Note: This page contains sample records for the topic folic acid antagonists from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: November 12, 2013.
1

Experiments on the biological activities of various fractions of the folic acid antagonist "X-methyl" folic acid.  

PubMed

A crude synthetic preparation called crude "X-methyl" folate has previously been shown to function as a folate antagonist for rats and chicks. This product has been shown to contain two folate antagonists: 9-methyl folate, present as 6% by weight of the product and which has low activity as a folate antagonist for Streptococcus faecalis, and pyrrofolic acid, a compound present in small amounts (0.04%), but having high anti-folate biological activity for S. faecalis. These experiments deal with the antifolate activity of these two fractions for the rat as measured by their effects on histidine oxidation. Rats were fed a purified diet based on 20% vitamin-free casein and containing 1.0% sulfasuxidine. When this diet was supplemented with a marginal amount of folic acid (0.3 mg per kg diet), the addition of 4 g of crude antagonist decreased histidine oxidation and decreased liver folate levels. The addition of 240 mg of pure 9-methyl folic acid (amount of 9-methyl folic acid in 4 g of crude) produced similar decreases in histidine oxidation and liver folate levels. A concentrate of pyrrofolic acid (equivalent to 4 g of crude) free of 9-methyl folic acid produced no decrease in histidine oxidation and minimal changes in liver folate. This indicates that the folate antagonist activity observed previously with animals is probably due to the 9-methyl folic acid component rather than to the pyrrofolic acid activity. PMID:3789733

Stokstad, E L; Okinaka, O; Kusano, G

1986-11-15

2

Effects of the Teratogenic Folic Acid Antagonist, 9Methyl Pteroylglutamic Acid on Uronic Acid Levels in Fetal Rat Limbs  

Microsoft Academic Search

Experimental pregnant rats were placed on a transitory folic acid-deficient regimen, i.e. dietary restriction of folic acid plus the teratogen and folic acid antagonist, 9-methyl pteroylglutamic acid; a regimen resulting in multiple congenital skeletal malformations. Controls received a folic acid-supplemented regimen. Accumulation of a primary component of the extracellular matrix, glycosaminoglycans (GAG), was quantitatively evaluated by measuring uronic acid concentrations

B. V. Paynton; R. R. Schmidt; J. M. Cotler

1978-01-01

3

Potential Antagonist of Folic Acid Metabolism as Malarial Drugs.  

National Technical Information Service (NTIS)

The focal point of attack for drug design in the present investigation was to exploit the known differences of folic acid matabolism in man and the malarial parasite. It was therefore desirable to prepare target compounds in three series of nitrogen heter...

J. W. Jones R. Masingale

1982-01-01

4

Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes  

PubMed Central

Background In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy. Methods We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents. Results We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results. Interpretation Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.

Wen, Shi Wu; Zhou, Jia; Yang, Qiuying; Fraser, William; Olatunbosun, Olufemi; Walker, Mark

2008-01-01

5

Facts about Folic Acid  

MedlinePLUS

... INFO (800-232-4636) TTY: (888) 232-6348 Contact CDC-INFO flo@cdc.gov Folic Acid Homepage Facts Quiz Questions & Answers Cereals with Folic Acid Data and Statistics Research Global Initiative Articles & Key Findings Recommendations Free Materials Links ...

6

Folic Acid Quiz  

MedlinePLUS

... INFO (800-232-4636) TTY: (888) 232-6348 Contact CDC-INFO flo@cdc.gov Folic Acid Homepage Facts Quiz Questions & Answers Cereals with Folic Acid Data and Statistics Research Global Initiative Articles & Key Findings Recommendations Free Materials Links ...

7

Circulating folic acid in plasma: relation to folic acid fortification  

PubMed Central

Background The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated concentrations after fortification and the possibility of adverse effects. Objective We assessed the effect of folic acid fortification on circulating concentrations of folic acid and 5-methyltetrahydrofolate in the Framingham Offspring Cohort. Design This is a cross-sectional study that used plasma samples from fasting subjects before and after fortification. Samples were measured for folate distribution with the use of an affinity-HPLC method with electrochemical detection. Results Among nonsupplement users, the median concentration of folic acid in plasma increased from 0.25 to 0.50 nmol/L (P < 0.001) after fortification, and among supplement users the median increased from 0.54 to 0.68 nmol/L (P = 0.001). Among nonsupplement users, the prevalence of high circulating folic acid (?85th percentile) increased from 9.4% to 19.1% (P = 0.002) after fortification. Among supplement users, the prevalence of high circulating folic acid increased from 15.9% to 24.3% (P = 0.02). Folic acid intake and total plasma folate were positively and significantly related to high circulating folic acid after adjustment for potential confounding factors (P for trend < 0.001). Conclusions Folic acid fortification has resulted in increased exposure to circulating folic acid. The biochemical and physiologic consequences of this are unknown, but these findings highlight the need to understand the effects of chronic exposure to circulating folic acid.

Kalmbach, Renee D; Choumenkovitch, Silvina F; Troen, Aron M; D'Agostino, Ralph; Jacques, Paul F; Selhub, Jacob

2013-01-01

8

Folic Acid Questions and Answers  

MedlinePLUS

... INFO (800-232-4636) TTY: (888) 232-6348 Contact CDC-INFO flo@cdc.gov Folic Acid Homepage Facts Quiz Questions & Answers Cereals with Folic Acid Data and Statistics Research Global Initiative Articles & Key Findings Recommendations Free Materials Links ...

9

Ultraviolet photodegradation of folic acid  

Microsoft Academic Search

The vitamin folate is vital for all living creatures. Scientists have suggested that ultraviolet degradation of folate in vivo played a role in the evolution of mankind. In order to better understand the photodegradation of folate, we have provided a spectroscopic study of the ultraviolet photodegradation of aqueous folic acid under aerobic conditions. We found strong indications that the folic

Morten Kristian Off; Arnfinn Engeset Steindal; Alina Carmen Porojnicu; Asta Juzeniene; Alexander Vorobey; Anders Johnsson; Johan Moan

2005-01-01

10

Ultraviolet photodegradation of folic acid.  

PubMed

The vitamin folate is vital for all living creatures. Scientists have suggested that ultraviolet degradation of folate in vivo played a role in the evolution of mankind. In order to better understand the photodegradation of folate, we have provided a spectroscopic study of the ultraviolet photodegradation of aqueous folic acid under aerobic conditions. We found strong indications that the folic acid molecule is cleaved into p-aminobenzoyl-L-glutamic acid and 6-formyl pterin when exposed to ultraviolet radiation. When the irradiation continues, 6-formyl pterin is degraded to pterin-6-carboxylic acid. The photodegradation of folic acid is divided into three phases. In the first phase, the formation of photoproducts follows a zero order rate law. In the second phase the presence of photoproducts sensitizes the degradation of folic acid and the degradation process is accelerated. In the third phase the degradation of 6-formyl pterin to pterin-6-carboxylic acid is the dominating process. This reaction follows a first order rate law. We show that both 6-formyl pterin and pterin-6-carboxylic acid sensitize the photodegradation of folic acid. However, experiments performed in heavy water indicate that generation of singlet oxygen is probably not the explanation for the photosensitizing of folic acid. PMID:15963436

Off, Morten Kristian; Steindal, Arnfinn Engeset; Porojnicu, Alina Carmen; Juzeniene, Asta; Vorobey, Alexander; Johnsson, Anders; Moan, Johan

2005-04-13

11

The Effect of a Folic Acid Antagonist, AMethopterin, on the Level of the Circulating Eosinophils in Humans  

Microsoft Academic Search

W HILE THE MECHANISM of action of the fohic acid antagonists is tsot at present clearly and fully uisderstood, there is evidence of a relation- ship between these drugs and the adrenal cortex. Higgiisstm observed hyperplasia of the adrenal glands with atrophy of the spleen and thymus its rats ots autopsy, followiisg the administration of A-Methopterits. Higgins and Woods2 reported

JANE C. WRIGHT

1952-01-01

12

The in situ localization of folic acid  

Microsoft Academic Search

Synopsis  A histochemical azo-coupling method for localizing folic acidin situ is described. Cat and rat liver, kidney, bone marrow and brain were found to be rich in folic acid; stomach, intestine, salivary glands, and blood contained less. Folic acid was localized in the cytoplasm of tissues having a very active metabolism, but in the nucleus of highly specialized cells such as

Doina Onicescu; Maria Popescu; Lumini?a Ta?cå

1975-01-01

13

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...

14

Congenital isolated folic acid malabsorption.  

PubMed Central

We report a case of congenital isolated malabsorption of folic acid, the first in a boy. Only seven previous cases have been reported, and we discuss two aspects--namely, the tendency to infection, with evidence of impairment of both cellular and humoral immunity, and the absence of neurological disturbances.

Urbach, J; Abrahamov, A; Grossowicz, N

1987-01-01

15

Folic acid in diet  

MedlinePLUS

... certain types of anemias . Folate works along with vitamin B12 and vitamin C to help the body break ... Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, ...

16

Is folic acid good for everyone?  

PubMed

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 fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole. PMID:18326588

Smith, A David; Kim, Young-In; Refsum, Helga

2008-03-01

17

Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring  

Technology Transfer Automated Retrieval System (TEKTRAN)

Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use and periconceptional folic acid supplementation. The effect of maternal and postweaning folic acid supplementation on colorectal cancer risk ...

18

9Methyl Pteroylglutamic Acid, a Synthetic Analogue of Folic Acid: Its Effects on Hexosamine Levels in Fetal Rat Limbs and Other Fetal Tissues  

Microsoft Academic Search

Pregnant rats were administered the teratogen and synthetic analogue of folic acid, 9-methyl pteroylglutamic acid, on the 11th day of gestation and placed on a semi-synthetic diet containing the antagonist but lacking the vitamin until the 14th gestational day. This transitory maternal folic acid deficiency results in multiple congenital skeletal malformations. Control animals were administered a folic acid-supplemented regimen. Hexosamine

Richard R. Schmidt; Patricia K. Abbott; Jerome M. Cotler

1982-01-01

19

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2013 CFR

... 2013-04-01 2013-04-01 false Folic acid (folacin). 172.345 Section 172.345 Food...Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No. 59-30-3), also known...

2013-04-01

20

Periconceptional folic acid containing multivitamin supplementation  

Microsoft Academic Search

Objective: A summary about the final results of the Hungarian double-blind placebo controlled randomised trial of periconceptional folic acid containing multivitamin and trace element supplementation. Results: The major finding is a significant prevention of the first occurrence of neural-tube defect, urinary tract and cardiovascular defects, in addition a decrease in the rate of limb deficiencies and congenital hypertrophic pyloric stenosis.

Andrew E. Czeizel

1998-01-01

21

Neural Tube Defects, Folic Acid and Methylation  

PubMed Central

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.

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

2013-01-01

22

Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread  

PubMed Central

Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population's folic acid intake from fortified foods. Food Standards Australia New Zealand's (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200??g/100?g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159??g per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid.

Dugbaza, Jacinta; Cunningham, Judy

2012-01-01

23

Irradiation stability of folic Acid in powder and aqueous solution.  

PubMed

This study attempts to examine the folic acid stability after irradiation treatment, under different physical states, pH values, and atmosphere conditions. Aqueous folic acid samples, folic acid in powder, and wheat flour fortified with folic acid were irradiated by an electron beam (E-beam) between 0 (control) and 10.0 kGy. It was realized that the physical state of folic acid plays an important role on its stability toward E-beam processing, being largely unstable in solution, no matter the pH and atmosphere conditions assayed. Otherwise, folic acid in powder showed huge irradiation stability, even when mixed in a dry food matrix, such as fortified wheat flour samples. PMID:21275389

Araújo, Michel M; Marchioni, Eric; Bergaentzle, Martine; Zhao, Minjie; Kuntz, Florent; Hahn, Emeline; Villavicencio, Anna Lucia C H

2011-01-28

24

Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children  

PubMed Central

Objective: Gingival overgrowth is an important adverse effect of phenytoin (PHT) therapy, occurring in about half of the patients. This study aimed to evaluate the effect of oral folic acid supplementation (0.5 mg/day) for the prevention of PHT-induced gingival overgrowth (PIGO) in children with epilepsy aged 6–15 years on PHT monotherapy for 6 months. Methods: This was a randomized, double-blind, placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009. Children aged 6–15 years started on PHT monotherapy within last 1 month were eligible for inclusion. Preexisting gingival overgrowth, use of other folic acid antagonists, and macrocytic anemia were exclusion criteria. Trial subjects were randomized to receive either folic acid or placebo. The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy. The trial was registered with clinicaltrials.gov (NCT00781196). Results: A total of 120 children were recruited, 62 and 58, respectively, in folic acid and placebo arms. The 2 arms were comparable at baseline. Twenty-one percent of patients in the folic acid arm developed PIGO, as compared with 88% receiving placebo (p < 0.001). Absolute risk reduction of PIGO by folic acid was 67% (95% confidence interval 54%–80%), and relative risk reduction was 0.76. Conclusions: Oral folic acid was found to decrease the incidence of PIGO in children on PHT monotherapy, in a statistically significant and clinically relevant manner. Classification of evidence: This study provides Class I evidence that folic acid supplementation, 0.5 mg/day, is associated with prevention of gingival overgrowth in children taking PHT monotherapy.

Arya, R.; Kabra, M.; Sahu, J.K.; Kalra, V.

2011-01-01

25

Fluorescence spectroscopic behaviour of folic acid  

NASA Astrophysics Data System (ADS)

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.

Tyagi, A.; Penzkofer, A.

2010-02-01

26

Folic Acid Consumption in Fars Province, Southern Iran  

Microsoft Academic Search

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:

Massumi SJ; Shenavar R. MSc

27

Folic acid in the monkey brain: an immunocytochemical study.  

PubMed

The present report describes the first visualization of folic acid-immunoreactive fibers in the mammalian central nervous system using a highly specific antiserum directed against this vitamin. The distribution of folic acid-immunoreactive structures was studied in the brainstem and thalamus of the monkey using an indirect immunoperoxidase technique. We observed fibers containing folic acid, but no folic acid-immunoreactive cell bodies were found. In the brainstem, no immunoreactive structures were visualized in the medulla oblongata, pons, or in the medial-caudal mesencephalon, since at this location immunoreactive fibers containing folic acid were only found at the rostral level in the dorsolateral mesencephalon (in the mesencephalic-diencephalic junction). In the thalamus, the distribution of folic acid-immunoreactive structures was more widespread. Thus, we found immunoreactive fibers in the midline, in nuclei close to the midline (dorsomedial nucleus, centrum medianum/parafascicular complex), in the ventral region of the thalamus (ventral posteroinferior nucleus, ventral posteromedial nucleus), in the ventrolateral thalamus (medial geniculate nucleus, lateral geniculate nucleus, inferior pulvinar nucleus) and in the dorsolateral thalamus (lateral posterior nucleus, pulvinar nucleus). The highest density of fibers containing folic acid was observed in the dorsolateral mesencephalon and in the pulvinar nucleus. The distribution of folic acid-immunoreactive structures in the monkey brain suggests that this vitamin could be involved in several mechanisms, such as visual, auditory, motor and somatosensorial functions. PMID:15158027

Mangas, A; Coveñas, R; Geffard, K; Geffard, M; Marcos, P; Insausti, R; Dabadie, M P

2004-05-27

28

Folic acid to reduce neonatal mortality from neural tube disorders  

PubMed Central

Background Neural tube defects (NTDs) remain an important, preventable cause of mortality and morbidity. High-income countries have reported large reductions in NTDs associated with folic acid supplementation or fortification. The burden of NTDs in low-income countries and the effectiveness of folic acid fortification/supplementation are unclear. Objective To review the evidence for, and estimate the effect of, folic acid fortification/supplementation on neonatal mortality due to NTDs, especially in low-income countries. Methods We conducted systematic reviews, abstracted data meeting inclusion criteria and evaluated evidence quality using adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Where appropriate, meta-analyses were performed. Results Meta-analysis of three randomized controlled trials (RCTs) of folic acid supplementation for women with a previous pregnancy with NTD indicates a 70% [95% confidence interval (CI): 35–86] reduction in recurrence (secondary prevention). For NTD primary prevention through folic acid supplementation, combining one RCT with three cohort studies which adjusted for confounding, suggested a reduction of 62% (95% CI: 49–71). A meta-analysis of eight population-based observational studies examining folic acid food fortification gave an estimated reduction in NTD incidence of 46% (95% CI: 37–54). In low-income countries an estimated 29% of neonatal deaths related to visible congenital abnormalities are attributed to NTD. Assuming that fortification reduces the incidence of NTDs, but does not alter severity or case-fatality rates, we estimate that folic acid fortification could prevent 13% of neonatal deaths currently attributed to congenital abnormalities in low-income countries. Discussion Scale-up of periconceptional supplementation programmes is challenging. Our final effect estimate was therefore based on folic acid fortification data. If folic acid food fortification achieved 100% population coverage the number of NTDs in low-income countries could be approximately halved. Conclusion The evidence supports both folic acid supplementation and fortification as effective in reducing neonatal mortality from NTDs.

Blencowe, Hannah; Cousens, Simon; Modell, Bernadette; Lawn, Joy

2010-01-01

29

Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification?  

Microsoft Academic Search

BACKGROUND: Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI 1 recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase

Mary R Sweeney; Anthony Staines; Leslie Daly; Aisling Traynor; Sean Daly; Steven W Bailey; Patricia B Alverson; June E Ayling; John M Scott

2009-01-01

30

THE EFFECT OF FOLIC ACID SUPPLEMENTATION IN BETA THALASSEMIA MAJOR: A RANDOMIZED PLACEBO CONTROLLED CLINICAL TRIAL  

Microsoft Academic Search

Folic acid is a coenzyme for many important biochemical reactions including synthesis of purines, pyrimidines, and nucleoproteins. The recommended daily allowance of folic acid is 65 - 200 µg\\/day for infants and children. The recommended dose for deficiency states is 1000 µg\\/day; the effects of excess amounts of folic acid are unknown. The role of folic acid in preventing progression

Fereidoon Mojtahedzadeh; Mehrnoush Kosaryan; Mohammad-Reza Mahdavi; Jafar Akbari

2006-01-01

31

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

PubMed

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 blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin B(12) deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korea might be worth consideration. PMID:20368933

Lindzon, Gillian; O'Connor, Deborah L

2007-09-30

32

Folate during reproduction: the Canadian experience with folic acid fortification  

PubMed Central

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 blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin B12 deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korea might be worth consideration

Lindzon, Gillian

2007-01-01

33

Folic acid consumption among Missouri women in the periconceptional period.  

PubMed

Periconceptional folic acid consumption significantly reduces the risk for neural tube defects. The purpose of this study was to identify the risk factors for poor periconceptional folic acid supplementation among Missouri women. Sixty-five percent of Missouri women reported not taking periconceptional multivitamins regularly. Unintended pregnancy (aOR = 0.49), maternal adolescent age (aOR = 0.44) and smoking before pregnancy (aOR = 0.53) were significantly associated with poor periconceptional multivitamin use. Folic acid interventions targeting specific sub-groups of women are needed in Missouri. PMID:19052012

Garikapaty, Venkata P S; Feyerharm, Robert; Zhu, Baoping

34

Nutritional interpretation of folic acid interventions.  

PubMed

Folate is an essential micronutrient, and its nutritional inadequacy is widespread; hence, programs to increase its intake are necessary. However, many concerns about possible adverse effects due to excesses have been raised. Serum folate levels are directly correlated with intake and, when low, are associated with neural tube defects (NTD), high blood homocysteine levels, and megaloblastic anemia. Serum folate cutoff points have been identified for each abnormality, and all can be associated with intakes related to the current recommended dietary parameters. Likewise, high intakes that overwhelm the physiological capacity to process folic acid into biologically active folate derivatives are near the recommended tolerable upper intake level. Although we do not know with certainty the minimum efficacious dose that prevents all folate-dependent NTD, it may actually be much lower than the current recommendation, especially when provided through food fortification; supplemental intakes around 100 microg/day appear to be appropriate. PMID:19335717

Dary, Omar

2009-04-01

35

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2013 CFR

...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)...

2013-04-01

36

[Effect of folic acid on metabolic processes in wounds].  

PubMed

In experiments on rats the effect of folic acid on the redox and energy-producing processes as well as upon the synthesis of collagen and protein fractions of the muscular tissue in the area of the wound was investigated. Low doses of folic acid are shown to intensify in the muscles of intact animals anaerobic, and in the wound muscles--aerobic processes. High doses of folic acid produce an opposite effect on the wound muscles, by intensifying anaerobic processes. Folic acid manifests itself as an activator of anabolic processes by intensifying the gluconeogenesis in the wound tissues, the biosynthesis of collagen in the muscles of intact animals, and to a lesser degree in the muscles of surgically treated animals. PMID:421894

Nosova, I M; Za?denberg, M A; Korotkina, R N

37

The Basis of Differential Responses to Folic Acid Supplementation  

Microsoft Academic Search

Background\\/Aims: Elevated levels of total homocysteine (tHcy) are associated with an increased risk of many common diseases. Supplementation with folic acid has been shown to significantly reduce tHcy levels. We used the classical twin model to partition the variability in changes in plasma tHcy levels through folic acid supplementation into genetic, environmental, and confounding epidemiological factors. Methods: We carried out

Ioana Cotlarciuc; Toby Andrew; Tracy Dew; Gail Clement; Raj Gill; Gabriela Surdulescu; Roy Sherwood; Kourosh R. Ahmadi

2011-01-01

38

Molecularly Imprinted Membranes with Affinity Properties for Folic Acid  

Microsoft Academic Search

The extraction of folic acid from aqueous solutions was proposed through a novel procedure based on the membrane separation process using the approach of molecular imprinting. Molecularly imprinted membranes were prepared via the phase inversion technique using poly(acrylonitrile-co-acrylamide) copolymer as the membrane material and folic acid as the template molecule. Poly(acrylonitrile)-based membranes were also prepared as the reference material. Polymer

L. Donato; F. Tasselli; E. Drioli

2010-01-01

39

Folic acid fortification and public health: Report on threshold doses above which unmetabolised folic acid appear in serum  

PubMed Central

Background All flour in the USA is fortified with folic acid at a level of 140 ?g/100 g which is estimated to supply an extra 100 ?g daily to the average diet. Some researchers have advocated that this be increased to double and even four times this amount. Based on previous research these higher levels are likely to lead to the appearance of unmetabolised vitamin in the circulation, which may have safety implications for sub-groups of the population. The UK and the Republic of Ireland will likely introduce mandatory fortification also in the next year or so. The aim of this study was to capture the short-term effect of folic acid fortification on unmetabolised folic acid in serum after chronic consumption of folic acid. Methods After pre-saturation with 400 ?g folic acid supplements daily for 14-weeks, healthy folate replete adults (n = 20) consumed folic acid fortified bread, at three different levels (400 ?g, 200 ?g, 100 ?g) over a period of one week each. The dose was administered in two-equal sized slices consumed at 09.00 hrs and 13.00 hrs. Serum samples for total folate and folic acid were collected at baseline, after 14-weeks of supplementation, and pre and post (at 1, 2, 3 and 4 hours) each dose tested. Results Unmetabolised folic acid was detected after the 14-week supplementation period. Folic acid was not detected in either the 200 ?g or 100 ?g (current US regime) doses tested but was present at the highest level (400 ?g) tested. Conclusion Our findings suggest that persons exposed to the current US fortification programme supplying an average of 100 ?g per day or less are unlikely to have unmetabolised folic acid in serum. It also seems that daily consumption of the higher level of 200 ?g or less is unlikely to be problematic. Increasing the level however to 400 ?g on the other hand is likely to lead to unmetabolised folic acid appearance.

Sweeney, Mary Rose; McPartlin, Joseph; Scott, John

2007-01-01

40

[Folic acid and vitamin deficiency caused by oral contraceptives].  

PubMed

Recently there have been reports that long-term use of estrogen- containing oral contraceptives (OCs) can induce folic acid and vitamin B deficiency which can lead to hematopoiesis. The symptoms are paleness, forgetfulness, sleeplessness, and euphoric and depressive states. This deficiency occurs when serum folic content falls below 8 nmol/1 or 3 ng/ml. According to a nutrition group blood folic acid level declined up to 40% in patients taking OCs. In a Sri Lanka study of healthy women aged 20-45 taking Ovulen 50 (.05 mg of ethinyl estradiol and 1 mg of ethynodiol diacetate) folic acid level dropped in the 1st 6 months stabilizing at 2.2 ng/ml in those from the lowest social classes and at 2.9 ng/ml in those from privileged classes. Prophylactic substitution of folic acid in the diet was recommended by WHO, but it is less effective since it appears in the diet as polyglutamate that has to be broken down to absorbable monoglutamate. A US study found that taking OCs for 60 months resulted in a 40% reduction of the vitamin B12 serum level, while vitamin B12 concentrations in erythrocytes and peripheral blood stayed normal. Vitamin B12 helps recover tetrahydrofolic acid from N-methyltetrahydrofolic acid. Possibly this is another manifestation of OC-induced folic acid hypovitaminosis. OCs can also influence tryptophan metabolism reducing its blood concentration whereby less 5-hydroxytryptamine (serotonin) is produced. This results in headache, concentration decreases irritability, and sleep disturbances. In addition, lower riboflavin (vitamin B2) and thiamin concentration in erythrocytes was reported after using OCs. Counseling on the possible effect on vitamin stores and on proper nutrition including folic acid as monoglutamate is necessary for women who use OCs or estrogen substitution therapy for postmenopause or for osteoporosis prophylaxis. PMID:1921842

Bielenberg, J

1991-08-01

41

Chemiluminescence flow sensor for folic acid with immobilized reagents  

NASA Astrophysics Data System (ADS)

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 ?g ml -1, and the detection limit was 3.5 ng ml -1 folic acid (3 ?). 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%.

Song, Zhenghua; Zhou, Xin

2001-11-01

42

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

PubMed Central

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.

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

2012-01-01

43

The etiology of neural tube defects: the role of folic acid  

Microsoft Academic Search

DiscussionWhile the cause of neural tube defects in humans is considered to be multifactorial, it is apparent that folic acid can prevent 70% of open neural tube defects. Even in laboratory animals with known genetic defects, folic acid can prevent the genetic expression.ConclusionWhile some of the metabolic pathways for folic acid are known, the true effects of folic acid on

David G. McLone

2003-01-01

44

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

Microsoft Academic Search

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

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

2011-01-01

45

Congenital Heart Defects in Canadian Inuit: Is More Folic Acid Making a Difference?  

Microsoft Academic Search

Introduction: Grain fortification of flour with folic acid has successfully reduced neural tube defects (NTDs) by approximately one half of the pre-fortification rate. The knowledge that the use of multivitamins with folic acid has also been shown to reduce some birth defects has prompted interest in determining whether folic acid may also play a role in the prevention of non-neural

L. Arbour; R. Rupps; S. MacDonald; M. Forth; J. Yang; G. Osborne

46

Efficacy of adding folic acid to foods.  

PubMed

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

Fajardo, Violeta; Varela-Moreiras, Gregorio

2012-06-01

47

Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test.  

PubMed

The opioid system has been implicated in major depression and in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of the water-soluble B-vitamin folic acid in the forced swimming test (FST). The effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective delta-opioid receptor antagonist), naloxonazine (10 mg/kg, i.p., a selective mu(1)-opioid receptor antagonist, 24 h before), but not with naloxone methiodide (1 mg/kg, s.c., a peripherally acting opioid receptor antagonist). In addition, a sub-effective dose of folic acid (1 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (1 mg/kg, s.c.). A further approach was designed to investigate the possible relationship between the opioid system and NMDA receptors in the mechanism of action of folic acid in the FST. Pretreatment of the animals with naloxone (1 mg/kg, i.p.) prevented the synergistic antidepressant-like effect of folic acid (1 nmol/site, i.c.v.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA receptor antagonist). Together the results firstly indicate that the anti-immobility effect of folic acid in the FST is mediated by an interaction with the opioid system (mu(1) and delta), likely dependent on the inhibition of NMDA receptors elicited by folic acid. PMID:19162083

Brocardo, Patrícia S; Budni, Josiane; Lobato, Kelly R; Santos, Adair Roberto S; Rodrigues, Ana Lúcia S

2009-01-08

48

Folic Acid Functionalized Nanoparticles for Enhanced Oral Drug Delivery.  

PubMed

The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (P(app)) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability. PMID:22670575

Roger, Emilie; Kalscheuer, Stephen; Kirtane, Ameya; Guru, Bharath Raja; Grill, Alex E; Whittum-Hudson, Judith; Panyam, Jayanth

2012-06-13

49

Influence of Folic Acid on Postprandial Endothelial Dysfunction  

Microsoft Academic Search

Triglyceride-rich lipoproteins that circulate postprandially are increasingly being recognized as potentially athero- genic. These particles also have been shown to cause endothelial dysfunction. We recently demonstrated that acute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data suggested that this effect could be mediated by a reduction of radical

Hanneke W. Wilmink; Erik S. G. Stroes; Willem D. Erkelens; Wim B. Gerritsen; Robert Wever; Jan-Dirk Banga; Ton J. Rabelink

2010-01-01

50

Periconceptional folic acid\\/multivitamin supplementation and twin pregnancy  

Microsoft Academic Search

ObjectiveResults of our previous randomized controlled trial suggested an increase of twin pregnancies that was associated with the use of a multivitamin that contained folic acid during the periconceptional period. These findings were confirmed by US and Swedish studies, but not in the Chinese population. The aim of this analysis is to evaluate this possible association in a population-based data

Andrew E. Czeizel; Peter Vargha

2004-01-01

51

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

ERIC Educational Resources Information Center

|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.…

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

2007-01-01

52

Folic Acid and Birth Defects: A Case Study (Iran)  

PubMed Central

The aim of this study was to evaluate the impact of folic acid use in pregnancy for the reduction of neural tube defects (NTDs) in the northwest region of Iran. We studied 243 women with pregnancies complicated by some forms of birth defect(s). These patients were identified by medical diagnostic tests as having a fetus with some types of congenital anomalies. The prevalence of NTDs among pregnant women who were referred for therapeutic termination of pregnancy was 24.7 percent. Consumption of folic acid prevented NTDs by 79 percent (Odds Ratio?=?0.21,?CI 95%:?0.12–0.40) and 94 percent (Odds Ratio?=?0.06,?CI 95%:?0.03–0.15) compared to pregnancies complicated by other anomalies and normal pregnancies, respectively. Hydrops fetalis, hydrocephaly, Down syndrome, and limb anomalies did not have any significant association with the folic acid use. Along with the advice for the consumption of folic acid for pregnant women, they should be offered prenatal screening or diagnostic tests to identify fetal abnormalities for possible termination of pregnancy.

Hosseini, Mohammad Bager; Khamnian, Zhila; Dastgiri, Saeed; Samadi Raad, Bahram; Ravanshad, Yalda

2011-01-01

53

Folic acid acts through DNA methyltransferases to induce the differentiation of neural stem cells into neurons.  

PubMed

The present study investigated the roles of folic acid and DNA methyltransferases (DNMTs) in the differentiation of neural stem cells (NSCs). Neonatal rat NSCs were grown in suspended neurosphere cultures and identified by their expression of SOX2 protein and capacity for self-renewal. Then NSCs were assigned to five treatment groups for cell differentiation: control (folic acid-free differentiation medium), low folic acid (8 ?g/mL), high folic acid (32 ?g/mL), low folic acid and DNMT inhibitor zebularine (8 ?g/mL folic acid and 150 nmol/mL zebularine), and high folic acid and zebularine (32 ?g/mL folic acid and 150 nmol/mL zebularine). After 6 days of cell differentiation, immunocytochemistry and western blot analyses were performed to identify neurons by ?-tubulin III protein expression and astrocytes by GFAP expression. We observed that folic acid increased DNMT activity which may be regulated by the cellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and the abundance of neurons but decreased the number of astrocytes. Zebularine blocked these effects of folic acid. In conclusion, folic acid acts through elevation of DNMT activity to increase neuronal differentiation and decrease astrocytic differentiation in NSCs. PMID:23292356

Luo, Suhui; Zhang, Xumei; Yu, Min; Yan, Hai; Liu, Huan; Wilson, John X; Huang, Guowei

2013-07-01

54

Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity.  

PubMed

In previous studies conducted in female rats and in women, oral contraceptives (OC) were found to induce a platelet hyperactivity that was related to an oxidative stress. Because cases of megaloblastic anemia have been reported to occur in women taking OC, these treatments are suspected of depleting folate stores. In the study presented herein, which was conducted in rats, we sought to determine the influence of dietary folic acid deficiency (FD) on the thrombogenicity of OC. Animals were fed for 6 weeks with either a folic acid-deficient diet (250 micrograms/kg folic acid) or a control diet (750 micrograms/kg). One-half of the animals in each group were treated with OC (ethinyl estradiol plus lynestrenol). FD and OC individually potentiated platelet aggregation in response to thrombin and ADP and the release and metabolism of arachidonic acid, in particular, the biosynthesis of thromboxane. These platelet activities were further enhanced in animals given both the folic acid-deficient diet and the OC treatment. In addition, FD enhanced the pro-oxidant state in OC-treated rats characterized by (1) a fall in platelet and plasma n-3 fatty acids, (2) an increase in plasma lipid peroxidation products such as conjugated dienes, lipid peroxides, and thiobarbituric reactive substances, (3) a rise in ex vivo erythrocyte susceptibility to free radicals. Moreover, we found that OC treatment led to a reduction of plasma and erythrocyte folate concentrations associated with a moderate hyperhomocysteinemia. Under our experimental conditions, we did not find significant synergistic effects between OC and FD. We propose that, although the untoward effects associated with the OC treatment may not primarily be dependent on FD, the folic acid deficiency magnified OC-induced oxidative stress, which resulted in platelet hyperactivity by elevating the pro-oxidant homocysteine plasma concentration. Despite the limitations of this animal model, the data of the present study suggest that in addition to cigarette smoking, inadequate folic acid intake might predispose those taking OC to vascular thrombosis. PMID:9351357

Durand, P; Prost, M; Blache, D

1997-10-01

55

Synthesis of an indole analog of folic acid  

SciTech Connect

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.

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

1987-06-01

56

Knowledge and use of folic acid in women of reproductive age.  

PubMed

Folic acid reduces the risk of neural tube defects. As approximately 50% of pregnancies are unintended, women of reproductive age should be aware of the importance of folic acid. We reviewed the existing literature on these women's knowledge of folic acid and neural tube defects. Databases searched were PubMed, CINAHL, and Health Reference Center Academic. We used terms such as "folic acid knowledge" and "folic acid awareness" to search articles published from 1998 to 2010. Awareness of the benefits of folic acid before conception and during pregnancy was low, although knowledge levels were associated with education and household income. Women who were already knowledgeable about folic acid cited health care professionals, magazines and newspapers, and radio and television as common sources of information. Effective knowledge translation is needed to ensure that women are informed about the benefits of folic acid during the reproductive years. This knowledge will allow them to make informed decisions about folic acid consumption. Health care professionals play an influential role in promoting folic acid knowledge among women of childbearing age. Lower levels of knowledge among women with lower levels of education and/or household income must be addressed. PMID:22146120

Fehr, Kelly R S; Fehr, Kelsey D H; Protudjer, Jennifer Lisa Penner

2011-01-01

57

Contactless conductivity biosensor in microchip containing folic acid as bioreceptor.  

PubMed

We report a glass/PDMS-based microfluidic biosensor that integrates contactless conductivity transduction and folic acid, a target for tumor biomarker, as a bioreceptor. The device presents relevant advantages such as direct determination--dismiss the use of redox mediators as in faradaic electrochemical techniques--and the absence of the known drawbacks related to the electrode-solution interface. Characterizations of the functionalization processes and chemical sensor are described in this communication. PMID:22549415

Lima, Renato S; Piazzetta, Maria H O; Gobbi, Angelo L; Rodrigues-Filho, Ubirajara P; Nascente, Pedro A P; Coltro, Wendell K T; Carrilho, Emanuel

2012-05-02

58

Study of the photolysis of folic acid and 6-formylpterin in acid aqueous solutions  

Microsoft Academic Search

Folic acid and 6-formylpterin solutions of pH in the range 4.5–6.0 were photolysed at 350nm at room temperature. The photochemical reactions were followed by UV–VIS spectrophotometry, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). In the presence of oxygen, folic acid is photochemically cleavaged yielding 6-formylpterin and p-aminobenzoylglutamic acid. As the photolysis proceeds, 6-carboxypterin arises from 6-formylpterin, as

Andrés H. Thomas; Gustavo Suárez; Franco M. Cabrerizo; Raúl Martino; Alberto L. Capparelli

2000-01-01

59

Application of the social ecological model in folic acid public health initiatives.  

PubMed

All women of childbearing age who are capable of becoming pregnant should consume 0.4 mg/400 microg of folic acid daily. Folic acid decreases the incidence of neural tube defects in newborns. Despite continued public health initiatives, many women still do not consume the recommended daily requirement. This article analyzes the use of the social ecological model in folic acid public health initiatives and emphasizes assessing the outcomes of such initiatives. PMID:16282224

Quinn, Lisa A; Thompson, Sharon J; Ott, M Katherine

60

The Activity of Synthetic Folic Acid in Purified Rations for the Chick.  

PubMed

The addition of 25gamma of synthetic folic acid per 100 grams of our basal ration prevents the reduced growth, poor feathering condition, and low hemoglobin and hematocrit values consistently obtained when the basal ration is fed to chicks. More than 25gamma are needed when the diet contains sulfasuxidine. Evidence for the possible indirect action of folic acid is summarized. Vitamin C or whole liver powder gives a slight response in the presence of adequate amounts of synthetic folic acid. PMID:17750514

Luckey, T D; Moore, P R; Elvehjem, C A; Hart, E B

1946-06-01

61

Clinical Utility of Folic Acid Testing for Patients with Anemia or Dementia  

PubMed Central

Background Serum folic acid tests are routinely ordered by physicians for evaluating anemia and sometimes ordered for evaluating dementia and altered mental status. Objective To determine the utility of routine folic acid testing for patients with anemia or dementia/altered mental status in the era of folic acid fortification. Design Retrospective analysis of consecutive folic acid tests performed on adults over a 4-month period; chart review of patients without anemia. Measurements and Main Results Serum folic acid level, mean corpuscular volume (MCV), and hematocrit. We reviewed 1,007 folic acid tests performed on 980 patients. The average age was 63.8 years, and 62% of the tests were from outpatient facilities. Only 4 (0.4%) patients had folic acid levels <3 ng/mL, while 10 (1%) patients had levels of 3–4 ng/mL (borderline). Thirty-five percent of the folic acid tests were performed on patients who were not anemic; most of these were ordered to evaluate dementia or altered mental status and folic acid level was normal in all these patients. Only 7% of the patients tested had a macrocytic anemia; these patients were more likely than those without macrocytic anemia to have low folic acid levels (2.8% vs 0.4%, p?folic acid levels were rarely detected in a series of patients being evaluated for anemia, dementia, or altered mental status. The test should be reserved for patients with macrocytic anemia and those at high risk for folic acid deficiency.

Cook, James R.; Rothberg, Michael B.

2008-01-01

62

Folic Acid Supplementation Stimulates Notch Signaling and Cell Proliferation in Embryonic Neural Stem Cells  

PubMed Central

The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14–16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system.

Liu, Huan; Huang, Guo-wei; Zhang, Xu-mei; Ren, Da-lin; X. Wilson, John

2010-01-01

63

Folic Acid Food Fortification--Its History, Effect, Concerns, and Future Directions  

PubMed Central

Periconceptional intake of folic acid is known to reduce a woman’s risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.

Crider, Krista S.; Bailey, Lynn B.; Berry, Robert J.

2011-01-01

64

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

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

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

2009-01-01

65

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

Microsoft Academic Search

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

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

2008-01-01

66

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

PubMed

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

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

67

Solution structure of folic acid. Molecular mechanics and NMR investigation  

NASA Astrophysics Data System (ADS)

The structure of folic acid in solution was investigated by nuclear magnetic resonance (NMR) and theoretical calculations. Dynamical information and geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear NOESY spectra and hetero-nuclear 1H- 13C NOE experiments. This set of experimental data was used for the molecular mechanics and molecular dynamic calculations. The accuracy of the final structure was established by the RNMR factor, which was calculated comparing the experimental NOESY cross-peaks intensities and the corresponding values simulated by using the complete relaxation matrix analysis (CORMA) approach.

Bonechi, C.; Donati, A.; Lampariello, R.; Martini, S.; Picchi, M. P.; Ricci, M.; Rossi, C.

2004-06-01

68

Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma  

Technology Transfer Automated Retrieval System (TEKTRAN)

Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

69

KNOWLEDGE AND USE OF FOLIC ACID AMONG WOMEN IN THE MISSISSIPPI DELTA  

Technology Transfer Automated Retrieval System (TEKTRAN)

Efforts to increase folic acid knowledge and use may not be reaching large segments of the population. This study examines folic acid knowledge and use among women of childbearing age in a representative, low income, rural sample. A random digit dialing telephone survey was conducted with 646 women ...

70

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

ERIC Educational Resources Information Center

|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…

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

2006-01-01

71

Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure?  

Microsoft Academic Search

Background—Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. Methods and Results—In a

J. Thambyrajah; M. J. Landray; F. J. McGlynn; H. J. Jones; D. C. Wheeler; J. N. Townend

2010-01-01

72

Cost-effectiveness of a folic acid fortification program in Chile  

Microsoft Academic Search

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.

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

2007-01-01

73

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

Microsoft Academic Search

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,

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

2002-01-01

74

Recurrent aphthae: treatment with vitamin B12, folic acid, and iron  

Microsoft Academic Search

A series of 130 consecutive outpatients with recurrent aphthous stomatitis were screened at the oral medicine department, Glasgow Dental Hospital, for deficienciesin vitamin b12, folic acid, and iron. In 23 patients (17.7%) such deficiencies werefound; five were deficient in vitamin B12, seven in folic acid, and 15 in iron. Four had more than one deficiency. Out of 130 controls matched

D Wray; M M Ferguson; D K Mason; A W Hutcheon; J H Dagg

1975-01-01

75

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

Microsoft Academic Search

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

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

2006-01-01

76

Chemiluminescence determination of folic acid by a flow injection analysis assembly  

NASA Astrophysics Data System (ADS)

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.

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

2013-03-01

77

Promoting folic acid to Spanish-speaking Hispanic women: evaluating existing campaigns to guide new development.  

PubMed

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 focus groups with Hispanic mothers (N = 18) were conducted to garner insights on these issues. Results suggested that these women understood the benefits of folic acid, did not see major cultural barriers to consuming folic acid-rich foods, and did not perceive insurmountable challenges to consuming a multivitamin with folic acid. For many women, an initial pregnancy served as their initial cue to action, suggesting a need for the continued development of education strategies that communicate the benefits of folic acid supplementation prior to pregnancy. Such strategies may necessitate targeting younger audiences, including teenagers. PMID:20711950

Mackert, Michael; Kahlor, Leeann; Silva, Kristi; Padilla, Yolanda

2010-06-01

78

High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring  

PubMed Central

Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold. In vitro, acute application of folic acid or its metabolite 4Hfolate to neurons induced hyper-excitability and bursting. Cultured neuronal networks which develop in the presence of a low concentration (50?nM) of 4Hfolate had reduced capacity to stabilize their network dynamics after a burst of high-frequency activity, and an increase in the frequency of mEPSCs. Networks reared in the presence of the folic acid metabolite 5M4Hfolate developed a spontaneous, distinctive bursting pattern, and both metabolites produced an increase in synaptic density.

Girotto, Fernando; Scott, Lucas; Avchalumov, Yosef; Harris, Jacqueline; Iannattone, Stephanie; Drummond-Main, Chris; Tobias, Rose; Bello-Espinosa, Luis; Rho, Jong M.; Davidsen, Jorn; Teskey, G. Campbell; Colicos, Michael A.

2013-01-01

79

High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring.  

PubMed

Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold. In vitro, acute application of folic acid or its metabolite 4Hfolate to neurons induced hyper-excitability and bursting. Cultured neuronal networks which develop in the presence of a low concentration (50 nM) of 4Hfolate had reduced capacity to stabilize their network dynamics after a burst of high-frequency activity, and an increase in the frequency of mEPSCs. Networks reared in the presence of the folic acid metabolite 5M4Hfolate developed a spontaneous, distinctive bursting pattern, and both metabolites produced an increase in synaptic density. PMID:23492951

Girotto, Fernando; Scott, Lucas; Avchalumov, Yosef; Harris, Jacqueline; Iannattone, Stephanie; Drummond-Main, Chris; Tobias, Rose; Bello-Espinosa, Luis; Rho, Jong M; Davidsen, Jörn; Teskey, G Campbell; Colicos, Michael A

2013-01-01

80

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...

81

Folic acid as a Fenton-modulator: possible physiological implication.  

PubMed

Acting as a redox switch, folic acid (1) might be a promising iron modulator to protect cellular machinery against oxidative stress and iron overload. The vitamin 1 can directly control the iron concentration by oxidizing it even if present in chelated forms. In addition, during its role as a reducing agent for the biologically relevant reactive oxygen species (ROS), it furnishes 6-formyl pterin. This folate-derived intermediate possesses a stronger Fe2+-oxidizing capacity than 1. Thus, compound 1 can reduce the iron toxicity in two ways. Although, the Fe2+-oxidizing capacity is nullified in the presence of a strong biological reductant like ascorbic acid, this property may play a predominant role during pathogenesis when the cellular ascorbic acid levels deplete significantly. The iron-modulatory property of 1 was also confirmed with the L929 mouse fibroblast cell line. PMID:16848754

Patro, Birija S; Adhikari, Soumyakanti; Mukherjee, Tulsi; Chattopadhyay, Subrata

2006-07-01

82

Separation of Folic Acid Reductase from Streptococcus faecium (ATCC 8043)1  

PubMed Central

A strain of Streptococcus faecium (ATCC 8043) which is highly resistant to the antifolic acid compound, amethopterin, was gently ruptured by exposing protoplasts of the organism to a hypotonic solution. The crude lysate resulting there-from was treated by various chemical and physical techniques designed to separate folic acid reductase from dihydrofolic acid reductase. In the process, the enzyme was purified approximately 160-fold; however, throughout the process, the enzyme preparation maintained the ability to reduce folic acid to tetrahydrofolic acid. Attempts to isolate mutants showing a deficiency in either folic acid reductase or dihydrofolic acid reductase were unsuccessful. Based on these results, it is concluded that folic acid is reduced to tetrahydrofolic acid by one enzyme in S. faecium (ATCC 8043). The crude lysate was also subjected to ultracentrifugation. An analysis of the supernatant fluid and the sediment indicated that the reductive activity is located in the soluble fraction of the cell.

Speck, Eugene L.; Affronti, Lewis F.

1969-01-01

83

Maternal folic acid supplement use in early pregnancy and child behavioural problems: The Generation R Study.  

PubMed

Folate deficiency during embryogenesis is an established risk factor for neural tube defects in the fetus. An adequate folate nutritional status is also important for normal fetal growth and brain development. The aim of the present research was to study the association between folic acid use of the mother during pregnancy and child behavioural development. Within a population-based cohort, we prospectively assessed folic acid supplement use during the first trimester by questionnaire. Child behavioural and emotional problems were assessed with the Child Behaviour Checklist at the age of 18 months in 4214 toddlers. Results showed that children of mothers who did not use folic acid supplements in the first trimester had a higher risk of total problems (OR 1.44; 95 % CI 1.12, 1.86). Folic acid supplement use protected both from internalising (OR of no supplement use 1.65; 95 % CI 1.24, 2.19) and externalising problems (OR 1.45; 95 % CI 1.17, 1.80), even when adjusted for maternal characteristics. Birth weight and size of the fetal head did not mediate the association between folic acid use and child behaviour. In conclusion, inadequate use of folic acid supplements during early pregnancy may be associated with a higher risk of behavioural problems in the offspring. Folic acid supplementation in early pregnancy, aimed to prevent neural tube defects, may also reduce mental health problems in children. PMID:19772683

Roza, Sabine J; van Batenburg-Eddes, Tamara; Steegers, Eric A P; Jaddoe, Vincent W V; Mackenbach, Johan P; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

2009-09-22

84

Knowledge, Attitudes, and Practice among Women and Doctors Concerning the Use of Folic Acid.  

PubMed

Background and Objective. Daily folic acid intake, prior to conception and in early pregnancy, significantly reduces neural tube defects (NTDs). We compared folic acid consumption among Jewish and Bedouin women and the recommendations of family physicians and gynecologists. Methods. We compared 64 Muslim Bedouin women and 65 Jewish women. We also compared 39 gynecologists and 60 family physicians. Results. Fifty-one Jewish women (78.5%) took folic acid during pregnancy, but only seven (10.8%) before conception. Sixty Bedouin women (93.75%) took folic acid during pregnancy, but only four (6.25%) before conception (P < .05). Five Jewish women (7.7%) and two Bedouin women (3.1%) took folic acid three months before conception. Thirty-three gynecologists (87%) recommend preconception folic acid compared with thirty-six family physicians (60%) (P < .05). Conclusions. The majority of women use folic acid during pregnancy, but only few do so to prevent NTDs. There is a significant difference between doctors' recommendations and actual practice. PMID:21647220

Auriel, Eithan; Biderman, Aya; Belmaker, Ilana; Freud, Tamar; Peleg, Roni

2010-10-03

85

The use of folic acid for the prevention of birth defects in Puerto Rico  

PubMed Central

Introduction The occurrence of neural tube defects (NTD) has been shown to vary by race/ethnicity, with the highest rates among women of Hispanic ethnicity. Women of reproductive age are advised to use folic acid to prevent NTD and other birth defects. Since 1994, Puerto Rico has a campaign to promote the use of folic acid and since 1998 there is fortification of enriched grain products. After fortification, there has been a reduction in the incidence of NTD in the island. The objective of this study is to assess the use of folic acid by women of reproductive age in Puerto Rico and determine factors associated to its use. Methods A self-administered questionnaire was answered by 964 women around the island. Results Folic acid consumption was reported by 30% of the participants, 21% reported to consume it at least 4 times per week, and only 14% consumed it the day before the survey. Knowledge about the recommendation for women to consume folic acid was reported by 97% of the participants. The use of folic acid was lower among women of lower education and lower social class. Women with higher education were 8.3 times more likely to consume folic acid. Conclusion The folic acid campaign has improved women’s knowledge about the recommendation for folic acid supplementation. Nevertheless, its use is lower than desired to continue reducing the incidence of birth defects in Puerto Rico. Education and social class continue to represent barriers to eliminate the disparities in the pre-conception health of our population.

Garcia-Fragoso, Lourdes; Garcia-Garcia, Ines; Rivera, Cynthia E.

2009-01-01

86

Altered brain neurotrophins at birth: consequence of imbalance in maternal folic acid and vitamin B?? metabolism.  

PubMed

Folic acid fortification to pregnant women is suggested to mask vitamin B?? deficiency leading to adverse neurologic consequences. The present study examines the effect of maternal folic acid supplementation at normal and excess levels both in the presence and absence of vitamin B?? on levels and expression of brain neurotrophins in Wistar Albino rats. Pregnant female rats were assigned to six dietary groups with varying levels of folic acid and vitamin B??, that is, (NFB: 2 mg folic acid+B??; NFBD: 2 mg folic acid-B??; EFB: 8 mg folic acid+B??; EFBD: 8 mg folic acid-B??; NFBDO: 2 mg folic acid-B??+DHA and EFBDO: 8 mg folic acid-B??+DHA). On day 20 of gestation pup brain samples were collected to assess protein and mRNA levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Brain BDNF protein and mRNA levels were reduced (P<0.01 for both) in the EFBD group as compared to control. However, NGF protein levels were reduced (P<0.05) only in the EFBD group in comparison to EFB and control. Maternal supplementation of DHA improved pup brain NGF protein levels only in the NFBDO (P<0.05) and EFBDO (P<0.05) groups compared to NFBD and EFBD respectively. Our results suggest that maternal micronutrients during pregnancy play an important role in regulating protein and mRNA levels of neurotrophins. Maternal DHA supplementation to a micronutrient imbalanced diet could ameliorate the negative effects only for NGF but not for BDNF. PMID:21640168

Sable, P; Dangat, K; Kale, A; Joshi, S

2011-06-01

87

Folic acid conjugated amino acid-based star polymers for active targeting of cancer cells.  

PubMed

Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L-cystine)(core)) with peripheral allyl functionalities were synthesized by sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs) via the arm-first approach, using N-(trimethylsilyl)allylamine as the initiator. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic acid conjugate via thiol-ene click chemistry afforded poly(PEG-b-L-lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with folic acid targeting moieties. Similarly, a control was prepared without folic acid, using just PEG. A fluorophore was used to track both star polymers incubated with breast cancer cells (MDA-MB-231) in vitro. Confocal microscopy and flow cytometry revealed that the stars could be internalized into the cells, and higher cell internalization was observed when folic acid moieties were present. Cytotoxicity studies indicate that both stars are nontoxic to MDA-MB-231 cells at concentrations of up to 50 ?g/mL. These results make this amino acid-based star polymer an attractive candidate in targeted drug delivery applications including chemotherapy. PMID:21854075

Sulistio, Adrian; Lowenthal, Justin; Blencowe, Anton; Bongiovanni, Marie N; Ong, Lydia; Gras, Sally L; Zhang, Xiaoqing; Qiao, Greg G

2011-09-02

88

Preparing for a healthy future today: Folic acid formative research with young Latina adults.  

PubMed

Young Latina adults require targeted health messages to meet the unique needs of this life stage. Folic acid messages for the prevention of neural tube defects that are effective for other women might not be relevant to this group. The aim of this study was to identify barriers and motivators to folic acid consumption for this population and develop educational materials and messages that address their needs. This article presents 3 phases of formative research that formed the basis for the development of Spanish-language print materials and radio advertisements aimed at promoting folic acid consumption among young Latina adults. PMID:20736757

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

89

Mechanism of photooxidation of folic acid sensitized by unconjugated pterins.  

PubMed

Folic acid, or pteroyl-l-glutamic acid (PteGlu), is a precursor of coenzymes involved in the metabolism of nucleotides and amino acids. PteGlu is composed of three moieties: a 6-methylpterin (Mep) residue, a p-aminobenzoic acid (PABA) residue, and a glutamic acid (Glu) residue. Accumulated evidence indicates that photolysis of PteGlu leads to increased risk of several pathologies. Thus, a study of PteGlu photodegradation can have significant ramifications. When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of the degradation increases with irradiation time. The mechanism involved in this "auto-photo-catalytic" effect was investigated in aqueous solutions using a variety of tools. Whereas PteGlu is photostable under anaerobic conditions, it is converted into 6-formylpterin (Fop) and p-aminobenzoyl-l-glutamic acid (PABA-Glu) in the presence of oxygen. As the reaction proceeds and enough Fop accumulates in the solution, a photosensitized electron-transfer process starts, where Fop photoinduces the oxidation of PteGlu to Fop, and H(2)O(2) is formed. This process also takes place with other pterins as photosensitizers. The results are discussed with the context of previous mechanisms for processes photosensitized by pterins, and their biological implications are evaluated. PMID:20922252

Dántola, M Laura; Denofrio, M Paula; Zurbano, Beatriz; Gimenez, Carlos S; Ogilby, Peter R; Lorente, Carolina; Thomas, Andrés H

2010-10-05

90

SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION OF FOLIC ACID, PYRIDOXINE, RIBOFLAVIN, AND THIAMINE BY PARTIAL LEAST-SQUARES REGRESSION  

Microsoft Academic Search

A new method for the simultaneous spectrophotometric determination of folic acid, pyridoxine, riboflavin and thiamine based on total absorbance measurements and their processing by partial least square regression is proposed. The concentration ranges used to construct the calibration matrix were 1.02–14.3 µg mL, 1.01–16.2 µg mL, 1.02– 10.2 µg mL and 6.00–20.0 µg mL for folic acid, pyridoxine, riboflavin and thiamine, respectively. Estimated limits of detection were: folic

F. J. Aberásturi; A. I. Jiménez; J. J. Arias; F. Jiménez

2002-01-01

91

Cardiovascular effects of milk enriched with ?-3 polyunsaturated fatty acids, oleic acid, folic acid, and vitamins E and B6 in volunteers with mild hyperlipidemia  

Microsoft Academic Search

ObjectiveResults from epidemiologic studies and clinical trials have indicated that consumption of ?-3 fatty acids, oleic acid, and folic acid have beneficial effects on health, including decreased risk of cardiovascular disease. We evaluated the combined effects of these nutrients through the consumption of milk enriched with ?-3 polyunsaturated fatty acids, oleic acid, vitamins E and B6, and folic acid on

Juan J Carrero; Luis Baró; Juristo Fonollá; María González-Santiago; Antonio Martínez-Férez; Rafael Castillo; Jesús Jiménez; Julio J Boza; Eduardo López-Huertas

2004-01-01

92

Folic acid may be a potential addition to diabetic foot ulcer treatment - a hypothesis.  

PubMed

Delayed wound healing in diabetes is a challenging medical and societal problem for which there is currently no efficacious treatment. One of the major contributors of this problem is nitric oxide (NO) deficiency. NO is a critical signalling molecule essential for normal wound repair. Sustained hyperglycaemia in diabetes leads to increased vascular superoxide production, which inactivates NO and causes vascular dysfunction. New therapeutic regiments and strategies to enhance endothelial NO production are a new hope to improve impaired diabetic wound healing. One of the agents that have the ability to improve endothelial NO generation in diabetic patients is folic acid. Folic acid ability to conserve NO bioactivity may be due to homocysteine-lowering effects of folates, antioxidant actions and effects on cofactor availability. Considering these data, we hypothesised that folic acid supplementation may ameliorate delayed diabetic wound healing by increasing NO bioavailability. The potential of exogenous folic acid as an inexpensive and safe oral therapy stimulates ongoing investigations. PMID:21854546

Bagheri, Mansooreh; Jahromi, Behnam Moein; Zamani, Ali

2011-08-19

93

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

PubMed

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

Sici?ska, Ewa; Pelc, Anna

2011-01-01

94

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

PubMed

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

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

2008-10-01

95

Studies on the Hydrolysis and Absorption of Folic Acid Polyglutamates in Tropical Sprue.  

National Technical Information Service (NTIS)

A method was found for the isolation of folic acid polyglutamate from yeast extract. Utilizing this substrate a reproducible assay for 'conjugase' (gamma glutamyl carboxypeptidase) has been established. The pH optima, buffer specificity and gastro intesti...

L. H. Bernstein S. Gutstein S. V. Weiner S. Pollack

1969-01-01

96

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

Microsoft Academic Search

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

GregoryJ Locksmith; Patrick Duff

1998-01-01

97

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

Microsoft Academic Search

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

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

2007-01-01

98

Folic acid and glutathione in the water column of the North East Atlantic  

NASA Astrophysics Data System (ADS)

Reactive folic acid and glutathione were determined in the water column of the north east Atlantic between 30 and 54°N, 20°W. Cathodic stripping voltammetry (CSV) was used to determine these compounds on board ship at low nanomolar levels after minimal sample pretreatment. Folic acid was found to occur throughout the water column, whereas glutathione was found only in the upper water column as it was undetectable in deep waters. The concentration of glutathione ranged from <1 to 15 nmol/l, the folic acid concentrations generally between 0.10 and 4.0 nmol/l. Folic acid was found to follow the same trend as the Chl- a fluorescence in the upper water column but not in deeper waters. The data show that both folic acid and glutathione are very reactive in the oceanic water column, presumably as a result of in situ production and uptake by microorganisms. The high bioactivity was confirmed by rapid decreases in the concentrations of folic acid and glutathione in unfiltered seawater during storage over periods of hours.

Christine, Anne; Gall, Le; Van Den Berg, Constant M. G.

99

Women's awareness and periconceptional use of folic acid: data from a large European survey  

PubMed Central

Objective To investigate the awareness and use of folic acid in European women of child-bearing age, particularly in the setting of pregnancy and pregnancy planning. Methods Between November 2009 and December 2009, women aged 15–49 years old from 18 European countries completed a 30-minute structured questionnaire either online or via face-to-face interviews. To achieve nationally representative samples for each country quotas were set for age, education, income, and regional distribution. Results A total of 22,925 women participated in the survey. Of the respondents, 58% had at least one biological child, and of these 38% reported that their first pregnancy was not planned. Nearly 60% of women who planned their pregnancy indicated that they had stopped using their method of contraception without first consulting a doctor or another health care professional. Overall, 70% reported that they had heard of folic acid and 40% stated that they knew the benefits of folic acid. However, when prompted to indicate which diseases and/or birth defects folic acid can protect against, only 17% knew that folic acid can reduce the risk of neural tube defects/spina bifida. Conclusions A large proportion of European women of child-bearing age in this survey were unaware that periconceptional folic acid supplementation reduces the risk of birth defects.

Bitzer, Johannes; von Stenglin, Ariane; Bannemerschult, Ralf

2013-01-01

100

Surface-Modified Gold Nanoparticles with Folic Acid as Optical Probes for Cellular Imaging  

PubMed Central

In this study, we demonstrate that the uptake rate of the surface-modified gold nanoparticles (GNPs) with folic acid by specific cells can be increased significantly, if the membranes of these cells have sufficient folic-acid receptors. Two human breast cancer cell lines were studied; one is MDA-MB-435S cell, and the other T-47D cell. The expression of the folic acid receptors of the former is much higher than that of the latter. These cells were incubated with media containing bare GNPs or GNPs conjugated with folic acid individually. Due to the unique optical behavior (i.e. surface plasmon resonance) of GNPs, the uptake amount of GNPs by cells can be identified by using the laser scanning confocal microscopy. Our experiments show that the uptake amount of GNPs in MDA- MB-435S cells is higher than that in T-47D cells for the same culture time, if the culture medium contains bare GNPs. Moreover, if the GNPs conjugated with folic acid are used for the culture, the uptake rate of GNPs by MDA-MB-435S cells is improved more. In contrast, the uptake rates of both GNPs are almost the same by T-47D cells. The phenomenon indicates that the uptake rate of GNPs can be improved via the ligand- receptor endocytosis, compared with the nonspecific endocytosis. Therefore, the uptake rate of GNPs conjugated with folic acid by MDA-MB-435S cells is higher than that of bare GNPs.

Tsai, Shiao-Wen; Liaw, Jiunn-Woei; Hsu, Fu-Yin; Chen, Yi-Yun; Lyu, Mei-Jhih; Yeh, Ming-His

2008-01-01

101

Knowledge and use of folic acid for birth defect prevention among women of childbearing age in Shanghai, China: A prospective cross-sectional study  

PubMed Central

Summary Background This study aimed to assess the knowledge, attitude, and practice of folic acid intake for prevention of birth defects in Chinese women of child-bearing age. Material/Methods In this prospective cross-sectional study, a total of 1,338 women aged 20–45 years were randomly selected for interview. Data on folic acid knowledge and information on folic acid intake in the subjects were collected. Age, education, contraception, and status of family planning were used as the independent variables in multivariate logistic regression. Results 55.6% of the subjects took contraception at all times, and 33.9% had pregnancy planning in the next six months. 49.7% of the interviewed women knew the benefits of folic acid and 34.6% realized the correct time of folic acid intake; and 14.9% of these women actually took folic acid daily. Planning to be pregnant in the next six months was associated with knowledge of folic acid benefits, correct time of folic acid intake and actual intake. A higher education level was correlated with the knowledge of folic acid benefits and correct time of folic acid intake, but was not linked to actual intake of folic acid. Conclusions The knowledge and use of folic acid were at low to moderate levels in women at childbearing age in Shanghai, China, and general knowledge of folic acid benefits and correct time of folic acid intake should be conveyed to these women.

Liang, Huan; Ma, Duan; Zhou, Shu-Feng; Li, Xiaotian

2011-01-01

102

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

Microsoft Academic Search

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

Rashmi Tupe; Vaishali Agte

2010-01-01

103

Cancer risk with folic acid supplements: a systematic review and meta-analysis.  

PubMed

Objective To explore if there is an increased cancer risk associated with folic acid supplements given orally. Design Systematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included. Data sources Cochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals. Results From 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38?233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality. Conclusions A meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk. PMID:22240654

Wien, Tale Norbye; Pike, Eva; Wisløff, Torbjørn; Staff, Annetine; Smeland, Sigbjørn; Klemp, Marianne

2012-01-12

104

Cancer risk with folic acid supplements: a systematic review and meta-analysis  

PubMed Central

Objective To explore if there is an increased cancer risk associated with folic acid supplements given orally. Design Systematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included. Data sources Cochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals. Results From 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38?233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality. Conclusions A meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk.

Wien, Tale Norbye; Pike, Eva; Wisl?ff, Torbj?rn; Staff, Annetine; Smeland, Sigbj?rn

2012-01-01

105

Combined Iron and Folic Acid Supplementation with or without Zinc Reduces Time to Walking Unassisted among Zanzibari Infants  

Microsoft Academic Search

Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron1folic acid (FeFA) (12.5 mg Fe 1 50 mg folic acid), zinc (Zn) (10 mg), and iron1folic acid1zinc (FeFA1Zn) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba, Zanzibar. The

Deanna K. Olney; Ernesto Pollitt; Patricia K. Kariger; Sabra S. Khalfan; Nadra S. Ali; James M. Tielsch; Sunil Sazawal; Robert Black; Lindsay H. Allen; Rebecca J. Stoltzfus

106

A survey of knowledge and use of folic acid among women of child-bearing age in Dublin  

Microsoft Academic Search

Background The Medical Research Council vitamin trial highlighted the importance of folic acid in the prevention of neural tube defects. Since 1993, the Irish Department of Health has recommended periconceptional folic acid supple- ments. The objective of this study was to document the knowledge and behaviour of women in child-bearing years to periconceptio nal folic acid. Methods A cross-sectional community-base

G. M. Sayers; N. Hughes; E. Scallan; Z. Johnson

107

Evaluating food fortification options: general principles revisited with folic acid.  

PubMed Central

OBJECTIVES. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. METHODS. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. RESULTS. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. CONCLUSIONS. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply. Images FIGURE 4 FIGURE 5

Crane, N T; Wilson, D B; Cook, D A; Lewis, C J; Yetley, E A; Rader, J I

1995-01-01

108

Simultaneous analysis of folic acid and pantothenic acid in foods enriched with vitamins by stable isotope dilution assays  

Microsoft Academic Search

Folic and pantothenic acid were quantified in multivitamin products by stable isotope dilution assays using [2H4]folic acid and [13C3,15N]pantothenic acid as the internal standards. Detection was achieved by liquid chromatography\\/mass spectrometry which enabled unequivocal determination of the vitamins. Due to the very simple extraction procedure, analysis of the vitamins was completed within 2h. When analyzing multivitamin sweets, the intra-assay and

Michael Rychlik

2003-01-01

109

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

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

Godfrey P Oakley

1997-01-01

110

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

PubMed

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

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

2012-01-01

111

Pregnancy intentions and folic acid supplementation exemplars: findings from the Central Pennsylvania Women's Health Study.  

PubMed

One Healthy People 2010 objective is that 80% of women in the United States start a pregnancy with optimal levels of folic acid. This often requires women to use folic acid supplements preconceptionally to get adequate levels. Efforts to achieve the objective have resulted in a suboptimal floor effect at less than 50% of women. We advance a framework based on exemplification theory, identifying supplementation as an additive action in which two role models exemplify folic acid supplementation among women of reproductive age able to become pregnant (n = 1,258). The women were participants in Phase I of the Central Pennsylvania Women's Health Study (CePAWHS). One exemplar identified represents the positive habits aligned with supplementers considering a pregnancy sometime in their future, while the other resides in the exemplification of positive habits aligned with supplementers not considering a pregnancy sometime in their future but still able to become pregnant. Among women not considering a future pregnancy, daily green salad consumption, weekly fish consumption, having had a health care visit in the past year, and having had any ob/gyn visit in the past 2 years resulted in increased odds of folic acid supplement use in a multivariable model. In the same model, an increase in age resulted in increased odds of folic acid supplement use. Among women considering a future pregnancy, not smoking cigarettes, having higher levels of psychosocial stress, and having higher levels of interaction social support resulted in increased odds of folic acid supplement use in a multivariable model. In the same model, those who have had a health care visit in the past year, as well as those who have received pregnancy planning counseling, were also more likely to use a folic acid supplement. Implications for strategic communication are considered. PMID:19466648

Parrott, Roxanne; Volkman, Julie E; Hillemeier, Marianne M; Weisman, Carol S; Chase, Gary A; Dyer, Anne-Marie

2009-06-01

112

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

PubMed Central

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.

2013-01-01

113

Effect of maternal folic acid supplementation on hepatic one-carbon unit associated gene expressions in newborn piglets.  

PubMed

Intrauterine growth retardation (IUGR) induces alterations to hepatic gene expressions which might program poor postnatal growth and health status. Maternal folic acid supplementation was administered in gilt diets to test whether hepatic mRNA expressions of some important genes induced by IUGR could be rescued by folic acid supplementation. Thirty-two Yorkshire gilts were allotted to two treatment groups of control (C folic acid 1.3 mg/kg) or folic acid supplementation (FS folic acid 30 mg/kg) after mating, to study the effects of maternal folic acid supplementation on the mRNA expression of methionine adenosyltransferase (MAT), cystathionine-?-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), DNA methyltransferase1 (DNMT1), peroxisomal proliferator-activated receptor (PPAR?), glucocorticoid receptor (GR), obesity receptor (ob-R) and Acyl-CoA oxidase (AOX) in the liver of IUGR and NBW piglets. Blood and liver samples were collected for determinations of serum folic acid and gene expressions. The total number of born piglets, number of piglets born alive, average birth weight and 21 days average weight were not affected by dietary treatment (P>0.05), and serum folic acid concentration of piglets was greater in FS than C groups (P<0.05). Real-time PCR indicated that gene expression of MAT1A, MAT2A and DNMT1 were lower in IUGR piglets but could be elevated by maternal folic acid supplementation. Transcript expression levels of PPAR?, GR and AOX were higher in IUGR piglets, but were decreased to the level of normal piglets by maternal folic acid supplementation. Our results suggested that maternal folic acid supplementation be an effective way to rescue the gene expressions negatively induced by IUGR. PMID:21108044

Liu, Jing-Bo; Chen, Dai-Wen; Yu, Bing; Mao, Xiang-bing

2010-11-25

114

Folic acid and primary prevention of birth defects.  

PubMed

Birth defects (BDs) are an important public health problem, due to their overall incidence, occurring in 2-3% of live births in European Union. Neural tube defects (NTDs) are among major NTDs, due to their severity and relatively high incidence; in the meanwhile NTDs are also the most effectively preventable BDs to date. In particular, an adequate folic acid (FA) intake reduces both the occurrence and the recurrence of NTDs; FA is the synthetic form of folates, naturally occurring vitamins in a number of foods, especially vegetables. The daily intake of 0.4 mg of FA should be recommended to all women of childbearing age who plan to become pregnant. The Italian Network for Primary Prevention of BDs through FA Promotion has achieved a significant improvement in FA awareness and use in the periconceptional period. Nevertheless, primary prevention of BDs needs to make further progress; the Italian National Centre for Rare Diseases participates in european sureveillance of congenital anomalies (EUROCAT) Joint Action as coordinator of activities on the effectiveness of BDs prevention. Mandatory food fortification with FA has not been introduced in any European country. The health benefits of FA in reducing the risk of NTDs are undisputed; however mechanistic and animal studies suggest a relationship between high FA intakes and increased cancer promotion, while human studies are still inconsistent and inconclusive. A Working Group organized by the European Food Safety Authority pointed out significant uncertainties about fortification safety and the need for more studies; currently, FA intake from fortified foods and supplements should not exceed 1 mg/day in adults. In conclusion, based on up-to-date scientific evidence, the Italian Network strategy pivots on periconceptional supplementation integrated with promotion of healthy eating habits, support to health education, enhancing the role of women in managing life choices about their health and pregnancy and increasing the scientific knowledge about BDs primary prevention. PMID:21915935

Taruscio, Domenica; Carbone, Pietro; Granata, Orietta; Baldi, Francesca; Mantovani, Alberto

115

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

PubMed

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

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

116

Complexation of anthracene with folic acid studied by FTIR and UV spectroscopies  

NASA Astrophysics Data System (ADS)

Toxicity and transformation process of polycyclic aromatic hydrocarbons (PAHs) is strongly depended on the interaction between PAHs and the coexisting compounds. Complexation between folic acid (FA) and a typical PAH, anthracene, was investigated using FTIR and UV spectra. Appearance of a new IR band at 2362 cm -1 demonstrates that NH 2-C dbnd N(1)- moiety on pterin (PT) ring in FA is protonated when anthracene is introduced. The shift of the characteristic IR band of the PT ring and the emergence of two charge transfer bands at 254 nm and 246 nm in UV difference spectra show the presence of ?-? complexation between folic acid and anthracene. These experiments confirm that anthracene could combine with the pterin ring of folic acid through ?-? donor-acceptor interaction (EDA) and induce the protonation process in FA upon strengthening electron accepting ability of PT ring.

He, Y. Y.; Wang, X. C.; Jin, P. K.; Zhao, Bo; Fan, Xiaoyuan

2009-05-01

117

Maternal Milk and Serum Vitamin B12, Folic Acid, and Protein Levels in Indian Subjects  

PubMed Central

Serum vitamin B12 and folic acid activity levels were studied in 47 mothers. The mean serum vitamin B12 value in non-vegetarian mothers was 228 ??g./ml. ± 38·9 SE, as compared to mean values 97 ??g./ml. ± 20·7 SE in lacto-vegetarians. There was no significant difference in folic acid levels, haemoglobin, and total proteins among the different dietetic groups. Analysis of milk revealed mean vitamin B12 values of 103 ??g./ml. in non-vegetarians as compared to 91 ??g./ml. in lacto-vegetarians; the difference was not statistically significant. Mean total protein and folic acid levels for milk were similar in different dietetic groups. The figures obtained for vitamin B12 content of human milk in these mothers are considerably lower than those reported in similar studies from Western countries.

Jathar, V. S.; Kamath, S. A.; Parikh, M. N.; Rege, D. V.; Satoskar, R. S.

1970-01-01

118

Folic acid for prevention of neural tube defects: pediatric anticipatory guidance.  

PubMed

The incidence of neural tube defects including myelomeningocele, which is one of the most common causes of infant and childhood disability, can be substantially reduced by folic acid supplementation to the diet of women before and during the early stages of pregnancy. All females of childbearing age should be taking folic acid supplements of 0.4 mg/day (400 micrograms/day) and consuming a diet rich in folate. Because many pregnancies are unplanned, supplementation should not await plans for pregnancy. Because pediatric nurse practitioners are in frequent contact with both adolescent patients and patients whose mothers are of childbearing age, and because pediatric nurse practitioners have an interest in preventing neural tube defects in future pediatric patients, they are in a good position to provide the necessary anticipatory guidance regarding the critical need for adequate folic acid intake by females of childbearing age. This article discusses and includes guidelines for providing this anticipatory guidance. PMID:9592437

Morrow, J D; Kelsey, K

119

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

SciTech Connect

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.

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

1987-09-01

120

Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-20061-3  

Microsoft Academic Search

Background: The term total folate intake is used to represent folate that occurs naturally in food as well as folic acid from fortified foods and dietary supplements. Folic acid has been referred to as a double-edged sword because of its beneficial role in the preven- tion of neural tube defects and yet possible deleterious effects on certain cancers and cognitive

Regan L Bailey; Kevin W Dodd; Jaime J Gahche; Johanna T Dwyer; Margaret A McDowell; Elizabeth A Yetley; Christopher A Sempos; Vicki L Burt; Kathy L Radimer; Mary Frances Picciano

121

Effect of Baking Process on Added Folic Acid and Endogenous Folates Stability in Wheat and Rye Breads  

Microsoft Academic Search

In Poland bread as a staple food both made from wheat and rye flour can be a potential product for future fortification with folic acid. The objective of the study was to examine the effect of fermentation and baking on added folic acid and some endogenous folates stability during breadmaking of rye and wheat breads. Breads were produced using the

El?bieta Gujska; Katarzyna Majewska

2005-01-01

122

Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification1-3  

Microsoft Academic Search

Background: A relation between low folate status and depression has been recognized since the 1960s. Since 1998, flour in the United States has been fortified with folic acid, and the prevalence of folate deficiency has decreased dramatically. Objective: We investigated whether, in this era of folic acid forti- fication, low folate status is a determinant of depressive symptoms in a

Marisa I Ramos; Lindsay H Allen; Mary N Haan; Ralph Green; Joshua W Miller

123

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

Microsoft Academic Search

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

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

124

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

PubMed Central

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.

Lee, Soo-Jung; Kang, Myung-Hee

2011-01-01

125

Efficacy of homocysteine lowering therapy with folic acid in stroke prevention: a meta-analysis  

PubMed Central

Background and Purpose Although lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized controlled trials (RCTs) have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of RCTs to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods Salient trials were identified by formal literature search. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between folic acid supplementation and risk of stroke, pooling data across trials using a fixed-effects model. Results The search identified 13 RCTs of folic acid therapy to reduce homocysteine, enrolling 39,005 participants, in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR 0.93, 95% CI 0.85-1.03; p=0.16). The RR for non-secondary prevention trials was 0.89 (95% CI 0.79-0.99; p=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR 0.83, 0.71-0.97; p=0.02) and in the trials which disproportionately enrolled male patients (men/women > 2, RR 0.84, 0.74-0.94; p=0.003). Conclusions Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation.

Lee, Meng; Hong, Keun-Sik; Chang, Shen-Chih; Saver, Jeffrey L.

2010-01-01

126

Folic acid deficiency inhibits neural rosette formation and neuronal differentiation from rhesus monkey embryonic stem cells.  

PubMed

Evidence from epidemiological studies has proved that periconceptional use of folic acid (FA) can significantly reduce the risk of neural tube defects (NTDs). However, it is hard to explore when and how FA plays roles in neurogenesis and brain development in vivo, especially in human or other nonhuman primate systems. Primate embryonic stem cell (ESC) lines are ideal models for studying cell differentiation and organogenesis in vitro. In the present study, the roles of FA in neural differentiation were assessed in a rhesus monkey ESC system in vitro. The results showed no significant difference in the expression of neural precursor markers, such as nestin, Sox-1, or Pax-6, among neural progenitors obtained from different FA concentrations or with the FA antagonist methotrexate (MTX). However, FA depletion decreased cell proliferation and affected embryoid body (EB) and neural rosette formation, as well as neuronal but not neuroglia differentiation. Our data imply that the ESC system is a suitable model for further exploring the mechanism of how FA works in prevention of NTDs in primates. PMID:22411734

Chen, Yongchang; Wang, Zhengbo; Xie, Yunhua; Guo, Xiangyu; Tang, Xianghui; Wang, Shufen; Yang, Shihua; Chen, Kai; Niu, Yuyu; Ji, Weizhi

2012-03-13

127

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

PubMed Central

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.

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

2013-01-01

128

Folic acid use in pregnant patients presenting to the emergency department  

Microsoft Academic Search

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

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

2011-01-01

129

Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89 through decreased host toxicity with oral folic acid.  

PubMed

The purpose of this investigation was to determine whether antitumor selectivity of the third generation thymidylate synthase inhibitor 1843U89 could be enhanced by a combination of the drug with folic acid. The effects of folic acid on toxicity of 1843U89 to the dog and mouse and on antitumor efficacy of 1843U89 in the mouse were studied. These data were compared to the effect of folic acid on the in vitro cell culture antitumor activity of 1843U89. The sensitivity of eight cancer cell lines (three ovarian, one colon, one ileocecal, one epidermoid, one osteosarcoma, and one breast line) to 1843U89 was tested in vitro in the presence and absence of folic acid. Folic acid concentrations greater than 100 microM were required to decrease 1843U89 activity in seven of the cell lines. Only the activity in HCT-8, the ileocecal line, was reserved at folic acid concentrations below 100 microM. Oral folic acid given 30 min prior to an i.v. dose of 1843U89 increased the maximally tolerated dose and the lethal dose of 1843U89, both in dogs and in thymidine-depleted mice. In mice, oral folic acid produced little or no effect upon the antitumor efficacy of 1843U89 in two of three tumor cell lines in vivo. HCT-8, the line that was sensitive to folate reversal in vitro, was also sensitive in vivo. The results show that an oral dose of folic acid 30 min prior to i.v. 1843U89 can block mouse and dog intestinal toxicity without decreasing efficacy of 1843U89 in two of three human tumor lines in the nude mouse. Thus, the data reported here indicate that the antitumor selectivity of 1843U89 may be enhanced through a combination of 1843U89 with oral folic acid. PMID:8521402

Smith, G K; Amyx, H; Boytos, C M; Duch, D S; Ferone, R; Wilson, H R

1995-12-15

130

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

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

Alida Melse-Boonstra; Henk J Blom; Petra Verhoef

131

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

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

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

2006-06-14

132

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

SciTech Connect

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.

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

133

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

Microsoft Academic Search

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

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

2005-01-01

134

Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis  

Microsoft Academic Search

It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability

Wen-lin Xiao; Min Wu; Bing Shi

2006-01-01

135

Increased awareness, knowledge and utilization of preconceptional folic acid in Israel following a national campaign  

Microsoft Academic Search

Background. To decrease the risk of neural tube defects (NTDs), the Israeli Ministry of Health (MOH) issued guidelines in August 2000 recommending daily folic acid (FA) supplementation for women in their childbearing age, and concurrently launched a national FA campaign. Campaign effects were assessed by comparing the results of a survey done in 2002 with a baseline survey done in

Yona Amitai; Nirah Fisher; Miri Haringman; Hana Meiraz; Nira Baram; Alex Leventhal

2004-01-01

136

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

Microsoft Academic Search

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

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

2012-01-01

137

Inverse Correlation of Low Vitamin B12, Folic Acid and Homocysteine Levels in Diabetic Retinopathy  

Microsoft Academic Search

Purpose: Evaluation of total plasma homocysteine, serum vitamin B12 and folic acid levels in patients with diabetic retinopathy. Materials and Methods: Fifty patients having insulin dependent diabetes mellitus were included and subdivided into 3 groups: Diabetics without retinopathy (n=10), with background retinopathy (n=20), and proliferative retinopathy (n=20). Ten nor- mal subjects served as controls. Plasma total homocysteine levels were measured

Soher A. Mohammed Ismail; Iman A. Fahmy; Samah Ali; Mostafa Farrag

138

Folic acid fortification prevents neural tube defects and may also reduce cancer risks.  

PubMed

The prevalence of neural tube defect (NTD)-affected pregnancies ranges between 0.4 and 2/1000 pregnancies in EU. NTDs result in severe malformations and sometimes miscarriages. Children born with NTD suffer for the rest of their life of disability and chronic healthcare issues, and many women therefore choose termination of pregnancy if NTD is diagnosed prenatally. Women planning for pregnancy are recommended to eat 400??g folic acid/d, whereas average figures across Europe indicate intakes of ?250??g/d for women of fertile age, a gap that could be bridged by implementation of folic acid fortification. The results of mandatory folic acid fortifications introduced in USA and Canada are a decrease between 25 and 45% of NTD pregnancies. Conclusion:? Evidence-based NTD prophylaxis is now practised in more than 60 countries worldwide. EU countries worry over possible cancer risks, but ignore a wealth of studies reporting decreasing cancer risks with folate intakes at recommended levels. Currently, there are indications of a U-shaped relationship, that is, higher cancer risks at low folate intakes (<150??g/day) and highly elevated folate intakes (>1?mg/day), respectively. However neither the global World Cancer Research review nor EU's European Food Safety Authority report present data on increased cancer risk at physiological folate intake levels. Therefore, EU should act to implement folic acid fortification as NTD prophylaxis as soon as possible. PMID:22783992

Jägerstad, Margaretha

2012-07-24

139

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

PubMed

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

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

2005-12-01

140

Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: A relation between low folate status and depression has been recognized since the 1960's. Since 1998, flour in the United States has been fortified with folic acid, and the prevalence of folate deficiency has decreased dramatically. OBJECTIVE: We investigated whether, in this era of fol...

141

Effect of folic acid fortification on the characteristics of lemon yogurt  

Microsoft Academic Search

Development of dairy products with new flavors and health benefits helps the dairy industry increase sales of products as well as provide consumers with products they enjoy. Folic acid is used in the prevention of neural tube defects, heart defects, facial clefts, urinary tract abnormalities, and limb deficiencies. The objective of this study was to determine the effect of different

C. A. Boeneke; K. J. Aryana

2008-01-01

142

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

ERIC Educational Resources Information Center

|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…

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

2010-01-01

143

Blocking tumor necrosis factor-? inhibits folic acid-induced acute renal failure  

Microsoft Academic Search

Systemic administration of mice with folic acid (FA) has been used for studying the pathogenesis of acute renal failure. However, the molecular mechanisms by which FA induces acute renal failure remain poorly understood. We found that CD-1 mice treated with FA developed acute renal failure characterized by increased blood urea nitrogen, necrosis, and apoptosis of tubular epithelial cells. Compared to

Bing Wan; Li Hao; Yuhua Qiu; Zhongwen Sun; Qi Cao; Yi Zhang; Tongyu Zhu; Hao Wang; Yanyun Zhang

2006-01-01

144

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...

145

“New” cardiovascular risk factors in patients with chronic kidney disease: Role of folic acid treatment  

Microsoft Academic Search

“New” cardiovascular risk factors in patients with chronic kidney disease: Role of folic acid treatment.Cardiovascular disease (CVD) is the principal cause of mortality in patients with chronic renal disease undergoing hemodialysis. In addition to the CVD risk factors, a new hypothesis has recently been aroused related to “new” factors involved in the development of atherosclerosis in the uremic patient; worthwhile

BEATRIZ BAYÉS; MARI CRUZ PASTOR; JORDI BONAL; RAMÓN ROMERO

2005-01-01

146

Folic Acid Supplements in Pregnancy and Severe Language Delay in Children  

PubMed Central

Context Prenatal folic acid supplements reduce the risk of neural tube defects and may have beneficial effects on other aspects of neurodevelopment. Objective To examine associations between mothers' use of prenatal folic acid supplements and risk of severe language delay in their children at age 3 years. Design, Setting, and Patients The prospective observational Norwegian Mother and Child Cohort Study recruited pregnant women between 1999 and December 2008. Data on children born before 2008 whose mothers returned the 3-year follow-up questionnaire by June 16, 2010, were used. Maternal use of folic acid supplements within the interval from 4 weeks before to 8 weeks after conception was the exposure. Relative risks were approximated by estimating odds ratios (ORs) with 95% CIs in a logistic regression analysis. Main Outcome Measure Children's language competency at age 3 years measured by maternal report on a 6-point ordinal language grammar scale. Children with minimal expressive language (only 1-word or unintelligible utterances) were rated as having severe language delay. Results Among 38 954 children, 204 (0.5%) had severe language delay. Children whose mothers took no dietary supplements in the specified exposure interval were the reference group (n=9052 [24.0%], with severe language delay in 81 children [0.9%]). Adjusted ORs for 3 patterns of exposure to maternal dietary supplements were (1) other supplements, but no folic acid (n=2480 [6.6%], with severe language delay in 22 children [0.9%]; OR, 1.04; 95% CI, 0.62-1.74); (2) folic acid only (n=7127 [18.9%], with severe language delay in 28 children [0.4%]; OR, 0.55; 95% CI, 0.35-0.86); and (3) folic acid in combination with other supplements (n=19005 [50.5%], with severe language delay in 73 children [0.4%]; OR, 0.55; 95% CI, 0.39-0.78). Conclusion Among this Norwegian cohort of mothers and children, maternal use of folic acid supplements in early pregnancy was associated with a reduced risk of severe language delay in children at age 3 years.

Roth, Christine; Magnus, Per; Schj?lberg, Synnve; Stoltenberg, Camilla; Suren, Pal; McKeague, Ian W.; Smith, George Davey; Reichborn-Kjennerud, Ted; Susser, Ezra

2013-01-01

147

Absorption of folic acid from a softgel capsule compared to a standard tablet.  

PubMed

Consumption of 400 ?g folic acid per day from fortified foods and/or supplements, plus food folate from a varied diet is recommended for women of childbearing potential to reduce the risk for neural tube defects during fetal development. This randomized crossover study was designed to evaluate the bioavailability of folic acid from a multivitamin softgel capsule vs a folic acid tablet in 16 premenopausal women (18 to 45 years of age). Participants were randomly assigned to receive a single dose of ?1,000 ?g folic acid in two tablets or ?1,000 ?g folic acid in a multivitamin softgel capsule, and then crossed over to receive the other study product ?1 week later. Products were administered with a low-folate breakfast. Blood samples were collected predose (0 hour) and 1, 2, 3, 4, 6, and 8 hours post-dose for serum folate analysis. Repeated measures analysis of variance was used to compare responses between treatments. Data from the two sequence groups (n=8 per sequence) were pooled. Mean serum folate total and net incremental areas under the curve (AUC(0-8 hours)) were not significantly different between tablets and softgel capsule (AUC(0-8 hours) 214.9±11.2 hours×ng/mL [487±25.4 hours×nmol/L] and 191.6±13.3 hours×ng/mL [434.2±30.1 hours×nmol/L]; net incremental AUC(0-8 hours) 117.3±8.5 hours×ng/mL [265.8±19.3 hours×nmol/L] and 105.8±12.5 hours×ng/mL [239.7±28.3 hours×nmol/L], respectively), nor was maximum folate concentration (45.1±2.5 ng/mL [102.2±5.7 nmol/L] and 42.5±3.8 ng/mL [96.3±8.6 nmol/L], respectively). Time to peak folate concentration was significantly (P<0.001) delayed for the softgel capsule vs tablet (3.9±0.3 vs 1.7±0.2 hours, respectively). In conclusion, apparent bioavailability of folic acid was similar for the folic acid tablets and a multivitamin softgel capsule. PMID:22579722

Maki, Kevin C; Ndife, Louis I; Kelley, Kathleen M; Lawless, Andrea L; Brooks, James R; Wright, Shannon B; Shields, Jocelyn M; Dicklin, Mary R

2012-05-11

148

Folic acid transport via high affinity carrier-mediated system in human retinoblastoma cells.  

PubMed

The primary objective of this study was to investigate the expression of a specialized carrier-mediated system for folic acid and to delineate its uptake mechanism and intracellular trafficking in a human derived retinoblastoma cell line (Y-79). Uptake of [3H]Folic acid was determined at various concentrations, pH, temperatures, in the absence of sodium and chloride ions and in the presence of structural analogs, methyltetrahydro folate (MTF) and methotrexate (MTX), vitamins, membrane transport and metabolic inhibitors to delineate the mechanism of uptake. Kinetics of uptake was studied in the presence of various intracellular regulatory pathways; protein kinases A and C (PKA and PKC), protein tyrosine kinase (PTK) and calcium-calmodulin modulators. Reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm the molecular identity of folate carrier systems. The uptake was found to be linear up to 30min. The rate of uptake followed saturation kinetics with apparent Km of 8.29+/-0.74nM, 17.03+/-1.98nM and 563.23+/-115.2nM and Vmax of 393.47+/-9.33, 757.58+/-26.21 and 653.17+/-31.7fmol/(minmg) protein for folic acid, MTF and MTX, respectively. The process was chloride, temperature and energy dependent but sodium and pH independent; inhibited by the structural analogs MTF and MTX but not by structurally unrelated vitamins. Membrane transport inhibitors did not affect the uptake of [3H]Folic acid, however endocytic inhibitor, colchicine, significantly inhibited the [3H]Folic acid uptake indicating the involvement of receptor mediated endocytosis process. PKC, PTK and Ca2+/calmodulin pathways appeared to play important roles in the regulation of folic acid uptake. Molecular evidence of the presence of folate receptor (FR) precursor was identified by RT-PCR analysis. This research work demonstrated, for the first time, the functional and molecular existence of a specialized high affinity carrier-mediated system for folic acid uptake, in human retinoblastoma cells. PMID:18207340

Kansara, Viral; Paturi, Durga; Luo, Shuanghui; Gaudana, Ripal; Mitra, Ashim K

2007-12-23

149

Folic Acid Enhances Early Functional Recovery in a Piglet Model of Pediatric Head Injury  

PubMed Central

For stroke and spinal cord injury, folic acid supplementation has been shown to enhance neurodevelopment and to provide neuroprotection. We hypothesized that folic acid would reduce brain injury and improve neurological outcome in a neonatal piglet model of traumatic brain injury (TBI), using 4 experimental groups of 3- to 5-day-old female piglets. Two groups were intubated, anesthetized and had moderate brain injury induced by rapid axial head rotation without impact. One group of injured (Inj) animals received folic acid (Fol; 80 ?g/kg) by intraperitoneal (IP) injection 15 min following injury, and then daily for 6 days (Inj + Fol; n = 7). The second group of injured animals received an IP injection of saline (Sal) at the same time points (Inj + Sal; n = 8). Two uninjured (Uninj) control groups (Uninj + Fol, n = 8; Uninj + Sal, n = 7) were intubated, anesthetized and received folic acid (80 ?g/kg) or saline by IP injection at the same time points as the injured animals following a sham procedure. Animals underwent neurobehavioral and cognitive testing on days 1 and 4 following injury to assess behavior, memory, learning and problem solving. Serum folic acid and homocysteine levels were collected prior to injury and again before euthanasia. The piglets were euthanized 6 days following injury, and their brains were perfusion fixed for histological analysis. Folic acid levels were significantly higher in both Fol groups on day 6. Homocysteine levels were not affected by treatment. On day 1 following injury, the Inj + Fol group showed significantly more exploratory interest, and better motor function, learning and problem solving compared to the Inj + Sal group. Inj + Fol animals had a significantly lower cognitive composite dysfunction score compared to all other groups on day 1. These functional improvements were not seen on day 4 following injury. Axonal injury measured by ?-amyloid precursor protein staining 6 days after injury was not affected by treatment. These results suggest that folic acid may enhance early functional recovery in this piglet model of pediatric head injury. This is the first study to describe the application of complex functional testing to assess an intervention outcome in a swine model of TBI.

Naim, Maryam Y.; Friess, Stuart; Smith, Colin; Ralston, Jill; Ryall, Karen; Helfaer, Mark A.; Margulies, Susan S.

2011-01-01

150

Folic acid supplementation diminishes diabetes- and glucose-induced dysmorphogenesis in rat embryos in vivo and in vitro.  

PubMed

Maternal administration of folic acid diminishes the risk of neural tube defects (NTDs) in offspring, but whether folic acid exerts a similar effect in diabetic pregnancy is unknown. The aim was to investigate whether maldevelopment in rat embryos caused by exposure to diabetes in vivo or high-glucose concentrations in vitro is affected by subcutaneous administration of folic acid to the pregnant mother or by adding the compound to the culture medium, respectively. Exposure of embryos to maternal diabetes in vivo or 30 mmol/l glucose in vitro yielded an increased malformation rate (71 and 88% NTD, respectively) and lowered somite number and crown-rump length compared with control embryos. When we injected folic acid into the diabetic pregnant rat, or added 2 mmol/l folic acid to the culture medium with high glucose, the embryonic parameters improved (3 and 5% NTD, respectively). The present work shows that administration of folic acid can diminish diabetes-induced maldevelopment. This suggests that folic acid supplementation may have a role in the prevention of malformations in diabetic pregnancy. PMID:15677514

Wentzel, Parri; Gäreskog, Mattias; Eriksson, Ulf J

2005-02-01

151

Determination of folate/folic acid level in milk by microbiological assay, immuno assay and high performance liquid chromatography.  

PubMed

A concurrent determination of folate versus folic acid in milk by microbiological assay (MA) with Lactobacillus rhamnosus as the assay organism, Enzyme Linked Immuno Sorbent Assay (ELISA) by competitive binding rapid ELISA kit (RIDASCREEN®) and high-pressure-liquid chromatography (HPLC) was done for detection of the folate form and its level. MA gave total folate content as Lb. rhamnosus showed similar response to most folate isomers formed by the tri-enzyme treatment in comparison with the other two methods which specifically estimated the folic acid. In case of ELISA, specificity was apparently limited to folic acid and dihydro folic acid and thereby showed a lower response for other folate derivatives. Estimation by HPLC with UV detector was highly specific and hence only folic acid could be detected without any cross reactivity. Among the different methods HPLC was observed to be the most sensitive method for determination of folic acid and hence can efficiently determine the folic acid fortification level while MA remained highly efficient, sensitive and reproducible method for estimation of total folate indicating its potential use for dietary folate estimation. PMID:23506679

Iyer, Ramya; Tomar, Sudhir Kumar

2013-03-18

152

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

PubMed Central

Purpose Since 1992, the Centers for Disease Control and Prevention recommends that women of childbearing age consume 400 µg of folic acid per day to reduce the risk of neural tube defects (NTD). It has been speculated that both NTD and nervous system tumors (NST) may share common mechanisms of altered development. It examines the association between folic acid supplementation and the risk for childhood NST. Methods Incident cases of children with cancer in Spain registered between 2004 and 2006 were identified through the MACAPE Network Group. Tumors were classified as tumors derived from the neuroectoderm (cases) and those with a mesoderm origin (controls). In a second analysis, NST were further divided into central nervous system tumors (CNST) and sympathetic nervous system tumors (SNST). We compared folic acid supplementation between the groups. Results Overall, folic acid supplementation any time during pregnancy was similar between cases and controls (odds ratio (OR)=1.05; 95% confidence interval (CI) 0.92–1.20). However, supplementation before the 21st and 36th days of gestation resulted in significantly lower NST than in children with mesoderm tumors (OR=0.34; 95% CI 0.17–0.69 and OR=0.58; 95% CI 0.37–0.91, respectively). Preconceptional intakes of folic acid were also lower in NST although marginally nonsignificant (OR=0.44; 95% CI 0.10–1.02). When NST were divided into CNST and SNST, significant differences between tumors of mesoderm origin were only found for CNST. Conclusions Our results support the hypothesis that folate supplementation reduces the risk of childhood NST, especially CNST. The specific mechanism and cellular role that folate may play in the development of CNST have yet to be elucidated.

Ferris-Tortajada, Josep; Claudio, Luz; Soldin, Offie Porat; Sanchez-Sauco, Miguel Felipe; Fuster-Soler, Jose Luis; Martinez-Lage, Juan Francisco

2011-01-01

153

Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy.  

PubMed

Folic acid has been shown to decrease the incidence of neural tube defects (NTDs) in normal and hyperglycemic conditions, but the influence of folic acid on the development of central nervous system is not fully understood. Here, we aimed to explore the effects of folic acid, especially high dose of folic acid, on the characteristics of neural progenitors in embryos of hyperglycemic and diabetic mouse. Hyperglycemic and diabetic pregnant mice were given 3 mg/kg or 15 mg/kg folic acid from embryonic day 0.5 (E0.5) and were euthanased on E11.5, E13.5 or E18.5. The incidence of NTDs at E13.5 was counted. The proliferation, apoptosis and differentiation of neural progenitors and neuronal migration were determined using BrdU incorporation assay, TUNEL assay, immunofluorescence, Western blot and real-time reverse transcriptase polymerase chain reaction. Both normal and high doses of folic acid decreased the incidence of NTDs, promoted proliferation and reduced apoptosis of neuroepithelial cells in embryos of hyperglycemic and diabetic mice. Importantly, folic acid, especially at high dose, might affect the premature differentiation of neural progenitors in embryos of hyperglycemic and diabetic pregnancy. This may be attributed to changes of messenger RNA expression levels of some basic-helix-loop-helix transcription factors. In addition, folic acid might be involved in regulating neuronal migration in embryos of hyperglycemic and diabetic pregnancy. These findings suggest that periconceptional supplementation of folic acid, especially at high dose, may be a double-edged sword because it may result in undesirable outcomes affecting both the neuronal and glial differentiation in hyperglycemic and diabetic pregnancy. PMID:23260036

Yuan, Qiuhuan; Zhao, Shidou; Liu, Shangming; Zhang, Yanmin; Fu, Jie; Wang, Fuwu; Liu, Qian; Ling, Eng-Ang; Hao, Aijun

2012-12-21

154

Pro-thrombotic effects of a folic acid deficient diet in rat platelets and macrophages related to elevated homocysteine and decreased n-3 polyunsaturated fatty acids  

Microsoft Academic Search

Folic acid deficiency represents a vitamin deficiency that may be due either to an inadequacy of the dietary supply or to an increased requirement. It leads to a number of abnormalities including hematological, neurological and cardiovascular disorders. In this study, we investigated whether folic acid deficiency would influence platelet and macrophage activities. For 6 weeks, rats were fed a test

Philippe Durand; Michel Prost; Denis Blache

1996-01-01

155

The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths  

PubMed Central

Background Pregnancy is a state of increased requirement of macro- and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes including stillbirths. Many nutritional interventions have been proposed during pregnancy according to the nutritional status of the mother and baseline risk factors for different gestational disorders. In this paper, we have reviewed three nutritional interventions including peri-conceptional folic acid supplementation, balanced protein energy supplementation and multiple micronutrients supplementation during pregnancy. This paper is a part of a series to estimate the effect of interventions on stillbirths for input to Live Saved Tool (LiST) model. Methods We systematically reviewed all published literature to identify studies evaluating effectiveness of peri-conceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths. The primary outcome was stillbirths. Meta-analyses were generated where data were available from more than one study. Recommendations were made for the Lives Saved Tool (LiST) model based on rules developed by the Child Health Epidemiology Reference Group (CHERG). Results There were 18 studies that addressed peri-conceptional folic acid supplementation for prevention of neural tube defects (NTDs). Out of these, 7 studies addressed folic acid supplementation while 11 studies evaluated effect of folic acid fortification. Pooled results from 11 fortification studies showed that it reduces primary incidence of NTDs by 41 % [Relative risk (RR) 0.59; 95 % confidence interval (CI) 0.52-0.68]. This estimate has been recommended for inclusion in the LiST as proxy for reduction in stillbirths. Pooled results from three studies considered to be of low quality and suggest that balanced protein energy supplementation during pregnancy could lead to a reduction of 45% in stillbirths [RR 0.55, 95 % CI 0.31-0.97]. While promising, the intervention needs more effectiveness studies before inclusion in any programs. Pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 – 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 – 1.25; random model]. No recommendations have been made for this intervention for inclusion in the LiST model. Conclusions Peri-conceptional folic acid supplementation reduces stillbirths due to NTDs by approximately 41%, a point estimate recommended for inclusion in LiST.

2011-01-01

156

Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry.  

PubMed

A stable isotope liquid chromatography-mass spectrometry (LC-MS) method was developed for the quantitative determination of 5-methyltetrahydrofolic acid (5-MTHFA) and folic acid in a variety of commercial citrus juices. Folates were extracted from juices, and the polyglutamyl side chain of 5-MTHFA was cleaved to the monoglutamate form using rat plasma conjugase. The folates were purified on a Bond-Elut column and analyzed by LC-MS with electrospray ionization. The analytes were quantified using the (13)C(5) analogues of 5-MTHFA and folic acid as internal standards. The relative standard error of the method was 3.35% based on replicate analyses (n = 4). This method was then applied to the determination of 5-MTHFA and folic acid in a variety of citrus juices obtained from local supermarkets. It was observed that although both "store" brands and "national" brands of fresh (nonfrozen) juices contained similar concentrations of 5-MTHFA, the "store" brands of fresh juices had on average >5-fold the amount of folic acid compared to the "national" brands. In addition, the "total" folate concentrations were generally below values listed on the food label. PMID:12590471

Thomas, Paul M; Flanagan, Vincent P; Pawlosky, Robert J

2003-02-26

157

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

Microsoft Academic Search

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

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

158

Enhanced Reduction of Fasting Total Homocysteine Levels With Supraphysiological Versus Standard Multivitamin Dose Folic Acid Supplementation in Renal Transplant Recipients  

Microsoft Academic Search

The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, $6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60

Andrew J. Beaulieu; Reginald Y. Gohh; Haewook Han; David Hakas; Paul F. Jacques; Jacob Selhub; Andrew G. Bostom

159

High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela  

Microsoft Academic Search

Background:There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease.Objective:This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population.Methods:A total of 5658 serum samples were processed

M N García-Casal; C Osorio; M Landaeta; I Leets; P Matus; F Fazzino; E Marcos

2005-01-01

160

Supplemental Dietary Folic Acid Has No Effect on Chromosome Damage in Erythrocyte Progenitor Cells of Mice123  

PubMed Central

Folate deficiency can cause chromosome damage, which could result from reduced de novo thymidylate synthesis or DNA hypomethylation. High folic acid intake has been hypothesized to inhibit folate-dependent one-carbon metabolism, which could also lead to DNA damage. A large proportion of the general population may have high folic acid intakes. In this study, 2 experiments were conducted to examine the effects of folate on chromosome damage. First, male mice were fed folic acid–deficient (D) (0 mg folic acid/kg diet), control (C) (2 mg/kg), or folic acid–supplemented (S) (6 mg folic acid/kg diet) diets from weaning to maturity. Second, female mice were fed the D, C, or S diet throughout pregnancy, lactation, and breeding for 3 generations; male mice from the F3 generation were fed the same diet as their mothers from weaning, producing D, C, and S F3 male mice. RBC micronucleus frequencies, a measure of chromosome damage or aneuploidy, were determined for both experimental groups. In mice fed diets from weaning to maturity, erythrocyte micronucleus frequency was 24% greater in D compared with C mice. F3 mice fed diet D had 260% and 174% greater reticulocyte and erythrocyte micronucleus frequencies compared with F3 C mice, respectively. The S diets did not affect micronucleus frequency, suggesting that excess folic acid at this level does not promote or protect against chromosome damage. The results suggest that chronic exposure to folic acid at the levels similar to those achieved through fortification is unlikely to be clastogenic or aneugenic.

Swayne, Breanne G.; Behan, Nathalie A.; Williams, Andrew; Stover, Patrick J.; Yauk, Carole L.; MacFarlane, Amanda J.

2012-01-01

161

Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness  

Microsoft Academic Search

Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13\\/25 (52%), vitamin B12 deficiency in 7\\/24 (29%), and folic acid

G Vreugdenhil; A W Wognum; H G van Eijk; A J Swaak

1990-01-01

162

HPLC Determination of Stability and Distribution of Added Folic Acid and Some Endogenous Folates During Breadmaking 1  

Microsoft Academic Search

Cereal Chem. 78(4):375-378 Bread flour was spiked with folic acid (1.40 mg\\/lb or 3.08 µg\\/g of flour) and processed into bread by the sponge and dough method. Changes that occurred to added folic acid and endogenous folate contents through different processing stages, including sponge formation, proofing, and baking, were assessed by reversed-phase ion-pair HPLC combined with UV and fluorometric detection.

Elolo S. Osseyi; Randy L. Wehling; Julie A. Albrecht

2001-01-01

163

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

PubMed Central

Background & Aims: At least 500 ?g of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 ?g of folate or with one 500 ?g capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: –15.9 to –1.2) and synthetic folic acid capsules by 8% (95% CI: –13.3 to –2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease.

2005-01-01

164

High-Performance Liquid Chromatography Method for the Determination of Folic Acid in Fortified Food Products  

PubMed Central

Reversed-phase high-performance liquid chromatography, coupled with coulometric electrochemical detection, was successfully applied for the quantification of added folic acid (FA) in fortified fruit juices and cereal products. The method allowed good separation of the 5-HCO-H4 folate and folic acid in cereal samples. The retention times of vitamins were repeatedly determined by isocratic elution using 40 mM sodium phosphate dibasic, heptahydrate buffer, and 8% acetonitrile (v/v) (0.9 mL/min, pH 5.5) as mobile phase with the Supelco LC 18 column 5 ?m (25 cm × 4.6 mm). Folate concentrations were measured using a trienzyme (hog kidney folate conjugase, ?-amylase, and protease) folate extraction method.

Lebiedzinska, A.; Dabrowska, M.; Szefer, P.; Marszall, M.

2008-01-01

165

Effect of vitamin B12 and folic acid deficiency on small intestinal absorption  

PubMed Central

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B12 may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B12 returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B12 was corrected by vitamin B12 therapy in the other two patients. The initial cause of the vitamin B12 deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B12 absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.

Forshaw, John

1969-01-01

166

Effects of Folic Acid on Cardiac Myocyte Apoptosis in Rats with Streptozotocin-induced Diabetes Mellitus  

Microsoft Academic Search

Backgrounds  The effect of folic acid on cardiac myocyte apoptosis secondary to diabetes is unknown.\\u000a \\u000a \\u000a \\u000a Methods  Diabetic rats were divided into diabetic control (DC, n?=?11), low-dose (LDF, 0.4 mg\\/kg\\/day, n?=?12) and high-dose (HDF, 1.2 mg\\/kg\\/day, n?=?12) folic acid groups. Non-diabetic rats (n?=?11) were used as the normal control (NC).\\u000a \\u000a \\u000a \\u000a Results  After 11 weeks of treatment, compared with the NC group, the DC group showed a reduced

Tong-Guo Wu; Wei-Hong Li; Zi-Qing Lin; Le-Xin Wang

2008-01-01

167

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

Microsoft Academic Search

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

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

168

Folic acid promotion for Hispanic women in Florida: A vitamin diary study  

Microsoft Academic Search

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 materials were given a supply of vitamins and reported, on a daily basis, how

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

2010-01-01

169

Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation  

Microsoft Academic Search

Summary: Purpose: To assess the prevalence of hyperhomo- cysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperho- mocysteinemic patients. Methods: 123 patients from three regional hospitals partic- ipated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing

Martina Huemer; Bernd Ausserer; Gunther Graninger; Michael Hubmann; Christian Huemer; Kurt Schlachter; Arthur Tscharre; Hanno Ulmer; Burkhard Simma

2005-01-01

170

Is adequate and balanced nutrition during pregnancy more effective than iron and folic acid supplements?  

Microsoft Academic Search

To provide instruction for pregnant women regarding adequate and balanced nutrition and determine whether iron and folic acid\\u000a supplementation is essential. The research was an experimental clinical intervention. The study was conducted between March\\u000a 2004 and May 2005 with 80 pregnant volunteers. The study participants were in their 16th to 24th weeks of pregnancy; all participants\\u000a were healthy, carried only

Funda Elmacioglu; Bulent Surucu; Tayfun Alper; Aliye Ozenoglu; Serdal Ugurlu

2010-01-01

171

Effects of nutrition on zinc, folic acid, and vitamin B 12 levels during pregnancy  

Microsoft Academic Search

In this article, we report the results of a case control study carried out on 290 Turkish pregnant women at 5–24 wk of gestation\\u000a to determine their zinc, folic acid, and vitamin B12 levels in relation to their nutritional and socioconomic status. The women were divided into two groups (n=145 each), depending on the stage of gestation. Group I consisted

Maturat Erdogan; Isik Üstüner; Bora Cengiz; Feride Söylemez; Ayhan O. Çavdar

2006-01-01

172

Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.  

PubMed

We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it. PMID:22367474

Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

2012-02-26

173

Folic Acid Transport to the Human Fetus Is Decreased in Pregnancies with Chronic Alcohol Exposure  

PubMed Central

Background During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption. Methodology/Principal Findings Serum folate was measured in maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure (n?=?23) and in non-drinking controls (n?=?24). In the alcohol-exposed pairs, the fetal?maternal serum folate ratio was ?1.0 in over half (n?=?14), whereas all but one of the controls were >1.0. Mean folate in cord samples was lower in the alcohol-exposed group than in the controls (33.15±19.89 vs 45.91±20.73, p?=?0.04). Conclusions/Significance Our results demonstrate that chronic and heavy alcohol use in pregnancy impairs folate transport to the fetus. Altered folate concentrations within the placenta and in the fetus may in part contribute to the deficits observed in the fetal alcohol spectrum disorders.

Hutson, Janine R.; Stade, Brenda; Lehotay, Denis C.; Collier, Christine P.; Kapur, Bhushan M.

2012-01-01

174

Childhood Cancer Incidence Trends in Association With US Folic Acid Fortification (1986-2008)  

PubMed Central

OBJECTIVE: Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996–1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification. METHODS: Using Surveillance, Epidemiology, and End Results program data (1986–2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models. RESULTS: From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns. CONCLUSIONS: These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification.

Johnson, Kimberly J.; Ross, Julie A.

2012-01-01

175

U.S. Provider Reported Folic Acid or Multivitamin Ordering for Non-Pregnant Women of Childbearing Age: NAMCS and NHAMCS, 2005–2006  

Microsoft Academic Search

Folic acid use started prior to pregnancy confers a decreased risk of neural tube defects, and yet 20–50% of pregnancies are\\u000a unplanned. We sought to determine whether medical providers order folic acid (FA) or folic acid-containing multivitamins (MVI)\\u000a for their non-pregnant female patients of childbearing age. This is a cross-sectional study using data from the CDC’s National Ambulatory\\u000a Medical Care

Heather H. BurrisMartha; Martha M. Werler

2011-01-01

176

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

Periconceptional folic acid supplementation is recommended to prevent congenital malformations, mainly neural tube defects,\\u000a but only 7% of pregnant women in Saxony-Anhalt (Germany) take folic acid at least 4 weeks before conception and in the first\\u000a 3 months of pregnancy. From March to June 2004, we sent standardized questionnaires about folic acid and its importance during\\u000a pregnancy to 33 schools

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

2006-01-01

177

High-Dose Folic Acid Acutely Improves Coronary Vasodilator Function in Patients With Coronary Artery Disease  

PubMed Central

OBJECTIVES We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans. BACKGROUND Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known. METHODS Fourteen patients with ischemic heart disease, age 62 ± 12 years (mean ± SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as “normal” versus “abnormal” on the basis of MBF response to adenosine 140 ?g/kg/min (normal = MBF > 1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis. RESULTS Folate was associated with a reduction in mean arterial pressure (100 ± 12 mm Hg vs. 96 ± 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 ± 0.59 ml/min/g vs. 2.16 ± 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 ± 0.59 vs. ml/min/g 1.41 ± 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 ± 0.61 ml/min/g vs. 2.12 ± 0.69 ml/min/g, placebo vs. folate, p = NS). CONCLUSIONS The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.

Tawakol, Ahmed; Migrino, Raymond Q.; Aziz, Kusai S.; Waitkowska, Justyna; Holmvang, Gotfred; Alpert, Nathaniel M.; Muller, James E.; Fischman, Alan J.; Gewirtz, Henry

2005-01-01

178

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

PubMed

In 1998, the United States introduced mandatory fortification of enriched cereal-grain products with folic acid 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 to assess folic acid intake took on greater importance. The purpose of the current study was to separate and quantify folic acid and 5-methyltetrahydrofolate, the most prominent naturally occurring folate in fortified foods, with a reliable and robust method. Folates were heat-extracted from food samples. A trienzyme treatment (alpha-amylase, rat plasma conjugase, and protease) was applied to the extracts followed by purification by affinity chromatography. Folic acid and 5-methyltetrahydrofolate were separated and quantified by reversed-phase HPLC with fluorescence and UV detection. A gradient elution with phosphate buffer and acetonitrile was used to separate the different forms of folates. The method gave a linear response in a range of 0.1-3 mumol/L and 0.0125-0.25 mumol/L for folic acid and 5-methyltetrahydrofolate, respectively. These ranges were similar to the expected levels in the samples. The CV of the peak areas of folic acid and 5-methyltetrahydrofolate for 5 commercial wheat flour samples extracted and run separately on the same day was 2.0 and 5.7% and, run over 5 consecutive days, was 7.2 and 7.3%, respectively. Total folate values in 45 samples of fortified food measured by HPLC and by the traditional microbiological assay demonstrated a high correlation (r(2) = 0.986). PMID:17116723

Póo-Prieto, Rosalia; Haytowitz, David B; Holden, Joanne M; Rogers, Gail; Choumenkovitch, Silvina F; Jacques, Paul F; Selhub, Jacob

2006-12-01

179

Spectrophotometric determination of folic acid in pharmaceutical preparations by coupling reactions with iminodibenzyl or 3-aminophenol or sodium molybdate–pyrocatechol  

Microsoft Academic Search

Novel coupling reagents are used for the simple and sensitive spectrophotometric determination of folic acid either in pure form or in its pharmaceutical preparations. The methods are based on the probable diazotization of the p-aminobenzoylglutamic acid obtained after reductive clevage of folic acid, followed by either coupling with iminodibenzyl to give a violet product with ?max of 580nm or coupling

Padmarajaiah Nagaraja; Ramanathapura A Vasantha; Hemmige S Yathirajan

2002-01-01

180

Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey  

PubMed Central

Background In September 2009, a folic acid fortification mandate (135 ?g/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 ?g folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ? 140 ?g/d, with a mean of 119 ?g/d (95% CI = 107 ?g/d-130 ?g/d). Based on these data, a fortification level of 160 ?g/100 g bread is required to achieve the targeted mean of 140 ?g folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous M?ori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a postgraduate education. Conclusions This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy.

2012-01-01

181

Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project.  

PubMed

Both a lack of maternal folic acid supplementation and the presence of genetic variants that reduce enzyme activity in folate pathway genes have been linked to meiotic nondisjunction of chromosome 21; however, the findings in this area of research have been inconsistent. To better understand these inconsistencies, we asked whether maternal use of a folic acid-containing supplement before conception reduces risk for chromosome 21 nondisjunction. Using questionnaire data from the National Down Syndrome Project, a population-based case-control study, we compared the use of folic acid-containing supplements among mothers of infants with full trisomy 21 due to maternal nondisjunction (n = 702) and mothers of infants born with no major birth defects (n = 983). Using logistic regression, adjusting for maternal age, race/ethnicity, and infant age at maternal interview, we found no evidence of an association between lack of folic acid supplementation and maternal nondisjunction among all case mothers (OR = 1.16; 95% CI: 0.90-1.48). In analyses stratified by meiotic stage and maternal age (<35 or ?35 years), we found an association among older mothers experiencing meiosis II nondisjunction errors (OR = 2.00; 95% CI: 1.08-3.71). These data suggest that lack of folic acid supplementation may be associated specifically with MII errors in the aging oocyte. If confirmed, these results could account for inconsistencies among previous studies, as each study sample may vary by maternal age structure and proportion of meiotic errors. PMID:23401135

Hollis, NaTasha D; Allen, Emily G; Oliver, Tiffany Renee; Tinker, Stuart W; Druschel, Charlotte; Hobbs, Charlotte A; O'Leary, Leslie A; Romitti, Paul A; Royle, Marjorie H; Torfs, Claudine P; Freeman, Sallie B; Sherman, Stephanie L; Bean, Lora J H

2013-02-07

182

A 19-Base Pair Deletion Polymorphism in Dihydrofolate Reductase Is Associated with Increased Unmetabolized Folic Acid in Plasma and Decreased Red Blood Cell Folate12  

PubMed Central

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. The functional impact of this polymorphism has not yet been demonstrated. The objective of this research was to determine the effects of the DHFR mutation with respect to folate status and assess influence of folic acid intake on these relations. The relationship between DHFR genotype and plasma concentrations of circulating folic acid, total folate, total homocysteine, and concentrations of RBC folate was determined in 1215 subjects from the Framingham Offspring Study. There was a significant interaction between DHFR genotype and folic acid intake with respect to the prevalence of high circulating unmetabolized folic acid (defined as >85th percentile). Folic acid intake of ?500 ?g/d increased the prevalence of high circulating unmetabolized folic acid in subjects with the deletion (del/del genotype (47.0%) compared with the wild type (WT)/del (21.4%) and wild type (WT)/WT genotypes (24.4%) (P for interaction = 0.03). Interaction between the DHFR polymorphism and folic acid intake was also seen with respect to RBC folate (P for interaction = 0.01). When folic acid intake was <250 ?g/d, the del/del genotype was associated with significantly lower RBC folate (732.3 nmol/L) compared with the WT/WT genotype (844.4 nmol/L). Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes.

Kalmbach, Renee D.; Choumenkovitch, Silvina F.; Troen, Aron P.; Jacques, Paul F.; D'Agostino, Ralph; Selhub, Jacob

2008-01-01

183

"New" cardiovascular risk factors in patients with chronic kidney disease: role of folic acid treatment.  

PubMed

Cardiovascular disease (CVD) is the principal cause of mortality in patients with chronic renal disease undergoing hemodialysis. In addition to the CVD risk factors, a new hypothesis has recently been aroused related to "new" factors involved in the development of atherosclerosis in the uremic patient; worthwhile mentioning are the homocysteine, inflammation, and oxidative stress, among others. The potential utility of the folic acid in the hyperhomocysteinemia control is well known, although its mechanism of action, either as antioxidant or anti-inflammatory, has not been established. Our results confirm that the patients undergoing dialysis demonstrate hyperhomocysteinemia, an increased inflammatory status, and an increase of the lipid peroxidation markers. The administration of IV folinic acid induces a reduction of homocysteine levels subordinate to the inflammatory status of the patient. Additionally, although no inflammatory effects were shown, the results provide evidence for the antioxidant effect of IV folinic acid administration by reducing the lipid peroxidation marker levels. The statistic analysis demonstrates no correlation among the 3 markers, in spite of its higher levels in these particular patients. Homocysteine does not independently predict mortality in patients taking oral folic acid. Nevertheless, the PCR (an inflammation marker) and the antibody antioxidative-LDL (a lipidic peroxidation marker) show a good prediction of mortality at the 24-month follow-up analysis. The knowledge of these "new" CV risk factors, as well as the factors that influence them, could be useful to prevent the development of atherosclerosis in patients with chronic renal disease. PMID:15613067

Bayés, Beatriz; Pastor, Mari Cruz; Bonal, Jordi; Romero, Ramón

2005-01-01

184

Determining and Surveying the Role of Carnitine and Folic Acid to Decrease Fatigue in ?-Thalassemia Minor Subjects.  

PubMed

Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P < .0001). Bone pain complaint and muscle weakness decreased with carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with ?-thalassemia minor. PMID:23458634

Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran

2013-03-04

185

[Folic acid intake before and after mandatory fortification: a population-based study in São Paulo, Brazil].  

PubMed

This study analyzed folic acid intake before and since mandatory fortification. Dietary data were collected by 24-hour recall in a health survey in São Paulo (ISA-Capital) in 2003 and 2007-2008, stratifying the population according to life stage and gender. Estimated average requirement (EAR) and tolerable upper intake level (UL) were used to assess intake. Prevalence of inadequate folic acid intake decreased in all groups, especially adolescents and adult males (72% to < 1% and 76% to 6%, respectively) but remained high in adult women (38%). Beans were the main source of folic acid before fortification. With fortification, bread became the main source, but beans remained important. Fortification was successful (increased intake within safe levels), but it raised concerns about the high proportion in the target group (adult women) who still fail to meet the recommended intake. PMID:24127102

Marchioni, Dirce Maria Lobo; Verly-Jr, Eliseu; Steluti, Josiane; Cesar, Chester Luis Galvão; Fisberg, Regina Mara

2013-10-01

186

Folate, Vitamin B12 and Homocysteine Status in Women of Childbearing Age: Baseline Data of Folic Acid Wheat Flour Fortification in Iran  

Microsoft Academic Search

Background: Folic acid fortification implemented mandatorily in many countries has been associated with significant increase in blood folate concentrations and reduction in the prevalence of neural tube defects. However, there are controversial findings on the probability of vitamin B12 deficiency being masked in the population after folic acid fortification. Baseline data on folate and vitamin B12 status are necessary before

Z. Abdollahi; I. Elmadfa; A. Djazayeri; S. Sadeghian; H. Freisling; F. Salehi Mazandarani; K. Mohamed

2008-01-01

187

Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice.  

PubMed

To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0mg/kg), control (2mg/kg) and supplemented (6mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity. PMID:22824165

Swayne, Breanne G; Kawata, Alice; Behan, Nathalie A; Williams, Andrew; Wade, Mike G; Macfarlane, Amanda J; Yauk, Carole L

2012-07-20

188

Effect of isotretinoin treatment on plasma holotranscobalamin, vitamin B12, folic acid, and homocysteine levels: non-controlled study.  

PubMed

Isotretinoin (Iso) has been used for the treatment of acne. Some previous studies reported elevated homocysteine (Hcy) levels after treatment with Iso. Some side effects have clinical presentations similar to vitamin B12, folic acid deficiencies, and hyperhomocysteinemia. In the present study we evaluated the plasma Hcy levels, the vitamins involved in its metabolism (vitamin B12 and folic acid), and holotranscobalamin (HoloTC), a transport system for vitamin B12 absorption in patients receiving Iso treatment for acne vulgaris. A total of 66 patients with acne vulgaris between the ages of 18 and 40 years were included. Screening for hemoglobin, creatinine, SGOT, SGPT, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), folic acid, vitamin B12, Hcy, and HoloTC were done just before initiation (pretreatment) and after four months of Iso treatment (posttreatment). Posttreatment vitamin B12, folic acid, and HoloTC levels were significantly lower while Hcy levels were significantly higher compared with initial values. Posttreatment total cholesterol, LDL-C, triglycerides, VLDL-C, SGPT, and SGOT levels were also higher, and HDL-C levels were lower compared with initial values while there was no change in hemoglobin levels during Iso treatment. We found that Iso usage might cause decreased vitamin B12, folic acid, and HoloTC. These Iso side effects might contribute to the missing link between Iso usage, hyperhomocysteinemia, and neuropsychiatric disorders. Trials may be made with the aim of demonstrating (clearly) if starting vitamin B12 and folic acid replacement therapies with Iso treatment initialization could be useful for preventing hyperhomocysteinemia and possibly related disorders. PMID:22098008

Karadag, Ayse Serap; Tutal, Emre; Ertugrul, Derun Taner; Akin, Kadir Okhan

2011-12-01

189

Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering.  

PubMed

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/- 2.7%, p = 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteine-lowering, but does not modulate markers of inflammation. PMID:16886840

Title, Lawrence M; Ur, Ehud; Giddens, Karen; McQueen, Matthew J; Nassar, Bassam A

2006-05-01

190

Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid.  

PubMed

Background: Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. Results: Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbs multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis, and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. Conclusions: Our results indicate that ethanol exposure interrupted divergent cardiac morphogenetic events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. Developmental Dynamics 242:1184-1201, 2013. © 2013 Wiley Periodicals, Inc. PMID:23832875

Sarmah, Swapnalee; Marrs, James A

2013-09-02

191

Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites  

Microsoft Academic Search

Eleven folic acid sensitive fragile sites (3p14, 7p13, 7q31.1, 7q32, 9q32, 11p13, 14q23, 15q22, 16q23, Xp22.2, Xq22) were detected in one individual, eight of them previously unknown. These sites seem to bear each its specific sensitivity to folic acid deficiency. Six of the sites were observed simultaneously on both homologous chromosomes in at least one cell. Each of these 11

G. Barbi; P. Steinbach; W. Vogel

1984-01-01

192

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

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.

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

2013-01-01

193

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

NASA Astrophysics Data System (ADS)

Compounds having general formula: [M(FO)(Cl) x(H 2O) y]· zH 2O, 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*, ? H*, ? S* and ? G* 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.

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

2008-09-01

194

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

PubMed Central

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.

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

195

Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects.  

PubMed

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects. Compared with control subjects, hyperhomocysteinaemic subjects had higher plasma levels of arginine and ADMA. More importantly, folic acid therapy significantly reduced plasma levels of arginine and ADMA. Furthermore, plasma levels of arginine and ADMA were positively correlated with plasma homocysteine levels and negatively correlated with plasma folate, as well as negatively correlated with plasma NOx. Our results suggest that ADMA may be a mediator of the atherogenic effects of homocysteine. PMID:12628031

Holven, Kirsten B; Haugstad, Tor S; Holm, Torbjørn; Aukrust, Pål; Ose, Leiv; Nenseter, Marit S

2003-03-01

196

Adaptive transport of folic acid across renal epithelia in folate-deficient rats.  

PubMed

Folate (vitamin B(9)) is an essential vitamin for a wide spectrum of biochemical reactions; however, unlike bacteria and plants, mammals are devoid of folate biosynthesis and thus must obtain this cofactor from exogenous sources. The activities of folate transporters on the kidneys play an important role in conserving folate excretion and reabsorption across the apical membrane of the renal proximal tubules. The different transport system activities may become identifiable in response to external stimuli, such as folate availability and exposure to chemotherapeutic agents. We have explored the effect of folate deficiency on the activity and expression of folate transporters in rat kidneys. Wistar rats were fed a folate-containing diet (2 mg folic acid kg(-1) diet) or a folic acid-free diet over a 3-month period, and mechanisms of folate transport were studied in renal brush border membrane vesicles and basolateral membrane vesicles. The renal folate uptake process is saturable and pH dependent, and it involves the folate receptor and reduced folate carrier (RFC) systems and possibly the proton coupled folate transporter (PCFT) system. We found that folate deficiency increased the renal brush border membrane and basolateral folate uptake by increasing the number of transporter molecules. The observed up-regulation of mRNA expression was also associated with a significant increase in RFC and PCFT expression at the protein level. PMID:22865158

Wani, Nissar Ahmad; Kaur, Jyotdeep

2012-08-04

197

Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic Acid in combined dosage forms.  

PubMed

Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations. PMID:20046784

Pathak, A; Rajput, S J

198

Simultaneous Derivative Spectrophotometric Analysis of Doxylamine Succinate, Pyridoxine Hydrochloride and Folic Acid in Combined Dosage Forms  

PubMed Central

Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 ?g/ml, 1-40 ?g/ml and 1-30 ?g/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

Pathak, A.; Rajput, S. J.

2008-01-01

199

Polygenic Association with Total Homocysteine in the Post Folic Acid Fortification Era: the CARDIA Study  

PubMed Central

Elevated plasma concentration of total homocysteine (tHcy) has been linked with many diseases. tHcy is associated with a variety of factors, including polymorphisms in genes involved in homocysteine metabolism. It is not clear whether US-mandated fortification of grain products with folic acid has affected the association of genetic variants with tHcy levels. We determined tHcy concentrations in sera from 997 Caucasians and 692 African Americans participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study before and after folic acid fortification. DNA was genotyped for variants present in four genes involved in homocysteine metabolism: cystathionine ?-synthase (CBS) 844ins68, methionine synthase (MS) 2756A>G; methionine synthase reductase (MTRR) 66A>G, and methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C. A greater number of African Americans were homozygous for the MS 2756GG, MTRR 66GG and CBS 844ins68 genotypes compared to Caucasians, while prevalence of MTHFR 677TT and 1298CC genotypes was substantially lower in African Americans compared to Caucasians. The overall variance in tHcy levels at y 0, 7, and 15 that can be explained by the combined presence of all five variants increased slightly over time in Caucasians (17%, y 0; 21%, y 7 and 26%, y 15) and in African Americans (13%, y 0; 17% y 7; 18% y 15) largely due to decrease in tHcy variance.

Tsai, Michael Y.; Loria, Catherine M.; Cao, Jing; Kim, Yongin; Siscovick, David S.; Schreiner, Pamela J.; Hanson, Naomi Q.

2009-01-01

200

Polygenic association with total homocysteine in the post-folic acid fortification era: the CARDIA study.  

PubMed

Elevated plasma concentration of total homocysteine (tHcy) has been linked with many diseases. tHcy is associated with a variety of factors, including polymorphisms in genes involved in homocysteine metabolism. It is not clear whether US-mandated fortification of grain products with folic acid has affected the association of genetic variants with tHcy levels. We determined tHcy concentrations in sera from 997 Caucasians and 692 African Americans participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study before and after folic acid fortification. DNA was genotyped for variants present in four genes involved in homocysteine metabolism: cystathionine beta-synthase (CBS) 844ins68, methionine synthase (MS) 2756A>G; methionine synthase reductase (MTRR) 66A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C. A greater number of African Americans were homozygous for the MS 2756GG, MTRR 66GG and CBS 844ins68 genotypes compared to Caucasians, while prevalence of MTHFR 677TT and 1298CC genotypes was substantially lower in African Americans compared to Caucasians. The overall variance in tHcy levels at y 0, 7 and 15 that can be explained by the combined presence of all five variants increased slightly over time in Caucasians (17%, y 0; 21%, y 7; and 26%, y 15) and in African Americans (13%, y 0; 17% y 7; and 18% y 15) largely due to decrease in tHcy variance. PMID:19577940

Tsai, Michael Y; Loria, Catherine M; Cao, Jing; Kim, Yongin; Siscovick, David S; Schreiner, Pamela J; Hanson, Naomi Q

2009-06-06

201

Effect of baking process on added folic acid and endogenous folates stability in wheat and rye breads.  

PubMed

In Poland bread as a staple food both made from wheat and rye flour can be a potential product for future fortification with folic acid. The objective of the study was to examine the effect of fermentation and baking on added folic acid and some endogenous folates stability during breadmaking of rye and wheat breads. Breads were produced using the formulation containing enriched flour with 0.2 mg folic acid/100 g product, baker's yeast and additionally ascorbic acid for wheat bread and lactic acid for rye bread. Folates were extracted with Hepes/Ches buffer (pH = 7.85) followed by destruction of matrix by amylase and protease and deconjugation with rat serum conjugase. Affinity chromatography (FBP bovine milk) was used to purify and concentrate samples. The folates were separated by HPLC with C18 column and with a combination of fluorescence and UV detection. For both rye and wheat breads there was a decrease of folic acid from flour to bread stage. The total losses depend on baking process and ranged from 12 to 21%. Some changes in the level of different native folate forms during the stage of baking process were also observed. PMID:16021829

Gujska, Elzbieta; Majewska, Katarzyna

2005-06-01

202

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

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

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

203

DNA degradation in the kidney of folic acid-treated guinea pigs.  

PubMed

Previous investigators agree on the increased DNA synthesis and destruction of tissues caused by folic acid (FA) administered parenterally. This study aims to clarify whether DNA degradation due to the destruction of cells and nuclei precedes DNA synthesis following FA administration. Forty guinea pigs were divided into four groups: group 1, contained 10 controls; in group 2, ten animals received intraperitoneally 300 mg/kg of body wt FA; in group 3, ten animals received FA and 12 h later frusemide intramuscularly in a dose of 7 mg/kg body wt; and finally in group 4, ten animals received frusemide as in group 3. FA produced necrosis of the epithelial cells of the convoluted tubules as the detection of the beta-aminoisobutyric acid end product of DNA and thymine catabolism indicated. Frusemide administered in group 3 had a favourable effect on the acute renal failure induced by FA. PMID:10885507

Zeis, P M; Tzaki, M; Nakopoulou, L; Nicolaidou, P; Kavazarakis, E; Messaritaki, A; Moustaki, M; Zeis, M P; Gourgiotis, D

2000-01-01

204

Possible relationship of folic acid supplementation and improved flow-mediated dilation in premenopausal, eumenorrheic athletic women  

Microsoft Academic Search

The purpose of this study was to determine if six weeks of folic acid supplementation would improve brachial artery endothelial- dependent flow-mediated dilation in eumenorrheic female run- ners with previously normal serum folate levels. This was a prospective, double-blinded, randomized pilot study with con- venience sampling. Sixteen eumenorrheic subjects who were not taking birth control pills and who ran at

Anne Z. Hoch; Nicholas M. Pajewski; Raymond G. Hoffmann; Jane E. Schimke

2009-01-01

205

Folic acid conjugated self-assembled layered double hydroxide nanoparticles for high-efficacy-targeted drug delivery.  

PubMed

Enhanced selectivity and efficacy is important for advanced drug delivery. Herein, a novel type of folic acid conjugated self-assembled layered double hydroxide nanoparticles is reported. These nanoparticles have a drug loading capacity of 27 wt% and are able to enter cell nuclei and dramatically improve the efficacy of MTX. PMID:24129414

Yan, Li; Chen, Wei; Zhu, Xiaoyue; Huang, Longbiao; Wang, Zhigang; Zhu, Guangyu; Roy, V A L; Yu, K N; Chen, Xianfeng

2013-10-29

206

A Systematic Review of Interventions to Increase Awareness, Knowledge, and Folic Acid Consumption Before and During Pregnancy  

Microsoft Academic Search

Objective. We conducted a systematic review of studies designed to increase awareness of, knowledge about, and consumption of folic acid before and during pregnancy. Data sources. Studies were identified from Cochrane Library, Medline, and the references of primary studies and reviews. Study inclusion and exclusion criteria. Studies included randomized controlled trials, quasi- experimental interrupted time series studies, follow-up studies, case-control

Corina Mihaela Chivu; Theodore H. Tulchinsky; Karla Soares-Weiser; Rony Braunstein; Mayer Brezis

2008-01-01

207

Preparation, characterization, and in vivo evaluation of doxorubicin loaded BSA nanoparticles with folic acid modified dextran surface.  

PubMed

Biocompatible and biodegradable doxorubicin loaded nanoparticles with targeting ability were prepared from BSA-dextran-folic acid conjugate via a pH adjustment and heating process. The BSA-dextran-folic acid conjugate was produced by an esterification reaction between folic acid and dextran and then the Maillard reaction between the modified dextran and BSA. The nanoparticles have a size about 90nm and excellent dispersibility at pH 7.4 aqueous solution. The doxorubicin loading efficiency and loading amount of the nanoparticles are larger than 90% and 14%, respectively. The antitumor activity and toxicity of the nanoparticles were evaluated through murine ascites hepatoma H22 tumor-bearing mice. The nanoparticles allow the administration of the doxorubicin with higher dose. At doxorubicin dose of 10mg/kg, the nanoparticles can achieve 88.9% of the tumor inhibition rate that is the same as the free doxorubicin at the dose of 5mg/kg. Importantly, the nanoparticles can decrease the toxicity of doxorubicin that results in a significant increase of the average life time in comparison with the free doxorubicin as well as the nanoparticles without folic acid. PMID:23370437

Hao, Hequn; Ma, Qingming; Huang, Chong; He, Fen; Yao, Ping

2013-01-28

208

College Women's Reported Behaviors and Beliefs Regarding Fish and Folic Acid and Their Roles in Birth Defects  

Microsoft Academic Search

The purpose of the current study was to examine college women's beliefs and behaviors regarding birth defect prevention via folic acid intake and avoidance of fish with high mercury levels. We surveyed 313 college women and found that the majority of them reported eating fish despite their awareness that certain types of fish contained levels of mercury that are dangerous

Lydia J. Burak; Pamela Costello

2006-01-01

209

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...

210

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

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study was to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of neural tube defects, with a concurrent assessment of other potential benefits or adverse effects. The evaluation was based on a systematic review of the published ...

211

Folic acid knowledge and use in a multi-ethnic pregnancy cohort: the role of language proficiency  

Microsoft Academic Search

Objective To investigate the role of language proficiency as determinant of folic acid knowledge and use in a multi-ethnic pregnancy cohort. Design Prospective cohort study. Setting and population Pregnant women from Amsterdam attending obstetric care for their first antenatal visit. Number approached: 12 373 women, response rate: 67% (8266 women aged 14-49 years). Ethnicity was based on the country of

Eijsden van M; Wal van der M. F; G. J. Bonsel

2006-01-01

212

Is Weekly Iron and Folic Acid Supplementation as Effective as Daily Supplementation for Decreasing Incidence of Anemia in Adolescent Girls?  

Microsoft Academic Search

T HIS CLINICAL TRIAL1 compared the effective- ness of weekly vs daily administration of iron plus folic acid for the treatment of anemia in adolescent Nepalese girls, a population with an extremely high prevalence of ane- mia. The study was conducted in a single government- run school in Dharan, an urban foothill town in Nepal. Girls from the 8th to

DIMITRI A. CHRISTAKIS; HAROLD P. LEHMANN

213

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...

214

Mechanism of cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cells in vitro and modulation of the drug activity by folic or folinic acid.  

PubMed Central

Inhibition of clonogenic potential by the glycinamideribonucleosyl transformylase inhibitor 5,10-dideazatetrahydrofolic acid (DDATHF, Lometrexol) was evaluated in vitro in a human ovarian carcinoma cell line, SW626. Drug-induced inhibition of clonogenic potential is a function of the dose and time of exposure and is independent of the formation of DNA single-strand breaks or de novo synthesis of protein. Simultaneous treatment with 100 microM hypoxanthine completely prevented the inhibition of clonogenic potential caused by 0.5 microM DDATHF. DDATHF blocked cells in the early-middle S-phases of the cell cycle, and there was a corresponding marked reduction in the rate of DNA synthesis after drug withdrawal. The cytotoxic potential of DDATHF was modulated by the folic acid concentration present in the medium. In a medium containing 0.22 microM folic acid, DDATHF cytotoxicity was at least 100 times that in a regular medium containing 2.22 microM folic acid, levels which, however, are about 100 times those found in human plasma. DDATHF cytotoxicity differed moderately when folic acid concentrations varied between 0.22 and 0 microM, suggesting that folic acid does not necessarily antagonise DDATHF anti-tumour activity. Folinic acid at a concentration as low as 0.1 microM can completely rescue cells when given simultaneously with 0.5 microM DDATHF. When folinic acid was given 24 h after DDATHF, a reversal of cytotoxicity was observed at 0.5 and 1 microM, but to a much lesser extent than simultaneous treatment. When folinic acid was added after 48 or 72 h of DDATHF washout, even at a high concentration and for a long time, no reduction in DDATHF cytotoxicity was found. In conclusion, the study highlights the modulation of DDATHF cytotoxicity by folic acid or by folinic acid and provides further rationale for in vivo clinical investigation with these combinations.

Erba, E.; Sen, S.; Sessa, C.; Vikhanskaya, F. L.; D'Incalci, M.

1994-01-01

215

[Effect of folic acid for treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency].  

PubMed

Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. Only 28 patients have been reported so far. A 15-year-old boy with mild mental retardation was admitted in our hospital because of progressive difficulty in walking. He is the second child. The paternal grandparents are first cousins. On admission, clinical examination revealed mild disturbance of consciousness, left hemiparesis, truncal ataxia, pyramidal tract signs in the lower limbs and sensory disturbance in his feet. There was no marfanoid symptoms nor ectopia lentis. EEGs showed slow activity with sporadic spike and wave complexes. Peak latencies of N20 of median nerves SEPs, the third and 5th wave of ABR and P100 of VEP were delayed. The CT scan showed mild cortical atrophy and MRI revealed increased intensity on T2-weighted images in the cerebral white matter. Biochemical studies revealed homocystinuria with homocystinemia. Both plasma methionine and serum folic acid were low. Serum vitamin B12 and methylmalonic acid in urine were normal. The lymphoblastoid cell line, transformed by Epstein-Barr virus of lymphocytes of the patient, could not grow when homocysteine was substituted in the culture medium for methionine. The normal control cell line grew naturally under the same condition. A diagnosis of homocystinuria due to MTHFR deficiency was made. The patient was on various therapeutic regimens for about 70 days. Treatment with high doses of folic acid (400 mg/day) resulted in disappearance of homocysteine in plasma, remarkable decrease of homocysteine in urine and increase of methionine in plasma of the patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8124871

Takenaka, T; Shimomura, T; Nakayasu, H; Urakami, K; Takahashi, K

1993-11-01

216

Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects123  

PubMed Central

Background: Understanding the full effect of chronic low-dose folic acid is important in interpreting the effect of the mandatory folic acid fortification program in North America. Objective: We aimed to describe the rate of attainment and steady state (plateau) of red blood cell (RBC) folate in response to long-term intake of 140 ?g (designed to mimic fortification) and 400 ?g (recommended dose for the primary prevention of neural tube defects) folic acid/d in reproductive-aged women living in a country with minimal fortification. Design: On the basis of pharmacokinetics principles, it was recently proposed that a steady state should be reached after 40 wk. Thus, 144 women aged 18–40 y were randomly assigned to receive a daily folic acid supplement of 140 (n = 49) or 400 (n = 48) ?g or placebo (n = 47) for 40 wk. RBC folate was measured at baseline and at 6, 12, 29, and 40 wk. Results: After 40 wk, RBC folate did not reach a plateau in either treatment group. Kinetic modeling of the data indicated that RBC folate would approximately double from 779 to 1356 nmol/L in response to 140 ?g folic acid/d with only ?50% of model-estimated steady state conditions achieved at 40 wk. An average RBC folate concentration of 1068 nmol/L after 12 wk of supplementation with 400 ?g folic acid/d was readily achieved at 36 wk after continuous intake of 140 ?g/d. Conclusion: Our model shows the considerable length of time required to attain the full effect of low-dose folic acid, which suggests that 140 ?g folic acid/d could be as effective as 400 ?g folic acid/d taken during the periconceptional period if given sufficient time. This trial is registered at www.anzctr.org.au as ACTRN12609000215224.

Gray, Andrew R; Rose, Meredith C; Miller, Jody C; Hurthouse, Nicola A; Gregory, Jesse F

2011-01-01

217

Folic acid-conjugated graphene oxide for cancer targeted chemo-photothermal therapy.  

PubMed

Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA-NGO-PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA-NGO-PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy. PMID:23357205

Qin, X C; Guo, Z Y; Liu, Z M; Zhang, W; Wan, M M; Yang, B W

2012-12-29

218

Disulfide bond reduction-triggered molecular hydrogels of folic acid-Taxol conjugates.  

PubMed

Molecular hydrogels of therapeutic agents are a novel kind of self-delivery system that can sustain release of drugs or pro-drugs. We have previously developed a molecular hydrogelator of folic acid (FA)-Taxol conjugate triggered by phosphatase. In this paper, we report a novel molecular hydrogelator system of FA-Taxol conjugates with improved synthetic strategy. The hydrogels are formed by the reduction of disulfide bond by glutathione (GSH). These hydrogels could sustain release of Taxol through ester bond hydrolysis. Compared with intravenous (i.v.) injection of clinically used Taxol® with four times the dosage, our hydrogel could inhibit tumor growth more efficiently by a single dose of intra-tumor (i.t.) administration. These observations suggested the big potential of this novel gelation system of Taxol for cancer therapy. PMID:23989242

Yang, Chengbiao; Li, Dongxia; Fengzhao, Qianqi; Wang, Lianyong; Wang, Ling; Yang, Zhimou

2013-09-25

219

Targeted folic acid-PEG nanoparticles for noninvasive imaging of folate receptor by MRI.  

PubMed

The surface of superparamagnetic iron oxide nanoparticles (SPIO) with different molecular weight of poly(ethylene glycol) (PEG) and folic acid (FA) were synthesized. The SPIO-PEG-FA nanoparticles are well-dispersed and have good stability in various pH solutions. The lack of hysterestis and remanence at ambient temperatures is characteristic of superparamagnetic materials for SPIO-PEG-FA. The uptake by macrophage for SPIO-PEG-FA is lower than that of Feridex I.V. even at higher concentration. Internalization of SPIO-PEG-FA in targeted cells (KB cells) was observed by flow-cytometric analysis and in vitro MR imaging. The intensity change of positive KB cell tumor (-20 to 25%) is significantly lower than that of negative HT-1080 cell tumor from precontrast to postcontrast images of the tumor by in vivo MR imaging. These preliminary results demonstrated that SPIO-PEG-FA have the ability to target folate receptor. PMID:18085650

Chen, Ting-Jung; Cheng, Tsan-Hwang; Hung, Yu-Chin; Lin, Kuei-Tang; Liu, Gin-Chung; Wang, Yun-Ming

2008-10-01

220

Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells  

PubMed Central

Summary Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and re-direct CPMV particles to cells of interest, we attached a novel folic acid-PEG conjugate using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.

Destito, Giuseppe; Yeh, Robert; Rae, Chris S.; Finn, M. G.; Manchester, Marianne

2007-01-01

221

Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells.  

PubMed

Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV-specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors. PMID:17961827

Destito, Giuseppe; Yeh, Robert; Rae, Chris S; Finn, M G; Manchester, Marianne

2007-10-01

222

Pressurized liquid extraction and HPLC quantification of folic acid in fortified wheat flours.  

PubMed

A pressurized liquid extraction (PLE) method using phosphate buffer as solvent was applied for folic acid (FA) extraction from fortified wheat flours and was compared to a standard solid-liquid extraction (SLE) method. Extracted FA was quantified by reverse phase high-performance liquid chromatography (RP-HPLC) hyphenated with a phenyl column and an absorption photometric detector (? = 280 nm). Detection and quantification limits were 0.12 and 0.4 ng, respectively, corresponding to 0.06 and 0.2 ?g g(-1) of analyzed wheat flour. Equivalent FA contents were found by both extraction methods, but a single PLE allowed a total recovery of FA content, whereas at least three successive SLEs were needed to achieve a total recovery of FA. The obtained results indicated that PLE is a rapid and efficient technique for FA extraction from fortified wheat flour. PMID:22827771

Araújo, Michel Mozeika; Marchioni, Eric; Villavicencio, Anna Lucia Casañas Haasis; Zhao, Minjie; Zimmermann, Pierre; El-Khoury, Etienne; Bergaentzle, Martine

2012-07-27

223

Role of Uncoupled eNOS in Abdominal Aortic Aneurysm Formation: Treatment with Folic Acid  

PubMed Central

It has been shown that eNOS uncoupling occurs in hypertension and atherosclerosis. However its causal role in vascular pathogenesis has not been previously characterized. Here, we challenged eNOS pre-uncoupled hph-1 mice (deficient in eNOS cofactor tetrahydrobiopterin biosynthetic enzyme GTPCHI) with Ang II (0.7 mg/kg/day, 14 days). Both wild-type (WT) and hph-1 groups developed hypertension similarly up to day 6 to 7. Thereafter approximately 14% of Ang II-infused (0.7 mg/kg/day) hph-1 mice (n=72) started to die suddenly of ruptured AAA. Among the survivors, 65% developed AAA, resulting in a total morbidity rate of 79%. In contrast, none of the Ang II-infused WT mice died or developed AAA. Ang II progressively deteriorated eNOS uncoupling in hph-1 mice, while augmenting H4B and nitric oxide (NO•) deficiencies. The abundance of the H4B salvage enzyme dihydrofolate reductase (DHFR) in the endothelium was decreased in hph-1 mice and further diminished by Ang II infusion. Intriguingly, restoration of DHFR expression by oral administration of folic acid (FA), or overexpression of DHFR, completely prevented AAA formation in Ang II-infused hph-1 mice while attenuating progressive uncoupling of eNOS. Folic acid also attenuated vascular remodelling and inflammation characterized by medial elastin break down, augmented MMP2 activity and activation of MMP9, as well as macrophage infiltration. In conclusion, these data innovatively suggest a causal role of eNOS uncoupling/H4B deficiency in AAA formation. Therefore oral FA administration, endothelium targeted DHFR gene therapy, and perhaps other countermeasures directed against eNOS uncoupling, could be used as new therapeutics for AAA.

Gao, Ling; Siu, Kin Lung; Chalupsky, Karel; Nguyen, Andrew; Chen, Peng; Weintraub, Neal L.; Galis, Zorina; Cai, Hua

2013-01-01

224

Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes.  

PubMed

Folate deficiency may be associated with an increased risk of cancer at certain sites. There is a need to measure folate status and putative biomarkers of cancer risk in the same target tissue, or in surrogate tissues. A study was carried out to develop a method for the rapid measurement of folate in human buccal mucosa and lymphocytes and to evaluate the responsiveness of this measurement in both tissues to folic acid supplementation in healthy subjects, relative to conventional markers of folate status. Three hundred and twenty-three adults, ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty-five subjects with red cell folate between 200 and 650 nmol/L participated in a randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r = 0.36, P < 0.01) was observed between red cell folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly associated with plasma 5-MeTHF (r = 0.28, P < 0.05) and plasma total homocysteine concentration (r = -0.34, P < 0.05). Buccal mucosa total folate showed no correlation with either red cell folate or 5-MeTHF, but was significantly associated with lymphocyte total folate (r = 0.35, P < 0.01). Supplementation elicited a significant increase in lymphocyte total folate (P < 0.01), and this was strongly associated with the increase in RBC total folate (P < 0.01) and plasma 5-MeTHF (P < 0.01). Buccal mucosa total folate was not influenced by folate supplementation. Methods have been developed for the rapid measurement of lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to folate intake and is reflected by plasma 5-MeTHF. PMID:15247137

Basten, Graham P; Hill, Marilyn H; Duthie, Susan J; Powers, Hilary J

2004-07-01

225

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

PubMed

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 3.05-5.625µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1(50mg: 50mg) 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

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

2013-12-01

226

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

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.

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

227

Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-?B/p53 pathway mediated by folic acid receptor.  

PubMed

Folate is important for normal cell division. Folate deficiency has been implicated in various diseases, including atherosclerosis, neural tube defects, and cancer. However, the effect of folate on angiogenesis was unclear. The aim of this study was to investigate the anti-angiogenic action of folic acid (FA). FA (0-10 ?mol/L) concentration-dependently decreased DNA synthesis and proliferation in cultured human umbilical venous endothelial cells (HUVEC). Western blot analyses demonstrated that the levels of p21, p27 and p53 protein in HUVEC were increased by FA. The FA-inhibited [3H]thymidine incorporation was completely blocked when the expressions of p21 and p27 were knocked-down together. Knock-down of p53 prevented the FA-induced increases in p21 and p27 protein level. The levels of phosphorylated Src (p-Src) and p-Src-FA receptor (FR) complex in HUVEC were increased by FA. Knock-down of FR reduced the FA-induced increases of p-Src and p53. The FA-induced increases of p21, p27 and p53 protein levels were abolished when cSrc was knocked-down. FA also increased NF-?B nuclear translocation and binding onto the p53 promoter. The FA-induced up-regulation of the p53 promoter activity was prevented by knocked-down of ERK. Matrigel angiogenesis assay in mice demonstrate the anti-angiogenic effect of FA in vivo. In conclusion, our data indicate that FA bound to FR in HUVEC, subsequently activated the cSrc/ERK 2/NF-?B/p53 signaling pathway, which in turn up-regulated the expression of p21 and p27, and finally resulted in cell cycle arrest at the G0/G1 phase. In the present study, we uncover a completely novel role of FA for anti-angiogenesis. PMID:22843228

Lin, Shyr-Yi; Lee, Woan-Ruoh; Su, Yi-Fan; Hsu, Sung-Po; Lin, Hsu-Chen; Ho, Pei-Yin; Hou, Tien-Chi; Chou, Yu-Pei; Kuo, Chun-Ting; Lee, Wen-Sen

2012-07-29

228

Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  

PubMed Central

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B12 lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

Kulkarni, Asmita; Dangat, Kamini; Kale, Anvita; Sable, Pratiksha; Chavan-Gautam, Preeti; Joshi, Sadhana

2011-01-01

229

A Review of the Benefits of Nutrient Supplements during Pregnancy: From Iron-Folic-Acid to Long-Chain Polyunsaturated Fatty Acids to Probiotics  

Microsoft Academic Search

This review summarizes current knowledge on the effectiveness of prenatal nutrient supplements ranging from iron-folic-acid (IFA), which is standard of care in many parts of the world, to more novel ones such as ?–3 fatty acids and probiotics in improving maternal and child health outcomes. Randomized controlled trials have shown that prenatal IFA supplements reduce the risk of anemia and

Usha Ramakrishnan

2010-01-01

230

Cyclodextrin compound modified with folic acid, process for production thereof, drug delivery agent for targeting drug delivery system, pharmaceutical composition, and imaging agent  

US Patent & Trademark Office Database

Disclosed is a cyclodextrin compound comprising glucopyranoses constituting cyclodextrin, the glucopyranoses having substituents each having folic acid substituted for two or more primary hydroxy groups at position-6 of the glucopyranoses.

2012-07-17

231

Periconceptional Maternal Folic Acid Use of 400 ug per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child  

PubMed Central

Background Countries worldwide recommend women planning pregnancy to use daily 400 µg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic acid use and markers of global DNA methylation potential (S-adenosylmethionine and S-adenosylhomocysteine blood levels) in mothers and children affect methylation of the insulin-like growth factor 2 gene differentially methylation region (IGF2 DMR) in the child. Moreover, we tested whether the methylation of the IGF2 DMR was independently associated with birth weight. Methodology/Principal Findings IGF2 DMR methylation in 120 children aged 17 months (SD 0.3) of whom 86 mothers had used and 34 had not used folic acid periconceptionally were studied. Methylation was measured of 5 CpG dinucleotides covering the DMR using a mass spectrometry-based method. Children of mother who used folic acid had a 4.5% higher methylation of the IGF2 DMR than children who were not exposed to folic acid (49.5% vs. 47.4%; p?=?0.014). IGF2 DMR methylation of the children also was associated with the S-adenosylmethionine blood level of the mother but not of the child (+1.7% methylation per SD S-adenosylmethionine; p?=?0.037). Finally, we observed an inverse independent association between IGF2 DMR methylation and birth weight (?1.7% methylation per SD birthweight; p?=?0.034). Conclusions Periconceptional folic acid use is associated with epigenetic changes in IGF2 in the child that may affect intrauterine programming of growth and development with consequences for health and disease throughout life. These results indicate plasticity of IGF2 methylation by periconceptional folic acid use.

Steegers-Theunissen, Regine P.; Obermann-Borst, Sylvia A.; Kremer, Dennis; Lindemans, Jan; Siebel, Cissy; Steegers, Eric A.; Slagboom, P. Eline; Heijmans, Bastiaan T.

2009-01-01

232

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

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

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

2008-01-01

233

Folate and vitamin B12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification14  

Microsoft Academic Search

Background:Historicreportsonthetreatmentofperniciousanemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 defi- ciency, which affects many seniors. This idea is controversial, how- ever, because observational data are few and inconclusive. Further- more, experimental investigation is unethical. Objective: We examined the relations between serum folate and vitamin B-12 status relative to

Martha Savaria Morris; Paul F Jacques; Irwin H Rosenberg; Jacob Selhub

234

Association between inhibited binding of folic acid to folate receptor ? in maternal serum and folate-related birth defects in Norway  

PubMed Central

BACKGROUND Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor ? (FR?), as well as possible effects of parental demographics or prenatal exposures. METHODS We conducted a nested case–control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n= 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n= 221). The inhibition of folic acid binding to FR? was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors. RESULTS There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0–1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FR? (CL/P aOR = 0.7, 95% CI 0.6–1.0; CPO aOR = 1.1, 95% CI 0.8–1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FR?. CONCLUSIONS Inhibition of folic acid binding to FR? in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.

Boyles, A.L.; Ballard, J.L.; Gorman, E.B.; McConnaughey, D.R.; Cabrera, R.M.; Wilcox, A.J.; Lie, R.T.; Finnell, R.H.

2011-01-01

235

Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype  

Microsoft Academic Search

This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailor-made prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebo-controlled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known

Koichi Miyaki; Mitsuru Murata; Haruhito Kikuchi; Izumi Takei; Takeo Nakayama; Kiyoaki Watanabe; Kazuyuki Omae

2005-01-01

236

Influence of human serum albumin on photodegradation of folic acid in solution.  

PubMed

It has been proposed that photodegradation of folates may be the reason for the pigmentation of races living under high fluence rates of ultraviolet radiation. The photodegradation of folic acid (FA) induced by ultraviolet-A (UV-A) radiation, in solution and in the presence of human serum albumin (HSA), was studied with absorption and fluorescence spectroscopy. FA photodegradation, with formation of p-aminobenzoyl-l-glutamic acid, 6-formylpterin and pterin-6-carboxylic acid, was found to follow an exponential trend. A scheme of FA photodegradation, which involves photosensitization of FA degradation by its photoproducts, was proposed. The rate of FA photodegradation decreased drastically in the presence of HSA, whereas the spectral characteristics of the photoproducts remained constant. The reduction of the FA photodegradation rate by HSA was accompanied by degradation of tryptophan in HSA. Tryptophan, when added to solutions of FA, had a similar effect as HSA. In solutions of FA and HSA the FA photoproducts cause photodamage mainly to HSA rather than to FA itself. The oxygen dependence of FA photodegradation and the inhibition of this process by sodium azide indicate that singlet oxygen may participate in the photosensitizing activity of FA photoproducts. PMID:16454580

Vorobey, Pavel; Steindal, Arnfinn Engeset; Off, Morten Kristian; Vorobey, Alexander; Moan, Johan

237

Folic acid administration reduces neointimal thickening, augments neo-vasa vasorum formation and reduces oxidative stress in saphenous vein grafts from pigs used as a model of diabetes  

PubMed Central

Aims/hypothesis There is evidence that plasma homocysteine augments vein graft failure and that it augments both micro- and macro-angiopathy in patients with diabetes mellitus. It is therefore suggested that homocysteine may augment vein graft thickening, a major cause of vein graft failure, in diabetic patients, as well as impairing adaptive growth of a new vasa vasorum, possibly through overproduction of superoxide. In order to test these proposals, the effect of folic acid administration, which lowers plasma homocysteine, on vein graft thickening and microvessel density was studied in pigs used as a model of diabetes. Methods Non-ketotic hyperglycaemia was induced in Landrace pigs by intravenous injection of streptozotocin, and folic acid was fed daily for 1 month. Vein grafts were excised and the thickness of the neointima and media and microvessel density were assessed by planimetry and superoxide formation. Results Plasma total homocysteine was significantly reduced by folic acid in both control and diabetic pigs, whereas glucose was unchanged. Compared with controls, diabetic pigs showed increased neointimal thickness and superoxide formation and decreased adventitial microvessel density. Folic acid reduced neointimal thickness and superoxide formation and augmented microvessel density in diabetic but not in control pigs. Conclusions Folic acid administration reduces neointimal thickening, augments vasa vasorum neoformation and reduces oxidative stress in saphenous vein grafts from diabetic pigs. Folic acid may therefore be particularly effective in reducing vein graft failure in diabetic patients.

2013-01-01

238

Folic acid supplementation provided in utero and during lactation reduces the number of terminal end buds of the developing mammary glands in the offspring.  

PubMed

Folate may prevent or promote cancer development and progression depending on the timing of intervention. Intrauterine exposure to folic acid has drastically increased in North America due to mandatory fortification and supplemental use of folic acid, which may influence the risk of breast cancer in the offspring. We investigated the effect of maternal folic acid supplementation, equivalent to the likely average post-fortification folate intake of a North American woman taking multivitamins containing folic acid, on terminal end buds, which reliably predict mammary tumor risk at adulthood in rodents. Female rats were placed on a control or supplemental diet for 3 weeks prior to mating and throughout pregnancy and lactation. Female pups were placed on the control diet at weaning until 50 days of age. The pups from the folic acid supplemented dams had a significantly lower number of terminal end buds than the pups from the dams fed the control diet (p=0.014). Our data suggest for the first time that folic acid supplementation provided in utero and during lactation may lower mammary tumor risk in the offspring. PMID:19264391

Sie, Karen K Y; Chen, Jianmin; Sohn, Kyong-Jin; Croxford, Ruth; Thompson, Lilian U; Kim, Young-In

2009-03-04

239

Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35.  

PubMed

Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in beta-amyloid (Abeta) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Abeta31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties. PMID:19331699

Yu, Huan-Ling; Li, Li; Zhang, Xiao-Hong; Xiang, Li; Zhang, Jie; Feng, Jin-Fang; Xiao, Rong

2009-03-31

240

Methionine, folic acid and vitamin B12 in growing-finishing pigs: Impact on growth performance and meat quality  

Microsoft Academic Search

Growth performance, metabolic variables, and meat quality were measured in 78 growing-finishing pigs using supplements of 0 (C), or 0.2% of DL-methionine (M), and three combinations of folic acid [mg\\/kg] and cyanocobalamin [?g\\/kg], respectively 0 and 0 (V0), 10 and 25 (V1), and 10 and 150 (V2) in a 2 × 3 factorial arrangement. Feed conversion was lower (p = 0.05) in M than

Alain Giguère; Christiane L. Girard; J. Jacques Matte

2008-01-01

241

High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic acid flour fortification  

Microsoft Academic Search

Summary Vitamin B12 deficiency may be an independent risk factor for neural tube defects (NTD). We determined the prevalence of biochemical B12 deficiency (<125 pmol\\/l) among 10 622 Ontarian women aged 15-46 years who underwent con- comitant testing of serum bhCG and B12 9 years after the implementation of Canadian folic acid flour fortification. The overall prevalence of bio- chemical

J. G. Ray; J. Goodman; P. R. A. O'Mahoney; M. M. Mamdani; D. Jiang

2008-01-01

242

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

Microsoft Academic Search

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

JASMINA BRBORIC; SOTE VLADIMIROV

2005-01-01

243

Moderate or Supranormal Folic Acid Supplementation Does Not Exert a Protective Effect for Homocysteinemia and Methylation Markers in Growing Rats  

Microsoft Academic Search

Background\\/Aims: Folic acid (FA) deficiency\\/supplementation effects seem to be dependent on age group and\\/or physiological status. The aim was to evaluate changes associated with rapid growth in relation to methionine metabolism in rats. Methods: Four groups (n = 10 each) of male Sprague Dawley rats (5 weeks old) were on diets that varied in their FA content: 0 mg FA\\/kg

T. Partearroyo; N. Úbeda; E. Alonso-Aperte; G. Varela-Moreiras

2010-01-01

244

A validated ultra high pressure liquid chromatographic method for qualification and quantification of folic acid in pharmaceutical preparations  

Microsoft Academic Search

A fully validated UHPLC method for the identification and quantification of folic acid in pharmaceutical preparations was developed. The starting conditions for the development were calculated starting from the HPLC conditions of a validated method. These start conditions were tested on four different UHPLC columns: Grace Vision HT™ C18-P, C18, C18-HL and C18-B (2mm×100mm, 1.5?m). After selection of the stationary

E. Deconinck; S. Crevits; P. Baten; P. Courselle; J. De Beer

2011-01-01

245

Adequacy of prenatal care as a major determinant of folic acid, iron, and vitamin intake during pregnancy  

Microsoft Academic Search

This study aimed to quantify the association be- tween adequacy of prenatal care and prevalence of folic acid, iron, and multivitamin intake dur- ing pregnancy. Data were obtained on socio-de- mographics, prenatal care, pregnancy complica- tions, and use of vitamin\\/mineral supplements for 836 women, using a postpartum interview. Associations with the use of vitamin\\/mineral supplements were quantified with risk ratios

Nuno Lunet; Teresa Rodrigues; Sofia Correia; Henrique Barros

2008-01-01

246

Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women  

Microsoft Academic Search

Objective: Our aim was to determine if a once-a-week folic acid supplement increases women's red blood cell folate to concentrations (>905 nmol\\/l) that are associated with a low risk of bearing a child with a neural tube defect.Design: Randomized control trial.Setting: General community.Subjects: In total, 114 nonpregnant women (18–40 y) volunteers, with red blood cell folate concentrations between 295 and

B Norsworthy; C M Skeaff; C Adank; T J Green

2004-01-01

247

Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure  

Microsoft Academic Search

Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure.BackgroundParathyroid hormone (PTH)-related protein (PTHrP) is present in many normal tissues, including the kidney. Current evidence supports that PTHrP is involved in renal pathophysiology, although its role on the mechanisms of renal damage and\\/or repair is unclear. Our present study examined the changes in PTHrP and the PTH\\/PTHrP receptor (type

Soledad Santos; Ricardo J. Bosch; Arantxa Ortega; Raquel Largo; Teresa Fernández-Agulló; Rosa Gazapo; Jesús Egido; Pedro Esbrit

2001-01-01

248

Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition1  

Microsoft Academic Search

The objectives of the present study were to assess the impact of lactation on the folate status of adolescents and determine the effect of ingestion of a low-dose postpartum (PP) folic acid supplement on maternal folate and zinc status and milk composition. Pregnant adolescents (aged 14-19 y; n = 71) were recruited; those who initiated breast-feeding on delivery were randomly

Rosalind S Gibson

249

Nanostructured ?-Fe2O3 platform for the electrochemical sensing of folic acid.  

PubMed

?-Fe(2)O(3) nanofibers are synthesized by a simple and efficient electrospinning method and the selective determination of folic acid (FA) is demonstrated in the presence of an important physiological interferent, ascorbic acid (AA), using the ?-Fe(2)O(3) nanofiber modified glassy carbon (GC) electrode at physiological pH. Bare GC electrode fails to determine the concentration of FA in the presence of a higher concentration of AA due to the surface fouling caused by the oxidized products of AA and FA. However, modification with ?-Fe(2)O(3) nanofibers not only separates the voltammetric signals of AA and FA by 420 mV between AA and FA, but also enhances higher oxidation current. The amperometric current response is linearly dependent on FA concentration in the range of 60-60,000 nM, and the ?-Fe(2)O(3) nanofiber modified electrode displayed an excellent sensitivity for FA detection with an experimental detection limit of 60 nM (1.12 × 10(-10) M (S/N = 3)). Furthermore, the ?-Fe(2)O(3) nanofiber modified electrode showed an admirable selectivity towards the determination of FA even in the presence of a 1000-fold excess of AA and other common interferents. This modified electrode has been successfully applied for determination of FA in human blood serum samples. PMID:23364807

Maiyalagan, Thandavarayan; Sundaramurthy, J; Kumar, P Suresh; Kannan, Palanisamy; Opallo, Marcin; Ramakrishna, Seeram

2013-01-31

250

Online pre-column derivatization with chromatographic separation to determine folic acid.  

PubMed

A simple, sensitive, and selective online pre-column derivatization high-performance liquid chromatographic method was developed and validated for the first time to determine trace levels of folic acid (FA). An oxidant cerium (IV) trihydroxyhydroperoxide packed reactor was used for pre-column oxidation and was combined by column switching with a C18 analytical column for sample enrichment and separation. The method was based on oxidative cleavage of FA into highly fluorescence products, 2-amino-4-hydroxypteridine-6-carboxaldehyde and the corresponding 2-amino-4-hydroxypteridine-6-carboxylic acid, during the flow of 0.04 M phosphate buffer (pH 3.5) containing the analyte through packed reactor at a flow rate of 0.2 mL/min and 40°C. The fluorescent products were enriched on the head of the analytical column for the final separation. The separation was performed at room temperature using a mobile phase consisting of phosphate buffer (0.04 M, pH 3.5) and acetonitrile (90:10, v/v). The eluents were monitored at emission and excitation wavelengths of 463 and 367 nm, respectively. The method showed excellent recovery, precision and accuracy with detection limits of 0.067 ng/mL from 500 µL of sample FA. The developed method was successfully applied to the determination of FA in pharmaceutical formulations and showed a recovery of 99.31% and a relative standard deviation of 1.72%. PMID:23097580

Emara, Samy; Masujima, Tsutomu; Zarad, Walaa; Kamal, Maha; Ei-Bagary, Ramzia

2012-10-24

251

[Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].  

PubMed

The aim of this work was to evaluate of efficacy and safety of complex Heptral, Vitamin B6 and Folic Acid in experimental hepatitis therapy compared with monotherapy. Experiments were carried out on pubertal rats. Eperimental hepatitis models were induced by Tetrachlormethane. The tetrachlormethane intoxication was reproduced by subcutaneous injection of CCL(4) 1ml/kg dissolved in 1ml of olive oil. Cytochrome P450, cytochrome b5, reduced glutation,activity of glutationetranspherase and content of ATP in hepatocytes were measured by the spectrophotometric techniques,but content of homocysteine by chromophtography techniques. Under CCL(4) intoxication disturbance of liver detoxication function, energy deficit and surplus of homocysteine were observed. Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine. Complex therapy with Heptral and B6 and folic acid reveal more expressive hepatoprotective effect and safety than monotherapy with Heptral. Complex therapy improves not only the parameters of biotransformation (metabolic and conjugation phase), but also normalizes the level of ATP and homocystein. Vitamins B6 and folic acid increases the efficacy and safety of Heptral. This complex was recomended for treatment of hepatitis. PMID:17984565

Antelava, N A; Gogoluari, M I; Gogoluari, L I; Pirtskhala?shvili, N N; Okudzhava, M V

2007-09-01

252

Altered jejunal surface pH in coeliac disease: its effect on propranolol and folic acid absorption.  

PubMed

1. Propranolol and folic acid absorption were studied separately in healthy subjects, non-coeliac patients and patients with treated and untreated coeliac disease. 2. The surface pH of jejunal biopsy samples was measured with a pH electrode. 3. When compared with values found in healthy subjects, plasma propranolol levels were elevated in coeliac disease and, in contrast, serum folic acid levels were depressed after oral administration of the drug. Jejunal surface pH was more alkaline in the coeliac groups than in the healthy and non-coeliac subjects. 4. Pharmacokinetic analysis of the plasma drug levels allowed evaluation of the rate constants associated with absorption and elimination. The absorption rate constant was decreased for folic acid in the coeliac group, but increased for propranolol. These changes correlated with variation in surface pH. 5. Although the changes in drug disposition in treated and untreated coeliac disease are the result of several factors, it is suggested that jejunal surface pH may affect the rate of absorption and therefore the plasma concentration-time profile of drugs which undergo dissociation. PMID:7105632

Kitis, G; Lucas, M L; Bishop, H; Sargent, A; Schneider, R E; Blair, J A; Allan, R N

1982-10-01

253

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

PubMed Central

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.

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

2011-01-01

254

Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology  

PubMed Central

Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.

Joseph, Jacob; Loscalzo, Joseph

2013-01-01

255

[Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials].  

PubMed

Despite the causal association between defects of the metabolism of the folate (hyperhomocysteinemia) and risk of neural tube defects are both well documented, the association between folate deficiency and other pregnancy pathologies is still not entirely clear. The present article aims to gather the data published about the relationship between serum folate and pregnancy pathologies, distinguishing between the evidences emerged from the observational studies and the results of the clinical trials. We carried out a brief examination of the relationships between folate metabolism and homocysteine. Observational studies have suggested that a good level of folate in pregnancy is associated with higher birthweight, increased placental weight and fewer preterm birth. These results were not entirely consistent with findings from clinical trials. We have identified 12 randomized clinical studies with folate supplementation versus placebo. In the clinical studies where folic acid (FA) could improve pregnancy outcomes, its effect was not statistically significant, except for three studies where FA showed a significant decrease of low birthweight. With regard to preterm birth, pre-eclampsia and abruptio placentae, although in some observational studies AF was found to be associated with a reduction of these adverse outcomes, in currently available controlled clinical trials, FA supplementation had no statistically significant effects. PMID:20827247

Chiaffarino, F; Ascone, G B; Bortolus, R; Mastroia-Covo, P; Ricci, E; Cipriani, S; Parazzini, F

2010-08-01

256

Folic acid conjugated guar gum nanoparticles for targeting methotrexate to colon cancer.  

PubMed

It was envisaged to develop surface modified Guar Gum Nanoparticles (GGNP) with Folic acid (FA) charged with methotrexate (MTX) to target the colon specifically. The MTX loaded FA functionalized GGNP (MTX-FA-GGNP) have been prepared by emulsion crosslinking method. These surface modified nanoparticles were compared with unmodified MTX loaded GGNP (MTX-GGNP). The developed formulations were evaluated for size and size distribution, zeta potential, Differential Scanning Calorimetry (DSC), release profile and uptake studies. The nanoparticles have been found to have average size of 325 nm in diameter having polydispersity index (PDI) 0.177 indicating mono-disperse particles. The zeta potential of the particles was found to be -36.9 mV. The percent growth inhibition of Caco 2 cells with MTX-FA-GGNP was found to be better than MTX-GGNP indicating folate receptor mediated uptake. The MTX-GGNP protects the release of MTX in upper gastrointestinal tract while maximum release of MTX occurred in simulated colonic fluids of pH 6.8. The in vivo uptake studies revealed preferential uptake of nanoparticles formulation in the colon. These studies provide evidences that MTX-FA-GGNP holds promise to address colorectal cancer over-expressing folate receptors. This prototype formulation enjoys dual advantage of having propensity to release the drug in the colon and in the conditions of colorectal carcinoma; it could be better localized and targeted with improved therapy due to over-expression of folate receptors. PMID:23627072

Sharma, Monika; Malik, Ritu; Verma, Ashwni; Dwivedi, Pankaj; Banoth, Gabbar Singh; Pandey, Nagendra; Sarkar, Jayant; Mishra, Prabhat Ranjan; Dwivedi, Anil Kumar

2013-01-01

257

Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease.  

PubMed

Folic acid (FA) is a member of the B-vitamin family with cardiovascular roles in homocysteine regulation and endothelial nitric oxide synthase (eNOS) activity. Its interaction with eNOS is thought to be due to the enhancement of tetrahydrobiopterin bioavailability, helping maintain eNOS in its coupled state to favor the generation of nitric oxide rather than oxygen free radicals. FA also plays a role in the prevention of several cardiac and noncardiac malformations, has potent direct antioxidant and antithrombotic effects, and can interfere with the production of the endothelial-derived hyperpolarizing factor. These multiple mechanisms of action have led to studies regarding the therapeutic potential of FA in cardiovascular disease. To date, studies have demonstrated that FA ameliorates endothelial dysfunction and nitrate tolerance and can improve pathological features of atherosclerosis. These effects appear to be homocysteine independent but rather related to their role in eNOS function. Given the growing evidence that nitric oxide synthase uncoupling plays a major role in many cardiovascular disorders, the potential of exogenous FA as an inexpensive and safe oral therapy is intriguing and is stimulating ongoing investigations. PMID:18375715

Moens, An L; Vrints, Christiaan J; Claeys, Marc J; Timmermans, Jean-Pierre; Champion, Hunter C; Kass, David A

2008-03-28

258

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

PubMed

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

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

2013-07-11

259

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

PubMed

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

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

2011-06-21

260

Excited-State Dynamics in Folic Acid and 6-CARBOXYPTERIN upon Uva Excitation  

NASA Astrophysics Data System (ADS)

The excited-state dynamics of folic acid (FA) and 6-carboxypterin (6CP) are poorly understood and work is needed to uncover the relaxation pathways that ultimately lead to their oxidative damage of DNA. In our approach, broad-band transient absorption spectroscopy was used to monitor the evolution of the excited states in FA and 6CP in basic aqueous solution upon excitation at 350 nm. In addition, quantum-chemical calculations were performed to assist in the interpretation of the experimental results and in the postulation of kinetic mechanisms. The combined experimental and computational results support a kinetic model where excitation of FA results in ultrafast charge separation (? = 0.6 ps), which decays back to the ground state primarily by charge recombination with a lifetime of 2.2 ps. A small fraction of the charge transfer state undergoes intersystem crossing to populate the lowest-energy triplet state with a lifetime of 200 ps. On the other hand, a large fraction of the initially excited singlet state in 6CP decays by fluorescence emission with a lifetime of 100 ps, while intersystem crossing to the triplet state occurs with a lifetime of 4.4 ns. The potential implications of these results to the oxidative damage of DNA by FA and 6CP will be discussed. Funding from the National Science Foundation is gratefully acknowledged (CHE-1255084).

Huang, Huijuan; Vogt, R. Aaron; Crespo-Hernandez, Carlos E.

2013-06-01

261

Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.  

PubMed

A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases ?5 desaturase activity but decreases mRNA levels, decreases ?6 desaturase activity but not mRNA levels as compared to control. mRNA level of ?5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver. PMID:22133376

Wadhwani, Nisha S; Manglekar, Rupali R; Dangat, Kamini D; Kulkarni, Asmita V; Joshi, Sadhana R

2011-11-30

262

Detection of ascorbic acid and folic acid based on water-soluble CuInS2 quantum dots.  

PubMed

In this paper, water-soluble CuInS(2) ternary quantum dots (QDs) modified by mercaptopropionic acid (MPA) were directly synthesized by hydrothermal method. Ascorbic acid (AA) can induce the fluorescence enhancement of MPA-capped CuInS(2) QDs and can be used for the detection of AA. Under the optimized conditions, the relationship between the fluorescence intensity of the CuInS(2) QDs and AA concentration was linear in the range of 0.25-200 ?mol L(-1). Most relevant molecules and physiological ions had no effect on the detection of AA. The fluorescence intensity of CuInS(2) QDs enhanced by a certain amount of AA could be reduced in the presence of folic acid (FA) and thus can be used for the detection of FA with the linear range of 0.2-100 ?mol L(-1). Compared with previous reports, the established approach utilized a simple, sensitive, and selective strategy to develop the QDs probe based on fluorescence enhancing and quenching phenomena without complicated immobilization. PMID:22898753

Liu, Siyu; Hu, Junjie; Su, Xingguang

2012-10-01

263

Broadcasting behavior change: a comparison of the effectiveness of paid and unpaid media to increase folic acid awareness, knowledge, and consumption among Hispanic women of childbearing age.  

PubMed

Awareness about folic acid's effectiveness in reducing the risk of certain birth defects has increased among women in the United States; however, few Hispanic women are consuming enough folic acid daily. A 1998 survey conducted by the Gallup Organization for the National March of Dimes Birth Defects Foundation found that English-speaking Hispanic women had lower folic acid awareness (53% vs. 72%) and lower daily consumption (29% vs. 33%) than non-Hispanic White women. In 1999, the Centers for Disease Control and Prevention (CDC) conducted baseline surveys with Spanish-speaking Hispanic women in selected U.S. markets to measure folic acid awareness, knowledge, and consumption. A Spanish-language public service announcement (PSA) volunteer campaign and a paid Spanish-language media and community education campaign were conducted in 2000 and 2002, respectively. Comparisons of postcampaign surveys indicate that the paid media campaign was significantly more effective than the PSA campaign in increasing folic acid awareness, knowledge, and consumption among Spanish-speaking Hispanic women. PMID:17003248

Flores, Alina L; Prue, Christine E; Daniel, Katherine Lyon

2006-09-26

264

Enzymatic and Non-enzymatic Antioxidative Effects of Folic Acid and Its Reduced Derivates.  

PubMed

A great part of the population appears to have insufficient folate intake, especially subgroups with higher demand, as determined through more sensitive methods and parameters currently in use. As the role of folate deficiency in congenital defects, e.g. in cardiovascular and neurodegenerative diseases, and in carcinogenesis has become better understood, folate has been recognized as having great potential to prevent these many disorders through folate supplementation or fortification for the general population. Folates are essential cofactors in the transfer and utilization of one-carbon groups in the process of DNA-biosynthesis with implications for genomic repair and stability. Folate acts indirectly to lower homocysteine levels and insures optimal functioning of the methylation cycle. Homocysteine was shown to be an independent risk factor for neurodegenerative and cardiovascular disease, which includes peripheral vascular disease, coronary artery disease, cerebrovascular disease and venous thrombosis. In fact, it was long believed that the beneficial effects of folate on vascular function and disease are related directly to the mechanism of homocysteine-diminution. Recent investigations have, however, demonstrated beneficial effects of folates unrelated to homocysteine-diminution, suggesting independent properties. One such mechanism could be free radical scavenging and antioxidant activity, as it is now recognized that free radicals play an important role in the oxidative stress leading to many diseases. It was found that folic acid and, in particular, its reduced derivates act both directly and indirectly to produce antioxidant effects. Folates interact with the endothelial enzyme NO synthase (eNOS) and, exert effects on the cofactor bioavailability of NO and thus, on peroxynitrite formation. Folate metabolism provides an interesting example of gene-environmental interaction. PMID:22116698

Stanger, Olaf; Wonisch, Willibald

2012-01-01

265

Photoinduced Electron Transfer in Folic Acid Investigated by Ultrafast Infrared Spectroscopy  

PubMed Central

Conformational control of excited-state intramolecular electron transfer (ET) in folic acid (FA) has been investigated using femtosecond time-resolved infrared (TRIR) spectroscopy. Ultrafast excited-state ET between the pterin and the 4-aminobenzoyl subunits of FA is observed for the anionic form (at pH 10.0). An ET lifetime of 2.5 ps is estimated from Marcus theory for FA in the “U” conformation, in close agreement with the observed lifetime of 2.0 ps. Return to the ground state through the reverse ET reaction happens almost as rapidly, within 5 ps, resulting in rapid quenching of the singlet excited state. In mixed water:dimethyl sulfoxide solvent, ET becomes more unfavorable as FA adopts a more open conformation, thereby increasing the effective donor–acceptor distance and reducing the coupling energy. In contrast, no ET is observed for the cationic form of FA at low pH (6.0). In this case, the initial singlet excited state is localized on the pterin moiety of FA, and the excited-state charge distribution evolves with time. The charge redistribution in the pterin that occurs with intersystem crossing to the triplet state is characterized by changes in the transient IR spectrum. The excited-state lifetime is much longer in the absence of an ET quenching pathway. These results provide new insight into the mechanism of photodegradation and toxicity of FA. Ultrafast intramolecular ET in closed conformations of FA rapidly quenches the excited state and prevents efficient triplet state formation. Thus, conformations of FA that allow ultrafast intra-ET and rapid quenching of the singlet excited state play a key role in inhibiting pathological pathways following photoexcitation of FA.

Li, Guifeng; Magana, Donny; Dyer, R. Brian

2012-01-01

266

Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI.  

PubMed

We report the development and in vitro study of a nanoconjugate serving as a targeted magnetic resonance imaging (MRI) contrast enhancement agent for detection of cancer cells overexpressing the folate receptor. The nanoconjugate was synthesized by coating superparamagnetic iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG), followed by conjugation with folic acid (FA). The specificity of the nanoconjugate targeting cancerous cells was demonstrated by comparative intracellular uptake of the nanoconjugate and PEG-/dextran-coated nanoparticles by human adenocarcinoma HeLa cells. Preferential targeting to cancerous cells was studied by comparing the uptake of the nanoconjugate by HeLa cells and by non-FR expressing osteosarcoma MG-63 cells. Uptake of the nanoconjugate by HeLa cells after 4 h incubation was found to be a 12-fold higher than that of PEG- or dextran-coated nanoparticles as quantified by inductively coupled plasma spectroscopy. A significant negative contrast enhancement was observed with magnetic resonance (MR) phantom imaging for HeLa cells over MG-63 cells, when both were cultured with the nanoconjugate. Specificity of the nanoconjugate for folate receptors was also verified with a competitive inhibition assay, in which HeLa cells were incubated with both NP-PEG-FA and free FA. The bifunctional PEG used has amide linkages within the PEG chains that can form interchain hydrogen bonding, leading to improved stability of the PEG coating. Self-assembled PEG can be controlled at the molecular level and are suitable for nanoscale coatings. PMID:16736484

Sun, Conroy; Sze, Raymond; Zhang, Miqin

2006-09-01

267

Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives.  

PubMed

A group of studies on indigent hospital patients were conducted on the role of folate supplements, pregnancy and oral contraceptives in megaloblastic anemia. First 25 pregnant women, given 500 mg iron dextran and 30 mg folic acid for 2-3 months, had 12.4% hemoglogin at delivery, compared with 49 women given only iron who had 12.5% hemoglobin, and 49 untreated women who had 11.3% hemoglobin. Second, plasma folate levels in groups of pregnant women were compared: mean folate was 4.7 ng/ml in 82 normal women, 3.1 in 21 treated epileptics, and about 1.2 in 31 women with megaloblastic anemia. In 77 pregnancies in 43 epileptic women there were no reasons to blame low folate levels for pregnancy wastage since no abruptio placentae or bleeding occurred; and incidence of low birth weight, perinatal death, and prematurity was lower than in the general population. Third, the effect of oral contraceptives on folate levels was observed. Mean plasma folate levels were 8.1 ng/ml in 55 control women, 8.0 in 57 women using the pill, 4.7 in normal women in late pregnancy, and about 1.1 in pregnant women with megaloblastic anemia. Fourth, mean hemoglobin levels rose from 7.6 to 13.4 9m/100 ml within a few weeks in 5 women with gestational megaloblastic anemia after treatment with normal diet, without supplement, and oral contraceptives. One woman with puerperal megaloblastic anemia failed to respond to a regular diet while taking Ovulen, 6 tablets daily. The results suggest that plasma folate levels were neither lower in oral contracepting women nor did the pill prevent the increase in folate in megaloblastic anemia patients treated with diet. Thus the authors concluded that folate supplement is not needed for pill users. PMID:5549181

Pritchard, J A; Scott, D E; Whalley, P J

1971-02-01

268

Photoinduced electron transfer in folic acid investigated by ultrafast infrared spectroscopy.  

PubMed

Conformational control of excited-state intramolecular electron transfer (ET) in folic acid (FA) has been investigated using femtosecond time-resolved infrared (TRIR) spectroscopy. Ultrafast excited-state ET between the pterin and the 4-aminobenzoyl subunits of FA is observed for the anionic form (at pH 10.0). An ET lifetime of 2.5 ps is estimated from Marcus theory for FA in the "U" conformation, in close agreement with the observed lifetime of 2.0 ps. Return to the ground state through the reverse ET reaction happens almost as rapidly, within 5 ps, resulting in rapid quenching of the singlet excited state. In mixed water:dimethyl sulfoxide solvent, ET becomes more unfavorable as FA adopts a more open conformation, thereby increasing the effective donor-acceptor distance and reducing the coupling energy. In contrast, no ET is observed for the cationic form of FA at low pH (6.0). In this case, the initial singlet excited state is localized on the pterin moiety of FA, and the excited-state charge distribution evolves with time. The charge redistribution in the pterin that occurs with intersystem crossing to the triplet state is characterized by changes in the transient IR spectrum. The excited-state lifetime is much longer in the absence of an ET quenching pathway. These results provide new insight into the mechanism of photodegradation and toxicity of FA. Ultrafast intramolecular ET in closed conformations of FA rapidly quenches the excited state and prevents efficient triplet state formation. Thus, conformations of FA that allow ultrafast intra-ET and rapid quenching of the singlet excited state play a key role in inhibiting pathological pathways following photoexcitation of FA. PMID:22364409

Li, Guifeng; Magana, Donny; Dyer, R Brian

2012-03-06

269

Use of folic acid-containing supplements after a diagnosis of colorectal cancer in the Colon Cancer Family Registry  

PubMed Central

Background Supplement use among cancer patients is high, and folic acid intake in particular may adversely affect the progression of colorectal cancer. Few studies have evaluated the use of folic acid-containing supplements (FAS) and its predictors in colorectal cancer patients. Objective To assess the use of FAS, change in use, and its predictors after colorectal cancer diagnosis. Design We used logistic regression models to investigate predictors of FAS use and its initiation after colorectal cancer diagnosis in 1,092 patients recruited through the Colon Cancer Family Registry (C-CFR). Results The prevalence of FAS use was 35.4% before and 55.1% after colorectal cancer diagnosis (p=0.004). Women were more likely than men to use FAS after diagnosis (OR 1.47, 95% CI 1.14-1.89), as were those consuming more fruit (ptrend<0.0001) or vegetables (ptrend=0.001), and US residents (p<0.0001). Less likely to use FAS after diagnosis were non-white patients (OR 0.66, 95% CI 0.45-0.97), current smokers (OR 0.67, 95% CI 0.46-0.96), and those with higher meat intake (ptrend=0.03). Predictors of FAS initiation after diagnosis were generally similar to those of FAS use after diagnosis, though associations with race and vegetable intake were weaker and those with exercise stronger. Conclusions Our analysis showed substantial increases in the use of folic acid-containing supplements after diagnosis with colorectal cancer, with use or initiation more likely among women, Caucasians, U.S. residents, and those with a health-promoting lifestyle. Impact Studies of cancer prognosis that rely on pre-diagnostic exposure information may result in substantial misclassification.

Holmes, Rebecca S.; Zheng, Yingye; Baron, John A.; Li, Lin; McKeown-Eyssen, Gail; Newcomb, Polly A.; Stern, Mariana C.; Haile, Robert W.; Grady, William M.; Potter, John D.; Marchand, Loic Le; Campbell, Peter T.; Figueiredo, Jane C.; Limburg, Paul J.; Jenkins, Mark A.; Hopper, John L.; Ulrich, Cornelia M.

2012-01-01

270

Periconceptional use of folic acid and risk of miscarriage - Findings of Oral Cleft Prevention Program in Brazil  

PubMed Central

We report on the risk of miscarriage due to high dosage periconceptional folic acid (FA) supplementation from a double blind randomized clinical trial for prevention of orofacial clefts in Brazil. The miscarriage rate was 14.2% in the low dose FA group (0.4 mg per day) and 11.3% for the high dose (4 mg per day) group (p=0.4877); the population miscarriage rate is 14%. These results indicate that high dose FA does not increase miscarriage risk in this population and add further information to the literature on the safety of high FA supplementation for prevention of birth defect recurrence.

Vila-Nova, C; Wehby, GL; Queiros, F; Chakraborty, H; Felix, TM; Goco, N; Moore, J; Gewehr, EV; Lins, L; Affonso, CMC; Murray, JC

2013-01-01

271

Use of an oral/intravenous dual-label stable-isotope protocol to determine folic acid bioavailability from fortified cereal grain foods in women.  

PubMed

Folic acid fortification, mandatory in the United States, is currently being considered by the UK. The hypothesis that the matrix of some cereal-product vehicles may result in low fortificant bioavailability was tested using a dual oral/intravenous (i.v.) isotopic-label approach, which was evaluated concurrently. Fifteen women received 225 microg oral folate (capsules, fortified white bread and fortified branflakes), mainly as folic acid labeled with (13)C on 6 carbons of the benzoyl ring ((13)C(6)-PteGlu), followed by i.v. injection of 100 microg folic acid labeled with (2)H on 4 hydrogens of the glutamic acid group ((2)H(4)-PteGlu). The urinary excretion ratio (UER) in intact folate of the percentage of labeled oral dose excreted divided by the percentage of i.v. dose excreted was used as the primary index of absorption. The geometric mean (95% confidence interval) UER for folic acid capsules was 3.68 (1.90, 7.14) at 24 h and 2.18 (1.24, 3.83) at 48 h. Because these were significantly in excess of 1.0, indicative of 100% absorption of the oral dose, it was concluded that oral and i.v. labeled folic acid are handled differently by the body and that "absolute" absorption cannot be calculated. Compared with the 48-h UER for folic acid capsules, the "relative" 48-h UER for white bread and branflakes was 0.71 and 0.37, respectively, indicating that some cereal-based vehicles may inhibit absorption of fortificant. However, even the validity of this "relative" approach is questioned. PMID:11983817

Finglas, Paul M; Witthöft, Cornelia M; Vahteristo, Liisa; Wright, Anthony J A; Southon, Susan; Mellon, Fred A; Ridge, Brian; Maunder, Peter

2002-05-01

272

Effect of deworming vs Iron-Folic acid supplementation plus deworming on growth, hemoglobin level, and physical work capacity of schoolchildren.  

PubMed

The effect of deworming vs deworming and weekly Iron-Folic acid (IFA) on growth, hemoglobin level, and physical work capacity of children was studied. Children from three rural schools studying from 4th to 7th standard were selected. One set of school children were given deworming tablet (400 mg albendezole) once in six months while the second school children received deworming tablet along with weekly dose of Iron Folic acid Tablet (60 mg of elemental iron and 0.5 mg folic acid). Anthropometric measurements, hemoglobin, and physical work capacity was estimated. No significant change was noticed in the prevalence of malnutrition or physical work capacity of the children. As compared to only deworming, IFA + Deworming showed 17.3% increase in the hemoglobin levels (P<0.001). Thus weekly IFA along with deworming has shown beneficial effect on the hemoglobin levels of the children. PMID:22962239

Bhoite, Rachana M; Iyer, Uma M

2012-08-01

273

Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced nitric oxide synthase dysfunction and tolerance: A human in vivo study  

PubMed Central

INTRODUCTION Continuous treatment with nitroglycerin (GTN) causes tolerance and endothelial dysfunction, both of which may involve endothelial nitric oxide synthase (eNOS) dysfunction. eNOS dysfunction may be linked to depletion of tetrahydrobiopterin, and folic acid may be involved in the regeneration of this cofactor. It has been demonstrated that 10 mg/day folic acid supplementation prevents the development of GTN tolerance and GTN-induced endothelial dysfunction. However, the efficacy of daily lower-dose folic acid supplementation for preventing these phenomena has not been investigated. OBJECTIVE To determine the effect of 1 mg/day folic acid supplementation on responses to sustained GTN therapy. METHODS AND RESULTS On visit 1, 20 healthy male volunteers were randomly assigned to receive either oral folic acid (1 mg/day) or placebo for one week in a double- blind study. All subjects also received continuous transdermal GTN (0.6 mg/h). On visit 2, forearm blood flow was measured using venous occlusion strain-gauge plethysmography in response to incremental intra-arterial infusions of acetylcholine, N-monomethyl-L-arginine and GTN. Subjects in both groups displayed significantly decreased responses to acetylcholine and N-monomethyl-L-arginine infusions compared with a control group that received no treatment. Responses to GTN were also significantly diminished in both groups (P<0.05 for all). DISCUSSION The present data demonstrate that daily supplementation with 1 mg folic acid does not prevent the development of GTN-induced eNOS dysfunction or tolerance.

DiFabio, Jonathan M; Gori, Tommaso; Thomas, George R; Jedrzkiewicz, Sean J; Parker, John D

2010-01-01

274

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project  

PubMed Central

BACKGROUND Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects, and may be associated with a reduced risk for congenital heart defects, and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of folic acid-containing supplements. These data were used to determine whether lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race/ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (OR=1.69; 95% CI, 1.08–2.63; P=0.011) or atrial septal defects (OR=1.69; 95% CI, 1.11–2.58; P=0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race/ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR=1.26; 95% CI, 0.85–1.87; P=0.124). CONCLUSIONS Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome.

Bean, Lora J. H.; Allen, Emily G.; Tinker, Stuart W.; Hollis, NaTasha D.; Locke, Adam E.; Druschel, Charlotte; Hobbs, Charlotte A.; O'Leary, Leslie; Romitti, Paul A.; Royle, Marjorie H.; Torfs, Claudine P.; Dooley, Kenneth J.; Freeman, Sallie B.; Sherman, Stephanie L.

2011-01-01

275

Effect of various amounts of folic acid added to rat food on food intake and some parameters of carbohydrate metabolism.  

PubMed

Male Wistar rats were given for 14 days folic acid as an addition to standard LSM food at the doses of 0.22 mg (group II), 2.2 mg (group III), 2.6 mg (group IV), 11 mg (group V) and 16.5 mg (group VI) per day/rat. In the beginning a decrease in body weight was observed and from the 7th day the weight started to increase to reach control value in all groups on the 14th day. Food intake was deteriorating with the acid concentration. The increased glucose and decreased insuline level in rat blood serum which were highly significant for groups IV and V as compared to control for the former parameter and significant for group V as compared to groups I and II for insuline indicate an effect of the excess of vitamin on endocrine function of pancreas. Increase in the muscle glicogen may result from intensified glicogenesis and gliconeogenesis processes due to folic acid. PMID:8891180

Prusiewicz-Witaszek, U; Maciejewska, M

1994-01-01

276

Equivalent absorption and in vivo kinetics of tritiated folic acid and 5-formyl-tetrahydrofolic acid in rats  

SciTech Connect

The intestinal absorption and in vivo turnover kinetics of ({sup 3}H)folic acid (FA) and (6S)-5-formyl-({sup 3}H)tetrahydrofolate (5-CHO-THF) were examined to determine whether differences exist in the inherent bioavailability of these forms of the vitamin. Following oral administration of 2 {mu}Ci/100 g body weight (in 50 mM sodium ascorbate, pH 7), a biphasic pattern of urinary tritium excretion was observed for each labeled folate. The following kinetic results were obtained (n=9). Little tritium was found in the GI tract after 8 hours, which indicated nearly complete absorption of each folate. HPLC analysis of urine revealed similar excretory patterns over 0-8 days post-dose for each folate administered, and the patterns of hepatic ({sup 3}H)folates were equivalent when examined after 8 hours and 4 days post-dose. These findings indicate that the bioavailability FA and 5-formyl-THF is equivalent.

Bhandari, S.D.; Gregory, J.F. (Univ. of Florida, Gainesville (United States))

1990-02-26

277

Mefolinate (5-methyltetrahydrofolate), but not folic acid, decreases mortality in an animal model of severe methylenetetrahydrofolate reductase deficiency.  

PubMed

Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) results in homocystinuria, with a variety of neurological and vascular complications, and sometimes death in the first year of life. MTHFR (EC 1.5.1.20) catalyses the synthesis of 5-methyltetrahydrofolate (5-methylTHF) which is required for homocysteine remethylation to methionine. Mthfr (-/-) mice are a good animal model of severe MTHFR deficiency in humans. They have marked hyperhomocysteinaemia and a high rate of mortality in the neonatal period. We attempted to rescue Mthfr (-/-) mice from postnatal death by treating their Mthfr (+/-) mothers with mefolinate (a synthetic form of 5-methylTHF, dissolved in their drinking water) or with a folic acid-enriched diet throughout pregnancy and lactation. We monitored pups' vitality and body weights until 3 weeks of age. The majority of Mthfr (-/-) pups from the control groups died during the first week of life. Body weights of -/- pups from control groups were significantly less than those of their Mthfr (+/-) and Mthfr ( +/+ ) littermates. Mefolinate treatment significantly improved survival rates (64% survival) in the -/- pups and improved morphology of the cerebellum. Folic acid supplementation did not affect the survival rate or body weights of the -/- pups. Our study suggests that MTHFR is important for postnatal growth and vitality, and that 5-methylTHF deficiency contributes to the high postnatal mortality. Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency. PMID:18415702

Li, D; Karp, N; Wu, Q; Wang, X-L; Melnyk, S; James, S J; Rozen, R

2008-04-14

278

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

PubMed

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

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

2012-06-28

279

Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada  

PubMed Central

Objective To investigate whether the 1998 government policy for mandatory fortification of flour and pasta products with folate was followed by a reduction in the prevalence of severe congenital heart defects. Design Time trend analysis. Setting Province of Quebec, Canada. Participants Infants born in 1990-2005 identified with severe congenital heart defects (tetralogy of Fallot, endocardial cushion defects, univentricular hearts, truncus arteriosus, or transposition complexes) in Quebec administrative databases. Methods Data analysed in two time periods (before and after fortification). Birth prevalence measured annually as infants (live and stillbirths) with severe congenital heart defects per 1000 births in Quebec. Changes in the birth prevalence from the period before to the period after fortification were estimated with Poisson regression. Results Among the 1?324?440 births in Quebec in 1990-2005 there were 2083 infants born with severe congenital heart defects, corresponding to an average birth prevalence of 1.57/1000 births. Time trend analysis showed no change in the birth prevalence of severe birth defects in the nine years before fortification (rate ratio 1.01, 95% confidence interval 0.99 to 1.03), while in the seven years after fortification there was a significant 6% decrease per year (0.94, 0.90 to 0.97). Conclusions Public health measures to increase folic acid intake were followed by a decrease in the birth prevalence of severe congenital heart defects. These findings support the hypothesis that folic acid has a preventive effect on heart defects.

2009-01-01

280

Effect of Therapy with Vitamin B12 and Folic Acid on Elderly Patients with Low Concentrations of Serum Vitamin B12 or Erythrocyte Folate but Normal Blood Counts  

Microsoft Academic Search

To help understand the haematological significance of the low concentrations of serum vitamin B12 and erythrocyte folate occurring in elderly patients, 17 acute admissions to a geriatric unit with a low concentration of serum vitamin B12 or erythrocyte folate but a normal blood count were treated with vitamin B12 and folic acid for 3 months. Bone marrow deoxyuridine supression was

J. H. Matthews; D. M. Clark; G. M. Abrahamson

1988-01-01

281

Folate Requirements of Children. II. Response of Children Recovering from Protein-Calorie Malnutrition to Graded Doses of Parenterally Administered Folic Acid.  

National Technical Information Service (NTIS)

Twenty-three cases of protein-calorie malnutrition exhibiting signs of iron and folate deficiency were given a diet nutritionally adequate in all nutrients except folic acid. This was provided by a low folate diet that supplied 5.8 micro g free and 6.3 mi...

K. Kamel C. I. Waslien Z. El-Ramly S. Guindy K. A. Mourad

1972-01-01

282

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

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

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

2009-01-01

283

Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study  

Microsoft Academic Search

BACKGROUND: Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress play a role in endothelial progenitor cell dysfunction in these patients. Folic acid, a B-vitamin with anti-oxidant properties, may be able

Olivia van Oostrom; Dominique PV de Kleijn; Joost O Fledderus; Mario Pescatori; Andrew Stubbs; Attie Tuinenburg; Sai Kiang Lim; Marianne C Verhaar

2009-01-01

284

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

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

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

285

Weekly iron-folic acid supplementation to improve iron status and prevent pregnancy anemia in Filipino women of reproductive age: the Philippine experience through government and private partnership.  

PubMed

With the participation of the government and private sectors in the Philippines, weekly iron-folic acid supplementation introduced within a social marketing framework and a social mobilization campaign successfully improved knowledge and practice of buying and regularly taking supplements by women of reproductive age, both pregnant and non-pregnant. Adolescent girls in school were also active participants. PMID:16466086

Paulino, Lourdes S; Angeles-Agdeppa, Imelda; Etorma, Unita Mari M; Ramos, Adelisa C; Cavalli-Sforza, Tommaso

2005-12-01

286

Assessment of the efficacy of combination therapy with folic acid and tadalafil for the management of erectile dysfunction in men with type 2 diabetes mellitus.  

PubMed

INTRODUCTION.: Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated. AIM.: To evaluate the efficacy and safety of combination therapy with folic acid and tadalafil for the management of ED in men with type 2 diabetes mellitus. METHODS.: Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10?mg every other day plus folic acid 5?mg daily and group B received tadalafil 10?mg every other day plus placebo daily for 3 months. The mean International Index of Erectile Function (IIEF) scores before and after treatment in each groups were recorded. Men with diagnosis of psychological ED, spinal cord injury, or who used folic acid in the past 3 months and patients with any contradiction for use of PDE5Is were excluded. MAIN OUTCOMES MEASURES.: The cross tabulation and independent t-test were used to evaluate the difference between baseline characteristic of the patients in the two groups. Wilcoxon signed-ranks test and Mann-Whitney U-test were used to evaluate the IIEF score and also its changes before and after treatment in the two groups. RESULTS.: The mean IIEF scores before and after treatment were 11.65?±?2.67 and 16.80?±?4.03 in group A (P?folic acid and tadalafil were well tolerated by all the patients. CONCLUSION.: Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe. PMID:23347176

Hamidi Madani, Ali; Asadolahzade, Ahmad; Mokhtari, Gholamreza; Shahrokhi Damavand, Reza; Farzan, Alireza; Esmaeili, Samaneh

2013-01-24

287

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

PubMed Central

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.

2010-01-01

288

Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age  

PubMed Central

Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (?14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ?25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.

Berry, Robert J.; Hao, Ling; Li, Zhu; Maneval, David; Yang, Thomas P.; Rasmussen, Sonja A.; Yang, Quanhe; Zhu, Jiang-Hui; Hu, Dale J.; Bailey, Lynn B.

2011-01-01

289

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

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.

Morse, Nancy L.

2012-01-01

290

Synthesis, characterization, and in vitro testing of superparamagnetic iron oxide nanoparticles targeted using folic Acid-conjugated dendrimers.  

PubMed

Organic-coated superparamagnetic iron oxide nanoparticles (OC-SPIONs) were synthesized and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. OC-SPIONs were transferred from organic media into water using poly(amidoamine) dendrimers modified with 6-TAMRA fluorescent dye and folic acid molecules. The saturation magnetization of the resulting dendrimer-coated SPIONs (DC-SPIONs) was determined, using a superconducting quantum interference device, to be 60 emu/g Fe versus 90 emu/g Fe for bulk magnetite. Selective targeting of the DC-SPIONs to KB cancer cells in vitro was demonstrated and quantified using two distinct and complementary imaging modalities: UV-visible and X-ray fluorescence; confocal microscopy confirmed internalization. The results were consistent between the uptake distribution quantified by flow cytometry using 6-TAMRA UV-visible fluorescence intensity and the cellular iron content determined using X-ray fluorescence microscopy. PMID:19206610

Landmark, Kevin J; Dimaggio, Stassi; Ward, Jesse; Kelly, Christopher; Vogt, Stefan; Hong, Seungpyo; Kotlyar, Alina; Myc, Andrzej; Thomas, Thommey P; Penner-Hahn, James E; Baker, James R; Holl, Mark M Banaszak; Orr, Bradford G

2008-04-01

291

Increased Birth Weight Associated with Regular Pre-Pregnancy Deworming and Weekly Iron-Folic Acid Supplementation for Vietnamese Women  

PubMed Central

Background Hookworm infections are significant public health issues in South-East Asia. In women of reproductive age, chronic hookworm infections cause iron deficiency anaemia, which, upon pregnancy, can lead to intrauterine growth restriction and low birth weight. Low birth weight is an important risk factor for neonatal and infant mortality and morbidity. Methodology We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam. The program was made available to all women of reproductive age (estimated 51,623) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection. Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention, but had similar maternal and child health indicators and socio-economic backgrounds. The primary outcome was low birth weight. Principal Findings The birth weights of 463 infants born in district hospitals in the intervention (168) and control districts (295) were recorded. Twenty-six months after the program was started, the prevalence of low birth weight was 3% in intervention districts compared to 7.4% in control districts (adjusted odds ratio 0.29, 95% confidence interval 0.10 to 0.81, p?=?0.017). The mean birth weight was 124 g (CI 68 - 255 g, p<0.001) greater in the intervention districts compared to control districts. Conclusions/Significance The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam. The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive randomised-controlled trial.

Passerini, Luca; Casey, Gerard J.; Biggs, Beverley A.; Cong, Dai T.; Phu, Luong B.; Phuc, Tran Q.; Carone, Marco; Montresor, Antonio

2012-01-01

292

Treatment of experimental adjuvant arthritis with a novel folate receptor-targeted folic acid-aminopterin conjugate  

PubMed Central

Introduction Folate receptor (FR)-expressing macrophages have been shown to accumulate at sites of inflammation, where they promote development of inflammatory symptoms. To target such a macrophage population, we designed and evaluated the biologic activity of EC0746, a novel folic acid conjugate of the highly potent antifolate, aminopterin. Methods Using a FR-positive subclone of murine macrophage-derived RAW264.7 cells and rat thioglycollate-elicited macrophages, we studied the effect of EC0746 on dihydrofolate reductase activity, cell proliferation, and cellular response towards bacterial lipopolysaccharide as well as IFN? activation. The EC0746 anti-inflammatory activity, pharmacokinetics, and toxicity were also evaluated in normal rats or in rats with adjuvant-induced arthritis; that is, a FR-positive macrophage model that closely resembles rheumatoid arthritis in humans. Results EC0746 suppresses the proliferation of RAW264.7 cells and prevents the ability of nonproliferating rat macrophages to respond to inflammatory stimuli. In the macrophage-rich rat arthritis model, brief treatment with subcutaneously administered EC0746 is shown to mediate an FR-specific anti-inflammatory response that is more potent than either orally administered methotrexate or subcutaneously delivered etanercept. More importantly, EC0746 therapy is also shown to be ~40-fold less toxic than unmodified aminopterin, with fewer bone marrow and gastrointestinal problems. Conclusions EC0746 is the first high FR-binding dihydrofolate reductase inhibitor that demonstrates FR-specific anti-inflammatory activities both in vitro and in vivo. Our data reveal that a relatively toxic anti-inflammatory drug, such as aminopterin, can be targeted with folic acid to inflammatory macrophages and thereby relieve inflammatory symptoms with greatly reduced toxicity.

2011-01-01

293

Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging.  

PubMed

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

Zhou, Zhijun; Zhang, Chunlei; Qian, Qirong; Ma, Jiebing; Huang, Peng; Zhang, Xi; Pan, Liyuan; Gao, Guo; Fu, Hualin; Fu, Shen; Song, Hua; Zhi, Xiao; Ni, Jian; Cui, Daxiang

2013-05-29

294

Inhibition of Carcinoma Cell Motility by Epoxyeicosatrienoic Acid (EET) Antagonists  

PubMed Central

Summary Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNAs and proteins, were expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in these cells. Blocking the EET synthesis by a selective CYP epoxygenase inhibitor (MS-PPOH) inhibited tonic (basal) invasion and migration (motility) while exogenously added EETs induced cell motility in a concentration-dependent manner. An EGFR kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12-EET-induced cell migration. Importantly, synthetic EET antagonists (14,15-EEZE, 14,15-EEZE-PEG and 14,15-EEZE-mSI) inhibited EET-induced cell invasion and migration. 11,12-EET induced cell stretching and myosin-actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473) while 14,15-EEZE inhibited these effects. These results suggest that EETs induce and EET antagonists inhibit cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt pathways, and suggest EET antagonists as potential therapeutic agents for prostate cancer.

Nithipatikom, Kasem; Brody, Daniel M.; Tang, Alan T.; Manthati, Vijaya L.; Falck, John R.; Williams, Carol L.; Campbell, William B.

2012-01-01

295

Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists.  

PubMed

Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA and proteins, were expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in these cells. Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide [MS-PPOH]) inhibited tonic (basal) invasion and migration (motility) while exogenously added EET induced cell motility in a concentration-dependent manner. An epidermal growth factor receptor (EGFR) kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12-EET-induced cell migration. Importantly, synthetic EET antagonists (14,15-epoxyeicosa-5(Z)-enoic acid [14,15-EEZE], 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester [14,15-EEZE-PEG] and 14,15-epoxyeicosa-5(Z)-enoic-methylsulfonylimide [14,15-EEZE-mSI]) inhibited EET-induced cell invasion and migration. 11,12-EET induced cell stretching and myosin-actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473), while 14,15-EEZE inhibited these effects. These results suggest that EET induce and EET antagonists inhibit cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt pathways, and suggest that EET antagonists are potential therapeutic agents for prostate cancer. PMID:20804500

Nithipatikom, Kasem; Brody, Daniel M; Tang, Alan T; Manthati, Vijaya L; Falck, John R; Williams, Carol L; Campbell, William B

2010-08-27

296

Convegno annuale. Network Italiano Promozione Acido Folico per la Prevenzione Primaria di Difetti Congeniti. (Annual Conference. Italian Network for the Promotion of Folic Acid and Prevention of Congenital Defects.)  

National Technical Information Service (NTIS)

Use of folic acid during periconceptional period to prevent some birth defects is universally recognized. Major scientific organizations involved in prevention and public health are engaged in detailed assessment of the risk-benefit and effectiveness of v...

D. Taruscio P. Carbone

2009-01-01

297

Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells  

PubMed Central

The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol?1 · sec?l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer.

Kumar, Manoj; Singh, Gurpal; Arora, Vikas; Mewar, Sujeet; Sharma, Uma; Jagannathan, NR; Sapra, Sameer; Dinda, Amit K; Kharbanda, Surender; Singh, Harpal

2012-01-01

298

Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study123  

PubMed Central

Background: Periconceptional folate is essential for proper neurodevelopment. Objective: Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD). Design: Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews. Results: Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 ?g, respectively; P < 0.01). A mean daily folic acid intake of ?600 ?g (compared with <600 ?g) during P1 was associated with reduced ASD risk (adjusted OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with increased folic acid (P-trend = 0.001). The association between folic acid and reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T variant genotypes. A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders. Conclusions: Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.

Schmidt, Rebecca J; Tancredi, Daniel J; Ozonoff, Sally; Hansen, Robin L; Hartiala, Jaana; Allayee, Hooman; Schmidt, Linda C; Tassone, Flora; Hertz-Picciotto, Irva

2012-01-01

299

Synthesis, Spectroscopic and Thermal Characterization of Copper(II) and Iron(III) Complexes of Folic Acid and Their Absorption Efficiency in the Blood  

PubMed Central

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.

Hamed, E.; Attia, M. S.; Bassiouny, K.

2009-01-01

300

A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles  

PubMed Central

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy.

Zu, Yuangang; Wang, Dan; Zhao, Xiuhua; Jiang, Ru; Zhang, Qi; Zhao, Dongmei; Li, Yong; Zu, Baishi; Sun, Zhiqiang

2011-01-01

301

Effects of Intramuscular Injections of Vitamin B12 on Lactation Performance of Dairy Cows Fed Dietary Supplements of Folic Acid and Rumen-Protected Methionine  

Microsoft Academic Search

The experiment was undertaken to determine the effects of i.m. injections of vitamin B12 on lactational performance of primiparous dairy cows fed dietary sup- plements of folic acid and rumen-protected methionine from 4 to 18 wk of lactation. Fourteen primiparous Hol- stein cows were assigned to 7 blocks of 2 cows each, according to milk production during the third week

C. L. Girard; J. J. Matte

2005-01-01

302

U.S. provider reported folic acid or multivitamin ordering for non-pregnant women of childbearing age: NAMCS and NHAMCS, 2005-2006.  

PubMed

Folic acid use started prior to pregnancy confers a decreased risk of neural tube defects, and yet 20-50% of pregnancies are unplanned. We sought to determine whether medical providers order folic acid (FA) or folic acid-containing multivitamins (MVI) for their non-pregnant female patients of childbearing age. This is a cross-sectional study using data from the CDC's National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) (2005 and 2006). Among non-pregnant, female patients of childbearing age (15-44), the proportion of preventive visits during which a provider ordered FA/MVI supplements was determined and compared to pregnant patients. Next, the rates of FA/MVI orders were examined according to race/ethnicity, age, insurance status, region of the country, provider type, contraceptive care, income and education. Analyses were conducted using SAS-callable Sudaan to account for survey design and to obtain population estimates. There were 4,634 preventive visits for non-pregnant women of childbearing age, representing 32.1 million visits nationally. Of these visits, 7.2% included provider-ordered FA/MVI. Multivariable logistic regression analyses revealed that provider-ordered FA/MVI was most common for women ages 30-34, who receive Medicaid, and whose race/ethnicity was other than White, Black or Hispanic. Preventive care visits represent an important venue for counseling regarding the benefits of FA for women of childbearing age, but appear to be under-utilized in all women. Our findings suggest that annually there may be over 29 million missed opportunities to recommend folic acid to non-pregnant women seeking preventive care. PMID:20204479

Burris, Heather H; Werler, Martha M

2011-04-01

303

Determination of folic acid by ion-pair RP-HPLC in vitamin-fortified fruit juices after solid-phase extraction  

Microsoft Academic Search

A sensitive and reliable method was developed for the determination of folic acid (FA) in vitamin-fortified fruit juices and fruit drinks. After solid-phase extraction clean-up with strong-anion-exchange material, FA was determined by ion-pair reversed phase high-performance liquid chromatography (RP-HPLC). Limits of detection (LOD) and quantitation (LOQ) were 0.04 and 0.06 mg\\/l, respectively. Average recoveries at two fortified levels (0.5 and

Dietmar E Breithaupt

2001-01-01

304

Antenatal supplementation with folic acid + iron + zinc improves linear growth and reduces peripheral adiposity in school-age children in rural Nepal123  

PubMed Central

Background: We previously reported that a randomized controlled trial of antenatal micronutrient supplements in rural Nepal decreased the risk of low birth weight by ?15%. Objective: The objective was to examine the effects of micronutrient supplementation on growth and body composition in children of supplemented mothers through school age. Design: Mothers received 1 of 5 micronutrient supplements daily: folic acid, folic acid + iron, folic acid + iron + zinc, multiple micronutrients, or a control. All of the supplements contained vitamin A. Children born during this trial were revisited at age 6–8 y to measure height, weight, midupper arm circumference, waist circumference, and triceps and subscapular skinfold thicknesses. Arm fat and muscle area were estimated by using standard formulas, and height-for-age, weight-for-age, and body mass index–for-age z scores were calculated by using the World Health Organization growth standard. Results: Of the 3771 surviving children, 3324 were revisited and consented to anthropometric measurements. Maternal supplementation with folic acid + iron + zinc resulted in an increase in mean height (0.64 cm; 95% CI: 0.04, 1.25) and a reduction in mean triceps skinfold thickness (?0.25 mm; 95% CI: ?0.44, ?0.06), subscapular skinfold thickness (?0.20 mm; 95% CI: ?0.33, ?0.06), and arm fat area (?0.18 cm2; ?0.34, ?0.01). No significant differences were found between groups in mean weight or body mass index–for-age z scores, waist circumference, or arm muscle area. Other micronutrient combinations including a multiple micronutrient formulation failed to show a growth benefit. Conclusion: Antenatal supplementation with zinc may benefit child growth, particularly in areas where a deficiency of this nutrient is common.

Stewart, Christine P; LeClerq, Steven C; West, Keith P; Khatry, Subarna K

2009-01-01

305

Effect of Homocysteine-Lowering Treatment With Folic Acid and B Vitamins on Risk of Type 2 Diabetes in Women: A Randomized, Controlled Trial  

Microsoft Academic Search

OBJECTIVE—Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—The Women's Anti- oxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 fe- male

Yiqing Song; Nancy R. Cook; Christine M. Albert; Martin Van Denburgh; JoAnn E. Manson

2009-01-01

306

Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes—evidence for breakage–fusion-bridge cycles in the cytokinesis-block micronucleus assay  

Microsoft Academic Search

We have validated the analysis of nucleoplasmic bridges (NPBs) and nuclear buds as biomarkers of genomic instability within the cytokinesis-block micronucleus assay in long-term lymphocyte cultures. Lymphocytes from 20 subjects were cultured in medium containing 12–120nM folic acid for 9 days. Binucleate cells were scored for micronuclei (MN), NPBs and nuclear budding on day nine after 24h incubation in the

Michael Fenech; Jimmy W Crott

2002-01-01

307

Impact of CuO nanoleaves on MWCNTs/GCE nanocomposite film modified electrode for the electrochemical oxidation of folic acid  

NASA Astrophysics Data System (ADS)

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.

Manoj, D.; Ranjith Kumar, D.; Santhanalakshmi, J.

2012-09-01

308

Practice Parameter update: Management issues for women with epilepsy--Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding  

PubMed Central

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. Methods: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. Results: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. Recommendations: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Harden, C. L.; Pennell, P. B.; Koppel, B. S.; Hovinga, C. A.; Gidal, B.; Meador, K. J.; Hopp, J.; Ting, T. Y.; Hauser, W. A.; Thurman, D.; Kaplan, P. W.; Robinson, J. N.; French, J. A.; Wiebe, S.; Wilner, A. N.; Vazquez, B.; Holmes, L.; Krumholz, A.; Finnell, R.; Shafer, P. O.; Le Guen, C.

2009-01-01

309

Effects of folic acid deficiency and MTHFRC677T polymorphisms on cytotoxicity in human peripheral blood lymphocytes  

SciTech Connect

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.

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

310

Effects of the storage time on the folic acid added to ready-to-eat meat products manufactured by irradiation  

NASA Astrophysics Data System (ADS)

Three different meat products enriched with folic acid (FA) (2.4 mg/100 g) were manufactured: hamburgers, cooked and dry fermented sausages. They were prepared as ready-to-eat (RTE) products using E-beam radiation (2 and 3 kGy) to ensure their safety. The stability of FA and sensory properties of the irradiated meat products were studied during three months of storage under freezing conditions for hamburgers and refrigeration conditions for cooked and dry fermented sausages. FA content was stable in non-irradiated and irradiated hamburgers and cooked sausages over the storage period, whereas it decreased 20% in non-irradiated dry fermented sausages and 12-8% in irradiated samples at 2 and 3 kGy, respectively. Nevertheless, the final amount remained sufficient to provide the recommended daily intake. Panelists rated the sensory properties of the hamburger as satisfactory even after irradiation and 90 days of storage. The overall acceptability of RTE cooked and dry fermented sausages improved slightly with storage (P>0.05).

Galán, I.; García, M. L.; Selgas, M. D.

2013-04-01

311

Population prevalence, attributable risk, and attributable risk percentage for high methylmalonic acid concentrations in the post-folic acid fortification period in the US  

PubMed Central

Background Serum methylmalonic acid (MMA) is regarded as a sensitive marker of vitamin B-12 status. Elevated circulating MMA is linked to neurological abnormalities. Contribution of age, supplement use, kidney dysfunction, and vitamin B-12 deficiency to high serum MMA in post-folic acid fortification period is unknown. Methods We investigated prevalence, population attributable risk (PAR), and PAR% for high MMA concentrations in the US. Data from 3 cross-sectional National Health and Nutrition Examination Surveys conducted in post-folic acid fortification period were used (n = 18569). Results Likelihood of having high serum MMA for white relative to black was 2.5 (P < 0.0001), ? 60 y old persons relative to < 60 y old persons was 4.0 (P < 0.0001), non-supplement users relative to supplement users was 1.8 (P < 0.0001), persons with serum creatinine ? 130 ?mol/L relative to those with < 130 ?mol/L was 12.6 (P < 0.0001), and persons with serum vitamin B-12 < 148 pmol/L relative to those with ? 148 pmol/L was 13.5 (P < 0.0001). PAR% for high MMA for old age, vitamin B-12 deficiency, kidney dysfunction, and non-supplement use were 40.5, 16.2, 13.3, and 11.8, respectively. By improving serum vitamin B-12 (? 148 pmol/L), prevalence of high MMA would be reduced by 16-18% regardless of kidney dysfunction. Conclusions Old age is the strongest determinant of PAR for high MMA. About 5 cases of high serum MMA/1000 people would be reduced if vitamin B-12 deficiency (< 148 pmol/L) is eliminated. Large portion of high MMA cases are not attributable to serum vitamin B-12. Thus, caution should be used in attributing high serum MMA to vitamin B-12 deficiency.

2012-01-01

312

Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan-folic acid micelles  

PubMed Central

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.

Wang, Feihu; Chen, Yuxuan; Zhang, Dianrui; Zhang, Qiang; Zheng, Dandan; Hao, Leilei; Liu, Yue; Duan, Cunxian; Jia, Lejiao; Liu, Guangpu

2012-01-01

313

Folic acid inhibits endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway.  

PubMed

Previously, our in vivo studies demonstrated that folic acid (FA) could inhibit angiogenesis and in vitro studies showed that FA reduced vascular endothelial cell proliferation through activating the cSrc/ERK-2/NF?B/p53 pathway mediated by FA receptor (FR). Here, we further examined the effect of FA on endothelial cell migration. Our results showed that FA (10 ?M) inhibited the formation of lamellipodia, migration and capillary-like tube formation of human umbilical venous endothelial cells (HUVEC). These inhibition effects induced by FA treatment were not due to reduction of cell survival and cell adhesion on the collagen-coated plate. Treatment of HUVEC with FA (10 ?M) increased the activity of cSrc and p190RhoGAP and decreased the activity of RhoA. Over-expression of the constitutively active RhoA construct (RhoA V14) prevented the FA-induced inhibition of migration and capillary-like tube formation in HUVEC. However, these preventive effects were abolished by pretreatment of HUVEC with a ROCK inhibitor, Y27632. Pretreatment with a cSrc inhibitor, PP2, prevented the FA-induced activation of p190GAP, reduction of the RhoA activity and migration inhibition in HUVEC. Moreover, pre-transfection with p190RhoGAP siRNA abolished the FA-induced reduction in the RhoA activity and migration inhibition in HUVEC. Taken together, our results suggest that FA might inhibit endothelial cell migration through inhibiting the RhoA activity mediated by activating the FR/cSrc/p190RhoGAP-signaling pathway. These findings further support the anti-angiogenic activity of FA. PMID:23178654

Hou, Tien-Chi; Lin, Jheng-Jhe; Wen, Heng-Ching; Chen, Li-Ching; Hsu, Sung-Po; Lee, Wen-Sen

2012-11-23

314

Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging.  

PubMed

We report a facile polyethyleneimine (PEI)-mediated approach to synthesizing folic acid (FA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo magnetic resonance (MR) imaging of tumors. In this study, stable PEI-coated Fe3O4 NPs were prepared by a one-pot hydrothermal route. The aminated Fe3O4 NPs with PEI coating enabled covalent conjugation of fluorescein isothiocyanate (FI) and folate-conjugated polyethylene glycol (PEG) with one end of carboxyl groups (FA-PEG-COOH). Followed by final acetylation, FA-targeted PEGylated Fe3O4 NPs (Fe3O4-PEI-Ac-FI-PEG-FA NPs) were formed. The formed multifunctional Fe3O4 NPs were characterized via different techniques. We show that the PEI-mediated approach along with the PEGylation conjugation enables the generation of water-dispersible and stable multifunctional Fe3O4 NPs, and the particles are quite cytocompatible and hemocompatible in the given concentration range as confirmed by in vitro cytotoxicity assay, cell morphology observation, and hemolysis assay. In addition, flow cytometry and confocal microscopy data show that the multifunctional Fe3O4 NPs are able to target a model cancer cell line (KB cells) overexpressing FA receptors in vitro. Importantly, the FA-targeted Fe3O4 NPs are able to be used as an efficient nanoprobe for MR imaging of cancer cells in vitro and a xenografted tumor model in vivo via an active FA targeting pathway. With the facile PEI-mediated formation strategy and PEGylation conjugation chemistry, the Fe3O4 NPs may be multifunctionalized with other biological ligands for MR imaging of different biological systems. PMID:23932250

Li, Jingchao; Zheng, Linfeng; Cai, Hongdong; Sun, Wenjie; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

2013-08-07

315

Folic acid modified cationic ?-cyclodextrin-oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery.  

PubMed

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

Zhao, Feng; Yin, Hui; Zhang, Zhongxing; Li, Jun

2013-01-16

316

Differential coulometric oxidation following post column-switching high pressure liquid chromatography for fluorescence measurement of unmetabolized folic acid in human plasma.  

PubMed

Although many countries have fortified their grain supplies with folic acid (FA) to decrease the incidence of neural tube defects, others have not due to concerns that this synthetic folate might have some adverse effects. Persistent unmetabolized FA has been found even in plasma from fasted subjects. To facilitate measurement of low levels of folic acid in human plasma, post-column coulometric oxidative cleavage was used to convert poorly fluorescent FA into a highly fluorescent compound determined to be 6-formyl-pterin. To minimize sample work-up and maximize recovery, column-switching HPLC transferred a window of eluate containing the FA from the first column (C8) onto a second column (phenyl-hexyl). The pH of two mobile phases were adjusted to be above and then below a pK of the FA ?-carboxyl group, thus promoting separation from compounds coeluting from the C8-column. This permitted sample preparation using only a simple high recovery protein precipitation. Definitive identification of FA in human plasma was accomplished by duplicate injections of sample with the electrochemical voltage set above and below its half-potential. The LOD (S/N=3) was 0.10nM. The intra- and inter-assay CV's were 2.3% and 5%, respectively. Comparison of these results with those obtained by HPLC/MS/MS with stable isotope internal standard showed a slope of 1.00±0.019. This simple, sensitive, and repeatable assay facilitates a more thorough investigation of the response of various human populations to folic acid intake. Post-column differential coulometric electrochemistry can expand the variety of compounds amenable to fluorescence detection. PMID:24094483

Bailey, Steven W; Ayling, June E

2013-09-11

317

Elimination of Iron Deficiency Anemia and Soil Transmitted Helminth Infection: Evidence from a Fifty-four Month Iron-Folic Acid and De-worming Program  

PubMed Central

Background Intermittent iron-folic acid supplementation and regular de-worming are effective initiatives to reduce anemia, iron deficiency, iron deficiency anemia, and soil transmitted helminth infections in women of reproductive age. However, few studies have assessed the long-term effectiveness of population-based interventions delivered in resource-constrained settings. Methodology/Principal Findings The objectives were to evaluate the impact of weekly iron-folic acid supplementation and de-worming on mean hemoglobin and the prevalence of anaemia, iron deficiency, and soil transmitted helminth infection in a rural population of women in northern Vietnam and to identify predictive factors for hematological outcomes. A prospective cohort design was used to evaluate a population-based supplementation and deworming program over 54 months. The 389 participants were enrolled just prior to commencement of the intervention. After 54 months 76% (95% CI [68%, 84%]) were taking the iron-folic acid supplement and 95% (95% CI [93%, 98%]) had taken the most recently distributed deworming treatment. Mean hemoglobin rose from 122 g/L (95% CI [120, 124]) to 131 g/L (95% CI [128, 134]) and anemia prevalence fell from 38% (95% CI [31%, 45%]) to 18% (95% CI [12%, 23%]); however, results differed significantly between ethnic groups. Iron deficiency fell from 23% (95% CI [17%, 29%]) to 8% (95% CI [4%, 12%]), while the prevalence of iron deficiency anemia was reduced to 4% (95% CI [1%, 7%]). The prevalence of hookworm infection was reduced from 76% (95% CI [68%, 83%]) to 11% (95% CI [5%, 18%]). The level of moderate or heavy infestation of any soil-transmitted helminth was reduced to less than 1%. Conclusions/Significance Population-based interventions can efficiently and effectively reduce anemia and practically eliminate iron deficiency anemia and moderate to heavy soil transmitted helminth infections, maintaining them below the level of public health concern.

Casey, Gerard J.; Montresor, Antonio; Cavalli-Sforza, Luca T.; Thu, Hoang; Phu, Luong B.; Tinh, Ta T.; Tien, Nong T.; Phuc, Tran Q.; Biggs, Beverley-Ann

2013-01-01

318

Combined iron and folic acid supplementation with or without zinc reduces time to walking unassisted among Zanzibari infants 5- to 11-mo old.  

PubMed

Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 mug folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Zn) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba, Zanzibar. The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5-11 mo at the start of supplementation. Treatment effects on changes in hemoglobin (Hb) and zinc protoporphyrin (ZPP) and height-for-age (HAZ) and weight-for-age (WAZ) Z scores were evaluated using linear regression. Attained motor milestone was recorded every 2 wk for 1 y. Hb, ZPP, HAZ, and WAZ were measured at baseline and after 6 mo of treatment. FeFA with or without Zn reduced the time it took for children to walk assisted. Children who received any iron walked unassisted sooner than those who received no iron [median difference approximately 15 d, P = 0.035, risk ratio (RR) = 1.28, 95% CI = 1.02, 1.61] and this effect was stronger in those who had iron deficiency anemia (IDA) at baseline (median difference was approximately 30 d; P = 0.002; RR = 1.68; 95% CI = 1.21, 2.32). FeFA alone and Zn alone improved Hb and ZPP compared with placebo. There were no significant treatment effects on changes in HAZ or WAZ. The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin, but were not mediated through improvements in growth. PMID:16920865

Olney, Deanna K; Pollitt, Ernesto; Kariger, Patricia K; Khalfan, Sabra S; Ali, Nadra S; Tielsch, James M; Sazawal, Sunil; Black, Robert; Allen, Lindsay H; Stoltzfus, Rebecca J

2006-09-01

319

Mandatory Fortification with Folic Acid in the United States is associated with Increased Expression of DNA Methyltransferase 1 in the Cervix  

PubMed Central

Objective The objective of this study was to evaluate whether mandatory fortification of grain products with folic acid in the USA is associated with changes in DNA methyltransferase (Dnmt) 1 expression in cells involved in cervical carcinogenesis. Methods Archived specimens of cervical intraepithelial neoplasia (CIN) diagnosed before (1990-92) and after mandatory folic acid fortification (2000-02) were used to examine the expression of Dnmt 1 in specific lesions involved in cervical carcinogenesis by immunohistochemistry. The total number of lesions examined was 101 in the pre-fortification period and 96 in the post-fortification period. Immunohistochemical staining for Dnmt 1, its assessment and data entry were blinded with regard to the fortification status. Results Age- and race-adjusted mean percentage of cells positive for Dnmt 1 or the Dnmt 1 score was significantly higher in all lesion types (i.e., normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN or carcinoma in situ) detected in the post-fortification period compared to pre-fortification period (P < 0.05, all comparisons). The degree of Dnmt 1 was significantly higher (P < 0.0001) in ? CIN 2 lesions compared to ? CIN 1 lesions, regardless of the fortification group. Conclusions These results suggest that mandatory fortification with folic acid in the United States seem to have resulted in a change in the degree of expression of Dnmt 1 in cells involved in cervical carcinogenesis. Because the approach we have taken to demonstrate these differences have limitations inherent to a study of this nature and this is the first study to report a folate fortification associated change in Dnmt 1, validating these results in other study populations and or with other techniques of assessing Dnmt 1 will increase the scientific credibility of these findings.

Piyathilake, Chandrika J; Celedonio, Jorge E; Macaluso, Maurizio; Bell, Walter C; Azrad, Maria; Grizzle, William E

2008-01-01

320

Clinical Utility of Genotyping the 677C>T Variant of Methylenetetrahydrofolate Reductase in Humans Is Decreased in the Post-Folic Acid Fortification Era12  

PubMed Central

Moderate hyperhomocysteinemia is associated with many diseases. Major factors affecting plasma total homocysteine (tHcy) concentrations include folate concentrations and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Because U.S.-mandated fortification of grain products with folic acid has improved folate and tHcy status in Americans, we investigated the effect of the MTHFR 677C>T variant before and after fortification. We determined tHcy and folate concentrations in sera from 844 Caucasian and 587 African American participants in the Coronary Artery Risk Development in Young Adults study before and after fortification and we genotyped the MTHFR 677C>T variant. MTHFR 677TT homozygotes had higher (P < 0.01) tHcy concentrations both before and after fortification compared with MTHFR 677CC homozygotes. However, the difference between these 2 genotypes decreased from 2.5 ?mol/L before fortification to <0.7 ?mol/L postfortification (P < 0.01). In addition, the prevalence of moderate hyperhomocysteinemia (tHcy > 13 ?mol/L) in 677TT homozygotes decreased from 33% before fortification to 12% postfortification (P < 0.01). Using a cutoff value of 13 ?mol/L to define moderate hyperhomocysteinemia, the sensitivity of the MTHFR 677TT genotype to predict elevations in homocysteine was low (?30%) both before and after folic acid fortification. Increasing the cutoff from 13 to 19 ?mol/L increased the sensitivity of the assay before fortification to 62% but decreased the sensitivity to 17% postfortification. We conclude that after folic acid fortification in the US, measurement of tHcy rather than genotyping of MTHFR 677TT should be used as the primary assay for the diagnosis and monitoring of moderate hyperhomocysteinemia.

Tsai, Michael Y.; Loria, Catherine M.; Cao, Jing; Kim, Yongin; Siscovick, David; Schreiner, Pamela J.; Hanson, Naomi Q.

2009-01-01

321

Weekly iron-folic acid supplements to prevent anemia among Cambodian women in three settings: process and outcomes of social marketing and community mobilization.  

PubMed

Social marketing and community mobilization approaches were applied in a pilot program to introduce weekly iron-folic acid supplementation to prevent anemia in Cambodian women of reproductive age. The program was implemented in three very different environments: secondary school girls, women working in garment factories in the vicinity of Phnom Penh, and women in rural villages. Each population provided its own challenges and obstacles. However, all three groups of women showed substantial improvements in knowledge about the causes, consequences, and prevention of anemia, and the large majority reported interest in continuing to take the supplements. PMID:16466088

Kanal, Koum; Busch-Hallen, Jennifer; Cavalli-Sforza, Tommaso; Crape, Byron; Smitasiri, Suttilak

2005-12-01

322

Survivin mRNA Antagonists Using Locked Nucleic Acid, Potential for Molecular Cancer Therapy  

Microsoft Academic Search

We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced synergistic effect when combining the mRNA antagonists against Survivin with the chemotherapeutic Taxol. This effect was demonstrated at

Niels Fisker; Majken Westergaard; Henrik Frydenlund Hansen; Jens Bo Hansen

2007-01-01

323

Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor.  

PubMed

The Eph receptor-ephrin system is an emerging target for the development of novel antiangiogenetic agents. We recently identified lithocholic acid (LCA) as a small molecule able to block EphA2-dependent signals in cancer cells, suggesting that its (5?)-cholan-24-oic acid scaffold can be used as a template to design a new generation of improved EphA2 antagonists. Here, we report the design and synthesis of an extended set of LCA derivatives obtained by conjugation of its carboxyl group with different ?-amino acids. Structure-activity relationships indicate that the presence of a lipophilic amino acid side chain is fundamental to achieve good potencies. The l-Trp derivative (20, PCM126) was the most potent antagonist of the series disrupting EphA2-ephrinA1 interaction and blocking EphA2 phosphorylation in prostate cancer cells at low ?M concentrations, thus being significantly more potent than LCA. Compound 20 is among the most potent small-molecule antagonists of the EphA2 receptor. PMID:23489211

Incerti, Matteo; Tognolini, Massimiliano; Russo, Simonetta; Pala, Daniele; Giorgio, Carmine; Hassan-Mohamed, Iftiin; Noberini, Roberta; Pasquale, Elena B; Vicini, Paola; Piersanti, Silvia; Rivara, Silvia; Barocelli, Elisabetta; Mor, Marco; Lodola, Alessio

2013-03-22

324

Synthesis and characterization of polyion complex micelles and their controlled release of folic acid  

Microsoft Academic Search

Stable and narrow distribution polyion complex micelles (PICMs) were prepared in an aqueous milieu through electrostatic interaction between a pair of oppositely charged block copolymers poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PVP-b-PAMPS) and monomethoxy poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP). The critical aggregate concentration (CAC), hydrodynamic size, and surface morphology of the prepared PICMs were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron

Ya-Li Luo; Jin-Fang Yuan; Jia-Hua Shi; Qing-Yu Gao

2010-01-01

325

A pH-sensitive gene delivery system based on folic acid-PEG-chitosan - PAMAM-plasmid DNA complexes for cancer cell targeting.  

PubMed

In this study, pH-sensitive biomaterials coated polymer/DNA nanocomplexes containing a high mobility group box 1 (HMGB1) were developed as an efficient non-viral gene delivery system. HMGB1 is a family of endogenous molecules that contains nuclear locating sequences (NSL). Polyethylene glycol tethered carboxylated chitosan modified with folic acid (FA-PEG-CCTS) was synthesized and its buffering capacity was determined by acid-base titration. A pH-sensitive core-shell system FA-PEG-CCTS/PAMAM/HMGB1/pDNA nanocomplexes (FPCPHDs), was prepared and characterized. Electrophoresis showed that FPCPHDs were resistant to heparin replacement and DNase I digestion. FPCPHDs exhibited only minor toxic effects on HepG2 and KB cells. The results of both luciferase activity assay and RFP fluorescence intensity analysis showed that FPCPHDs enhanced gene transfection and expression in KB cells. Moreover, gene transfection and expression in KB cells were inhibited by free folic acid. Intracellular trafficking of FPCPHDs in KB cells showed that FPCPHDs could rapidly escape from endo-lysosomes and become exclusively located in the nucleus at 3 h post transfection. In addition, FPCPHDs exhibited increased red fluorescence protein (RFP) expression at the tumor site of S180 xenograft nude mice. All results suggest that FPCPHDs is an efficient approach to improve the transfection and expression efficiency in most FR-positive cancer cells. PMID:24094823

Wang, Mingyue; Hu, Haiyang; Sun, Yuqi; Qiu, Lipeng; Zhang, Jie; Guan, Guannan; Zhao, Xiuli; Qiao, Mingxi; Cheng, Liang; Cheng, Lifang; Chen, Dawei

2013-10-02

326

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.  

PubMed

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

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

2012-03-14

327

2-(1H-Pyrazol-4-yl)acetic acids as CRTh2 antagonists.  

PubMed

High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors. PMID:23601708

Andrés, Miriam; Bravo, Mónica; Buil, Maria Antonia; Calbet, Marta; Castro, Jordi; Domènech, Teresa; Eichhorn, Peter; Ferrer, Manel; Gómez, Elena; Lehner, Martin D; Moreno, Imma; Roberts, Richard S; Sevilla, Sara

2013-04-02

328

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  

Microsoft Academic Search

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

Ximena Duque; Sergio Flores-Hernández; Samuel Flores-Huerta; Ignacio Méndez-Ramírez; Sergio Muñoz; Bernardo Turnbull; Gloria Martínez-Andrade; Rosa I Ramos; Marco González-Unzaga; María E Mendoza; Homero Martínez

2007-01-01

329

Influence of a fat-rich diet, folic acid supplementation and a human-relevant concentration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on the induction of preneoplastic lesions in the rat colon.  

PubMed

In the present study, the effect of three controversially discussed risk factors for colorectal cancer, a fat-rich diet (16% raw fat content), dietary folic acid supplementation (50 mg folic acid/kg lab chow) and a human-relevant concentration (0.1 ppm) of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), either alone or in combination, on the induction of aberrant crypt foci (ACF) in the colon of male Fischer 344 rats was analyzed. The mean number of ACF per rat in the case of the four groups fed a fat-rich diet tended to be higher than that of the four groups being fed a standard diet. However, the increase in the mean number of ACF per rat only reached statistical significance in the case of the rats receiving a fat-rich lab chow supplemented with 50 mg/kg folic acid. Moreover, a concentration of 0.1 ppm PhIP per se, either in the standard or in the fat-rich lab chow, did not lead to an increase in the mean number of ACF per rat. In conclusion, the present study provides additional evidence for a colon cancer promoting effect of folic acid supplementation when rodents are fed the compound in supraphysiological concentrations. PMID:22371238

Nicken, Petra; Brauer, Nicole; Lampen, Alfonso; Steinberg, Pablo

2012-02-28

330

A long-term study of the excretion of folate and pterins in a human subject after ingestion of '4C folic acid, with observations on the effect of diphenylhydantoin administration1' 2  

Microsoft Academic Search

After the administration of 2-14C folic acid to a human volunteer, urinary and fecal radioactivity, as well as urinary excretion of folate ( Lactobacillus casei assay) and biopterin-like material (Crithidia fasciculata assay) were determined at intervals over a 129 day period of observation . From two 24 hr urine samples erythroneopterin , bioterin , threoneopterin, pterin, isoxanthopterin, and xanthopterin were

Carlos L. Krumdieck; Kazuo Fukushima; Takeshi Fukushima; Tetsuo Shiota; C. E. Butterworth

331

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

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.

Diefenbach, Konstanze; Trummer, Dietmar; Ebert, Frank; Lissy, Michael; Koch, Manuela; Rohde, Beate; Blode, Hartmut

2013-01-01

332

Effects of supplements of folic acid, vitamin B12, and rumen-protected methionine on whole body metabolism of methionine and glucose in lactating dairy cows.  

PubMed

The present experiment was undertaken to determine the effects of dietary supplements of rumen-protected methionine and intramuscular injections of folic acid and vitamin B(12), given 3 wk before to 16 wk after calving, on glucose and methionine metabolism of lactating dairy cows. Twenty-four multiparous Holstein cows were assigned to 6 blocks of 4 cows each according to their previous milk production. Within each block, 2 cows were fed a diet estimated to supply methionine as 1.83% metabolizable protein, equivalent to 76% of methionine requirement, whereas the 2 other cows were fed the same diet supplemented daily with 18 g of rumen-protected methionine. Within each diet, the cows were administrated either no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid plus 10 mg of vitamin B(12.) To investigate metabolic changes at 12 wk of lactation, glucose and methionine kinetics were measured by isotope dilution using infusions of 3[U-(13)C]glucose, [(13)C]NaHCO(3) and 3[1-(13)C,(2)H(3)] methionine. Milk and plasma concentrations of folic acid and vitamin B(12) increased with vitamin injections. Supplementary B-vitamins increased milk production from 34.7 to 38.9 +/- 1.0 kg/d and increased milk lactose, protein, and total solids yields. Whole-body glucose flux tended to increase with vitamin supplementation with a similar quantitative magnitude as the milk lactose yield increase. Vitamin supplementation increased methionine utilization for protein synthesis through increased protein turnover when methionine was deficient and through decreased methionine oxidation when rumen-protected methionine was fed. Vitamin supplementation decreased plasma concentrations of homocysteine independently of rumen-protected methionine feeding, although no effect of vitamin supplementation was measured on methionine remethylation, but this could be due to the limitation of the technique used. Therefore, the effects of these B-vitamins on lactation performance were not mainly explained by methionine economy because of a more efficient methylneogenesis but were rather related to increased glucose availability and changes in methionine metabolism. PMID:19164680

Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Matte, J J; Desrochers, A; Girard, C L

2009-02-01

333

Fabrication of reduced graphene oxide and sliver nanoparticle hybrids for Raman detection of absorbed folic acid: a potential cancer diagnostic probe.  

PubMed

Reduced graphene oxide (RGO) and silver nanoparticle (AgNP) hybrids (RGO-AgNP) were prepared by a facile one-pot method using Poly (N-vinyl-2-pyrrolidone) as reductant and stabilizer. Folic acid (FA) molecules were attached to the RGO-AgNP by physisorption for targeting specific cancer cells with folate receptors (FRs) and using as Raman reporter molecules. The internalization of the FA loaded RGO-AgNP (RGO-AgNP-FA) inside the FRs-positive cancer cell was confirmed by confocal laser scanning and transmission electron microscopy. The Raman signals of the FA in live cancer cells were detected by confocal Raman spectroscope at 514 nm excitation, indicating that the RGO-AgNP-FA material has great potential as a Raman probe for cancer diagnosis in vitro. PMID:23629451

Hu, Chaofan; Liu, Yingliang; Qin, Jinlan; Nie, Guangting; Lei, Bingfu; Xiao, Yong; Zheng, Mingtao; Rong, Jianhua

2013-05-23

334

Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs.  

PubMed

Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs. PMID:15762681

Licciardi, M; Tang, Y; Billingham, N C; Armes, S P; Lewis, A L

335

Development, optimization and validation of a sub-minute analytical enantioselective high performance liquid chromatographic separation for a folic acid precursor in normal phase mode.  

PubMed

A sub-minute enantioselective normal phase high performance liquid chromatographic (HPLC) method for the analysis of a chiral precursor molecule employed frequently in folic acid syntheses was developed, optimized and successfully validated according to ICH-guidelines. It could be shown that ultra-high performance chromatography (UHPLC) can give significant advantages compared to traditional HPLC not only in reversed phase HPLC, but also for enantioselective separations in normal phase mode. Novel 3 ?m-particle sizes allow developing analytical chromatographic methods completely resolving two enantiomers in the shortest time possible while preserving high efficiency and low detection limits. By offering increased resolution, sensitivity and speed, enantioselective UHPLC (eUHPLC) improves sample throughput, productivity and provides considerably faster access to information on enantiomeric purity also under non-aqueous conditions. PMID:23102632

Frühauf, Doris; Juza, Markus

2012-09-24

336

Electrochemical sensor for selective determination of N-acetylcysteine in the presence of folic acid using a modified carbon nanotube paste electrode.  

PubMed

In the present paper, a novel benzoylferrocene (BF) modified carbon nanotube paste electrode (BFCNPE) was prepared. The modified electrode was further used for the successful determination of N-acetylcysteine (NAC), and it showed an excellent electrocatalytic oxidation activity toward NAC with a lower overvoltage, pronounced current response, and good sensitivity. Under the optimized experimental conditions, the proposed electrochemical NAC sensor exhibited a linear calibration plot that ranged from 3.0×10(-7) to 7.0×10(-4) M with a detection limit of 9.0×10(-8) M. Also, Square wave voltammetry (SWV) was used for simultaneous determination of NAC and folic acid (FA) at the modified electrode. Finally, the proposed method was applied to the determination of NAC in NAC tablets. PMID:23827545

Beitollahi, Hadi; Taher, Mohammad Ali; Mirrahimi, Fatemeh; Hosseinzadeh, Rahman

2012-12-11

337

gamma-Aminobutyric acid antagonists decrease junctional communication between L-horizontal cells of the retina.  

PubMed Central

The antagonists of gamma-aminobutyric acid, bicuculline and picrotoxin, were found to narrow the receptive field profile of the large field horizontal cell (L1HC) in the turtle retina when added to the perfusion medium in micromolar concentrations. The coupling resistance between neighboring L1HCs was increased by bicuculline or picrotoxin. Under control conditions, the dye Lucifer yellow injected into one L1HC diffused into a large number of neighboring L1HCs; bicuculline or picrotoxin greatly restricted dye passage between these same cells. We conclude that antagonists of gamma-aminobutyric acid decrease the conductance of gap junctions between L1HCs. Images

Piccolino, M; Neyton, J; Witkovsky, P; Gerschenfeld, H M

1982-01-01

338

Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice  

PubMed Central

Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although clinical trials were inconclusive regarding the role of Hcy in MI, in animal models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in drinking water) was administered for 4 wk after the surgery. Cardiac function was assessed by echocardiography and by a Millar pressure-volume catheter. The levels of Hcy-metabolizing enzymes, cystathionine ?-synthase (CBS), cystathionine ?-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The results suggest that FA administered post-MI significantly improved cardiac ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE, and 5-MTHFR. We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease.

Qipshidze, Natia; Tyagi, Neetu; Sen, Utpal; Givvimani, Srikanth; Metreveli, Naira; Lominadze, David

2010-01-01

339

Plasma reduced folates, reproductive performance, and conceptus development in sows in response to supplementation with oxidized and reduced sources of folic acid.  

PubMed

The study was conducted to determine the response of sows to oxidized and reduced forms of supplemental folic acid in the diet. Gilts were mated and fed a standard corn-soybean meal diet with no supplemental folic acid. On d 105 of gestation, gilts were randomly assigned to one of four dietary treatments for the remainder of the study. Treatments were: 1) diet with no supplemental folate (control), 2) diet with 2.1 ppm (calculated) of added folate supplied by a synthetic pteroylmonoglutamate form (MG), 3) diet with 2.1 ppm (calculated) of added folate supplied by N5-formyl-5,6,7,8-tetrahydrofolic acid (THFA), or 4) a commercial bacterial cell powder source (Aj-PG) rich in reduced folates. Blood samples for high-performance liquid chromotography determination of reduced plasma folates were collected from gilts on d 105 of gestation, at weaning, at mating, and when the females were slaughtered on d 45 after mating for the second parity. There were 19, 18, 18, and 22 sows for the control, MG, THFA, and Aj-PG treatments, respectively. Supplementing folacin just before farrowing and during lactation had no effect on sow and litter performance during parity 1 (P > 0.10). Live fetuses at d 45 of gestation in Parity 2 were 10.06, 12.23, 10.87, and 11.07 for the control, MG, THFA, and Aj-PG treatments, respectively, and did not differ (P > 0.10). Fetal survival and placental size and protein content were generally unaffected by folate treatment. Concentration of reduced folates in sow plasma was 13.50, 13.58, 22.50, and 17.79 nM at weaning and 12.55, 19.29, 18.96, and 21.88 nM at mating for the control, MG, THFA, and Aj-PG treatments, respectively, with the THFA treatment elevated above the controls at weaning (P < 0.05) and the Aj-PG treatment greater than controls at mating (P < 0.05). At weaning, the reduced sources of supplemental folate (THFA and Aj-PG) were more effective in elevating plasma reduced folates than the oxidized folate supplement (MG; P < 0.05). Nonetheless, folate supplementation did not significantly improve sow reproductive performance in the subsequent parity, and there was no indication that reduced folate sources were superior to the oxidized pteroylmonoglutamate form as folate supplements for sows. PMID:12661654

Harper, A F; Knight, J W; Kokue, E; Usry, J L

2003-03-01

340

Ursolic acid, an antagonist for transforming growth factor (TGF)-?1  

Microsoft Academic Search

Transforming growth factor-? (TGF-?), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-?1 receptor binding and TGF-?1-induced cellular functions in vitro. Ursolic acid inhibited [125I]-TGF-?1 receptor binding to Balb\\/c 3T3 mouse fibroblasts with an IC50 value of

Shigeru Murakami; Hajime Takashima; Mariko Sato-Watanabe; Sumi Chonan; Koji Yamamoto; Masako Saitoh; Shiuji Saito; Hiromitsu Yoshimura; Koko Sugawara; Junshan Yang; Nannan Gao; Xinggao Zhang

2004-01-01

341

Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor.  

PubMed

A series of novel acylsulfonamide, acylsulfamide, and sulfonylurea bioisosteres of carboxylic acids were prepared as CXCR2 antagonists. Structure-activity relationships are reported for these series. One potent orally bioavailable inhibitor had excellent PK properties and was active in a lung injury model in hyperoxia-exposed newborn rats. PMID:18308567

Winters, Michael P; Crysler, Carl; Subasinghe, Nalin; Ryan, Declan; Leong, Lynette; Zhao, Shuyuan; Donatelli, Robert; Yurkow, Edward; Mazzulla, Marie; Boczon, Lisa; Manthey, Carl L; Molloy, Christopher; Raymond, Holly; Murray, Lynne; McAlonan, Laura; Tomczuk, Bruce

2008-02-07

342

Investigation of folic acid stability in fortified instant noodles by use of capillary electrophoresis and reversed-phase high performance liquid chromatography.  

PubMed

A single enzyme treatment with alpha-amylase, prior to the quantification of added folic acid (FA) in fortified instant fried Asian noodles with analysis performed by capillary zone electrophoresis (CZE) and reversed-phase high performance liquid chromatography (RP-HPLC) with UV detection, is described. The method was validated and optimized for capillary electrophoresis (CE) with separation achieved using a 8 mM phosphate-12 mM borate run buffer with 5% MeOH at pH 9.5. FA was well separated from matrix components with nicotinic acid (NA) employed as an internal standard. In a comparative study, separation of FA was performed using HPLC with a mobile phase consisting of 27% MeOH (v/v) in aqueous potassium phosphate buffer (3.5 mM KH(2)PO(4) and 3.2 mM K(2)HPO(4)), pH 8.5, and containing 5 mM tetrabutylammonium dihydrogen phosphate as an ion-pairing agent. For both methods, excellent results were obtained for various analytical parameters including linearity, accuracy and precision. The limit of detection was calculated to be 2.2 mg/L for CE without sample stacking and 0.10 mg/L with high performance liquid chromatography (HPLC). Sample extraction involved homogenization and enzymatic extraction with alpha-amylase. Results indicated that FA was stable during four main stages of instant fried noodle manufacturing (dough crumbs, cut sheets, steaming and frying). PMID:18930464

Hau Fung Cheung, Rodney; Morrison, Paul D; Small, Darryl M; Marriott, Philip J

2008-10-04

343

Fabrication and characterization of a triple functionalization of graphene oxide with Fe3O4, folic acid and doxorubicin as dual-targeted drug nanocarrier.  

PubMed

A novel triple functionalized drug delivery system was synthesized by encapsulation of superparamagnetic graphene oxide (GO) and doxorubicin (DOX) with folic acid (FA) conjugated chitosan (CHI). The carrier exhibited a high loading efficiency (0.98 mg/mg), a high saturation magnetization (10.5 emu/g) and a prolonged release rate. A real-time monitoring method on the drug release from graphene oxide (GO) was reported using DOX as the model drug. The release mechanism of DOX at different pH was investigated via monitoring the time dependency of the accumulative drug release. Results show that the drug release of DOX was pH sensitive as observed at pH 5.3 and pH 7.4 PBS solutions, the lower pH values lead to weaker hydrogen bonds and degradation of CHI, and thus result in a higher release rate of DOX. Especially, this system could be applied as a dual-targeted drug nanocarrier by combined biological (active) and magnetical (passive) targeting capabilities. Our research suggests that a novel triple functionalized, pH-responsive nanocarrier for anticancer drug has been synthesized. PMID:23434692

Wang, Zonghua; Zhou, Chengfeng; Xia, Jianfei; Via, Brian; Xia, Yanzhi; Zhang, Feifei; Li, Yanhui; Xia, Linhua

2013-01-24

344

[Pharmacokinetics, tissue distribution and magnetic resonance's response characterstics of folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles in mice and rats].  

PubMed

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging. PMID:22010356

Gao, Wen-Hui; Liu, Shi-Ting; Fan, Cai-Xia; Qi, Lin-Yan; Chen, Zhi-Liang

2011-07-01

345

A simple and efficient electrochemical sensor for folic acid determination in human blood plasma based on gold nanoparticles-modified carbon paste electrode.  

PubMed

Folic acid (FA) is a water soluble vitamin that exists in many natural species. The lack of FA causes some deficiencies in human body, so finding a simple and sensitive method for determining the FA is important. A new chemically modified electrode was fabricated for determination of FA in human blood plasma using gold nanoparticles (AuNPs) and carbon paste electrode (CPE). Gold nanoparticles-modified carbon paste electrode (AuNPs/CPE) was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The experimental parameters such as pH, scan rate (?) and amount of modifier were studied by cyclic voltammetry and the optimized values were chosen. The electrochemical parameters such as diffusion coefficient of FA (D(FA)), electrode surface area (A) and electron transfer coefficient (?) were calculated. Square wave voltammetry as an accurate technique was used for quantitative calculations. A good linear relation was observed between anodic peak current (ipa) and FA concentration (CFA) in the range of 6×10(-8) to 8×10(-5) mol L(-1), and the detection limit (LOD) achieved 2.7×10(-8) mol L(-1), that is comparable with recently studies. This paper demonstrated a novel, simple, selective and rapid sensor for determining the FA in the biological samples. PMID:23706236

Arvand, Majid; Dehsaraei, Mohammad

2013-04-24

346

Conjugates of folic acids with BSA-coated quantum dots for cancer cell targeting and imaging by single-photon and two-photon excitation.  

PubMed

Bovine serum albumin (BSA)-coated CdTe/ZnS quantum dots (BSA-QDs) were selected to conjugate with folic acid (FA), forming FA-BSA-QDs. This study aims to develop these small FA-BSA-QDs (less than 10 nm) for the diagnosis of cancers in which the FA receptor (FR) is overexpressed. The enhancement of cellular uptake in FR-positive human nasopharyngeal carcinoma cells (KB cells) for FA-BSA-QDs was found by means of confocal fluorescence microscopy under single-photon and two-photon excitation. The uptake enhancement for FA-BSA-QDs was further evaluated by flow-cytometric analysis in 10(4) KB cells, and was about 3 times higher than for BSA-QDs on average. The uptake enhancement was suppressed when KB cells had been pretreated with excess FA, reflecting that the enhancement was mediated by the association of FR at cell membranes with FA-BSA-QDs. When human embryonic kidney cells (293T) (FR-negative cells) and KB cells, respectively, were incubated with FA-BSA-QDs (1 ?M) for 40 min, the FA-BSA-QD uptake by 293T cells was much weaker than that by KB cells, demonstrating that FA-BSA-QDs could undergo preferential binding on FR-positive cancer cells. These characteristics suggest that FA-BSA-QDs are potential candidates for cancer diagnosis. PMID:20890718

Meng, He; Chen, Ji-Yao; Mi, Lan; Wang, Pei-Nan; Ge, Mei-Ying; Yue, Yang; Dai, Ning

2010-10-02

347

Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats.  

PubMed

We aimed to investigate the extent to which maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes, vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis-associated proteins in the yolk sacs of rat embryos on gestational days 10 and 11. Commencing at conception and throughout pregnancy, half of the streptozotocin-diabetic and half of the control rats received daily FA injections. Maternal diabetes impaired vascular morphology and decreased CuZnSOD and GPX-1 gene expression in yolk sacs. Maternal diabetes also increased the levels of CuZnSOD protein, increased the Bax/Bcl-2 protein ratio and decreased Vegf-A protein distribution. FA treatment normalized vascular morphology, decreased mRNA levels of all three SOD isoforms and increased Vegf-A mRNA levels, rectified CuZnSOD protein distribution and Bax/Bcl-2 ratio. A teratogenic diabetic environment produces a state of vasculopathy, oxidative stress, and mild apoptosis in the yolk sac. FA administration normalizes vascular morphology, diminishes apoptotic rate, and increases Vegf-A gene expression and protein distribution in the yolk sac of diabetic rats. PMID:17482424

Zabihi, Sheller; Eriksson, Ulf J; Wentzel, Parri

2007-03-31

348

Rapid determination of thiamine, riboflavin, niacinamide, pantothenic acid, pyridoxine, folic acid and ascorbic acid in Vitamins with Minerals Tablets by high-performance liquid chromatography with diode array detector.  

PubMed

A simple, isocratic, and stability-indicating high-performance liquid chromatography (HPLC) method has been developed for the rapid determination of thiamine (VB(1)), niacinamide (VB(3)), pyridoxine (VB(6)), ascorbic acid (VC), pantothenic acid (VB(5)), riboflavin (VB(2)) and folic acid (VB(9)) in Vitamins with Minerals Tablets (VMT). An Alltima C(18) column (250 mm × 4.6 mm i.d., 5 ?m) was used for the separation at ambient temperature, with 50mM ammonium dihydrogen phosphate (adjusting with phosphoric acid to pH 3.0) and acetonitrile as the mobile phase at the flow rate of 0.5 ml min(-1). VB(1), VB(3), VB(6), VC and VB(5) were extracted with a solution containing 0.05% phosphoric acid (v/v) and 0.3% sodium thiosulfate (w/v), and were then simultaneously analyzed by using the mobile phase of phosphate buffer-acetonitrile (95:5, v/v), while VB(2) and VB(9) were extracted with a solution containing 0.5% ammonium hydroxide solution (v/v), and were then simultaneously analyzed by using the mobile phase of phosphate buffer-acetonitrile (85:15, v/v). The detection wavelengths were 275 nm for VB(1), VB(3), VB(6), VC, 210 nm for VB(5), and 282 nm for VB(2) and VB(9). The method showed good system suitability, sensitivity, linearity, specificity, precision, stability and accuracy. All the seven water-soluble vitamins were well separated from other ingredients and degradation products. Method comparison indicated good concordance between the developed method and the USP method. The developed method was reliable and convenient for the rapid determination of VB(1), VB(3), VB(6), VC, VB(5), VB(2) and VB(9) in VMT. PMID:22785377

Jin, Pengfei; Xia, Lufeng; Li, Zheng; Che, Ning; Zou, Ding; Hu, Xin

2012-06-23

349

The metabotropic glutamate receptor antagonist l-2-amino-3-phosphonopropionic acid inhibits phosphoserine phosphatase  

Microsoft Academic Search

Phosphoserine phosphatase catalyzes the final step in the major pathway of l-serine biosynthesis in brain. Using d-phosphoserine as substrate, the metabotropic glutamate receptor antagonist l-2-amino-3-phosphonopropionic acid (l-AP3) inhibits phosphoserine phosphatase partially purified from rat brain with a Ki of 151 ?M. In contrast to AP3 enantioselectivity at metabotropic receptors, d-AP3 (Ki 48 ?m) is more potent as an inhibitor of

Jon E. Hawkinson; Manuel Acosta-Burruel; Paul L. Wood

1996-01-01

350

QSAR study of 2,4-disubstituted phenoxyacetic acid derivatives as a CRTh 2 receptor antagonists  

Microsoft Academic Search

In pursuit of better CRTh2 receptor antagonist agents, QSAR studies were performed on a series of 2,4-disubstituted phenoxyacetic acid derivatives.\\u000a Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical\\u000a significance and predictive power by internal and external validation. The best QSAR model was selected; having the correlation\\u000a coefficient R = 0.904, standard

Abhishek K. Jain; Veerasamy Ravichandran; Rajesh Singh; Vishnukanth Mourya; Ram K. Agrawal

2009-01-01

351

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 Central

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.

Slock, J; Stahly, D P; Han, C Y; Six, E W; Crawford, I P

1990-01-01

352

Excitatory amino acid antagonists and their potential for the treatment of ischaemic brain damage in man.  

PubMed Central

1. A wide range of therapeutic strategies has been explored in humans and experimental animals with the aim of improving outcome after brain ischaemia but few have shown convincing clinical benefit. 2. The massive increase in the extracellular concentration of glutamate which occurs in cerebral ischaemia is a key component in the sequence of neurochemical events which leads to neuronal death. Pharmacological blockade of the action of glutamate at the N-methyl-D-aspartate (NMDA) receptor, (the glutamate receptor subtype principally involved in the neurotoxic effects of the amino acid) provides a novel therapeutic approach to cerebral ischaemia. 3. The effects of NMDA receptor antagonists in animal models of focal cerebral ischaemia are uniquely consistent, viz, a marked reduction in the amount of irreversible ischaemic damage irrespective of the species, the model of cerebral ischaemia, when the animals are sacrificed after the ischaemic episode, whether ischaemia is permanent or temporary and followed by reperfusion and which particular NMDA antagonist was employed. 4. NMDA receptor antagonists have marked effects on brain function in normal animals. The balance between these potential adverse effects and the anti-ischaemic efficacy of these drugs will ultimately determine the clinical utility of this class of drugs. 5. The data which are reviewed provide the basis for the current clinical evaluation of NMDA receptor antagonists in stroke and head trauma.

McCulloch, J

1992-01-01

353

MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults  

PubMed Central

Background This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults. Methods A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks. Results After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P < 0.05 for either of these genotypes) and TT genotype in the high FA group (P < 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, P = 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989). Conclusions This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.

2012-01-01

354

Potential antagonistic effects of nine natural fatty acids against Meloidogyne incognita.  

PubMed

Fatty acids, the essential components of life, were widely present in various seed cakes, gutter oil, and other resources. The objective of this study was to evaluate the potential antagonistic effects of nine fatty acids (FAs) against Meloidogyne incognita (root-knot nematodes). The results showed that butyric, caprylic, capric, lauric, myristic, palmitic, and oleic acids significantly reduced M. incognita reproduction, whereas cucumber (Cucumus sativus) biomass was not adversely affected by the tested FAs and was even significantly increased in several fatty acids treatments. All nine tested fatty acids showed apparent inhibitory effects on egg hatching on day 21, especially capric acid with which the hatching rate was reduced to 15.8% as compared to that using sterile distilled water. Caproic, caprylic, capric, lauric, myristic, and palmitic acids caused significantly higher mortality of the second-stage juvenile of M. incognita than the other three FAs, and both caprylic and capric acids resulted in approximately 50% mortality (2000 ?mol/L) after a 24 h exposure. In conclusion, fatty acids showed the nematicidal effect differently, among which capric acid showed a strong nematicidal effect and might be a powerful active substance for integrated M. incognita management. Given the general nematicidal properties of FAs, farmers might utilize waste resources, such as oil seed cake, gutter oil, etc., containing various FAs or use pure FAs for effective M. incognita management. PMID:23121218

Zhang, Wei-pu; Ruan, Wei-bin; Deng, Yun-ying; Gao, Yu-bao

2012-11-09

355

Effect of Folic Acid Supplementation on Levels of Circulating Monocyte Chemoattractant Protein-1 and the Presence of Intravascular Ultrasound Derived Virtual Histology Thin-Cap Fibroatheromas in Patients with Stable Angina Pectoris  

PubMed Central

Background Virtual Histology Intravascular Ultrasound (VH–IVUS) may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1) is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment. Methods In a randomized, prospective study, 102 patients with stable angina pectoris (SAP) received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (±B6) or placebo (±B6) for 1 year before VH–IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA) in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI). Results Patients treated with folic acid/vitamin B12 had a geometric mean (SD) MCP-1 level of 79.95 (1.49) versus 86.00 (1.43) pg/mL for patients receiving placebo (p-value 0.34). VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47). Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92) times higher in patients with VH-TCFA lesions than in those without (p-value 0.005). Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI), which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006) and VH-TCFA (p-value 0.01). Conclusions In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. ClinicalTrials.gov Identifier: NCT00354081.

L?land, Kjetil H.; Bleie, ?yvind; Strand, Elin; Ueland, Per M.; Nordrehaug, Jan E.; Garcia-Garcia, Hector M.; Serruys, Patrick W.; Nygard, Ottar

2013-01-01

356

Selective antagonist activity of 5-aminohex-2-enedioic acid on amino acid excitation of cat spinal neurones.  

PubMed

D- and L-5-aminohex-2-enedioic acid (AHED) and the DL-2-bromo derivative, which are conformationally restricted analogues of the excitatory amino acid antagonist D-alpha-aminoadipic acid (D alpha AA), were tested microelectrophoretically on cat spinal neurones. D-AHED reduced the excitatory action of N-methyl-D-aspartate (NMDA) to a greater extent than that of L-glutamate and the potency of this action was a half to a third that of D alpha AA. The DL-2-bromo derivative excited neurons, an effect greater than that of L-glutamate and not blocked by either D alpha AA or L-glutamic acid diethyl ester. PMID:6133238

Allan, R D; Bornstein, J C; Curtis, D R; Johnston, G A; Lodge, D

1980-01-01

357

Effects of gamma-aminobutyric acid agonist and antagonist drugs on local cerebral glucose utilization  

SciTech Connect

The (/sup 14/C)2-deoxy-D-glucose method of Sokoloff et al. was used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.

Palacios, J.M.; Kuhar, M.J.; Rapoport, S.I.; London, E.D.

1982-07-01

358

Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors.  

PubMed

Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic acids initially isolated and characterized from the bath fluid of stimulated gut over 50 years ago. Despite similar structural and biological profiles, Darmstoff analogs have not previously been examined as potential LPA mimetics. Here, we report a facile method for the synthesis of potassium salts of Darmstoff analogs. To understand the effect of stereochemistry on lysophosphatidic acid mimetic activity, synthesis of optically pure stereoisomers of selected Darmstoff analogs was achieved starting with chiral methyl glycerates. Each Darmstoff analog was evaluated for subtype-specific LPA receptor agonist/antagonist activity, PPARgamma activation, and autotaxin inhibition. From this study we identified compound 12 as a pan-antagonist and several pan-agonists for the LPA(1-3) receptors. Introduction of an aromatic ring in the lipid chain such as analog 22 produced a subtype-specific LPA(3) agonist with an EC(50) of 692 nM. Interestingly, regardless of their LPA(1/2/3) ligand properties all of the Darmstoff analogs tested activated PPARgamma. However, these compounds are weak inhibitors of autotaxin. The results indicate that Darmstoff analogs constitute a novel class of lysophosphatidic acid mimetics. PMID:16290140

Gududuru, Veeresa; Zeng, Kui; Tsukahara, Ryoko; Makarova, Natalia; Fujiwara, Yuko; Pigg, Kathryn R; Baker, Daniel L; Tigyi, Gabor; Miller, Duane D

2005-11-14

359

The gastrin-receptor antagonist L-365,260 inhibits stimulated acid secretion in humans  

Microsoft Academic Search

We investigated the effect of a novel gastrin—cholecystokinin-B receptor antagonist, L-365,260 [(3R)-3(N?-3-methylphenyl)ureido)-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one], on gastric acid secretion in humans. In a double-blind, four-period crossover study, eight subjects received single oral doses of placebo or of 2.5, 10, or 50 mg L-365,260, followed by an intravenous infusion of pentagastrin at doses of 0.05, 0.4, and 2 µg\\/kg\\/hr for successive 30-minute periods. L-365,260

M Gail Murphy; Bozena Sytnik; Thomas O G Kovacs; Howard Mertz; Daria Ewanik; Sumiko Shingo; Juinn H Lin; Barry J Gertz; John H Walsh

1993-01-01

360

Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist.  

PubMed

A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3',5'-(CF(3))(2)-Bn], 20 [Ac-Aba-Gly-NMe-3',5'-(CF(3))(2)-Bn], and 23 [Ac-Tic-NMe-3',5'-(CF(3))(2)-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist of the series, 20 [Ac-Aba-Gly-NMe-3',5'-(CF(3))(2)-Bn], was then used in the design of a novel, potent chimeric opioid agonist-NK1 receptor antagonist, 35 [Dmt-D-Arg-Aba-Gly-NMe-3',5'-(CF(3))(2)-Bn], which combines the N terminus of the established Dmt(1)-DALDA agonist opioid pharmacophore (H-Dmt-D-Arg-Phe-Lys-NH(2)) and 20, the NK1R ligand. The opioid component of the chimeric compound 35, that is, Dmt-D-Arg-Aba-Gly-NH(2) (36), also proved to be an extremely potent and balanced ? and ? opioid receptor agonist with subnanomolar binding and in vitro functional activity. PMID:21413804

Ballet, Steven; Feytens, Debby; Buysse, Koen; Chung, Nga N; Lemieux, Carole; Tumati, Suneeta; Keresztes, Attila; Van Duppen, Joost; Lai, Josephine; Varga, Eva; Porreca, Frank; Schiller, Peter W; Vanden Broeck, Jozef; Tourwé, Dirk

2011-03-17

361

Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist  

PubMed Central

A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3?,5?-(CF3)2-Bn], 20 [Ac-Aba-Gly-NMe-3?,5?-(CF3)2-Bn] and 23 [Ac-Tic-NMe-3?,5?-(CF3)2-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist of the series, 20 [Ac-Aba-Gly-NMe-3?,5?-(CF3)2-Bn], was then used in the design of a novel, potent chimeric opioid agonist-NK1 receptor antagonist, 35 [Dmt-D-Arg-Aba-Gly-NMe-3?,5?-(CF3)2-Bn], which combines the N-terminus of the established Dmt1-DALDA agonist opioid pharmacophore (H-Dmt-D-Arg-Phe-Lys-NH2) and 20, the NK1R ligand. The opioid component of the chimeric compound 35, i.e. Dmt-D-Arg-Aba-Gly-NH2 36, also proved to be an extremely potent and balanced ?- and ? opioid receptor agonist with subnanomolar binding and in vitro functional activity.

Ballet, Steven; Feytens, Debby; Buysse, Koen; Chung, Nga N.; Lemieux, Carole; Tumati, Suneeta; Keresztes, Attila; Van Duppen, Joost; Lai, Josephine; Varga, Eva; Porreca, Frank; Schiller, Peter W.; Broeck, Jozef Vanden; Tourwe, Dirk

2011-01-01

362

Toxicity of folic acid analogs in cultured human cells: a microtiter assay for the analysis of drug competition.  

PubMed Central

We have used a microtiter assay to study the toxicity of various folate analogs in a series of cultured human cell lines that exhibit different degrees of resistance to methotrexate, an inhibitor of dihydrofolate reductase. These cells retain their sensitivity to the lipophilic antifolate BW301U despite the amplification of dihydrofolate reductase genes. Because the cell lines under investigation grow very slowly and have poor plating efficiencies in unconditioned medium, an assay was developed that relies on cell proliferation rather than colony formation as a measure of toxicity. This approach is easily generalized to provide a rapid and inexpensive assay of drug competition. Two-dimensional studies indicate that methotrexate and BW301U show differences in patterns of toxicity, competition, and rescue by folinic acid, suggesting that the two drugs act on different targets. Further applications of the microtiter assay to the analysis of multidrug interactions are discussed. Images

Roos, D S; Schimke, R T

1987-01-01

363

Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1.  

PubMed

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-beta1 receptor binding and TGF-beta1-induced cellular functions in vitro. Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse fibroblasts with an IC(50) value of 6.9+/-0.8 microM. Ursolic acid dose-dependently recovered reduced proliferation of Minc Mv1Lu cells in the presence of 5 nM of TGF-beta1 and attenuated TGF-beta1-induced collagen synthesis and production in human fibroblasts. Molecular dynamics simulations suggest that ursolic acid may interact with the hydrophobic region of the dimeric interface and thereby inhibit the binding of TGF-beta1 to its receptor. All these findings taken together show that ursolic acid functions as an antagonist for TGF-beta1. This is the first report to show that a small molecule can inhibit TGF-beta1 receptor binding and influence functions of TGF-beta1. PMID:15147868

Murakami, Shigeru; Takashima, Hajime; Sato-Watanabe, Mariko; Chonan, Sumi; Yamamoto, Koji; Saitoh, Masako; Saito, Shiuji; Yoshimura, Hiromitsu; Sugawara, Koko; Yang, Junshan; Gao, Nannan; Zhang, Xinggao

2004-05-21

364

Succinate reverses in-vitro platelet inhibition by acetylsalicylic acid and P2Y receptor antagonists.  

PubMed

High on-treatment platelet reactivity has been associated with adverse cardiovascular events in patients receiving anti-platelet agents, but the molecular mechanisms underlying this phenomenon remain incompletely understood. Succinate, a citric acid cycle intermediate, is released into the circulation under conditions of mitochondrial dysfunction due to hypoxic organ damage, including sepsis, stroke, and myocardial infarction. Because the G protein-coupled receptor (GPCR) for succinate, SUCNR1 (GPR91), is present on human platelets, we hypothesized that succinate-mediated platelet stimulation may counteract the pharmacological effects of cyclooxygenase-1 and ADP receptor antagonists. To test this hypothesis in a controlled in-vitro study, washed platelets from healthy donors were treated with acetylsalicylic acid (ASA) or small-molecule P2Y(1) or P2Y(12) inhibitors and subsequently analyzed by light transmittance aggregometry using arachidonic acid (AA), ADP and succinate as platelet agonists. Aggregation in response to succinate alone was highly variable with only 29% of donors showing a (mostly delayed) platelet response. In contrast, succinate reproducibly and concentration-dependently (10-1000?µM) enhanced platelet aggregation in response to low concentrations of exogenous ADP. Furthermore, while succinate alone had no effect in the presence of platelet inhibitors, responsiveness of platelets to ADP after pretreatment with P2Y(1) or P2Y(12) antagonists was fully restored, when platelets were co-stimulated with 100?µM succinate. Similarly, succinate completely (at 1000?µM) or partially (at 100?µM) reversed the inhibitory effect of ASA on AA-induced platelet aggregation. In contrast, succinate failed to restore platelet responsiveness in the presence of both ASA and the P2Y(12) antagonist, suggesting that concomitant signaling via different GPCRs was required. Essentially identical results were obtained, when flow cytometric analysis of surface CD62P expression was used as a different readout for platelet activation. In summary, extracellular succinate may have a co-stimulatory role in platelet aggregation and, by (partially) antagonizing the effects of platelet inhibitors, may contribute to the inter-individual variability frequently observed in platelet function testing. PMID:21736422

Spath, Brigitte; Hansen, Arne; Bokemeyer, Carsten; Langer, Florian

2011-07-07

365

Calcium Antagonists Inhibit Sustained Gibberellic Acid-Induced Growth of Avena (Oat) Stem Segments.  

PubMed Central

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.

Montague, M. J.

1993-01-01

366

A comparative study of some convulsant substances as ?-aminobutyric acid antagonists in the feline cerebral cortex  

PubMed Central

1. By the use of microiontophoretic techniques, quantitative estimates were obtained of the depressant effects of ?-aminobutyric acid (GABA) on single feline cortical neurones. 2. Picrotoxin, bicuculline, strychnine, (+)-tubocurarine, penicillin and leptazol were also applied microiontophoretically to single neurones. Sequential GABA applications were made before, during and after the microiontophoresis of these substances and any effects on the time course of the GABA depression were measured as an estimate of antagonism or potentiation of GABA. 3. (+)-Tubocurarine was found to be a potent GABA antagonist. Picrotoxin and bicuculline were rather less potent and strychnine and penicillin only weakly active as GABA antagonists. Leptazol appeared to be inactive against GABA depressions. 4. In addition, bicuculline and strychnine were found to be capable of potentiating the depressant action of GABA. This property was not shared by the other substances studied. 5. All the substances studied produced changes in neuronal firing rate that did not correlate with GABA antagonism. 6. In conclusion, several potent convulsants have been shown to be capable of GABA antagonism. It is not yet clear that this effect, rather than a direct effect on neuronal excitability, is the prime mechanism behind their convulsant properties.

Hill, R. G.; Simmonds, M. A.; Straughan, D. W.

1973-01-01

367

Synthesis of tricyclic indole-2-carboxylic [correction of caboxylic] acids as potent NMDA-glycine antagonists.  

PubMed

The practical synthesis of a series of tricyclic indole-2-carboxylic acids, 7-chloro-3-arylaminocarbonylmethyl-1,3,4,5-tetrahydrobenz[cd]indole-2-carboxylic acids, as a new class of potent NMDA-glycine antagonists is described. The synthetic route to the key intermediate 12a comprises a regioselective iodination of 4-chloro-2-nitrotoluene, modified Reissert indole synthesis, Jeffery's Heck-type reaction with allyl alcohol, Wittig-Horner-Emmons reaction, and iodination at the indole C-3 position. The key step in the route is an intramolecular cyclization of 12a to give the tricyclic indole structure. Two methods of cyclization, (1) an intramolecular radical cyclization of 12a and (2) a sequence of intramolecular Heck reaction of 12a followed by a 1,4-reduction, were performed. The resulting tricyclic indole diester 13a was selectively hydrolyzed to afford the desired tricyclic indole monocarboxylic acid 16 on a multihundred gram scale without any chromatographic purifications. Optical resolution of 16 to (-)-isomer 17 and (+)-isomer 18 was carried out, and the resulting isomers were derivatized, respectively. Evaluation of the optically active derivatives for affinity to the NMDA-glycine binding site using the radio ligand binding assay with [(3)H]-5,7-dichlorokynurenic acid revealed that the derivatives of (-)-isomer 17 were more potent than the others and that especially substituted anilide (-)-isomer 24 (K(i) = 0.8 nM) showed high affinity. PMID:11348132

Katayama, S; Ae, N; Nagata, R

2001-05-18

368

Workshop Annuale del Network Italiano Promozione Acido Folico per la Prevenzione Primaria di Difetti Congeniti, Istituto Superiore di Sanita, Roma, 5 Ottobre 2007. Riassunti (annual Workshop Italian Network for the Promotion of Folic Acid and Prevention of Congenital Defects, Istituto Superiore di Sanita, Rome, 5 October 2007. Abstracts Book).  

National Technical Information Service (NTIS)

The Italian Network for the Promotion of Folic Acid and Primary Prevention of Congenital Defects was set up in April 2004 and is coordinated by the National Center Rare Diseases of the Istituto Superiore di Sanita. Its main objective is to promote, coordi...

D. Taruscio M. Salvatore

2007-01-01

369

Design, Synthesis and Bioactivity of Pyrazole Acid Derivatives as ET Receptor Antagonists.  

PubMed

A series of novel pyrazole carboxylic acid derivatives have been designed and synthesized, with their antagonism effect screened on ET-1 induced contraction in the rat thoracic aortic ring and radio receptor assay for the potency on ET receptor. Some target compounds demonstrated significant inhibitory activity, especially compound 7m showed potent inhibition percentage higher than the contrast compound BQ123. Further binding and selectivity for ET assay showed that 7m demonstrated more potent binding activity on ETA in nanomole level, and the ratio of ETA/ ETB was 36. Therefore we inferred that 7m was a non-selective antagonist of ETA and ETB, and had potential for further development in cardiovascular diseases. PMID:23521004

Cai, Jin; Liu, Ligang; Chen, Junqing; Cao, Meng; Ji, Min

2013-03-18

370

Synthesis and structure-activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists.  

PubMed

Carboxylic acid derivatives of pyridoxal were developed as potent P2X(1) and P2X(3) receptor antagonists with modifications of a lead compound, pyridoxal-5'-phosphate-6-azophenyl-2',5'-disulfonate (5b, iso-PPADS). The designing strategies included the modifications of aldehyde, phosphate or sulfonate groups of 5b, which may be interacted with lysine residues of the receptor binding pocket, to weak anionic carboxylic acid groups. The corresponding carboxylic acid analogs of pyridoxal-5'-phosphate (1), 13 and 14, showed parallel antagonistic potencies. Also, most of 6-azophenyl derivatives (24-28) of compound 13 or 14 showed potent antagonistic activities similar to that of 5b at human P2X(3) receptors with 100 nM range of IC(50) values in two-electrode voltage clamp (TEVC) assay system on the Xenopus oocyte. The results indicated that aldehyde and phosphoric or sulfonic acids in 5b could be changed to a carboxylic acid without affecting antagonistic potency at mouse P2X(1) and human P2X(3) receptors. PMID:23510563

Jung, Kwan-Young; Cho, Joong-Heui; Lee, Jung Sun; Kim, Hyo Jun; Kim, Yong-Chul

2013-02-22

371

Inhibition of gastric acid secretion in the dog by the H2-receptor antagonists, ranitidine, cimetidine, and metiamide  

Microsoft Academic Search

The new H2-receptor antagonist, ranitidine, has been compared with cimetidine and metiamide as an inhibitor of gastric acid secretion in the dog. All three compounds were effective both intravenously or by mouth in inhibiting secretion induced by histamine, pentagastrin, or bethanechol. This inhibition was mainly attributable to a reduction in the volume of secretion, although there was also a significant

M J Daly; J M Humphray; R Stables

1980-01-01

372

Urethane-induced somatostatin mediated inhibition of gastric acid: Reversal by the somatostatin 2 receptor antagonist, PRL2903  

Microsoft Academic Search

Urethane increases the release of somatostatin (SRIF) which inhibits gastric acid secretion. The SRIF monoclonal antibody, CURE.S6 and the novel sst2 antagonist, PRL-2903 injected intravenously at maximal effective doses increased gastric acid secretion by 2 and 10 fold respectively from basal values within 30 min in urethane-anesthetized rats. Plasma gastrin levels were elevated 2.5 fold within 15 min by PRL-2903

Keishi Kawakubo; David H. Coy; John H. Walsh; Yvette Taché

1999-01-01

373

(3-Aminocyclopentyl)methylphosphinic acids: novel GABA(C) receptor antagonists.  

PubMed

Our understanding of the role GABA(C) receptors play in the central nervous system is limited due to a lack of specific ligands. Here we describe the pharmacological effects of (+/-)-cis-3- and (+/-)-trans-3-(aminocyclopentyl)methylphosphinic acids ((+/-)-cis- and (+/-)-trans-3-ACPMPA) as novel ligands for the GABA(C) receptor showing little activity at GABA(A) or GABA(B) receptors. (+/-)-cis-3-ACPMPA has similar potency to (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at human recombinant rho1 (K(B)=1.0+/-0.2microM) and rat rho3 (K(B)=5.4+/-0.8microM) but is 15 times more potent than TPMPA on human recombinant rho2 (K(B)=1.0+/-0.3microM) GABA(C) receptors expressed in Xenopus oocytes. (+/-)-cis- and (+/-)-trans-3-ACPMPA are novel lead compounds for developing into more potent and selective GABA(C) receptor antagonists with increased lipophilicity for in vivo studies. PMID:17098260

Chebib, Mary; Hanrahan, Jane R; Kumar, Rohan J; Mewett, Kenneth N; Morriss, Gwendolyn; Wooller, Soraya; Johnston, Graham A R

2006-11-13

374

Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, And N-acetylcysteine in chicken embryo model  

Microsoft Academic Search

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

Chiu-Lan Hsieh; Hui-Er Wang; Wan-Jane Tsai; Chiung-Chi Peng; Robert Y. Peng

375

Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs.  

PubMed

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

Bowery, N G; Dray, A

1978-05-01

376

The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A  

PubMed Central

The lipid A from nitrogen-fixing bacterial species R. sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-? production by human monocytes induced by E. coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2?, compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure activity relationships are important for the design of compounds for the treatment of septic shock.

Zhang, Yanghui; Wolfert, Margreet A.; Boons, Geert-Jan

2007-01-01

377

Acidic biphenyl derivatives: Synthesis and biological activity of a new series of potent 5-HT4 receptor antagonists.  

PubMed

Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT4 receptors in the atrium and ventricle of the heart. Recent investigations have revealed increased expression of the 5-HT4(b) isoform in cardiomyocytes of chronic arrhythmic and failing hearts, and that the use of 5-HT4 receptor antagonists may be beneficial for treating these conditions. The 5-HT4 receptor possesses a transmembrane (TM) binding site important for ligand affinity and recognition, as well as a capacity to accommodate bulky ligands. A new series of peripherally-acting 5-HT4 receptor antagonists were prepared by combining the acidic biphenyl group from the class of angiotensin II receptor blockers (ARBs) with the SB207266 (piboserod) scaffold. The new compounds were pharmacologically evaluated and carboxylic acid 21 was identified as a potent and promising 5-HT4 receptor antagonist with moderate affinity for the AT1 receptor. The permeability of carboxylic acid 21 in a Caco-2 assay was low and the corresponding prodrug esters 23a-f were therefore prepared. The pharmacokinetics of methyl ester 20 and n-butyl ester 23c were evaluated in a rat model, revealing incomplete metabolism to carboxylic acid 21. However, methyl ester 20 is a potent 5-HT4 receptor antagonist with binding affinities in the low picomolar range. Methyl ester 20 has promising oral bioavailability and pharmacokinetics and may target 5-HT4 receptors in both CNS and peripheral organs. PMID:24113240

Brudeli, Bjarne; Andressen, Kjetil Wessel; Moltzau, Lise Román; Nilsen, Nils Olav; Levy, Finn Olav; Klaveness, Jo

2013-09-11

378

Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation.  

PubMed

A series of o-, m- and p-benzyl tetrazole derivatives 11a-c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes. PMID:20607324

Agelis, George; Resvani, Amalia; Matsoukas, Minos-Timotheos; Tselios, Theodore; Kelaidonis, Konstantinos; Kalavrizioti, Dimitra; Vlahakos, Demetrios; Matsoukas, John

2010-07-06

379

Antiepileptic effects of focal micro-injection of excitatory amino acid antagonists  

Microsoft Academic Search

Summary The role of excitatory synaptic activity at various brain regions in the development and spread of seizure activity has been investigated by the focal microinjection of 2-amino-7-phosphono-heptanoate (2-APH), a selective antagonist at the N-methyl-D-aspartate preferring receptor, or?-D-glutamylaminomethyl sulphonate (GAMS), a partially selective antagonist at the kainate receptor. In genetically epilepsy prone rats the seizure response to a loud sound

B. Meldrum; M. Millan; S. Patel; G. de Sarro

1988-01-01

380

Efficacy and safety of twice-weekly administration of three RDAs of iron and folic acid with and without complement of 14 essential micronutrients at one or two RDAs: a placebo-controlled intervention trial in anemic Cambodian infants 6 to 24 months of age  

Microsoft Academic Search

Objective:To determine the differential efficacy and safety of twice-weekly administration of 3 RDAs of iron and folic acid, with and without a complement of 2 RDAs of 11, and 1 RDA of 3 additional essential micronutrients as compared to a placebo control (PlbCON) given as foodLETs.Subjects\\/Methods:A total of 250 children aged 6–24 months were enrolled after recruitment by village health

K Schümann; P Longfils; D Monchy; S von Xylander; H Weinheimer; N W Solomons; med. K Schümann

2009-01-01

381

The retinoic acid receptor antagonist, BMS453, inhibits normal breast cell growth by inducing active TGF? and causing cell cycle arrest  

Microsoft Academic Search

We have previously shown that a retinoic acid receptor (RAR) antagonist BMS453, which does not activate RAR-dependent gene transcription in breast cells, inhibits normal breast cell growth. In this study we have investigated the mechanisms by which this retinoid receptor antagonist inhibits cell growth. Both all trans retinoic acid (atRA) and BMS453 inhibited the proliferation of normal breast cell growth

Limin Yang; Jacek Ostrowski; Peter Reczek; Powel Brown

2001-01-01

382

Toxicity of di(2-ethylhexyl)phthalate (DEHP) and di(2-ethylhexyl)adipate (DEHA) under conditions of renal dysfunction induced with folic acid in rats: enhancement of male reproductive toxicity of DEHP is associated with an increase of the mono-derivative.  

PubMed

F344 male rats were given five consecutive weekly subcutaneous injections of folic acid for induction of chronic renal dysfunction and then di(2-ethylhexyl)phthalate (DEHP) or di(2-ethylhexyl)adipate (DEHA) in the diet at a concentration of 0, 6000 or 25,000 ppm for 4 weeks in order to investigate whether male reproductive toxicity of the two chemicals might be enhanced under conditions of renal disease. Control animals also received DEHP or DEHA in the same manner but without folic acid pretreatment. Decreased testicular weights, seminiferous atrophy with vacuolization of sertoli cells and diminished sperm counts were more prominent in rats given folic acid and then 25,000 ppm DEHP as compared to those exposed to DEHP alone. No such reproductive toxicity was evident in rats given 6000 ppm DEHP or either dose of DEHA. An increased concentration of the mono-derivative of DEHP (mono(2-ethylhexyl)phthalate, MEHP) in the blood, testis and urine was considered relevant to the enhanced reproductive toxicity observed with DEHP. PMID:16952438

Nabae, Kyoko; Doi, Yuko; Takahashi, Satoru; Ichihara, Toshio; Toda, Chitose; Ueda, Koji; Okamoto, Yoshinori; Kojima, Nakao; Tamano, Seiko; Shirai, Tomoyuki

2006-07-21

383

Pomolic acid, triterpenoid isolated from Licania pittieri, as competitive antagonist of ADP-induced aggregation of human platelets.  

PubMed

Pomolic acid (PA), triterpenoid isolated from Licania pittieri, has previously shown a potent ability to inhibit adenosine diphosphate (ADP)- and epinephrine-induced human platelet aggregation. To investigate whether PA could be an antagonist of ADP-activated receptors of human platelets (P2Y(1) and P2Y(12)), pharmacological studies were conducted to examining its ability to modulate the platelet shape change induced by a selective P2Y(1) receptor agonist MRS2365 and also the nature of its possible interaction with ADP receptors by analyzing the characteristics of log concentration-response curves of ADP constructed in the absence and in the presence of fixed concentrations of PA, using in vitro platelet aggregation assays. PA did not interfere with the activation of P2Y(1) receptor by MRS2365 to induce platelet shape change and displayed a competitive antagonism of ADP-induced platelet aggregation, which most probably involves competition for a single binding site in platelets. The estimated equilibrium dissociate constant (K(b)) of PA as ADP receptor antagonist was 15.4±0.06nM. Together, these findings give indirect evidence for the idea that PA could be a potent competitive antagonist of P2Y(12) receptor, and open the possibility to consider it as new member of the non-nucleotide generation of antiplatelet drugs. PMID:22402243

Alvarado-Castillo, Claudia; Estrada, Omar; Carvajal, Edilmo

2012-03-06

384

On-line solid-phase enrichment coupled to packed reactor flow injection analysis in a green analytical procedure to determine low levels of folic acid using fluorescence detection  

PubMed Central

Background Analysis of folic acid (FA) is not an easy task because of its presence in lower concentrations, its lower stability under acidic conditions, and its sensitiveness against light and high temperature. The present study is concerned with the development and validation of an automated environmentally friendly pre-column derivatization combined by solid-phase enrichment (SPEn) to determine low levels of FA. Results Cerium (IV) trihydroxyhydroperoxide (CTH) as a packed oxidant reactor has been used for oxidative cleavage of FA into highly fluorescent product, 2-amino-4-hydroxypteridine-6-carboxylic acid. FA was injected into a carrier stream of 0.04 M phosphate buffer, pH 3.4 at a flow-rate of 0.25 mL/min. The sample zone containing the analyte was passed through the CTH reactor thermostated at 40°C, and the fluorescent product was trapped and enriched on a head of small ODS column (10 mm x 4.6 mm i.d., 5 ?m particle size). The enriched product was then back-flush eluted by column-switching from the small ODS column to the detector with a greener mobile phase consisting of ethanol and phosphate buffer (0.04M, pH 3.4) in the ratio of 5:95 (v/v). The eluent was monitored fluorimetrically at emission and excitation wavelengths of 463 and 367 nm, respectively. The calibration graph was linear over concentrations of FA in the range of 1.25-50 ng/mL, with a detection limit of 0.49 ng/mL. Conclusion A new simple and sensitive green analytical procedure including on-line pre-column derivatization combined by SPEn has been developed for the routine quality control and dosage form assay of FA at very low concentration level. The method was a powerful analytical technique that had excellent sensitivity, sufficient accuracy and required relatively simple and inexpensive instrumentation.

2012-01-01

385

Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice.  

PubMed Central

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.

De Sarro, G; Nava, F; Calapai, G; De Sarro, A

1997-01-01

386

20-125Iodo-14,15-epoxyeicosa-5(Z)-enoic acid: a high-affinity radioligand used to characterize the epoxyeicosatrienoic acid antagonist binding site.  

PubMed

Epoxyeicosatrienoic acids (EETs) are endothelium-derived metabolites of arachidonic acid. They relax vascular smooth muscle by membrane hyperpolarization. These actions are inhibited by the EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE). We synthesized 20-(125)iodo-14,15-EE5ZE (20-(125)I-14,15-EE5ZE), a radiolabeled EET antagonist, and characterized its binding to cell membranes. 14,15-EET (10(-9)-10(-5)M) caused a concentration-related relaxation of the preconstricted bovine coronary artery and phosphorylation of p38 in U937 cells that were inhibited by 20-(125)I-14,15-EE5ZE. Specific 20-(125)I-14,15-EE5ZE binding to U937 cell membranes reached equilibrium within 5 min and remained unchanged for 30 min. The binding was saturable and reversible, and it exhibited K(D) and B(max) values of 1.11 +/- 0.13 nM and 1.13 +/- 0.04 pmol/mg protein, respectively. Guanosine 5'-O-(3-thio)triphosphate (10 muM) did not change the binding, indicating antagonist binding of the ligand. Various EETs and EET analogs (10(-10)-10(-5)M) competed for 20-(125)I-14,15-EE5ZE binding with an order of potency of 11,12-EET = 14,15-EET > 8,9-EET = 14,15-EE5ZE > 15-hydroxyeicosatetraenoic acid = 14,15-dihydroxyeicosatrienoic acid. 8,9-Dihydroxyeicosatrienoic acid and 11-hydroxyeicosatetraenoic acid did not compete for binding. The soluble and microsomal epoxide hydrolase inhibitors (1-cyclohexyl-3-dodecyl-urea, elaidamide, and 12-hydroxyl-elaidamide) and cytochrome P450 inhibitors (sulfaphenazole and proadifen) did not compete for the binding. However, two cytochrome P450 inhibitors, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) and miconazole competed for binding with K(i) of 1558 and 315 nM, respectively. Miconazole and MS-PPOH, but not proadifen, inhibited 14,15-EET-induced relaxations. These findings define an EET antagonist's binding site and support the presence of an EET receptor. The inhibition of binding by some cytochrome P450 inhibitors suggests an alternative mechanism of action for these drugs and could lead to new drug candidates that target the EET binding sites. PMID:19762546

Chen, Yuenmu; Falck, John R; Tuniki, Venugopal R; Campbell, William B

2009-09-17

387

20-125Iodo-14,15-Epoxyeicosa-5(Z)-enoic Acid: a High-Affinity Radioligand Used to Characterize the Epoxyeicosatrienoic Acid Antagonist Binding Site  

PubMed Central

Epoxyeicosatrienoic acids (EETs) are endothelium-derived metabolites of arachidonic acid. They relax vascular smooth muscle by membrane hyperpolarization. These actions are inhibited by the EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE). We synthesized 20-125iodo-14,15-EE5ZE (20-125I-14,15-EE5ZE), a radiolabeled EET antagonist, and characterized its binding to cell membranes. 14,15-EET (10?9-10?5M) caused a concentration-related relaxation of the preconstricted bovine coronary artery and phosphorylation of p38 in U937 cells that were inhibited by 20-125I-14,15-EE5ZE. Specific 20-125I-14,15-EE5ZE binding to U937 cell membranes reached equilibrium within 5 min and remained unchanged for 30 min. The binding was saturable and reversible, and it exhibited KD and Bmax values of 1.11 ± 0.13 nM and 1.13 ± 0.04 pmol/mg protein, respectively. Guanosine 5?-O-(3-thio)triphosphate (10 ?M) did not change the binding, indicating antagonist binding of the ligand. Various EETs and EET analogs (10?10-10?5M) competed for 20-125I-14,15-EE5ZE binding with an order of potency of 11,12-EET = 14,15-EET > 8,9-EET = 14,15-EE5ZE > 15-hydroxyeicosatetraenoic acid = 14,15-dihydroxyeicosatrienoic acid. 8,9-Dihydroxyeicosatrienoic acid and 11-hydroxyeicosatetraenoic acid did not compete for binding. The soluble and microsomal epoxide hydrolase inhibitors (1-cyclohexyl-3-dodecyl-urea, elaidamide, and 12-hydroxyl-elaidamide) and cytochrome P450 inhibitors (sulfaphenazole and proadifen) did not compete for the binding. However, two cytochrome P450 inhibitors, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) and miconazole competed for binding with Ki of 1558 and 315 nM, respectively. Miconazole and MS-PPOH, but not proadifen, inhibited 14,15-EET-induced relaxations. These findings define an EET antagonist's binding site and support the presence of an EET receptor. The inhibition of binding by some cytochrome P450 inhibitors suggests an alternative mechanism of action for these drugs and could lead to new drug candidates that target the EET binding sites.

Chen, Yuenmu; Falck, John R.; Tuniki, Venugopal R.

2009-01-01

388

Interactions between ?-tocopherol and rosmarinic acid and its alkyl esters in emulsions: synergistic, additive, or antagonistic effect?  

PubMed

Many antioxidants can interact to produce synergistic interactions that can more effectively inhibit lipid oxidation in foods. Esterification of rosmarinic acid produces a variety of compounds with different antioxidant activity due to differences in polarity and thus differences in partitioning in oil, water, and interfacial regions of oil-in-water emulsions (O/W). Therefore, rosmarinic acid and rosmarinate esters provide an interesting tool to study the ability of antioxidant to interact in O/W emulsions. In O/W emulsions, rosmarinic acid (R0) exhibited the strongest synergistic interaction with ?-tocopherol while butyl (R4) and dodecyl (R12) rosmarinate esters exhibited small synergistic interaction and eicosyl rosmarinate esters (R20) exhibited slightly antagonistic interaction. Fluorescence quenching and electron paramagnetic resonance (EPR) studies showed that water-soluble rosmarinic acid (R0) exhibited more interactions with ?-tocopherol than any of the tested esters (R4, R12, R20). This was also confirmed in O/W emulsions where R0 altered the formation of ?-tocopherol quinone and ?-tocopherol increased the formation of caffeic acid from R0. This formation of caffeic acid was proposed to be responsible for the synergistic activity of R0 and ?-tocopherol since the formation of an additional antioxidant could further increase the oxidative stability of the emulsion. PMID:22988974

Panya, Atikorn; Kittipongpittaya, Ketinun; Laguerre, Mickaël; Bayrasy, Christelle; Lecomte, Jérôme; Villeneuve, Pierre; McClements, D Julian; Decker, Eric A

2012-10-04

389

Actions of excitatory amino acid agonists and antagonists on the primary afferents of the vestibular system of the axolotl (Ambystoma mexicanum)  

Microsoft Academic Search

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

Enrique Soto; Rosario Vega

1988-01-01

390