100% after twelve weeks of supplementation (P < 0.05); however, the increase in concentrations did not reach statistical significance and the effect was not sustained. Moreover, there were no significant differences between the two doses. This suggests that there are mechanisms by which the body adapts to high folic acid intakes to limit exposure to unmetabolized folic acid. PMID:22529856

  19. Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age

    Microsoft Academic Search

    Timothy J Green; C Murray Skeaff; Jennifer EP; Bernard J Venn

    2005-01-01

    Daily consumption of 400 µg folic acid prior to conception and during early pregnancy is recommended for the prevention of neural tube defects (NTD). Strategies to increase folic acid consumption include supplements and fortified foods. Milk is consumed by women and can be fortified with folic acid but little is known about the effect of fortified milk on blood folate

  20. Survival of Infants With Neural Tube Defects in the Presence of Folic Acid Fortification

    Microsoft Academic Search

    Kirk A. Bol; Julianne S. Collins; Russell S. Kirby

    2010-01-01

    OBJECTIVE.Neural tube defects (NTDs) are preventable through preconceptional and periconceptional folic acid intake. Although decreases in the prevalence of NTDs have been reported since folic acid fortification of United States grain products began, it is not known whether folic acid plays a role in reducing the severity of occurring NTDs. Our aim was to determine whether survival among infants born

  1. Efficacy of Flour Fortification with Folic Acid in Women of Childbearing Age in Iran

    Microsoft Academic Search

    Z. Abdollahi; I. Elmadfa; A. Djazayery; M. J. Golalipour; J. Sadighi; F. Salehi; S. Sadeghian Sharif

    2011-01-01

    Background: Flour fortification with folic acid is one of the main strategies for improving folate status in women of childbearing age. No interventional trial on the efficacy of folic acid fortification has been conducted so far in Iran. Objectives: To study the effects of flour fortification with folic acid on any reduction in neural tube defects (NTDs) and folate status

  2. Will mandatory folic acid fortification prevent or promote cancer?1-3

    Microsoft Academic Search

    Young-In Kim

    An overwhelming body of evidence for a protective effect of periconceptional folic acid supplementation against neural tube de- fects (NTDs) led to mandatory folic acid fortification in the United States. The effectiveness of folic acid fortification in improving folate status has already been shown to be quite striking, with a dramatic increase in blood measurements of folate in the United

  3. Benefits and risks of folic acid to the nervous system

    PubMed Central

    Reynolds, E

    2002-01-01

    During three decades of neurological practice I have witnessed a remarkable change in attitudes to the benefits and risks of folic acid therapy in nervous system disorders. In the 1960s all that was known and taught was that folic acid was harmful to the nervous system, especially in precipitating or exacerbating the neurological complications of vitamin B12 deficiency. So deeply held was this view that the possibility of neuropsychological benefits from this vitamin was initially viewed with considerable scepticism.1 PMID:11971038

  4. Efficacy of adding folic acid to foods.

    PubMed

    Fajardo, Violeta; Varela-Moreiras, Gregorio

    2012-06-01

    In the past, food fortification along with nutritional education and the decrease in food costs relative to income have proven successful in eliminating common nutritional deficiencies. These deficiencies such as goiter, rickets, beriberi, and pellagra have been replaced with an entirely new set of "emergent deficiencies" that were not previously considered a problem [e.g., folate and neural tube defects (NTDs)]. In addition, the different nutrition surveys in so-called affluent countries have identified "shortfalls" of nutrients specific to various age groups and/or physiological status. Complex, multiple-etiology diseases, such as atherosclerosis, diabetes, cancer, and obesity have emerged. Food fortification has proven an effective tool for tackling nutritional deficiencies in populations; but today a more reasonable approach is to use food fortification as a means to support but not replace dietary improvement strategies (i. e. nutritional education campaigns). Folic acid (FA) is a potential relevant factor in the prevention of a number of pathologies. The evidence linking FA to NTD prevention led to the introduction of public health strategies to increase folate intakes: pharmacological supplementation, mandatory or voluntary fortification of staple foods with FA, and the advice to increase the intake of folate-rich foods. It is quite contradictory to observe that, regardless of these findings, there is only limited information on food folate and FA content. Data in Food Composition Tables and Databases are scarce or incomplete. Fortification of staple foods with FA has added difficulty to this task. Globally, the decision to fortify products is left up to individual food manufacturers. Voluntary fortification is a common practice in many countries. Therefore, the "worldwide map of vitamin fortification" may be analyzed. It is important to examine if fortification today really answers to vitamin requirements at different ages and/or physiological states. The real impact of vitamin fortification on some key biomarkers is also discussed. An important question also to be addressed: how much is too much? It is becoming more evident that chronic excessive intakes may be harmful and a wide margin of safety seems to be a mandatory practice in dietary recommendations. Finally, the "risk/benefit" dilemma is also considered in the "new" FA-fortified world. PMID:23258398

  5. Predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001-20041-3

    Microsoft Academic Search

    Heather C Hamner; Joseph Mulinare; Mary E Cogswell; Alina L Flores; Coleen A Boyle; Christine E Prue; Chia-Yih Wang; Alicia L Carriquiry; Owen Devine

    Background: Folic acid can prevent up to 70% of neural tube defects (NTDs) if taken before pregnancy. Compared with other race-ethnicities, Hispanic women have higher rates of NTDs, lower rates of folic acid supplement use, and lower total folic acid intakes. Objective: The objective was to assess potential effects of fortify- ing corn masa flour with folic acid on Mexican

  6. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

    Microsoft Academic Search

    Xiaobin Wang; Xianhui Qin; Hakan Demirtas; Jianping Li; Guangyun Mao; Yong Huo; Ningling Sun; Lisheng Liu; Xiping Xu

    2007-01-01

    METHODS: We collected data from eight randomized trials of folic acid that had stroke reported as one of the endpoints. Relative risk (RR) was used as a measure of the effect of folic acid supplementation on the risk of stroke with a random effect model. The analysis was further stratified by factors that could affect the treatment effects. FINDINGS: Folic

  7. Folate during reproduction: the Canadian experience with folic acid fortification

    Microsoft Academic Search

    Gillian Lindzon; Deborah L. O'Connor

    2007-01-01

    Folate has received international attention regarding its role in the risk-reduction of birth defects, specifically neural tube defects (NTDs). In 1998, health officials in Canada, like the United States, mandated the addition of folic acid to white flour and select grain products to increase the folate intake of reproductive-aged women. Subsequent to this initiative there has been an increase in

  8. Economic evaluation of folic acid food fortification in The Netherlands

    Microsoft Academic Search

    Janneke Jentink; Nienke W. van de Vrie-Hoekstra; Lolkje T. W. de Jong-van den Berg; Maarten J. Postma

    2008-01-01

    NTD at birth, life-time costs of care, and folic acid fortification costs were estimated using Dutch registrations, Dutch guidelines for costing, (inter)national literature and expert opinions. Both net cost per discounted life year gained and net cost per discounted quality adjusted life year (QALY) gained were estimated for the base case and sensitivity analyses. Results: In the base case and

  9. Physicians' Knowledge of Alcohol, Tobacco and Folic Acid in Pregnancy

    ERIC Educational Resources Information Center

    Lefebvre, L. G.; Ordean, A.; Midmer, D.; Kahan, M.; Tolomiczenko, G.

    2007-01-01

    Objective: To assess: (1) physicians' knowledge and clinical confidence regarding problematic substance use in pregnancy compared to folic acid, and (2) physicians' desire for education in this area and their preferred learning modalities tools. Design: Self-administered survey. Setting: "Family Medicine Forum 2004" in Toronto, Canada.…

  10. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy.

    PubMed

    Zhen, Zipeng; Tang, Wei; Zhang, Weizhong; Xie, Jin

    2015-06-01

    We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis. PMID:25998995

  11. Studies on the folic acid activity of human serum

    Microsoft Academic Search

    A. H. Waters; D. L. Mollin; Josephine Pope; Thurl Towler

    1961-01-01

    A method for the measurement of serum folic acid activity is described, which is a modification of previous methods.The material in serum with activity for L. casei is made up of a stable and a labile component. The amount of stable component in normal subjects and patients with megaloblastic anaemia is similar. The amount of labile component varies. In patients

  12. Folic acid deficiency and cancer: mechanisms of DNA instability

    Microsoft Academic Search

    Susan J. Duthie

    1999-01-01

    Folic acid deficiency in humans has been linked with megaloblastic anaemia, neural tube defects in the neonate, and heart disease. Folate has also been implicated in the development of cancer, especially cancer of the colorectum. There appear to be two principal mechanisms through which low folate status may increase the risk of malignancy. Folate deficiency, by reducing intracellular S-adenosylmethionine (SAM),

  13. Role of Folic Acid on Symptoms of Chronic Arsenic Toxicity

    PubMed Central

    Ghose, Nelima; Majumdar, Kunal Kanti; Ghose, A. K.; Saha, C. K.; Nandy, A. K.; Mazumder, D. N. Guha

    2014-01-01

    Background: Chronic arsenic toxicity (Arsenicosis) due to drinking of arsenic contaminated ground water is a global problem. However, its treatment is unsatisfactory. Methylation of arsenic facilitates its urinary excretion. Persons with relatively lower proportion of urinary dimethyl arsenic acid (DMA) are found to have at greater risk of developing symptoms of arsenicosis including its complications. The biochemical pathway responsible for methylation of arsenic is a folate-dependent pathway. Studies in rodents and humans suggest that folate nutritional status influences the metabolism of arsenic. Methods: The present study compares the effect of giving folic acid on 32 arsenicosis patients during a 6-month period and comparing the results with clinical effect of taking only arsenic-free safe water on 45 age and sex-matched arsenic-affected people for the same period. Results: There was significant improvement of arsenical skin lesion score of both patients treated with folic acid (2.96 ± 1.46 to 1.90 ± 0.90, P < 0.001) and arsenic free safe water (2.91 ± 1.26 to 1.62 ± 1.05, P < 0.001) for a period of 6 months. Significant improvement in systemic disease score was also observed from the baseline systemic score in folic acid treated group (4.78 ± 3.43 to 1.00 ± 1.56, P < 0.001) and the group treated with arsenic-free water (1.87 ± 2.11 to 0.82 ± 1.62, P < 0.001). However, there was a significant increased improvement of systematic disease score in the folic acid treated group compared to the control group taking arsenic free water (P < 0.001). Conclusions: This study provides evidence that folic acid treatment in arsenicosis cases could help in reducing clinical symptoms of arsenicosis. PMID:24554997

  14. Knowledge of periconceptional folic acid use among pregnant women at Ain Shams University Hospital, Cairo, Egypt.

    PubMed

    Al-Darzi, W; Al-Mudares, F; Farah, A; Ali, A; Marzouk, D

    2014-09-01

    Egypt has a high incidence of neural tube defects. Folic acid supplementation in the periconceptional period is known to lower the risk of such defects. This cross-sectional study aimed to measure the level of knowledge about periconceptional folic acid use among pregnant women attending for antenatal care at Ain Shams University Hospital, Cairo, Egypt in 2012. Questionnaires were filled through personal interviews with 660 pregnant women. Of the respondents, 62.4% had heard of folic acid and 39.2% knew about the role of folic acid supplementation in prevention of congenital anomalies. Knowledge about using folic acid before and in the first trimester of pregnancy was highest among university-educated women and those working in professional occupations. Only 18.8% of women reported taking folic acid, and 8.8% had used it before conception. Awareness campaigns are suggested to improve knowledge about folic acid among women in the childbearing period in Egypt. PMID:25343469

  15. Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels

    Microsoft Academic Search

    David S. Wald; Lucy Bishop; Nicholas J. Wald; Malcolm Law; Enid Hennessy; Donald Weir; Joe McPartlin; John Scott

    2001-01-01

    Methods: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg\\/d) or placebo. Fasting blood samples for serum ho- mocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after fo- lic acid use was discontinued. Results: Median serum homocysteine level

  16. Synthesis of an indole analog of folic acid

    SciTech Connect

    Shengeliya, M.S.; Avramenko, V.G.; Kuleshova, L.N.; Ershova, Yu.A.; Chernov, V.A.; Surorov, N.N.

    1987-06-01

    The authors study the replacement of the p-aminobenzoic acid (PABA) moiety. The authors synthesized an indole analog of folic acid, namely dimethyl N-(5-(2'-amino-4'-oxo-6'-pteridinyl)methylaminoindol-2-yl)glutamate. The physicochemical properties and the chemical shifts in the PMR spectra of the compounds obtained are shown. The examination of the compound for antitumor activity was carried out using rats and mice.

  17. Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda

    PubMed Central

    Bannink, Femke; Larok, Rita; Kirabira, Peter; Bauwens, Lieven; van Hove, Geert

    2015-01-01

    Introduction The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Methods Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. Results 1/4 mothers of children with spina bifida took folic acid during late pregnancy, none preconception. None had knowledge about folic acid and spina bifida prevention. 33.5% of women attending ANC had ever heard about spina bifida, 1% knew folic acid intake can prevent spina bifida. 42.4% took folic acid supplements in late pregnancy, 8.1% during the first trimester, none preconception. All women said to have eaten food rich in folic acid. None were aware about fortified foods. 7% of health workers understood the importance of early folic acid intake. All health workers recommended folic acid intake to women attending ANC. 20% of the health workers and 25% of the women said folic acid supplements are not always available. Conclusion Folic acid intake is limited in northern Uganda. This is attributed to limited education and understanding of women and health workers about the importance of early folic acid intake, late presentation of women at ANC, poor supply chain and dilapidated health services caused by war and poverty. A combination of food fortification, sensitization of health workers, women, and improving folic acid supply is recommended.

  18. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements.

    PubMed

    Kelly, P; McPartlin, J; Goggins, M; Weir, D G; Scott, J M

    1997-06-01

    Periconceptual consumption of folic acid has been shown to decrease the incidence of neural tube defects. The strategy of universal fortification of staple foodstuffs with folic acid presents the possibility of life-long exposure to unmetabolized folic acid. Chief among the risks of exposure to folic acid in the circulation is that of masking the diagnosis of cobalamin deficiency in pernicious anemia and the progression of neurologic disease. Other effects are unknown. For instance, the effect of in vivo chronic exposure of adult and fetal cells to the synthetic form of the vitamin has never been investigated at the population level. This study examined the acute appearance of unmetabolized folic acid in serum in response to the consumption of some fortified foodstuffs by young and elderly volunteers. Subjects on a 5-d regimen of fortified ready-to-eat-cereal and bread in addition to their normal diet had a threshold intake of 266 micrograms folic acid per meal at which unaltered folic acid appeared in the serum. Subjects given folic acid in either isotonic saline, milk, or white bread also had a threshold > 200 micrograms. From patterns of food consumption in the United States, the implementation of flour fortification at 1.4 mg/kg is unlikely to lead to folic acid appearance in serum, assuming that consumption is spread throughout the day. Increasing this level of fortification, however, as has been advocated by some agencies, may result in the repeated appearance of folic acid in serum over many years, particularly in consumers in nontargeted populations of large amounts of fortified foods. The "safe level of intake" of 1 mg folate/d set by the US Food and Drug Administration may cause a serum folic acid effect. Furthermore, a repeated serum folic acid response is likely to be found in many women complying with the advice to take 400 micrograms folic acid/d to prevent the occurrence of neural tube defects. PMID:9174474

  19. Folic acid supplementation promotes mammary tumor progression in a rat model.

    PubMed

    Deghan Manshadi, Shaidah; Ishiguro, Lisa; Sohn, Kyoung-Jin; Medline, Alan; Renlund, Richard; Croxford, Ruth; Kim, Young-In

    2014-01-01

    Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression of established mammary tumors. The potential tumor-promoting effect of folic acid supplementation in breast cancer patients and survivors needs further clarification. PMID:24465421

  20. Carbamazepine and folic acid in trigeminal neuralgia patients.

    PubMed Central

    al-Musaed, A A; Zakrzewska, J M; Bain, B J

    1992-01-01

    The effect of carbamazepine monotherapy on the red cell folate level of 133 patients with trigeminal neuralgia was evaluated. The patient group had a significantly lower mean value of red cell folate levels compared with 110 controls. No significant correlation was found between the red cell folate levels and the mean cell volume or haemoglobin values in either the carbamazepine or control group. In addition no significant correlation was found between the red cell folate levels and drug dosage. Administration of folic acid supplements raised the mean value of red cell folate significantly. Dietary folate intake was assessed in 43 trigeminal neuralgia patients and 33 matched control patients and there was no significant difference between the groups. Patients taking carbamazepine should be advised on a well-balanced diet rich in folate as opposed to being given a routine prescription of folic acid. PMID:1548649

  1. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhen, Zipeng; Tang, Wei; Zhang, Weizhong; Xie, Jin

    2015-06-01

    We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis.We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis. Electronic supplementary information (ESI) available: Details of experiments and ex vivo imaging results. See DOI: 10.1039/c5nr01833a

  2. Study of wheat breakfast rolls fortified with folic acid

    Microsoft Academic Search

    Madelene Johansson; Cornelia M. Witthöft; Åke Bruce; Margaretha Jägerstad

    2002-01-01

    Summary.   Background: Folate has come into focus due to its protective role against child birth defects such as neural tube defects (NTD). Swedish\\u000a authorities recommend all fertile women to increase their folate intake to 400 ?g\\/day by eating folate-rich foods. Because\\u000a not all women follow these recommendations, there is a discussion today about whether Sweden should introduce folic acid fortification

  3. Progesterone Inhibits Folic Acid Transport in Human Trophoblasts

    Microsoft Academic Search

    Elisa Keating; Pedro Gonçalves; Clara Lemos; Fernanda Costa; Isabel Campos; Sylvia B. Smith; Christy C. Bridges; Fátima Martel

    2007-01-01

    The aim of this work was to test the putative involvement of members of the ABC superfamily of transporters on folic acid\\u000a (FA) cellular homeostasis in the human placenta. [3H]FA uptake and efflux in BeWo cells were unaffected or hardly affected by multidrug resistance 1 (MDR1) inhibition (with\\u000a verapamil), multidrug resistance protein (MRP) inhibition (with probenecid) or breast cancer resistance

  4. Determination of folic acid by capillary electrophoresis with chemiluminescence detection

    Microsoft Academic Search

    Shulin Zhao; Hongyan Yuan; Chao Xie; Dan Xiao

    2006-01-01

    A rapid and simple method is presented for the determination of folic acid (FA) by capillary electrophoresis (CE) with chemiluminescence (CL) detection. This method was based on enhance effect of FA on the CL reaction between luminol and BrO? in alkaline aqueous solution. Optimal separation and determination was obtained with an electrophoretic buffer of 35mM sodium borate (pH 9.4) containing

  5. Folic Acid Reverts Dysfunction of Endothelial Nitric Oxide Synthase

    Microsoft Academic Search

    E. S. G. Stroes; E. E. van Faassen; M. Yo; P. Martasek; P. Boer; R. Govers; T. J. Rabelink

    Methyltetrahydrofolate (MTHF), the active form of folic acid, has been reported to restore NO status in hypercholesterolemic patients. The mechanism of this effect remains to be established. We assessed the effects of L- and D-MTHF on tetrahydrobiopterin (BH4)-free and partially BH4-repleted endothelial NO synthase (eNOS). Superoxide production of eNOS and the rate constants for trapping of superoxide by MTHF were

  6. Economic burden of neural tube defects and impact of prevention with folic acid: a literature review

    Microsoft Academic Search

    Yunni Yi; Marion Lindemann; Antje Colligs; Claire Snowball

    Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to\\u000a reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of\\u000a folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most

  7. Prevention of Neural-Tube Defects with Periconceptional Folic Acid, Methylfolate, or Multivitamins?

    Microsoft Academic Search

    Andrew E. Czeizel; István Dudás; László Paput; Ferenc Bánhidy

    2011-01-01

    Background\\/Aims: To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD). Methods and Results: The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in

  8. Global Prevention of All Folic Acid-Preventable Spina bifida and Anencephaly by 2010

    Microsoft Academic Search

    2002-01-01

    Folic acid-preventable spina bifida and anencephaly are pandemic, affecting 225,000 children a year. These birth defects are as preventable as polio. As we near the eradication of polio, it is time to make the commitment to global prevention of all folic acid-preventable spina bifida and anencephaly (FA-P SBA) by 2010. Folic acid fortification of centrally processed foods, such as wheat

  9. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally

    Microsoft Academic Search

    G. M Shaw; C. R Wasserman; C. D O'Malley; M. M Tolarova; E. J Lammer

    1995-01-01

    SummaryWomen are advised to take folic acid before they conceive as a precaution against neural-tube defects. However, the use of folic acid in preventing orofacial clefts is unknown. We investigated whether a woman's periconceptional use of multivitamins containing folic acid was associated with a reduced risk of orofacial clefts.We derived data from a population-based case-control study of fetuses and liveborn

  10. Factors contributing to the success of folic acid public health campaigns

    PubMed Central

    Rofail, D.; Colligs, A.; Abetz, L.; Lindemann, M.; Maguire, L.

    2012-01-01

    Background Studies in the 1990s have found that periconceptional dietary folate, supplementation of folic acid or supplemental multivitamins containing folic acid, help prevent neural tube defect (NTDs) if taken at the right time. This literature review assesses the extant folic acid public health campaigns literature and identifies some common variables used in folic acid consumption campaign evaluations. Methods This review was part of a larger study that searched PUBMED, PsycINFO and Embase from 1976 to 2010 to identify articles related to the psychosocial and economic impact of NTDs (especially spina bifida) on patients and caregivers. Results Awareness of folic acid levels prior to conception improved post-campaign from 6 to 41%. Knowledge about consumption and correct periconceptional use of folic acid also improved. However, in most studies more than 50% of women did not take folic acid as prescribed. Many factors were associated with or without taking folic acid post-campaign, including incomplete outreach, prior awareness and knowledge, closeness to pregnancy, demographics and other personal characteristics. Conclusions Sustained campaigning to maintain awareness about and promote periconceptional consumption of folic acid in order to reduce the incidence of NTDs is clearly needed. Additional initiatives could complement existing public health strategies. PMID:21727078

  11. Synthesis and luminescence of a folic acid-europium chelate conjugate

    NASA Astrophysics Data System (ADS)

    Pavich, T. A.; Vorobey, A. V.; Arabei, S. M.; Solovyov, K. N.

    2012-09-01

    We have synthesized a folic acid-europium complex conjugate which shows promise for biomedical applications. We have studied the absorption spectra, the luminescence spectra, and the luminescence excitation spectra of folic acid-spacer-amino-substituted phenanthroline and folic acid-spacer-europium chelate conjugates, and also of the individual components of the synthesized triads. All the spectral luminescence data obtained confirm that a folic acid-europium complex conjugate is fogrmed. Binding of the synthesized conjugate to a folate receptor on HeLa tumor cells is demonstrated.

  12. Evaluation of Educational Materials from a Social Marketing Campaign to Promote Folic Acid Use Among Hispanic Women: Insight from Cuban and Puerto Rican Ethnic Subgroups

    Microsoft Academic Search

    Gwendolyn P. Quinn; Kamilah B. Thomas; Kimberlea Hauser; Nydia Y. Rodríguez; Nazach Rodriguez-Snapp

    2009-01-01

    Current data indicate significant disparities in awareness and use of folic acid between Hispanic and non-Hispanic women.\\u000a Hispanic women are less likely to have heard about folic acid, to know that folic acid can prevent birth defects, to take\\u000a folic acid daily, and to take folic acid before pregnancy. “Three Sisters\\/Las Tres Hermanos” is a folic acid social marketing\\u000a campaign

  13. Ten years after the Dutch public health campaign on folic acid: the continuing challenge

    Microsoft Academic Search

    Hermien E. K. de Walle; Lolkje T. W. de Jong-van den Berg

    2008-01-01

    Background  Folic acid use in the periconceptional period reduces the risk of neural tube defects (NTDs). However, applying this knowledge\\u000a in daily practice is not an easy task. We report here the current level of folic acid use in the Netherlands and discuss the\\u000a figures within the framework of a national governmental campaign held in 1995 promoting the use of folic

  14. [Photobiochemistry of folates: a photochemical reduction of folic acid].

    PubMed

    Vechtomova, Iu L; Telegina, T A; Kolesnikov, M P; Kritski?, M S

    2010-01-01

    Exposure of deaerated folic acid solutions containing an electron donor to UV radiation (310-390 nm, I = 0.4 W m(-2)) induced formation of dihydrofolic acid (DHFA), a photoexcitation which gave tetrahydrofolic acid (THFA). Only DHFA was formed in the presence of EDTA (E'o = +0.40 V), while the presence of stronger reductants-NADH (E'o = -0.32 V) and boron hydride (E'o = -0.48 V)-induced photoreduction to THFA. It was demonstrated that UV radiation had no effect on the THFA formylation, giving the coenzyme 5,10-methenyltetrahydrofolic acid and its transformation into another coenzyme, 5-formyltetrahydrofolic acid. PMID:20586292

  15. Awareness and Use of Folic Acid among Women in the Lower Mississippi Delta

    ERIC Educational Resources Information Center

    Robbins, James M.; Hopkins, Sarah E.; Mosley, Bridget S.; Casey, Patrick H.; Cleves, Mario A.; Hobbs, Charlotte A.

    2006-01-01

    Context: National and state efforts to increase folic acid awareness and use may not be reaching large segments of the population. Purpose: This study examines folic acid awareness and use among women of childbearing age in a representative, economically at-risk rural sample and identifies factors that influence awareness and use. Methods: A…

  16. A Collaborative Effort to Reduce Ntd's: Indiana's Statewide Folic Acid Awareness Caimpaign

    Microsoft Academic Search

    TD Van Meter; CA Friesen

    1999-01-01

    The Indiana State Department of Health (ISDH) is sponsoring a Folic Acid Awareness Campaign. The goal of this collaborative campaign (Children's Special Health Care Services, Maternal and Child Health Services, and WIC) is to decrease the incidence of neural tube defects using a statewide educational campaign promoting adequate folic acid consumption preconception and during the first trimester of pregnancy. The

  17. Incidence of open neural tube defects in Nova Scotia after folic acid fortification

    Microsoft Academic Search

    Vidia L. Persad; Michiel C. Van den Hof; Johanne M. Dubé; Pamela Zimmer

    2002-01-01

    Background: With the goal of preventing open neural tube defects (NTDs), recom- mendations for folic acid supplementation before conception were introduced in Canada in 1994, and by November 1998 Canadian grain products were being fortified with folic acid. We wished to determine whether the annual incidence of open NTDs in Nova Scotia, including those in stillbirths and terminated preg- nancies,

  18. Awareness of the use of folic acid to prevent neural tube defects in a Mediterranean area

    Microsoft Academic Search

    Oriol Coll; Sonia Pisa; Montserrat Palacio; Llorenç Quintó; Vicenç Cararach

    2004-01-01

    Objectives: The risk of neural tube defects (NTDs) is decreased in women who take folic acid during the periconceptional period. The main objective of our study was to evaluate the awareness of the need for folic acid supplementation and also the actual intake during the periconceptional period to prevent neural tube defects in a Mediterranean area. Study design: A retrospective

  19. Folic Acid Fortification and Supplementation—Good for Some but Not So Good for Others

    Microsoft Academic Search

    Young-In Kim

    2007-01-01

    Evidence has established the protective effect of folic acid (FA) fortification and periconceptional supplemen- tation on neural tube defects (NTDs). Folic acid fortifi- cation and periconceptional supplementation of women may reduce the risk of certain childhood cancers in their offspring. However, recent human studies have sug- gested that FA supplementation and fortification may promote the progression of already existing, undiag-

  20. Promoting PreConceptional Use of Folic Acid to Hispanic Women: A Social Marketing Approach

    Microsoft Academic Search

    Gwendolyn P. Quinn; Kimberlea Hauser; Bethany A. Bell-Ellison; Nydia Y. Rodriguez; Jaime L. Frías

    2006-01-01

    Objective: To develop a culturally appropriate communication initiative in an effort to promote the use of pre-conceptional folic acid among Hispanic women of childbearing age. The materials were designed to communicate information about the risks of neural tube defects and the value of folic acid supplementation before conception. Methods: The initiative was developed using a social marketing approach. A series

  1. The importance of folic acid in the primary prevention of congenital malformations

    Microsoft Academic Search

    JACEK WYSOCKI

    2008-01-01

    Folic acid is a vitamin essential to the normal functioning of all human cells. Tetrahydrofolate (THF) is the biologically active form of folic acid. Its main function is to transfer one-carbon units between compounds participating in many important biochemical processes such as purines and thymidylate biosynthesis, and S-adenosylmethionine synthesis. A deficiency of folates in a daily diet or disturbances in

  2. THE USE OF FOLIC ACID FOR THE PREVENTION OF BIRTH DEFECTS IN PUERTO RICO

    Microsoft Academic Search

    Lourdes Garcia-Fragoso; Ines Garcia-Garcia; Cynthia E. River

    Introduction: The occurrence of neural tube defects (NTDs) varies by race\\/ethnicity, and the highest rates are among women of Hispanic ethnicity. Women of reproductive age are advised to use folic acid to prevent NTDs and other birth defects. Since 1994, Puerto Rico has had a campaign to promote the use of folic acid, and since 1998, enriched grain products have

  3. Weekly Administration of Folic Acid and Epidemiology of Neural Tube Defects

    Microsoft Academic Search

    Laura E. Martínez de Villarreal; Patricia Arredondo; Ricardo Hernández; Jesús Z. Villarreal

    2006-01-01

    Objective: In 1999, a folic acid campaign for prevention of neural tube defects was started in Nuevo León, México, with the recommendation of taking a 5000 -mcg tablet of folic acid per week. The purpose of this study was to compare the epidemiology of neural tube defects after four years of the campaign. Methods: Cases of anencephaly, spina bifida, and

  4. Characteristics of Reduced Fat Milks As Influenced By the Incorporation of Folic Acid

    Microsoft Academic Search

    K. Achanta; C. A. Boeneke; K. J. Aryana

    2007-01-01

    Folic acid plays an importantrole in the prevention of neural tube defects (e.g., spina bifida and anencephaly), heart defects, facial clefts, urinary abnormalities, and limb deficiencies. Milk and milk products serve as a potential source for folic acid fortification because of the presence of folate-binding proteins that seem to be involved in folate bioavailability. Although milk is not a good

  5. Folic Acid and Vitamin B12 Fortification of Flour: A Global Basic Food Security Requirement

    Microsoft Academic Search

    Godfrey P. Oakley

    Folic acid is an essential water soluble B vitamin which has been used for decades in the prevention of folate deficiency anemia of pregnancy. In 1991, folic acid taken prior to the start of pregnancy was shown unequivocally to prevent spina bifida and anencephaly—two of the most serious and common birth (neural tube) defects. Soon governments recommended that women of

  6. Cost-effectiveness of a folic acid fortification program in Chile

    Microsoft Academic Search

    Adolfo Llanos; Eva Hertrampf; Fanny Cortes; Andrea Pardo; Scott D. Grosse; Ricardo Uauy

    2007-01-01

    ObjectivePericonceptional intake of folic acid reduces the risk of neural tube defects (NTDs), a frequent birth defect that can cause significant infant mortality and disability. In Chile, fortification of wheat flour with folic acid has resulted in significant reduction in the risk of anencephaly and spina bifida. We investigated the cost-effectiveness implications of this policy.

  7. Folic Acid: Nutritional Biochemistry, Molecular Biology, and Role in Disease Processes

    Microsoft Academic Search

    Mark Lucock

    2000-01-01

    This paper reviews the chemistry, metabolism, and molecular biology of folic acid, with a particular emphasis on how it is, or may be, involved in many disease processes. Folic acid prevents neural tube defects like spina bifida, while its ability to lower homocysteine suggests it might have a positive influence on cardiovascular disease. A role for this B vitamin in

  8. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial

    Microsoft Academic Search

    Alec Coppen; John Bailey

    2000-01-01

    Background: A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine. Methods: 127 patients were randomly assigned to receive either 500 ?g folic acid or

  9. Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene

    Microsoft Academic Search

    A. Melse-Boonstra; K. J. Lievers; H. J. Blom; P. Verhoef

    2004-01-01

    BACKGROUND: Before dietary folate is absorbed, polyglutamate folates are deconjugated to monoglutamates by folylpoly-gamma-glutamyl carboxypeptidase in the small intestine. The 1561T allele of the glutamate carboxypeptidase II gene (GCPII), which codes for folylpoly-gamma-glutamyl carboxypeptidase, may impair intestinal absorption of dietary folates. OBJECTIVE: Our aim was to study the bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid

  10. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

    Microsoft Academic Search

    Shiliang Liu; Roy West; Edward Randell; Linda Longerich; Kathleen Steel O'Connor; Helen Scott; Marian Crowley; Angeline Lam; Victor Prabhakaran; Catherine McCourt

    2004-01-01

    BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits

  11. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance among American seniors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folate deficiency has serious consequences for the fetus. Folic acid fortification of food addresses this problem. However, clinical consequences of vitamin B-12 deficiency may be worsened by high folic acid intakes, perhaps as a direct result of unmetabolized folic acid, which does not occur natura...

  12. Chemiluminescence determination of folic acid by a flow injection analysis assembly

    NASA Astrophysics Data System (ADS)

    Wabaidur, Saikh Mohammad; Alam, Seikh Mafiz; Lee, Sang Hak; Alothman, Zeid Abdullah; Eldesoky, Gaber E.

    2013-03-01

    A flow injection (FI) method is reported for the determination of folic acid by chemiluminescence method. This method is based on the reaction of folic acid with Ru(bipy)32+ and Ce(IV) to produce chemiluminescence. The calibration curve was linear over the range of 2.5 × 10-5-3.1 × 10-7 mol/L with a detection limit of 2.3 × 10-8 mol/L (S/N = 3). The relative standard deviation of 1.0 × 10-6 mol/L folic acid was found 3.5% (n = 11). The influences of potential interfering substances were studied. The recovery was higher than 95.3%. The method was accurate, sensitive, and effective for assay of folic acid. This CL method was successfully applied to the determination of folic acid in pharmaceutical preparations. The mechanism of CL reaction was also studied.

  13. Intestinal transport of zinc and folic acid: a mutual inhibitory effect

    SciTech Connect

    Ghishan, F.K.; Said, H.M.; Wilson, P.C.; Murrell, J.E.; Greene, H.L.

    1986-02-01

    Recent observations suggest an inverse relationship between folic acid intake and zinc nutriture and indicate an interaction between folic acid and zinc at the intestinal level. To define that interaction, we designed in vivo and in vitro transport studies in which folic acid transport in the presence of zinc, as well as zinc transport in the presence of folic acid was examined. These studies show that zinc transport is significantly decreased when folate is present in the intestinal lumen. Similarly folic acid transport is significantly decreased with the presence of zinc. To determine whether this intestinal inhibition is secondary to zinc and folate-forming complexes, charcoal-binding studies were performed. These studies indicate that zinc and folate from complexes at pH 2.0, but that at pH 6.0, these complexes dissolve. Therefore, our studies suggest that under normal physiological conditions a mutual inhibition between folate and zinc exists at the site of intestinal transport.

  14. Association of low potassium diet and folic acid deficiency in patients with CKD

    PubMed Central

    Hassan, Kamal

    2015-01-01

    Background Most of the folic acid sources are rich also in potassium. Patients with chronic kidney disease (CKD) usually receive a low potassium diet. We investigated the possibility of an association between low potassium diet and folic acid deficiency. Methods In total, 128 CKD patients participated in this cross-sectional study. Sixty-four patients with CKD grades 1 and 2 were on an unrestricted potassium diet when enrolled in the study, and 64 patients with CKD grades 3 and 4 had received instructions to restrict their intake of potassium at least 6 months before enrollment in the study. Subjects were evaluated for daily intake of folic acid (DIFA), daily intake of potassium (DIK), and serum folic acid levels (SFA). Results DIFA correlated with the estimated glomerular filtration rate, the DIK, and the SFA (P<0.001). SFA correlated with the estimated glomerular filtration rate (P<0.001). Mean DIFA and mean SFA were lower among patients with CKD grades 3 and 4 than among those with CKD grades 1 and 2 (P<0.001). The mean DIFA in patients with folic acid deficiency was lower than that in those with SFA ?7.1 nmol/L (P<0.001). There was lower SFA and threefold greater frequency of folic acid deficiency among patients with CKD grades 3 and 4 who had received instructions to restrict their intake of potassium than among patients with CKD grades 1 and 2 who were on an unrestricted potassium diet. Conclusion A potassium-restricted diet offered to patients with CKD grades 3 and 4 may be associated with folic acid deficiency. Serum levels of folic acid should be investigated before starting potassium restriction in patients with CKD grades 3 and 4, in order to identify individuals with folic acid deficiency or with marginal serum levels who should receive folic acid replacement therapy.

  15. High Dosage Folic Acid Supplementation, Oral Cleft Recurrence and Fetal Growth

    PubMed Central

    Wehby, George L.; Félix, Têmis Maria; Goco, Norman; Richieri-Costa, Antonio; Chakraborty, Hrishikesh; Souza, Josiane; Pereira, Rui; Padovani, Carla; Moretti-Ferreira, Danilo; Murray, Jeffrey C.

    2013-01-01

    Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth. PMID:23380913

  16. Association of Folic Acid Supplementation During Pregnancy and Infant Bronchiolitis

    PubMed Central

    Veeranki, Sreenivas P.; Gebretsadik, Tebeb; Dorris, Stacy L.; Mitchel, Edward F.; Hartert, Tina V.; Cooper, William O.; Tylavsky, Frances A.; Dupont, William; Hartman, Terryl J.; Carroll, Kecia N.

    2014-01-01

    Viral bronchiolitis affects 20%–30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995–2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid–containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: “none” (no prescription filled), “first trimester only,” “after first trimester,” and “both” (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the “none” group, infants born to women in the “first trimester only” group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis. PMID:24671071

  17. L-FOLINIC ACID VERSUS FOLIC ACID FOR THE TREATMENT OF HYPERHOMOCYSTEINEMIA IN HEMODIALYSIS PATIENTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid (FA). We evaluated whether a high-dose L-folinic acid- based regimen provided improved total homocysteine (tHcy)-lowering efficacy in...

  18. Knowledge, attitude and practice regarding folic acid deficiency; A hidden hunger

    PubMed Central

    Hisam, Aliya; Rahman, Mahmood Ur; Mashhadi, Syed Fawad

    2014-01-01

    Objectives: To find the Knowledge Attitude and Practice regarding Folic Acid Deficiency among Women of Child Bearing Age (WPCBA). To find out the Association of Education Level with Practice of Folic Acid in WPCBA. Methods: A Descriptive cross sectional study (Knowledge Practice and Attitude) was conducted at Military Hospital and Combined Hospital Rawalpindi from September 2012 to February 2013. About 400 married females of age group 21-42 years were included by convenient sampling technique. After taking informed verbal consent, a closed ended interviewer administered questionnaire was filled. Data was entered and analyzed using SPSS version 20. Results: Mean age of the respondents was 30.31 + 5.280 years. Illiterate and literate were 165 (41.25%) and 235 (58.75%) respectively. The knowledge regarding folic acid need was 172 (43%). Only 161 (40.25%) thought that folic acid deficiency in pregnant women results in abnormality in newborn. In pregnancy, 205 (51.25%) had received folic acid supplementation. Association between education level and practice of folic acid was significant (p= 0.009) at 95% confidence level. Conclusion: Knowledge regarding folic acid deficiency among WOCBA was low along with the poor attitude. Practice was also not satisfactory. Education status plays important role in preventing micronutrient deficiency. PMID:24948984

  19. Folic acid administration inhibits amyloid ?-peptide accumulation in APP/PS1 transgenic mice.

    PubMed

    Li, Wen; Liu, Huan; Yu, Min; Zhang, Xumei; Zhang, Meilin; Wilson, John X; Huang, Guowei

    2015-08-01

    Alzheimer's disease (AD) is associated with malnutrition, altered one-carbon metabolism and increased hippocampal amyloid-? peptide (A?) accumulation. Aberrant DNA methylation may be an epigenetic mechanism that underlies AD pathogenesis. We hypothesized that folic acid acts through an epigenetic gene silencing mechanism to lower A? levels in the APP/PS1 transgenic mouse model of AD. APP/PS1 mice were fed either folate-deficient or control diets and gavaged daily with 120?g/kg folic acid, 13.3mg/kg S-adenosylmethionine (SAM) or both. Examination of the mice after 60days of treatment showed that serum folate concentration increased with intake of folic acid but not SAM. Folate deficiency lowered endogenous SAM concentration, whereas neither intervention altered S-adenosylhomocysteine concentration. DNA methyltransferase (DNMT) activity increased with intake of folic acid raised DNMT activity in folate-deficient mice. DNA methylation rate was stimulated by folic acid in the amyloid precursor protein (APP) promoter and in the presenilin 1 (PS1) promoter. Folate deficiency elevated hippocampal APP, PS1 and A? protein levels, and these rises were prevented by folic acid. In conclusion, these findings are consistent with a mechanism in which folic acid increases methylation potential and DNMT activity, modifies DNA methylation and ultimately decreases APP, PS1 and A? protein levels. PMID:25959374

  20. [Fortified food products as a potential source of folic acid in human nutrition].

    PubMed

    Sici?ska, Ewa; Pelc, Anna

    2011-01-01

    The aim of the study was to analysis the number and variety offoodproducts fortified with folic acid available on the Warsaw market and to assess consumers' knowledge about these products. Information about food products was based on label declaration, in summer 2009. In addition knowledge about fortified food was studied in the group of 94 market customers. There were 166 foodstuffs fortified with folic acid from various food categories, like breakfast cereals, wheat flour, fruit juices and drinks, sweets, margarine, instant cocoa and tea instant as well as milk products. Breakfast cereals and juices, nectars and fruit drinks were the largest groups. Less than half of market customers correctly defined term 'fortified product", less than 40% of respondents answered properly on question concerning folic acid. There is possibility to increase the folates intake by consuming various products fortified with folic acid. The wide public education is essential for increasing the role of these products in nutrition. PMID:21980869

  1. Absorption of folic acid from the small intestine of the rat

    PubMed Central

    Burgen, A. S. V.; Goldberg, N. J.

    1962-01-01

    The absorption of folic acid from segments of the small intestine of the rat has been measured in situ with tritium-labelled folic acid. The fraction absorbed was independent of concentration below 10-6 M but was depressed to half at 4×10-5 M. Direct measurements of fluxes showed that the mucosal ? serosal flux was about 14 times the serosal ? mucosal flux, and therefore that uptake of folic acid is an active process. In the ileum but not in the duodeno-jejunum, absorption was depressed by the presence of electrolyte. There was little difference in absorptive capacity between jejunum and ileum nor was there any significant change in animals suffering from a dietary deficiency of folic acid. PMID:14016958

  2. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

  3. Antiatherogenic and radioprotective role of folic acid in whole body gamma-irradiated mice.

    PubMed

    Pote, Madan Sadashiv; Gandhi, Nitin Motilal; Mishra, Kaushala Prasad

    2006-11-01

    Free radical mediated oxidative damage is one of the prime factors for atherogenic changes in humans. We have shown that the folic acid administration reduced the risk of the atherogenic factors induced by gamma-radiation. Folic acid administration prevented the radiation induced increase in the plasma lipoprotein lipase activity and also prevented the radiation-induced increase in the hepatic cholesterol and triglycerides levels. These results indicate the role of folic acid as an antiatherogenic agent. Further, we also report the radioprotective property of folic acid as demonstrated by reduction in the radiation induced membrane damage as measured by lipid peroxidation products and DNA damage, which was measured by alkaline comet assay. PMID:17031576

  4. But I've already had a healthy baby: folic acid formative research with Latina mothers.

    PubMed

    Prue, Christine E; Flores, Alina L; Panissidi, Paula; Lira, Andrea

    2008-10-01

    Each year, approximately 3000 pregnancies in the United States are affected by neural tube defects (NTDs), serious birth defects of the brain and spine. Daily periconceptional consumption of folic acid can reduce the incidence of NTDs by 50%-70%. This study was designed to understand Latina mothers' folic acid awareness, knowledge, and behaviors and to capture their reactions to advertising concepts and draft educational materials. The goal of the materials was to increase folic acid consumption through the use of a daily multivitamin. This study presents three phases of research that led to the development of Spanish language print advertisements, posters, a brochure, and radio ads that promote folic acid consumption in a manner that addresses the needs of Latina mothers. PMID:18752460

  5. Estimated folic acid intakes from simulated fortification of the New Zealand food supply

    Microsoft Academic Search

    Tim Green; Rebecca Newton; Diane Bourn

    Aim To identify a folic acid food fortification programme that will maximise the percentage of women of child-bearing age receiving at least 400 µg folic acid\\/day, the amount shown to reduce the risk of neural tube defect-affected pregnancies, while not putting population groups at risk of excessive intakes. Methods 1997 New Zealand National Nutrition Survey data and a computer modelling

  6. Growing Gap in Folic Acid Intake with Respect to Level of Education in the Netherlands

    Microsoft Academic Search

    H. E. K. de Walle; L. T. W. de Jong-van den Berg

    2007-01-01

    Objective: To evaluate the prevalence of the awareness of and the behaviour towards folic acid in 2003 and the trend of folic acid use among pregnant Dutch women between 1995 and 2003 with regard to socio-economic status (SES). Method: We conducted 2-yearly cross-sectional studies among pregnant women who filled in a questionnaire during the first or second antenatal visit. The

  7. Case control study of periconceptional folic acid intake and nervous system tumors in children

    Microsoft Academic Search

    Juan Antonio Ortega-García; Josep Ferrís-Tortajada; Luz Claudio; Offie Porat Soldin; Miguel Felipe Sanchez-Sauco; Jose Luís Fuster-Soler; Juan Francisco Martínez-Lage

    2010-01-01

    Purpose  Since 1992, the Centers for Disease Control and Prevention recommends that women of childbearing age consume 400 µg of folic\\u000a acid per day to reduce the risk of neural tube defects (NTD). It has been speculated that both NTD and nervous system tumors\\u000a (NST) may share common mechanisms of altered development. It examines the association between folic acid supplementation and\\u000a the

  8. Preventing neural tube defects: The importance of periconceptional folic acid supplements

    Microsoft Academic Search

    GregoryJ Locksmith; Patrick Duff

    1998-01-01

    Objective: To inform the obstetrician-gynecologist of recent scientific evidence regarding the use of supplemental folic acid for prevention of neural tube defects (NTDs).Data Sources: We selected English language articles via MEDLINE published from January 1990 through February 1997, using the search terms “folic acid” and “neural tube defect.” Additional sources were identified through cross-referencing and through searching selected journals published

  9. Awareness of the Benefit of Periconceptional Folic Acid Supplementation in South America

    Microsoft Academic Search

    Eduardo E. Castilla; Maria da Graça Dutra; Jorge S. Lopez-Camelo; Mónica Rittler; Iêda M. Orioli

    2000-01-01

    Awareness of the benefit of periconceptional supplementation with folic acid was surveyed in 2,810 postpartum women by the Latin American Collaborative Study of Congenital Malformations (ECLAMC) during 1996. While 48.8% of the women claimed to know that some vitamins were good for the baby in gestation, only 0.5% mentioned folic acid. Although 13.9% of the women declared to know about

  10. Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering

    Microsoft Academic Search

    Sagar N. Doshi; Ian F. W. McDowell; Stuart J. Moat; Nicola Payne

    2002-01-01

    Background—Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg\\/d. High-dose folic acid (5 mg\\/d) improves endothelial function

  11. The impact of folic acid intake on the association between diabetes, obesity, and spina bifida

    PubMed Central

    Parker, Samantha E; Yazdy, Mahsa M; Tinker, Sarah C; Mitchell, Allen A; Werler, Martha M

    2013-01-01

    Objective To investigate the relationship between spina bifida and two established risk factors, pregestational diabetes and obesity, in both the presence and absence of the recommended daily folic acid intake in the periconceptional period. Study Design Cases of spina bifida (n=1154) and controls (n=9439) from the Slone Epidemiology Center Birth Defects Study (1976–2011) were included. Information on preexisting diabetes (collected 1976+) and obesity (collected 1993+), defined as BMI ?30 kg/m2, were collected through interviews conducted within six months of delivery. Periconceptional folic acid intake was calculated using both dietary and supplement information. Mothers were classified as consuming more or less than 400µg/day of folic acid, with food folate included at a 30% discount for its lower bioavailability. Logistic regression models, adjusted for maternal race, education, and study site, were used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the joint effects of low folic acid intake coupled with diabetes or obesity. Results Mothers of cases were more likely to have diabetes or be obese (0.7% and 19.0%, respectively) than control mothers (0.4% and 10.8%, respectively). The joint effect of diabetes and lower folic acid intake on spina bifida was larger (aOR:3.95; CI: 1.56, 10.00) than that of diabetes and higher folic acid intake (aOR:1.31; CI: 0.17, 10.30). Folic acid intake made little difference on the association between obesity and spina bifida. Conclusion Our findings suggest that folic acid further attenuates, though does not eliminate, the risk of spina bifida associated with diabetes, than that with obesity. PMID:23711668

  12. Folic acid handling by the human gut: implications for food fortification and supplementation123

    PubMed Central

    Patanwala, Imran; King, Maria J; Barrett, David A; Rose, John; Jackson, Ralph; Hudson, Mark; Philo, Mark; Dainty, Jack R; Wright, Anthony JA; Finglas, Paul M; Jones, David E

    2014-01-01

    Background: Current thinking, which is based mainly on rodent studies, is that physiologic doses of folic acid (pterylmonoglutamic acid), such as dietary vitamin folates, are biotransformed in the intestinal mucosa and transferred to the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic acid (5-MTHF) before entering the liver and the wider systemic blood supply. Objective: We tested the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa. Design: We conducted a crossover study in which we sampled portal and peripheral veins for labeled folate concentrations after oral ingestion with physiologic doses of stable-isotope–labeled folic acid or the reduced folate 5-formyltetrahydrofolic acid (5-FormylTHF) in 6 subjects with a transjugular intrahepatic porto systemic shunt (TIPSS) in situ. The TIPSS allowed blood samples to be taken from the portal vein. Results: Fifteen minutes after a dose of folic acid, 80 ± 12% of labeled folate in the hepatic portal vein was unmodified folic acid. In contrast, after a dose of labeled 5-FormylTHF, only 4 ± 18% of labeled folate in the portal vein was unmodified 5-FormylTHF, and the rest had been converted to 5-MTHF after 15 min (postdose). Conclusions: The human gut appears to have a very efficient capacity to convert reduced dietary folates to 5-MTHF but limited ability to reduce folic acid. Therefore, large amounts of unmodified folic acid in the portal vein are probably attributable to an extremely limited mucosal cell dihydrofolate reductase (DHFR) capacity that is necessary to produce tetrahydrofolic acid before sequential methylation to 5-MTHF. This process would suggest that humans are reliant on the liver for folic acid reduction even though it has a low and highly variable DHFR activity. Therefore, chronic liver exposure to folic acid in humans may induce saturation, which would possibly explain reports of systemic circulation of unmetabolized folic acid. This trial was registered at clinicaltrials.gov as NCT02135393. PMID:24944062

  13. The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

    PubMed Central

    Liang, Shuang; Zhou, Yuanpeng; Wang, Huijun; Qian, Yanyan; Ma, Duan; Tian, Weidong; Persaud-Sharma, Vishwani; Yu, Chen; Ren, Yunyun; Zhou, Shufeng; Li, Xiaotian

    2014-01-01

    Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid. PMID:24524080

  14. Awareness of the benefits of folic acid and prevalence of the use of folic acid supplements to prevent neural tube defects among Thai women

    Microsoft Academic Search

    Katika Nawapun; Vorapong Phupong

    2007-01-01

    Objective  To determine the level of knowledge about the usefulness of periconceptional folic acid supplementation among pregnant women.\\u000a \\u000a \\u000a \\u000a Materials and methods  An anonymous questionnaire was completed by selected subjects to assess folic acid awareness. The questionnaire was administered\\u000a to pregnant women who were seeking antenatal care at King Chulalongkorn Memorial Hospital May to December 2005. The questions\\u000a covered their knowledge and use

  15. Interaction of Zinc, Ascorbic Acid, and Folic Acid in Glycation with Albumin as Protein Model

    Microsoft Academic Search

    Rashmi Tupe; Vaishali Agte

    2010-01-01

    Using albumin as model, we conducted series of in vitro glycation experiments to examine role of zinc in glycation using glucose\\u000a at 4–100 mg\\/ml, incubations at 37°C or 60°C, duration of 2 or 4 weeks and in presence of zinc or ascorbic acid (AA) or folic\\u000a acid (FA). Modifications of bovine serum albumin (BSA) were examined by using fluorescence of advanced glycation

  16. Encapsulation of folic acid and its stability in sodium alginate-pectin-poly(ethylene oxide) electrospun fibres.

    PubMed

    Alborzi, Solmaz; Lim, Loong-Tak; Kakuda, Yukio

    2013-01-01

    In this study, we investigated the effect of alginate-pectin-poly(ethylene oxide) (PEO) electrospun fibres on the stability of folic acid. Fibre-forming solutions containing folic acid were prepared by blending low- or medium-viscosity alginate with pectin. PEO was added to make the electrospinning process possible. Folic acid encapsulated in electrospun fibres achieved close to 100% retention when stored in the dark at pH 3 after 41 days of storage. By contrast, recovery of unencapsulated folic acid was 0% and 8% within the first day when stored at pH 3 in the presence and the absence of light, respectively. Electrospun fibres produced from the combination of alginate-pectin resulted in higher retention of folic acid compared to that of alginate alone. Nucleic magnetic resonance and FTIR results show that folic acid has been encapsulated in electrospun fibres through physical entrapment. PMID:22703229

  17. Observations on the prevention of cleft palate in dogs by folic acid and potential relevance to humans

    Microsoft Academic Search

    J. M. Elwood; T. A. Colquhoun

    1997-01-01

    Folic acid has been shown to prevent neural tube defects in humans, but its effects on other defects is unknown. In a consistent breeding programme of Boston terrier dogs started in 1974, folic acid supplementation (5 mg\\/day) was introduced in 1981. The frequency of cleft palate fell from 9\\/51 (17.6%) without folic acid to 8\\/191 (4.2%) after its introduction, giving

  18. Photoinactivation of tyrosinase sensitized by folic acid photoproducts.

    PubMed

    Laura Dántola, M; Zurbano, Beatriz N; Thomas, Andrés H

    2015-08-01

    Tyrosinase catalyzes in mammals the first and rate-limiting step in the biosynthesis of the melanin, the main pigment of the skin. Pterins, heterocyclic compounds able to photoinduce oxidation of biomolecules, accumulate in the skin of patients suffering from vitiligo, where there is a lack of melanin. Folic acid (PteGlu) is a conjugated pterin widespread in biological systems. Aqueous solutions of tyrosinase were exposed to UV-A irradiation (350nm) in the presence of PteGlu and its photoproducts (6-formylpterin and 6-carboxypterin). The reactions were followed by UV-Vis spectrophotometry, enzyme activity measurement, fluorescence spectroscopy and HPLC. In this work, we present data that demonstrate unequivocally that solutions of tyrosinase exposed to UV-A irradiation in the presence of PteGlu, undergo enzyme inactivation. However, PteGlu itself causes a negligible effect on the activity of the enzyme. In contrast, PteGlu photoproducts are efficient photosensitizers. The tyrosinase inactivation involves two different pathways: (i) a photosensitization process and (ii) the oxidation of the enzyme by the hydrogen peroxide produced during the photooxidation of PteGlu and its photoproduct. The former pathway affects both the active site and the tryptophan residues, whereas the latter affects only the active site. The biological implications of the results are discussed. PMID:26086354

  19. Determination of folic acid by capillary electrophoresis with chemiluminescence detection.

    PubMed

    Zhao, Shulin; Yuan, Hongyan; Xie, Chao; Xiao, Dan

    2006-02-24

    A rapid and simple method is presented for the determination of folic acid (FA) by capillary electrophoresis (CE) with chemiluminescence (CL) detection. This method was based on enhance effect of FA on the CL reaction between luminol and BrO(-) in alkaline aqueous solution. Optimal separation and determination was obtained with an electrophoretic buffer of 35 mM sodium borate (pH 9.4) containing 0.8 mM luminol, and an oxidizer solution of 1.6 mM NaBrO in 100 mM NaCO(3) buffer solution (pH 12.0). Under the optimal conditions, the determination of FA was achieved in less than 20 min, and the detection limit was 2.0 x 10(-8) M (S/N=3). The relative standard deviations (RSDs) on peak area and migration time were in the 1.5 and 1.1%, respectively. The present CE-CL method was applied to the determination of FA in commercial pharmaceutical tablets, apple juices and human urine. PMID:16413558

  20. Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.

    PubMed

    Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

    2012-01-01

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits. PMID:21210201

  1. Doubling the number of women consuming vitamin supplement pills containing folic acid: An urgently needed birth defect prevention complement to the folic acid fortification of cereal grains

    Microsoft Academic Search

    Godfrey P Oakley

    1997-01-01

    The major known environmental causes of birth defects are ancient agents that have been in the environment for centuries but have been only recently discovered—rubella, alcohol, and folic acid deficiency. In the United States, we have made great progress in preventing congenital rubella syndrome. We also have a great opportunity to prevent spina bifida and anencephaly (SBA) by increasing the

  2. Effect of folic acid supplementation on homocysteine concentration and association with training in handball players

    PubMed Central

    2013-01-01

    Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 ?g folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Results Bivariate analysis showed a significant negative correlation (P?folic acid concentrations (r?=??0.84) at Week 8, reflecting a significant change in Hcy concentration (P?folic acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against alterations that can lead to cardiovascular events related to exertion during competition. PMID:23432819

  3. Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

    PubMed Central

    Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

    2012-01-01

    Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240

  4. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

    PubMed

    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone. PMID:23935126

  5. Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy.

    PubMed

    Nematollahi-Mahani, S N; Azizollahi, G H; Baneshi, M R; Safari, Z; Azizollahi, S

    2014-04-01

    Varicocele is among the most common problems which may lead to male infertility. Spermatogenesis is impaired as a consequence of this vascular defect, through mechanisms that are not well described. This study aimed to evaluate serum hormonal level (inhibin B, FSH and testosterone) and seminal plasma antioxidant defence levels after folic acid and zinc sulphate administration in varicocelectomised patients. Participants were randomly allocated to four experimental groups. Our randomisation schedule was as follows: zinc sulphate/folic acid, folic acid, zinc sulphate and placebo. The patients underwent varicocelectomy, before which a blood and semen sample were obtained and also three and six months after varicocelectomy for evaluation of blood hormonal level (FSH, testosterone, inhibin B) and seminal oxidative stress status (nitric oxide, superoxide dismutase, total antioxidant capacity). Patients in different groups took orally one capsule per day after dinner following varicocelectomy for 6 months. A significant rise in peripheral blood inhibin B and seminal plasma activity was detected in the zinc sulphate/folic acid group after 6 months. The present clinical trial indicates a change in the hormonal status of varicocelectomised patients following long-term administration of zinc sulphate and folic acid. PMID:23356505

  6. Characterization of ZnO nanoparticles grown in presence of Folic acid template

    PubMed Central

    2012-01-01

    Background ZnO nanoparticles (grown in the template of folic acid) are biologically useful, luminescent material. It can be used for multifunctional purposes, e.g., as biosensor, bioimaging, targeted drug delivery and as growth promoting medicine. Methods Sol–gel chemical method was used to develop the uniform ZnO nanoparticles, in a folic acid template at room temperature and pH?~?7.5. Agglomeration of the particles was prevented due to surface charge density of folic acid in the medium. ZnO nanoparticle was further characterized by different physical methods. Results Nanocrystalline, wurtzite ZnO particles thus prepared show interesting structural as well as band gap properties due to capping with folic acid. Conclusions A rapid, easy and chemical preparative method for the growth of ZnO nanoparticles with important surface physical properties is discussed. Emphatically, after capping with folic acid, its photoluminescence properties are in the visible region. Therefore, the same can be used for monitoring local environmental properties of biosystems. PMID:22788841

  7. Quantum dot-folic acid conjugates as potential photosensitizers in photodynamic therapy of cancer.

    PubMed

    Morosini, Vincent; Bastogne, Thierry; Frochot, Céline; Schneider, Raphaël; François, Aurélie; Guillemin, François; Barberi-Heyob, Muriel

    2011-05-01

    This study examined the in vitro potential of bioconjugated quantum dots (QDs) as photosensitizers for photodynamic therapy (PDT). According to our previous approaches using photosensitizers, folic acid appears to be an optimal targeting ligand for selective delivery of attached therapeutic agents to cancer tissues. We synthesized hydrophilic near infrared emitting CdTe(S)-type QDs conjugated with folic acid using different spacers. Photodynamic efficiency of QDs conjugated or not with folic acid was evaluated on KB cells, acting as a positive control due to their overexpression of FR-?, and HT-29 cells lacking FR-?, as negative control. A design of experiments was suggested as a rational solution to evaluate the impacts of each experimental factor (QD type and concentration, light fluence and excitation wavelength, time of contact before irradiation and cell phenotype). We demonstrated that, for concentrations lower than 10 nM, QDs displayed practically no cytotoxic effect without light exposure for both cell lines. Whereas QDs at 2.1 nM displayed a weak photodynamic activity, a concentration of 8 nM significantly enhanced the photodynamic efficiency characterized by a light dose-dependent response. A statistically significant difference in photodynamic efficiency between KB and HT-29 cells was evidenced in the case of folic acid-conjugated QDs. Optimal conditions led to an enhanced photocytotoxicity response, allowing us to validate the ability of QDs to generate a photodynamic effect and of folic acid-conjugated QDs for targeted PDT. PMID:21479314

  8. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse

    PubMed Central

    Leung, Kit-Yi; De Castro, Sandra C.P.; Savery, Dawn; Copp, Andrew J.

    2013-01-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone. PMID:23935126

  9. [Stability of folic acid and vitamin B12 in TPN].

    PubMed

    Almodóvar, M J; Hernández Jaras, M V; León-Sanz, M; Ortuño, B; Estenoz, J; Negro Vega, E; Marfagón, N; Herreros de Tejada, A

    1991-01-01

    The stability of folic acid (FA) in mixtures of Total Parenteral Nutrition has been and is a controversial subject, with discussion concerning the influence of factors such as temperature, light and storage time. As regards the stability of the vitamin B12, there are few studies in scientific literature. For all those reasons, we consider it necessary to make a proper study to evaluate the influence of different factors in the stability of both vitamins. The study was made on 3 liter TPN bags of the EVA type, the composition of which was as follows: AA (85g), glucosa (225g), fat (50g), Na (86mEq), K (60 mEq), Ca (15 mEq), Cl (90 mEq), P (17 mmol) acetate (149 mEq) and 10 ml of MVI-12 which contain 400 micrograms of PA and 5 micrograms of Vitamin B 12. Consideration was also given to the stability of these two vitamins in the same diet, to which were added 10 ml of a commercial preparation of oligo-elements. Six TPN bags were prepared (without oligo-elements); two of them were kept in a fridge and protected from the light, two were kept at room temperature and protected from the light and the other two at room temperature without protection from the light. Samples were taken from all the bags immediately after their preparation and after 24, 48, 72 and 96 hours. The same process was carried with other TPN bags which did contain oligo-elements. The method for determining FA and Vitamin B12 was by radioassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1764534

  10. [Integral bread development with soybean, chia, linseed, and folic acid as a functional food for women].

    PubMed

    Justo, Mayela Bautista; Alfaro, Alejandra Denisse Castro; Aguilar, Ernesto Camarena; Wrobel, Katarzyna; Wrobel, Kazimierz; Guzmán, Guadalupe Alanís; Sierra, Zeferino Gamiño; Zanella, Victor Da Mota

    2007-03-01

    Six bread formulations were developed, using different proportions of whole-wheat flour, chia seeds and flaxseed flour. All of our formulations were added with folic acid. Sensorial and texture evaluations were performed, showing good acceptance of the products. Proximal chemical analysis was carried out; in addition, the following parameters were determined: calcium, phosphorus, total dietary fiber, folic acid, water hydration capacity, Glucose Dialysis Retardation Index (GDRI) and fatty acids. The results obtained showed higher protein levels in the developed breads (23.23-30.24 (g/100g dry matter) as compared to a control (21.00% of proteins in bread elaborated without chia or flaxseed). Furthermore, the breads contained 10.07-12.15 of lipids (g/100g dry matter) (linoleic acid: 2.43-4.05%; linolenic acid: 1.12-4.46 %; oleic acid: 2.93-6.13 %), GDRI values were between 89.1 and 98.1 % and folic acid was in the range 699.44 - 991.3 (microg/100g dry matter). The same parameters were determined in the chia seed and in the flaxseed flour. It was concluded that; due to their high levels of protein, insaturated fatty acids (omega-3 and omega-6), dietary fiber and folic acid, these breads have a high nutritional value, so they could have special benefits for woman. PMID:17824203

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

    PubMed

    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 ? (FR?). The function of FR? 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 FR? 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 FR?-positive HeLa cells, but not in FR?-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 FR?-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 FR? adds complexity to the established roles of B9 vitamins in cancer and neural tube defects. PMID:25841994

  12. Intestinal absorption, liver uptake, and excretion of /sup 3/H-folic acid in folic acid-deficient, alcohol-consuming nonhuman primates

    SciTech Connect

    Blocker, D.E.; Thenen, S.W.

    1987-09-01

    Nonhuman primates fed folic acid-deficient diets +/- 30% kcal ethanol were used to determine alcohol effects on megaloblastic anemia development and folate bioavailability. Lower hemoglobin (Hb) and red blood cell (RBC) counts and higher mean corpuscular volume (MCV) occurred after 13 wk in alcohol-fed monkeys, later in controls. Plasma, RBC, and liver folate declined and urinary formiminoglutamic acid (FIGLU) was elevated in both groups with FIGLU increasing more among alcohol-fed monkeys at 38 wk. After 40 wk, the bioavailability of oral /sup 3/H-folic acid was investigated and showed increased fecal and reduced urinary tritium excretion in alcohol-fed monkeys compared with controls while plasma uptake and liver and whole body tritium retention were similar in both groups. These observations demonstrate that chronic alcohol consumption impairs folate coenzymes, accelerates appearance of hematologic indices of megaloblastic anemia, and causes possible malabsorption of enterohepatically circulated folates in folate deficiency even when other essential nutrients are provided.

  13. The scientific basis for eliminating folic acid-preventable spina bifida: a modern miracle from epidemiology.

    PubMed

    Oakley, Godfrey P

    2009-04-01

    One of the most remarkable successes of epidemiology was the demonstration in the late twentieth century that spina bifida and anencephaly-two of the most common and severe birth defects-are caused primarily by folate deficiency. This article reviews the descriptive epidemiological studies that began when we did not have a clue about etiology. The paper tells the success story of the trials that proved that folic acid would prevent folic-acid-preventable spina bifida. Finally, it will tell how difficult it is to get prevention policy implemented, even when the scientific evidence is compelling. It concludes by noting that the inaction or inappropriate actions of food regulatory bodies in so many countries means that only 10% of folic-acid-preventable spina bifida is actually being prevented--a serious failure of public health policy. PMID:19344858

  14. Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials

    PubMed Central

    Qin, Tingting; Du, Mulong; Du, Haina; Shu, Yongqian; Wang, Meilin; Zhu, Lingjun

    2015-01-01

    Numerous studies have investigated the effects of folic acid supplementation on colorectal cancer risk, but conflicting results were reported. We herein performed a meta-analysis based on relevant studies to reach a more definitive conclusion. The PubMed and Embase databases were searched for quality randomized controlled trials (RCTs) published before October 2014. Eight articles met the inclusion criteria and were subsequently analyzed. The results suggested that folic acid treatment was not associated with colorectal cancer risk in the total population (relative risk [RR]?=?1.00, 95% confidence interval [CI]?=?0.82–1.22, P?=?0.974). Moreover, no statistical effect was identified in further subgroup analyses stratified by ethnicity, gender, body mass index (BMI) and potential confounding factors. No significant heterogeneity or publication bias was observed. In conclusion, our meta-analysis demonstrated that folic acid supplementation had no effect on colorectal cancer risk. However, this finding must be validated by further large studies. PMID:26131763

  15. Computational and experimental studies of the interaction between single-walled carbon nanotubes and folic acid

    NASA Astrophysics Data System (ADS)

    Castillo, John J.; Rozo, Ciro E.; Castillo-León, Jaime; Rindzevicius, Tomas; Svendsen, Winnie E.; Rozlosnik, Noemi; Boisen, Anja; Martínez, Fernando

    2013-03-01

    This Letter involved the preparation of a conjugate between single-walled carbon nanotubes and folic acid that was obtained without covalent chemical functionalization using a simple 'one pot' synthesis method. Subsequently, the conjugate was investigated by a computational hybrid method: our own N-layered Integrated Molecular Orbital and Molecular Mechanics (B3LYP(6-31G(d):UFF)). The results confirmed that the interaction occurred via hydrogen bonding between protons of the glutamic moiety from folic acid and ? electrons from the carbon nanotubes. The single-walled carbon nanotube-folic acid conjugate presented herein is believed to lead the way to new potential applications as carbon nanotube-based drug delivery systems.

  16. Intestinal Absorption of Tritium-Labelled Folic Acid in Idiopathic Steatorrhea

    PubMed Central

    Kinnear, D. G.; Johns, D. G.; MacIntosh, P. C.; Burgen, A. S. V.; Cameron, D. G.

    1963-01-01

    The intestinal absorption of folic acid in patients with idiopathic steatorrhea was studied by the oral administration of tritium-labelled folic acid in a dosage of 15 ?g./kg. Results were expressed as a percentage of the orally administered folic acid radioactivity excreted in the urine over 24 hours. The mean excretion of radioactivity in 38 normal subjects was 48.2 ± 16.6% (mean ± SD), whereas eight patients with untreated idiopathic steatorrhea excreted only 16.7 ± 3.4% (mean ± SE). The ability of the gluten-free diet to correct this absorptive defect was demonstrated by the finding of normal values in 11 patients in complete clinical remission for periods exceeding six months after institution of the diet. Serial studies in individual patients indicated that a significant improvement was obtainable in as short a period as two weeks following exclusion of gluten from the diet. PMID:14077269

  17. Preschool iron-folic acid and zinc supplementation in children exposed to iron-folic acid in utero confers no added cognitive benefit in early school-age.

    PubMed

    Christian, Parul; Morgan, Mary E; Murray-Kolb, Laura; LeClerq, Steven C; Khatry, Subarna K; Schaefer, Barbara; Cole, Pamela M; Katz, Joanne; Tielsch, James M

    2011-11-01

    In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7-9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001-2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007-2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (-0.29, 95% CI: -0.55, -0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (-1.92, 95% CI: -3.12, -0.71) and C-IFAZn (-1.78, 95% CI: -2.63, -0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc. PMID:21956955

  18. Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian Mother and Child Cohort Study13

    Microsoft Academic Search

    Roy M Nilsen; Stein E Vollset; Håkon K Gjessing; Per Magnus; Helle M Meltzer; Margaretha Haugen; Per M Ueland

    Background: Patterns and predictors of maternal folic acid supple- ment use have not been examined in large prospective studies of pregnant women. Objective: We examined the patterns and predictors of maternal folic acid supplement use from 2 mo before pregnancy through the eighth month of pregnancy. Design: Data from 22 500 women in the Norwegian Mother and Child Cohort Study

  19. Use of the affinity/HPLC method for quantitative estimation of folic acid enriched cereal grain products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 1998, mandatory fortification of enriched cereal-grain products with folic acid was introduced in the United States to reduce the incidence of neural tube defects. As a consequence, substantial amounts of folic acid, the synthetic form of folate, were added to the American diet and the ability t...

  20. Impact of multiple micronutrient vs. iron - folic acid supplements on maternal anemia and micronutrient status in pregnancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Multiple micronutrient (MMN) supplements could increase hemoglobin and improve micronutrient status of pregnant women more than iron ± folic acid supplements alone. Objective. To compare the effects of MMN vs. iron ± folic acid supplements on hemoglobin and micronutrient status of pregn...

  1. Effect of oral folic acid supplementson zinc, copper, and iron absorption and excretion1-3

    Microsoft Academic Search

    DB Mime

    Effects offolicacidsupplements on zinc excretion patterns were seen during studies of mild zinc deficiency in men. During these studies eight men were fed diets containing 150 ?g of folacin (by analysis) per day. Four of the men were supplemented with 400 ,ug of pteroylglutamic acid (folic acid) every other day. All of the men were fed diets containing about 3.5

  2. Folic acid supplementation reduces oxidative stress and hepatic toxicity in rats treated chronically with ethanol

    PubMed Central

    Lee, Soo-Jung; Kang, Myung-Hee

    2011-01-01

    Folate deficiency and hyperhomocysteinemia are found in most patients with alcoholic liver disease. Oxidative stress is one of the most important mechanisms contributing to homocysteine (Hcy)-induced tissue injury. However it has not been examined whether exogenous administration of folic acid attenuates oxidative stress and hepatic toxicity. The aim of this study was to investigate the in vivo effect of folic acid supplementation on oxidative stress and hepatic toxicity induced by chronic ethanol consumption. Wistar rats (n = 32) were divided into four groups and fed 0%, 12%, 36% ethanol, or 36% ethanol plus folic acid (10 mg folic acid/L) diets. After 5 weeks, chronic consumption of the 36% ethanol diet significantly increased plasma alanine transaminase (ALT) (P < 0.05) and aspartate transaminase (AST) (P < 0.05), triglycerides (TG) (P < 0.05), Hcy (P < 0.001), and low density lipoprotein conjugated dienes (CD) (P < 0.05) but decreased total radical-trapping antioxidant potential (TRAP) (P < 0.001). These changes were prevented partially by folic acid supplementation. The 12% ethanol diet had no apparent effect on most parameters. Plasma Hcy concentration was well correlated with plasma ALT (r = 0.612**), AST (r = 0.652*), CD (r = 0.495*), and TRAP (r = -0.486*). The results indicate that moderately elevated Hcy is associated with increased oxidative stress and liver injury in alcohol-fed rats, and suggests that folic acid supplementation appears to attenuate hepatic toxicity induced by chronic ethanol consumption possibly by decreasing oxidative stress. PMID:22259676

  3. Effect of folic acid fortification on the incidence of neural tube defects.

    PubMed

    Amarin, Zouhair O; Obeidat, Ahmed Z

    2010-07-01

    In a few countries enriched cereal grains have been fortified with folic acid to reduce the incidence of neural tube defects. The objective of this study was to analyse the effect of folic acid fortified foods on the incidence of neural tube defects in live newborns at Princess Badea Teaching Hospital, in the north of Jordan, before and after the national food fortification with folic acid was implemented. For the 7-year period from 1 January 2000 to 31 December 2006, we retrospectively extracted the total number of births at Princess Badea Hospital, as well as the number of pregnancies affected by spina bifida and anencephaly, per 1000 births during the periods before (2000-01), during (2002-04) and after (2005-06) folic acid fortification of grain products, was implemented. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10): anencephaly, encephalocele and spina bifida. A total of 78 subjects with neural tube defects were recorded among 61 447 births during the study period. The incidence of neural tube defects decreased from 1.85 per 1000 births before fortification [95% confidence interval (CI) 1.2, 2.4] to 1.07 per 1000 births during the fortification period [95% CI 0.7, 1.5], and 0.95 after full fortification [95% CI 0.5, 1.5], a 49% reduction. The difference between incidence of neural tube defects in the periods before and after food fortification with folic acid was statistically significant. We conclude that food fortification with folic acid was associated with a significant reduction in the rate of neural tube defects in north Jordan. PMID:20618724

  4. Knowledge among young people about folic acid and its importance during pregnancy: a survey in the Federal State of Saxony-Anhalt (Germany)

    Microsoft Academic Search

    Simone Pötzsch; Jana Hoyer-Schuschke; Manuela Seelig; Volker Steinbicker

    2006-01-01

    Periconceptional folic acid supplementation is recommended to prevent congenital malformations, mainly neural tube defects, but only 7% of pregnant women in Saxony-Anhalt (Germany) take folic acid at least 4 weeks before conception and in the first 3 months of pregnancy. From March to June 2004, we sent standardized questionnaires about folic acid and its importance during pregnancy to 33 schools

  5. Investigation, using rat embryo culture, of the role of methionine supply in folic acid-mediated prevention of neural tube defects

    Microsoft Academic Search

    L. A. G. J. M. Vanaerts

    1995-01-01

    Peri-conceptional folic acid supplementation has become a well established way to prevent neural tube defects (NTDs) and such supplementation reduces the prevalence of these defects by approximately 70%. However, the mechanism of the preventive effect of folic acid is not clear. This overview focuses on the biochemical basis of folic acid-preventable NTDs and on the results obtained with whole embryo

  6. Are 5–7 Days of Folic Acid Supplementation Necessary prior to Pemetrexed? Observations from a Case Series

    PubMed Central

    Griffin, Benjamin R.; Stephens, Elisabeth K.; Jatoi, Aminah

    2013-01-01

    Objective Current regulatory guidelines advise 5–7 days of folic acid supplementation prior to pemetrexed. Although taking folic acid during and after pemetrexed therapy is important, it remains unclear whether premedication is truly necessary, particularly as it can be inconvenient for patients, can contribute to their anxiety by delaying chemotherapy, and can create challenges in scheduling chemotherapy. Methods and Results We retrospectively sought to identify and evaluate outcomes among non-small cell lung cancer patients who received less than the advised folic acid premedication. Only 8 patients were identified. However, upon critical examination of first-cycle chemotherapy outcomes, we observed no major adverse events with a shortened course of folic acid premedication. Conclusion In the very rare circumstance where urgent therapy is warranted, a healthcare provider can lookto this small case series and find modest precedent for the safe administration of pemetrexed in the absence of a full week of folic acid premedication. PMID:23898278

  7. The direct electrochemistry of folic acid at a 2-mercaptobenzothiazole self-assembled gold electrode

    Microsoft Academic Search

    Qijin Wan; Nianjun Yang

    2002-01-01

    A pair of well-defined redox waves of folic acid at a 2-mercaptobenzothiazole self-assembled gold electrode (MBT\\/SAM\\/Au) was achieved. Folic acid can bind strongly to MBT\\/SAM\\/Au and form a closely packed monolayer, whose average electron transfer rate is 0.085 s?1 with a two-electron\\/two proton transfer, a maximum surface coverage of 2.8×10?10 mol cm?2, an adsorption equilibrium constant of (4.0±0.2)×105 l mol?1,

  8. Folic acid use in pregnant patients presenting to the emergency department

    Microsoft Academic Search

    Jacob Steenblik; Erika Schroeder; Burke Hatch; Steven Groke; Camille Broadwater-Hollifield; Michael Mallin; Matthew Ahern; Troy Madsen

    2011-01-01

    Background  The US Preventive Services Task Force has recommended daily folic acid supplementation for women planning on becoming pregnant\\u000a in an effort to prevent fetal neural tube defects. We evaluated pregnant patients presenting to the emergency department to\\u000a determine rates of folic acid supplementation.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We surveyed a convenience sample of pregnant patients who presented to the University of Utah Emergency Department

  9. Awareness, knowledge, and use of folic acid among women: a study from Turkey

    Microsoft Academic Search

    Zeynep Baykan; Ahmet Öztürk; Serpil Poyrazo?lu; ?skender Gün

    2011-01-01

    Purpose  To investigate the awareness, knowledge, and behaviors relevant to folic acid intake in women aged 15–49 years.\\u000a \\u000a \\u000a \\u000a Materials and methods  A questionnaire designed by the researchers was administered to 1,083 women who attended to family health care centers for\\u000a any reason, between 1 and 15 of December 2009.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Half of the women (53.7%) surveyed did not hear or read about folic acid.

  10. Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose

    Microsoft Academic Search

    M. Y. Yanaguita; C. M. Gutierrez; C. N. M. Ribeiro; G. A. Lima; H. R. Machado; L. C. Peres

    2008-01-01

    Introduction  Maternal folic acid deficiency is the most important metabolic factor in the etiology of neural tube defects (NTD) and is\\u000a reduced by ethanol, which is extensively consumed by young women.\\u000a \\u000a \\u000a \\u000a Objective  The objective of the study was to determine whether folic acid supplementation in dietary saccharose is efficient in the prevention\\u000a NTD induced by ethanol in fetuses of Swiss mice.\\u000a \\u000a \\u000a \\u000a Materials

  11. Periconceptional folic acid prevents miscarriage in Irish families with neural tube defects

    Microsoft Academic Search

    J. Byrne

    2011-01-01

    Background  Miscarriages occur to excess in sibships with neural tube defects (NTDs) and among maternal versus paternal relatives in NTD\\u000a families. Folic acid prevents most NTDs. Its potential to prevent miscarriages has been controversial.\\u000a \\u000a \\u000a \\u000a \\u000a Aim  We evaluated the relationship of maternal line and periconceptional folic acid with miscarriage.\\u000a \\u000a \\u000a \\u000a Methods  First cousins in Irish families with NTDs were interviewed about pregnancy outcomes and the

  12. The effect of folic acid on porphyrin synthesis in tumors and normal skin of mice treated with 5-aminolevulinic acid or methyl 5-aminolevulinate.

    PubMed

    Ma, LiWei; Steindal, Arnfinn E; Juzeniene, Asta; Iani, Vladimir; Moan, Johan

    2006-08-01

    5-Aminolevulinic acid (ALA) or its derivative methyl 5-aminolevulinate (MAL) combined with folic acid was applied in nude mice bearing human colon adenocarcinoma. The aim of the study is to see whether folic acid may increase biosynthesis of porphyrins in tumor tissue after systemic or topical administration of ALA or MAL. The production of porphyrins was determined by spectrofluorometric measurements with an optical fibre probe. It was found that the porphyrin production after i.p injection of 200 mg kg(-1) ALA or MAL was significantly increased by i.p injection of 100 mg kg(-1) folic acid. However, in the case of topically applied 20% ALA, folic acid had no effect. In the case of topically applied 20% MAL, folic acid (i.p or topically applied) reduced the porphyrin synthesis. This might be used for the protection of normal skin against photosensitization. The effects of folic acid were similar in tumors and normal skin. Two mechanisms may explain the results: enhancement of the efficiency of the rate-limiting enzyme porphobilinogen deaminase by folic acid or interference of folic acid with the transport of ALA and MAL to and into the cells synthesizing porphyrins in the tissues. The present data seem to favour the latter mechanism. Folic acid may have a role as an adjuvant in photodynamic therapy with systemically administered ALA and its derivatives. PMID:16886091

  13. Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene1-3

    Microsoft Academic Search

    Alida Melse-Boonstra; Henk J Blom; Petra Verhoef

    Background: Before dietary folate is absorbed, polyglutamate fo- lates are deconjugated to monoglutamates by folylpoly--glutamyl carboxypeptidase in the small intestine. The 1561T allele of the glutamate carboxypeptidase II gene (GCPII), which codes for folylpoly--glutamyl carboxypeptidase, may impair intestinal ab- sorption of dietary folates. Objective: Our aim was to study the bioavailability of polyglutamyl folic acid relative to that of monoglutamyl

  14. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    SciTech Connect

    Dawson, Jennifer E. [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M. [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M. [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6 (Canada)]. E-mail: winnl@biology.queensu.ca

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  15. Maternal micronutrients (folic acid and vitamin B 12) and omega 3 fatty acids: Implications for neurodevelopmental risk in the rat offspring

    Microsoft Academic Search

    Suchitra Roy; Anvita Kale; Kamini Dangat; Pratiksha Sable; Asmita Kulkarni; Sadhana Joshi

    Altered maternal micronutrients (folic acid, vitamin B12) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B12 and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and

  16. Industry experience in promoting weekly iron-folic acid supplementation in the Philippines.

    PubMed

    Garcia, Josel; Datol-Barrett, Eva; Dizon, Maynilad

    2005-12-01

    After participating in a pilot project under a government-industry partnership to promote the adoption of weekly iron-folic acid supplementation among women of reproductive age in the Philippines in 1998, United Laboratories (UNILAB), the Philippines' largest private pharmaceutical company, decided in April 2002 to launch a weekly iron-folic acid supplement for pregnant and non-pregnant women under the brand name Femina. The business objective set for the Femina brand was to build the category of preventive iron-folic acid supplements in line with the Philippine Department of Health's advocacy on weekly supplementation as an alternate to daily dosing to reduce the prevalence of anemia in the country. The brand was supported with an integrated mix of traditional advertising media with complementary direct-to-consumer educational programs that aimed to create awareness of iron-deficiency anemia, its causes and effects, and the role of weekly intake of iron-folic acid in preventing the condition. Aggressive marketing support for 1 year was successful in creating awareness among the target women. Significant lessons derived from consumers identified opportunity areas that can be further addressed in developing advocacy programs on weekly iron supplementation implemented on a nationwide scale in the future. PMID:16466091

  17. Folic Acid Supplementation of Pregnant Mice Suppresses Heat Induced Neural Tube Defects in the

    Microsoft Academic Search

    Jae-Ho Shin; Kohei Shiota

    Neural tube defects (NTD) are a group of mal- formations that result from the failure of the neural tube to close early in embryonic development and among the most common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the

  18. The Role of Folic Acid Fortification in Neural Tube Defects: A Review

    Microsoft Academic Search

    Anja Osterhues; Nyima S. Ali; Karin B. Michels

    2012-01-01

    The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past thirty years but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a

  19. Effect of food fortification on folic acid intake in the United States1-3

    Microsoft Academic Search

    Eoin P Quinlivan; Jesse F Gregory

    Background: The addition of folic acid to all enriched cereal- grain foods, mandated by the Food and Drug Administration (FDA), was initiated in January 1998. Although this program was designed such that typical folate intakes would be increased by ? 100 ? g\\/d and that the risk of intakes > 1000 ? g\\/d (the FDA's safe upper limit of daily

  20. Folic acid fortification, maternal obesity and neural tube defects: Policy implications

    Microsoft Academic Search

    Parisa Assassi

    2008-01-01

    In 1996, the Food and Drug Administration (FDA) mandated that beginning in January 1998, flour and other enriched grain products be fortified with 140 ?g of folic acid per 100 g of grain to prevent neural tube defects (NTDs) that occur in approximately 1 in 1,000 pregnancies in the United States (U.S.). Although this program has demonstrated important public health

  1. Impact of folic acid supplementation in the United States: markedly diminished high maternal serum AFPs

    Microsoft Academic Search

    Mark I. Evans; Ronald J. Wapner; Joseph E. O’Brien; Elena Dvorin; Xiouha Huang; Harold Harrison

    2001-01-01

    Objective: Folic acid supplementation of breads and grains was implemented in the United States in 1998 to try to reduce the incidence of neural tube defects (NTDs). Complete birth registry outcome data will take several years to accumulate. Here we sought to use high maternal serum alpha-fetoprotein (MSAFP) values as a surrogate for likelihood of NTDs, both before and after

  2. Commentaries Scientific Evidence Supporting Folic Acid Fortification of Flour in Australia and New Zealand

    Microsoft Academic Search

    Godfrey P. Oakley; Mary Beth Weber; Karen N. Bell; Paul Colditz

    BACKGROUND: Fortification of flour with folic acid is a safe, sustainable, and cost-effective approach for preventing spina bifida and anencephaly, and it is likely to confer multiple health benefits to the adult population. Scientists and advocates are bringing this intervention to the attention of policymakers in countries around the world, and consequently the demand for sound, science-backed policy rationale is

  3. Knowledge and Use of Folic Acid by Women of Childbearing Age — United States, 1997

    Microsoft Academic Search

    1997-01-01

    Each year in the United States, approximately 4000 pregnancies are affected by spina bifida and anencephaly. Babies born with spina bifida usually survive, often with serious disability, but anencephaly is invariably fatal. The B vitamin folic acid can re- duce the occurrence of spina bifida and anencephaly by at least 50% when consumed daily before conception and during early pregnancy.

  4. Folic Acid Promotion for Hispanic Women in Florida: A Vitamin Diary Study

    ERIC Educational Resources Information Center

    Thomas, Kamilah B.; Hauser, Kimberlea; Rodriguez, Nydia Y.; Quinn, Gwendolyn P.

    2010-01-01

    Objective: To assess the barriers and benefits of taking multivitamins among Hispanic women exposed to a folic acid social marketing campaign in Florida, USA. Design and setting: Evaluation of non-pregnant women aged 18-35 from multiple Hispanic subgroups. Method: For 6 months, participants exposed to social marketing campaign educational…

  5. CHINESE STUDY OF THE EFFECTIVENESS OF FOLIC ACID IN A COMMUNITY INTERVENTION

    EPA Science Inventory

    The study was conducted jointly between CDC and Chinese health officials in 1998 to determine folic acid's effectiveness in reducing rates of neural tube defects (NTDs) in two areas of China. In summary, this study showed that in northern China, which has a high incidence of NTDs...

  6. Folic Acid Supplements and Risk of Facial Clefts: National Population Based Case-Control Study

    Microsoft Academic Search

    Allen J. Wilcox; Rolv Terje Lie; Kari Solvoll; Jack Taylor; D Robert McConnaughey; Hallvard Vindenes; Stein Emil Vollset; Christian A. Drevon

    2007-01-01

    Objective To explore the role of folic acid supplements, dietary folates, and multivitamins in the prevention of facial clefts. Design National population based case-control study. Setting Infants born 1996-2001 in Norway. Participants 377 infants with cleft lip with or without cleft palate; 196 infants with cleft palate alone; 763 controls. Main outcome measures Association of facial clefts with maternal intake

  7. Folic acid fortification and cancer risk: plea for objective evaluation of the evidence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The letter from Bayston and colleagues,1 representing the Association for Spina Bifida and Hydrocephalus, dismisses concerns raised by two recent studies2, 3 of a possible increase in colorectal cancer (CRC) risk following a high intake of folic acid. In relation to the postulated link between forti...

  8. A folic acid conjugated silica-titania porous hollow nanosphere for improved topical photodynamic therapy.

    PubMed

    Jang, Yoonsun; Kim, Sojin; Oh, Wan-Kyu; Kim, Chanhoi; Lee, Inkyu; Jang, Jyongsik

    2014-12-18

    The folic acid conjugated hollow nanosphere is used to encapsulate protoporphyrin IX and is utilized for photodynamic therapy. This system represents a 3.33 times higher photodynamic efficiency than previous protoporphyrin IX-based systems. The result proposes a new opportunity for effective photodynamic therapy of folate receptor positive tumor cells. PMID:25348554

  9. Moderately high intake of folic acid has a negative impact on mouse embryonic development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20-fold h...

  10. Folic acid—the scientific debate as a base for public health policy

    Microsoft Academic Search

    M. C. Cornel; D. J. de Smit; L. T. W. de Jong-van den Berg

    2005-01-01

    Randomized controlled trials have proven that periconceptional folic acid intake reduces the risk of neural tube defects (NTDs). This lead to different public health policies: fortification of foods in many countries and supplementation in some others. We concentrate here on pro's and con's of fortification policies. Meanwhile, new beneficial but also potential adverse effects are being hypothesized. Highest level evidence

  11. Public health significance of supplementation or fortification of grain products with folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The need for supplemental folate can be traced to the initial phase of the discovery of this vitamin as a micronutrient for the prevention of pregnancy related anemia. In the post discovery era, folic acid was used primarily to prevent deficiency as manifested by low blood folate levels and megalob...

  12. Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

    Microsoft Academic Search

    Eva Lonn; Salim Yusuf; D. Phil; J. Arnold; Patrick Sheridan; Janice Pogue; Mary Micks; Matthew J. McQueen; Jeffrey Probstfield

    We randomly assigned 5522 patients 55 years of age or older who had vascular dis- ease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from

  13. Reduction of Incidence of Prematurity by Folic Acid Supplementation in Pregnancy

    Microsoft Academic Search

    Naomi Baumslag; T. Edelstein; J. Metz

    1970-01-01

    Folic acid administered to pregnant Bantu, whose diet is low in folate, was associated with a significant reduction in the incidence of prematurity. No such effect could be demonstrated in White patients subsisting on an average Western diet. This suggests that folate deficiency may contribute to the “pregnancy wastage” in populations whose dietary folate intake is low, and is a

  14. Prevention of Neural Tube Defects: A Cross-Sectional Study of the Uptake of Folic Acid Supplementation in Nearly Half a Million Women

    PubMed Central

    Bestwick, Jonathan P.; Huttly, Wayne J.; Morris, Joan K.; Wald, Nicholas J.

    2014-01-01

    Background Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down’s syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. Methods and Findings 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%–35%) in 1999–2001 to 31% (30%–31%) in 2011–2012. 6% (5%–6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%–17%), Oriental 25% (24%–25%) and South Asian 20% (20%–21%) compared with 35% (35%–35%) for Caucasian women. 51% (48%–55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. Conclusions The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world. PMID:24586711

  15. A Study of the Prevalence of Serum Vitamin B12 and Folic Acid Deficiency in Western Maharashtra

    PubMed Central

    Mahajan, Sanket K.; Aundhakar, Swati C.

    2015-01-01

    Context: This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice. Aims and Objectives: 1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels. Materials and Methods: The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency. Results: Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency. Conclusion: In a small study, it was found that megaloblastic anemia may have symptoms and signs referable to several systems including hematology, dermatology, gastrointestinal, neurology, and neuropsychiatry. PMID:25810991

  16. Homocysteine, vitamin B12 and folic acid levels in psoriatic patients and correlation with disease severity.

    PubMed

    Brazzelli, V; Grasso, V; Fornara, L; Moggio, E; Gamba, G; Villani, S; Borroni, G

    2010-01-01

    Hyperhomocysteinaemia represents an independent risk factor for atherosclerotic cardiovascular disease, stroke, peripheral arterial occlusive disease and venous thrombosis. Psoriasis is a chronic inflammatory skin disease associated with increased atherothrombosis and cardiovascular risk profile. The aim of this study is to investigate homocysteine, folic acid and vitamin B12 levels in a cohort of psoriatic patients and its relationship with the severity of the disease. A retrospective observational study in 98 patients with chronic plaque psoriasis and 98 healthy controls was performed. Total plasma homocysteine level, folic acid, vitamin B12 and PASI index were assessed in every patient. Patients with psoriasis had plasma homocysteine levels higher than controls (57% of cases and 25% of controls; p<0.0001). Folic acid and vitamin B12 plasma levels were lower in psoriatic patients than in controls (p = NS), lower levels of vitamin B12 were found in patients with hyperhomocysteinaemia compared to patients with a normal value of homocysteine (p = 0.0009). The severity of psoriasis assessed according to PASI (19.51+/-16.26) did not directly correlate either with higher levels of homocysteine or with vitamin B12 and folic acid plasma levels. In conclusion, a significantly higher prevalence of hyperhomocysteinaemia was found in psoriatic patients compared to healthy controls. A significant correlation between hyperhomocysteinaemia and lower vitamin B12 levels, but not folic acid, was evidenced. On the contrary, our data do not correlate the high level of homocysteine with higher PASI scores or psoriasis type, suggesting that homocysteine level can be considered an independent risk factor in psoriatic patients. PMID:20943063

  17. The effect of subchronic supplementation with folic acid on homocysteine induced seizures.

    PubMed

    Rasic-Markovic, A; Rankov-Petrovic, B; Hrncic, D; Krstic, D; Colovic, M; Macut, Dj; Djuric, D; Stanojlovic, Olivera

    2015-06-01

    Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na(+)/K(+)-ATPase and Mg(2+)-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na(+)/K(+)-ATPase and Mg(2+)-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases. PMID:26100305

  18. Role of sodium ion in transport of folic acid in the small intestine

    SciTech Connect

    Zimmerman, J.; Selhub, J.; Rosenberg, I.H.

    1986-08-01

    The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the influx chamber and isoalted brush-border membrane vesicles. Preincubation of tissue in Na -free medium did not have a consistent effect on folic acid influx provided that Na was present in the test solution. Replacement of Na in the test solution by choline resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na -free solution were exposed to test solutions containing either Na , Li , K , Rb , Cs , Tris , or guanidinium as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na by Rb did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb . Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na than in the presence of K , but was not different from uptake in the presence of K plus valinomycin. These data suggest that 1) the saturable component of folate transport is not Na dependent, and 2) nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na in this process in vivo derives from the fact that Na is the most permeant cation available at the absorptive site in the small intestine.

  19. Influence of acid surrogates toward potency of VLA4 antagonist

    Microsoft Academic Search

    Shankar Venkatraman; Jongwon Lim; Merryl Cramer; Michael F. Gardner; Joyce James; Kenneth Alves; Russell B. Lingham; Richard A. Mumford; Benito Munoz

    2005-01-01

    A series of VLA-4 antagonist were synthesized wherein carboxylic acid was replaced by various acid surrogates. The effect of these acid surrogates toward potency was evaluated in a binding assay. A number of acid surrogates were potent antagonist of VLA-4, albeit significantly less potent than the corresponding carboxylic acid. Heterocyclic acid surrogate, oxadiazolidinone 3, demonstrated an improved pharmacokinetic property when

  20. Folic acid absorption determined by a single stool sample test--a double-isotope technique. The folic acid absorption capacity in children

    SciTech Connect

    Hjelt, K. (Univ. of Copenhagen, Hellerup (Denmark))

    1989-10-01

    The fractional folic acid absorption (FAFol) was determined in 66 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST) as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.8 years (mean 6.3 years). The test dose was administered orally and consisted of 50 micrograms of (3H)folic acid (monoglutamate) (approximately 20 muCi), carmine powder, and 2 mg 51CrCl3 (approximately 1.25 muCi) as the unabsorbable tracer. The whole-body radiation given to a 1-year-old child averaged 4.8 mrad only. The stool and napkin contents were collected and homogenized by the addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin contents, as well as 300 ml chromium sulfuric acid (75% vol/vol) containing the standards, were counted for the content of 51Cr in a broad-based well counter. The quantity of (3H)folic acid was determined by liquid scintillation, after duplicate distillation. Estimated by SSST, the FAFol, which employs the stool with the highest content of 51Cr corresponding to the most carmine-colored stool, correlated closely with the FAFol based on complete stool collection (r = 0.96, n = 39, p less than 0.0001). The reproducibility of FAFol determined by SSST was assessed from repeated tests in 18 patients. For a mean of 81%, the SD was 4.6%, which corresponded to a coefficient of variation of 5.7%.

  1. Introduction of biotin or folic acid into polypyrrole magnetite core-shell nanoparticles

    SciTech Connect

    Nan, Alexandrina; Turcu, Rodica [National Institute of Research and Development for Isotopic and Molecular Technologies, Donath 65-103, Cluj-Napoca (Romania)] [National Institute of Research and Development for Isotopic and Molecular Technologies, Donath 65-103, Cluj-Napoca (Romania); Liebscher, Jürgen [National Institute of Research and Development for Isotopic and Molecular Technologies, Donath 65-103, Cluj-Napoca, Romania and Institute of Chemistry, Humboldt-University Berlin, Brook-Taylor 2, D-12489 Berlin (Germany)] [National Institute of Research and Development for Isotopic and Molecular Technologies, Donath 65-103, Cluj-Napoca, Romania and Institute of Chemistry, Humboldt-University Berlin, Brook-Taylor 2, D-12489 Berlin (Germany)

    2013-11-13

    In order to contribute to the trend in contemporary research to develop magnetic core shell nanoparticles with better properties (reduced toxicity, high colloidal and chemical stability, wide scope of application) in straightforward and reproducible methods new core shell magnetic nanoparticles were developed based on polypyrrole shells functionalized with biotin and folic acid. Magnetite nanoparticles stabilized by sebacic acid were used as magnetic cores. The morphology of magnetite was determined by transmission electron microscopy TEM, while the chemical structure investigated by FT-IR.

  2. Introduction of biotin or folic acid into polypyrrole magnetite core-shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

    2013-11-01

    In order to contribute to the trend in contemporary research to develop magnetic core shell nanoparticles with better properties (reduced toxicity, high colloidal and chemical stability, wide scope of application) in straightforward and reproducible methods new core shell magnetic nanoparticles were developed based on polypyrrole shells functionalized with biotin and folic acid. Magnetite nanoparticles stabilized by sebacic acid were used as magnetic cores. The morphology of magnetite was determined by transmission electron microscopy TEM, while the chemical structure investigated by FT-IR.

  3. Time dependent inhibition of xanthine oxidase in irradiated solutions of folic acid, aminopterin and methotrexate

    SciTech Connect

    Robinson, K.; Pilot, T.F.; Meany, J.E. (Department of Chemistry, Seattle University, WA (USA))

    1990-01-01

    The xanthine oxidase catalyzed oxidation of hypoxanthine was followed by monitoring the formation of uric acid at 290 nm. Inhibition of xanthine oxidase occurs in aqueous solutions of folic acid methotrexate and aminopterin. These compounds are known to dissociate upon exposure to ultraviolet light resulting in the formation of their respective 6-formylpteridine derivatives. The relative rates of dissociation were monitored spectrophotometrically by determining the absorbance of their 2,4-dinitrophenylhydrazine derivatives at 500 nm. When aqueous solutions of folic acid, aminopterin and methotrexate were exposed to uv light, a direct correlation was observed between the concentrations of the 6-formylpteridine derivatives existing in solution and the ability of these solutions to inhibit xanthine oxidase. The relative potency of the respective photolysis products were estimated.

  4. Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Teow, Yiwei; Valiyaveettil, Suresh

    2010-12-01

    Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized via reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 ?g ml-1 for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

  5. Effects of folic acid on epithelial apoptosis and expression of Bcl2 and p53 in premalignant gastric lesions

    Microsoft Academic Search

    Da-Zhong Cao; Wei-Hao Sun; Xi-Long Ou; Qian Yu; Ting Yu; You-Zhen Zhang; Zi-Ying Wu; Qi-Ping Xue; Yun-Lin Cheng

    2005-01-01

    Abstract Abstract Abstract Abstract Abstract AIM: To evaluate,the effects, of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric

  6. Electropolymerized molecularly imprinted polymer films of a bis-terthiophene dendron: folic acid quartz crystal microbalance sensing.

    PubMed

    Apodaca, Dahlia C; Pernites, Roderick B; Ponnapati, Ramakrishna R; Del Mundo, Florian R; Advincula, Rigoberto C

    2011-02-01

    A folic acid sensor was prepared via an electropolymerized molecularly imprinted polymer (E-MIP) film of a bis-terthiophene dendron on a quartz crystal microbalance (QCM). The cyclic voltammetry (CV) electrodeposition of the imprinted polymer film was monitored by electrochemical QCM or E-QCM, enabling in situ monitoring and characterization of E-MIP film formation and the viscoelastic behavior of the film. A key component of the E-MIP process is the use of a bifunctional monomer design to precomplex with the template and function as a cross-linker. The complex was electropolymerized and cross-linked by CV to form a polythiophene matrix. Stable cavities were formed that specifically fit the size and shape of the folic acid template. The same substrate surface was used for folic acid sensing. The predicted geometry of the 1:2 folic acid/terthiophene complex was obtained through semiempirical AM1 quantum calculations. The analytical performance, expressed through the figures of merit, of the sensor in aqueous solutions of the analyte was investigated. A relatively good linearity, R(2) = 0.985, was obtained within the concentration range 0-100 ?M folic acid. The detection limit was found to be equal to 15.4 ?M (6.8 ?g). The relative cross selectivity of the folic acid imprinted polymer against the three molecules follows this trend: pteroic acid (= 50%) > caffeine (= 41%) > theophylline (= 6%). The potential and limitations of the E-MIP method were also discussed. PMID:21080660

  7. In vitro antioxidant activity and in vivo antifatigue effect of layered double hydroxide nanoparticles as delivery vehicles for folic acid

    PubMed Central

    Qin, Lili; Wang, Wenrui; You, Songhui; Dong, Jingmei; Zhou, Yunhe; Wang, Jibing

    2014-01-01

    Folic acid antioxidants were successfully intercalated into layered double hydroxides (LDH) nanoparticles according to a previous method with minor modification. The resultant folic acid-LDH constructs were then characterized by X-ray powder diffraction and transmission electron microscopy. The in vitro antioxidant activities, cytotoxicity effect, and in vivo antifatigue were examined by a series of assays. The results showed that folic acid-LDH antioxidant system can scavenge 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals and chelate pro-oxidative Cu2+. The in vitro cytotoxicity assays indicated that folic acid-LDH antioxidant system had no significant cytotoxic effect or obvious toxicity to normal cells. It also prolonged the forced swimming time of the mice by 32% and 51% compared to folic acid and control groups, respectively. It had an obvious effect on decreasing the blood urea nitrogen and blood lactic acid, while increasing muscle and hepatic glycogen levels. Therefore, folic acid-LDH might be used as a novel antioxidant and antifatigue nutritional supplement. PMID:25506219

  8. Assessing Awareness, Knowledge and Use of Folic Acid in Kansas Women Between the Ages of 18 and 44 Years

    Microsoft Academic Search

    Glynda F. Sharp; Lorenda A. Naylor; Jinwen Cai; Melissa L. Hyder; Pradeep Chandra; V. James Guillory

    2009-01-01

    Taking folic acid daily, before and during early pregnancy, has been proven to reduce neural tube birth defects (NTD). Unfortunately,\\u000a many women fail to take it daily as recommended. Objectives To assess women’s self-reported awareness, knowledge and use of folic acid. Methods Data were obtained by cross-sectional, random digit-dialing, computer-assisted telephone interviews with 250 women in Kansas.\\u000a Associations were determined

  9. Folic acid and the prevention of neural tube defects: A position paper of the national society of genetic counselors

    Microsoft Academic Search

    Bonnie Jeanne Baty; Leslie Cohen; Lorna Phelps; Marcy C. Speer; Pamela Stengel; Lori Williamson-Kruse

    1996-01-01

    Considerable scientific evidence demonstrates the reduction in risk for neural tube defects (NTDs) associated with maternal preconceptional folic acid supplementation. The National Society of Genetic Counselors (NSGC) endorses the U.S. Public Health Service recommendations for folic acid supplementation at the 0.4 mg level for women in the general population and at the 4.0 mg level for women at high or

  10. Awareness and Intake of Folic Acid for the Prevention of Neural Tube Defects Among Lebanese Women of Childbearing Age

    Microsoft Academic Search

    Claudine Nasr Hage; Maya Jalloul; Mohamad Sabbah; Salim M. Adib

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period\\u000a as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient.\\u000a To assess the awareness and actual intake of folic acid among married Lebanese women aged 18–45 years, a cross-sectional study\\u000a was conducted among 600 women selected from all

  11. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial

    Microsoft Academic Search

    Wai Yee Wong; Hans M. W. M Merkus; Chris M. G Thomas; Roelof Menkveld; Gerhard A Zielhuis; Régine P. M Steegers-Theunissen

    2002-01-01

    Objective: To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.Design: Double-blind, placebo-controlled interventional study.Setting: Two outpatient fertility clinics and nine midwifery practices in The Netherlands.Participant(s): One hundred eight fertile and 103 subfertile men.Intervention(s): Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and

  12. Effect of Folic Acid and Vitamin B12 on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells

    PubMed Central

    Yang, Tsung-Ying; Chang, Gee-Chen; Hsu, Shih-Lan; Huang, Yi-Rou; Chiu, Ling-Yen

    2013-01-01

    Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p21WAF1/Cip1 expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients. PMID:23984356

  13. Electrochemical sensor for folic acid based on a hyperbranched molecularly imprinted polymer-immobilized sol–gel-modified pencil graphite electrode

    Microsoft Academic Search

    Bhim Bali Prasad; Rashmi Madhuri; Mahavir Prasad Tiwari; Piyush Sindhu Sharma

    2010-01-01

    Contrary to the ‘substructure imprinting approach’ of larger molecule like folic acid, which often leads molecular recognition for both folic acid and structural analogues containing pteridine and glutamic acid substructures, a molecularly imprinted polymer capable of binding specifically folic acid has been prepared by stoichiometric imprinting process (template\\/monomer molar ratio, 1:3) creating multiple binding sites within the cross-linked hyperbranched polymer.

  14. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid.

    PubMed

    Heseker, Helmut B; Mason, Joel B; Selhub, Jacob; Rosenberg, Irwin H; Jacques, Paul F

    2009-07-01

    Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a 'floor effect' for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups. PMID:19079944

  15. [Effects of excess folic acid on growth and metabolism of water-soluble vitamins in weaning rats].

    PubMed

    Fukuwatari, Tsutomu; Shibata, Katsumi

    2008-02-01

    In order to determine the tolerable upper intake level of folic acid in humans, we investigated the effects of excessive folic acid administration on the body weight gain, food intake, tissue weight, and metabolism of B-group vitamins in weaning rats. The rats were freely fed ordinary diet containing 0.0002% folic acid (control diet) or the same diet with 0.01%, 0.1%, or 1.0% folic acid for 29 days. The body weight gains and food intakes did not differ among the four groups. Diarrhea was not seen even in the 1.0% group. Excess folic acid did not affect the tissue weights of the brain, heart, liver, kidney, spleen, lung, or testis, or urinary excretion of other B-group vitamins. These results clearly showed that feeding a diet containing up to 1.0% folic acid did not affect the food intake, body weight gain, tissue weight, or urinary excretion of B-group vitamins in weaning rats. PMID:18344659

  16. Vitamin B12 and Folic Acid Imbalance Modifies NK Cytotoxicity, Lymphocytes B and Lymphoprolipheration in Aged Rats

    PubMed Central

    Partearroyo, Teresa; Úbeda, Natalia; Montero, Ana; Achón, María; Varela-Moreiras, Gregorio

    2013-01-01

    Different vitamin B12 and folic acid concentrations could exacerbate the immune response. The aim was to evaluate different dietary folic acid and vitamin B12 levels on the immune response in aged rats. Male Sprague Dawley aged rats were assigned to three folic acid groups (deficient, control, supplemented) each in absence of vitamin B12 for 30 days. Several parameters of innate and acquired immune responses were measured. Serum and hepatic folate levels increased according to folic acid dietary level, while vitamin B12 levels decreased. There was a significant decrease in natural killer cell-mediated cytotoxicity in the spleen for the vitamin B12 deficient diet and folic acid control diet groups. Significant changes in CD45 lymphocyte subsets were also observed according to dietary imbalance. Lymphoproliferative response to concanavalin A and phytohemagglutinin did not differ significantly between groups. The spleen response to lipopolysaccharide increased significantly, but was unmodified for the other organs. An imbalance between dietary vitamin B12 and folic acid concentrations alters some immunological parameters in aged rats. Therefore, the ratio between folate and vitamin B12 could be as important as their absolute dietary concentrations. PMID:24288024

  17. Arnold Chiari malformation with spina bifida: a lost opportunity of folic Acid supplementation.

    PubMed

    Ganesh, Deepa; Sagayaraj, Benjamin M; Barua, Ravi Kumar; Sharma, Nidhi; Ranga, Upasana

    2014-12-01

    In Arnold Chiari (kee-AHR-ee) II malformation elongated cerebellar tonsils are displaced inferiorly through the Foramen Magnum into the upper cervical spinal canal. It is a complex anomaly with skull, dura, brain, spine and cord manifestations. Meningomyelocele is seen in all cases. We present a case of type II Arnold Chiari Malformation diagnosed in utero in a pregnant lady .There was no periconceptional folic acid supplementation. As the role of the Methylene Tetra Hydro Folate Reductase gene polymorphism in neural tube defects is becoming evident, a simple opportunity as folic acid supplementation should not be missed. Folate supplementation as fortification of cereal grains will also prevent other conditions like congenital heart defects, urinary tract anomalies, orofacial defects, limb defects and pyloric stenosis. PMID:25653995

  18. CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification.

    PubMed

    2010-08-13

    Neural tube defects (NTDs) are serious birth defects that result from the failure of the neural tube to close in the cranial region (anencephaly) or more caudally along the spine (spina bifida) by the 28th day of gestation. Infants born with anencephaly usually die within a few days of birth, and those with spina bifida have life-long disabilities with varying degrees of paralysis. Currently, identified risk factors for NTDs include a mother who previously had an NTD-affected pregnancy, maternal diabetes, obesity, hyperthermia, certain antiseizure medications, genetic variants, race/ethnicity, and nutrition (particularly folic acid insufficiency). In the United States, during 1995-1996, approximately 4,000 pregnancies were affected by an NTD. This number declined to 3,000 pregnancies in 1999-2000 after fortification of enriched cereal grain products with folic acid was mandated. Worldwide, in 1998, approximately 300,000 births were affected by an NTD. PMID:20703205

  19. Characteristics of Dispersed ZnO-Folic acid Conjugate in Aqueous Medium

    E-print Network

    Sreetama Dutta; Bichitra Nandi Ganguly

    2013-12-04

    The focus of this article is based on the aqueous dispersed state properties of inorganic ZnO nanoparticles (average size lessthan or equal to 4 nm), their surface modification and bio-functionalization with folic acid at physiological pH ~ 7.5, suitable for bio-imaging and targeted therapeutic application. While TEM studies of the ZnO nano-crystallites have been performed to estimate their size and morphology in dry state, the band gap properties of the freshly prepared samples, the hydrodynamic size in aqueous solution phase and the wide fluorescence range in visible region have been investigated to establish the fact that the sol is particularly suitable for the bio-medical purpose in the aqueous dispersed state. Key words: ZnO nanoparticle; folic acid; band gap; hydrodynamic size; fluorescence.

  20. Biogenic gold nanoparticles as fotillas to fire berberine hydrochloride using folic acid as molecular road map.

    PubMed

    Pandey, Sunil; Mewada, Ashmi; Thakur, Mukeshchand; Shah, Ritu; Oza, Goldie; Sharon, Madhuri

    2013-10-01

    Use of biologically modified gold nanoparticles (GNPs) as molecular vehicle to ferry potential anti-cancer drug berberine hydrochloride (BHC) using folic acid (FA) as targeting molecule is reported in this work. A tropical fruit peel, Trapa bispinosa is used to fabricate highly monodispersed GNPs, passivated with essential functional groups which were used as linkers to attach FA and BHC via amide linkage. Flocculation Parameter (FP) of biologically synthesized GNPs was calculated under different salt concentrations which were found to be very ideal under a physiological condition. Various statistical models were used to find drug release profile out of which Higuchi was found to be the most ideal. GNP-FA-BHC complexes were found to be active against folic acid expressing HeLa cells. PMID:23910269

  1. Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India

    Microsoft Academic Search

    Anoop Misra; Naval K. Vikram; R. M. Pandey; Manjari Dwivedi; Faiz Uddin Ahmad; Kalpana Luthra; Kajal Jain; Nidhi Khanna; J. Rama Devi; Rekha Sharma; Randeep Guleria

    2002-01-01

    Summary  \\u000a Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing\\u000a stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which\\u000a may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy

  2. Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in Apc Min\\/+ mice

    Microsoft Academic Search

    Jody M Tucker; Celestia Davis; Maria E Kitchens; Marlene A Bunni; David G Priest; H. Trent Spencer; Franklin G Berger

    2002-01-01

    5-Fluorouracil (5-FU) has been the foundation of advanced colorectal cancer treatment for over 40 years. The ApcMin\\/+ mouse, which is genetically predisposed to intestinal neoplasia, was used to examine the effects of 5-FU in this system and the impact of dietary folic acid on those effects. 5-FU treatment resulted in a 60–80% reduction in tumor number. Clinically relevant toxicities, including

  3. Periconceptional folic acid use and the prevalence of neural tube defects in The Netherlands

    Microsoft Academic Search

    Karin M. van der Pal-de Bruin; Simone E. Buitendijk; A. Lya den Ouden

    2003-01-01

    Objective: To study the effect of increased folic acid intake on the prevalence of neural tube defects (NTD) in The Netherlands. Study design: Using the capture–recapture method, the prevalence of NTD was estimated on the basis of five different registries on births affected by NTD. Results: Total prevalence over the 1988–1998 period varied between 1.43 and 1.96 per 1000 live

  4. Promoting Folic Acid to Spanish-Speaking Hispanic Women: Evaluating Existing Campaigns to Guide New Development

    Microsoft Academic Search

    Michael Mackert; LeeAnn Kahlor; Kristi Silva; Yolanda Padilla

    2010-01-01

    Hispanic women are 1.5–3 times as likely as non-Hispanic white women to have a child affected by neural tube defects. This disparity exists in spite of varied interventions designed to address the problem. The purpose of this research was to investigate Hispanic women's knowledge of folic acid, perceptions of existing education campaigns, and provide guidance for future promotion efforts. Three

  5. The influence of folic acid supplementation on maternal and fetal bone turnover

    Microsoft Academic Search

    Arash Hossein-nezhad; Khadijeh Mirzaei; Zhila Maghbooli; Azam Najmafshar; Bagher Larijani

    2011-01-01

    The aim of our study was to investigate the relationship between maternal and fetal bone turnover markers and folic acid supplementation\\u000a during pregnancy. In an observational study performed in Tehran University of Medical Sciences related hospitals, 113 healthy\\u000a pregnant women with gestational age between 8 and 12 weeks and aged between 15 and 42 years were recruited and followed until\\u000a delivery time.

  6. Reproductive toxicity of methomyl insecticide in male rats and protective effect of folic acid

    Microsoft Academic Search

    M. A. Shalaby; H. Y. El Zorba; Reem M. Ziada

    2010-01-01

    The acute toxicity (LD50) of insecticide methomyl and its effects on male reproduction in rats were carried out. Methomyl was given orally to male rats daily for 65 successive days at two doses (0.5 and 1.0mgkg?1b.wt., corresponding to 1\\/40 and 1\\/20 LD50) alone and in combination with folic acid (1.1mgkg?1b.wt., corresponding to acceptable daily intake, ADI). Fertility index, weight of

  7. The role of folic acid and Vitamin B12 in genomic stability of human cells

    Microsoft Academic Search

    Michael Fenech

    2001-01-01

    Folic acid plays a critical role in the prevention of chromosome breakage and hypomethylation of DNA. This activity is compromised when Vitamin B12 (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.

  8. High dose of maternal folic acid supplementation is associated to infant asthma.

    PubMed

    Yang, Liu; Jiang, Liwen; Bi, Meirong; Jia, Xiaodong; Wang, Youqing; He, Chuan; Yao, Yao; Wang, Jun; Wang, Zhiping

    2015-01-01

    Maternal folic acid supplementation had a positive effect on preventing neural tube defects (NTDs), but its effects in infant asthma remained unclear. A hospital-based case-control study was conducted with outpatients between March 2010 and March 2011 including 150 onset infant asthma cases and 212 controls, together with a meta-analysis involving 14,438 participants, was performed. The association between maternal folic acid supplementation and the risk of infant asthma was not significant either in the meta-analysis (OR?=?1.06, 95% CI?=0.99-1.14) or in the case-control study (OR?=?0.72, 95% CI?=0.37-1.39). However, quantitative analysis of the supplementation dose demonstrated that the risk of infant asthma significantly increased for the infants whose mother were with high-dose supplementation (>72,000?µg•d; OR?=?3.16, 95% CI?=1.15-8.71) after adjusting for confounding factors in the case-control study. Meanwhile, the risk of infant asthma significantly decreased for the infants whose mother were with low-dose supplementation (<36,000?µg•d; OR?=?0.36, 95% CI?=0.17-0.77). A high dose of folic acid supplementation for mother during pregnancy was associated with an increased risk of infant asthma, whereas supplementation with a relatively low-dose was associated with a decreased risk of infant asthma. These findings should be further investigated in a large population. PMID:25449200

  9. The role of folic acid fortification in neural tube defects: a review.

    PubMed

    Osterhues, Anja; Ali, Nyima S; Michels, Karin B

    2013-01-01

    The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past 30 years, but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a significant portion of NTDs still persists. Population data suggest that women of childbearing age may not yet be adequately targeted, while the general population may be overfortified with folic acid. While an excessive folate intake may be associated with adverse effects, there remains uncertainty about the minimum effective folate intake and status required for NTD prevention, and the safe upper folate level. Besides folate, several other lifestyle and environmental factors as well as genetic variations may influence NTD development, possibly by affecting one-carbon metabolism and thus epigenetic events. In conclusion, mandatory folic acid fortification plays a significant part in the reduction of NTD prevalence, but possibly at a cost and with a portion of NTDs remaining. More effective preventive strategies require better understanding of the etiology of this group of birth defects. PMID:24007422

  10. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via ?-? interactions.

    PubMed

    Fan, Hailong; Yu, Xiang; Liu, Yang; Shi, Zujin; Liu, Huihui; Nie, Zongxiu; Wu, Decheng; Jin, Zhaoxia

    2015-06-01

    Recent research has indicated that polydopamine and synthetic eumelanins are optoelectronic biomaterials in which one-dimensional aggregates composed of ordered-stacking oligomers have been proposed as unique organic semiconductors. However, improving the ordered-stacking of oligomers in polydopamine nanostructures is a big challenge. Herein, we first demonstrate how folic acid molecules influence the morphology and nanostructure of polydopamine via tuning the ?-? interactions of oligomers. MALDI-TOF mass spectrometry reveals that porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA) nanofibers. X-ray diffraction combined with simulation studies indicate that these oligomers favour aggregation into graphite-like ordered nanostructures via strong ?-? interactions. High-resolution TEM characterization of carbonized FA-PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains is over 100 nm. The addition of folic acid in polydopamine enhances the ordered stacking of oligomers in its nanostructure. Our study steps forward to discover the mystery of the structure-property relationship of FA-PDA hybrids. It paves a way to optimize the properties of PDA through the design and selection of oligomer structures. PMID:25959650

  11. Effect of trans-retinoic acid and folic acid on apoptosis in human gastric cancer cell lines MKN-45 and MKN-28

    Microsoft Academic Search

    Jing-Yuan Fang; Shu-Dong Xiao

    1998-01-01

    :   Induction of apoptosis has been implicated as an anticarcinogentic mechanism of both folic acid and retinoic acid. The ability\\u000a of retinoic acid or folic acid to induce gastric cancer cell apoptosis was investigated in the human gastric cancer cell lines\\u000a MKN-45 and MKN-28, and DNA fragmentation was studied in situ by terminal deoxynucleotidyl transferase-mediated dUTP-biotin\\u000a nick end labeling and

  12. Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study1-3

    Microsoft Academic Search

    Bernard J Venn; Timothy J Green; Rudolf Moser; Jim I Mann

    Background: Food fortification with folic acid has been intro- duced in several countries for the prevention of neural tube defects. Fortification has lowered total homocysteine (tHcy) con- centrations in the US population, a consequence that may have health benefits. However, folic acid fortification could mask vita- min B-12 deficiency. Synthetic L-5-methyltetrahydrofolate (L- MTHF) may be more appropriate than folic acid

  13. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages

    Microsoft Academic Search

    Lutfi Jaber; Igbaria A. Karim; Abu Moch Jawdat; Mawasi Fausi; Paul Merlob

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50–70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of

  14. [Characterization of antagonistic and acid formation properties of Lactobacillus casei].

    PubMed

    Saduakhasova, S A; Kushugulova, A R; Rakhimova, S E; Oralbaeva, S S; Bisenova, N M; Almagambetov, K Kh

    2007-01-01

    Cultural, morphologic, and biochemical characteristics of Lactobacillus casei were studied as well as their acid-forming and antagonistic activity and resistance to antibiotics. 60 cultures identified as L. caseiwere isolated from 250 samples of sour-milk products and clinical specimens. All isolated strains had respectively high antagonistic activity regardless of their source. Dependence between antagonistic activity and acid formation was not detected. Conclusion about promise for using these lactobacilli for manufacturing of probiotics has been done. PMID:17523487

  15. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

    PubMed

    Williams, Jennifer; Mai, Cara T; Mulinare, Joe; Isenburg, Jennifer; Flood, Timothy J; Ethen, Mary; Frohnert, Barbara; Kirby, Russell S

    2015-01-16

    In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States. PMID:25590678

  16. The micronutrient supplements, zinc sulphate and folic acid, did not ameliorate sperm functional parameters in oligoasthenoteratozoospermic men.

    PubMed

    Raigani, M; Yaghmaei, B; Amirjannti, N; Lakpour, N; Akhondi, M M; Zeraati, H; Hajihosseinal, M; Sadeghi, M R

    2014-11-01

    We investigated the effects of folic acid and zinc sulphate supplementation on the improvement of sperm function in subfertile oligoasthenoteratozoospermic (OAT) men. Eighty-three OAT men participated in a 16-week intervention randomised, double-blind clinical trial with daily treatment of folic acid (5 mg day(-1) ) and zinc sulphate (220 mg day(-1) ), or placebo. Before and after treatment, semen and blood samples were obtained for determining sperm concentration, motility, and morphology, sperm viability, sperm mitochondrial function, sperm chromatin status using toluidine blue, aniline blue, acridine orange and chromomycin A3 staining; and semen and blood folate, zinc, B12 , total antioxidant capacity (TAC) and malondialdehyde (MDA) concentrations. Sperm concentration (×10(6)  ml(-1) ) increased in subfertile men receiving the combined treatment of folic acid and zinc sulphate and also in the group receiving only folic acid treatment; however, it was not statistically significant (P = 0.056 and P = 0.05, respectively). Sperm chromatin integrity (%) increased significantly in subfertile men receiving only zinc sulphate treatment (P = 0.048). However, this improvement in sperm quality was not significant after adjusting placebo effect. This study showed that zinc sulphate and folic acid supplementation did not ameliorate sperm quality in infertile men with severely compromised sperm parameters, OAT. Male infertility is a multifactorial disorder, and also nutritional factors play an important role in results of administration of supplementation on sperm parameters. However, these results should be confirmed by multiple studies in larger populations of OAT men. PMID:24147895

  17. The Effect of Folic Acid on Menopausal Hot Flashes: A Randomized Clinical Trial

    PubMed Central

    Bani, Soheila; Hasanpour, Shirin; Farzad Rik, Leila; Hasankhani, Hadi; Sharami, Seiedeh Hajar

    2013-01-01

    Introduction: The use of alternative therapies for the treatment of menopausal hot flashes has increased due to the serious risk of hormone therapy. Most alternative therapies have not been accepted by women. Therefore, conducting a study to find effective treatment, which has a low rate of complications and is more acceptable, is necessary. The aim of this study was to assess the effects of folic acid on menopausal hot flashes. Methods: In the present study 70 menopausal women were placed into two groups of 35 with random allocation, and were treated with folic acid 1 mg tablets and placebo tablets once a day during four weeks. Information was gathered by questionnaire, interviews, and hot flash diary during five stages. Comparisons of within-group Results were performed by ANOVA and between-group results were performed using ANCOVA. Data were analyzed by SPSS for Windows. Results: There was a significant difference between mean severity, duration, and frequency of hot flashes before and after treatment within both groups. In comparing the results between the groups, mean hot flash severity in second, third, and fourth weeks were significantly different. The mean hot flash frequency was significantly different in third and fourth weeks, and the mean hot flash duration was significantly different in the fourth week. Conclusion: The results of the present study indicated that folic acid was effective in reducing the severity, duration, and frequency of hot flashes during menopause. Therefore, it can be recommended as an affordable and accessible method for treating menopausal hot flash for women. PMID:25276719

  18. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

    PubMed

    Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

    2015-06-01

    Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity. © 2015 Wiley Periodicals, Inc. PMID:25846410

  19. Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia

    PubMed Central

    Regland, Björn; Forsmark, Sara; Halaouate, Lena; Matousek, Michael; Peilot, Birgitta; Zachrisson, Olof; Gottfries, Carl-Gerhard

    2015-01-01

    Background Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders. Objective To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years. Methods 38 patients were included in a cross-sectional survey. Based on a validated observer’s rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects. Results Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as “very much” or “much” improved, while Mild responders rated “much” or “minimally” improved. Conclusions Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It’s important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed. PMID:25902009

  20. Fortification of corn masa flour with folic acid in the United States: an overview of the evidence

    PubMed Central

    Hamner, Heather C.; Tinker, Sarah C.

    2015-01-01

    Corn masa flour, used to make products such as corn tortillas, is a staple food for Hispanic populations residing in the United States, particularly among Mexican Americans and Central Americans. Research has indicated that Hispanic women in the United States continue to be at a higher risk of having a neural tube defect–affected pregnancy than women of other races/ethnicities, even after the introduction of folic acid fortification of cereal grain products labeled as “enriched.” Corn masa flour has, therefore, been suggested as a potential food vehicle for folic acid in the United States. This paper explores the potential impact that folic acid fortification of corn masa flour could have on the Hispanic population in the United States. PMID:24494975

  1. Fortification of corn masa flour with folic acid in the United States: an overview of the evidence.

    PubMed

    Hamner, Heather C; Tinker, Sarah C

    2014-04-01

    Corn masa flour, used to make products such as corn tortillas, is a staple food for Hispanic populations residing in the United States, particularly among Mexican Americans and Central Americans. Research has indicated that Hispanic women in the United States continue to be at a higher risk of having a neural tube defect-affected pregnancy than women of other races/ethnicities, even after the introduction of folic acid fortification of cereal grain products labeled as "enriched." Corn masa flour has, therefore, been suggested as a potential food vehicle for folic acid in the United States. This paper explores the potential impact that folic acid fortification of corn masa flour could have on the Hispanic population in the United States. PMID:24494975

  2. Neural tube defects in Mexican-Americans living on the US-Mexico border: The effects of folic acid and dietary folate

    Microsoft Academic Search

    Lucina Suarez; Katherine A. Hendricks; Sharon P. Cooper; Anne M. Sweeney; Robert J. Hardy; Russell D. Larsen

    1998-01-01

    Neural tube defects (NTDs) are malformations of the developing brain and spinal cord; the most common are anencephaly and spina bifida. Evidence from many populations suggests that 50% of NTDs can be prevented through daily consumption of folic acid. A recent study has reported that folic acid may not protect populations of Mexican descent. This finding has serious implications for

  3. The Costs and Benefits of Folic Acid Fortification in the United States: A Comparison of Ex Ante and Ex Post Economic Evaluations

    Microsoft Academic Search

    Scott D. Grosse; Norman J. Waitzman; Patrick S. Romano; Joseph Mulinare

    2004-01-01

    The United States Food and Drug Administration (FDA) required that manufacturers of enriched cereal-grain products as of January 1, 1998 fortify their products with folic acid to reduce the number of pregnancies affected a by neural tube defect (NTD). Prior to adoption of the regulation in 1996, three economic evaluations projected net economic benefits or cost savings from folic acid

  4. IADR 2010: Karl Kingsley, Mark Keiserman, Christine Bergman Based upon evidence of human health outcomes correlated with folic acid intake, the US Food and Drug

    E-print Network

    Ahmad, Sajjad

    IADR 2010: Karl Kingsley, Mark Keiserman, Christine Bergman Based upon evidence of human health outcomes correlated with folic acid intake, the US Food and Drug Administration adopted of slowdeveloping cancers, such as oral cancer. Method: Proliferative effects of folic acid on phenotypic

  5. Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol.

    PubMed

    Keil, Kimberly P; Abler, Lisa L; Altmann, Helene M; Wang, Zunyi; Wang, Peiqing; Ricke, William A; Bjorling, Dale E; Vezina, Chad M

    2015-06-15

    Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid-enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which mimics changing hormone levels in aging humans. T+E2 treatment increased mouse urine output, time between voiding events, and bladder capacity and compliance. Consumption of a folic acid-enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. T+E2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid-enriched diet. Another potential mechanism involves neural control of micturition. The folic acid-enriched diet, fed to T+E2-treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of the capsaicin-sensitive cation channel transient receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root ganglia (DRG) neurons. T+E2 treatment and a folic acid-enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse T+E2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function. PMID:25855514

  6. Folic Acid and Trastuzumab Functionalized Redox Responsive Polymersomes for Intracellular Doxorubicin Delivery in Breast Cancer.

    PubMed

    Lale, Shantanu V; Kumar, Arun; Prasad, Shyam; Bharti, Alok C; Koul, Veena

    2015-06-01

    Redox responsive biodegradable polymersomes comprising of poly(ethylene glycol)-polylactic acid-poly(ethylene glycol) [PEG-s-s-PLA-s-s-PLA-s-s-PEG] triblock copolymer with multiple disulfide linkages were developed to improve intracellular delivery and to enhance chemotherapeutic efficacy of doxorubicin in breast cancer with minimal cardiotoxicity. Folic acid and trastuzumab functionalized monodispersed polymersomes of size ?150 nm were prepared by nanoprecipitation method while achieving enhanced doxorubicin loading of ?32% in the polymersomes. Multiple redox responsive disulfide linkages were incorporated in the polymer in order to achieve complete disintegration of polymersomes in redox rich environment of cancer cells resulting in enhanced doxorubicin release as observed in in vitro release studies, where ?90% doxorubicin release was achieved in pH 5.0 in the presence of 10 mM glutathione (GSH) as compared to ?20% drug release in pH 7.4. Folic acid and trastuzumab mediated active targeting resulted in improved cellular uptake and enhanced apoptosis in in vitro studies in breast cancer cell lines. In vivo studies in Ehrlich ascites tumor bearing Swiss albino mice showed enhanced antitumor efficacy and minimal cardiotoxicity of polymersomes with ?90% tumor regression as compared to ?38% tumor regression observed with free doxorubicin. The results highlight therapeutic potential of the polymersomes as doxorubicin delivery nanocarrier in breast cancer therapy with its superior antitumor efficacy and minimal cardiotoxicity. PMID:25918899

  7. Folic acid knowledge and use among relatives in Irish families with neural tube defects: An intervention study

    Microsoft Academic Search

    J Byrne

    2003-01-01

    Background Relatives in families where a child has a neural tube defect (NTD) may be at higher risk of having an affected child. Little\\u000a is known of their level of knowledge and use of folic acid.\\u000a \\u000a \\u000a Aim To carry out an intervention study intended to increase knowledge and use of folic acid among relatives.\\u000a \\u000a \\u000a \\u000a \\u000a Methods One hundred aunts and female

  8. Methionine, folic acid, vitamin B b12 sand unidentified factors in the nutrition of the growing chick 

    E-print Network

    Welch, Billy E

    1951-01-01

    KETHIONINE ~ FOLIC ACID ~ VITAMIN Big AND UNIDENTIFIED FACTORS IN THE NUTRITION OF THE GROWING CHICK A Thesis by Billy E. Welch Appr ed o tyls and content by Chairman oi Committee YATHIONINE y FOLIC ACID ~ VITAMIN Big AND UNIDENTIFIED... FACTORS IN THE NUTRITION OF THE GROWING CHICK by B1lly E. Welch A Thesis Submitted to ths Graduate School of the Agr1cultural and Mschan1oal College of Texas in partial fulfillment of the requirements for the degree of :lASTER OF SCIENCE Na...

  9. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: Systematic review and meta-analysis

    PubMed Central

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-01-01

    BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council’s Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. RESULTS: Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. CONCLUSION: From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid–preventable NTDs across different ethnic groups. Birth Defects Research (Part A) 97:444–451, 2013. © 2013 Wiley Periodicals, Inc. PMID:23873812

  10. Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics

    PubMed Central

    2011-01-01

    Background Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). Results The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. Conclusions The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics. PMID:22074171

  11. Synthesis, spectroscopic and thermal characterization of some transition metal complexes of folic acid.

    PubMed

    El-Wahed, M G Abd; Refat, M S; El-Megharbel, S M

    2008-09-01

    Compounds having general formula: [M(FO)(Cl)x(H2O)y]x zH2O, where (M=Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II), FO=folate anion, x=2 or 4, y=2 or 4 and z=0, 1, 2, 3, 5 or 15) were prepared. The obtained compounds were characterized by elemental analysis, infrared as well as electronic spectra, thermogravimetric analysis and the conductivity measurements. The results suggested that all folate complexes were formed by 2:1 molar ratio (metal:folic acid) as a bidentate through both of the two carboxylic groups. The molar conductance measurements proved that the folate complexes are electrolytes. The kinetic thermodynamic parameters such as: E*, DeltaH*, DeltaS* and DeltaG* were estimated from the DTG curves. The antibacterial evaluation of the folic acid and their complexes was also done against some Gram positive/negative bacteria as well as fungi. PMID:18024191

  12. Double-Blind Therapeutic Trial in Angelman Syndrome Using Betaine and Folic Acid

    PubMed Central

    Peters, Sarika U.; Bird, Lynne M.; Kimonis, Virginia; Glaze, Daniel G.; Shinawi, Lina M.; Bichell, Terry Jo; Barbieri-Welge, Rene; Nespeca, Mark; Anselm, Irina; Waisbren, Susan; Sanborn, Erica; Sun, Qin; O’Brien, William E.; Beaudet, Arthur L.; Bacino, Carlos A.

    2011-01-01

    Angelman syndrome (AS) is caused by reduced or absent expression of the maternally inherited ubiquitin protein ligase 3A gene (UBE3A), which maps to chromosome 15q11–q13. UBE3A is subject to genomic imprinting in neurons in most regions of the brain. Expression of UBE3A from the maternal chromosome is essential to prevent AS, because the paternally inherited gene is not expressed, probably mediated by antisense UBE3A RNA. We hypothesized that increasing methylation might reduce expression of the antisense UBE3A RNA, thereby increasing UBE3A expression from the paternal gene and ameliorating the clinical phenotype. We conducted a trial using two dietary supplements, betaine and folic acid to promote global levels of methylation and attempt to activate the paternally inherited UBE3A gene. We performed a number of investigations at regular intervals including general clinical and developmental evaluations, biochemical determinations on blood and urine, and electroencephalographic studies. We report herein the data on 48 children with AS who were enrolled in a double-blind placebo-controlled protocol using betaine and folic acid for 1 year. There were no statistically significant changes between treated and untreated children; however, in a small subset of patients we observed some positive trends. PMID:20635355

  13. Double-blind therapeutic trial in Angelman syndrome using betaine and folic acid.

    PubMed

    Peters, Sarika U; Bird, Lynne M; Kimonis, Virginia; Glaze, Daniel G; Shinawi, Lina M; Bichell, Terry Jo; Barbieri-Welge, Rene; Nespeca, Mark; Anselm, Irina; Waisbren, Susan; Sanborn, Erica; Sun, Qin; O'Brien, William E; Beaudet, Arthur L; Bacino, Carlos A

    2010-08-01

    Angelman syndrome (AS) is caused by reduced or absent expression of the maternally inherited ubiquitin protein ligase 3A gene (UBE3A), which maps to chromosome 15q11-q13. UBE3A is subject to genomic imprinting in neurons in most regions of the brain. Expression of UBE3A from the maternal chromosome is essential to prevent AS, because the paternally inherited gene is not expressed, probably mediated by antisense UBE3A RNA. We hypothesized that increasing methylation might reduce expression of the antisense UBE3A RNA, thereby increasing UBE3A expression from the paternal gene and ameliorating the clinical phenotype. We conducted a trial using two dietary supplements, betaine and folic acid to promote global levels of methylation and attempt to activate the paternally inherited UBE3A gene. We performed a number of investigations at regular intervals including general clinical and developmental evaluations, biochemical determinations on blood and urine, and electroencephalographic studies. We report herein the data on 48 children with AS who were enrolled in a double-blind placebo-controlled protocol using betaine and folic acid for 1 year. There were no statistically significant changes between treated and untreated children; however, in a small subset of patients we observed some positive trends. PMID:20635355

  14. FOLIC ACID METABOLISM IN ANTIFOLIC-RESISTANT MUTANTS OF STREPTOCOCCUS FAECALIS

    PubMed Central

    Johnson, Alva H.; Hutchison, Dorris J.

    1964-01-01

    Johnson, Alva H. (Sloan-Kettering Institute for Cancer Research, Rye, N.Y.), and Dorris J. Hutchison. Folic acid metabolism in antifolic-resistant mutants of Streptococcus faecalis. J. Bacteriol. 87:786–791. 1964.—Streptococcus faecalis ATCC 8043 and three of its mutants resistant to amethopterin were compared for their quantitative requirements for serine, purines, and thymine; for their quantitative requirements of folic acid (FA) for the synthesis de novo of serine, purines, and thymine; for the susceptibility to amethopterin of each pathway; and for the relative capacity of resting cells of each culture to synthesize N5-formyltetrahydrofolate (5-CHOFAH4) from FA and serine or FA and formate. The mutants were found to be both qualitatively and quantitatively different from one another and from the wild strain. The growth conditions, specifically the composition of the medium in which each mutant strain was selected, had a marked effect on the metabolic capacities of the mutants. The ability to synthesize serine, purines, and thymine, as observed from the FA requirements, directly reflected the level of resistance of each pathway to amethopterin. The resistant mutants were more efficient than the wild strain in the formation of 5-CHOFAH4 from FA and formate and, furthermore, this formate activation paralleled their capacities in the synthesis de novo of serine. Alterations in purine and thymine biosyntheses were also observed. PMID:14137614

  15. Recommendations for accelerating global action to prevent folic acid-preventable birth defects and other folate-deficiency diseases: Meeting of experts on preventing folic acid-preventable neural tube defects

    Microsoft Academic Search

    Godfrey P. Oakley; Karen N. Bell; Mary Beth Weber

    2004-01-01

    BACKGROUND: In April of 2003, The Micronutrient Initiative, in collaboration with several other organizations, convened a group of knowledgeable scientists and policy experts to discuss ways to accelerate the global pace at which countries implement effective and sustainable programs to prevent folic acid-preventable birth defects and other folate-deficiency diseases. Programs implemented to date by fewer than 40 countries have prevented

  16. Hemoglobin and hematocrit values are higher and prevalence of anemia is lower in the post-folic acid fortification period than in the pre-folic acid fortification period in US adults1,2

    Microsoft Academic Search

    Vijay Ganji; Mohammad R Kafai

    Background: It is not known whether the improved folate status from mandatory folic acid fortification had any impact on indexes and prevalence of anemias in the United States. Objective: We investigated trends in indexes and prevalence of anemia and macrocytosis with a focus on comparison of prefortifi- cation data with postfortification data. Design: Hemoglobin, hematocrit, mean corpuscular volume (MCV) and

  17. Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey

    Microsoft Academic Search

    Quan-He Yang; Heather K Carter; Joseph Mulinare; RJ Berry; JM Friedman; J David Erickson

    Background: Neural tube defects are serious birth defects of the brain and spinal cord. Up to 70% of neural tube defects can be prevented by the consumption of folic acid by women before and early during pregnancy. Objective:Theobjectivewastoexaminefolicacidintakeinwomen of childbearing age in the United States. Design: We analyzed nutrient intake data reported by 1685 non- pregnant women aged 15-49 y

  18. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration.

    PubMed

    Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik; Jain, Sanyog

    2014-01-13

    The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin entrapped within the freeze-dried formulation was found stable both chemically as well as conformationally and developed formulation exhibited excellent stability in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies revealed higher uptake of folic acid functionalized layersomes in comparison with their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution. Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery. PMID:24283460

  19. Study on the interaction between CdTe quantum dots and folic acid by two-photon excited fluorescence spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Du, Jie; Wu, Yongzhong; Hao, Xiaopeng; Zhao, Xian

    2011-12-01

    Water-soluble CdTe QDs modified by thioglycolic acid were synthesized with a facile one-pot method. Two-photon excited fluorescence spectroscopic technique was used to study the interaction between TGA-capped CdTe quantum dots and folic acid. Experiments results showed that the two-photon fluorescence of TGA-capped CdTe QDs in PBS buffer solution was quenched in the presence of folic acid. A good linear relationship was observed between the two-photon fluorescence intensity of TGA-capped CdTe QDs and the concentration of folic acid. The two-photon excited fluorescence quenching mechanism was also presented.

  20. Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted chitosan micelles

    PubMed Central

    Du, Yong-Zhong; Cai, Li-Li; Li, Jin; Zhao, Meng-Dan; Chen, Feng-Ying; Yuan, Hong; Hu, Fu-Qiang

    2011-01-01

    Background Cationic polymers have been accepted as effective nonviral vectors for gene delivery with low immunogenicity unlike viral vectors. However, the lack of organ or cell specificity sometimes hampers their application and the modification of polymeric vectors has also shown successful improvements in achieving cell-specific targeting delivery and in promoting intracellular gene transfer efficiency. Methods A folic acid-conjugated stearic acid-grafted chitosan (FA-CS-SA) micelle, synthesized by a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-coupling reaction, was designed for specific receptor-mediated gene delivery. Results Due to the cationic properties of chitosan, the micelles could compact the plasmid DNA (pDNA) to form micelle/pDNA complexes nanoparticles. The particle size and zeta potential of the FA-CS-SA/pDNA complexes with different N/P ratios were 100–200 nm and ?20 to ?10 mV, respectively. The DNase I protection assay indicated that the complexes can efficiently protect condensed DNA from enzymatic degradation by DNase I. A cytotoxicity study indicated that the micelles exhibited less toxicity in comparison with LipofectamineTM 2000. Using SKOV3 and A549 as model tumor cells, the cellular uptake of micelles was investigated. Conclusion It was found that cellular uptake of FA-CS-SA in SKOV3 cells with higher folate receptor expression was faster than that in A549 cells with a short incubation time. Luciferase assay and green fluorescent protein detection were used to confirm that FA-CS-SA could be an effective gene vector. Transfection efficiency of the FA-CS-SA/pDNA complexes in SKOV3 cells was enhanced up to 2.3-fold compared with that of the CS-SA/pDNA complexes. However, there was no significant difference between the transfection efficiencies of the two complexes in A549 cells. Importantly, the transfection efficiency of FA-CS-SA/pDNA decreased with free FA pretreatment in SKOV3 cells. It was concluded that the increase in transfection efficiency of the FA-CS-SA/pDNA complexes was attributed to folate receptor-mediated endocytosis. PMID:21845046

  1. Folic acid

    MedlinePLUS

    ... disease called vitiligo, and an inherited disease called Fragile-X syndrome. It is also used for reducing harmful side ... Chronic fatigue syndrome.Treating an inherited disease called Fragile-X syndrome.Preventing re-blockage of blood vessels after angioplasty, ...

  2. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?

    PubMed Central

    Botto, Lorenzo D; Lisi, Alessandra; Robert-Gnansia, Elisabeth; Erickson, J David; Vollset, Stein Emil; Mastroiacovo, Pierpaolo; Botting, Beverley; Cocchi, Guido; de Vigan, Catherine; de Walle, Hermien; Feijoo, Maria; Irgens, Lorentz M; McDonnell, Bob; Merlob, Paul; Ritvanen, Annukka; Scarano, Gioacchino; Siffel, Csaba; Metneki, Julia; Stoll, Claude; Smithells, Richard; Goujard, Janine

    2005-01-01

    Objectives To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review. Main outcome measures Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable). Results The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects. Conclusions Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements. PMID:15722368

  3. Supplementation of folic acid and vitamin B?? reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke.

    PubMed

    Xia, Xiao-Shuang; Li, Xin; Wang, Lin; Wang, Ji-Zuo; Ma, Jin-Ping; Wu, Cun-Jin

    2014-09-01

    Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 ?g twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke. PMID:24814858

  4. A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group

    Microsoft Academic Search

    P N Kirke; L E Daly; J H Elwood

    1992-01-01

    A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was

  5. Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa

    Microsoft Academic Search

    Abdul-Rauf Sayed; David Bourne; Robert Pattinson; Jo Nixon; Bertram Henderson

    2008-01-01

    BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South

  6. VITAMIN B6, B12 AND FOLIC ACID SUPPLEMENTATION AND COGNITIVE FUNCTION: A SYSTEMATIC REVIEW OF RANDOMIZED TRIALS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of vitamins B6, B12, and folic acid supplementation on cognitive function was performed. Literature search conducted in MEDLINE with supplemental articles from re...

  7. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid

    Microsoft Academic Search

    S. Padmanabhan; D. N. Tripathi; A. Vikram; P. Ramarao; G. B. Jena

    2009-01-01

    Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic

  8. DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro

    Microsoft Academic Search

    S. J. DUTHIE; A. HAWDON

    Folic acid is essential for the synthesis and repair of DNA. We report the effects of folate de- pletion on DNA stability in normal human lymphocytes in vitro. DNA strand breakage, uracil misincorporation, oxidative DNA base damage, and DNA repair capability were determined using variants of the comet assay (sin- gle cell gel electrophoresis). Lymphocyte proliferation was measured as an

  9. DOSE-DEPENDENT EFFECTS OF FOLIC ACID ON BLOOD CONCENTRATIONS OF HOMOCYSTEINE: A META-ANALYSIS OF THE RANDOMIZED TRIALS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary supplementation with B vitamins that lower blood homocysteine concentrations is expected to reduce cardiovascular disease risk, but there has been uncertainty about the optimum regimen to use for this purpose. The objectives were to ascertain the lowest dose of folic acid associated with th...

  10. Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence. In the January issue of this journal, Johnston (1) includes our group’s recent analysis of data from the 1999-2002 National Health and Nutrition Examination...

  11. Antagonistic activity in plant-associated lactic acid bacteria

    Microsoft Academic Search

    Thomas Müller; Undine Behrendt; Marina Müller

    1996-01-01

    A total of 256 strains of lactic acid bacteria isolated from forage grasses were screened for antagonistic activities under conditions where the effects of organic acids and hydrogen peroxide were minimised. Thirty seven strains were shown to inhibit the growth of other lactic acid bacteria in the agar spot test with viable cells. Cell free supernatants from 16 of these

  12. Degradation of folic acid in fortified vitamin juices during long term storage.

    PubMed

    Frommherz, Lara; Martiniak, Yvonne; Heuer, Thorsten; Roth, Alexander; Kulling, Sabine E; Hoffmann, Ingrid

    2014-09-15

    Folic acid (FA) concentrations of nine fortified vitamin juices were determined with the aim to study the FA degradation and to investigate the deviation from the declared label value. The juices were received shortly after bottling and were analyzed monthly during controlled storage conditions (light and dark) over one year. The analyses were performed by HPLC-MS/MS, which included a fast "dilute and shoot" sample preparation. Average decreases in FA concentration of 46% were observed after one year. Fresh juices (shortly after bottling) showed the highest deviations from the declared label value (up to+89%). Label values did not reflect the actual concentration of FA in these products, making it difficult to determine the intake of this vitamin. PMID:24767034

  13. Folic acid functionalized ZnO quantum dots for targeted cancer cell imaging.

    PubMed

    Ma, Ying-Ying; Ding, Hui; Xiong, Huan-Ming

    2015-07-31

    Aqueous stable luminescent ZnO quantum dots (QDs) were successfully synthesized with primary amine groups on the surface, which were designed to conjugate with folic acid (FA) to produce the final ZnO-FA QDs. Such ZnO-FA QDs were able to target some specific cancer cells with overexpressed FA receptors on the membranes and thus differentiate the MCF-7 cancer cells from the normal 293T cells. The nanoparticle uptaking experiments by different cells were carried out in parallel and tracked by confocal laser microscopy dynamically. The results confirmed the specificity of our ZnO-FA QDs towards the FA-receptor overexpressed cancer cells, which had potential for diagnosing cancers in vitro. PMID:26148516

  14. Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice.

    PubMed

    Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R Lee; Gorantla, Santhi; Poluektova, Larisa; McMillan, JoEllyn; Gendelman, Howard E

    2015-08-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use. PMID:26026666

  15. Modified Carbon Nanotube Paste Electrode for Voltammetric Determination of Carbidopa, Folic Acid, and Tryptophan

    PubMed Central

    Esfandiari Baghbamidi, Sakineh; Beitollahi, Hadi; Karimi-Maleh, Hassan; Soltani-Nejad, Somayeh; Soltani-Nejad, Vahhab; Roodsaz, Sara

    2012-01-01

    A simple and convenient method is described for voltammetric determination of carbidopa (CD), based on its electrochemical oxidation at a modified multiwall carbon nanotube paste electrode. Under optimized conditions, the proposed method exhibited acceptable analytical performances in terms of linearity (over the concentration range from 0.1 to 700.0??M), detection limit (65.0?nM), and reproducibility (RSD = 2.5%) for a solution containing CD. Also, square wave voltammetry (SWV) was used for simultaneous determination of CD, folic acid (FA), and tryptophan (TRP) at the modified electrode. To further validate its possible application, the method was used for the quantification of CD, FA, and TRP in urine samples. PMID:22666634

  16. Folic acid supplementation in pregnancy and implications in health and disease

    PubMed Central

    2014-01-01

    Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies. PMID:25135350

  17. The cost-effectiveness of mandatory folic acid fortification in Australia.

    PubMed

    Rabovskaja, Viktoria; Parkinson, Bonny; Goodall, Stephen

    2013-01-01

    The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), life-years gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level. PMID:23223683

  18. Formulation and evaluation of niosomal nasal drug delivery system of folic acid for brain targeting.

    PubMed

    Ravouru, Nagaraju; Kondreddy, Pallavi; Korakanchi, Deepthy; Haritha, M

    2013-12-01

    Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drug delivery systems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625 µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4±1°C and 25±1°C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs. PMID:23863098

  19. Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life.

    PubMed

    Keating, Elisa; Correia-Branco, Ana; Araújo, João R; Meireles, Manuela; Fernandes, Rita; Guardão, Luísa; Guimarães, João T; Martel, Fátima; Calhau, Conceição

    2015-03-01

    The aim of this study was to understand whether high folic acid (HFA) exposure during the perigestational period induces metabolic dysfunction in the offspring, later in life. To do this, female Sprague-Dawley rats (G0) were administered a dose of folic acid (FA) recommended for pregnancy (control, C, 2?mg FA/kg of diet, n=5) or a high dose of FA (HFA, 40?mg FA/kg of diet, n=5). Supplementation began at mating and lasted throughout pregnancy and lactation. Body weight and food and fluid intake were monitored in G0 and their offspring (G1) till G1 were 13 months of age. Metabolic blood profiles were assessed in G1 at 3 and 13 months of age (3M and 13M respectively). Both G0 and G1 HFA females had increased body weight gain when compared with controls, particularly 22 (G0) and 10 (G1) weeks after FA supplementation had been stopped. G1 female offspring of HFA mothers had increased glycemia at 3M, and both female and male G1 offspring of HFA mothers had decreased glucose tolerance at 13M, when compared with matched controls. At 13M, G1 female offspring of HFA mothers had increased insulin and decreased adiponectin levels, and G1 male offspring of HFA mothers had increased levels of leptin, when compared with matched controls. In addition, feeding of fructose to adult offspring revealed that perigestational exposure to HFA renders female progeny more susceptible to developing metabolic unbalance upon such a challenge. The results of this work indicate that perigestational HFA exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state. PMID:25663705

  20. Preschool Iron-Folic Acid and Zinc Supplementation in Children Exposed to Iron-Folic Acid in Utero Confers No Added Cognitive Benefit in Early School-Age123

    PubMed Central

    Christian, Parul; Morgan, Mary E.; Murray-Kolb, Laura; LeClerq, Steven C.; Khatry, Subarna K.; Schaefer, Barbara; Cole, Pamela M.; Katz, Joanne; Tielsch, James M.

    2011-01-01

    In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7–9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001–2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007–2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (?0.29, 95% CI: ?0.55, ?0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (?1.92, 95% CI: ?3.12, ?0.71) and C-IFAZn (?1.78, 95% CI: ?2.63, ?0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc. PMID:21956955

  1. Bioavailability of iron, zinc, folic acid, and vitamin A from fortified maize.

    PubMed

    Moretti, Diego; Biebinger, Ralf; Bruins, Maaike J; Hoeft, Birgit; Kraemer, Klaus

    2014-04-01

    Several strategies appear suitable to improve iron and zinc bioavailability from fortified maize, and fortification per se will increase the intake of bioavailable iron and zinc. Corn masa flour or whole maize should be fortified with sodium iron ethylenediaminetetraacetate (NaFeEDTA), ferrous fumarate, or ferrous sulfate, and degermed corn flour should be fortified with ferrous sulfate or ferrous fumarate. The choice of zinc fortificant appears to have a limited impact on zinc bioavailability. Phytic acid is a major inhibitor of both iron and zinc absorption. Degermination at the mill will reduce phytic acid content, and degermed maize appears to be a suitable vehicle for iron and zinc fortification. Enzymatic phytate degradation may be a suitable home-based technique to enhance the bioavailability of iron and zinc from fortified maize. Bioavailability experiments with low phytic acid-containing maize varieties have suggested an improved zinc bioavailability compared to wild-type counterparts. The bioavailability of folic acid from maize porridge was reported to be slightly higher than from baked wheat bread. The bioavailability of vitamin A provided as encapsulated retinyl esters is generally high and is typically not strongly influenced by the food matrix, but has not been fully investigated in maize. PMID:24329552

  2. Combination of Folic Acid and Folinic Acid Antagonists in Human and Veterinary Medicine

    Microsoft Academic Search

    L. Havas; B. Hamza; M. Fernex; W. Rehm

    1973-01-01

    Based on the mutual potentiating effect, when diaminopyrimidíne derivatives and sulfonamides or sulfones are combined, several such combinations were tested for their efficacy in the treatment and prophylaxis of various infections in human and veterinary medicine. Successful combinations were: trimethoprim + sulfamethoxazole for the treatment of bacterial infections in human medicine; sulfadoxine + pyrimethamine for the treatment and prophylaxis of

  3. Red blood cell folate concentrations increase more after supplementation with (6S)-5-methyltetrahydrofolate than with folic acid in women of childbearing age1-4

    Microsoft Academic Search

    Yvonne Lamers; Reinhild Prinz-Langenohl; Susanne Bramswig; Klaus Pietrzik

    Background: For the primary prevention of neural tube defects (NTDs), public health authorities recommend women of childbear- ingagetotake400gfolicacid\\/d4wkbeforeconceptionandduring the first trimester. The biologically active derivate (6S)-5- methyltetrahydrofolate ((6S)-5-MTHF) could be an alternative to folic acid. Objective:Weinvestigatedtheeffectofsupplementationwith(6S)- 5-MTHF compared with that of folic acid on red blood cell folate concentration, an indicator of folate status. Design: The study was designed as

  4. Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

    Microsoft Academic Search

    Kathleen Green-Raleigh; Heather Carter; Joseph Mulinare; Christine Prue; Joann Petrini

    2006-01-01

    Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States\\u000a since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from\\u000a 1995–2005 in the United States. Results: The percentage

  5. Effect of Folic Acid Combined with Fluoxetine in Patients with Major Depression on Plasma Homocysteine and Vitamin B12, and Serotonin Levels in Lymphocytes

    Microsoft Academic Search

    Gustavo Resler; Renée Lavie; Julio Campos; Salvador Mata; Mary Urbina; Alberto García; Rafael Apitz; Lucimey Lima

    2008-01-01

    Objective(s): Folic acid, a micronutrient supporting the natural defense system, may elevate antidepressant responses, although the lymphocyte serotonergic system has not been explored in folate-supplemented depressed patients. Methods: Twenty-seven patients were randomly assigned to groups receiving fluoxetine (20 mg) and folic acid (10 mg\\/day) or fluoxetine and placebo for 6 weeks. Clinical outcome was assessed according to the Hamilton Depression

  6. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B 6 and B 12

    Microsoft Academic Search

    Arlene Lobo; Arabi Naso; Kristopher Arheart; Warren D Kruger; Tariq Abou-Ghazala; Fadi Alsous; Maher Nahlawi; Anjan Gupta; Ali Moustapha; Frederick van Lente; Donald W Jacobsen; Killian Robinson

    1999-01-01

    An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 ± 11 years (mean ± SD) with documented CAD. Patients in each

  7. Fabrication of folic acid sensor based on the Cu doped SnO2 nanoparticles modified glassy carbon electrode

    NASA Astrophysics Data System (ADS)

    Lavanya, N.; Radhakrishnan, S.; Sudhan, N.; Sekar, C.; Leonardi, S. G.; Cannilla, C.; Neri, G.

    2014-07-01

    A novel folic acid biosensor has been fabricated using Cu doped SnO2 nanoparticles (NPs) synthesized by a simple microwave irradiation method. Powder XRD and TEM studies confirmed that both the pure and Cu doped SnO2 (Cu: 0, 10, 20wt%) crystallized in tetragonal rutile-type structure with spherical morphology. The average crystallite size of pure SnO2 was estimated to be around 16 nm. Upon doping, the crystallite sizes decreased to 9 nm and 5 nm for 10 and 20wt% Cu doped SnO2 respectively. XPS studies confirmed the electronic state of Sn and Cu to be 4+ and 2+ respectively. Cu (20wt%) doped SnO2 NPs are proved to be a good sensing element for the determination of folic acid (FA). Cu-SnO2 NPs (20wt%) modified glassy carbon electrode (GCE) exhibited the lowest detection limit of 0.024 nM over a wide folic acid concentration range of 1.0 × 10-10 to 6.7 × 10-5 M at physiological pH of 7.0. The fabricated sensor is highly selective towards the determination of FA even in the presence of a 100 fold excess of common interferent ascorbic acid. The sensor proved to be useful for the estimation of FA content in pharmaceutical sample with satisfactory recovery.

  8. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    PubMed Central

    Czeizel, Andrew E.; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-01-01

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”. PMID:24284617

  9. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.

    PubMed

    Czeizel, Andrew E; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-11-01

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of prevention is better than a pound of care". PMID:24284617

  10. Decreased TGF-?1 and IGF-1 protein expression in rat embryo skull bone in folic acid-restricted diet

    Microsoft Academic Search

    Mochammad Istiadjid Eddy Santoso; Mohammad Saifur Rohman

    2006-01-01

    Folic acid deficiency during conception up to the end of the third month of gestation is believed to play the most important factor in neural tube defects (NTDs). However, the exact molecular mechanism remains to be elucidated. It has been suggested that transforming growth factor-? (TGF-?1) and insulin-like growth factor-1 (IGF-1) play a critical role in supporting bone formation. Therefore,

  11. Periconceptional Multivitamin Folic Acid Use, Dietary Folate, Total Folate and Risk of Neural Tube Defects in South Carolina

    Microsoft Academic Search

    Shirley J Thompson; Myriam E Torres; Roger E Stevenson; Jane H Dean; Robert G Best

    2003-01-01

    PURPOSE: To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies.METHODS: This population-based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 randomly selected controls. Women completed a food frequency

  12. RP-HPLC Determination of vitamins B1 ,B 3 ,B 6, folic acid and B12 in multivitamin tablets

    Microsoft Academic Search

    JASMINA BRBORIC; SOTE VLADIMIROV

    2005-01-01

    A simple and sensitive reversed-phase, ion-pair HPLC method was developed and validated for the simultaneous determination of B-group vitamins, thiamine chloride hydro- chloride (B1), nicotinamide (B3), pyridoxine hydrochloride (B6) and folic acid in Pentovit ® coated tablets. The cyanocobalamine (B12) was determined separately, because of its low concentration in the investigated multivitamin preparation. RP-HPLC analysis was per- formed with a

  13. Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion.

    PubMed

    Russell, R M; Rosenberg, I H; Wilson, P D; Iber, F L; Oaks, E B; Giovetti, A C; Otradovec, C L; Karwoski, P A; Press, A W

    1983-07-01

    The effect of ethanol on the kinetics of folic acid urinary excretion was studied in five chronic alcoholic patients who were maintained in a folate replete state. For 17 days, 95% ethanol was administered orally at 2-h intervals (X9). The folate pool(s) were labeled with the tritium labeled pteroyl glutamic acid at the start of the period of ethanol ingestion and at the start of a control abstinent period. The 24-h urine volume did not change with consumption of ethanol. Total urinary folate excretion was significantly greater by 20 to 40% in four of five patients during the ethanol administration period (p less than 0.05). The fall-off in urinary radioactivity corrected for total folate excretion (dpm/microgram Lactobacillus casei folate) was resolved into a biexponential decay with two distinct slopes. Ethanol caused the slope of the second component to flatten significantly with mean t1/2 of 63.7 days on ethanol versus 9.6 days off (p less than 0.05). These kinetic results are consistent with the known interference by ethanol of folate utilization in a functional tissue pool. PMID:6407299

  14. Folic-Acid-Targeted Self-Assembling Supramolecular Carrier for Gene Delivery.

    PubMed

    Liao, Rongqiang; Yi, Shouhui; Liu, Manshuo; Jin, Wenling; Yang, Bo

    2015-07-27

    A targeting gene carrier for cancer-specific delivery was successfully developed through a "multilayer bricks-mortar" strategy. The gene carrier was composed of adamantane-functionalized folic acid (FA-AD), an adamantane-functionalized poly(ethylene glycol) derivative (PEG-AD), and ?-cyclodextrin-grafted low-molecular-weight branched polyethylenimine (PEI-CD). Carriers produced by two different self-assembly schemes, involving either precomplexation of the PEI-CD with the FA-AD and PEG-AD before pDNA condensation (Method A) or pDNA condensation with the PEI-CD prior to addition of the FA-AD and PEG-AD to engage host-guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI-25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host-guest interactions, could be an effective, targeted, and low-toxicity carrier for delivering nucleic acid to target cells. PMID:26032689

  15. Folic Acid Conjugated ?-Valerolactone-Poly(ethylene glycol) Based Triblock Copolymer as a Promising Carrier for Targeted Doxorubicin Delivery

    PubMed Central

    Nair K, Lekha; Jagadeeshan, Sankar; Nair S, Asha; Kumar, G. S. Vinod

    2013-01-01

    The aim of this study is to test the hypothesis that the newly synthesized poly(?-valerolactone)/poly(ethylene glycol)/poly(?-valerolactone) (VEV) copolymer grafted with folic acid would impart targetability and further enhance the anti-tumor efficacy of doxorubicin (DOX). Here, folic acid conjugated VEV (VEV-FOL) was synthesized by a modified esterification method and characterized using IR and NMR. DOX loaded VEV-FOL micelles were synthesized using a novel solvent evaporation method and were obtained with a mean diameter of 97 nm with high encapsulation efficiency and sustained in vitro release profile. Comparative studies of polymer micelles with and without folate for cellular uptake and cytotoxicity were done on folate receptor-positive breast cancer cell line, MDAMB231. The intracellular uptake tests showed significant increase in folate micellar uptake when compared to non-folate-mediated micelles. MTT assay followed by apoptosis assays clearly indicated that folate decorated micelles showed significantly better cytotoxicity (IC50?=?0.014 µM) and efficiency to induce apoptosis than other treated groups. Moreover, a significant G2/M arrest was induced by DOX loaded VEV-FOL micelles at a concentration where free drug failed to show any activity. Thus, our results show that the folic acid-labeled VEV copolymer is a promising biomaterial with controlled and sustainable tumor targeting ability for anticancer drugs which can open new frontiers in the area of targeted chemotherapy. PMID:23990912

  16. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    SciTech Connect

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  17. Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries.

    PubMed

    López-Camelo, Jorge S; Castilla, Eduardo E; Orioli, Iêda M

    2010-10-01

    The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies. PMID:20814949

  18. Selenium or selenium plus folic acid intake improves the detrimental effects of ethanol on pups' selenium balance.

    PubMed

    Ojeda, M L; Jotty, K; Nogales, F; Murillo, M L; Carreras, O

    2010-12-01

    The levels of folic acid and selenium, two nutrients with antioxidant properties, decrease in dams exposed to ethanol during gestation and lactation. This decrease affects their antioxidant balance, and consequently the health of their offspring. In this study we have proved that a supplemented diet with Se (0.5 ppm) or with Se (0.5 ppm) plus folic acid (8 ppm) to ethanol-exposed (20%v/v) dams prevents the ethanol-provoked effects in their offspring's Se deposits. Se levels in milk, serum, urine, faeces and several tissues were measured by graphite-furnace atomic absorption spectrometry. Results show that ethanol decreases Se deposits in pups' heart, liver, kidney and testes. However Se levels in pancreas and in serum were increased by ethanol; it also compromised the weight and the length of the offspring at the end of lactation. Our supplemented diets to ethanol dams increased all of these impaired levels, and restored Se pancreas concentration to a control status. However Se-only therapy mainly displaces Se to serum, kidney and spleen, and co-treatment with Se plus folic acid, mainly displaces Se to liver and brain. This data demonstrate that the qualitative and quantitative Se organ deposits depend on ethanol consumption, Se status, and the presence of other antioxidants. PMID:20875836

  19. Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats.

    PubMed

    Liu, Huan; Cao, Jiasong; Zhang, Haihong; Qin, Shanchun; Yu, Min; Zhang, Xumei; Wang, Xuan; Gao, Yuxia; Wilson, John X; Huang, Guowei

    2013-11-01

    Folic acid (FA) stimulates neural stem cell (NSC) proliferation in vitro and enhances hippocampal neurogenesis in rats after middle cerebral artery occlusion (MCAO). The effect of FA supplementation on exogenous NSCs transplanted in MCAO rats was observed to determine if FA can stimulate NSC replacement after focal cerebral ischemia. Rats were randomly assigned to 3 groups: MCAO; MCAO and exogenous NSC transplantation (MCAO+NSCs); and MCAO, NSC transplantation and FA (MCAO+NSCs+FA). FA (0.8 mg/kg) or vehicle was administered by gavage daily for 28 days before MCAO and 23 days afterward. NSCs were labeled with superparamagnetic iron oxide (SPIO) and bromodeoxyuridine (BrdU) prior to transplantation into the striatum, contralateral to the ischemic zone, at 2 days post-MCAO. Magnetic resonance imaging tracking and fluorescent immunohistochemistry, as well as measurement of serum folate concentration, were performed at intervals up to 21 days after transplantation. FA supplementation caused sustained increases of 400-600% in serum folate concentration. Magnetic resonance images indicated that SPIO-labeled NSCs were more abundant at the transplantation and ischemic brain sites in MCAO+NSCs+FA rats than in MCAO+NSCs rats. Similarly, immunohistochemistry showed that the numbers of Sox-2/BrdU double positive cells at the transplantation and ischemic sites were higher in the rats that received FA. In conclusion, after focal cerebral ischemia, FA supplementation stimulates transplanted NSCs to proliferate and migrate to ischemic sites. PMID:23850087

  20. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival.

    PubMed

    Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

    2011-09-15

    Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure. PMID:21693562

  1. Effects of a parenteral supplement of folic acid and its interaction with level of feed intake on hepatic tissues and growth performance of young dairy heifers.

    PubMed

    Dumoulin, P G; Girard, C L; Matte, J J; St-Laurent, G J

    1991-04-01

    Forty-seven dairy heifers of approximately 10 d of age were assigned to a factorial experiment in which a supplement of folic acid (0 or 40 mg) administered weekly by i.m. injection and level of feed intake were the two factors studied. The heifers were weaned after 5 wk of experimentation. Following weaning, and until the end of the experiment, 11 wk later, they had ad libitum access to grass hay and concentrates at two different levels, ad libitum or restricted, to allow a body weight gain of 700 g/d. A supplement of folic acid (P less than .05) and ad libitum access to feed (P less than .05) increased the mean concentration of serum folates. Blood hemoglobin and packed cell volume were not affected by the level of feed intake. However, they were both increased (P less than .05) by the supplement of folic acid. Average daily gain was analyzed over three different periods: 0 to 5 wk (before weaning), 5 to 10 wk, and 10 to 16 wk. Average daily gain was increased by the supplement of folic acid during the second period (P less than .05) and by ad libitum access to feed during the last two periods (P less than .05). Ad libitum access to feed increased (P less than .05) weight of the liver, decreased the (P less than .05) concentrations of RNA and DNA, and increased (P less than .05) the ratios of protein/DNA and RNA/DNA. The supplement of folic acid decreased (P less than .05) weight of the liver and increased the ratio RNA/DNA (P less than .05). These effects of supplement of folic acid on growth performance and on hematological cells may reflect a lack of folic acid during the weeks after weaning. PMID:1712767

  2. Highly selective electrochemical biosensor for the determination of folic acid based on DNA modified-pencil graphite electrode using response surface methodology.

    PubMed

    Mirmoghtadaie, Leila; Ensafi, Ali A; Kadivar, Mahdi; Norouzi, Parviz

    2013-04-01

    An electrochemical DNA biosensor was proposed as a screening device for the rapid analysis of folic acid using a pencil graphite electrode modified with salmon sperm ds-DNA. At first, immobilization of the ds-DNA on pencil graphite electrode was optimized using response surface methodology. Solution pH, DNA concentration, time of DNA deposition and potential of deposition was optimized each at three levels. The optimum combinations for the reaction were pH 4.8, DNA concentration of 24 ?g mL(-1), deposition time of 304 s, and deposition potential of 0.60 V, by which the adenine signal was recorded as 3.04 ?A. Secondly the binding of folic acid to DNA immobilized on a pencil graphite electrode was measured through the variation of the electrochemical signal of adenine. Folic acid could be measure in the range of 0.1-10.0 ?mol L(-1) with a detection limit of 1.06×10(-8) ?mol L(-1). The relative standard deviations for ten replicate differential pulse voltammetric measurements of 2.0 and 5.0 ?mol L(-1) folic acid were 4.6% and 4.3%, respectively. The biosensor was successfully used to measure folic acid in different real samples. PMID:23827633

  3. Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile.

    PubMed

    Cortés, Fanny; Mellado, C; Pardo, R A; Villarroel, L A; Hertrampf, E

    2012-08-01

    In January 2000, Chilean Ministry of Health mandated the addition of folic acid (FA) to wheat flour in order to reduce the risk of neural tube defects (NTDs). This policy resulted in significant increases in serum and red cell folate in women of fertile age 1 year after fortification. To evaluate the effect of wheat flour fortification on the prevalence of NTDs in Chile we designed a prospective hospital-based surveillance program to monitor the frequency of NTDs in all births (live and stillbirths) with birth weight?500?g at the nine public maternity hospitals of Santiago, Chile from 1999 to 2009. During the pre-fortification period (1999-2000) the NTD rate was 17.1/10,000 births in a total of 120,566 newborns. During the post-fortification period (2001-2009) the NTD rate decreased to 8.6/10,000 births in a total of 489,915 newborns, which translates into a rate reduction of 50% (RR: 0.5; 95% CI: 0.42-0.59) for all NTDs. The rate reduction by type of NTD studied was: 50% in anencephaly (RR: 0.5; 95% CI: 0.38-0.67), 42% in cephalocele (RR: 0.58; 95% CI: 0.37-0.89), and 52% in spina bifida (RR: 0.48; 95% CI: 0.38-0.6). Rates showed significant reduction both in stillbirths and live births: 510.3 to 183.6/10,000 (RR=0.36; 95% CI: 0.25-0.53) and 13.3 to 7.5/10,000 (RR=0.56; 95% CI: 0.47-0.68), respectively. In Chile, fortification of wheat flour with FA has proven to be an effective strategy for the primary prevention of NTDs. PMID:22711368

  4. Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

    PubMed

    Kondo, Atsuo; Morota, Nobuhito; Date, Hiroaki; Yoshifuji, Kazuhisa; Morishima, Toshibumi; Miyazato, Minoru; Shirane, Reizo; Sakai, Hideki; Pooh, Kyong Hon; Watanabe, Tomoyuki

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 ?g/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0·48 in the first period, and 0·53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan. PMID:25999131

  5. More folic acid, the five questions: why, who, when, how much, and how.

    PubMed

    Mastroiacovo, Pierpaolo; Leoncini, Emanuele

    2011-01-01

    In recent years, a number of studies have been performed to evaluate the possible health benefits of an increased intake of folic acid (FA) on human health. However, the only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40-42th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy. PMID:21674648

  6. Pharmacokinetics, biodistribution, and toxicity of folic acid-coated antiretroviral nanoformulations.

    PubMed

    Gautam, Nagsen; Puligujja, Pavan; Balkundi, Shantanu; Thakare, Rhishikesh; Liu, Xin-Ming; Fox, Howard S; McMillan, JoEllyn; Gendelman, Howard E; Alnouti, Yazen

    2014-12-01

    The drug delivery platform for folic acid (FA)-coated nanoformulated ritonavir (RTV)-boosted atazanavir (FA-nanoATV/r) using poloxamer 407 was developed to enhance cell and tissue targeting for a range of antiretroviral drugs. Such formulations would serve to extend the drug half-life while improving the pharmacokinetic profile and biodistribution to reservoirs of human immunodeficiency virus (HIV) infection. To this end, we now report enhanced pharmacokinetics and drug biodistribution with limited local and systemic toxicities of this novel nanoformulation. The use of FA as a targeting ligand for nanoATV/r resulted in plasma and tissue drug concentrations up to 200-fold higher compared to equimolar doses of native drug. In addition, ATV and RTV concentrations in plasma from mice on a folate-deficient diet were up to 23-fold higher for mice administered FA-nanoATV/r than for mice on a normal diet. Compared to earlier nanoATV/r formulations, FA-nanoATV/r resulted in enhanced and sustained plasma and tissue ATV concentrations. In a drug interaction study, ATV plasma and tissue concentrations were up to 5-fold higher in mice treated with FA-nanoATV/r than in mice treated with FA-nanoATV alone. As observed in mice, enhanced and sustained plasma concentrations of ATV were observed in monkeys. NanoATV/r was associated with transient local inflammation at the site of injection. There were no systemic adverse reactions associated with up to 10 weeks of chronic exposure of mice or monkeys to FA-nanoATV/r. PMID:25288084

  7. Folic Acid Mitigates Angiotensin-II-Induced Blood Pressure and Renal Remodeling

    PubMed Central

    Pushpakumar, Sathnur B.; Kundu, Sourav; Metreveli, Naira; Sen, Utpal

    2013-01-01

    Clinical data suggests an association between systolic hypertension, renal function and hyperhomocysteinemia (HHcy). HHcy is a state of elevated plasma homocysteine (Hcy) levels and is known to cause vascular complications. In this study, we tested the hypothesis whether Ang II-induced hypertension increases plasma Hcy levels and contributes to renovascular remodeling. We also tested whether folic acid (FA) treatment reduces plasma Hcy levels by enhancing Hcy remethylation and thus mitigating renal remodeling. Hypertension was induced in WT mice by infusing Ang II using Alzet mini osmotic pumps. Blood pressure, Hcy level, renal vascular density, oxidative stress, inflammation and fibrosis markers, and angiogenic- and anti-angiogenic factors were measured. Ang II hypertension increased plasma Hcy levels and reduced renal cortical blood flow and microvascular density. Elevated Hcy in Ang II hypertension was associated with decreased 4, 5-Diaminofluorescein (DAF-2DA) staining suggesting impaired endothelial function. Increased expression of Nox-2, -4 and dihydroethidium stain revealed oxidative stress. Excess collagen IV deposition in the peri-glomerular area and increased MMP-2, and -9 expression and activity indicated renal remodeling. The mRNA and protein expression of asymmetric dimethylarginine (ADMA) was increased and eNOS protein was decreased suggesting the involvement of this pathway in Hcy mediated hypertension. Decreased expressions of VEGF and increased anti-angiogenic factors, angiostatin and endostatin indicated impaired vasculogenesis. FA treatment partially reduced hypertension by mitigating HHcy in Ang II-treated animals and alleviated pro-inflammatory, pro-fibrotic and anti-angiogenic factors. These results suggest that renovascular remodeling in Ang II-induced hypertension is, in part, due to HHcy. PMID:24386282

  8. Nanoparticles of deoxycholic acid, polyethylene glycol and folic acid-modified chitosan for targeted delivery of doxorubicin.

    PubMed

    Shi, Zhonggen; Guo, Rui; Li, Weichang; Zhang, Yi; Xue, Wei; Tang, Yu; Zhang, Yuanming

    2014-03-01

    Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS-DCA-PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS-DCA-PEG-FA) with tumor cell targeting property. The structure of the conjugates was characterised using Fourier transform infrared and (1)H nuclear magnetic resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formed nanoparticles with a low critical aggregation concentration of 0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution. Transmission electron microscopy images showed that the DOX-loaded nanoparticles were spherical. The drug release was studied under different conditions. Furthermore, the cytotoxic activities of DOX in CS-DCA-PEG-FA nanoparticles against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3 cells were evaluated. These results suggested that the CS-DCA-PEG-FA nanoparticles may be a promising vehicle for the targeting anticancer drug to tumor cells. PMID:24327111

  9. Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?

    PubMed Central

    2014-01-01

    Background Neural tube defects (NTDs) are the second most common birth defect in humans. Dietary folic acid (FA) supplementation effectively and safely reduces the incidence of these often debilitating congenital anomalies. FA plays an established role in folate and homocysteine metabolism, but the means by which it suppresses occurrence of NTDs is not understood. In addition, many cases remain resistant to the beneficial effects of folic acid supplementation. To better understand the molecular, biochemical and developmental mechanisms by which FA exerts its effect on NTDs, characterized mouse models are needed that have a defined genetic basis and known response to dietary supplementation. Results We examined the effect of FA supplementation, at 5-fold the level in the control diet, on the NTD and vertebral phenotypes in Apob tm1Unc and Vangl2 Lp mice, hereafter referred to as Apob and Lp respectively. The FA supplemented diet did not reduce the incidence or severity of NTDs in Apob or Lp mutant homozygotes or the loop-tail phenotype in Lp mutant heterozygotes, suggesting that mice with these mutant alleles are resistant to FA supplementation. Folic acid supplementation also did not affect the rate of resorptions or the size of litters, but instead skewed the embryonic genotype distribution in favor of wild-type alleles. Conclusion Similar genotypic biases have been reported for several NTD models, but were interpreted as diet-induced increases in the incidence and severity of NTDs that led to increased embryonic lethality. Absence of differences in resorption rates and litter sizes argue against induced embryonic lethality. We suggest an alternative interpretation, namely that FA supplementation led to strongly skewed allelic inheritance, perhaps from disturbances in polyamine metabolism that biases fertilization in favor of wild-type gametes. PMID:25154628

  10. Inconsistent Effects of Iron-Folic Acid and/or Zinc Supplementation on the Cognitive Development of Infants

    PubMed Central

    Kordas, Katarzyna; Stoltzfus, Rebecca J.; Katz, Joanne; Khatry, Subarna K.; LeClerq, Steven C.; Tielsch, James M.

    2011-01-01

    Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 µg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (?85% correct; A-not-B), deteriorated performance (<75% correct and >1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio=0.67; 95% confidence interval 0.46-0.97; p<0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p>0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors. PMID:22283033

  11. Inconsistent effects of iron-folic acid and/or zinc supplementation on the cognitive development of infants.

    PubMed

    Siegel, Emily H; Kordas, Katarzyna; Stoltzfus, Rebecca J; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Tielsch, James M

    2011-12-01

    Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 microg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (> or = 85% correct; A-not-B), deteriorated performance (< 75% correct and > 1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio = 0.67; 95% confidence interval 0.46-0.97; p < 0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p > 0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors. PMID:22283033

  12. Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds.

    PubMed

    Duplessis, M; Girard, C L; Santschi, D E; Laforest, J-P; Durocher, J; Pellerin, D

    2014-04-01

    This study was undertaken to determine the effect of a combined folic acid and vitamin B12 supplement given in early lactation on culling rate, metabolic disorders and other diseases, and reproduction in commercial dairy herds. A total of 805 cows (271 primiparous and 534 multiparous cows) in 15 commercial dairy herds were involved. Every 2mo from February to December 2010 and within each herd, cows were assigned according to parity, previous 305-d milk production, and calving interval to 5mL of either (1) saline 0.9% NaCl (control group) or (2) 320mg of folic acid + 10mg of vitamin B12 (vitamin group). Treatments were administered weekly by intramuscular injections starting 3wk before the expected calving date until 8wk after parturition. A total of 221 cows were culled before the next dry period. Culling rate was not affected by treatment and was 27.5%; culling rate was greater for multiparous (32.2%) than for primiparous cows (18.8%). Within the first 60d in milk (DIM), 47 cows were culled, representing 21.3% of total culling, and no treatment effect was noted. Ketosis incidence based on a threshold ?100µmol/L of ?-hydroxybutyrate in milk was 38.3±2.9% for the vitamin group and 41.8±3.0% for the control group and was not affected by treatment. The combined supplement of folic acid and vitamin B12 did not decrease incidence of retained placenta, displaced abomasum, milk fever, metritis, or mastitis. However, the incidence of dystocia decreased by 50% in multiparous cows receiving the vitamin supplement, although no effect was observed in primiparous cows. The first breeding postpartum for multiparous cows occurred 3.8d earlier with the vitamin supplement compared with controls, whereas no treatment effect was seen for primiparous cows. Days open, first- and second-breeding conception rates, number of breedings per conception, and percentage of cows pregnant at 150 DIM were not affected by treatment. The reduced percentage of dystocia combined with the earlier DIM at first breeding for multiparous cows receiving the combined supplementation in folic acid and vitamin B12 indicates that the vitamin supplement had a positive effect in older cows. PMID:24485680

  13. Hif1? down-regulation is associated with transposition of great arteries in mice treated with a retinoic acid antagonist

    PubMed Central

    2010-01-01

    Background Congenital heart defect (CHD) account for 25% of all human congenital abnormalities. However, very few CHD-causing genes have been identified so far. A promising approach for the identification of essential cardiac regulators whose mutations may be linked to human CHD, is the molecular and genetic analysis of heart development. With the use of a triple retinoic acid competitive antagonist (BMS189453) we previously developed a mouse model of congenital heart defects (81%), thymic abnormalities (98%) and neural tube defects (20%). D-TGA (D-transposition of great arteries) was the most prevalent cardiac defect observed (61%). Recently we were able to partially rescue this abnormal phenotype (CHD were reduced to 64.8%, p = 0.05), by oral administration of folic acid (FA). Now we have performed a microarray analysis in our mouse models to discover genes/transcripts potentially implicated in the pathogenesis of this CHD. Results We analysed mouse embryos (8.5 dpc) treated with BMS189453 alone and with BMS189453 plus folic acid (FA) by microarray and qRT-PCR. By selecting a fold change (FC) ? ± 1.5, we detected 447 genes that were differentially expressed in BMS-treated embryos vs. untreated control embryos, while 239 genes were differentially expressed in BMS-treated embryos whose mothers had also received FA supplementation vs. BMS-treated embryos. On the basis of microarray and qRT-PCR results, we further analysed the Hif1? gene. In fact Hif1? is down-regulated in BMS-treated embryos vs. untreated controls (FCmicro = -1.79; FCqRT-PCR = -1.76; p = 0.005) and its expression level is increased in BMS+FA-treated embryos compared to BMS-treated embryos (FCmicro = +1.17; FCqRT-PCR = +1.28: p = 0.005). Immunofluorescence experiments confirmed the under-expression of Hif1? protein in BMS-treated embryos compared to untreated and BMS+FA-treated embryos and, moreover, we demonstrated that at 8.5 dpc, Hif1? is mainly expressed in the embryo heart region. Conclusions We propose that Hif1? down-regulation in response to blocking retinoic acid binding may contribute to the development of cardiac defects in mouse newborns. In line with our hypothesis, when Hif1? expression level is restored (by supplementation of folic acid), a decrement of CHD is found. To the best of our knowledge, this is the first report that links retinoic acid metabolism to Hif1? regulation and the development of D-TGA. PMID:20846364

  14. Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

    PubMed Central

    Yang, Rui; An, YanLi; Miao, FengQin; Li, MengFei; Liu, PeiDang; Tang, QiuSha

    2014-01-01

    Background This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored. Methods FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjugated to the surface of albumin nanospheres via amino groups. Results Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells. Conclusion Folic acid-conjugated bovine serum albumin nanospheres composed of mixed doxorubicin and magnetic iron oxide cores can enable controlled and targeted delivery of anticancer drugs and may offer a promising alternative to targeted doxorubicin therapy for nasopharyngeal carcinoma. PMID:25228802

  15. Folic Acid Supplementation Use and the MTHFR C677T Polymorphism in Orofacial Clefts Etiology: An Individual Participant Data Pooled-Analysis

    PubMed Central

    Butali, Azeez; Little, Julian; Chevrier, Cécile; Cordier, Sylvian; Steegers-Theunissen, Regine; Jugessur, Astanand; Oladugba, Bola; Mossey, Peter A.

    2013-01-01

    Background This study examines gene-environment interaction (GEI) between the MTHFR C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analyticapproach on four studies that used similar methods. Methods We used logistic regression to analyse the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal MTHFR C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non syndromic cleft palate (CP)] and control groups. Results There was a reduced risk of CL(P) with maternal folic acid use (p=0.008; OR=0.70, 95% CI: 0.65–0.94) and with supplements containing folic acid (p=0.028, OR=0.80, 95% CI: 0.65–0.94). Maternal smoking increased the risk of both CL(P) (p<10e?3; OR=1.62, 95% CI: 1.35–1.95) and CP (p=0.028; OR=1.38, 95% CI: 1.04–1.83). No significant risk was observed with either maternal or fetal MTHFR C677T genotypes. Conclusion This individual paticipant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes. PMID:23670871

  16. Folic acid supplemented goat milk has beneficial effects on hepatic physiology, haematological status and antioxidant defence during chronic Fe repletion.

    PubMed

    Alférez, María J M; Rivas, Emilio; Díaz-Castro, Javier; Hijano, Silvia; Nestares, Teresa; Moreno, Miguel; Campos, Margarita S; Serrano-Reina, Jose A; López-Aliaga, Inmaculada

    2015-02-01

    The aim of the current study was to asses the effect of goat or cow milk-based diets, either normal or Fe-overloaded and folic acid supplement on some aspects of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in liver, brain and erythrocyte of control and anaemic rats after chronic Fe repletion. 160 male Wistar rats were placed on 40 d in two groups, a control group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet. Lately, the rats were fed with goat and cow milk-based diets during 30 d, with normal-Fe content or Fe-overload and either with normal folic or folic acid supplemented. Fe-overload increased plasma alanine transaminase and aspartate transaminase levels when cow milk was supplied. Dietary folate supplementation reduced plasma transaminases levels in animals fed goat milk with chronic Fe overload. A remarkable increase in the superoxide dismutase activity was observed in the animals fed cow milk. Dietary folate supplement lead to a decrease on the activity of this enzyme in all the tissues studied with both milk-based diets. A concomitant increment in catalase was also observed. The increase in lipid peroxidation products levels in rats fed cow milk with Fe-overload, suggest an imbalance in the functioning of the enzymatic antioxidant defence. In conclusion, dietary folate-supplemented goat milk reduces both plasma transaminases levels, suggesting a hepatoprotective effect and has beneficial effects in situation of Fe-overload, improving the antioxidant enzymes activities and reducing lipid peroxidation. PMID:25394837

  17. Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study

    PubMed Central

    Ban, Lu; Fleming, Kate M.; Doyle, Pat; Smeeth, Liam; Hubbard, Richard B.; Fiaschi, Linda; Tata, Laila J.

    2015-01-01

    Background Antenatal antiepileptic drug (AED) use has been found to be associated with increased major congenital anomaly (CA) risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily) folic acid supplementation is still unclear. Methods We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR) were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception). Results CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21). Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46-4.74 and aOR 2.01,1.12-3.59 respectively) and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group); however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy. Conclusions Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be effective during the organogenic period or selective prescribing to those with more severe morbidity may explain these findings. PMID:26147467

  18. Synthesis of multifunctional Ag@Au@phenol formaldehyde resin particles loaded with folic acids for photothermal therapy.

    PubMed

    Yang, Ping; Xu, Qi-Zhi; Jin, Sheng-Yu; Lu, Yang; Zhao, Yang; Yu, Shu-Hong

    2012-07-23

    Multifunctional Ag@Au@ phenol formaldehyde resin (PFR) particles loaded with folic acids (FA) have been designed for killing tumor cells through photothermy conversion under the irradiation of near-infrared (NIR) light. Possessing the virtue of good fluorescence, low toxicity, and good targeting, the nanocomposite consists of an Ag core, an Au layer, a PFR shell, and folic acids on the PFR shell. The Ag@PFR core-shell structure can be prepared with a simple hydrothermal method after preheating. We then filled the PFR shell with a layer of Au by heating and modified the shell with polyelectrolyte to change its surface charge state. To capture tumor cells actively, FA molecules were attached onto the surface of the Ag@Au@PFR particles in the presence of 1-ethyl-3-(3-dimethly aminopropyl) carbodiimide (EDAC) and N-hydroxysuccinimide (NHS). Owing to the excellent property of Au NPs and Ag NPs as photothermal conversion agents, the Ag@Au@ PFR@FA particles can be utilized to kill tumor cells when exposed to NIR light. PMID:22744779

  19. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  20. Apoptosis selectively induced in BEL-7402 cells by folic acid-modified magnetic nanoparticles combined with 100 Hz magnetic field

    PubMed Central

    Wen, Jian; Jiang, Shulian; Chen, Zhiqiang; Zhao, Wei; Yi, Yongxiang; Yang, Ruili; Chen, Baoan

    2014-01-01

    Objective To explore the effect of folic acid-modified magnetic nanoparticles (FA-MNPs) combined with a 100 Hz extremely low-frequency electromagnetic field (ELF-EMF) on the apoptosis of liver cancer BEL-7402 cells. Materials and methods MNPs (20 nm) were prepared by coprecipitation, and then folic acid was coated onto MNPs to prepare FA-MNPs. BEL-7402 cells and HL7702 cells were selected as liver cancer cells and normal liver cells, respectively. The ELF-EMF was generated from a solenoid coil. Cellular uptake of NPs was determined by inductively coupled plasma atomic emission spectroscopy. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cell inhibition. Apoptosis was analyzed by flow cytometry. Statistical analyses were performed using two-way analysis of variance. Results FA-MNPs combined with a 100 Hz magnetic field significantly inhibited cell proliferation and induced higher apoptosis compared to either the ELF-EMF alone or FA-MNPs alone. FA-MNPs showed a better apoptosis effect and higher iron uptake in BEL-7402 cells compared to in HL7702 cells. On the basis of the ELF-EMF, higher doses of FA-MNPs brought higher apoptosis and higher iron uptake in either BEL-7402 cells or HL7702 cells. Conclusion These results suggest that FA-MNPs may induce apoptosis in a cellular iron uptake-dependent manner when combined with an ELF-EMF in BEL-7402 cells. PMID:24790442

  1. Synthesis of lipid A monosaccharide analogues containing acidic amino acid: Exploring the structural basis for the endotoxic and antagonistic activities

    Microsoft Academic Search

    Masao Akamatsu; Yukari Fujimoto; Mikayo Kataoka; Yasuo Suda; Shoichi Kusumoto; Koichi Fukase

    2006-01-01

    For elucidation of the structural and conformational requirements on the endotoxic and antagonistic activity of lipid A derivatives, we designed and synthesized lipid A analogues containing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was observed depending on the difference of the acidic groups (phosphoric acid or carboxylic

  2. Formic acid–sodium benzoate preserved slaughterhouse offal and supplementary folic acid in mink diet

    Microsoft Academic Search

    I Pölönen; P Niemelä; Y Xiao; L Jalkanen; H Korhonen; J Mäkelä

    1999-01-01

    Slaughterhouse offal from beef slaughtering was preserved with 16gkg?1 formic acid and 3gkg?1 sodium benzoate and used in mink feed throughout the production year. The ensiled offal replaced 0, 0.5 or 1.0 parts of the frozen stored slaughterhouse offal in the basal diet, the level of which was 300, 200 and 260gkg?1 during growth-furring, breeding and lactation periods respectively. Because

  3. E! ect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial

    Microsoft Academic Search

    Jane Durga; Martin P J van Boxtel; Evert G Schouten; Frans J Kok; Jelle Jolles; Martijn B Katan; Petra Verhoef

    2007-01-01

    Background Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the e! ect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the

  4. Folic acid mediated attenuation of loss of heterozygosity of DCC tumor suppressor gene in the colonic mucosa of patients with colorectal adenomas

    Microsoft Academic Search

    Kiran K Nagothu; Richard Jaszewski; Lathika Moragoda; Arun K Rishi; Raphaela Finkenauer; Martin Tobi; Jo Ann Naumoff; Ravi Dhar; Murray Ehrinpreis; Omer Kucuk; Adhip P. N Majumdar

    2003-01-01

    Loss of heterozygosity (LOH) and\\/or inactivation of tumor suppressor genes are implicated in the initiation and progression of many malignancies, including colorectal cancer. Although accumulating evidence suggests a chemopreventive role for folate in colorectal cancer, regulatory mechanisms are poorly understood. The primary objective of the current investigation was to determine whether folic acid would prevent LOH of the three tumor

  5. Folic Acid and the Prevention of Neural Tube Defects: A Survey of Awareness Among Latina Women of Childbearing Age Residing in Southeast Michigan

    Microsoft Academic Search

    Srimathi Kannan; Elaine Menotti; Holly K. Scherer; Jennifer Dickinson; Kimberly Larson

    2007-01-01

    Periconceptional intake of folic acid is known to reduce the risk for neural tube defects (NTDs). To inform southeast Michigan Latina women of childbearing age about the benefits of food and supplemental sources of the micronutrient in the prevention of NTDs, Spanish-English bilingual health educators carried out 20 education events in supermarkets and community organizations serving Latina women. One hundred

  6. Effects of multivitamins and low-dose folic acid supplements on flow-mediated vasodilation and plasma homocysteine levels in older adults

    Microsoft Academic Search

    Cynthia M. Carlsson; Lisa M. Pharo; Susan E. Aeschlimann; Carol Mitchell; Gail Underbakke; James H. Stein

    2004-01-01

    BackgroundHyperhomocysteinemia is associated with aging, endothelial dysfunction, and increased risk of coronary heart disease in older adults; however, the effects of homocysteine-lowering therapy on vascular reactivity in older persons are unknown. The objective of this study was to determine the effects of multivitamins (MV) and folic acid (FA) supplements on flow-mediated vasodilation (FMD) in older adults.

  7. A Temporal Association between Folic Acid Fortification and an Increase in Colorectal Cancer Rates May Be Illuminating Important Biological Principles: A Hypothesis

    Microsoft Academic Search

    Joel B. Mason; Aaron Dickstein; Paul F. Jacques; Paul Haggarty; Jacob Selhub; Gerard Dallal; Irwin H. Rosenberg

    Nationwide fortification of enriched uncooked cereal grains with folic acid began in the United States and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the United States and Canada experienced abrupt reversals of the downward trend in colorectal cancer (CRC) incidence that

  8. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historic data on folic acid treatment of pernicious anemia suggested that high-level fortification would delay diagnosis or exacerbate effects of vitamin B12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive and experime...

  9. A Temporal Association between Folic Acid Fortification and a Rise in Colorectal Cancer Rates May be Illuminating Important Biological Principles: a Hypothesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nationwide fortification of enriched uncooked cereal grains with folic acid began in the U.S. and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the U.S. and Canada experienced ab...

  10. Breakfast cereal fortified with folic acid, vitamin B6, and vitamin B12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial1-3

    Microsoft Academic Search

    Katherine L Tucker; Beth Olson; Peter Bakun; Gerard E Dallal; Jacob Selhub; Irwin H Rosenberg

    Background: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults. Objective: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocys- teine status. Design: A randomized, double-blind trial was conducted in 189 volunteers

  11. A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women

    Microsoft Academic Search

    Gerard J Casey; Tran Q Phuc; Lachlan MacGregor; Antonio Montresor; Seema Mihrshahi; Tran D Thach; Nong T Tien; Beverley-Ann Biggs

    2009-01-01

    BACKGROUND: Anemia due to iron deficiency is recognized as one of the major nutritional deficiencies in women and children in developing countries. Daily iron supplementation for pregnant women is recommended in many countries although there are few reports of these programs working efficiently or effectively. Weekly iron-folic acid supplementation (WIFS) and regular deworming treatment is recommended for non-pregnant women living

  12. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). A 19-bp noncoding deletion allele maps to intron 1, beginning 60 bases from the splice donor site, and has been implicated in neural tube defects and cancer, presumably by influencing folate metabolism. T...

  13. Folic Acid-Tagged Protein Nanoemulsions Loaded with CORM-2 Enhance the Survival of Mice Bearing Subcutaneous A20 Lymphoma Tumors

    E-print Network

    Loureiro, Ana; Bernardes, Gonçalo J. L.; Shimanovich, Ulyana; Sárria, Marisa P.; Nogueira, Eugénia; Preto, Ana; Gomes, Andreia C.; Cavaco-Paulo, Artur

    2015-03-16

    Folic Acid (FA)-tagged protein nanoemulsions were found to be preferentially internalized on B-cell lymphoma cell line (A20 cell line), which, for the first time, are reported to express folate receptor (FR)-alpha. Carbon monoxide releasing molecule...

  14. Concentrations of blood folate in Brazilian studies prior to and after fortification of wheat and cornmeal (maize flour) with folic acid: a review

    PubMed Central

    Britto, Jéssica Carrilho; Cançado, Rodolfo; Guerra-Shinohara, Elvira Maria

    2014-01-01

    Background 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. Objective 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. Methods 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. Results 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. Conclusion Folic acid fortification of wheat flour and cornmeal increased the blood folate concentrations and reduced the incidence of neural tube defects. PMID:25031167

  15. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

    PubMed Central

    Morse, Nancy L.

    2012-01-01

    Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064

  16. Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction after functionalization with folic and glucuronic acids.

    PubMed

    Sánchez Lafarga, Ana Karen; Pacheco Moisés, Fermín P; Gurinov, Andrey; Ortiz, Genaro Gabriel; Carbajal Arízaga, Gregorio Guadalupe

    2015-03-01

    The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity. PMID:25579955

  17. Paclitaxel-Loaded, Folic-Acid-Targeted and TAT-Peptide-Conjugated Polymeric Liposomes: In Vitro and In Vivo Evaluation

    Microsoft Academic Search

    Peiqi Zhao; Hanjie Wang; Man Yu; Shuzhen Cao; Fei Zhang; Jin Chang; Ruifang Niu

    2010-01-01

    Objective  Folic acid and TAT peptide were conjugated on the octadecyl-quaternized, lysine-modified chitosan-cholesterol polymeric liposomes\\u000a (FA-TATp-PLs) to investigate their potential feasibility for tumor-targeted drug delivery.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  FA-TATp-PLs encapsulating paclitaxel or calcein were synthesized and characterized. Cellular uptake of PLs, FA-PLs, TATp-PLs\\u000a and FA-TATp-PLs was studied by confocal laser scanning microscopy (CLSM) in folate receptor (FR)-positive KB nasopharyngeal\\u000a epidermal carcinoma cells and FR-deficient

  18. Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging

    PubMed Central

    2013-01-01

    Background Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells. Method AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated AuNCs@SiO2 nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(?) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging. Results FA-conjugated AuNCs@SiO2 nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging. Conclusion The high-performance FA-conjugated AuNCs@SiO2 nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future. PMID:23718865

  19. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification.

    PubMed

    Barboza-Argüello, María de la Paz; Umaña-Solís, Lila M; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-03-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

  20. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism.

    PubMed

    Kale, Anvita; Naphade, Nilesh; Sapkale, Swati; Kamaraju, Marellasv; Pillai, Anilkumar; Joshi, Sadhana; Mahadik, Sahebarao

    2010-01-30

    Abnormal one-carbon metabolism has long been suggested as one of the mechanisms for neuropathology and psychopathology of schizophrenia. Variable levels of components of one-carbon metabolism (folic acid and vitamin B12) and consequent altered levels of homocysteine and phospholipid docosahexaenoic acid (DHA) have been independently reported, mostly in medicated patients. This study examined the simultaneous levels of these key components of one-carbon metabolism and its consequences in unique, medication-naïve first-episode psychotic patients (FEP, n=31) and healthy controls (HC, n=48) matched for confounds such as race, diet and lifestyle to reduce the variability. Significantly lower levels of folate and vitamin B12 in plasma and folate in red blood cells were observed in FEP compared to HC. These reductions paralleled the significant increase in plasma homocysteine and cortisol levels. Significantly reduced levels of membrane DHA were also observed in FEP compared to HC. This study, using a unique cohort, provided a broader mechanism (disturbed folic acid-vitamin B12-DHA balance) of altered one-carbon metabolism and one of its key consequential components, an increased homocysteine level that together with cortisol, can contribute to the neuropathology of psychosis. These data may have important implications for the amelioration of psychopathology in schizophrenia. PMID:19969375

  1. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.

    PubMed

    Chrencik, Jill E; Roth, Christopher B; Terakado, Masahiko; Kurata, Haruto; Omi, Rie; Kihara, Yasuyuki; Warshaviak, Dora; Nakade, Shinji; Asmar-Rovira, Guillermo; Mileni, Mauro; Mizuno, Hirotaka; Griffith, Mark T; Rodgers, Caroline; Han, Gye Won; Velasquez, Jeffrey; Chun, Jerold; Stevens, Raymond C; Hanson, Michael A

    2015-06-18

    Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease. PMID:26091040

  2. Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, and N-acetylcysteine in chicken embryo model.

    PubMed

    Hsieh, Chiu-Lan; Wang, Hui-Er; Tsai, Wan-Jane; Peng, Chiung-Chi; Peng, Robert Y

    2012-01-27

    The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the risk of VPA-teratogenicity. The effect was varying. In order to promote the preventive prescription, to find out its action mechanism can be rather crucial. We used chicken embryo model to try the effect of folic acid (FA), ascorbic acid (AA), and N-acetyl cysteine (NAC). VPA at 30mM showed the higher malformation rate (66.7%) with the least mortality (22.2%). Pathological findings indicated that the cervical muscle was more susceptible to VPA injury than the ankle muscle. VPA downregulated levels of superoxide dismutase (SOD), glutathione (GSH), histone deacetylase (HDAC) and folate, and upregulated H(2)O(2) and homocysteine. FA, AA, and NAC significantly upregulated SOD, but only AA alone activated GSH. AA and NAC downregulated H(2)O(2), while FA was totally ineffective. All three nutraceutics comparably rescued HDAC with simultaneously suppressed homocysteine accumulation and folate re-elevation, although less effectively by NAC. Based on these data, we conclude VPA possesses "Multiple Point Action Mechanism". In addition to affecting the cited transcription and translation levels, we hypothesize that VPA competitively antagonize the glutamic acid to couple with pteroic acid in biosynthesis of dihydrofolic acid (DHFA). H(2)O(2) directly destroyed the NADPH reducing system at dihydrofolate reductase (DHFR) and methylene tetrahydrofolate reductase (MTHFR) levels, while completely restored by AA, an implication in preservation of intact apoenzymes. In addition, the GSH-GSSG system is sandwiched between the reducing systems NADPH/NADP and DHA-AA, its net balance is highly dependent on in situ in vivo Redox state, hence folic acid transformation is varying. To rescue the VPA-induced teratogenicity, simultaneous multiple prescriptions are suggested. PMID:22051200

  3. Kinetic Model of Folate Metabolism in Nonpregnant Women Consuming ( 2H2 )Folic Acid: Isotopic Labeling of Urinary Folate and the Catabolite para-Acetamidobenzoylglutamate Indicates Slow, Intake-Dependent, Turnover of Folate Pools1,2

    Microsoft Academic Search

    Jesse F. Gregory; Jerry Williamson; Jo-Fu Liao; Lynn B. Bailey; John P. Toth

    In a 10-wk study of folate metabolism in nonpregnant women (21-27 y, n 55- 6 per group), subjects were fed a diet containing ;68 nmol\\/d (30 mg\\/d) folate from food. The remainder of the ingested folate was provided as folic acid in apple juice (as nonlabeled during wk 1-2, as (2H2)folic acid during wk 3-10) to yield a constant intake

  4. Synthesis, Spectroscopic and Thermal Characterization of Copper(II) and Iron(III) Complexes of Folic Acid and Their Absorption Efficiency in the Blood

    PubMed Central

    Hamed, E.; Attia, M. S.; Bassiouny, K.

    2009-01-01

    The absorption efficiency of any drug in blood is of prime importance. Compounds having the general formula: Kn[M(FO)2(H2O)2] · xH2O, where (M = Cu(II) or Fe(III), n = 2 or 1, FO = folate anion, x = 2 or 3 with respect), were prepared, and their absorption efficiency in rodent's blood was determined. The obtained compounds were characterized by elemental analysis, infrared as well as thermogravimetric analysis and polarization of light. The results suggest that the two folate complexes were formed in 1 : 2 molar ratio (metal : folic acid) which acted as a bidentate ligand through both carboxylic groups. Polarization of light proved that the folate complexes have symmetric geometry. Biological application proved that Cu(II) and Fe(III) complexes were absorbed more efficiently in rodent blood than folic acid itself. PMID:19746175

  5. Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro

    Microsoft Academic Search

    Jimmy W. Crott; Susan T. Mashiyama; Bruce N. Ames; Michael F. Fenech

    MnTHF is available to provide methyl groups for the conversion of uracil to thymidine. Folic acid deficiency homocysteine concentrations (4,7,8), which is thought to be causes the intracellular accumulation of dUMP and the due to the inefficient recycling of homocysteine to methionine. subsequent incorporation of uracil into DNA. The removal The TT genotype is associated with an elevated risk for

  6. Reassessing folic acid consumption patterns in the United States (1999-2004): potential effect on neural tube defects and overexposure to folate1-3

    Microsoft Academic Search

    Eoin P Quinlivan; Jesse F Gregory

    Background: In the United States, folic acid fortification of cereal- grainfoodshassignificantlyincreasedfolatestatus.However,blood folate concentrations have decreased from their postfortification high as a result, in part, of decreasing food fortification concentra- tions and the popularity of low-carbohydrate weight-loss diets. Objectives:The objectives of the study were to quantify changes in folateintakeafterfolicacidfortificationandtoestimatetheeffecton neural tube defect (NTD) occurrence. Design: Expanding on an earlier model, we

  7. Synthesis and Preclinical Evaluation of a Folic Acid Derivative Labeled with 18F for PET Imaging of Folate Receptor-Positive Tumors

    Microsoft Academic Search

    Andrea Bettio; Michael Honer; M atthias Bruhlmeier; Ursina Muller; Roger Schibli; Viola Groehn; August P. Schubiger; Simon M. Ametamey

    Folicacidwaslinkedregioselectivelythroughits a-andg-carboxyl groups to 4-fluorobenzylamine (FBA), and the a -a ndg-FBA- folate regioisomers were evaluated for their ability to bind to folate receptor-positive cells. The 18F-labeled a\\/g-FBA-folate counter- part was examined for in vivo tumor targeting efficiency in nude mice bearing folate receptor-positive tumor cells. Methods: 18F- a\\/g-FBA-folate was prepared in a 4-step reaction sequence start- ing from folic acid.

  8. The use of imidazolium ionic liquid/copper complex as novel and green catalyst for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals.

    PubMed

    Azizi, Seyed Naser; Shakeri, Parmis; Chaichi, Mohammad Javad; Bekhradnia, Ahmadreza; Taghavi, Mehdi; Ghaemy, Mousa

    2014-03-25

    A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu(2+) and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1×10(-9)-1×10(-)(6) M of folic acid with a correlation coefficient (R(2)) of 0.9991. The limit of detection of this system was found to be 1×10(-)(10) M. This method is not only simple, sensitive and low cost, but also reliable for practical applications. PMID:24322762

  9. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial

    PubMed Central

    Kvestad, Ingrid; Taneja, Sunita; Kumar, Tivendra; Hysing, Mari; Refsum, Helga; Yajnik, Chittaranjan S.; Bhandari, Nita; Strand, Tor A.

    2015-01-01

    Objectives Deficiencies of vitamin B12 and folate are associated with delayed development and neurological manifestations. The objective of this study was to measure the effect of daily supplementation of vitamin B12 and/or folic acid on development in young North Indian children. Methods In a randomized, double blind trial, children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention. Results Compared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 ?mol/L) or in those who were younger than 24 at end study. With the exception of a significant improvement on gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes. Conclusion Our findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children. Trial Registration ClinicalTrials.gov NCT00717730 PMID:26098427

  10. The use of imidazolium ionic liquid/copper complex as novel and green catalyst for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals

    NASA Astrophysics Data System (ADS)

    Azizi, Seyed Naser; Shakeri, Parmis; Chaichi, Mohammad Javad; Bekhradnia, Ahmadreza; Taghavi, Mehdi; Ghaemy, Mousa

    2014-03-01

    A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu2+ and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1 × 10-9-1 × 10-6 M of folic acid with a correlation coefficient (R2) of 0.9991. The limit of detection of this system was found to be 1 × 10-10 M. This method is not only simple, sensitive and low cost, but also reliable for practical applications.

  11. Comparative Transcriptome Analysis Reveals the Influence of Abscisic Acid on the Metabolism of Pigments, Ascorbic Acid and Folic Acid during Strawberry Fruit Ripening

    PubMed Central

    Luo, Zisheng; Mou, Wangshu; Mao, Linchun; Ying, Tiejin

    2015-01-01

    A comprehensive investigation of abscisic acid (ABA) biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker) treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA) and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of ?-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and ?-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient’s biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA’s role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future. PMID:26053069

  12. Impact of CuO nanoleaves on MWCNTs/GCE nanocomposite film modified electrode for the electrochemical oxidation of folic acid

    NASA Astrophysics Data System (ADS)

    Manoj, D.; Ranjith Kumar, D.; Santhanalakshmi, J.

    2012-09-01

    The salient features of the present work focus on the synthesis of CuO nanoleaves by alcoholic reduction of Cu(II) chloride in the presence of poly(diallyldimethylammonium chloride) (PDDA) for the application of folic acid oxidation in simulated body fluid environment. PDDA-assisted polyol process allows a conventional impregnation method for the formation of CuO with well-defined leaf-like structure. The structure and morphology of the CuO nanoleaves were characterized by Fourier-transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. Field emission scanning electron microscope (FESEM) image confirms the formations of CuO with leaf-like morphology and branched side edges. The average size of the resultant CuO nanoleaves was calculated to be 400 nm in length and 150 nm in width. The electrochemical performance of the CuONs/MWCNTs/GCE nanocomposite modified electrode was characterized by cyclic voltammetric (CV) studies. The CuONs/MWCNTs/GCE nanocomposite modified electrode shows good electrochemical activity and it was also found that it possessed prominent electrocatalytic activity toward the oxidation of folic acid with as high a sensitivity as 3.35 ?A/?M and a low detection limit (3 ?) of 15.2 nM (S/N = 3). Besides, the CuO nanocomposite modified electrode lowers the over potential of folic acid oxidation than the unmodified electrodes.

  13. Potent dual antagonists of endothelin and angiotensin II receptors derived from ?-phenoxyphenylacetic acids (Part III)

    Microsoft Academic Search

    Thomas F. Walsh; Kenneth J. Fitch; David L. Williams; Kathryn L. Murphy; Nancy A. Nolan; Douglas J. Pettibone; Raymond S. L. Chang; Stacey S. O'Malley; Bradley V. Clineschmidt; Daniel F. Veber; William J. Greenlee

    1995-01-01

    Screening a collection of ?-phenoxyphenylacetic acid derived angiotensin II antagonists identified weak actives in an endothelin receptor binding assay. Synthetic modification of one of these leads has provided L-746,072 (13), a highly potent dual antagonist of angiotensin II and endothelin receptors.

  14. Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan–folic acid micelles

    PubMed Central

    Wang, Feihu; Chen, Yuxuan; Zhang, Dianrui; Zhang, Qiang; Zheng, Dandan; Hao, Leilei; Liu, Yue; Duan, Cunxian; Jia, Lejiao; Liu, Guangpu

    2012-01-01

    Background A critical disadvantage for successful chemotherapy with paclitaxel (PTX) is its nontargeting nature to cancer cells. Folic acid has been employed as a targeting ligand of various anticancer agents to increase their cellular uptake within target cells since the folate receptor is overexpressed on the surface of such tumor cells. In this study, a novel biodegradable deoxycholic acid-O-carboxymethylated chitosan–folic acid conjugate (DOMC-FA) was used to form micelles for encapsulating the anticancer drug PTX. Methods and results The drug-loading efficiency, encapsulation efficiency, in vitro drug release and physicochemical properties of PTX-loaded micelles were investigated in detail. In vitro cell culture studies were carried out in MCF-7 cells, a human breast carcinoma cell line, with folate receptor overexpressed on its surface. An increased level of uptake of folate-conjugated micelles compared to plain micelles in MCF-7 cells was observed, and the enhanced uptake of folate-micelles mainly on account of the effective process of folate receptor-mediated endocytosis. The MTT assay, morphological changes, and apoptosis test implied that the folate-conjugated micelles enhanced the cell death by folate-mediated active internalization, and the cytotoxicity of the FA-micellar PTX (DOMC-FA/PTX) to cancer cells was much higher than micelles without folate (DOMC/PTX) or the commercially available injectable preparation of PTX (Taxol). Conclusion Results indicate that the PTX-loaded DOMC-FA micelle is a successful anticancertargeted drug-delivery system for effective cancer chemotherapy. PMID:22287842

  15. Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells

    PubMed Central

    2014-01-01

    Background The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa). Results In this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines. Conclusions Results showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs. PMID:25026938

  16. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD1 mice

    Microsoft Academic Search

    Jennifer E. Dawson; Angela M. Raymond; Louise M.. Winn

    2006-01-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of

  17. Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis

    NASA Astrophysics Data System (ADS)

    Su, Dongyue; Yang, Xin; Xia, Qingdong; Zhang, Qi; Chai, Fang; Wang, Chungang; Qu, Fengyu

    2014-09-01

    In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were selected as a colorimetric and a ‘turn on’ fluorescent sensor for detecting Hg2+. After being added into Hg2+, AgNPs can emit stable fluorescence at 440 nm when the excitation wavelength is selected at 275 nm. The absorbance and fluorescence of the FA-AgNPs could reflect the concentration of the Hg2+ ions. Thus, we developed a simple, sensitive analytical method to detect Hg2+ based on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits two linear response ranges between absorbance and fluorescence intensity with Hg2+ concentration, respectively. Meanwhile, a detection limit of 1 nM is estimated based on the linear relationship between responses with a concentration of Hg2+. The high specificity of Hg2+ with FA-AgNPs interactions provided the excellent selectivity towards detecting Hg2+ over other metal ions (Pb2+, Mg2+, Zn2+, Ni2+, Cu2+, Co2+, Ca2+, Mn2+, Fe2+, Cd2+, Ba2+, Cr6+ and Cr3+). This will provide a simple, effective and multifunctional colorimetric and fluorescent sensor for on-site and real-time Hg2+ ion detection. The proposed method can be applied to the analysis of trace Hg2+ in lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the reduction of 4-nitrophenol and potassium hexacyanoferrate (III).

  18. Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis.

    PubMed

    Su, Dongyue; Yang, Xin; Xia, Qingdong; Zhang, Qi; Chai, Fang; Wang, Chungang; Qu, Fengyu

    2014-09-01

    In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were selected as a colorimetric and a 'turn on' fluorescent sensor for detecting Hg(2+). After being added into Hg(2+), AgNPs can emit stable fluorescence at 440 nm when the excitation wavelength is selected at 275 nm. The absorbance and fluorescence of the FA-AgNPs could reflect the concentration of the Hg(2+) ions. Thus, we developed a simple, sensitive analytical method to detect Hg(2+) based on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits two linear response ranges between absorbance and fluorescence intensity with Hg(2+) concentration, respectively. Meanwhile, a detection limit of 1 nM is estimated based on the linear relationship between responses with a concentration of Hg(2+). The high specificity of Hg(2+) with FA-AgNPs interactions provided the excellent selectivity towards detecting Hg(2+) over other metal ions (Pb(2+), Mg(2+), Zn(2+), Ni(2+), Cu(2+), Co(2+), Ca(2+), Mn(2+), Fe(2+), Cd(2+), Ba(2+), Cr(6+) and Cr(3+)). This will provide a simple, effective and multifunctional colorimetric and fluorescent sensor for on-site and real-time Hg(2+) ion detection. The proposed method can be applied to the analysis of trace Hg(2+) in lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the reduction of 4-nitrophenol and potassium hexacyanoferrate (III). PMID:25116278

  19. Effects of folic acid deficiency and MTHFRC677T polymorphisms on cytotoxicity in human peripheral blood lymphocytes

    SciTech Connect

    Wu Xiayu; Liang Ziqing [School of Life Sciences, Yunnan Normal University, Kunming Yunnan 650092 (China); Zou Tianning [Thirdary Affiliated hospital of Kunming Medical College, Kunming Yunnan 650101 (China); Wang Xu [School of Life Sciences, Yunnan Normal University, Kunming Yunnan 650092 (China)], E-mail: wangxu@fudan.edu.cn

    2009-02-13

    Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicity was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.

  20. [Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification].

    PubMed

    Fujimori, Elizabeth; Baldino, Camila Florido; Sato, Ana Paula Sayuri; Borges, Ana Luiza Vilela; Gomes, Murilo Novaes

    2013-01-01

    This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC) and presented prevalence rates according to maternal characteristics with odds ratios (OR) and 95% confidence intervals (95%CI). Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube defects decreased by 35%, from 0.57/1,000 to 0.37/1,000 live births after fortification (OR = 0.65; 95%CI: 0.59-0.72). There was a reduction among newborns of mothers with the following characteristics: all age groups (except < 15 years), more than three years of schooling, and seven or more prenatal visits. There was a reduction over time and in most of São Paulo State, except in a few municipalities (counties) located in the western region of the State. Other factors may have contributed to the observed decline, but the results corroborate flour fortification as an important measure to prevent neural tube defects. Further research is needed to elucidate the lack of a decline in neural tube defects in the western part of São Paulo State. PMID:23370034

  1. Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer.

    PubMed

    Gunduz, Ufuk; Keskin, Tugba; Tans?k, Gulistan; Mutlu, Pelin; Yalcin, Serap; Unsoy, Gozde; Yakar, Arzu; Khodadust, Rouhollah; Gunduz, Gungor

    2014-07-01

    Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500?g/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy. PMID:25194441

  2. The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines.

    PubMed

    Farias, Nathan; Ho, Nelson; Butler, Stacey; Delaney, Leanne; Morrison, Jodi; Shahrzad, Siranoush; Coomber, Brenda L

    2015-08-01

    Folate and its synthetic form, folic acid (FA), are essential vitamins for the regeneration of S-adenosyl methionine molecules, thereby maintaining adequate cellular methylation. The deregulation of DNA methylation is a contributing factor to carcinogenesis, as alterations in genetic methylation may contribute to stem cell reprogramming and dedifferentiation processes that lead to a cancer stem cell (CSC) phenotype. Here, we investigate the potential effects of FA exposure on DNA methylation and colonosphere formation in cultured human colorectal cancer (CRC) cell lines. We show for the first time that HCT116, LS174T, and SW480 cells grown without adequate FA demonstrate significantly impaired colonosphere forming ability with limited changes in CD133, CD166, and EpCAM surface expression. These differences were accompanied by concomitant changes to DNA methyltransferase (DNMT) enzyme expression and DNA methylation levels, which varied depending on cell line. Taken together, these results demonstrate an interaction between FA metabolism and CSC phenotype in vitro and help elucidate a connection between supplemental FA intake and CRC development. PMID:25804133

  3. The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes.

    PubMed

    Cao, Yunlei; Zhang, Zhaofeng; Zheng, Yanmin; Yuan, Wei; Wang, Jian; Liang, Hong; Chen, Jianping; Du, Jing; Shen, Yueping

    2014-05-01

    The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively). PMID:24728915

  4. A novel drug "copper acetylacetonate" loaded in folic acid-tagged chitosan nanoparticle for efficient cancer cell targeting.

    PubMed

    Pramanik, Arindam; Laha, Dipranjan; Pramanik, Panchanan; Karmakar, Parimal

    2014-01-01

    Several copper compounds have proven anti-cancer activity. Similarly, curcumin a derivative of 1,3 diketone, which is not plenty in nature, has comparable anti-cancer activity. In this work, we have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group. The cytotoxicity of the copper acetylacetonate (CuAA) complex was evaluated on various cancer cells and LD50 doses were determined. To investigate the mechanism, various biochemical assays were performed and reactive oxygen species as well as the glutathione level in the cell were found to be increased after the treatment with the above-mentioned complex. Further this reagent induced apoptosis and reduced mitochondrial membrane potential of the cells. Because of the poor solubility and reasonable cytotoxicity of CuAA, polymer nanoparticles (NPs) of chitosan derivatives were used for delivery in cancer cells. For the targeted delivery, folic acid-tagged hydrophobic-modified chitosan NPs were developed and the CuAA was encapsulated. Finally, these drug-encapsulated NPs were successfully delivered to folate receptor over-expressed cancer cells. Thus using nanotechnology, we developed an anti-cancer agent suitable for targeted delivery. PMID:23987131

  5. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery.

  6. Intermediate states in the binding process of folic acid to folate receptor ?: insights by molecular dynamics and metadynamics.

    PubMed

    Della-Longa, Stefano; Arcovito, Alessandro

    2015-01-01

    Folate receptor ? (FR?) is a cell surface, glycophosphatidylinositol-anchored protein which has focussed attention as a therapeutic target and as a marker for the diagnosis of cancer. It has a high affinity for the dietary supplemented folic acid (FOL), carrying out endocytic transport across the cell membrane and delivering the folate at the acidic pH of the endosome. Starting from the recently reported X-ray structure at pH 7, 100 ns classical molecular dynamics simulations have been carried out on the FR?-FOL complex; moreover, the ligand dissociation process has been studied by metadynamics, a recently reported method for the analysis of free-energy surfaces (FES), providing clues on the intermediate states and their energy terms. Multiple dissociation runs were considered to enhance the configurational sampling; a final clustering of conformations within the averaged FES provides the representative structures of several intermediate states, within an overall barrier for ligand escape of about 75 kJ/mol. Escaping of FOL to solvent occurs while only minor changes affect the FR? conformation of the binding pocket. During dissociation, the FOL molecule translates and rotates around a turning point located in proximity of the receptor surface. FOL at this transition state assumes an "L" shaped conformation, with the pteridin ring oriented to optimize stacking within W102 and W140 residues, and the negatively charged glutamate tail, outside the receptor, interacting with the positively charged R103 and R106 residues, that contrary to the bound state, are solvent exposed. We show that metadynamics method can provide useful insights at the atomistic level on the effects of point-mutations affecting functionality, thus being a very promising tool for any study related to folate-targeted drug delivery or cancer therapies involving folate uptake. PMID:25323390

  7. Folic acid modified cationic ?-cyclodextrin-oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery.

    PubMed

    Zhao, Feng; Yin, Hui; Zhang, Zhongxing; Li, Jun

    2013-02-11

    For an efficient folate-targeted delivery, while the interaction between the folate on the carriers and the folate receptor (FR) on the cells is necessary, the recovering and recycling of FR to maintain a high density level of FR on the cellular membrane is also important. Herein, we demonstrate a design and synthesis of a new star-shaped cationic polymer containing a ?-cyclodextrin (?-CD) core and multiple oligoethylenimine (OEI) arms with folic acid (FA) linked by a bioreducible disulfide bond for efficient targeted gene delivery. The newly synthesized cationic polymer, named ?-CD-OEI-SS-FA, could be cleaved efficiently, and FA was readily released under reductive condition similar to intracellular environment. The ?-CD-OEI-SS-FA polymer was well-characterized and studied in terms of its gene delivery properties in FR-positive KB cells and FR-negative A549 cells under various conditions, in comparison with cationic polymers such as high molecular weight branched polyethylenimine (PEI), ?-CD-OEI star-shaped cationic polymer, ?-CD-OEI-FA polymer where FA was directed linked to the star polymer without disulfide linker. Our data have demonstrated that the new ?-CD-OEI-SS-FA gene carrier had low cytotoxicity and possessed capacity to target and deliver DNA to specific tumor cells that overexpress FRs, as well as functions to recover and recycle FRs onto cellular membranes to facilitate continuous FR-mediated endocytosis to achieve very high levels of gene expression. This study has expanded the strategy of FA-targeted delivery by combining the smart FR-recycling function to achieve the significant enhancement of gene expression. The new FA-targeted and bioreducible carrier may be a promising efficient gene delivery system for potential cancer gene therapy. PMID:23323627

  8. Functional assessment of zinc nutriture using changes in plasma zinc after exercise in men supplemented with folic acid

    SciTech Connect

    Lukaski, H.C.; Bolonchuk, W.W.; Milne, D.B.

    1986-03-05

    Recently, the authors proposed that changes in plasma zinc (Zn) and copper (Cu) content after maximal exercise could be a functional test of human trace element nutriture. To test this hypothesis, they studied the effect of folic acid (FA) supplements, previously shown to affect zinc absorption on the exercise-induced changes in plasma Zn and Cu in 7 men aged 28.6 +/- 1.2 yr (mean +/- SEM). The men were fed a constant diet with intakes of Cu (1.01 +/- 0.06 mg/d), Zn (12.7 +/- 0.3 mg/d) and FA (200 mg/d) for two 4 wk periods. This basal diet was supplemented with 400 or 800 mg/d FA and it was fed for 4 wk periods alternating with the unsupplemented diet. Pre and post-exercise hematocrit (Hct), hemoglobin (Hb), and plasma Zn and Cu were not affected by FA supplements. To correct for hemoconcentration during exercise, the van Beaumont quotient was calculated from pre and post-exercise Hct, Hb, and plasma Zn and Cu. When the basal diet was fed, the quotient for Zn was 3.4 +/- 1.4 and 2.3 +/- 1.4%, and it declined (p < 0.05) to -5.93 +/- 1.9% and -7.4 +/- 1.8% with 400 and 800 mg/d supplementation, resp. FA supplementation had no effect on the quotient for plasma Cu. These data suggest that Zn mobilization from stores during exercise is impaired with high intakes of FA.

  9. Size control in the synthesis of 1-6 nm gold nanoparticles using folic acid-chitosan conjugate as a stabilizer

    NASA Astrophysics Data System (ADS)

    Liu, Lili; Zhang, Xianwen; Chaudhuri, Jharna

    2014-09-01

    We report a simple and practical method for the preparation of folic acid (FA)-chitosan functionalized gold nanoparticles (AuNPs) with a very small size (1-6 nm). Sodium borohydride was used as a reducing agent. The size of the AuNPs was controlled by adjusting the mass fraction of FA-chitosan conjugate to Au. The AuNPs were characterized using UV-vis spectroscopy and transmission electron microscopy (TEM). The results indicated that the size distribution of AuNPs decreased ranging from 6 nm to 1 nm with increasing the fraction of FA-chitosan conjugate in the reaction systems.

  10. Metabolic interrelationships between folic acid, vitamin B12 and the citrovorum factor 

    E-print Network

    Doctor, Vasant Manilal

    1953-01-01

    role of ascorbic acid in increasing the CP content of chick liver homogenates is not due to its influence on the con? version of PGA to CP, but is the result of activation of the CF-liberating enzyme present in chick liver it s e l f . On the other... deals with the necessary experimental conditions for the enzymatic release of CF by autolysis (pH 6 .3 ) and for the synthesis of CP from added PGA by chick liver homogenate. The influence of PGA upon various enzyme systems both in vivo and in vitro...

  11. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid.

    PubMed

    Padmanabhan, S; Tripathi, D N; Vikram, A; Ramarao, P; Jena, G B

    2009-02-19

    Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice. PMID:19110071

  12. Actions of excitatory amino acid antagonists on synaptic inputs to the rat medial vestibular nucleus: an electrophysiological study in vitro

    Microsoft Academic Search

    K. Doi; T. Tsumoto; T. Matsunaga

    1990-01-01

    The actions of excitatory amino acid (EAA) antagonists on synaptic inputs to neurons in the rat medial vestibular nucleus (MVN) from ipsilateral vestibular afferents and vestibular commissures were studied in brain stem slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist for the quisqualate\\/kainate (non-NMDA) type

  13. Combating Iron Deficiency Anemia among School Going Adolescent Girls in a Hilly State of North India: Effectiveness of Intermittent Versus Daily Administration of Iron Folic Acid Tablets

    PubMed Central

    Gupta, Anmol; Parashar, Anupam; Thakur, Anita; Sharma, Deepak; Bhardwaj, Parveen; Jaswal, Saroj

    2014-01-01

    Background: National surveys in India have documented an increasing number of adolescent girls suffering from anemia. Efforts to build iron stores in adolescent girls will help them improve their prepregnancy hemoglobin level. To assess the effectiveness of school-based supervised weekly, bi–weekly, and daily regimen of iron folic tablets in the treatment of anemia among adolescent girls. Methods: This randomized clinical trial included 331 anemic school going adolescent girls of Shimla district of North India. Study subjects were randomized to once weekly, bi–weekly, and daily iron folic acid regimen group. An intent-to-treat approach was used to analyze the change in hemoglobin level and serum ferritin levels at the end of the trial period. Results: The rate of change of hemoglobin and serum ferritin levels from baseline to the end of the intervention was found to be similar in all the three groups (P = 0.64 and 0.98 for change in hemoglobin and serum ferritin). Bi-weekly treatment regimen results in comparatively more increase in hemoglobin levels (3.1 g/dl) as compared to once weekly (2.4 g/dl) and daily groups (2.3 g/dl) (ANOVA F statistics = 6.08, P = 0.003). Among the study subjects who reported side effects, more were from daily regimen group (55%) as compared to intermittent regimen group (25% in bi-weekly group; 18% in weekly group; P < 0.001). Conclusions: In Shimla hills of North India, school-based intermittent iron-folic acid therapy is a feasible and effective intervention for increasing hemoglobin and serum ferritin levels of anemic adolescent girls. PMID:25538845

  14. 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.

    PubMed

    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 < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After 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. PMID:25758536

  15. One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice

    PubMed Central

    Wen, Xiaoyan; Peng, Zhiyong; Li, Yingjian; Wang, Hongzhi; Bishop, Jeffrey V.; Chedwick, Lisa R.; Singbartl, Kai; Kellum, John A.

    2012-01-01

    Background In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory cytokine expression and inhibits leukocyte migration. It is also a potent inhibitor of mitochondrial permeability, protecting cells from death. These properties make it a potentially valuable drug to prevent or treat AKI. It does, however, carry a significant risk of nephrotoxicity, especially with chronic use. By contrast, a single dose of CsA may be protective while limiting the risk of nephrotoxicity. Methods We conducted a controlled animal experiment in male CD-1 mice. Specifically, mice were subjected to folic acid (FA)-induced AKI and then randomly assigned to sham operation or one of three dosage of CsA treatment groups. Results Intraperitoneal injection of FA consistently induced AKI. Serum interleukin (IL)-6 and urinary neutrophil gelatinase-associated lipocalin (NGAL) rose 1 day after FA injection. Compared to sham treatment, one dose (1 and 5 mg/kg body weight) of CsA significantly reduced kidney tubular cell apoptosis, serum creatinine, blood urea, serum IL-6 and urinary NGAL 2 days after FA injection. It was also shown to block the inflammatory mediator tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression, nuclear factor kappa-B (NF?B) activation, inflammatory cell infiltration and interstitial fibrosis 14 days after treatment in a dose-dependent fashion. By contrast, a dose of 10 mg/kg body weight CsA resulted in nephrotoxicity in the setting of FA-induced AKI. Conclusions A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI. PMID:22294776

  16. Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring

    PubMed Central

    Kuizon, Salomon; Buenaventura, Diego; Stapley, Nathan W.; Ruocco, Felicia; Begum, Umme; Guariglia, Sara R.; Brown, W. Ted; Junaid, Mohammed A.

    2014-01-01

    Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the life course may have lasting effects, with alterations in brain development resulting in changes in behavior. PMID:25006883

  17. Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

    PubMed Central

    2014-01-01

    A synthetic method to prepare a core-shell-structured Fe3O4@SiO2 as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe3O4@SiO2-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy. PMID:24667013

  18. Role of Hyperhomocysteinemia in the Regulation of Oxidative Stress and Inflammatory Responses in the Kidney: Protective Effect of Folic Acid Supplementation

    NASA Astrophysics Data System (ADS)

    Hwang, Sun-Young

    Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) level, is an independent risk factor for cardiovascular disease. Folic acid supplementation can effectively reduce blood Hcy levels. Recent studies have demonstrated that hyperhomocysteinemia is also associated with kidney disease. However, the underlying mechanisms remain unclear. The overall objective of the study was to investigate the biochemical and molecular mechanisms of Hcy-induced kidney injury and the effect of folic acid supplementation on Hcy-induced kidney injury. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 12 weeks. An elevation of serum total Hcy level was observed in hyperhomocysteinemic rats. Hyperhomocysteinemia-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation resulted in oxidative stress in the kidney. Reduction of oxidative stress by inhibiting superoxide anion production effectively ameliorated hyperhomocysteinemia-induced kidney injury. Inflammatory responses such as increased chemokine expression have been implicated as one of the mechanisms of kidney disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in kidney disease. Nuclear factor-kappa B (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism responsible for such an effect in rat kidneys as well as in human kidney proximal tubular cells.

  19. Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum.

    PubMed

    Krais, Annette; Wortmann, Laura; Hermanns, Laura; Feliu, Neus; Vahter, Marie; Stucky, Stefan; Mathur, Sanjay; Fadeel, Bengt

    2014-10-01

    Targeted delivery of nanoparticles to cells or tissues of interest is arguably the "holy grail" of nanomedicine. Using primary human macrophages and ovarian cancer cells, we evaluated the biocompatibility and specific targeting of folic acid (FA)-conjugated iron oxide nanoparticles with organic [poly(ethylene glycol), PEG] or inorganic (SiO2) intermediate surface coatings. Reduction of folate receptor-? expression using specific siRNA resulted in a significant decrease in cellular uptake of the SiO2-coated nanoparticles, but did not affect uptake of PEG-coated nanoparticles. Notably, specific (i.e. FA-dependent) uptake was observed only in the presence of serum proteins. The strategy presented here for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable targeting of nanoparticles for therapeutic and imaging applications. From the clinical editor: In this study the receptor specific uptake of folic acid-functionalized iron oxide nanoparticles was determined in ovarian cancer cells. It was found that the presence of serum proteins is an absolute requirement for the uptake of these nanoparticles. The described strategy for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable a better targeting of nanoparticles for additional therapeutic and imaging applications. PMID:24491397

  20. The effects of feeding rats diets deficient in folic acid and related methyl donors on the blood pressure and glucose tolerance of the offspring.

    PubMed

    Maloney, Christopher A; Hay, Susan M; Rees, William D

    2009-05-01

    In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring. Poor folate status transiently increased fetal growth but did not produce a long-term change in body weight. There were, however, small changes in the hearts of the female offspring. When folate deficiency was combined with low intakes of methionine and choline, the kidneys of the male offspring were proportionately smaller, probably because of the limited availability of methionine. There was no effect on the blood pressure of either the male or female offspring. The pancreatic insulin content of fetuses from animals fed the folate-deficient diets were higher than those of the controls. Following an oral glucose challenge, there was a weak trend for glucose-stimulated insulin release to be increased in the offspring of dams fed the folate-deficient diet. The changes in insulin concentrations were, however, much smaller than the corresponding changes observed in the offspring of animals fed protein-deficient diets. These results suggest that folate deficiency during gestation causes modest changes to the insulin axis of the fetus. PMID:18782463

  1. Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

    PubMed

    Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

    2012-06-01

    A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. PMID:22446630

  2. Role of substance P and tachykinin receptor antagonists in citric acid-induced cough in pigs.

    PubMed

    Moreaux, B; Nemmar, A; Vincke, G; Halloy, D; Beerens, D; Advenier, C; Gustin, P

    2000-11-24

    The purpose of this work was to investigate the role of tachykinins in cough induced by citric acid (0.8 M) in pigs. With this object, we have studied the effect of citric acid on substance P content in the tracheo-bronchial tree and the effects of substance P and of tachykinin receptor antagonists on citric acid-induced cough. Citric acid exposure significantly increased substance P concentration in both broncho-alveolar and tracheal lavage fluids, while it decreased significantly the substance P content in tracheal mucosa. Substance P did not elicit cough, but significantly potentiated the citric acid-induced cough frequency. Tachykinin NK(1), NK(2) or NK(3) receptor antagonists, SR 140333 (nolpitantium), SR 48968 (saredutant) and SR 142801 (osanetant), respectively, significantly inhibited citric acid-induced cough. The same inhibitory effect of tachykinin receptor antagonists was observed, when substance P was nebulised before citric acid challenge. We conclude that citric acid induces in pigs a release of substance P in the tracheo-bronchial tree, which plays a sensitising role on the cough reflex. The involvement of tachykinin NK(1), NK(2), NK(3) receptors are also demonstrated in this reflex. PMID:11090648

  3. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

  4. Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids

    PubMed Central

    2011-01-01

    Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (Ki < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC50 CYP2C9 and 2C19 > 1 ?M). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development. PMID:24900284

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

    PubMed Central

    Diefenbach, Konstanze; Trummer, Dietmar; Ebert, Frank; Lissy, Michael; Koch, Manuela; Rohde, Beate; Blode, Hartmut

    2013-01-01

    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 of EE-drospirenone-levomefolate calcium treatment. Plasma and RBC folate levels remained above baseline values in 41.3% and 89.3% of women, respectively, at the end of the 20-week elimination phase. Conclusion Improvements in folate status were comparable between EE-drospirenone-levomefolate calcium and EE-drospirenone + folic acid. Plasma and RBC folate levels remained elevated for several months following cessation of treatment with EE-drospirenone-levomefolate calcium. PMID:23610531

  6. Weekly Iron-Folic Acid Supplementation with Regular Deworming Is Cost-Effective in Preventing Anaemia in Women of Reproductive Age in Vietnam

    PubMed Central

    Horton, Susan E.; Phuc, Tran Q.; Phu, Luong B.; Thach, Dang T.; Dai, Tran C.; Fattore, Giovanni; Montresor, Antonio; Biggs, Beverley-A.

    2011-01-01

    Background To estimate the cost and cost-effectiveness of a project administering de-worming and weekly iron-folic acid supplementation to control anaemia in women of reproductive age in Yen Bai province, Vietnam. Methods and Findings Cost effectiveness was evaluated using data on programmatic costs based on two surveys in 2006 and 2009 and impact on anaemia and iron status collected in 2006, 2007, and 2008. Data on initial costs for training and educational materials were obtained from the records of the National Institute of Malariology, Parasitology and Entomology and the Yen Bai Malaria Control Program. Structured questionnaires for health workers at district, commune and village level were used to collect ongoing distribution and monitoring costs, and for participants to collect transport and loss of earnings costs. The cost per woman treated (defined as consuming at least 75% of the recommended intake) was USD0.76 per annum. This estimate includes financial costs (for supplies, training), and costs of health care workers' time. Prevalence of anaemia fell from 38% at baseline, to 20% after 12 months. Thus, the cost-effectiveness of the project is assessed at USD 4.24 per anaemia case prevented per year. Based on estimated productivity gains for adult women, the benefit:cost ratio is 6.7?1. Cost of the supplements and anthelminthics was 47% of the total, while costs of training, monitoring, and health workers' time accounted for 53%. Conclusion The study shows that weekly iron-folic acid supplementation and regular de-worming is a low-cost and cost-effective intervention and would be appropriate for population-based introduction in settings with a high prevalence of anaemia and iron deficiency and low malaria infection rates. PMID:21931611

  7. Fabrication and spectroscopic studies of folic acid-conjugated Fe3O4@Au core-shell for targeted drug delivery application.

    PubMed

    Karamipour, Sh; Sadjadi, M S; Farhadyar, N

    2015-09-01

    Gold coated magnetite core shell is a kind of nanoparticle that include magnetic iron oxide core with a thin layer nanogold. Fe3O4-gold core-shell nanostructure can be used in biomedical applications such as magnetic bioseparation, bioimaging, targeting drug delivery and cancer treatment. In this study, the synthesis and characterization of gold coated magnetite nanoparticles were discussed. Magnetite nanoparticles with an average size of 6nm in diameter were synthesized by the chemical co-precipitation method and gold-coated Fe3O4 core-shell nanostructures were produced with an average size of 11.5nm in diameter by reduction of Au(3+) with citrate ion in the presence of Fe3O4. Folate-conjugated gold coated magnetite nanoparticles were synthesized to targeting folate receptor that is overexpressed on the surface of cancerous cells. For this purpose, we used l-cysteine, as a bi-functional linker for attachment to gold surface and it was linked to the gold nanoparticles surface through its thiol group. Then, we conjugated amino-terminated nanoparticles to folic acid with an amide-linkage formation. These gold magnetic nanoparticles were characterized by various techniques such as X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrometer (FT-IR), UV-visible spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dispersive analysis of X-ray (EDAX) and vibrating sample magnetometer (VSM) analysis. The magnetic and optical properties of Fe3O4 nanostructure were changed by gold coating and attachment of l-cysteine and folic acid to Fe3O4@Au nanoparticles. PMID:25879984

  8. Fabrication and spectroscopic studies of folic acid-conjugated Fe3O4@Au core-shell for targeted drug delivery application

    NASA Astrophysics Data System (ADS)

    Karamipour, Sh.; Sadjadi, M. S.; Farhadyar, N.

    2015-09-01

    Gold coated magnetite core shell is a kind of nanoparticle that include magnetic iron oxide core with a thin layer nanogold. Fe3O4-gold core-shell nanostructure can be used in biomedical applications such as magnetic bioseparation, bioimaging, targeting drug delivery and cancer treatment. In this study, the synthesis and characterization of gold coated magnetite nanoparticles were discussed. Magnetite nanoparticles with an average size of 6 nm in diameter were synthesized by the chemical co-precipitation method and gold-coated Fe3O4 core-shell nanostructures were produced with an average size of 11.5 nm in diameter by reduction of Au3+ with citrate ion in the presence of Fe3O4. Folate-conjugated gold coated magnetite nanoparticles were synthesized to targeting folate receptor that is overexpressed on the surface of cancerous cells. For this purpose, we used L-cysteine, as a bi-functional linker for attachment to gold surface and it was linked to the gold nanoparticles surface through its thiol group. Then, we conjugated amino-terminated nanoparticles to folic acid with an amide-linkage formation. These gold magnetic nanoparticles were characterized by various techniques such as X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrometer (FT-IR), UV-visible spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dispersive analysis of X-ray (EDAX) and vibrating sample magnetometer (VSM) analysis. The magnetic and optical properties of Fe3O4 nanostructure were changed by gold coating and attachment of L-cysteine and folic acid to Fe3O4@Au nanoparticles.

  9. ?-Phenoxyphenylacetic acid derived angiotensin II antagonists with low nanomolar AT 1\\/AT 2 receptor subtype affinity (Part II)

    Microsoft Academic Search

    Thomas F. Walsh; Kenneth J. Fitch; Raymond S. L. Chang; Kristie A. Faust; Tsing-Bau Chen; Salah D. Kivlighn; Gloria J. Zingaro; Victor J. Lotti; Peter K. S. Siegl; Arthur A. Patchett; William J. Greenlee

    1995-01-01

    Directed synthesis and pharmacological evaluation in a recently described class of ?-phenoxyphenylacetic acid bearing angiotensin II (AII) receptor antagonists has afforded further potent AT1-selective AII antagonists. Substitution in the central aromatic ring significantly increases AT2 receptor affinity such that the n-propyl derivative 7g displayed low nanomolar potency at both AT1 and AT2 receptor subtypes.

  10. Malonamic acid derivatives as M1 selective muscarinic receptor antagonists.

    PubMed

    Turconi, M; Banfi, A; Schiavi, G B; Donetti, A

    1991-09-01

    A series of malonamic acid esters with suitable amino alcohols, typical of antimuscarinic compounds, was synthesized and the affinities for the three pharmacologically defined muscarinic receptor subtypes, namely M1, M2 and M3, were evaluated by radioligand displacement experiments. It was found that the esters with 3-quinuclidinol 7b, 7f-g, 8 and 9 are ligands with intermediate to high affinity for the M1 receptors, for which they show a preferential binding. Unexpectedly, the ester 7a with tropine bound with negligible affinity to all the receptors investigated. The introduction of a phenyl group on the carboxamido moiety of 7b gave compound 9, which showed an affinity for the M1 receptor comparable with that of the reference drug Pirenzepine 1. PMID:1807294

  11. AT 1 selective angiotensin II antagonists with phenoxyphenylacetic acid as a biphenyl replacement part I

    Microsoft Academic Search

    K. J. Fitch; T. F. Walsh; A. A. Patchett; R. S. L. Chang; P. K. S. Siegl; K. A. Faust; T.-B. Chen; V. J. Lotti; S. D. Kivlighn; G. J. Zingaro; W. J. Greenlee

    1995-01-01

    A series of nonpeptidic AT1 selective angiotensin II (AII) antagonists containing a phenoxyphenylacetic acid element as a biphenyl tetrazole replacement have been identified. This series yielded compound 20 which exhibited binding affinities of AT1 = 16 nM; AT2 = 22 ?M and demonstrated modest in vivo duration in blockade of AII pressor response in conscious rats after either i.v. or

  12. Roles of Amino Acids and Subunits in Determining the Inhibition of Nicotinic Acetylcholine Receptors by Competitive Antagonists

    PubMed Central

    Dilger, James P.; Vidal, Ana Maria; Liu, Man; Mettewie, Claire; Suzuki, Takahiro; Pham, Anh; Demazumder, Deeptankar

    2008-01-01

    Background Binding sites for agonists and competitive antagonists (nondepolarizing neuromuscular blocking agents) are located at the ?–? and ?–? subunit interfaces of adult nicotinic acetylcholine receptors. Most information about the amino acids that participate in antagonist binding comes from binding studies with (+)-tubocurarine and metocurine. These bind selectively to the ?–? interface but are differentially sensitive to mutations. To test the generality of this observation, the authors measured current inhibition by five competitive antagonists on wild-type and mutant acetylcholine receptors. Methods HEK293 cells were transfected with wild-type or mutant (?Y198F, ?D59A, ?D59N, ?D173A, ?D173N, ?D180K) mouse muscle acetylcholine receptor complementary DNA. Outside-out patches were excised and perfused with acetylcho-line in the absence and presence of antagonist. Concentration–response curves were constructed to determine antagonist IC50. An antagonist-removal protocol was used to determine dissociation and association rates. Results Effects of mutations were antagonist specific. ?Y198F decreased the IC50 of (+)-tubocurarine 10-fold, increased the IC50 of vecuronium 5-fold, and had smaller effects on other antagonists. (+)-Tubocurarine was the most sensitive antagonist to ?D173 mutations. ?D59 mutations had large effects on metocurine and cisatracurium. ?D180K decreased inhibition by pancuronium, vecuronium, and cisatracurium. Inhibition by these antagonists was increased for receptors containing two ? subunits but no ? subunit. Differences in IC50 arose from differences in both dissociation and association rates. Conclusion Competitive antagonists exhibited different patterns of sensitivity to mutations. Except for pancuronium, the antagonists were sensitive to mutations at the ?–? interface. Pancuronium, vecuronium, and cisatracurium were selective for the ?–? interface. This suggests the possibility of synergistic inhibition by pairs of antagonists. PMID:17525594

  13. Naturally Occurring Eccentric Cleavage Products of Provitamin A ?-Carotene Function as Antagonists of Retinoic Acid Receptors*

    PubMed Central

    Eroglu, Abdulkerim; Hruszkewycz, Damian P.; dela Sena, Carlo; Narayanasamy, Sureshbabu; Riedl, Ken M.; Kopec, Rachel E.; Schwartz, Steven J.; Curley, Robert W.; Harrison, Earl H.

    2012-01-01

    ?-Carotene is the major dietary source of provitamin A. Central cleavage of ?-carotene catalyzed by ?-carotene oxygenase 1 yields two molecules of retinaldehyde. Subsequent oxidation produces all-trans-retinoic acid (ATRA), which functions as a ligand for a family of nuclear transcription factors, the retinoic acid receptors (RARs). Eccentric cleavage of ?-carotene at non-central double bonds is catalyzed by other enzymes and can also occur non-enzymatically. The products of these reactions are ?-apocarotenals and ?-apocarotenones, whose biological functions in mammals are unknown. We used reporter gene assays to show that none of the ?-apocarotenoids significantly activated RARs. Importantly, however, ?-apo-14?-carotenal, ?-apo-14?-carotenoic acid, and ?-apo-13-carotenone antagonized ATRA-induced transactivation of RARs. Competitive radioligand binding assays demonstrated that these putative RAR antagonists compete directly with retinoic acid for high affinity binding to purified receptors. Molecular modeling studies confirmed that ?-apo-13-carotenone can interact directly with the ligand binding site of the retinoid receptors. ?-Apo-13-carotenone and the ?-apo-14?-carotenoids inhibited ATRA-induced expression of retinoid responsive genes in Hep G2 cells. Finally, we developed an LC/MS method and found 3–5 nm ?-apo-13-carotenone was present in human plasma. These findings suggest that ?-apocarotenoids function as naturally occurring retinoid antagonists. The antagonism of retinoid signaling by these metabolites may have implications for the activities of dietary ?-carotene as a provitamin A and as a modulator of risk for cardiovascular disease and cancer. PMID:22418437

  14. Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors

    PubMed Central

    Mierzecki, Artur; K?oda, Karolina; Bukowska, Hanna; Che?stowski, Kornel; Makarewicz-Wujec, Magdalena; Koz?owska-Wojciechowska, Ma?gorzata

    2013-01-01

    Background Folic acid (FA) is one of the B complex vitamins. It is thought that FA deficiency promotes atherosclerosis formation in arterial endothelium. FA, acting through reducing homocysteine (Hcy) levels, may contribute to decreased cholesterol (Ch) synthesis. The aim of this study was to analyze the association of low-dose folic acid supplementation with blood lipids concentrations in subjects with atherosclerosis risk factors. Material/Methods The study enrolled 124 Caucasian individuals (60 M, ages 20–39; and 64 F, ages 19–39) with atherosclerosis risk factors (family history of premature ischemic stroke, arterial hypertension, dyslipidemia, overweight and obesity, cigarette smoking, and low level of physical activity). The participants were asked to take FA at a low dose of 0.4 mg/24 h for 12 weeks. Results FA levels increased in females (6.3 vs. 12.5 ng/dL; p=0.001) and males (6.4 vs. 11.4 ng/dL; p=0.001) and Hcy levels decreased (10.6 vs. 8.3 ?mol/L; p=0.001 and 11.5 vs. 9.3; p=0.001, respectively). A significant reduction in mean concentration of total cholesterol in females (203.4 vs. 193.1 mg/dL; p=0.001) and in males (209.5 vs. 201.9; p=0.002) was observed. The low-density lipoprotein cholesterol (LDL-C) levels decreased in females and in males (107.4 vs. 99.9 mg/dL; p=0.001 and 121.5 vs. 115.1; p=0.002, respectively). The apoAI concentrations increased in smoking women and in men with BMI ?25 kg/m2 (p=0.032 and p=0.024, respectively). Conclusions Low-dose FA supplementation has a beneficial effect on blood lipids through decreasing concentrations of total cholesterol and LDL-C and increasing concentrations of apoAI. PMID:24002360

  15. Inhibition against growth of glioblastoma multiforme in vitro using etoposide-loaded solid lipid nanoparticles with p-aminophenyl-?-D-manno-pyranoside and folic acid.

    PubMed

    Kuo, Yung-Chih; Lee, Chia-Hao

    2015-05-01

    Solid lipid nanoparticles (SLNs) grafted with p-aminophenyl-?-D-manno-pyranoside (APMP) and folic acid (FA) (APMP-FA-SLNs) were applied to encapsulate 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-?-D-glucopyranoside) (etoposide) (ETP) for promoting the antiproliferation of malignant glioblastoma multiforme. ETP-loaded APMP-FA-SLNs (APMP-FA-ETP-SLNs) were used to penetrate the blood-brain barrier (BBB) and retard the propagation of U87MG cells. An incorporation of APMP and FA increased the particle size, the cytotoxicity to U87MG cells, and the permeability coefficient for propidium iodide and ETP across the BBB. In addition, an increase in the APMP and FA concentration reduced the zeta potential, the grafting efficiency of APMP and FA, the dissolution rate of ETP, and the transendothelial electrical resistance. Immunochemical staining images evidenced that APMP-FA-ETP-SLNs could infiltrate the BBB via glucose transporter 1 and recognize U87MG cells via folate receptor. APMP-FA-ETP-SLNs can be an effective pharmacotherapeutic formulation in targeting delivery to the brain and in inhibitory efficacy against tumorous cells for cancer therapy. PMID:25694089

  16. Determinants of neural tube defect (NTD)-protective circulating concentrations of folate in women of child-bearing age in the US post-folic acid fortification era.

    PubMed

    Piyathilake, Chandrika; Eom, Sang Yong; Hyun, Taisun; Badiga, Suguna; Robinson, Constance; Rahman, Nuzhat; Kim, Heon; Johanning, Gary L

    2013-08-01

    We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake. PMID:23964320

  17. Ovarian Cancer Immunotherapy Using PD-L1 siRNA Targeted Delivery from Folic Acid-Functionalized Polyethylenimine: Strategies to Enhance T Cell Killing.

    PubMed

    Teo, Pei Yun; Yang, Chuan; Whilding, Lynsey M; Parente-Pereira, Ana C; Maher, John; George, Andrew J T; Hedrick, James L; Yang, Yi Yan; Ghaem-Maghami, Sadaf

    2015-06-01

    Adoptive T cell immunotherapy is a promising treatment strategy for epithelial ovarian cancer (EOC). However, programmed death ligand-1 (PD-L1), highly expressed on EOC cells, interacts with programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. This study aims to block PD-1/PD-L1 interactions by delivering PD-L1 siRNA, using various folic acid (FA)-functionalized polyethylenimine (PEI) polymers, to SKOV-3-Luc EOC cells, and investigate the sensitization of the EOC cells to T cell killing. To enhance siRNA uptake into EOC cells, which over express folate receptors, PEI is modified with FA or PEG-FA so that siRNA is complexed into nanoparticles with folate molecules on the surface. PEI modification with a single functional group lowers the polymer cytotoxicity compared to unmodified PEI. FA-conjugated polymers increase siRNA uptake into SKOV-3-luc cells and decrease unspecific uptake into monocytes. All polymers result in 40% to 50% PD-L1 protein knockdown. Importantly, SKOV-3-Luc cells treated with either PEI-FA or PEI- polyethylene glycol (PEG)-FA/PD-L1 siRNA complexes are up to twofold more sensitive to T cell killing compared to scrambled siRNA treated controls. These findings are the first to demonstrate that PD-L1 knockdown in EOC cells, via siRNA/FA-targeted delivery, are able to sensitize cancer cells to T cell killing. PMID:25866054

  18. Folic acid-conjugated, SERS-labeled silver nanotriangles for multimodal detection and targeted photothermal treatment on human ovarian cancer cells.

    PubMed

    Boca-Farcau, Sanda; Potara, Monica; Simon, Timea; Juhem, Aurelie; Baldeck, Patrice; Astilean, Simion

    2014-02-01

    The effectiveness of a therapeutic agent for cancer stands in its ability to reduce and eliminate tumors without harming the healthy tissue nearby. Nanoparticles peripherally conjugated with targeting moieties offer major improvements in therapeutics through site specificity. In this study we demonstrate this approach by targeting the folate receptor of NIH:OVCAR-3 human ovary cancer cell line. Herein we used silver nanotriangles which were biocompatibilized with chitosan (bio)polymer, labeled with para-aminothiophenol (pATP) Raman reporter molecule, and conjugated with folic acid. The nanoparticles conjugation and efficient labeling was investigated by localized surface plasmon resonance (LSPR), zeta potential, and surface-enhanced Raman scattering (SERS) measurements. Conjugated particles were proven to be highly stable in aqueous and cellular medium. The targeted uptake of conjugated nanoparticles by human ovary cancer cells was confirmed by dark field microscopy and scattering spectra of the particles inside cells. Comparative studies revealed specific internalization of the conjugated nanoparticles in comparison with similar bare nanoparticles. Moreover, the SERS identity of the particles was proven to be highly conserved inside cells. Targeted cancer cell treatment conducted by irradiating the nanoparticle-treated cells with a continuous wave-nearinfrared (cw-NIR) laser in resonance with their plasmonic band proved an efficient therapeutic response. By integrating the advantages of multimodal optical imaging and SERS detection with hyperthermia capabilities through site specificity, these nanoparticles can represent a real candidate for personalized medicine. PMID:24304361

  19. A folic acid labelled carbon quantum dot-protoporphryin IX conjugate for use in folate receptor targeted two-photon excited photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Nicholas, Dean; Fowley, Colin; McHale, Anthony P.; Kamila, Sukanta; Sheng, Jason; Atchison, Jordan; Callan, John F.

    2015-03-01

    Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a CQD-protoporphyrin IX (CQD-PPIX) conjugate to folate receptor positive (FR+) HeLa cells for use in two-photon excited Photodynamic Therapy (TPE-PDT). FA was covalently attached to the CQD-PPIX conjugate to form a FA-CQD-PPIX conjugate. The uptake of the FA-CQD-PPIX conjugate in FR+ HeLa cells was shown to be 7 times greater than the CQD-PPIX conjugate, while both conjugates showed a similar uptake in FR negative (FR-) HT-47 cells. TPE-PDT experiments, using HeLa cells as a target, revealed a 30% improved cytotoxicity for cells treated with the FA-CQD-PPIX conjugate and TPE compared to controls treated with the CQD-PPIX conjugate and TPE. Collectively, these results suggest the presence of FA can facilitate targeting of CQD-sensitiser conjugates to FR+ cells resulting in an improved PDT effect.

  20. Folic acid-conjugated TiO2-doped mesoporous carbonaceous nanocomposites loaded with Mitoxantrone HCl for chemo-photodynamic therapy.

    PubMed

    Li, Zhi; Ou-Yang, Ya; Liu, Yang; Wang, Yi-Qiu; Zhu, Xia-Li; Zhang, Zhen-Zhong

    2015-06-01

    Recently, porous carbons have showed great potential in many areas. In this study, TiO2-doped mesoporous carbonaceous (TiO2@C) nanoparticles were obtained by a simple one-pot hydrothermal treatment, folic acid (FA) was conjugated to TiO2@C through an amide bond, then Mitoxantrone HCl (MTX) was adsorbed onto TiO2@C-FA and a drug delivery system, TiO2@C-FA/MTX was obtained. TiO2@C-FA/MTX showed a much faster MTX release at pH 4.5 than at pH 6.0 and pH 7.4. Furthermore, compared with free MTX, this drug delivery system showed a dose-dependent cytotoxicity by varying the irradiance, and afforded higher antitumor efficacy in cultured PC3 cells in vitro. The ability of TiO2@C-FA/MTX to combine chemotherapy with photodynamic activity enhanced the cancer cell killing effect in vitro, demonstrating that TiO2@C-FA/MTX has a great potential for cancer therapy in the future. PMID:25997891

  1. Determinants of neural tube defect (NTD)-protective circulating concentrations of folate in women of child-bearing age in the US post-folic acid fortification era

    PubMed Central

    Eom, Sang Yong; Hyun, Taisun; Badiga, Suguna; Robinson, Constance; Rahman, Nuzhat; Kim, Heon; Johanning, Gary L

    2013-01-01

    We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake. PMID:23964320

  2. AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.

    PubMed

    Lale, Shantanu V; R G, Aswathy; Aravind, Athulya; Kumar, D Sakthi; Koul, Veena

    2014-05-12

    Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ?140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (?70%) compared to pH 7.4 (?25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others. PMID:24689987

  3. Differential Regulation of Hepatic Transcription Factors in the Wistar Rat Offspring Born to Dams Fed Folic Acid, Vitamin B12 Deficient Diets and Supplemented with Omega-3 Fatty Acids

    PubMed Central

    Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana

    2014-01-01

    Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n?=?8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at ?80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPAR? and PPAR? expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXR? and RXR? expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPAR? and PPAR? but reduced (p<0.05) SREBP-1c, LXR? and RXR? expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPAR?, SREBP-1c and RXR? expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring. PMID:24587285

  4. An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene.

    PubMed

    Slock, J; Stahly, D P; Han, C Y; Six, E W; Crawford, I P

    1990-12-01

    McDonald and Burke (J. Bacteriol. 149:391-394, 1982) previously cloned a sulfanilamide-resistance gene, sul, residing on a 4.9-kb segment of Bacillus subtilis chromosomal DNA, into plasmid pUB110. In this study we determined the nucleotide sequence of the entire 4.9-kb fragment. Genes identified on the fragment include pab, trpG, pabC, sul, one complete unidentified open reading frame, and one incomplete unidentified open reading frame. The first three of these genes, pab, trpG, and pabC, are required for synthesis of p-aminobenzoic acid. The trpG gene encodes an amphibolic glutamine amidotransferase required for synthesis of both p-aminobenzoate and anthranilate, the latter an intermediate in the tryptophan biosynthetic pathway. The pabC gene may encode a B. subtilis analog of enzyme X, an enzyme needed for p-aminobenzoate synthesis in Escherichia coli. The sul gene probably encodes dihydropteroate synthase, the enzyme responsible for formation of 7,8-dihydropteroate, the immediate precursor of folic acid. All six of the cloned genes are arranged in a single operon. Since all four of the identified genes are needed for folate biosynthesis, we refer to this operon as a folic acid operon. Expression of the trpG gene is known to be negatively controlled by tryptophan. We propose that this regulation is at the level of translation. This hypothesis is supported by the finding of an apparent Mtr-binding site which overlaps with the trpG ribosome-binding site. PMID:2123867

  5. Piperazine-2,3-dicarboxylic acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors

    PubMed Central

    Irvine, Mark W.; Costa, Blaise M.; Dlaboga, Daniel; Culley, Georgia; Hulse, Richard; Scholefield, Caroline L.; Atlason, Palmi; Fang, Guangyu; Eaves, Richard; Morley, Richard; Mayo-Martin, Maria B.; Amici, Mascia; Bortolotto, Zuner A.; Donaldson, Lucy; Collingridge, Graham L.; Molnár, Elek; Monaghan, Daniel T.; Jane, David E.

    2011-01-01

    Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype-selectivity among the more distantly related kainate receptor family. Compounds 18i and (?)-4 were the most potent kainate receptor antagonists and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/Kg i.p.) showed antinociceptive effects in an animal model of mild nerve injury. PMID:22111545

  6. In vivo targeted magnetic resonance imaging and visualized photodynamic therapy in deep-tissue cancers using folic acid-functionalized superparamagnetic-upconversion nanocomposites

    NASA Astrophysics Data System (ADS)

    Zeng, Leyong; Luo, Lijia; Pan, Yuanwei; Luo, Song; Lu, Guangming; Wu, Aiguo

    2015-05-01

    Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM-1 s-1 (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers.Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM-1 s-1 (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01932j

  7. Calcium Antagonists Inhibit Sustained Gibberellic Acid-Induced Growth of Avena (Oat) Stem Segments.

    PubMed Central

    Montague, M. J.

    1993-01-01

    The elongation response of Avena sativa (oat) stem segments to gibberellic acid (GA3) is of large magnitude, with high hormonal sensitivity and specificity, but without cell division activity. This system is therefore an excellent model for mechanistic studies on higher plant cell elongation and the action of gibberellin. At millimolar concentrations, the calcium antagonists verapamil, D-600, nicardipine, diltiazem, bepridil, 8-(N,N,-diethylamino)-octyl-3,4,5-trimethoxybenzoate HCl, and lanthanum substantially inhibited the growth of GA3-treated segments but had no effect on the elongation of nonhormone-treated segments. Although verapamil reduced the maximum growth rate and caused premature cessation of growth, even preincubation of the segments with the drug prior to treatment with GA3 failed to inhibit the earliest measured stimulation of growth by the hormone. Inhibition by verapamil was not reversed by increased concentrations of GA3 or calcium. Neither the calcium ionophore A23187 nor agonist BAY K 8644 had any effect on growth. Light microscopic examination of epidermal peels from antagonist-treated internodal tissue revealed no obvious differences from the control except that the cells were not as elongated. Although these results may support a role for calcium ion movement in maintaining the GA3-induced growth of Avena stem segments, they do not support the involvement of calcium ion movement in the hormone-mediated initiation of growth. PMID:12231695

  8. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors.

    PubMed

    Al Jammaz, I; Al-Otaibi, B; Amer, S; Okarvi, S M

    2011-10-01

    In an attempt to visualize folate receptors that overexpress on many cancers, [(18)F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([(18)F]-1, [(18)F]-2-folates and [(18)F]-8, [(18)F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [(18)F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [(18)F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [(18)F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [(18)F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment. PMID:21982573

  9. Augmented anticancer activity of a targeted, intracellularly activatable, theranostic nanomedicine based on fluorescent and radiolabeled, methotrexate-folic Acid-multiwalled carbon nanotube conjugate.

    PubMed

    Das, Manasmita; Datir, Satyajit R; Singh, Raman Preet; Jain, Sanyog

    2013-07-01

    The present study reports the design, synthesis, and biological evaluation of a novel, intravenously injectable, theranostic prodrug based on multiwalled carbon nanotubes (MWCNTs) concomitantly decorated with a fluorochrome (Alexa-fluor, AF488/647), radionucleide (Technitium-99m), tumor-targeting module (folic acid, FA), and anticancer agent (methotrexate, MTX). Specifically, MTX was conjugated to MWCNTs via a serum-stable yet intracellularly hydrolyzable ester linkage to ensure minimum drug loss in circulation. Cell uptake studies corroborated the selective internalization of AF-FA-MTX-MWCNTs (1) by folate receptor (FR) positive human lung (A549) and breast (MCF 7) cancer cells through FR mediated endocytosis. Lysosomal trafficking of 1 enabled the conjugate to exert higher anticancer activity as compared to its nontargeted counterpart that was mainly restricted to cytoplasm. Tumor-specific accumulation of 1 in Ehlrich Ascites Tumor (EAT) xenografted mice was almost 19 and 8.6 times higher than free MTX and FA-deprived MWCNTs. Subsequently, the conjugate 1 was shown to arrest tumor growth more effectively in chemically breast tumor induced rats, when compared to either free MTX or nontargeted controls. Interestingly, the anticancer activities of the ester-linked CNT-MTX conjugates (including the one deprived of FA) were significantly higher than their amide-linked counterpart, suggesting that cleavability of linkers between drug and multifunctional nanotubes critically influence their therapeutic performance. The results were also supported by in silico docking and ligand similarity analysis. Toxicity studies in mice confirmed that all CNT-MTX conjugates were devoid of any perceivable hepatotoxicity, cardiotoxicity, and nephrotoxicity. Overall, the delivery property of MWCNTs, high tumor binding avidity of FA, optical detectability of AF fluorochromes, and radio-traceability of (99m)Tc could be successfully integrated and partitioned on a single CNT-platform to augment the therapeutic efficacy of MTX against FR overexpressing cancer cells while allowing a real-time monitoring of treatment response through multimodal imaging. PMID:23683251

  10. Folic acid supplementation during pregnancy induces sex-specific changes in methylation and expression of placental 11?-hydroxysteroid dehydrogenase 2 in rats.

    PubMed

    Penailillo, Reyna; Guajardo, Angelica; Llanos, Miguel; Hirsch, Sandra; Ronco, Ana Maria

    2015-01-01

    In the placenta, 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11?-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring. PMID:25793274

  11. Individual and Facility-Level Determinants of Iron and Folic Acid Receipt and Adequate Consumption among Pregnant Women in Rural Bihar, India

    PubMed Central

    Wendt, Amanda; Stephenson, Rob; Young, Melissa; Webb-Girard, Amy; Hogue, Carol; Ramakrishnan, Usha; Martorell, Reynaldo

    2015-01-01

    Background In Bihar, India, high maternal anemia prevalence and low iron and folic acid supplement (IFA) receipt and consumption have continued over time despite universal IFA distribution and counseling during pregnancy. Purpose To examine individual and facility-level determinants of IFA receipt and consumption among pregnant women in rural Bihar, India. Methods Using District Level Household Survey (2007–08) data, multilevel modeling was conducted to examine the determinants of two outcomes: IFA receipt (any IFA receipt vs. none) and IFA consumption (?90 days vs. <90 days). Individual-level and facility-level factors were included. Factor analysis was utilized to construct antenatal care (ANC) quality and health sub-center (HSC) capacity variables. Results Overall, 37% of women received any IFA during their last pregnancy. Of those, 24% consumed IFA for 90 or more days. Women were more likely to receive any IFA when they received additional ANC services and counseling, and attended ANC earlier and more frequently. Significant interactions were found between ANC quality factors (odds ratio (OR): 0.37, 95% confidence interval (CI): 0.25, 0.56) and between ANC services and ANC timing and frequency (OR: 0.68, 95% CI: 0.56, 0.82). No HSC factors were significantly associated with IFA receipt. Women were more likely to consume IFA for ?90 days if they attended at least 4 ANC check-ups and received more ANC services. IFA supply at the HSC (OR: 1.37, 95% CI: 1.04, 1.82) was also significantly associated with IFA consumption. Conclusions Our findings indicate that individual and ANC factors (timing, frequency, and quality) play a key role in facilitating IFA receipt and consumption. Although HSC capacity factors were not found to influence our outcomes, significant variation at the facility level indicates unmeasured factors that could be important to address in future interventions. PMID:25793866

  12. Earlier Initiation and Use of a Greater Number of Iron-Folic Acid Supplements during Pregnancy Prevents Early Neonatal Deaths in Nepal and Pakistan

    PubMed Central

    Nisar, Yasir Bin; Dibley, Michael J.

    2014-01-01

    Introduction Early neonatal deaths account for 75% of neonatal deaths globally. Antenatal iron-folic acid (IFA) supplementation has significantly reduced the risk of early neonatal deaths in China and Indonesia. We investigated the impact of antenatal IFA supplements on the risk of early neonatal deaths in Nepal and Pakistan during the last decade. Methods Data from the most recent singleton live-births of 8,186 from two Nepal Demographic and Health Surveys (DHS) and 13,034 from two Pakistan DHS were selected for the current study. The primary outcome was early neonatal deaths and the main study variable was antenatal IFA supplementation. Analyses used multivariate Cox proportional regression, adjusted for the cluster sampling design and for 18 potential confounders. Findings The adjusted risk of early neonatal deaths was significantly reduced by 51% (aHR?=?0.49, 95% CI?=?0.32–0.75) in Nepal and 23% (aHR?=?0.77, 95% CI?=?0.59–0.99) in Pakistan with any use of IFA compared to none. When IFA supplementation started at or before the 5th month of pregnancy, the adjusted risk of early neonatal mortality was significantly reduced by 53% in Nepal, and 28% in Pakistan, compared to no IFA. When >90 IFA supplements were used and started at or before 5th months, the adjusted risk of early neonatal deaths was significantly reduced by 57% in Nepal, and 45% in Pakistan. In Nepal 4,600 and in Pakistan 75,000 early neonatal deaths could be prevented annually if all pregnant women used >90 IFA supplements and started at or before the 5th month of pregnancy. Conclusions Any use of IFA supplements was significantly associated with reduced risk of early neonatal deaths in Nepal and Pakistan. The greatest mortality sparing effect of IFA on early neonatal deaths in both countries was with early initiation and use of a greater number of supplements. PMID:25398011

  13. Cobalamin and Folic Acid Status in Relation to the Etiopathogenesis of Pancytopenia in Adults at a Tertiary Care Centre in North India

    PubMed Central

    Premkumar, M.; Gupta, N.; Singh, T.; Velpandian, T.

    2012-01-01

    Background. Pancytopenia has multiple etiologies like megaloblastic anemia, aplastic anemia, leukemia, and various infections. We investigated the clinical, etiological and hematological profile including bone marrow morphology of patients with pancytopenia in relation to their vitamin B12 and folic acid status at a tertiary care referral hospital in north India. Methods. A total of 140 consecutive patients with pancytopenia were selected from June 2007 to December 2008. Bone marrow examination and other tests were carried out as warranted, including serum cobalamin and folate assays using liquid chromatography mass spectroscopy (LC MS/MS). Results. The study population consisted of 92 males and 48 females with a mean age of 32.8 years. Megaloblastic anemia 60.7%, aplastic anemia (7.8%), and leukemia (9.2%) were common causes. Infectious causes (16.4% of all cases) included leishmaniasis, HIV–AIDS, malaria and tuberculosis. Severe cobalamin deficiency (B12 < 100?pg/mL) was seen in 81% of all patients including 91.6% of patients with MA. In contrast, only 7.14% of all pancytopenic patients were folate deficient. Folate deficiency (<5?ng/mL) was seen in just 5% MA patients. Combined cobalamin and folate deficiency was seen in 5 patients (3.51%). Conclusion. Cobalamin deficiency was found to be more common in our setting and is largely underdiagnosed in the age of folate supplementation. Infectious diseases like tuberculosis, leishmaniasis, and increasingly HIV are important and treatable causes of pancytopenia. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia. PMID:22545211

  14. Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

    PubMed

    Enneman, Anke W; Swart, Karin M A; van Wijngaarden, Janneke P; van Dijk, Suzanne C; Ham, Annelies C; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Dhonukshe-Rutten, Rosalie A M; van der Cammen, Tischa J M; de Groot, Lisette C P G M; van Meurs, Joyce; Lips, Paul; Uitterlinden, André G; Zillikens, M Carola; van Schoor, Natasja M; van der Velde, Nathalie

    2015-05-01

    High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ?65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement. PMID:25712255

  15. Prevalence of anemia and deficiency of iron, folic acid, and zinc in children younger than 2 years of age who use the health services provided by the Mexican Social Security Institute

    PubMed Central

    Duque, Ximena; Flores-Hernández, Sergio; Flores-Huerta, Samuel; Méndez-Ramírez, Ignacio; Muñoz, Sergio; Turnbull, Bernardo; Martínez-Andrade, Gloria; Ramos, Rosa I; González-Unzaga, Marco; Mendoza, María E; Martínez, Homero

    2007-01-01

    Background In Mexico, as in other developing countries, micronutrient deficiencies are common in infants between 6 and 24 months of age and are an important public health problem. The objective of this study was to determine the prevalence of anemia and of iron, folic acid, and zinc deficiencies in Mexican children under 2 years of age who use the health care services provided by the Mexican Institute for Social Security (IMSS). Methods A nationwide survey was conducted with a representative sample of children younger than 2 years of age, beneficiaries, and users of health care services provided by IMSS through its regular regimen (located in urban populations) and its Oportunidades program (services offered in rural areas). A subsample of 4,955 clinically healthy children was studied to determine their micronutrient status. A venous blood sample was drawn to determine hemoglobin, serum ferritin, percent of transferrin saturation, zinc, and folic acid. Descriptive statistics include point estimates and 95% confidence intervals for the sample and projections for the larger population from which the sample was drawn. Results Twenty percent of children younger than 2 years of age had anemia, and 27.8% (rural) to 32.6% (urban) had iron deficiency; more than 50% of anemia was not associated with low ferritin concentrations. Iron stores were more depleted as age increased. Low serum zinc and folic acid deficiencies were 28% and 10%, respectively, in the urban areas, and 13% and 8%, respectively, in rural areas. The prevalence of simultaneous iron and zinc deficiencies was 9.2% and 2.7% in urban and rural areas. Children with anemia have higher percentages of folic acid deficiency than children with normal iron status. Conclusion Iron and zinc deficiencies constitute the principal micronutrient deficiencies in Mexican children younger than 2 years old who use the health care services provided by IMSS. Anemia not associated with low ferritin values was more prevalent than iron-deficiency anemia. The presence of micronutrient deficiencies at this early age calls for effective preventive public nutrition programs to address them. PMID:18053140

  16. Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

    Microsoft Academic Search

    P Bauerfeind; T Cilluffo; C J Fimmel; C Emde; C von Ritter; W Kohler; R Gugler; T Gasser; A L Blum

    1987-01-01

    The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300

  17. Intrathecal non-NMDA excitatory amino acid receptor antagonists inhibit pain behaviors in a rat model of postoperative pain

    Microsoft Academic Search

    Peter K Zahn; Eric Umali; Timothy J Brennan

    1998-01-01

    Evidence indicates that excitatory amino acids (EAAs) like glutamate and aspartate are important in the processing of nociceptive information in the dorsal horn of the spinal cord. Recently, the role of particular EAA receptors in pain transmission and facilitated pain states has been examined utilizing spinal administration of specific receptor antagonists. Most investigators have studied the involvement of N-methyl-d-aspartate (NMDA)

  18. Hif1? down-regulation is associated with transposition of great arteries in mice treated with a retinoic acid antagonist

    Microsoft Academic Search

    Francesca Amati; Laura Diano; Luisa Campagnolo; Lucia Vecchione; Daria Cipollone; Susana Bueno; Gianluca Prosperini; Alessandro Desideri; Gregorio Siracusa; Giovanni Chillemi; Bruno Marino; Giuseppe Novelli

    2010-01-01

    BACKGROUND: Congenital heart defect (CHD) account for 25% of all human congenital abnormalities. However, very few CHD-causing genes have been identified so far. A promising approach for the identification of essential cardiac regulators whose mutations may be linked to human CHD, is the molecular and genetic analysis of heart development. With the use of a triple retinoic acid competitive antagonist

  19. Hereditary folate malabsorption: A positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding

    SciTech Connect

    Lasry, Inbal; Berman, Bluma [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)] [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Glaser, Fabian [Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa 32000 (Israel)] [Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa 32000 (Israel); Jansen, Gerrit [Department of Rheumatology, VU University Medical Center, Amsterdam (Netherlands)] [Department of Rheumatology, VU University Medical Center, Amsterdam (Netherlands); Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)

    2009-08-28

    The proton-coupled folate transporter (PCFT/SLC46A1) mediates intestinal folate uptake at acidic pH. Some loss of folic acid (FA) transport mutations in PCFT from hereditary folate malabsorption (HFM) patients cluster in R113, thereby suggesting a functional role for this residue. Herein, unlike non-conservative substitutions, an R113H mutant displayed 80-fold increase in the FA transport Km while retaining parental Vmax, hence indicating a major fall in folate substrate affinity. Furthermore, consistent with the preservation of 9% of parental transport activity, R113H transfectants displayed a substantial decrease in the FA growth requirement relative to mock transfectants. Homology modeling based on the crystal structures of the Escherichia coli transporter homologues EmrD and glycerol-3-phosphate transporter revealed that the R113H rotamer properly protrudes into the cytoplasmic face of the minor cleft normally occupied by R113. These findings constitute the first demonstration that a basic amino acid at position 113 is required for folate substrate binding.

  20. Effect of methionine, methionine hydroxy analogue, vitamin B?? and folic acid on blood and liver glutathione content in chicks 

    E-print Network

    Gabay, Sabit

    1954-01-01

    2. 55 67 3 133. 0 2. 42 69. 9 133. 6 Statistical @is bi i 0. 0. 01 Treatmeot: Blood GSH 10. 0 13. 4 Treatmemt:Liver GBH 14. 4 19. 3 C TABLE III TBE EFFECT QF ADOIBG THE CALCIIR SALT CF ALPHA-AMIBO-GO%-HKEOXI-hKBCAI'TO-JEE BBTIBIC ACID (NBA.... U. /g) PARA 69. 5 22 5 2 5 5. 0 ~ 75 'm~i~ 6 15 100 . 2 2000 5 6 1000 1000 20 CONPOGITIOS QF HALTS IVe C 3PCA E2 H POt Cs C03 Ng XA, 7H20 Ea Cl. Fe C6H507~ 6H20 X I 50. 0 l. 5. 0 4. 5 10. 2. 16. 8 2. 75 2. 0 0. 025 0...

  1. Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice.

    PubMed

    Trevisan, Gabriela; Rossato, Mateus F; Tonello, Raquel; Hoffmeister, Carin; Klafke, Jonatas Z; Rosa, Fernanda; Pinheiro, Kelly V; Pinheiro, Francielle V; Boligon, Aline A; Athayde, Margareth L; Ferreira, Juliano

    2014-07-01

    The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions. PMID:24722818

  2. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity

    PubMed Central

    Mueller, Michaela; Thorell, Anders; Claudel, Thierry; Jha, Pooja; Koefeler, Harald; Lackner, Carolin; Hoesel, Bastian; Fauler, Guenter; Stojakovic, Tatjana; Einarsson, Curt; Marschall, Hanns-Ulrich; Trauner, Michael

    2015-01-01

    Background & Aims Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. Methods In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery. Results Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7?-hydroxylase induction mirrored by elevated C4 and 7?-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. Conclusion These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. PMID:25617503

  3. Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound

    PubMed Central

    Jetson, Rachael; Malik, Neha; Luniwal, Amarjit; Chari, Venkatesh; Ratnam, Manohar; Erhardt, Paul

    2013-01-01

    Retinoic acid receptor alpha (RAR?) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RAR? antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure–activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR? for both compounds. Molecular modeling within the RAR? binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist. PMID:23474897

  4. A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women

    PubMed Central

    Casey, Gerard J; Phuc, Tran Q; MacGregor, Lachlan; Montresor, Antonio; Mihrshahi, Seema; Thach, Tran D; Tien, Nong T; Biggs, Beverley-Ann

    2009-01-01

    Background Anemia due to iron deficiency is recognized as one of the major nutritional deficiencies in women and children in developing countries. Daily iron supplementation for pregnant women is recommended in many countries although there are few reports of these programs working efficiently or effectively. Weekly iron-folic acid supplementation (WIFS) and regular deworming treatment is recommended for non-pregnant women living in areas with high rates of anemia. Following a baseline survey to assess the prevalence of anemia, iron deficiency and soil transmitted helminth infections, we implemented a program to make WIFS and regular deworming treatment freely and universally available for all women of reproductive age in two districts of a province in northern Vietnam over a 12 month period. The impact of the program at the population level was assessed in terms of: i) change in mean hemoglobin and iron status indicators, and ii) change in the prevalence of anemia, iron deficiency and hookworm infections. Method Distribution of WIFS and deworming were integrated with routine health services and made available to 52,000 women. Demographic data and blood and stool samples were collected in baseline, and three and 12-month post-implementation surveys using a population-based, stratified multi-stage cluster sampling design. Results The mean Hb increased by 9.6 g/L (95% CI, 5.7, 13.5, p < 0.001) during the study period. Anemia (Hb<120 g/L) was present in 131/349 (37.5%, 95% CI 31.3, 44.8) subjects at baseline, and in 70/363 (19.3%, 95% CI 14.0, 24.6) after twelve months. Iron deficiency reduced from 75/329 (22.8%, 95% CI 16.9, 28.6) to 33/353 (9.3%, 95% CI 5.7, 13.0) by the 12-mnth survey, and hookworm infection from 279/366 (76.2%,, 95% CI 68.6, 83.8) to 66/287 (23.0%, 95% CI 17.5, 28.5) over the same period. Conclusion A free, universal WIFS program with regular deworming was associated with reduced prevalence and severity of anemia, iron deficiency and hookworm infection when made available to Vietnamese women over a 12-month period. PMID:19630954

  5. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands

    PubMed Central

    2014-01-01

    Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161. PMID:24884885

  6. Analogues of a potent oxytocin antagonist with truncated C-terminus or shorter amino acid side chain of the basic amino acid at position 8.

    PubMed

    Flouret, George; Chaloin, Olivier; Slaninová, Jirina

    2003-06-01

    Twelve analogues were synthesized, their structure derived from modifications of [(S)Pmp1, D-Trp2, Pen6, Arg8]oxytocin, PA, in which (S)Pmp = beta,beta-(3-thiapentamethylene-beta-mercaptopropionic acid). PA is a potent antagonist of the uterotonic effect of oxytocin in the rat (uterotonic test in vitro, pA2 = 8.86) and in the baboon. Truncated analogues of PA from the C-terminus were systematically prepared ending in either the free acid or the amide, i.e. PA1-9 acid, PA1-8 acid, PA1-7 acid, PA1-6 acid, PA1-8 amide, PA1-7 amide and PA1-6 amide. PA1-8 amide was roughly as potent as PA in the rat uterotonic assay in vitro, and the shorter amides were only somewhat weaker antagonists. All four acid analogues were weaker antagonists than PA but still maintained rather high antagonistic potency. These findings suggest that, if these truncated acids form as metabolites in vivo, they may contribute to the overall biological effect of PA and their contribution should be taken into account. Furthermore, using these analogues, the radioimmunoassay measurements of PA may be standardized, as they may cross react with PA antibodies and interfere with the determination. In addition, five analogues were made by substituting Arg8 of PA with Lys, Orn8, Dab8, Dap8 and Cit8. All of these analogues maintained high potency as OTAs in the uterotonic assay, although their activity was only about 1.5-3 times lower than PA. The most potent analogue in the uterotonic assay, [Dap8]PA, pA2 = 8.53, had weak pressor activity (pA2 = 6.90) and no antidiuretic effect. The pressor activity was lower for all tested acids, and for PA1-6 acid it was even below the detection limit. Additionally, PA1-9 acid, PA1-7 acid and PA1-6 acid showed no antidiuretic activity. Hence, the PA1-6 acid is a potent OTA with pA2 = 8.27 and no measurable effect in the pressor or antidiuretic tests and thus it is a pure oxytocin antagonist. This fact makes it an attractive candidate for further studies on inhibition of OT biological effects and on preterm labour. PMID:12846485

  7. Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions.

    PubMed

    Takeuchi, Jun; Okamoto, Masanori; Akiyama, Tomonori; Muto, Takuya; Yajima, Shunsuke; Sue, Masayuki; Seo, Mitsunori; Kanno, Yuri; Kamo, Tsunashi; Endo, Akira; Nambara, Eiji; Hirai, Nobuhiro; Ohnishi, Toshiyuki; Cutler, Sean R; Todoroki, Yasushi

    2014-06-01

    The plant stress hormone abscisic acid (ABA) is critical for several abiotic stress responses. ABA signaling is normally repressed by group-A protein phosphatases 2C (PP2Cs), but stress-induced ABA binds Arabidopsis PYR/PYL/RCAR (PYL) receptors, which then bind and inhibit PP2Cs. X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA's 3' ring CH that opens at the PP2C binding interface. Here, ABA analogs with sufficiently long 3' alkyl chains were predicted to traverse this tunnel and block PYL-PP2C interactions. To test this, a series of 3'-alkylsulfanyl ABAs were synthesized with different alkyl chain lengths. Physiological, biochemical and structural analyses revealed that a six-carbon alkyl substitution produced a potent ABA antagonist that was sufficiently active to block multiple stress-induced ABA responses in vivo. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class. PMID:24792952

  8. Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs.

    PubMed

    Bowery, N G; Dray, A

    1978-05-01

    1 The effects of pentobarbitone (PB) and other sedative/hypnotic drugs have been examined in relation to gamma-aminobutyric acid (GABA) in vitro on the superfused isolated superior cervical ganglion of the rat and in vivo on single units in the brain stem of the anaesthetized rat.2 PB, and other barbiturates, depolarized the ganglion in a dose-dependent manner (threshold concentration 100-300 muM, cf. GABA depolarization threshold 1 muM). The depolarization was reduced in the presence of the selective GABA antagonist (+)-bicuculline methochloride (Bic). Other non-barbiturate sedatives e.g. chlordiazepoxide, amitriptyline, promethazine at concentrations up to 2mM produced no depolarization.3 PB, tested at concentrations up to 80 muM, produced variable effects on the dose-response curve to GABA. On most occasions a slight potentiation occurred in responses to low concentrations of GABA (below 10 muM) coupled with a depression in the responses to concentrations of GABA greater than 10 muM.4 Superfusion with PB in the presence of Bic reversed the depression in the response to GABA produced by Bic. This reversal phenomenon occurred at concentrations of PB too low to depolarize the ganglion and was dependent not only on the concentration of PB but also on that of Bic.5 The reversal potency within an homologous series of barbiturates increased with the size of the alkyl substituent (R2) at C5 on the barbiturate ring. The most potent occurred when the substituent contained 5 carbon atoms (pentobarbitone and amylobarbitone); above this, activity decreased.6 PB reversed the effects of the other GABA antagonists, tetramethylenedisulphotetramine and isopropyl bicyclophosphate and also the non-selective antagonism produced by strychnine. A concomitant reduction by strychnine of responses to the cholinomimetic, carbachol, was not reversed by PB.7 Non-barbiturate sedative/hypnotics also reversed the GABA antagonism produced by Bic. The benzodiazepines were effective at lower concentrations than PB (chlordiazepoxide threshold concentration 0.5 muM, cf. PB 5 muM), however, they only produced a partial reversal even at concentrations much higher than the maximally effective concentration of PB.8 The Bic reversal effect of chloridazepoxide (and other benzodiazepines) lasted many hours after removal from the superfusion solution. By contrast the effect of PB lasted only 15-30 min after its removal.9 Chlordiazepoxide (30 muM) applied in the absence of Bic did not affect the response to GABA but did reduce the depression produced by the subsequent application of Bic even though the chlordiazepoxide had been removed 40 min earlier.10 In the rat brain stem in vivo PB, applied iontophoretically in amounts which neither decreased the spontaneous neuronal firing rate nor affected the response to GABA or glycine, reversed the GABA antagonism induced by iontophoretic application of Bic (in all 23 neurones tested). PB also reversed the antagonism produced by strychnine of responses to glycine although this was less readily observed (5 out of 14 neurones tested).11 Iontophoretic application of other barbiturates and chlordiazepoxide also reversed the effect of Bic. Chlordiazepoxide only produced a partial reversal, as in the isolated ganglion, and no reversal could be demonstrated with flurazepam.12 Intravenous administration of thiopentone (1.3 mg/kg) pentobarbitone (0.4-5.5 mg/kg) hexobarbitone (0.4-0.8 mg/kg) and clonazepam (0.1-0.2 mg/kg) also reversed the effect of iontophoretically applied Bic. The reversal by clonazepam was of much longer duration than that produced by the barbiturates.13 It is suggested that the reversal exhibited by PB and the other hypnotics may be explained by assuming that the amino acids and their antagonists bind to the membrane at separate sites. If the reversal agent has particular affinity only for the antagonist binding site then it may displace the antagonist without affecting the receptor. PMID:206305

  9. Folic Acid: Data and Statistics

    MedlinePLUS

    ... received a doctor's recommendation. Â Top of Page Economic Cost The annual medical care and surgical costs for people with spina bifida exceed $200 million. [ Read article ] The total lifetime cost of care for a ... D, Dean JH, Stevenson RE. Economic evaluation of a neural tube defect recurrence prevention ...

  10. Blockade of the discriminative stimulus effects of ?-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS382

    Microsoft Academic Search

    Giancarlo Colombo; Roberta Agabio; Jacques Bourguignon; Fabio Fadda; Carla Lobina; Michel Maitre; Roberta Reali; Martine Schmitt; Gian Luigi Gessa

    1995-01-01

    The present study was designed to assess the ability of the newly synthetized, selective ?-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700

  11. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists.

    PubMed

    Andrés, Miriam; Buil, Maria Antonia; Calbet, Marta; Casado, Oscar; Castro, Jordi; Eastwood, Paul R; Eichhorn, Peter; Ferrer, Manel; Forns, Pilar; Moreno, Imma; Petit, Silvia; Roberts, Richard S

    2014-11-01

    Pyrrolopiperidinone acetic acids (PPAs) were identified as highly potent CRTh2 receptor antagonists. In addition, many of these compounds displayed slow-dissociation kinetics from the receptor. Structure-kinetic relationship (SKR) studies allowed optimisation of the kinetics to give potent analogues with long receptor residence half-lives of up to 23 h. Low permeability was a general feature of this series, however oral bioavailability could be achieved through the use of ester prodrugs. PMID:25437503

  12. Meso2,3-dimercaptosuccinic acid and sodium N-benzyl-N-dithiocarboxy-D-glucamine as antagonists for cadmium intoxication

    Microsoft Academic Search

    Mark M. Jones; Mark A. Basinger; Robert J. Topping; Glen R. Gale; Shirley G. Jones; Myron A. Holscher

    1988-01-01

    Orally administered meso-2,3-dimercaptosuccinic acid (DMSA) is an effective antagonist for acute oral cadmium chloride (1 mmol\\/kg) intoxication in mice when administered up to 8 h after cadmium ingestion. Administration of sodium N-benzyl-N-dithiocarboxy-d-glucamine (NaB) i.p. along with DMSA p.o. resulted in kidney and liver cadmium levels only marginally smaller than those obtained with DMSA alone. Both chelation treatment regimens permitted survival

  13. Etude exprimentale du dveloppement fœtal dans la dficience en acide folique induite par antivitamines

    E-print Network

    Paris-Sud XI, Université de

    -Bellevue. Summary. Fetal development under experimental folic acid deficiency induced by metho- trexate or X-methyl-folic acid. Tritium-labelled folic acid (10 [LCi/100 g) was given i. p. to normal pregnant rats to study increased 3.5-fold during that time. X-methyl-folic acid was given by oral route (0.5 p. 100 of the diet

  14. [Effect of gamma-aminobutyric acid, its agonists and antagonists on uterine smooth muscle].

    PubMed

    Sizov, P I; Iasnetsov, V S

    1985-11-01

    Experiments on isolated strips of the rabbit uterus showed the ability of GABA, GABAA-receptor agonist (diazepam) and GABAB-receptor antagonist (phenibut) to inhibit uterine contractility. GABAA-receptor antagonist (bicuculline) had a stimulating effect on contractility. It is assumed that GABA-ergic system plays an important role in the regulation of functional inhibition of contractile activity in the rabbit uterus, with GABA agonists regarded as potential gravidoprotectors in uterine hyperactivity or threatening miscarriage. PMID:2998506

  15. Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, And N-acetylcysteine in chicken embryo model

    Microsoft Academic Search

    Chiu-Lan Hsieh; Hui-Er Wang; Wan-Jane Tsai; Chiung-Chi Peng; Robert Y. Peng

    The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the risk of VPA-teratogenicity. The effect was varying. In order to promote the preventive prescription, to find out

  16. Molecular decodification of gymnemic acids from Gymnema sylvestre. Discovery of a new class of liver X receptor antagonists.

    PubMed

    Renga, Barbara; Festa, Carmen; De Marino, Simona; Di Micco, Simone; D'Auria, Maria Valeria; Bifulco, Giuseppe; Fiorucci, Stefano; Zampella, Angela

    2015-04-01

    The individual chemical components of commercial extract of Gymnema sylvestre, a medicinal plant used in the traditional systems of the Indian medicine for its antidiabetic and hypolipidemic properties, were isolated and evaluated for their capability to act as modulators of nuclear and membrane receptors involved in glucose and lipid homeostasis. The study disclosed for the first time that individual gymnemic acids are potent and selective antagonists for the ? isoform of LXR. Indeed the above activity was shared by the most abundant aglycone gymnemagenin (10) whereas gymnestrogenin (11) was endowed with a dual LXR?/? antagonistic profile. Deep pharmacological investigation demonstrated that gymnestrogenin, reducing the expression of SREBP1c and ABCA1 in vitro, is able to decrease lipid accumulation in HepG2 cells. The results of this study substantiate the use of G. sylvestre extract in LXR mediated dislypidemic diseases. PMID:25668616

  17. Folic acid-enhanced synergy for the combination of trimetrexate plus the glycinamide ribonucleotide formyltransferase inhibitor 4-[2-(2Amino4-oxo-4,6,7,8-tetrahydro-3 H-pyrimidino[5,4,6][1,4]thiazin-6-yl)-( S)-ethyl]-2,5-thienoylamino- l-glutamic acid (AG2034)

    Microsoft Academic Search

    Hélène M. Faessel; Harry K. Slocum; Youcef M. Rustum; William R. Greco

    1999-01-01

    Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Since this phenomenon is potentially therapeutically useful, we explored its universality by examining the combined action of a DHFR inhibitor, trimetrexate (TMQ), with a GARFT inhibitor, 4-[2-(2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4,6][1,4]thiazin-6-yl)-(S)-ethyl]-2,5-thienoylamino-l-glutamic acid (AG2034), in

  18. Actions of excitatory amino acid agonists and antagonists on the primary afferents of the vestibular system of the axolotl (Ambystoma mexicanum)

    Microsoft Academic Search

    Enrique Soto; Rosario Vega

    1988-01-01

    In order to determine the nature of the transmitter in the synapse between hair cells and primary afferent fibers, both resting and evoked spike activity of vestibular system afferents were recorded. Excitatory amino acid agonists and antagonists were applied by mi- cro perfusion. Excitatory amino acid agonists consistently increased the firing rate of these afferents. The rank order in potencies

  19. Simultaneous Determination of Gallic Acid, Ellagic Acid, and Eugenol in Syzygium aromaticum and Verification of Chemical Antagonistic Effect by the Combination with Curcuma aromatica Using Regression Analysis

    PubMed Central

    Seo, Chang-Seob; Kim, Seong-Sil; Ha, Hyekyung

    2013-01-01

    This study was designed to perform simultaneous determination of three reference compounds in Syzygium aromaticum (SA), gallic acid, ellagic acid, and eugenol, and to investigate the chemical antagonistic effect when combining Curcuma aromatica (CA) with SA, based on chromatographic analysis. The values of LODs and LOQs were 0.01–0.11??g/mL and 0.03–0.36??g/mL, respectively. The intraday and interday precisions were <3.0 of RSD values, and the recovery was in the range of 92.19–103.24%, with RSD values <3.0%. Repeatability and stability were 0.38–0.73% and 0.49–2.24%, respectively. Compared with the content of reference and relative peaks in SA and SA combined with CA (SAC), the amounts of gallic acid and eugenol were increased, while that of ellagic acid was decreased in SAC (compared with SA), and most of peak areas in SA were reduced in SAC. Regression analysis of the relative peak areas between SA and SAC showed r2 values >0.87, indicating a linear relationship between SA and SAC. These results demonstrate that the components contained in CA could affect the extraction of components of SA mainly in a decreasing manner. The antagonistic effect of CA on SA was verified by chemical analysis. PMID:23878761

  20. Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-?-cyclodextrin nanocarrier

    PubMed Central

    Li, Jin-Ming; Zhang, Wei; Su, Hua; Wang, Yuan-Yuan; Tan, Cai-Ping; Ji, Liang-Nian; Mao, Zong-Wan

    2015-01-01

    Systemic administration of chemotherapy for cancer often faces drug resistance, limiting its applications in cancer therapy. In this study, we developed a simple multifunctional nanocarrier based on polyethylenimine (PEI) to codeliver doxorubicin (DOX) and BCL2 small interfering RNA (siRNA) for overcoming multidrug resistance (MDR) and enhancing apoptosis in MCF-7/Adr cancer cells by combining chemotherapy and RNA interference (RNAi) therapy. The low-molecular-weight branch PEI was used to conjugate hydroxypropyl-?-cyclodextrin (HP-?-CD) and folic acid (FA), forming the codelivery nanocarrier (FA-HP-?-CD-PEI) to encapsulate DOX with the cavity HP-?-CD and bind siRNA with the positive charge of PEI for tumor-targeting codelivering drugs. The drug-loaded nanocomplexes (FA-HP-?-CD-PEI/DOX/siRNA) showed uniform size distribution, high cellular uptake, and significant gene suppression of BCL2, displaying the potential of overcoming MDR for enhancing the effect of anticancer drugs. Furthermore, the nanocomplexes achieved significant cell apoptosis through a mechanism of downregulating the antiapoptotic protein BCL2, resulted in improving therapeutic efficacy of the coadministered DOX by tumor targeting and RNA interference. Our study indicated that combined RNAi therapy and chemotherapy using our functional codelivery nanocarrier could overcome MDR and enhance apoptosis in MDR cancer cells for a potential application in treating MDR cancers. PMID:25960653

  1. Antagonist effects of veratric acid against UVB-induced cell damages.

    PubMed

    Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Lee, Kyung-Eun; Youm, Jong-Kyung; Park, Deokhoon

    2013-01-01

    Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection. PMID:23666007

  2. Cross-reactivity of acid-sensing ion channel and Na+–H+ exchanger antagonists with nicotinic acetylcholine receptors

    PubMed Central

    Santos-Torres, Julio; ?limak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

    2011-01-01

    Abstract Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na+–H+ exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited ?3?4-, ?7- and ?4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation. PMID:21911609

  3. Non-peptidic ? v? 3 antagonists containing indol-1-yl propionic acids

    Microsoft Academic Search

    Kristi Leonard; Wenxi Pan; Beth Anaclerio; Joan M. Gushue; Zihong Guo; Renee L. DesJarlais; Marge A. Chaikin; Jennifer Lattanze; Carl Crysler; Carl L. Manthey; Bruce E. Tomczuk; Juan Jose Marugan

    2005-01-01

    We describe the synthesis and structure\\/activity relationship of RGD mimetics that are potent inhibitors of the integrin ?v?3. Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified.

  4. Cartilage Acidic Protein1B (LOTUS), an Endogenous Nogo Receptor Antagonist for Axon Tract Formation

    Microsoft Academic Search

    Yasufumi Sato; Masumi Iketani; Yuji Kurihara; Megumi Yamaguchi; Naoya Yamashita; Fumio Nakamura; Yuko Arie; Takahiko Kawasaki; Tatsumi Hirata; Takaya Abe; Hiroshi Kiyonari; Stephen M. Strittmatter; Yoshio Goshima; Kohtaro Takei

    2011-01-01

    Neural circuitry formation depends on the molecular control of axonal projection during development. By screening with fluorophore-assisted light inactivation in the developing mouse brain, we identified cartilage acidic protein--1B as a key molecule for lateral olfactory tract (LOT) formation and named it LOT usher substance (LOTUS). We further identified Nogo receptor--1 (NgR1) as a LOTUS-binding protein. NgR1 is a receptor

  5. Cis-acting DNA Elements Responsive to Gibberellin and Its Antagonist Abscisic Acid

    Microsoft Academic Search

    Karen Skriver; Finn Lok Olsen; John C. Rogers; John Mundy

    1991-01-01

    We have used a transient expression assay in aleurone protoplasts of barley to delineate hormone response elements of the abscisic acid (ABA)-responsive rice gene Rab-16A and of the gibberellin A_3 (GA_3)-responsive barley alpha-amylase gene Amy 1\\/6-4. Our approach used transcriptional fusions between their 5' upstream sequences and a bacterial chloramphenicol acetyltransferase reporter gene. A chimeric promoter containing six copies of

  6. Antagonistic effect of fat on the antibotulinal activity of food preservatives and fatty acids

    Microsoft Academic Search

    Kathleen A Glass; Eric A Johnson

    2004-01-01

    The effect of fat on the antibotulinal activity of 11 food preservatives, 12 free fatty acids, and nine lots of enzyme-modified cheese (EMC) was evaluated in a media system. Anhydrous milkfat or soybean oil was added to tubes of Trypticase–peptone–glucose–yeast extract medium (TPGY) supplemented with the additives (final pH adjusted to 5.9). Treatments were inoculated with 3-log10 proteolytic Clostridium botulinumspores\\/ml

  7. Folic acid inhibits COLO-205 colon cancer cell proliferation through activating the FR?/c-SRC/ERK1/2/NF?B/TP53 pathway: in vitro and in vivo studies.

    PubMed

    Kuo, Chun-Ting; Chang, Chieh; Lee, Wen-Sen

    2015-01-01

    To investigate the molecular mechanism underlying folic acid (FA)-induced anti-colon caner activity, we showed that FA caused G0/G1 arrest in COLO-205. FA activated the proto-oncogene tyrosine-protein kinase Src (c-SRC)-mediated signaling pathway to enhance nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF?B) nuclear translocation and binding onto the tumor protein p53 (TP53) gene promoter, and up-regulated expressions of TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1B (CDKN1B). Knock-down of TP53 abolished FA-induced increases in the levels of CDKN1A and CDKN1B protein and G0/G1 arrest in COLO-205. Knock-down of folate receptor alpha (FR?) abolished FA-induced activations in the c-SRC-mediated pathway and increases in the levels of CDKN1A, CDKN1B and TP53 protein. These data suggest that FA inhibited COLO-205 proliferation through activating the FR?/c-SRC/mitogen-activated protein kinase 3/1 (ERK1/2)/NF?B/TP53 pathway-mediated up-regulations of CDKN1A and CDKN1B protein. In vivo studies demonstrated that daily i.p. injections of FA led to profound regression of the COLO-205 tumors and prolong the lifespan. In these tumors, the levels of CDKN1A, CDKN1B and TP53 protein were increased and von willebrand factor (VWF) protein levels were decreased. These findings suggest that FA inhibits COLO-205 colon cancer growth through anti-cancer cell proliferation and anti-angiogenesis. PMID:26056802

  8. Folic acid inhibits COLO-205 colon cancer cell proliferation through activating the FR?/c-SRC/ERK1/2/NF?B/TP53 pathway: in vitro and in vivo studies

    PubMed Central

    Kuo, Chun-Ting; Chang, Chieh; Lee, Wen-Sen

    2015-01-01

    To investigate the molecular mechanism underlying folic acid (FA)-induced anti-colon caner activity, we showed that FA caused G0/G1 arrest in COLO-205. FA activated the proto-oncogene tyrosine-protein kinase Src (c-SRC)-mediated signaling pathway to enhance nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF?B) nuclear translocation and binding onto the tumor protein p53 (TP53) gene promoter, and up-regulated expressions of TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1B (CDKN1B). Knock-down of TP53 abolished FA-induced increases in the levels of CDKN1A and CDKN1B protein and G0/G1 arrest in COLO-205. Knock-down of folate receptor alpha (FR?) abolished FA-induced activations in the c-SRC-mediated pathway and increases in the levels of CDKN1A, CDKN1B and TP53 protein. These data suggest that FA inhibited COLO-205 proliferation through activating the FR?/c-SRC/mitogen-activated protein kinase 3/1 (ERK1/2)/NF?B/TP53 pathway-mediated up-regulations of CDKN1A and CDKN1B protein. In vivo studies demonstrated that daily i.p. injections of FA led to profound regression of the COLO-205 tumors and prolong the lifespan. In these tumors, the levels of CDKN1A, CDKN1B and TP53 protein were increased and von willebrand factor (VWF) protein levels were decreased. These findings suggest that FA inhibits COLO-205 colon cancer growth through anti-cancer cell proliferation and anti-angiogenesis. PMID:26056802

  9. Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: from hit to clinic.

    PubMed

    Pizzonero, Mathieu; Dupont, Sonia; Babel, Marielle; Beaumont, Stéphane; Bienvenu, Natacha; Blanqué, Roland; Cherel, Laëtitia; Christophe, Thierry; Crescenzi, Benedetta; De Lemos, Elsa; Delerive, Philippe; Deprez, Pierre; De Vos, Steve; Djata, Fatoumata; Fletcher, Stephen; Kopiejewski, Sabrina; L'Ebraly, Christelle; Lefrançois, Jean-Michel; Lavazais, Stéphanie; Manioc, Murielle; Nelles, Luc; Oste, Line; Polancec, Denis; Quénéhen, Vanessa; Soulas, Florilène; Triballeau, Nicolas; van der Aar, Ellen M; Vandeghinste, Nick; Wakselman, Emanuelle; Brys, Reginald; Saniere, Laurent

    2014-12-11

    FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic. PMID:25380412

  10. Stapling Mimics Noncovalent Interactions of ?-Carboxyglutamates in Conantokins, Peptidic Antagonists of N-Methyl-d-Aspartic Acid Receptors*

    PubMed Central

    Platt, Randall J.; Han, Tiffany S.; Green, Brad R.; Smith, Misty D.; Skalicky, Jack; Gruszczy?ski, Pawe?; White, H. Steve; Olivera, Baldomero; Bulaj, Grzegorz; Gajewiak, Joanna

    2012-01-01

    Conantokins are short peptides derived from the venoms of marine cone snails that act as antagonists of the N-methyl-d-aspartate (NMDA) receptor family of excitatory glutamate receptors. These peptides contain ?-carboxyglutamic acid residues typically spaced at i,i+4 and/or i,i+7 intervals, which by chelating divalent cations induce and stabilize helical conformation of the peptide. Introduction of a dicarba bridge (or a staple) can covalently stabilize peptide helicity and improve its pharmacological properties. To test the hypothesis that stapling can effectively replace ?-carboxyglutamic acid residues in stabilizing the helical conformation of conantokins, we designed, synthesized, and characterized several stapled analogs of conantokin G (conG), with varying connectivities in terms of staple length and location along the face of the ?-helix. NMR studies confirmed that the ring-closing metathesis reaction yielded a single product with the Z configuration of the olefinic bond. Based on circular dichroism and molecular modeling, the stapled analogs exhibited significantly enhanced helicity compared with the native peptide in a metal-free environment. Stapling i,i+4 was benign with respect to effects on in vitro and in vivo pharmacological properties. One analog, namely conG[11–15,Si,i+4S(8)], blocked NR2B-containing NMDA receptors with IC50 = 0.7 ?m and provided significant protection in the 6-Hz psychomotor model of pharmacoresistant epilepsy in mice. Remarkably, unlike native conG, conG[11–15,Si,i+4S(8)] produced no behavioral motor toxicity. Our results extend the applications of peptide stapling to helical peptides with extracellular targets and provide a means for engineering conantokins with improved pharmacological properties. PMID:22518838

  11. Cartilage acidic protein-1B (LOTUS), an endogenous Nogo receptor antagonist for axon tract formation.

    PubMed

    Sato, Yasufumi; Iketani, Masumi; Kurihara, Yuji; Yamaguchi, Megumi; Yamashita, Naoya; Nakamura, Fumio; Arie, Yuko; Kawasaki, Takahiko; Hirata, Tatsumi; Abe, Takaya; Kiyonari, Hiroshi; Strittmatter, Stephen M; Goshima, Yoshio; Takei, Kohtaro

    2011-08-01

    Neural circuitry formation depends on the molecular control of axonal projection during development. By screening with fluorophore-assisted light inactivation in the developing mouse brain, we identified cartilage acidic protein-1B as a key molecule for lateral olfactory tract (LOT) formation and named it LOT usher substance (LOTUS). We further identified Nogo receptor-1 (NgR1) as a LOTUS-binding protein. NgR1 is a receptor of myelin-derived axon growth inhibitors, such as Nogo, which prevent neural regeneration in the adult. LOTUS suppressed Nogo-NgR1 binding and Nogo-induced growth cone collapse. A defasciculated LOT was present in lotus-deficient mice but not in mice lacking both lotus- and ngr1. These findings suggest that endogenous antagonism of NgR1 by LOTUS is crucial for normal LOT formation. PMID:21817055

  12. Expression of IL1?, IL1 Receptor Type I and IL1 Receptor Antagonist in Human Aortic Smooth Muscle Cells: Effects of all-trans-Retinoic Acid

    Microsoft Academic Search

    Dick Wågsäter; Ken Jatta; Pauline Ocaya; Jan Dimberg; Allan Sirsjö

    2006-01-01

    The proinflammatory cytokine interleukin (IL)-1? and the IL-1 receptor antagonist are expressed by atherosclerotic plaques and may be linked to the development of atherosclerosis. Existing evidence shows that retinoids and their receptors are involved in inflammatory response and that they are found in atherosclerotic plaques. In all-trans-retinoic acid (atRA)-treated human aortic smooth muscle cells (AOSMC), significant increases in IL-1? levels

  13. Structure-activity relationships and mechanism of action of Eph-ephrin antagonists: interaction of cholanic acid with the EphA2 receptor

    PubMed Central

    Tognolini, Massimiliano; Incerti, Matteo; Mohamed, Iftiin Hassan; Giorgio, Carmine; Russo, Simonetta; Bruni, Renato; Lelli, Barbara; Bracci, Luisa; Noberini, Roberta; Pasquale, Elena B.; Barocelli, Elisabetta; Vicini, Paola; Mor, Marco

    2012-01-01

    The Eph–ephrin system, including the EphA2 receptor and the ephrin-A1 ligand, plays a critical role in tumor and vascular functions during carcinogenesis. We previously identified (3?,5?)-3-hydroxycholan-24-oic acid (lithocholic acid) as an Eph-ephrin antagonist able to inhibit EphA2 receptor activation and therefore potentially useful as a novel EphA2 receptor targeting agent. Here, we explore the structure-activity relationships of a focused set of lithocholic acid derivatives, based on molecular modelling investigation and displacement binding assays. Our exploration shows that while the 3-?-hydroxyl group of lithocholic acid has a negligible role in the recognition of the EphA2 receptor, its carboxylate group is critical for disrupting the binding of ephrin-A1 to the EphA2. As a result of our investigation, we identified (5?)-cholan-24-oic acid (cholanic acid) as a novel compound that competitively inhibits EphA2-ephrin-A1 interaction with higher potency than lithocholic acid. Surface plasmon resonance analysis indicates that cholanic acid binds specifically and reversibly to the ligand-binding domain of EphA2, with a steady-state dissociation constant (KD) in the low micromolar range. Furthermore, cholanic acid blocks the phosphorylation of EphA2 and cell retraction and rounding in PC3 prostate cancer cells, two effects that depend on EphA2 activation by the ephrin-A1 ligand. These findings suggest that cholanic acid can be used as a template structure to design effective EphA2 antagonists, with potential impact in the elucidation of the role played by this receptor in pathological conditions. PMID:22529030

  14. Structural model for gamma-aminobutyric acid receptor noncompetitive antagonist binding: widely diverse structures fit the same site.

    PubMed

    Chen, Ligong; Durkin, Kathleen A; Casida, John E

    2006-03-28

    Several major insecticides, including alpha-endosulfan, lindane, and fipronil, and the botanical picrotoxinin are noncompetitive antagonists (NCAs) for the GABA receptor. We showed earlier that human beta(3) homopentameric GABA(A) receptor recognizes all of the important GABAergic insecticides and reproduces the high insecticide sensitivity and structure-activity relationships of the native insect receptor. Despite large structural diversity, the NCAs are proposed to fit a single binding site in the chloride channel lumen lined by five transmembrane 2 segments. This hypothesis is examined with the beta(3) homopentamer by mutagenesis, pore structure studies, NCA binding, and molecular modeling. The 15 amino acids in the cytoplasmic half of the pore were mutated to cysteine, serine, or other residue for 22 mutants overall. Localization of A-1'C, A2'C, T6'C, and L9'C (index numbers for the transmembrane 2 region) in the channel lumen was established by disulfide cross-linking. Binding of two NCA radioligands [(3)H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane and [(3)H] 3,3-bis-trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile was dramatically reduced with 8 of the 15 mutated positions, focusing attention on A2', T6', and L9' as proposed binding sites, consistent with earlier mutagenesis studies. The cytoplasmic half of the beta3 homopentamer pore was modeled as an alpha-helix. The six NCAs listed above plus t-butylbicyclophosphorothionate fit the 2' to 9' pore region forming hydrogen bonds with the T6' hydroxyl and hydrophobic interactions with A2', T6', and L9' alkyl substituents, thereby blocking the channel. Thus, widely diverse NCA structures fit the same GABA receptor beta subunit site with important implications for insecticide cross-resistance and selective toxicity between insects and mammals. PMID:16537435

  15. 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

    PubMed Central

    Badiga, Suguna; Johanning, Gary L.; Macaluso, Maurizio; Azuero, Andres; Chambers, Michelle M.; Siddiqui, Nuzhat R.; Piyathilake, Chandrika J.

    2014-01-01

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:25302494

  16. Rewarding and incentive motivational effects of excitatory amino acid receptor antagonists into the median raphe and adjacent regions of the rat

    PubMed Central

    Webb, Sierra M.; Vollrath-Smith, Fiori R.; Shin, Rick; Jhou, Thomas C.; Xu, Shengping

    2012-01-01

    Rationale The motivational process that regulates approach behavior toward salient distal stimuli (i.e., incentive motivation) plays a key role in voluntary behavior and motivational disorders such as addiction. This process may be mediated by many neurotransmitter systems and a network of many brain structures, including the median and dorsal raphe regions (MR and DR, respectively). Objective We sought to examine whether the blockade of excitatory amino acid receptors in the MR and DR is rewarding, using intracranial self-administration, and whether the self-administration effect can be explained by drug’s effectiveness to enhance incentive motivation, using a visual sensation seeking procedure. Results Rats learned to self-administer the AMPA receptor antagonist ZK 200775 into the vicinity of the MR, DR, or medial oral pontine reticular regions, but not the ventral tegmental area. The NMDA receptor antagonist AP5 was also self-administered into the MR, while it was not readily self-administered into other regions. When ZK 200775 was noncontingently administered into the MR, rats markedly increased approach responses rewarded by brief illumination of a light stimulus. In addition, contingent administration of ZK 200775 into the MR induced a conditioning effect on approach responses. Conclusions Rats self-administer excitatory amino acid receptor antagonists into the MR and adjacent regions. Self-administration effect of AMPA receptor antagonists into the MR can be largely explained by the manipulation’s properties to invigorate ongoing approach behavior and induces conditioned approach. Glutamatergic afferents to the median raphe and adjacent regions appear to tonically suppress incentive-motivational processes. PMID:22752328

  17. Cyclopentane-1,3-dione: A Novel Isostere for the Carboxylic Acid Functional Group. Application to the Design of Potent Thromboxane (A2)-Receptor Antagonists

    PubMed Central

    Ballatore, Carlo; Soper, James; Piscitelli, Francesco; James, Michael; Huang, Longchuan; Atasoylu, Onur; Huryn, Donna M.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Brunden, Kurt R.; Smith, Amos B.

    2011-01-01

    Cyclopentane-1,3-diones are known to exhibit pKa values typically in the range of carboxylic acids. To explore the potential of the cyclopentane-1,3-dione unit as a carboxylic acid isostere, the physical-chemical properties of representative congeners were examined and compared with similar derivatives bearing carboxylic acid or tetrazole residues. These studies suggested that cyclopentane-1,3-diones may effectively substitute for the carboxylic acid functional group. To demonstrate the use of the cyclopentane-1,3-dione isostere in drug-design, derivatives of a known thromboxane-A2 prostanoid (TP) receptor antagonist, 3-(3-(2-(4-chlorophenylsulfonamido)ethyl)-phenyl)propanoic acid (12), were synthesized and evaluated in both functional and radioligand-binding assays. A series of mono- and di-substituted cyclopentane-1,3-dione derivatives (41–45) were identified that exhibit nM IC50 and Kd values similar to 12. Collectively, these studies demonstrate that the cyclopentane-1,3-dione moiety comprises a novel isostere of the carboxylic acid functional group. Given the combination of the relatively strong acidity, tunable lipophilicity, and versatility of the structure, the cyclopentane-1,3-dione moiety may constitute a valuable addition to the palette of carboxylic acid isosteres. PMID:21863799

  18. Structure-activity relationships in a new series of insecticidally active dioxatricycloalkenes derived by structural comparison of the GABA (. gamma. -aminobutyric acid) antagonists bicycloorthocarboxylates and endosulfan

    SciTech Connect

    Ozoe, Yoshihisa; Sawada, Yoshihiro; Mochida, Kazuo; Nakamura, Toshiie (Shimane Univ. (Japan)); Matsumura, Fumio (Univ. of California, Davis (USA))

    1990-05-01

    To study structural requirements for picrotoxinin-type GABA ({gamma}-aminobutyric acid) antagonists to interact with the receptor site, 5-substituted 4,6-dioxatricyclo(7.2.1.0{sup 2,8})dodec-10-enes and related compounds were prepared and examined for their insecticidal activity and potency in displacing ({sup 35}S)tert-butylbicyclophosphorothionate (TBPS) binding. Compounds with high insecticidal activity possessed a phenyl group with an electron-withdrawing para substituent, a cycloalkyl group, or a C{sub 3}-C{sub 5} straight-chain alkyl group at the 5-position. The effect of the 5-substituents on insecticidal activity was very similar to that of the 1-substituents of the bicyloorthocarboxylate GABA antagonists. Representative dioxatricycloalkenes displaced the binding of the GABA antagonist ({sup 35}S)TBPS to housefly head membranes by 29-53% at 10 {mu}M. X-ray crystal structure analysis demonstrated that this class of compounds had structures superimposable on those of 4-tert-butylbicycloorthocarboxylates. These findings indicate that the dioxatricycloalkenes and some other analogues occupy the picrotoxinin binding site in such a way that the fourth interacting subsite of the receptor site accommodates the 5-substituent.

  19. Homocysteine, Folic Acid and Cardiovascular Disease

    MedlinePLUS

    Get Your Local Info Find out what is happening at your local American Heart area Search by State SELECT YOUR LANGUAGE ... learning more about: How to Donate Find Your Local American Heart Association Your Heart Score CPR Classes ...

  20. Spina Bifida and Folic Acid Awareness

    ERIC Educational Resources Information Center

    Exceptional Parent, 2007

    2007-01-01

    Spina bifida is the most common, permanently disabling birth defect in the United States. It is a birth defect that involves incomplete formation of the spine during the first month of pregnancy--often before a woman even knows she is pregnant. Everyday, an average of eight babies are born with spina bifida or a similar birth defect of the brain…

  1. Associations of erythrocyte membrane fatty acids with the concentrations of C-reactive protein, interleukin 1 receptor antagonist and adiponectin in 1373 men.

    PubMed

    Takkunen, M J; de Mello, V D F; Schwab, U S; Ågren, J J; Kuusisto, J; Uusitupa, M I J

    2014-10-01

    Dietary and endogenous fatty acids could play a role in low-grade inflammation. In this cross-sectional study the proportions of erythrocyte membrane fatty acids (EMFA) and the concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra) and adiponectin were measured and their confounder-adjusted associations examined in 1373 randomly selected Finnish men aged 45-70 years participating in the population based Metsim study in Eastern Finland. The sum of n-6 EMFAs, without linoleic acid (LA), was positively associated with concentrations of CRP and IL-1Ra (r partial=0.139 and r partial=0.115, P<0.001). These associations were especially strong among lean men (waist circumference <94 cm; r partial=0.156 and r partial=0.189, P<0.001). Total n-3 EMFAs correlated inversely with concentrations of CRP (r partial=-0.098, P<0.001). Palmitoleic acid (16:1n-7) correlated positively with CRP (r partial=0.096, P<0.001). Cis-vaccenic acid (18:1n-7) was associated with high concentrations of adiponectin (r partial=0.139, P<0.001). In conclusion, n-6 EMFAs, except for LA, correlated positively with the inflammatory markers. Palmitoleic acid was associated with CRP, whereas, interestingly, its elongation product, cis-vaccenic acid, associated with anti-inflammatory adiponectin. PMID:25087591

  2. Opioid Antagonists

    Microsoft Academic Search

    Youn Seon Choi; J. Andrew Billings

    2002-01-01

    Opioid antagonists have well-established indications in the reversal of life-threatening opioid toxicity, but also hold considerable promise for other applications in palliative care practice, particularly management of opioid-related constipation. We briefly review current understanding of opioid receptors, focusing on their complex role in gastrointestinal physiology. We summarize the pharmacology, conventional indications, and clinical usage of three major groups of opioid

  3. Lipoteichoic Acid Acts as an Antagonist and an Agonist of Lipopolysaccharide on Human Gingival Fibroblasts and Monocytes in a CD14-Dependent Manner

    PubMed Central

    Sugawara, Shunji; Arakaki, Rieko; Rikiishi, Hidemi; Takada, Haruhiko

    1999-01-01

    CD14 has been implicated as a receptor of lipoteichoic acid (LTA) and other bacterial components as well as lipopolysaccharide (LPS). Since the structures of LTAs from various gram-positive bacteria are heterogeneous, we analyzed the effects of LTAs on the secretion of interleukin-8 (IL-8) by high- and low-CD14-expressing (CD14high and CD14low) human gingival fibroblasts (HGF). While Bacillus subtilis LTA had an IL-8-inducing effect on CD14high HGF which was considerably weaker than that of LPS, Streptococcus sanguis and Streptococcus mutans LTAs had practically no effect on the cells. B. subtilis LTA had only a weak effect on CD14low HGF, as did LPS. S. sanguis and S. mutans LTAs at a 1,000-fold excess each completely inhibited the IL-8-inducing activities of both LPS and a synthetic lipid A on CD14high HGF. The effect of LPS was also inhibited by the presence of an LPS antagonist, synthetic lipid A precursor IVA (LA-14-PP), with a 100-fold higher potency than S. sanguis and S. mutans LTAs and by anti-CD14 monoclonal antibody (MAb). S. sanguis and S. mutans LTAs, LA-14-PP, and anti-CD14 MAb had no significant effect on phorbol myristate acetate-stimulated IL-8 secretion by HGF. These LTAs also inhibited the IL-8-inducing activity of B. subtilis LTA on CD14high HGF, as did LA-14-PP and anti-CD14 MAb. The antagonistic and agonistic functions of LTAs were also observed with human monocytes. Binding of fluorolabeled LPS to human monocytes was inhibited by S. sanguis LTA, although the inhibition was 100 times weaker than that of LPS itself, and anti-CD14 MAb inhibited fluorolabeled LPS and S. sanguis LTA binding. Binding of LTAs to CD14 was also observed with nondenaturing polyacrylamide gel electrophoresis. These results indicate that LTAs act as antagonists or agonists via a CD14-dependent mechanism, probably due to the heterogeneous structure of LTAs, and that an antagonistic LTA might be a useful agent for suppressing the periodontal disease caused by gram-negative bacteria. PMID:10084995

  4. Indomethacin/ibuprofen-like anti-inflammatory agents selectively potentiate the gamma-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on [35S]t-butylbicyclophosphorothionate binding.

    PubMed

    Squires, R F; Saederup, E

    1993-05-01

    Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin/ibuprofen-like arylalkanoic acid (AAA) anti-inflammatory drugs alone had no effect on [35S]TBPS binding, or on its inhibition by GABA, but potentiated the GABA-antagonistic effects of the four quinolones. Felbinac (4-biphenylacetic acid) was most potent in this respect (EC50 = 110 nM, together with 5 microM norfloxacin), followed by flurbiprofen > anirolac > metiazinic acid > tolmetin = ketoprofen = fenbufen = indomethacin > fenoprofen > ibuprofen = (+)-naproxen = sulindac. Other anti-inflammatory analgesic drugs, including aspirin, diclofenac, diflunisal, meclofenamic acid, mefenamic acid, nambumetone, phenacetin, piroxicam, and phenylbutazone, failed to potentiate the GABA-antagonistic effect of norfloxacin. Felbinac (1 microM) increased the GABA-antagonistic potencies of norfloxacin and enoxacin about 26-fold, while increasing those of ciprofloxacin and pipemidic acid 7-fold and 2.3-fold, respectively. Using subsaturating concentrations of the four quinolones, concentration-response curves for felbinac yielded EC50 values ranging from 110 nM with 5 microM norfloxacin to 1.3 microM with 100 microM pipemidic acid. Three other piperazinoquinolone antibacterial agents (amifloxacin, difloxacin, and fleroxacin) and four nonpiperazinoquinolone anti-bacterial agents (oxolinic acid, cinoxacin, nalidixic acid, and piromidic acid) were much weaker GABA antagonists and were not significantly potentiated by felbinac. All other known GABAA receptor blockers tested, including R 5135, pitrazepin, bicuculline, SR 95531, strychnine, D-tubocurarine, thebaine, securinine, theophylline, and caffeine, were not potentiated by felbinac. Our results suggest that norfloxacin and related piperazinoquinolones, acting at GABAA receptors, may induce a high affinity binding site for indomethacin/ibuprofen-like anti-inflammatory agents (the AAA site) that, when occupied, reciprocally increases the affinities of the quinolones for GABAA receptors. The AAA binding site may be a new site in the GABAA receptor complex. PMID:8388990

  5. Relationship between the 19 base pair deletion polymorphism in DHFR and unmetabolized folic and in plasma and RBC folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: A 19 base pair (bp) deletion allele of dihydrofolate reductase (DHFR), an enzyme that makes folic acid metabolically active and reduces dihydrofolate to tetrahydrofolate to stimulate folate turnover, has been implicated in folate related health outcomes. Objective: Examine the effect ...

  6. 2'-[18F]Fluorofolic acid [2'-[18F]FFA

    E-print Network

    Levin, Judith G.

    structure for additional information in PubChem. Background [PubMed] Folic acid is a water-soluble vitamin B of [18F]4-fluorobenzylamine (FBA) with the - and -carboxyl groups of folic acid. [18F]/-FBA-folate has at the 2' position of the 4-amino-benzoyl moiety in folic acid to form 2'-[18F]fluorofolic acid (2'-[18F

  7. Molecular basis determining inhibition/activation of nociceptive receptor TRPA1 protein: a single amino acid dictates species-specific actions of the most potent mammalian TRPA1 antagonist.

    PubMed

    Banzawa, Nagako; Saito, Shigeru; Imagawa, Toshiaki; Kashio, Makiko; Takahashi, Kenji; Tominaga, Makoto; Ohta, Toshio

    2014-11-14

    The transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable, nonselective cation channel mainly expressed in a subset of nociceptive neurons. TRPA1 functions as a cellular sensor detecting mechanical, chemical, and thermal stimuli. Because TRPA1 is considered to be a key player in nociception and inflammatory pain, TRPA1 antagonists have been developed as analgesic agents. Recently, by utilizing species differences, we identified the molecular basis of the antagonistic action of A967079, one of the most potent mammalian TRPA1 antagonists. Here, we show a unique effect of A967079 on TRPA1 from diverse vertebrate species, i.e. it acts as an agonist but not as an antagonist for chicken and frog TRPA1s. By characterizing chimeric channels of human and chicken TRPA1s, as well as point mutants, we found that a single specific amino acid residue located within the putative fifth transmembrane domain was involved in not only the stimulatory but also the inhibitory actions of A967079. AP18, structurally related to A967079, exerted similar pharmacological properties to A967079. Our findings and previous reports on species differences in the sensitivity to TRPA1 antagonists supply useful information in the search for novel analgesic medicines targeting TRPA1. PMID:25271161

  8. Schedule-controlled behavioral effects of the selective 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic acid antagonist LY293558 in pigeons.

    PubMed

    Benvenga, M J; Ornstein, P L; Leander, J D

    1995-10-01

    Behavioral effects of the selective 2-amino-3-(5-methyl-3-hydroxyisoxazol-4- yl)propanoic acid (AMPA) antagonist LY293558, along with its racemate (LY215490) and opposing enantiomer (LY293559) were evaluated in pigeons. When responding was maintained under a multiple fixed ratio 50 responses, fixed interval 5 minute (FRFI) schedule of food presentation, LY215490 completely antagonized the rate suppression induced by AMPA (10 mg/kg) and by the AMPA analog, 2-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionic acid (ATPA; 40 mg/kg) at 1.25 and 2.5 mg/kg, respectively. In contrast, LY215490, up to 10 mg/kg, was unable to antagonize the rate suppression induced by N-methyl-D-aspartic acid. LY293558, at 0.32 mg/kg, completely blocked the rate suppression produced by AMPA in both components of the multiple schedule. Similarly, LY293558, at 0.64 mg/kg, blocked the rate suppression induced by ATPA in both components. In contrast, the opposing enantiomer, LY293559, up to 10 mg/kg, was without effect on rate suppression produced by AMPA in this model. In additional studies, behavior was maintained under a schedule in which responding was maintained by food presentation in the presence of one key color and in the presence of a second key color, responding was maintained by food and simultaneously suppressed by electric shock ("punished responding"). LY215490 significantly increased punished responding at 10 and 30 mg/kg, whereas unpunished responding was unaffected until 56 mg/kg depressed it. LY293558 significantly increased punished responding at 3 mg/kg without having an effect on unpunished responding. LY293559, on the other hand, was unable to significantly increase punished responding at doses up to 175 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7562545

  9. Antagonistic Changes between Abscisic Acid and Gibberellins in Citrus Fruits Subjected to a Series of Different Water Conditions

    Microsoft Academic Search

    Jalel Mahouachi; Aurelio Gómez-Cadenas; Eduardo Primo-Millo; Manuel Talon

    2005-01-01

    The relationship between absicisic acid (ABA) and gibberellin (GA) changes in developing fruitlets from both Clementina (Citrus clementina, Hort ex Tan) and Okitsu (Citrus unshiu, (Mak) Marc.) trees subjected to changing water conditions was investigated. The treatments consisted of a series of water\\u000a stress, rainfall, and re-irrigation periods. To confirm the effectiveness of the imposed water changes, leaf water potential

  10. Calcitonin gene-related peptide analogues with aza and indolizidinone amino acid residues reveal conformational requirements for antagonist activity at the human calcitonin gene-related peptide 1 receptor.

    PubMed

    Boeglin, Damien; Hamdan, Fadi F; Melendez, Rosa E; Cluzeau, Jérôme; Laperriere, Andre; Héroux, Madeleine; Bouvier, Michel; Lubell, William D

    2007-03-22

    Calcitonin gene-related peptide antagonists have potential for the treatment and prevention of disease states such as non-insulin-dependent diabetes mellitus, migraine headache, pain, and inflammation. To gain insight into the spatial requirements for CGRP antagonism, three strategies were employed to restrict the conformation of the potent undecapeptide antagonist, [D31,P34,F35]CGRP27-37. First, aza-amino acid scanning was performed, and ten aza-peptide analogues were synthesized and examined for biological activity. Second, (3S,6S,9S)-2-oxo-3-amino-indolizidin-2-one amino acid (I2aa) and (2S,6S,8S)-9-oxo-8-amino-indolizidin-9-one amino acid (I9aa) both were introduced at positions 31-32, 32-33, 33-34, and 34-35, regions of the backbone expected to adopt turns. Finally, the conformation of the backbone and side-chain of the C-terminal residue, Phe35-Ala36-Phe37-NH2, was explored employing (2S,4R,6R,8S)-9-oxo-8-amino-4-phenyl-indolizidin-9-one amino acid (4-Ph-I9aa) as a constrained phenylalanine mimic. The structure-activity relationships exhibited by our 26 analogues illustrate conformational requirements important for designing CGRP antagonists and highlight the importance of beta-turns centered at Gly33-Pro34 for potency. PMID:17319653

  11. Zhankuic Acid A Isolated from Taiwanofungus camphoratus Is a Novel Selective TLR4/MD-2 Antagonist with Anti-Inflammatory Properties

    PubMed Central

    Chen, Yu-Fon; Shiau, Ai-Li; Wang, Sheng-Hung; Yang, Jai-Sing; Chang, Sue-Joan

    2014-01-01

    TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections. PMID:24532584

  12. Antagonistic roles of abscisic acid and cytokinin during response to nitrogen depletion in oleaginous microalga Nannochloropsis oceanica expand the evolutionary breadth of phytohormone function.

    PubMed

    Lu, Yandu; Tarkowská, Danuše; Ture?ková, Veronika; Luo, Tingwei; Xin, Yi; Li, Jing; Wang, Qintao; Jiao, Nianzhi; Strnad, Miroslav; Xu, Jian

    2014-10-01

    The origin of phytohormones is poorly understood, and their physiological roles in microalgae remain elusive. Genome comparison of photosynthetic autotrophic eukaryotes has revealed that the biosynthetic pathways of abscisic acid (ABA) and cytokinins (CKs) emerged in unicellular algae. While ABA and CK degradation mechanisms emerged broadly in algal lineages, complete vascular plant-type conjugation pathways emerged prior to the rise of Streptophyta. In microalgae, a complete set of proteins from the canonical ABA and CK sensing and signaling pathways is not essential, but individual components are present, suggesting stepwise recruitment of phytohormone signaling components. In the oleaginous eustigmatophyte Nannochloropsis oceanica IMET1, UHPLC-MS/MS detected a wide array of plant hormones, despite a phytohormone profile that is very distinct from that of flowering plants. Time-series transcriptional analysis during nitrogen depletion revealed activation of the ABA biosynthetic pathway and antagonistic transcription of CK biosynthetic genes. Correspondingly, the ABA level increases while the dominant bioactive CK forms decrease. Moreover, exogenous CKs stimulate cell-cycle progression while exogenous ABA acts as both an algal growth repressor and a positive regulator in response to stresses. The presence of such functional flowering plant-like phytohormone signaling systems in Nannochloropsis sp. suggests a much earlier origin of phytohormone biosynthesis and degradation than previously believed, and supports the presence in microalgae of as yet unknown conjugation and sensing/signaling systems that may be exploited for microalgal feedstock development. PMID:25041627

  13. Zhankuic acid A isolated from Taiwanofungus camphoratus is a novel selective TLR4/MD-2 antagonist with anti-inflammatory properties.

    PubMed

    Chen, Yu-Fon; Shiau, Ai-Li; Wang, Sheng-Hung; Yang, Jai-Sing; Chang, Sue-Joan; Wu, Chao-Liang; Wu, Tian-Shung

    2014-03-15

    TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections. PMID:24532584

  14. Novel polymer monolith microextraction using a poly(methacrylic acid-ethylene glycol dimethacrylate) monolith and its application to simultaneous analysis of several angiotensin II receptor antagonists in human urine by capillary zone electrophoresis

    Microsoft Academic Search

    Min Zhang; Fang Wei; Yi-Fei Zhang; Jing Nie; Yu-Qi Feng

    2006-01-01

    Novel polymer monolith microextraction (PMME) using a poly(methacrylic acid-ethylene glycol dimethacrylate) (poly(MAA-EGDMA)) monolith in conjunction with capillary zone electrophoresis (CZE) was developed for the determination of several angiotensin II receptor antagonists (ARA-IIs) in human urine. The extraction device consisted of a regular plastic syringe (1mL), a poly(MAA-EGDMA) monolithic capillary (2cm×530?m I.D.) and a plastic pinhead connecting the former two components

  15. Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory.

    PubMed

    Liu, Lei; Li, Jian; Zhang, Yan; Zhang, Shenghui; Ye, Jianqin; Wen, Zhichao; Ding, Jianping; Kunapuli, Satya P; Luo, Xinping; Ding, Zhongren

    2014-10-01

    Salviae miltiorrhiza (Danshen) has been used for thousands of years in China and some other Asian countries to treat atherothrombotic diseases. Salvianolate which consists of three water-soluble ingredients purified from Salviae miltiorrhiza, has been approved by Chinese SFDA to treat coronary artery disease. So far, there is no evidence clearly showing the clinical efficiency of salvianolate and the underlying mechanism. This study is to evaluate the effects of salvianolate on platelets in patients with acute coronary syndrome and explore the underlying mechanism. We evaluated the effects of salvianolate on platelets in patients with acute coronary syndrome by measuring ADP-induced PAC-1 binding and P-selectin expression on platelets. Salvianolate significantly potentiated the antiplatelet effects of standard dual antiplatelet therapy. We also investigated the antiplatelet effects of salvianolatic acid B (Sal-B), the major component which composes 85% of salvianolate. Sal-B inhibits human platelet activation induced by multiple agonists in vitro by inhibiting phosphodiesterase (PDE) and antagonizing P2Y12 receptor. For the first time, we show the antiplatelet efficiency of salvianolate in ACS patients undergoing treatment with clopidogrel plus aspirin, and demonstrate that Sal-B, the major component of salvianolate inhibits human platelet activation via PDE inhibition and P2Y12 antagonism which may account for the clinical antiplatelet effects of salvianolate. Our results suggest that Sal-B may substitute salvianolate for clinical use. PMID:25077998

  16. Lysophosphatidic acid receptor 1 antagonist ki16425 blunts abdominal and systemic inflammation in a mouse model of peritoneal sepsis.

    PubMed

    Zhao, Jing; Wei, Jianxin; Weathington, Nathaniel; Jacko, Anastasia M; Huang, Hai; Tsung, Allan; Zhao, Yutong

    2015-07-01

    Lysophosphatidic acid (LPA) is a bioactive lipid mediator of inflammation via the LPA receptors 1-6. We and others have previously described proinflammatory and profibrotic activities of LPA signaling in bleomycin- or lipopolysaccharide (LPS)-induced pulmonary fibrosis or lung injury models. In this study, we investigated if LPA signaling plays a role in the pathogenesis of systemic sepsis from an abdominal source. We report here that antagonism of the LPA receptor LPA1 with the small molecule ki16425 reduces the severity of abdominal inflammation and organ damage in the setting of peritoneal endotoxin exposure. Pretreatment of mice with intraperitoneal ki16425 eliminates LPS-induced peritoneal neutrophil chemokine and cytokine production, liver oxidative stress, liver injury, and cellular apoptosis in visceral organs. Mice pretreated with ki16425 are also protected from LPS-induced mortality. Tissue myeloperoxidase activity is not affected by LPA1 antagonism. We have shown that LPA1 is associated with LPS coreceptor CD14 and the association is suppressed by ki16425. LPS-induced phosphorylation of protein kinase C ? (PKC?) and p38 mitogen-activated protein kinase (p38 MAPK) in liver cells and interleukin 6 production in Raw264 cells are likewise blunted by LPA1 antagonism. These studies indicate that the small molecule inhibitor of LPA1, ki16425, suppresses cytokine responses and inflammation in a peritoneal sepsis model by blunting downstream signaling through the LPA1-CD14-toll-like receptor 4 receptor complex. This anti-inflammatory effect may represent a therapeutic strategy for the treatment of systemic inflammatory responses to infection of the abdominal cavity. PMID:25701366

  17. Status of plasma folate after folic acid fortification of the food supply in pregnant African American women and the influences of diet, smoking, and alcohol consumption1-3

    Microsoft Academic Search

    Ken D Stark; Robert J Pawlosky; Skadi Beblo; Mahadev Murthy; Vincent P Flanagan; James Janisse; Michelle Buda-Abela; Helaine Rockett; Janice E Whitty; Robert J Sokol; John H Hannigan; Norman Salem Jr

    Background: African American women and socioeconomically challengedwomenareatriskofcompromisedfolatestatusand,thus, of folate-related birth defects. Data are limited on circulating folate concentrationsinpregnantAfricanAmericanwomenafterfolicacid fortification of the food supply was implemented. Objective:Theobjectivewastodeterminetheinfluenceofsmoking and alcohol consumption on plasma 5-methyltetrahydrofolic acid (5-MTHFA) concentrations in pregnant African American women. Design: Alcohol consumption, smoking exposure, and other char- acteristics of pregnant African American women reporting to an inner-city antenatal clinic

  18. The neuroprotective and hypothermic effect of GYKI-52466, a non-competitive ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-antagonist on histological and behavioural variables in the gerbil global ischemia model

    Microsoft Academic Search

    István Gyertyán; Gábor Gigler; Annamária Simó

    1999-01-01

    The neuroprotective activity of the non-competitive ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist GYKI-52466 (1-[4-aminophenyl]-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepine HCl; EGIS-8159) was studied in the gerbil bilateral carotid occlusion (BCO) model of global ischemia. Drug effect on hippocampal CA1 neuronal loss, hypermotility, and cognitive deficit (decrease in spontaneous alternation (SA) behaviour in the Y-maze) induced by 5-min or 3-min BCO were measured. GYKI-52466 was administered at 4

  19. Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor.

    PubMed

    Gunthorpe, Martin J; Hannan, Sara Luis; Smart, Darren; Jerman, Jeffrey C; Arpino, Sandra; Smith, Graham D; Brough, Stephen; Wright, Jim; Egerton, Julie; Lappin, Sarah C; Holland, Vicky A; Winborn, Kim; Thompson, Mervyn; Rami, Harshad K; Randall, Andrew; Davis, John B

    2007-06-01

    Vanilloid receptor-1 (TRPV1) is a nonselective cation channel, predominantly expressed by sensory neurons, which plays a key role in the detection of noxious painful stimuli such as capsaicin, acid, and heat. TRPV1 antagonists may represent novel therapeutic agents for the treatment of a range of conditions including chronic pain, migraine, and gastrointestinal disorders. Here we describe the in vitro pharmacology of N-(2-bromophenyl)-N'-[((R)-1-(5-trifluoromethyl-2-pyridyl)pyrrolidin-3-yl)]urea (SB-705498), a novel TRPV1 antagonist identified by lead optimization of N-(2-bromophenyl)-N'-[2-[ethyl(3-methylphenyl)amino]ethyl]urea (SB-452533), which has now entered clinical trials. Using a Ca(2+)-based fluorometric imaging plate reader (FLIPR) assay, SB-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the human TRPV1 receptor (pK(i) = 7.6) with activity at rat (pK(i) = 7.5) and guinea pig (pK(i) = 7.3) orthologs. Whole-cell patch-clamp electrophysiology was used to confirm and extend these findings, demonstrating that SB-705498 can potently inhibit the multiple modes of receptor activation that may be relevant to the pathophysiological role of TRPV1 in vivo: SB-705498 caused rapid and reversible inhibition of the capsaicin (IC(50) = 3 nM)-, acid (pH 5.3)-, or heat (50 degrees C; IC(50) = 6 nM)-mediated activation of human TRPV1 (at -70 mV). Interestingly, SB-705498 also showed a degree of voltage dependence, suggesting an effective enhancement of antagonist action at negative potentials such as those that might be encountered in neurons in vivo. The selectivity of SB-705498 was defined by broad receptor profiling and other cellular assays in which it showed little or no activity versus a wide range of ion channels, receptors, and enzymes. SB-705498 therefore represents a potent and selective multimodal TRPV1 antagonist, a pharmacological profile that has contributed to its definition as a suitable drug candidate for clinical development. PMID:17392405

  20. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists I.

    PubMed

    Alonso, Juan Antonio; Andrés, Miriam; Bravo, Mónica; Buil, Maria Antonia; Calbet, Marta; Castro, Jordi; Eastwood, Paul R; Eichhorn, Peter; Esteve, Cristina; Gómez, Elena; González, Jacob; Mir, Marta; Petit, Silvia; Roberts, Richard S; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere; Zanuy, Miriam

    2014-11-01

    A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure-kinetic relationships (SKR) opened up the possibility of long receptor residence times. PMID:25437504

  1. Excitatory amino acid receptor subtype agonists induce feeding in the nucleus accumbens shell in rats: opioid antagonist actions and interactions with ?-opioid agonists

    Microsoft Academic Search

    Joyce A Echo; Nicole Lamonte; Garrison Christian; Vladimir Znamensky; Tsippa F Ackerman; Richard J Bodnar

    2001-01-01

    Administration of ?-opioid receptor subtype agonists into the nucleus accumbens shell elicits feeding which is dependent upon the normal function of ?-, ?- and ?-opioid receptors, D1 dopamine receptors and GABAB receptors in the nucleus accumbens shell for its full expression. Whereas the AMPA antagonist, DNQX administered into the nucleus accumbens shell elicits a transient, though intense feeding response, feeding

  2. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: lead optimization.

    PubMed

    Alonso, Juan Antonio; Andrés, Miriam; Bravo, Mónica; Calbet, Marta; Eastwood, Paul R; Eichhorn, Peter; Esteve, Cristina; Ferrer, Manel; Gómez, Elena; González, Jacob; Mir, Marta; Moreno, Imma; Petit, Silvia; Roberts, Richard S; Sevilla, Sara; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere; Zanuy, Miriam

    2014-11-01

    Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles. PMID:25437505

  3. Studies on an (S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid (AMPA) Receptor Antagonist IKM-159: Asymmetric Synthesis, Neuroactivity, and Structural Characterization

    PubMed Central

    Juknait?, Lina; Sugamata, Yutaro; Tokiwa, Kazuya; Ishikawa, Yuichi; Takamizawa, Satoshi; Eng, Andrew; Sakai, Ryuichi; Pickering, Darryl S.; Frydenvang, Karla; Swanson, Geoffrey T.; Kastrup, Jette S.; Oikawa, Masato

    2015-01-01

    IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors. PMID:23432124

  4. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...285, 2101 Constitution Ave. NW., Washington, DC 20055 (Internet address http://www.nap.edu ), or may be examined...Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and...

  5. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...285, 2101 Constitution Ave. NW., Washington, DC 20055 (Internet address http://www.nap.edu ), or may be examined...Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and...

  6. Folic acid in the prevention of neural tube defects

    Microsoft Academic Search

    J. M. Scott; P. N. Kirke; D. G. Weir

    1992-01-01

    Failure of the embryonal neural tube to close gives rise to a group of severe congenital malformations known as neural tube defects (NTD). These anomalies include spina bifida, anenceph~us, encephalocoele and inencephaly. The prevalence rate at birth* of NTD in the Eastern Health Board area was 2.3 per 1,000 births in 19871 . The neural tube closes between 24 and

  7. Folates and Folic Acid: From Fundamental Research Toward Sustainable Health

    Microsoft Academic Search

    Dieter Blancquaert; Sergei Storozhenko; Karen Loizeau; Hans De Steur; Veerle De Brouwer; Jacques Viaene; Stéphane Ravanel; Fabrice Rébeillé; Willy Lambert; Dominique Van Der Straeten

    2010-01-01

    Folates are of paramount importance in one-carbon metabolism of most organisms. Plants and microorganisms are able to synthesize folates de novo, making them the main dietary source for humans and animals, which are dependent on food or feed supplies for folates. Folate deficiency is an increasing problem in the developing, as well as in the developed regions of the world,

  8. The pathogenesis of folic acid deficiency in man

    Microsoft Academic Search

    D. G. Weir

    1974-01-01

    ACH year in this lecture we honour the name of Dr. Robert Graves, a physician, writer and philosopher of the early nineteenth century. The lustre his name has added to Irish medicine throughout the world needs no elaboration. I must however confess that I was pleasantly surprised to learn of the approbation with which he was received by his contemporary

  9. Uracil misincorporation into DNA and folic acid supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Folate deficiency decreases thymidylate synthesis from deoxyuridylate, which results in an imbalance of deoxyribonucleotide that may lead to excessive uracil misincorporation (UrMis) into DNA during replication and repair. OBJECTIVE: We evaluated the relation between UrMis in different ...

  10. Role of two different guanine nucleotide-binding proteins in the antagonistic modulation of the S-type K+ channel by cAMP and arachidonic acid metabolites in Aplysia sensory neurons.

    PubMed Central

    Volterra, A; Siegelbaum, S A

    1988-01-01

    The role of guanine nucleotide-binding proteins (G proteins) in the cAMP-dependent action of serotonin (5-HT) and the antagonistic action of the neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF-amide), mediated by the lipoxygenase metabolites of arachidonic acid, was investigated in Aplysia sensory neurons. Intracellular injection of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) mimics the hyperpolarizing action of FMRF-amide due to activation of the S K+ current and alters the transient response to FMRF-amide into an irreversible (or only partially reversible) response. At higher concentrations, GTP[gamma-S] occludes the response to FMRF-amide. Injection of activated pertussis toxin inhibits the response to FMRF-amide but not to 5-HT. Injection of guanosine 5'-[beta-thio]diphosphate inhibits the response to FMRF-amide by approximately equal to 50% and completely blocks the response to 5-HT. Three lines of evidence suggest that the FMRF-amide-activated G protein is involved at an early stage of the arachidonic acid cascade, prior to the release of arachidonate. (i) Pertussis toxin injection blocks the hyperpolarizing response to FMRF-amide but not to exogenously applied arachidonic acid. (ii) Two blockers of the arachidonic acid cascade inhibit the hyperpolarizing responses to both FMRF-amide and GTP[gamma-S] (and unmask a 5-HT-like depolarizing response to the nucleotide). (iii) Concentrations of GTP[gamma-S] that alter the kinetics of the FMRF-amide response have no effect on the hyperpolarizing response to arachidonic acid. We conclude that a pertussis toxin-sensitive G protein most likely acts to couple the FMRF-amide receptor to phospholipase activation and arachidonic acid release, whereas a pertussis toxin-insensitive G protein couples the 5-HT receptor to adenylate cyclase. PMID:2845423

  11. Maternal supplementation of omega 3 fatty acids to micronutrient-imbalanced diet improves lactation in rat

    Microsoft Academic Search

    Kamini D. Dangat; Anvita A. Kale; Sadhana R. Joshi

    2011-01-01

    The present study aims to examine the effect of maternal supplementation of omega 3 fatty acids to a micronutrient (folic acid and vitamin B12)-imbalanced diet on gastric milk volume and long-chain polyunsaturated fatty acid composition. Pregnant female rats were divided into 6 groups at 2 levels of folic acid in both the presence and absence of vitamin B12. Both vitamin

  12. Synergistic and antagonistic effects between halide ions and carboxymethyl cellulose for the corrosion inhibition of mild steel in sulphuric acid solution

    Microsoft Academic Search

    S. A. Umoren; M. M. Solomon; I. I. Udosoro; A. P. Udoh

    2010-01-01

    The corrosion and corrosion inhibition effect of carboxymethyl cellulose (CMC) for mild steel in sulphuric acid medium was\\u000a investigated using chemical (weight loss and hydrogen evolution) techniques at 30–60 °C. The effect of addition of halide\\u000a ions (Cl?, Br?, and I?) was also studied. It was found that CMC functions as an inhibitor for acid induced corrosion for mild steel. Inhibition

  13. Perampanel, an antagonist of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, for the treatment of epilepsy: studies in human epileptic brain and nonepileptic brain and in rodent models.

    PubMed

    Zwart, R; Sher, E; Ping, X; Jin, X; Sims, J R; Chappell, A S; Gleason, S D; Hahn, P J; Gardinier, K; Gernert, D L; Hobbs, J; Smith, J L; Valli, S N; Witkin, J M

    2014-10-01

    Perampanel [Fycompa, 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile hydrate 4:3; Eisai Inc., Woodcliff Lake, NJ] is an AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist used as an adjunctive treatment of partial-onset seizures. We asked whether perampanel has AMPA receptor antagonist activity in both the cerebral cortex and hippocampus associated with antiepileptic efficacy and also in the cerebellum associated with motor side effects in rodent and human brains. We also asked whether epileptic or nonepileptic human cortex is similarly responsive to AMPA receptor antagonism by perampanel. In rodent models, perampanel decreased epileptic-like activity in multiple seizure models. However, doses of perampanel that had anticonvulsant effects were within the same range as those engendering motor side effects. Perampanel inhibited native rat and human AMPA receptors from the hippocampus as well as the cerebellum that were reconstituted into Xenopus oocytes. In addition, with the same technique, we found that perampanel inhibited AMPA receptors from hippocampal tissue that had been removed from a patient who underwent surgical resection for refractory epilepsy. Perampanel inhibited AMPA receptor-mediated ion currents from all the tissues investigated with similar potency (IC50 values ranging from 2.6 to 7.0 ?M). Cortical slices from the left temporal lobe derived from the same patient were studied in a 60-microelectrode array. Large field potentials were evoked on at least 45 channels of the array, and 10 ?M perampanel decreased their amplitude and firing rate. Perampanel also produced a 33% reduction in the branching parameter, demonstrating the effects of perampanel at the network level. These data suggest that perampanel blocks AMPA receptors globally across the brain to account for both its antiepileptic and side-effect profile in rodents and epileptic patients. PMID:25027316

  14. Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig.

    PubMed

    Barthó, Lorand; Undi, Sarolta; Benkó, Rita; Wolf, Matyas; Lázár, Zsofia; Lénárd, Laszlo; Maggi, Carlo A

    2006-05-01

    Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the gastrointestinal tract. The present study examined the motor effects of exogenous ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and the influence of drugs on the ATP-induced responses. High micromolar concentrations of ATP caused two types of contraction, a phasic, cholinergic response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M, respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M) caused guanethidine-resistant relaxation. This response was not influenced by tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5) M), in a surmountable manner. A high degree of tachyphylaxis was observed with the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M) of PPADS failed to influence ileum contractions to exogenous acetylcholine or histamine. It is concluded that, in addition to its direct contractile action in the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic neurones, an effect whose mechanism is largely different from that of alpha,beta-methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor-mediated effect on the smooth muscle. All motor effects of ATP are inhibited by the antagonist PPADS. PMID:16635108

  15. Discovery of trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid: an orally active, selective very late antigen-4 antagonist.

    PubMed

    Muro, Fumihito; Iimura, Shin; Sugimoto, Yuuichi; Yoneda, Yoshiyuki; Chiba, Jun; Watanabe, Toshiyuki; Setoguchi, Masaki; Iigou, Yutaka; Matsumoto, Keiko; Satoh, Atsushi; Takayama, Gensuke; Taira, Tomoe; Yokoyama, Mika; Takashi, Tohru; Nakayama, Atsushi; Machinaga, Nobuo

    2009-12-24

    We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety results in improvement of the PK profile. Consequently, our efforts have led to the discovery of trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (14e) with potent activity (IC(50) = 5.4 nM) and significantly improved bioavailability in rats, dogs, and monkeys (100%, 91%, 68%), which demonstrated excellent oral efficacy in murine and guinea pig models of asthma. Based on its overall profile, compound 14e was progressed into clinical trails. In a single ascending-dose phase I clinical study, compound 14e exhibited favorable oral exposure as expected and had no serious adverse events. PMID:19891440

  16. Opioid Antagonist Impedes Exposure.

    ERIC Educational Resources Information Center

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  17. Tandem antagonistic games

    Microsoft Academic Search

    Weijun Huang; Jewgeni H. Dshalalow

    2009-01-01

    We study an antagonistic sequential game of two players that undergoes two phases. Each phase is modeled by multi-dimensional random walk processes. During phase 1 (or game 1), the players exchange a series of random strikes of random magnitudes. Game 1 ends whenever one of the players sustains damages in excess of some lower threshold. However, the total damage does

  18. History of calcium antagonists.

    PubMed

    Fleckenstein, A

    1983-02-01

    The discovery of Ca++ antagonism as a new principle of action of coronary drugs reaches back to 1964, when we reported that two new compounds, later given the generic names verapamil (Iproveratril) and prenylamine, mimicked the cardiac effects of simple Ca++ withdrawal in that they diminished Ca++-dependent high energy phosphate utilization, contractile force, and oxygen requirement of the beating heart without impairing the Na+-dependent action potential parameters. Since these effects, clearly distinguishable from beta-receptor blockade, could promptly be neutralized with elevated Ca++, beta-adrenergic catecholamines, or cardiac glycosides, measures that restored the Ca++ supply to the contractile system, we introduced in 1969 the term Ca++ antagonist as a novel drug designation. In an extensive search for other Ca++ antagonists, a considerable number of substances that also met these criteria were identified in our laboratory, i.e., D 600, nifedipine, niludipine, nimodipine, perhexiline, fendiline, terodiline. In 1975 Japanese pharmacologists contributed diltiazem to this group. According to our studies, all specific Ca++ antagonists interfere with the uptake of labelled Ca++ into the myocardium and prevent myocardial necrotization arising from deleterious intracellular Ca++ overload; they also block excitation-contraction coupling of vascular smooth muscle, and in this manner, lower Ca++-dependent coronary vascular tone and neutralize all types of experimental coronary spasms. According to our voltage-clamp studies, these antagonists basically act as specific inhibitors of the slow transsarcolemmal Ca++ influx but do not (or only slightly) affect the fast Na+ current that initiates normal myocardial excitation. However, Ca++ antagonists can counteract SA and AV nodal automaticity, AV conduction, and ectopic impulse discharge because, in these cases, Ca++ ions necessarily act as transmembrane electric charge carriers. PMID:6339106

  19. Acid-induced sweetness of neoculin is ascribed to its pH-dependent agonistic-antagonistic interaction with human sweet taste receptor

    Microsoft Academic Search

    Ken-ichiro Nakajima; Yuji Morita; Ayako Koizumi; Tomiko Asakura; Tohru Terada; Keisuke Ito; Akiko Shimizu-Ibuka; Jun-ichi Maruyama; Katsuhiko Kitamoto; Takumi Misaka; Keiko Abe

    2008-01-01

    Neoculin (NCL) is a sweet protein that also has taste-modifying activity to convert sourness to sweetness. However, it has been unclear how NCL induces this unique sensation. Here we quantitatively evaluated the pH-dependent acid-induced sweetness of NCL using a cell-based assay system. The human sweet taste receptor, hT1R2-hT1R3, was functionally ex- pressed in HEK293T cells together with G protein. When

  20. Effect of 3-cyclopropyl-1-enlyl-propanoic acid sodium salt, a novel water soluble antagonist of ethylene action, on plant responses to ethylene

    Microsoft Academic Search

    Raphael Goren; Moshe Huberman; Joseph Riov; Eliezer E. Goldschmidt; Edward C. Sisler; Akiva Apelbaum

    A novel water soluble inhibitor of ethylene action, 3-cyclopropyl-1-enyl-propanoic acid sodium salt [(CPAS) Patent Application\\u000a number: PCT\\/IL2008\\/000995, US Application number 61\\/144758, International publication number: WO 2009\\/010981 AI] was synthesized\\u000a in a highly purified form, and its effect to retard various exogenous or endogenous ethylene-mediated processes was tested.\\u000a The inhibitor was applied by loading, dipping or spraying. CPAS retarded some ripening

  1. A Matched Case-Control Study of a Novel Acid-Pump Antagonist and Proton-Pump Inhibitor for the Treatment of Iatrogenic Ulcers Caused by Endoscopic Submucosal Dissection

    PubMed Central

    Kim, Yong Gil; Kim, Tae Nyeun

    2010-01-01

    Background/Aims Revaprazan, a novel acid-pump antagonist, and proton-pump inhibitors (PPIs) have pH-independent effects on ulcer healing. The addition of a PPI promotes the cell restitution rate as well as vessel regeneration and maturation for ulcer repair. Revaprazan is known to protect the mucosa by increasing the prostaglandin concentration. Methods We reviewed the medical records of patients who underwent endoscopic submucosal dissection (ESD) for gastric neoplasia at Yeungnam University Hospital between January 2008 and May 2009. We conducted a matched case-control study to compare the healing rates effected by revaprazan and rabeprazole. Results Each group consisted of 30 patients. The baseline characteristics did not differ significantly between the two groups. Stage S1 disease was observed in 97% and 100% of patients after 8 weeks of treatment in the revaprazan and rabeprazole groups, respectively. In the revaprazan group, only one patient had stage H2 disease: a 54-year-old man with a 5.5-cm lesion after ESD of the ulcer, type IIa early gastric cancer, and adenocarcinoma. No serious adverse effects occurred during the treatment period in either group. Conclusions The safety and efficacy profiles of revaprazan and rabeprazole are similar for the treatment of ESD-induced ulcers. PMID:20479909

  2. Global and regional cerebral metabolic rate of 2-[18F]fluoro-2-deoxy-D-glucose in the presence of ofloxacin, a gamma-aminobutyric acid a receptor antagonist.

    PubMed Central

    Camargo, E E; Sostre, S; Sadzot, B; Shafique, I; Szabo, Z; Links, J M; Dannals, R F; Wagner, H N

    1991-01-01

    We investigated the effects of ofloxacin, a new antibacterial quinolone gamma-aminobutyric acid A receptor antagonist, on the global and regional cerebral metabolic rates of glucose (cMRgl). Twelve healthy normal male volunteers (mean age, 26.7 years) were studied in a double-blind, placebo-controlled protocol of 11 days' duration. Results of a total of 42 positron emission tomography studies were obtained for these subjects: 12 base line, 18 during placebo, and 12 during ofloxacin administration. The conditions under which repeat positron emission tomography studies of the same subject were performed were reproduced as closely as possible. cMRgl was measured in 24 brain regions. The global cMRgl for base line, placebo, and ofloxacin were 8.82 +/- 1.17, 8.24 +/- 1.17, and 8.79 +/- 1.18 mg/min/100 g, respectively (mean +/- 1 standard deviation). The mean global differences between base line and placebo and between ofloxacin and placebo were 5.1 and 6.6%, respectively. Analysis of variance of both the global and the regional cMRgl showed no statistical difference between base-line, placebo, and ofloxacin studies. Variations in cMRgl found in this study were not related to the presence of ofloxacin. Results of our study demonstrate that ofloxacin does not increase or decrease cMRgl beyond the limits of variability of the study. PMID:1648886

  3. LXR antagonists induce ABCD2 expression.

    PubMed

    Gondcaille, Catherine; Genin, Emmanuelle C; Lopez, Tatiana E; Dias, Alexandre M M; Geillon, Flore; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Nury, Thomas; Lizard, Gérard; Weinhofer, Isabelle; Berger, Johannes; Kase, Eili T; Trompier, Doriane; Savary, Stéphane

    2014-02-01

    X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a beta-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCDI gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their beta-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative therapy for X-ALD patients. Since LXR activation was shown to repress ABCD2 expression, we investigated the effects of LXR antagonists in different cell lines. Cells were treated with GSK(17) (a LXR antagonist recently discovered from the GlaxoSmithKline compound collection), 22(S)-hydroxycholesterol (22S-HC, another LXR antagonist) and 22R-HC (an endogenous LXR agonist). We observed up-regulation of ABCD2,ABCD3 and CTNNB1 (the gene encoding for beta-catenin, which was recently demonstrated to induce ABCD2 expression) in human HepG2 hepatoma cells and in X-ALD skin fibroblasts treated with LXR antagonists. Interestingly, induction in X-ALD fibroblasts was concomitant with a decrease in oxidative stress. Rats treated with 22S-HC showed hepatic induction of the 3 genes of interest. In human, we show by multiple tissue expression array that expression of ABCD2 appears to be inversely correlated with NR1H3 (LXRalpha) expression. Altogether, antagonists of LXR that are currently developed in the context of dyslipidemia may find another indication with X-ALD. PMID:24239766

  4. Xanthines as Adenosine Receptor Antagonists

    Microsoft Academic Search

    Christa E. Müller; Kenneth A. Jacobson

    \\u000a The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the\\u000a literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogues were subsequently\\u000a synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of\\u000a the four AR subtypes.

  5. Fosinopril H(2)-receptor antagonists interaction studies by derivative spectroscopy.

    PubMed

    Sultana, Najma; Arayne, M Saeed; Sana, Aisha

    2007-01-01

    Fosinopril sodium, a phosphinic acid derivative is an angiotensin converting enzyme (ACE) inhibitor, which had been employed for the treatment of hypertension and congestive heart failure; long tem use of ACE inhibitor often result in stress ulcers due to which H(2) receptor antagonists are also concurrently prescribed. The later compete with histamine for H(2) receptors and block gastric acid secretion and some cardiovascular effects of histamine. Our studies are focused on the in vitro availability of fosinopril in presence of commonly used H(2) receptor antagonists. Derivative spectroscopy has been employed for the quantitation of fosinopril and H(2) receptor antagonists followed by linear regression analysis. These studies were carried out in buffers of pH 7.4 and 9 at 37, 48 and 60( masculine)C. Stability constant and thermodynamic function had also been calculated in order to evaluate the reaction mechanism. Commonly prescribed H(2) receptor antagonists like cimetidine, ranitidine and famotidine were used in these studies. Present study clearly indicated that most of the H(2) receptor antagonists studied decreased the availability of fosinopril which conclude that availability of fosinopril can be affected by the concurrent administration of H(2) receptor antagonists. PMID:17337423

  6. Biomolecular recognition of antagonists by ?7 nicotinic acetylcholine receptor: Antagonistic mechanism and structure-activity relationships studies.

    PubMed

    Peng, Wei; Ding, Fei

    2015-08-30

    As the key constituent of ligand-gated ion channels in the central nervous system, nicotinic acetylcholine receptors (nAChRs) and neurodegenerative diseases are strongly coupled in the human species. In recently years the developments of selective agonists by using nAChRs as the drug target have made a large progress, but the studies of selective antagonists are severely lacked. Currently these antagonists rest mainly on the extraction of partly natural products from some animals and plants; however, the production of these crude substances is quite restricted, and artificial synthesis of nAChR antagonists is still one of the completely new research fields. In the context of this manuscript, our primary objective was to comprehensively analyze the recognition patterns and the critical interaction descriptors between target ?7 nAChR and a series of the novel compounds with potentially antagonistic activity by means of virtual screening, molecular docking and molecular dynamics simulation, and meanwhile these recognition reactions were also compared with the biointeraction of ?7 nAChR with a commercially natural antagonist - methyllycaconitine. The results suggested clearly that there are relatively obvious differences of molecular structures between synthetic antagonists and methyllycaconitine, while the two systems have similar recognition modes on the whole. The interaction energy and the crucially noncovalent forces of the ?7 nAChR-antagonists are ascertained according to the method of Molecular Mechanics/Generalized Born Surface Area. Several amino acid residues, such as B/Tyr-93, B/Lys-143, B/Trp-147, B/Tyr-188, B/Tyr-195, A/Trp-55 and A/Leu-118 played a major role in the ?7 nAChR-antagonist recognition processes, in particular, residues B/Tyr-93, B/Trp-147 and B/Tyr-188 are the most important. These outcomes tally satisfactorily with the discussions of amino acid mutations. Based on the explorations of three-dimensional quantitative structure-activity relationships, the structure-antagonistic activity relationships of antagonists and the characteristics of ?7 nAChR-ligand recognitions were received a reasonable summary as well. These attempts emerged herein would not only provide helpful guidance for the design of ?7 nAChR antagonists, but shed new light on the subsequent researches in antagonistic mechanism. PMID:25963024

  7. Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents.

    PubMed

    Shah, Kiran; Patel, Dipam; Jadav, Pradip; Sheikh, Mubeen; Sairam, Kalapatapu V V M; Joharapurkar, Amit; Jain, Mukul R; Bahekar, Rajesh

    2012-09-15

    Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity. These preliminary results confirm discovery of potent and liver selective passive GR antagonist for the treatment of T2DM. PMID:22917520

  8. Effect of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy)benzamido)ethyl) benzoic acid (CJ-42794), a selective antagonist of prostaglandin E receptor subtype 4, on ulcerogenic and healing responses in rat gastrointestinal mucosa.

    PubMed

    Takeuchi, Koji; Tanaka, Akiko; Kato, Shinichi; Aihara, Eitaro; Amagase, Kikuko

    2007-09-01

    Recent research showed the involvement of prostaglandin E receptor subtype 4 (EP4) in hypersensitivity to inflammatory pain and suggested that the EP4 receptor is a potential target for the pharmacological treatment of inflammatory pain. We examined the effects of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy) benzamido)ethyl) benzoic acid (CJ-42794), a selective EP4 antagonist, on gastrointestinal ulcerogenic and healing responses in rats, in comparison with those of various cyclooxygenase (COX) inhibitors. CJ-42794 alone, given p.o., did not produce any damage in the gastrointestinal mucosa, similar to 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) (COX-1 inhibitor) or rofecoxib (COX-2 inhibitor), whereas indomethacin (nonselective COX inhibitor) caused gross lesions. Rofecoxib but not CJ-42794, however, damaged these tissues when coadministered with SC-560 and aggravated gastric lesions produced by aspirin. Indomethacin and SC-560 worsened the gastric ulcerogenic response to cold-restraint stress, yet neither CJ-42794 nor rofecoxib had any effect. Furthermore, indomethacin and SC-560 at lower doses damaged the stomach and small intestine of adjuvant arthritic rats. In arthritic rats, rofecoxib but not CJ-42794 provoked gastric ulceration, whereas CJ-42794 produced little damage in the small intestine. The repeated administration of CJ-42794 and rofecoxib as well as indomethacin impaired the healing of chronic gastric ulcers with a down-regulation of vascular endothelial growth factor expression in the ulcerated mucosa. These results suggest that CJ-42794 does not cause any damage in the normal rat gastrointestinal mucosa and in the arthritic rat stomach and does not worsen the gastric ulcerogenic response to stress or aspirin in normal rats, although this agent slightly damages the small intestine of arthritic rats and impairs the healing of gastric ulcers. PMID:17578900

  9. Role of vasopressin antagonists.

    PubMed

    Torres, Vicente E

    2008-07-01

    Alterations in intracellular calcium homeostasis and cyclic adenosine 3',5'-phosphate likely underlie the increased cell proliferation and fluid secretion in polycystic kidney disease. Hormone receptors that affect cyclic adenosine 3',5'-phosphate and are preferentially expressed in affected tissues are logical treatment targets. There is a sound rationale for considering the arginine vasopressin V2 receptor as a target. The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2-/WS25 mice), and nephronophthisis(pcy mouse). PCK rats that are homozygous for an arginine vasopressin mutation and lack circulating vasopressin are markedly protected. Administration of V2 receptor agonist 1-deamino-8-D-arginine vasopressin to these animals completely recovers the cystic phenotype. Administration of 1-deamino-8-D-arginine vasopressin to PCK rats with normal arginine vasopressin aggravates the disease. Suppression of arginine vasopressin release by high water intake is protective. V2 receptor antagonists may have additional beneficial effects on hypertension and chronic kidney disease progression. A number of clinical studies in polycystic kidney disease have been performed or are currently active. The results of phase 2 and 2-3 studies indicate that tolvaptan seems to be safe and well tolerated in autosomal dominant polycystic kidney disease. A phase 3,placebo-controlled, double-blind study in 18- to 50-yr-old patients with autosomal dominant polycystic kidney disease and preserved renal function but relatively rapid progression, as indicated by a total kidney volume >750 ml, has been initiated. PMID:18434616

  10. n -3 Fatty acids plus oleic acid and vitamin supplemented milk consumption reduces total and LDL cholesterol, homocysteine and levels of endothelial adhesion molecules in healthy humans

    Microsoft Academic Search

    L. BARÓ; J. FONOLLÁ; J. L. PEÑA; A. MARTÍNEZ-FÉREZ; A. LUCENA; J. JIMÉNEZ; J. J. BOZA; E. LÓPEZ-HUERTAS

    2003-01-01

    Background and aims: Numerous studies suggest n -3 polyunsaturated fatty acids (n -3 PUFA) and oleic acid intake have beneficial effects on health including risk reduction of coronary heart disease. The purpose of this study was to evaluate the effect of a commercially available skimmed milk supplemented with n -3 PUFA, oleic acid, and vitamins E, B6, and folic acid

  11. Synthesis of enantiomerically pure pyrrolidinones as endothelin receptor antagonists

    Microsoft Academic Search

    Shripad S. Bhagwat; Candido Gude; Kenneth Chan

    1996-01-01

    Enantiomerically pure pyrrolidinones were synthesized as endothelin receptor antagonists. A [2+2] cycloaddition of an imine and an enantiomerically pure acid chloride gave two diastereomeric ?-lactams which were separated and rearranged to give the enantiomerically pure pyrrolidinones which could be reduced to give the corresponding pyrrolidines.

  12. Effects of fibrinogen receptor antagonist GR144053F and aurintricarboxylic acid on platelet activation and degranulation 1 1 Abbreviations: ACD, citric acid\\/trisodium citrate\\/glucose (recipe A), blood anticoagulant; ATA, aurintricarboxylic acid; CT CADP, closure (occlusion) time determined with the use of collagen\\/ADP cassettes in PFA100; GPIb-IX-V, a complex of glycoproteins Ib, IX, and V, a vWF receptor; GPIIb-IIIa, a complex of glycoproteins IIb and IIIa, a fibrinogen receptor; ic 50, the concentration of an inhibitor, at which 50% of the maximal estimated inhibition occurred; the extent of maximal inhibition was calculated based on the mathematical resolving of the equation describing the inhibition of platelet aggregation; PE, R-phycoerythrin; PFA100™, platelet function analyzer; PRP, platelet-rich plasma; RGD, Arg-Gly-Asp; PBS, phosphate-buffered saline; TRAP, thrombin receptor activating peptide, SFLLRNPNDKYEPF; and vWF, von Willebrand factor

    Microsoft Academic Search

    Marcin Rozalski; Magdalena Boncler; Jacek Golanski; Cezary Watala

    2001-01-01

    Activated blood platelets play crucial role in restenosis due to their fundamental significance in thrombus formation. Therefore, platelets are attractive targets for the inhibition with a variety of antagonists. In this study, we present direct evidence that GR144053F [non-peptide antagonist of glycoprotein IIb-IIIa complex (GPIIb-IIIa)] inhibits activation and degranulation of human platelets, and opposes the action of aurintricarboxylic acid (ATA),

  13. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists III: the role of a hydrogen-bond acceptor in long receptor residence times.

    PubMed

    Alonso, Juan Antonio; Andrés, Miriam; Bravo, Mónica; Buil, Maria Antonia; Calbet, Marta; Castro, Jordi; Eastwood, Paul R; Esteve, Cristina; Ferrer, Manel; Forns, Pilar; Gómez, Elena; González, Jacob; Lozoya, Estrella; Mir, Marta; Moreno, Imma; Petit, Silvia; Roberts, Richard S; Sevilla, Sara; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere

    2014-11-01

    The correct positioning and orientation of an hydrogen bond acceptor (HBA) in the tail portion of the biaryl series of CRTh2 antagonists is a requirement for long receptor residence time. The HBA in combination with a small steric substituent in the core section (R(core) ? H) gives access to compounds with dissociation half-lives of ? 24h. PMID:25437506

  14. The AMPA receptor antagonist GYKI 52466 reverses the anti-cataleptic effects of the competitive NMDA receptor antagonist CGP 37849

    Microsoft Academic Search

    Wolfgang Hauber; Marc T. Waldenmeier

    1994-01-01

    The effects of the AMPA receptor antagonist GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzo- diazepine HCI) on haloperidol-induced catalepsy were tested in drug-naive rats and in rats pretreated with the competitive NMDA receptor antagonist CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid). CGP 37849 (4 mg\\/kg i.p.) given alone significantly reversed haloperidol-induced catalepsy (0.5 mg\\/kg i.p.) while GYKI 52466 (4.8 mg\\/kg i.p.) given alone was without effect. Administration

  15. In vitro interactions of captopril with H2-receptor antagonists.

    PubMed

    Sultana, Najma; Arayne, M Saeed; Quraish, Reeshanul

    2007-04-01

    Captopril is effective in the treatment of hypertension of all grades of severity. H2-receptors antagonists block gastric acid secretion and some cardiovascular effects of histamine. In view of the fact that, simultaneous administration of both drugs may alter the antihypertensive effect of captopril, present paper deals with the in vitro availability studies of captopril in presence of commonly used H2-receptor antagonists like cimetidine, ranitidine and famotidine. In order to simulate various pH levels in GI tract and to find out the kinetics and energetics of captopril-H2-receptor antagonist interactions, these studies were carried out in buffers of pH 4, 7.4 and 9 at 37 degrees C and at elevated temperatures. These studies clearly indicate that most of the H2-receptor antagonists bind to captopril, forming charge-transfer complexes. As a result, the availability of captopril was affected by the concurrent administration of H2-receptor antagonists. Accordingly coadministration of both the drugs should be avoided. PMID:17416569

  16. Effective use of TNF antagonists

    Microsoft Academic Search

    David Yocum

    2004-01-01

    Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs)

  17. TARP Auxiliary Subunits Switch AMPA Receptor Antagonists into Partial Agonists

    Microsoft Academic Search

    Karen Menuz; Robert M. Stroud; Roger A. Nicoll; Franklin A. Hays

    2008-01-01

    Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity

  18. TARP Auxiliary Subunits Switch AMPA Receptor Antagonists into Partial Agonists

    Microsoft Academic Search

    Karen Menuz; Robert M. Stroud; Roger A. Nicoll; Franklin A. Hays

    2007-01-01

    Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity

  19. Further studies at neuropeptide S position 5: discovery of novel neuropeptide S receptor antagonists

    PubMed Central

    Guerrini, Remo; Camarda, Valeria; Trapella, Claudio; Calo’, Girolamo; Rizzi, Anna; Ruzza, Chiara; Fiorini, Stella; Marzola, Erika; Reinscheid, Rainer K.; Regoli, Domenico; Salvadori, Severo

    2009-01-01

    Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly5 with D-amino acids generates NPSR antagonists. Eleven [D-Xaa5]NPS derivatives were synthesized and pharmacologically tested measuring [Ca2+]i in HEK293mNPSR cells. The present results confirmed that the [D-Xaa5] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed to identify the novel potent NPSR peptide antagonist [tBu-D-Gly5]NPS. PMID:19473027

  20. Tachykinin NK 1 Receptor Antagonists

    Microsoft Academic Search

    R. Patacchini; C. A. Maggi

    \\u000a This chapter is focused on the pharmacology of most relevant tachykinin NK1 receptor-selective compounds, with emphasis on the progress ofknowledge made possible by their use and on the therapeutic\\u000a perspectives of these drugs. The first peptide antagonists of SP, synthesized about 20 years ago, were hampered by poor selectivity\\u000a for NK1 receptors and other serious side effects. Since then the