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1

Synergistic Antimicrobial Activities of Folic Acid Antagonists and Nucleoside Analogs?  

PubMed Central

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

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

2010-01-01

2

Folic Acid  

MedlinePLUS

Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

3

Folic Acid  

MedlinePLUS

Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

4

Folic acid - test  

MedlinePLUS

Folic acid is a type of B vitamin. This article discusses the test to measure the amount of folic acid in the blood. ... that may interfere with test results, including folic acid supplements. Drugs that can decrease folic acid measurements ...

5

Folic Acid and Pregnancy  

MedlinePLUS

... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ... well as tissue formation. Continue Getting Enough Folic Acid The Centers for Disease Control and Prevention (CDC) ...

6

Facts about Folic Acid  

MedlinePLUS

... of the baby's brain and spine ( anencephaly and spina bifida ). How much folic acid a woman needs 400 ... audiocast about folic acid. Related Pages Healthy Pregnancy spina bifida Birth Defects CDC’s National Center on Birth Defects ...

7

Folic Acid  

MedlinePLUS Videos and Cool Tools

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

8

Folic Acid Quiz  

MedlinePLUS

... folic acid supplement d) eat a cup of broccoli 5. Spina bifida and anencephaly: Hint a) are ... acid every day. This question is tricky because broccoli is a natural source of food folate, however ...

9

[Folic acid treatment of epileptics].  

PubMed

The author describes the regimen of treatment with folic acid employed in 137 patients with epilepsy. The drug was given to 81 patients to control a complex of disturbances (psychic, neurologic, somatic) caused by folic acid hypovitaminosis secondary to a prolonged use of diphenin, phenobarbital and hexamidine and to another 56 patients to prevent its depletion and to improve the psychic condition. The author considers the questions of the theoretical justification of the pathogenetic treatment with folic acid of epileptic patients. PMID:3630498

Vaintrub, M Ia

1987-01-01

10

Folic Acid Helps Prevent Neural Tube Defects  

MedlinePLUS

... Submit What's this? Submit Button CDC Features Folic Acid Helps Prevent Neural Tube Defects Language: English Español ( ... day before and during pregnancy. What Is Folic Acid? Folic acid is a B vitamin. Our bodies ...

11

Folic Acid: Data and Statistics  

MedlinePLUS

... en... Favorites Delicious Digg Google Bookmarks Data and Statistics On This Page In the United States Hispanic/ ... Questions & Answers Cereals with Folic Acid Data and Statistics Research Birth Defects COUNT Articles & Key Findings Recommendations ...

12

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2013 CFR

...test system. (a) Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is...

2013-04-01

13

Folic acid absorption in various gastrointestinal disorders.  

PubMed

In a consecutive study of 228 patients with folate deficiency originating from various gastrointestinal and haematological disorders, the clinical value of the folic acid absorption (TRIFA) test is assessed. It is concluded that the test is a simple, rapid, and reliable index for folic acid malabsorption of importance as well as a research tool as in daily practice. PMID:1273509

Elsborg, L; Bastrup-Madsen, P

1976-01-01

14

Intestinal transport of zinc and folic acid: a mutual inhibitory  

Microsoft Academic Search

Recent observations suggest an inverse relationship between folic acid intake and zinc nutriture and indicate an interaction between folic acid and zinc at the intestinal level. To define that interaction, we designed in vivo and in vitro transport studies in which folic acid transport in the presence of zinc, as well as zinc transport in the presence of folic acid

Fayez K Ghishan; Hamid M Said; Peter C Wilson; Joel E Murrell; Harry L Greene

15

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

16

Neurologic disorders responsive to folic acid therapy.  

PubMed Central

Six women aged 31 to 70 years had folate deficiency and neuropsychiatric disorders. The three with acquired folate deficiency were depressed and had permanent muscular and intellectual fatigue, mild symptoms of restless legs, depressed ankle jerks, diminution of vibration sensation in the legs, stocking-type hypoesthesia and long-lasting constipation; D-xylos absorption was abnormal. The bone marrow was megaloblastic in only one patient, and she and one other had atrophy of the jejunal mucosa. The third was a vegan. All three recovered after folic acid therapy. The other three were members of a family with the restless legs syndrome, fatigability and diffuse muscular pain. One also had subacute combined degeneration of the spinal cord and kidney disease but no megaloblastosis; she improved spectacularly after receiving large daily doses of folic acid. The other two also had minor neurologic signs, controlled with 5 to 10 mg of folic acid daily. Unrecognized and treatable folate deficiency (with low serum folic acid values but normal erythrocyte folate values) may be the basis of a well defined syndrome of neurologic, psychiatric and gastroenterologic disorders, and the restless legs syndrome may represent the main clinical expression of acquired and familial (or inborn) folate deficiency in adults. Images FIG. 1 FIG. 2

Botez, M. I.; Cadotte, M.; Beaulieu, R.; Pichette, L. P.; Pison, C.

1976-01-01

17

Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates.  

PubMed

Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors. PMID:24257446

Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P

2014-05-25

18

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

PubMed Central

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

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

2013-01-01

19

Folic acid use in planned pregnancy: an Italian survey.  

PubMed

It is well known that periconceptional folic acid supplementation decreases the risk of neural tube defects. The aim of this study was to evaluate the attitudes and practices of women with planned pregnancies regarding periconceptional folic acid intake and to identify factors associated with the use of this supplement. During 2 years of observation, we surveyed women with planned pregnancies who called our Teratology Information Service. A total of 500 women were surveyed: 217 (43.4%) took folic acid before becoming pregnant, and 283 (56.6%) did not take it. The women who took folic acid before becoming pregnant had a high education level and received preconception counselling. Our results suggest that less than half of Italian women took folic acid before they became pregnant although they were trying to conceive. Knowledge about the benefits of this vitamin is inadequate also among women who planned the pregnancy and the level of information received from their physicians. PMID:22696105

De Santis, Marco; Quattrocchi, Tomasella; Mappa, Ilenia; Spagnuolo, Terryann; Licameli, Angelo; Chiaradia, Giacomina; De Luca, Carmen

2013-05-01

20

Avidity mechanism of dendrimer-folic Acid conjugates.  

PubMed

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

van Dongen, Mallory A; Silpe, Justin E; Dougherty, Casey A; Kanduluru, Ananda Kumar; Choi, Seok Ki; Orr, Bradford G; Low, Philip S; Banaszak Holl, Mark M

2014-05-01

21

Folic Acid and Orofacial Clefts: A Review of the Evidence  

PubMed Central

Orofacial clefts are common and burdensome birth defects with a complex genetic and environmental etiology. The contribution of nutritional factors and supplements to the etiology of orofacial clefts has long been theorized and studied. Multiple studies have evaluated the role of folic acid in the occurrence and recurrence of orofacial clefts, using observational and non-randomized interventional designs. While preventive effects of folic acid on orofacial clefts are commonly reported, the evidence remains generally inconsistent. This paper reviews the findings of the main studies of the effects of folic acid on orofacial clefts, summarize study limitations, and discuss research needs with a focus on studying the effects of high dosage folic acid on the recurrence of oral clefts using a randomized clinical trial design. The role of folic acid in the prevention of neural tube defects is also briefly summarized and discussed as a reference model for orofacial clefts.

Wehby, George

2010-01-01

22

Folate Status of Young Canadian Women after Folic Acid Fortification of Grain Products  

Microsoft Academic Search

Women of childbearing age are advised to consume folic acid–containing supplements. Whether this remains necessary after folic acid fortification of the food supply in North America has yet to be determined. The objectives of this study were to assess folate intakes and the contribution of folic acid to the diets of women of childbearing age in the post–folic acid fortification

Aysheh M. Shuaibi; James D. House; Gustaaf P. Sevenhuysen

2008-01-01

23

The neurology of folic acid deficiency.  

PubMed

The metabolism of folic acid and the metabolism of vitamin B12 are intimately linked such that deficiency of either vitamin leads to an identical megaloblastic anemia. The neurologic manifestations of folate deficiency overlap with those of vitamin B12 deficiency and include cognitive impairment, dementia, depression, and, less commonly, peripheral neuropathy and subacute combined degeneration of the spinal cord. In both deficiency states there is often dissociation between the neuropsychiatric and the hematologic complications. There is a similar overlap and dissociation between neurologic and hematologic manifestations of inborn errors of folate and vitamin B12 metabolism. Low folate and raised homocysteine levels are risk factors for dementia, including Alzheimer's disease, and depression. Even when folate deficiency is secondary to psychiatric illness due to apathy or poor diet it may eventually aggravate the underlying disorder in a vicious circle effect. Clinical responses to treatment with folates are usually slow over weeks and months, probably due to the efficient blood-brain barrier mechanism for the vitamin, perhaps in turn related to the experimentally demonstrated excitatory properties of folate derivatives. The inappropriate administration of folic acid in the presence of vitamin B12 deficiency may lead to both neurologic and, later, hematologic relapse. Impaired maternal folate intake and status increases the risk of neural tube defects. Periconceptual prophylactic administration of the vitamin reduces, but does not eliminate the risk of neural tube defects even in the absence of folate deficiency. Folates and vitamin B12 have fundamental roles in central nervous system function at all ages, especially in purine, thymidine, neucleotide, and DNA synthesis, genomic and nongenomic methylation and, therefore, in tissue growth, differentiation and repair. There is interest in the potential role of both vitamins in the prevention of disorders of central nervous system development, mood, dementia, including Alzheimer's disease, and aging. PMID:24365361

Reynolds, E H

2014-01-01

24

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2012 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) Identification....

2012-04-01

25

Regulation of Human Jejunal Glycolytic Enzymes by Oral Folic Acid.  

National Technical Information Service (NTIS)

The effect of oral folic acid on jejunal glycolytic enzyme activity in five fasting obese patients and in three normal male volunteers on a constant 3000 cal diet was studied. The glycolytic enzymes, fructokinase, hexokinase, glucokinase, fructose-1-phosp...

N. S. Rosensweig R. H. Herman F. B. Stifel Y. F. Herman

1969-01-01

26

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

27

Benefits and risks of folic acid to the nervous system  

PubMed Central

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

Reynolds, E

2002-01-01

28

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia  

Microsoft Academic Search

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

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

1999-01-01

29

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

30

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

PubMed Central

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 after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification. Methods Study 1. Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n = 50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2. Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n = 20), and from their infant's umbilical-cords (n = 20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate. Results Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%–99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%–96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%), comprising 2.25% of total plasma folate, Conclusion While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.

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

2009-01-01

31

Reversible malabsorption of folic acid in the elderly with nutritional folate deficiency.  

PubMed

In normal subjects, the folic acid absorption (TRIFA test) was independent of age and sex. Among 53 geriatric patients with nutritional folate deficiency, impaired absorption of folic acid was present in 19 (36%). After treatment with folic acid for 4 weeks, the absorption returned to normal. It is concluded that folate deficiency per se can produce a malabsorption syndrome resulting in further depletion of folate. Protein deficiency and weight loss alone do not impair the absorption of folic acid. PMID:816151

Elsborg, L

1976-01-01

32

Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery  

PubMed Central

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 (Papp) 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.

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

2012-01-01

33

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

34

Response of Low Birthweight Infants to Treatment with Folic Acid  

Microsoft Academic Search

Folate deficiency, detected by measuring serum and red cell levels, was seen within a group of low birthweight infants who had been followed for a period of 9 months. A similar group treated with 14 × 100 ?g folic acid by intramuscular injection over a period of 28 days during the first 5 weeks of life had significantly higher folate

W. L. Burland; K. Simpson; Juliet Lord

1971-01-01

35

Studies on the folic acid activity of human serum  

Microsoft Academic Search

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

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

1961-01-01

36

Role of Folic Acid on Symptoms of Chronic Arsenic Toxicity  

PubMed Central

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

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

2014-01-01

37

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

Microsoft Academic Search

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

Mary Rose Sweeney; Joseph McPartlin; John Scott

2007-01-01

38

Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels  

Microsoft Academic Search

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

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

2001-01-01

39

Phenytoin, folic acid and gingival enlargement: Breaking myths  

PubMed Central

Background: Epilepsy is described as a chronic neurological disorder characterized by recurrent seizures of cerebral origin, presenting with episodes of sensory, motor or autonomic phenomenon with or, without loss of consciousness. A recent meta-analysis of published and unpublished studies puts an overall prevalence rate of epilepsy in India at 5.59 per 1,000 populations. There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the anti-epileptic therapy in the prevention of anti-epileptic drug induced gingival enlargement. However, studies conducted in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy so as to justify the use of folic acid as a routine adjuvant to the usual anti-epileptic therapy to prevent this inevitable adverse effect without destabilizing the ongoing regimen leading to the precipitation of seizures in an otherwise stable patient (breakthrough seizures). Materials and Methods: A total of 100 patients between the ages 18 and 50 years were clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was performed prior to the start of and after 1 year of phenytoin therapy. Statistical Analysis Used: The statistical analysis was carried out using t-test and the baseline serum folate levels and the serum folate levels obtained after 1 year of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. Results: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin induced gingival enlargement. Conclusions: The results of the study suggest a higher incidence of gingival enlargement with an early onset and increased severity in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.

Nayyar, Abhishek Singh; Khan, Mubeen; Vijayalakshmi, K. R.; Suman, B.; Subhas, G. T.; Nataraju, B.; Anitha, M.

2014-01-01

40

Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes  

PubMed Central

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong

2014-01-01

41

"Click and go": simple and fast folic acid conjugation.  

PubMed

Folic acid targeting by functionalization of the terminal ?-carboxylic acid is one of the most important strategies to selectively deliver chemotherapeutics and dyes to cancer cells which overexpress folate receptors. However, conjugation of folic acid is limited by its unique solubility and by selectivity issues imposing the need for expensive preparative reverse-phase chromatographic purification to isolate ?-folate conjugates. Herein is provided a novel synthetic tool for the synthesis of new folic acid conjugates with excellent ?-purity based on strain-promoted alkyne-azide cycloadditions with a ?-folate-cyclooctyne conjugate 3. To demonstrate the potential of this methodology several new folate conjugates were synthesized with high ?-purity and without using any type of chromatographic purification by reacting conjugate 3 with several fluorescent probes, polymers and siliceous materials bearing azide. In addition, the cycloaddition reaction between conjugate 3 and an azido-derived fluorescent dye was successfully performed in cellular media leading to an increase of fluorescence in the cells which overexpress folate receptors (NCI-H460). PMID:24723199

Trindade, Alexandre F; Frade, Raquel F M; Maçôas, Ermelinda M S; Graça, Cátia; Rodrigues, Catarina A B; Martinho, José M G; Afonso, Carlos A M

2014-05-28

42

Imaging Pancreatic Cancer with Folic Acid Terminated Luminescent Silicon Nanocrystals  

NASA Astrophysics Data System (ADS)

Quantum dots have great potential for visualization of medically relevant targets such as cancer. However, potential toxicity, stemming from the use of heavy metal based semidonductor materials, has been a major impediment to use of quantum dots in vivo. Silicon is an inherently non-toxic element. By combining the unique optical properties of silicon quantum dots with fundamentals of cancer biology, we can develop probes that safely target and enable the visualization of cancer cells. Many cancer cells overexpress folate receptors, making the folate receptors a suitable target for cancer imaging evaluations. Here, we report the synthesis of folic acid coated silicon quantum dots for targeting pancreatic cancer cells. Folic acid on the silicon quantum dots improves selectivity and may decrease possible negative side effects. This demonstration adds to the evidence that silicon can be sucessfully used for biological imaging.

Erogbogbo, Folarin; Swihart, Mark T.

2010-10-01

43

Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility.  

PubMed

Folic acid supplements are commonly used by infertile women which leads to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to IVF pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P<0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P<0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility. Folate is one of the B vitamins which has been suggested to be related to infertility. Folic acid is an artificial form of folate which is commonly used in dietary supplements. Folic acid supplementation has been shown to increase folate concentrations and decrease concentrations of the amino acid homocysteine in the blood. Folic acid supplementation is commonly used by infertile women, but the effect on pregnancy outcome in women with a diagnosis of unexplained infertility has not been thoroughly investigated. In the present study, folic acid supplement use and folate status (concentrations of folate and homocysteine) in women with unexplained infertility were evaluated in relation to pregnancy outcome. In addition, the use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile control women. Our results showed that women with unexplained infertility used considerably more folic acid supplements and had higher total folic acid intake from supplements compared with fertile control women. Women with unexplained infertility had better blood folate and homocysteine concentrations than fertile women, but folic acid supplementation or folate status were not related to pregnancy outcome following the infertility treatment. In conclusion, high folic acid intake or good folate status did not increase the possibility of a birth of a healthy baby after infertility treatment in women with unexplained infertility. PMID:24745837

Murto, T; Skoog Svanberg, A; Yngve, A; Nilsson, T K; Altmäe, S; Wånggren, K; Salumets, A; Stavreus-Evers, A

2014-06-01

44

Folic acid in early pregnancy: a public health success story  

PubMed Central

Folate is a water-soluble B vitamin that must be obtained in the diet or through supplementation. For >50 yr, it has been known that folate plays an integral role in embryonic development. In mice, inactivation of genes in the folate pathway results in malformations of the neural tube, heart, and craniofacial structures. It has been shown that diets and blood levels of women who had a fetus with a neural tube defect are low for several micronutrients, particularly folate. Periconceptional use of folic acid containing supplements decreased recurrent neural tube defects in the offspring of women with a previously affected child and the occurrence of a neural tube defect and possibly other birth defects in the offspring of women with no prior history. Based on these findings, the U.S. Public Health Service recommended that all women at risk take folic acid supplements, but many did not. Mandatory food fortification programs were introduced in numerous countries, including the United States, to improve folate nutritional status and have resulted in a major decrease in neural tube defect prevalence. The success story of folate represents the cooperation of embryologists, experimentalists, epidemiologists, public health scientists, and policymakers.—Obi?an, S. G., Finnell, R. H., Mills, J. L., Shaw, G. M., Scialli, A. R. Folic acid in early pregnancy: a public health success story.

Obican, Sarah G.; Finnell, Richard H.; Mills, James L.; Shaw, Gary M.; Scialli, Anthony R.

2010-01-01

45

Folic acid supplementation delays atherosclerotic lesion development in apoE-deficient mice  

Microsoft Academic Search

Folic acid is a vitamin that when used as a dietary supplementation can improve endothelial function. To assess the effect of folic acid on the development of atherosclerosis, male apolipoprotein E-deficient mice fed a standard chow diet received either water (control group) or an aqueous solution of folic acid that provided a dose of 75 ?g\\/kg\\/day, for ten weeks. At the

Ricardo Carnicer; María A. Navarro; José M. Arbonés-Mainar; Sergio Acín; Mario A. Guzmán; Joaquín C. Surra; Carmen Arnal; Marcelo de las Heras; Francisco Blanco-Vaca; Jesús Osada

2007-01-01

46

Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity  

Microsoft Academic Search

The free radical scavenging properties and possible antioxidant activity of folic acid are reported. Pulse radiolysis technique is employed to study the one-electron oxidation of folic acid in homogeneous aqueous solution. The radicals used for this study are CCl3O2•, N3•, SO4•?, Br2•?, OH, and O•?. All these radicals react with folic acid under ambient condition at an almost diffusion-controlled rate

Ravi Joshi; S. Adhikari; B. S. Patro; S. Chattopadhyay; T. Mukherjee

2001-01-01

47

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

48

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

Microsoft Academic Search

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

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

2010-01-01

49

Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes.  

PubMed

The water-soluble B vitamins, folate and folic acid, play an important role in reproductive health, but little is known about the effects of folic acid on infertility. The present study tested the hypothesis that folic acid affects oocyte maturation, a possible cause of female infertility. We have studied the in vitro maturation of mouse and Xenopus oocytes. Hypoxanthine (Hx) was used as an inhibitor of mouse oocyte maturation to mimic in vivo conditions by maintaining high levels of cyclic-AMP. The frequency of first polar body (PB1) formation and germinal vesicle breakdown (GVBD) in mouse oocytes was decreased by Hx. This effect was counteracted by folic acid added to the medium. PB1 extrusion and GVBD percentages rose to 27·7 and 40·0% from 12·8 and 19·9%, respectively, by exposure to 500 ?M-folic acid. Folic acid also restored the spindle configuration, which had been elongated by Hx, as well as normalising the distribution of cortical granules (CG). In folic acid-treated Xenopus eggs, extracellular signal-regulated kinase 1 was phosphorylated, cyclin B2 and Mos were up-regulated and the frequency of GVBD was accelerated. Taken together, the findings suggest that folic acid facilitates oocyte maturation by altering the expression and phosphorylation of proteins involved in M-phase-promoting factor and mitogen-activated protein kinase pathways, as well as causing changes in spindle configuration and CG migration. PMID:22932126

Huang, Xiaoli; Gao, Shu; Xia, Wei; Hou, Shaoying; Wu, Kun

2013-04-28

50

Maternal and Cord Blood Homocysteine and Folic Acid Levels in Smoking and Nonsmoking Pregnant Women  

Microsoft Academic Search

Introduction: The homocysteine level in blood is affected by gender, diet, smoking, folic acid and B-complex vitamins. It is known that higher than normal homocysteine levels in plasma may cause vascular endothelium dysfunction, resulting in the promotion of thrombus formation. In our study, we aimed to assess the effects of smoking during pregnancy on the homocysteine and folic acid levels

Isil Coker; Ayfer Colak; Aybike Gunaslan Hasturk; Omur Yildiz; Hakan Turkon; Oya Halicioglu

2011-01-01

51

Multivitamins, Folic Acid and Birth Defects: Knowledge, Beliefs and Behaviors of Hispanic Women in North Carolina  

ERIC Educational Resources Information Center

Background: Consumption of folic acid prior to conception can prevent up to 70% of neural tube defect (NTD)-affected pregnancies. In 1992, the U.S. Public Health Service (USPHS) issued a recommendation that all women of childbearing age capable of becoming pregnant consume 400 [mu]g of folic acid daily to reduce their risk for a NTD-affected…

deRosset, Leslie; Mullenix, Amy; Zhang, Lei

2009-01-01

52

Case-Control Study of Periconceptio nal Folic Acid Supplementation and Oral Clefts  

Microsoft Academic Search

There is consistent evidence that the risk of neural tube defects is decreased by periconceptional supple- mentation with folic acid. A similar protective effect has been postulated for oral clefts. A case-control study was conducted in greater metropolitan Boston, Massachusetts; Philadelphia, Pennsylvania; and southeastern Ontario, Canada, from 1988 through 1991 to test the hypothesis that folic acid supplementation during the

Catherine Hayes; Martha M. Werier; Walter C. Willett; Allen A. Mitchell

53

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

54

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

55

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.  

PubMed

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process. PMID:10600765

Jaszewski, R; Khan, A; Sarkar, F H; Kucuk, O; Tobi, M; Zagnoon, A; Dhar, R; Kinzie, J; Majumdar, A P

1999-12-01

56

Association of folic acid supplementation during pregnancy and infant bronchiolitis.  

PubMed

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

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

2014-04-15

57

Soy protein/soy polysaccharide complex nanogels: folic acid loading, protection, and controlled delivery.  

PubMed

In this study, we developed a facile approach to produce nanogels via self-assembly of folic acid, soy protein, and soy polysaccharide. High-pressure homogenization was introduced to break down the original aggregates of soy protein, which benefits the binding of soy protein with soy polysaccharide and folic acid at pH 4.0. After a heat treatment that causes the soy protein denaturation and gelation, folic acid-loaded soy protein/soy polysaccharide complex nanogels were fabricated. The nanogels have a polysaccharide surface that makes the nanogels dispersible in acidic conditions where folic acid is insoluble and soy protein forms precipitates after heating. More importantly, the protein and polysaccharide can inhibit the reactions between dissolved oxygen and folic acid during UV irradiation. After the preparation and storage of the nanogels in the presence of heat, oxygen, and light in acidic conditions, most of the folic acid molecules in the nanogels remain in their natural structure and can be released rapidly at neutral pH, that is, in the intestine. Because most food and beverages are acidic, the nanogels are a suitable delivery system of folic acid in food and beverages. PMID:23758109

Ding, Xuzhe; Yao, Ping

2013-07-01

58

Assessment of folic Acid and DNA damage in cleft lip and cleft palate.  

PubMed

Studies have identified the risk factors like folic acid deficiency during gestational period, family history for orofacial clefts, drugs like antiepileptic, vitamin A. But, the data regarding the folic acid status in children with cleft lip/palate is hardly evaluated in depth. Here, an assessment of folic acid and DNA damage were carried out in children with orofacial anomalies. Folic acid level and DNA damage were evaluated by folic acid assay (direct chemiluminescent technology) and single cell gel electrophoresis or comet assay method respectively. The mean value of plasma folic acid by direct chemiluminescent technology was 6.5±3.6 nmol/L and the normal value in children ranges from 11.3 to 47.6 nmol/L. The amount of damaged DNA, measured as the tail length of the comet in cases, was 19.4±8.9 ?m and the mean percentage of DNA in tail was 16.5±3.7. Folic acid deficiency could be the reason for DNA damage. PMID:24847430

Brooklyin, Sivakumar; Jana, Rashmoni; Aravinthan, Singaravelu; Adhisivam, Bethou; Chand, Parkash

2014-03-27

59

Assessment of Folic Acid and DNA Damage in Cleft Lip and Cleft Palate  

PubMed Central

Studies have identified the risk factors like folic acid deficiency during gestational period, family history for orofacial clefts, drugs like antiepileptic, vitamin A. But, the data regarding the folic acid status in children with cleft lip/palate is hardly evaluated in depth. Here, an assessment of folic acid and DNA damage were carried out in children with orofacial anomalies. Folic acid level and DNA damage were evaluated by folic acid assay (direct chemiluminescent technology) and single cell gel electrophoresis or comet assay method respectively. The mean value of plasma folic acid by direct chemiluminescent technology was 6.5±3.6 nmol/L and the normal value in children ranges from 11.3 to 47.6 nmol/L. The amount of damaged DNA, measured as the tail length of the comet in cases, was 19.4±8.9 ?m and the mean percentage of DNA in tail was 16.5±3.7. Folic acid deficiency could be the reason for DNA damage.

Brooklyin, Sivakumar; Jana, Rashmoni; Aravinthan, Singaravelu; Adhisivam, Bethou; Chand, Parkash

2014-01-01

60

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

PubMed

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

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

2014-05-01

61

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

PubMed Central

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

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

2014-01-01

62

Trends in folic acid supplement intake among women of reproductive age--California, 2002-2006.  

PubMed

Daily intake of 400 microg of folic acid before conception can reduce by approximately 80% the risk for having an infant with a neural tube defect (NTD) such as spina bifida or anencephaly. Although other risk factors for NTDs exist, such as diabetes, obesity, and family history of NTDs, prevention measures have focused predominantly on promoting folic acid consumption. Women can ensure they are consuming the recommended amount of folic acid by eating one serving of breakfast cereal fortified with 100% of the recommended daily value of folic acid or by taking a supplement with 400 microg folic acid daily. Annual surveys conducted for the March of Dimes (MOD) Birth Defects Foundation indicate that 40% of all U.S. women of reproductive age (i.e., aged 15-45 years) took supplements containing folic acid in 2007 (MOD, unpublished data, 2007), up from 28% in 1995. To analyze trends in folic acid-containing supplement intake among California women aged 18-44 years during 2002-2006, the California Department of Public Health conducted trend analyses of data from the California Women's Health Survey (CWHS). This report summarizes the results of those analyses, which indicated that although the overall prevalence of intake of folic acid-containing supplements remained stable from 2002 (40%) to 2006 (41%) in California, use of such supplements decreased among Hispanic women and women with less education. Downward trends among Hispanic women are of particular concern because 1) Hispanic women are at increased risk for having a fetus or an infant with an NTD compared with women of other races/ethnicities, 2) the number of births to Hispanics in California increased during 1993-2003, and 3) Hispanics accounted for nearly 52% of all births in California in 2005 (California Department of Public Health, unpublished data, 2005). Development of additional targeted and evidence-based public health interventions for increasing folic acid intake among these populations is needed. PMID:17962802

2007-10-26

63

Women's Awareness of Periconceptional Use of Folic Acid Before and After Their Antenatal Visits  

PubMed Central

OBJECTIVE The aim of this study is to assess women’s awareness of the benefit and use of folic acid during pregnancy and to assess whether their knowledge has improved following hospital visits. METHOD This is a prospective survey conducted in a large teaching hospital in the UK. The survey questionnaire consisted of 28 questions about demographic variables, behavioral variables, and knowledge about folic acid and neural tube defects (NTDs). RESULT A total of 603 women participated in this study. Some of them attended for the first time and others had more than one visit, either in their current or previous pregnancies. In about 25% of cases, the pregnancy was not planned. Between 14 and 19% of the women of First and Two+ Visit groups consulted their doctor or other healthcare professional before conception. Nearly 98% of the women stated that they had heard of folic acid, but only 42–52% knew the medical condition it protects against. The main sources of information for women who were aware of folic acid were midwives and general practitioners. Nearly 90% of women who attended their first antenatal visit were taking folic acid. However, only 40% of women knew that they should take it before pregnancy, and only between 36 and 46% knew the dietary sources of folic acid, although about 84% know the foods that should be avoided during pregnancy. This study found that attending antenatal clinic has not increased women’s awareness about folic acid. CONCLUSION There is still a high proportion of women who do not know that folic acid should be taken before pregnancy and continued for the first three months of pregnancy. School education, primary care team, and family planning service should take the lead in providing information to women about folic acid.

Maher, Mark; Keriakos, Remon

2014-01-01

64

Preconceptional folic acid-containing supplement use in the national birth defects prevention study.  

PubMed

Background: Despite public health campaigns encouraging women to take a daily folic acid supplement, the proportion of reproductive age women, in the United States, who comply with this recommendation is less than optimal. The objective of this analysis was to identify predictors of preconceptional folic acid-containing supplement use to define subgroups of women who may benefit from targeted folic acid campaigns. Methods: This study included 6570 mothers of live born infants from the control population of National Birth Defects Prevention Study (1997-2005). Logistic regression analyses were used to identify predictors of preconceptional folic acid supplementation. A classification and regression tree (CART) analysis was used to define subgroups of women with different patterns of preconceptional folic acid supplementation. Results: Race/ethnicity, education, age at delivery, nativity, employment, income, number of dependents, smoking, and birth control use were significantly associated with preconceptional folic acid-containing supplement use. Based on a CART analysis, education, race/ethnicity, and age were the most distinguishing factors between women with different preconceptional supplementation patterns. Non-white women with <4 years of a college education were the least likely to use folic acid-containing supplements (11%). However, even in the most compliant subgroup (women with ?4 years of college), only 60% of women supplemented with folic acid. Conclusion: These results demonstrate the need for continued efforts to increase folic acid supplementation among all reproductive aged women. However, the success of such efforts may be improved if maternal characteristics such as education, race/ethnicity, and age, are considered in the development of future interventions. Birth Defects Research (Part A) 100:472-482, 2014. © 2014 Wiley Periodicals, Inc. PMID:24706436

Khodr, Zeina G; Lupo, Philip J; Agopian, A J; Canfield, Mark A; Case, Amy P; Carmichael, Suzan L; Mitchell, Laura E

2014-06-01

65

Folic acid - vitamin and panacea or genetic time bomb?  

PubMed

We live in a health-conscious age - many of us supplement our diet with essential micronutrients through the discretionary use of multivitamin pills or judicious selection of foods that have a health benefit beyond that conferred by the nutrient content alone - the so-called 'functional foods'. Indeed, the citizens of some nations have little choice, with a mandatory fortification policy in place for certain vitamins. But do we ever stop to consider the consequences of an increased exposure to micronutrients? We examine this issue in relation to the B-group vitamin folic acid, and ask whether supplementation with this vitamin could introduce a strong genetic selection pressure - one that has the side effect of increasing the prevalence of some of the most significant, human life-threatening diseases. Are we affecting our genetics - is this a case of human evolution in progress by altering our diet? PMID:15738964

Lucock, Mark; Yates, Zoë

2005-03-01

66

Folic acid-CdTe quantum dot conjugates and their applications for cancer cell targeting  

Microsoft Academic Search

In this study, we report the preparation, luminescence, and targeting properties of folic acid-CdTe quantum dot conjugates.\\u000a Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide\\u000a chemistry. The influence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy\\u000a transfer between them was observed. To investigate the efficiency of

Preethi Suriamoorthy; Xing Zhang; Guiyang Hao; Alan G. Joly; Surya Singh; Marius Hossu; Xiankai Sun; Wei Chen

2010-01-01

67

Absorption of folic acid from the small intestine of the rat  

PubMed Central

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

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

1962-01-01

68

Identifying women who might benefit from higher doses of folic acid in pregnancy  

PubMed Central

Abstract Question One of my epileptic patients who takes carbamazepine is planning to become pregnant. She told me that Motherisk advised her to take 5 mg of folic acid daily until the end of the first trimester. Are there other women who need more than the regular dose of folic acid included in prenatal vitamins? Answer Women who are at high risk of having babies with neural tube defects and who would benefit from higher doses of folic acid include those with certain folate-enzyme genotypes, previous pregnancies with neural tube defects, diabetes, malabsorption disorders, or obesity, or those who take antifolate medications or smoke. Such women should take 5 mg/d of folic acid for the 2 months before conception and during the first trimester.

Kennedy, Deborah; Koren, Gideon

2012-01-01

69

Effect of folic acid and vitamin B 12 administration on phenytoin induced toxicity in rats  

Microsoft Academic Search

Folic acid and vitamin B12 are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B12 on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated.\\u000a The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as\\u000a indices

Itemobong S. Ekaidem; Monday I. Akpanabiatu; Friday E. Uboh; Offiong U. Eka

2007-01-01

70

Folic acid for prevention of neural tube defects: Pediatric anticipatory guidance  

Microsoft Academic Search

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 ?g\\/day) and consuming

Judy D Morrow; Kristine Kelsey

1998-01-01

71

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

Microsoft Academic Search

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

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

2000-01-01

72

The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study  

Microsoft Academic Search

Objectives: To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine, an independent risk factor for occlusive vascular disease, in a general population.Design: A randomized double-blind placebo-controlled intervention study.Subjects: One hundred and nineteen healthy volunteers, whose intake of fortified or supplemental folic acid was low, were recruited by letter from the

CJ Schorah; H Devitt; M Lucock; AC Dowell; DJ Schorah

1998-01-01

73

Relevance of folic acid\\/polymer ratio in targeted PEG–epirubicin conjugates  

Microsoft Academic Search

A series of PEG–epirubicin conjugates with different folic acid contents per polymer chain was synthesized in order to study the influence of polymer\\/targeting moiety ratio on selective cytotoxicity, cellular uptake and intracellular localization. Analogous carboxyl-terminated conjugates without folic acid were studied as control. The heterobifunctional HO-PEG-COOH was used as polymeric carrier, allowing the synthesis of conjugates with a good control

Fabiana Canal; María J. Vicent; Gianfranco Pasut; Oddone Schiavon

2010-01-01

74

Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia.  

PubMed

Emerging evidence has suggested that folic acid-containing multivitamins may markedly reduce the risk of gestational hypertension or preeclampsia. We examined whether maternal supplementation with folic acid alone during early pregnancy can prevent the occurrence of gestational hypertension and preeclampsia. The data are from a large population-based cohort study established to evaluate the effectiveness of the campaign to prevent neural tube defects with folic acid supplementation in China. We selected participants who were registered in 2 southern provinces, had exact information on folic acid use, and were not affected by chronic hypertension or diabetes mellitus before 20 weeks gestation. A logistic regression model was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, parity, and multiple births. The study size had 99.9% power (?=0.05) to detect a decrease of 10% over the unexposed rate of 9.4% for gestational hypertension. Among the 193 554 women (47.9% took folic acid, 52.1% did not), the overall incidence of gestational hypertension and preeclampsia was 9.5% and 2.5%, respectively. The incidence of gestational hypertension and preeclampsia was 9.7% and 2.5% for women who took folic acid, and 9.4% and 2.4% for women who did not use it. The adjusted risk ratio associated with folic acid use was 1.08 (95% confidence interval, 1.04-1.11) for gestational hypertension and 1.11 (95% confidence interval, 1.04-1.18) for preeclampsia. Our findings suggest that daily consumption of 400 ?g folic acid alone during early pregnancy cannot prevent the occurrence of gestational hypertension and preeclampsia. PMID:23399716

Li, Zhiwen; Ye, Rongwei; Zhang, Le; Li, Hongtian; Liu, Jianmeng; Ren, Aiguo

2013-04-01

75

PMM.04?Women's awareness of periconceptional use of folic acid before and after their antenatal visits.  

PubMed

: This is a prospective survey performed in a large teaching hospital in the UK. The aim of the study is to assess the awareness amongst women of the benefit and use of folic acid during pregnancy and whether their knowledge improved following hospital visits. A total of 603 women participated in the study; some attending for the first time and others had more than one visit, either in their current or previous pregnancies. The survey consisted of 28 questions regarding demographic variables, including behavioural variables, and knowledge about folic acid and neural tube defects. In around 25% of cases the pregnancy was unplanned. Between 14-19% of the women that did plan their pregnancy consulted their doctor or other health care professional before conception. Nearly 98% of the women stated having heard of folic acid, however, only 42-52% knew the medical condition it protects against. The main sources of information in women who were aware of folic acid were midwives and GPs. Nearly 90% of women who attended their first antenatal visit were taking folic acid. However, only 40% knew that they should take it before pregnancy. Only between 36-46% of women knew the dietary sources of folic acid, although about 84% knew the foods that should be avoided during pregnancy. This study found that attending antenatal clinic hasn't increased women's awareness about folic acid. This study highlighted the importance of school education, Primary Care Team and Family Planning service in providing information to women about folic acid. PMID:25021001

Maher, M; Keriakos, R

2014-06-01

76

Folic acid and vitamin B12 levels in pregnancy and their relation to megaloblastic anaemia  

PubMed Central

There is a significant fall in the serum folic acid level during pregnancy, reaching its lowest level at term. This is most pronounced in twin pregnancies. A similar but less spectacular fall occurs in the vitamin B12 concentration. In megaloblastic anaemia both folic acid and vitamin B12 levels are lower than in other pregnant women. The degree of megaloblastic change in the bone marrow, as measured by the type and number of megaloblasts, is reflected in the vitamin levels, cases with florid megaloblastosis showing the most marked depression of vitamin B12 and folic acid activity. Although there is a significant difference in the mean folic acid levels between megaloblastic and normoblastic pregnant women, a considerable overlap exists between individual values in the two groups. When the labile folic-acid factor is determined separately the test becomes much more specific. In the present series, all cases of megaloblastic anaemia yielded labile-factor levels below 1·0 m?g. per ml., while a similar value was encountered in only one of 35 normal pregnancies. In five women with megaloblastic anaemia the vitamin B12 concentration was less than 100 ??g. per ml. but rose to normal levels on folic acid therapy alone. Images

Ball, E. W.; Giles, C.

1964-01-01

77

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

78

Folic Acid Supplementation and Preterm Birth: Results from Observational Studies  

PubMed Central

Introduction. Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. Aim of the Study. The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. Materials and Methods. We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. Results. The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB.

Franchi, Massimo

2014-01-01

79

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

80

Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.  

PubMed

Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions. PMID:18539928

Luebeck, E Georg; Moolgavkar, Suresh H; Liu, Amy Y; Boynton, Alanna; Ulrich, Cornelia M

2008-06-01

81

Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid.  

PubMed

Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC), is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by short plasma half-life, rapid metabolism and low selectivity towards tumor tissue. To overcome these limits, bioconjugates of gemcitabine were studied using poly(ethylene glycol) as polymeric carrier. Two types of conjugates were prepared, non-targeted and folic acid targeted conjugates. The formers were obtained starting from mPEG-OH of 5 and 20 kDa with linear or branched structure. The folic acid targeted conjugates, differing for the drug loading, were prepared exploiting a heterobifunctional PEG that allowed a consecutive coupling of the targeting agent and the drug. Folic acid was chosen as targeting agent because its receptor is often over-expressed in many tumors. To increase the polymer drug payload, the bicarboxylic amino acid, aminoadipic acid, was used. All conjugates were able to release the drug in a pH-dependent manner with no role of enzymes. The pharmacokinetic profiles are strictly related to the polymer molecular weight and the folic acid targeting increased 2-3 times the affinity towards the cells over-expressing folic acid receptors. These results are promising and encourage in vivo studies on these conjugates that act as polymeric prodrugs. PMID:18346806

Pasut, Gianfranco; Canal, Fabiana; Dalla Via, Lisa; Arpicco, Silvia; Veronese, Francesco M; Schiavon, Oddone

2008-05-01

82

Folate, folic acid and 5-methyltetrahydrofolate are not the same thing.  

PubMed

1. Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Mammals cannot synthesize folate and depend on supplementation to maintain normal levels. Low folate status may be caused by low dietary intake, poor absorption of ingested folate and alteration of folate metabolism due to genetic defects or drug interactions. 2. Folate deficiency has been linked with an increased risk of neural tube defects, cardiovascular disease, cancer and cognitive dysfunction. Most countries have established recommended intakes of folate through folic acid supplements or fortified foods. External supplementation of folate may occur as folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF). 3. Naturally occurring 5-MTHF has important advantages over synthetic folic acid - it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism. Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation. 4. We review the evidence for the use of 5-MTHF in preventing folate deficiency. PMID:24494987

Scaglione, Francesco; Panzavolta, Giscardo

2014-05-01

83

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

PubMed

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

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

2014-04-01

84

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

PubMed

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

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

2013-09-01

85

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

PubMed Central

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

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

2012-01-01

86

Characterization of ZnO nanoparticles grown in presence of Folic acid template  

PubMed Central

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

2012-01-01

87

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice.  

PubMed

More than 29 million adults in the United States have been diagnosed with hearing loss. Interestingly, elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy), are also associated with impaired hearing. However, the associated mechanism remains obscure. The collagen receptor such as discoidin domain receptor 1 and matrix metalloproteinase (MMP) play a significant role in inner ear structure and function. We hypothesize that HHcy increases hearing thresholds by compromise in inner ear vasculature resulted from impaired Hcy metabolism, increased oxidative stress, collagen IVa and collagen Ia turnover. The treatment with folic acid (FA) protects elevated hearing thresholds and prevents reduction in vessel density by lowering abundant collagen deposition and oxidative stress in inner ear. To test this hypothesis we employed 8 weeks old male wild type (WT), cystathionine-beta-synthase heterozygote knockout (CBS+/-) mice, WT + FA (0.0057 ?g/g/day, equivalent to a 400 ?g/70 kg/day human dose in drinking water); and CBS(+/-) +FA. The mice were treated for four weeks. The hearing thresholds were determined by recording the auditory brainstem responses. Integrity of vessels was analyzed by perfusion of horseradish peroxidase (HRP) tracer. Endothelial permeability was assessed, which indicated restoration of HRP leakage by FA treatment. A total Hcy level was increased in stria vascularis (SV) and spiral ligament (SL) of CBS+/- mice which was lowered by FA. Interestingly, FA treatment lowered Col IVa Immunostaining by affecting its turnover. The levels of MMP-2, -9, methylenetetrahydrofolate reductase (MTHFR) and cystathione gamma lyase (CSE) were measured by Western blot analysis. The oxidative stress was high in SV and SL of CBS+/- compared to WT however the treatment with FA lowered oxidative stress in CBS+/- mice. These data suggested that hearing loss in CBS+/- mice was primarily due to leakage in inner ear circulation, also partly by induced collagen imbalance, increase in Hcy and oxidative stress in inner ear. PMID:22222235

Kundu, Soumi; Munjal, Charu; Tyagi, Neetu; Sen, Utpal; Tyagi, Aaron C; Tyagi, Suresh C

2012-02-01

88

Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy  

Microsoft Academic Search

Background\\u000a   Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with\\u000a folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome.\\u000a \\u000a \\u000a \\u000a \\u000a Objective\\u000a   To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal\\u000a demise after week 20 of gestational age) in pregnant

Sabine Pittschieler; Christoph Brezinka; Beate Jahn; Eugen Trinka; Iris Unterberger; Judith Dobesberger; Gerald Walser; Andrea Auckenthaler; Norbert Embacher; Gerhard Bauer; Gerhard Luef

2008-01-01

89

Relevance of folic acid/polymer ratio in targeted PEG-epirubicin conjugates.  

PubMed

A series of PEG-epirubicin conjugates with different folic acid contents per polymer chain was synthesized in order to study the influence of polymer/targeting moiety ratio on selective cytotoxicity, cellular uptake and intracellular localization. Analogous carboxyl-terminated conjugates without folic acid were studied as control. The heterobifunctional HO-PEG-COOH was used as polymeric carrier, allowing the synthesis of conjugates with a good control over the chemical structure and the drug/polymer and polymer/targeting residue ratios. A dendron structure was synthesized at one end of the PEG chain with the aim to increase the number of folic acid molecules. L-2-aminoadipic acid was used as branching unit. The conjugates showed high stability under several physiological conditions. Biological evaluation was carried out in A549, HeLa and KB-3-1 human cell lines, as these cells have different levels of folate receptor (FR) expression. In particular A549 cells are FR negative (FR-), HeLa cells are FR positive (FR+) and KB-3-1 cells over-express FR (FR++). It was clearly shown that the biological activity of the conjugates was influenced by the presence and the number of folic acid molecules per polymer chain and by the level of FR expression on cell surface. Conjugates conformation in solution was also studied, as differences in size might well affect cell internalization. In the cell viability assay, conjugates without folic acid were unexpectedly more cytotoxic than the targeted conjugates, but their IC(50) values were similar in the three cell lines. Differently, the anti-proliferative activity of targeted derivatives markedly increased going from FR(-) to FR(++) cells. FACS and confocal microscopy studies showed greater cellular internalization with the targeted conjugates than with their non-targeted analogues; more importantly, this relationship is clearly dependent on folic acid content in the conjugates and FR expression level in the cell line used. PMID:20621587

Canal, Fabiana; Vicent, María J; Pasut, Gianfranco; Schiavon, Oddone

2010-09-15

90

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

PubMed

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

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

2007-03-01

91

Fortification of corn masa flour with folic acid in the United States.  

PubMed

Food fortification is an effective public health tool for addressing micronutrient deficiencies. The mandatory fortification of enriched cereal grains (e.g., wheat flour) with folic acid, which began in the United States in 1998, is an example of a successful intervention that significantly reduced the rate of neural tube defects (NTDs). However, despite the drop in NTD rates across all racial/ethnic groups after fortification, Hispanics continue to have the highest rates of this condition. One possible way to reduce this disparity is to fortify corn masa flour to increase the overall intake of folic acid in Hispanic women. We present the available evidence in favor of this approach, address possible safety issues, and outline next steps in the fortification of corn masa flour with folic acid in the United States. PMID:21680940

Fleischman, Alan R; Oinuma, Motoko

2011-08-01

92

Intestinal Absorption of Tritium-Labelled Folic Acid in Idiopathic Steatorrhea  

PubMed Central

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

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

1963-01-01

93

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

94

Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria  

Microsoft Academic Search

Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain. Therefore, the effects of supplementary treatment with iron or folic acid, given together with chloroquine or pyrimethamine-sulfadoxine (Fansidar®), has been assessed in 600 Gambian children with uncomplicated falciparum malaria. After one month, haematological recovery was significantly better in the group treated with Fansidar® than in

Michaël Boele van Hensbroek; Stephen Morris-Jones; Sarah Meisner; Shabbar Jaffar; Lang Bayo; Raduwan Dackour; Christine Phillips; Brian M. Greenwood

1995-01-01

95

Effects of Dietary Supplements of Folic Acid and Vitamin B12 on Metabolism of Dairy Cows in Early Lactation1  

Microsoft Academic Search

The present experiment was undertaken to deter- mine the effects of dietary supplements of folic acid and vitamin B12 given from 3 wk before to 8 wk after calving on lactational performance and metabolism of 24 mul- tiparous Holstein cows assigned to 6 blocks of 4 cows each according to their previous milk production. Sup- plementary folic acid at 0

B. Graulet; J. J. Matte; A. Desrochers; L. Doepel; M.-F. Palin; C. L. Girard

2007-01-01

96

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation  

Microsoft Academic Search

PurposeHyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function.

Kam S Woo; Ping Chook; Lindy L. T Chan; Alice S. P Cheung; Wing H Fung; M. u Qiao; Yvette I Lolin; G. N Thomas; John E Sanderson; Con Metreweli; David S Celermajer

2002-01-01

97

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

PubMed

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

Amarin, Zouhair O; Obeidat, Ahmed Z

2010-07-01

98

Prevalence of Anaemia, Deficiencies of Iron and Folic Acid and Their Determinants in Ethiopian Women  

PubMed Central

A cross-sectional community-based study with analytic component was conducted among Ethiopian women during June-July 2005 to assess the magnitude of anaemia and deficiencies of iron and folic acid and to compare the factors responsible for anaemia among anaemic and non-anaemic cases. In total, 970 women, aged 15-19 years, were selected systematically for haematological and other important parameters. The overall prevalence of anaemia, iron deficiency, iron-deficiency anaemia, deficiency of folic acid, and parasitic infestations was 30.4%, 50.1%, 18.1%, 31.3%, and 13.7% respectively. Women who had more children aged less than five years but above two years, open-field toilet habits, chronic illnesses, and having intestinal parasites were positively associated with anaemia. Women who had no formal education and who did not use contraceptives were negatively associated with anaemia. The major determinants identified for anaemia were chronic illnesses [adjusted odds ratio (AOR)=1.1, 95% confidence interval (CI) 1.15-1.55), deficiency of iron (AOR=0.4, 95% CI 0.35-0.64), and deficiency of folic acid (AOR=0.5, 95% CI 0.50-0.90). The odds for developing anaemia was 1.1 times more likely among women with chronic illnesses, 60% more likely in the iron-deficient and 40% more likely in the folic acid-deficient than their counterparts. One in every three women had anaemia and deficiency of folic acid while one in every two had iron deficiency, suggesting that deficiencies of both folic acid and iron constitute the major micronutrient deficiencies in Ethiopian women. The risk imposed by anaemia to the health of women ranging from impediment of daily activities and poor pregnancy outcome calls for effective public-health measures, such as improved nutrient supplementation, health education, and timely treatment of illnesses.

2010-01-01

99

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

Microsoft Academic Search

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

DB Mime

100

Folic acid blinded trial in identical twins with fragile X syndrome.  

PubMed Central

Monozygous twin 14-year-old mentally retarded boys with the fragile X syndrome were treated either with 10 mg folic acid by mouth daily or with a placebo for three test periods of 3-month duration each in a blind study. For each twin, tests of cognitive functioning, reading, spelling, and math skills, and linguistic and perceptual skills were compared. Although there was considerable variation in performance on these tests during the two baseline periods, there were no observable beneficial effects of therapy. The routine use of folic acid in patients with established mental retardation and the fragile X syndrome is not indicated.

Rosenblatt, D S; Duschenes, E A; Hellstrom, F V; Golick, M S; Vekemans, M J; Zeesman, S F; Andermann, E

1985-01-01

101

In vivo folic acid supplementation partially corrects in vitro methotrexate toxicity in patients with Down syndrome.  

PubMed

Patients with Down syndrome have been found to have characteristic in vivo and in vitro methotrexate toxicity. The in vitro methotrexate toxicity characteristic of Down syndrome can be diminished by the in vivo administration of supplemental high doses of folic acid. A possible explanation for the increased sensitivity to methotrexate which has been documented in patients with Down syndrome may be due to imbalances in nucleotide pools which result from a gene dosage effect and to greater methylation demands. Supplemental folic acid may be beneficial by virtue of a down-regulation of excess gene activity and may also provide needed monocarbons. PMID:7734380

Peeters, M A; Rethore, M O; Lejeune, J

1995-03-01

102

Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial1-4  

Microsoft Academic Search

Background: There are no large randomized trials of the effect of folic acid dosing regimens on blood folate and homocysteine con- centrations. Objective: We aimed to evaluate the changes in folate and homo- cysteine concentrations in response to different folic acid doses and to withdrawal in young women not exposed to other sources of folic acid. Design: Women (n 1108)

Ling Hao; Quan-He Yang; Zhu Li; Lynn B Bailey; Jiang-Hui Zhu; Dale J Hu; Bo-Lan Zhang; J David Erickson; Le Zhang; Jacqueline Gindler; Song Li; Robert J Berry

103

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice  

PubMed Central

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-? in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells.

Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

2006-01-01

104

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

Microsoft Academic Search

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

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

2011-01-01

105

The adaptive transport of folic acid in the intestine of laying hens with increased supplementation of dietary folic acid.  

PubMed

Different aspects of folic acid (FA) transport in the intestine of the laying hen have been characterized. Less is known about the adaptive response of this process to a dietary challenge. To this end, a study was conducted to evaluate the effect of increased dietary FA supplementation on the rate of intestinal FA transport and the expression of the intestinal folate transporter genes, the proton-coupled folate transporters (PCFT) and the reduced folate carrier (RFC), in the laying hen. Twenty-four Shaver White hens at 34 wk of age were randomly assigned to receive 1 of 3 dietary treatments: 1) basal diet with no supplemental folate (n = 8), 2) basal diet + 10 mg/kg of crystalline FA (n = 8), and 3) basal diet + 100 mg/kg of crystalline FA (n = 8). A completely randomized design with 3 dietary treatments was used. Production performance was not affected by FA supplementation; however, egg and plasma folate concentrations increased (P < 0.001), whereas plasma homocysteine concentrations decreased (P < 0.011) in birds fed 10 or 100 mg of FA/kg of diet, relative to controls. Mucosal to serosal uptake of FA in the duodenum was decreased (P < 0.002), but the mRNA levels of the duodenal PCFT and RFC genes were not affected when birds were fed 10 or 100 mg of FA/kg of diet. In the jejunum, the mucosal to serosal uptake of FA, as well as the mRNA levels of the PCFT and RFC genes, were not influenced by increased FA supplementation. Overall, increased dietary levels of FA resulted in decreased transport of FA in the duodenum but not in the jejunum of laying hens. This decrease was not associated with decreased mRNA expression of the duodenal PCFT and RFC genes. Therefore, a posttranscriptional or translational adaptation of the intestinal folate transporters may be involved in the much lower transport of FA in the duodenum of laying hens during increased dietary supplementation of FA. PMID:22184437

Tactacan, G B; Rodriguez-Lecompte, J C; O, K; House, J D

2012-01-01

106

Bacteriophage T4 baseplate components. I. Binding and location of the folic acid.  

PubMed Central

Two different proteins with high affinities for the pteridine ring of folic acid have been used to determine the location of this portion of the folate molecule in the tail plate of T4D and other T-even bacteriophage particles. The two proteins used were (i) antibody specific for folic acid and (ii) the folate-binding protein from bovine milk. Both proteins were examined for their effect on various intact and incomplete phage particles. Intact T2H was weakly inactivated by the antiserum but not by the milk protein. No other intact T-even phage, including T4D, was affected by these two proteins. When incomplete T4D particles were exposed in an in vitro morphogenesis system, it was found that neither of the two proteins affected either the addition of the long tail fibers to fiberless particles or the addition of tail cores to tail plates. On the other hand, these two proteins specifically blocked the addition of T4D gene 11 product to the bottom of T4D baseplates. After the addition of the gene 11 protein, these two reagents did not inhibit the further addition of the gene 12 protein to the baseplate. It can be concluded that the phage folic acid is a tightly bound baseplate constituent and that the pteridine portion of the folic acid is largely covered by the gene 11 protein.

Kozloff, L M; Lute, M; Crosby, L K

1975-01-01

107

Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid  

PubMed Central

Background: Magnetic nanoparticles show great promise for use as tools in a wide variety of biomedical applications. The purpose of this study was to investigate the potential effects of methacrylamido-folic acid (Ma-Fol)-modified magnetic nanoparticles on 5RP7 (H-ras-transformed rat embryonic fibroblasts) and NIH/3T3 (normal mouse embryonic fibroblasts). Methods: The cytotoxicity and viability of 5RP7 and NIH/3T3 cells were detected. The percentage of cells undergoing apoptosis was analyzed by flow cytometry using Annexin V-fluorescein isothiocyanate staining. Nanoparticle internalization into 5RP7 and NIH/3T3 cells was visualized by transmission electron microscopy. Conclusion: In this study, folic acid coupled to the surface of iron oxide for selective binding to cancer cells and immobilized the surfaces of magnetic nanoparticles. This complex improves cell internalization and targeting of cancer cells. We detected increased apoptosis using flow cytometry and transmission electron microscopy. Results: Folic acid modification of magnetic nanoparticles could be used to facilitate uptake to specific cancer cells for cancer therapy and diagnosis. Our results showed that the uptake of folic-acid modified nanoparticles by 5RP7 cancer cells was also much higher than that of 3T3 cells. This modification can be used for successful targeting of cancer cells expressing the folate receptor.

Saltan, Nagehan; Kutlu, H Mehtap; Hur, Deniz; Iscan, Arzu; Say, R?dvan

2011-01-01

108

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

109

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

Microsoft Academic Search

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

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

110

Biochemical Study on the Protective Role of Folic Acid in Rabbits Treated with Chromium (VI)  

Microsoft Academic Search

Deleterious effects of chromium (VI) compounds are diversified affecting almost all the organ systems in a wide variety of animals. Therefore, the present study was carried out to determine the effectiveness of folic acid (FA) in alleviating the toxicity of chromium (VI) on certain biochemical parameters, lipid peroxidation, and enzyme activities of male New Zealand white rabbits. Six rabbits per

FATMA M. EL-DEMERDASH; MOKHTAR I. YOUSEF; FATHIA A. M. ELASWAD

2006-01-01

111

Knowledge about folic acid and the prevention of neural tube defects in two general practice populations.  

PubMed Central

Knowledge about the link between folic acid supplementation in pregnancy and the prevention of neural tube defects was assessed in women from two contrasting general practices using a questionnaire. The persisting lack of awareness, particularly in the more at-risk group from the inner city area, lends support to the argument in favour of the fortification of flour.

Krischer, J

1997-01-01

112

Maternal trace elements, vitamin B12, vitamin A, folic acid, and fetal malformations  

Microsoft Academic Search

The demonstrated teratogenicity of maternal zinc deficiency in rats has led to burgeoning interest in zinc and other trace elements as important factors in embryonic development. Levels of zinc, copper, manganese, magnesium, folic acid, vitamin B12 and vitamin A were evaluated at the beginning of pregnancy in the plasma of pregnant women who later delivered a malformed newborn. Fetal chromosomal

Claude Stoll; Béatrice Dott; Yves Alembik; Christian Koehl

1999-01-01

113

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...

114

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

Microsoft Academic Search

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

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

2007-01-01

115

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

116

Protective Effects of Prenatal Administration of Folic Acid on Retinoic Acid-Induced Cellular Damages of Meckel's Cartilage in Rats  

Microsoft Academic Search

common congenital deformities. Meckel's cartilage plays a major role in the development of the mandible and is highly susceptible to maternal teratogenic drug use. We therefore investigated possible protective effects of prenatal administration of folic acid on a retino- ic-acid induced maxillofacial defect model. Sprague-Dawley pregnant female rats (n = 36) were used in this study. Retinoic acid was administered

Deniz Firat; Leyla Kuntsal; Yigit Sirin

2005-01-01

117

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

118

Folic acid enhances early functional recovery in a piglet model of pediatric head injury.  

PubMed

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. PMID:21212637

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

2010-01-01

119

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

120

Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged >=60 y in the United States1234  

PubMed Central

Background: Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer. Objective: The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged ?60 y. Design: Surplus sera were analyzed with the use of data from the National Health and Nutrition Examination Survey (NHANES) 2001–2002, a cross-sectional, nationally representative survey (n = 1121). Results: UMFA was detected in 38% of the population, with a mean concentration of 4.4 ± 0.6 nmol/L (median: 1.2± 0.2 nmol/L). The group with UMFA (UMFA+) had a significantly higher proportion of folic acid supplement users than did the group without UMFA (60% compared with 41%). UMFA+ men and women also had higher supplemental and total (food + supplements) folic acid intakes than did their counterparts without UMFA. Forty percent of the UMFA+ group was in the highest quartile of total folic acid intake, but total folic acid intake was only moderately related to UMFA concentrations (r2 = 0.07). Serum folate concentrations were significantly higher in the UMFA+ group and were predictive of UMFA concentrations (r2 = 0.15). Serum 5-methyltetrahydrofolate and vitamin B-12 concentrations were higher in the UMFA+ group, whereas there was no difference between the 2 UMFA groups in red blood cell folate, serum homocysteine, or methylmalonic acid concentrations. Conclusions: Approximately 40% of older adults in the United States have UMFA that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted.

Mills, James L; Yetley, Elizabeth A; Gahche, Jaime J; Pfeiffer, Christine M; Dwyer, Johanna T; Dodd, Kevin W; Sempos, Christopher T; Betz, Joseph M; Picciano, Mary Frances

2010-01-01

121

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

NASA Astrophysics Data System (ADS)

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

Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

2013-11-01

122

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

123

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

NASA Astrophysics Data System (ADS)

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

Teow, Yiwei; Valiyaveettil, Suresh

2010-12-01

124

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

SciTech Connect

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

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

1990-01-01

125

Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease  

Microsoft Academic Search

ObjectivesWe evaluated the effect of therapy with folic acid and cobalamin on coronary endothelial function, expressed as a change in volumetric coronary blood flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD).

Frank F Willems; Wim R. M Aengevaeren; Godfried H. J Boers; Henk J Blom; Freek W. A Verheugt

2002-01-01

126

Folic Acid for the Prevention of Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation  

MedlinePLUS

... the 5 May 2009 issue of Annals of Internal Medicine (volume 150, pages 626-631 and pages 632- ... by eating folic acid–forti?ed food. Annals of Internal Medicine Summaries for Patients I-50© 2009 American College ...

127

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

PubMed

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

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

2011-02-01

128

Monoamine concentrations changes in the PTU-induced hypothyroid rat brain and the ameliorating role of folic acid.  

PubMed

Thyroid hormones are recognized as the key metabolic hormones that play a critical role in the development of central nervous system (CNS) throughout life. The present study was designed to determine the changes in brain monoamine concentrations in 6-n-propyl thiouracil (PTU)-induced hypothyroid rats, in addition to the ameliorating role of folic acid treatment. Fifty male albino rats were equally divided into five groups; first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which the rats received PTU in drinking water for 6 weeks. The fourth and fifth groups were co- and post-treated folic acid groups with hypothyroid rats, respectively. Our results revealed that serotonin and norepinephrine concentrations were significantly decreased in the hypothalamus and cortex, while it significantly increased in the hippocampus of hypothyroid rats when compared with control group. Serotonin and norepinephrine concentrations were decreased in hypothalamus and cortex in co- and post-treated folic acid groups with hypothyroid rats, while the concentration of dopamine were significantly increased in the hypothalamus and hippocampus of the hypothyroid rats and co-treated folic acid group with hypothyroid rats. In cortex, the dopamine concentration was significantly increased in hypothyroid rats and post-treated folic acid group with hypothyroid rats, while it significantly decreased in co-treated folic acid group with hypothyroid rats when compared with the control group. Also, our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state by withdrawing PTU from the drinking water. PMID:21478293

Tousson, E; Ibrahim, W; Arafa, N; Akela, M A

2012-03-01

129

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese\\/diabetic mice  

Microsoft Academic Search

Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 ?g\\/kg\\/day for 4 weeks) on aortic relaxation was investigated using obese\\/diabetic (+db\\/+db) mice and lean littermate (+db\\/+m) mice. Acetylcholine-induced relaxation in +db\\/+db mice was less than

Sai Wang Seto; Tsz Yan Lam; Penelope Mei Yu; Wayne Yuk Wai Lee; Alice Lai Shan Au; Christina Chui Wa Poon; Rachel Wai Sum Li; Shun Wan Chan; John Hok Keung Yeung; George Pak Heng Leung; Simon Ming Yuen Lee; Sai Ming Ngai; Yiu Wa Kwan

2010-01-01

130

Effect of Iron/Folic Acid Supplementation on the Outcome of Malaria Episodes Treated with Sulfadoxine-Pyrimethamine  

PubMed Central

Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.

Black, Robert E.; Kabole, Ibrahim; Dhingra, Usha; Ramsan, Mahdi

2014-01-01

131

Bioinspired nanodevice based on the folic acid/titanium dioxide system.  

PubMed

A new bioinspired nanomaterial has been obtained by chemisorption of folic acid onto nanocrystalline titanium dioxide. The organic chromophore is linked with the semiconductor surface via the glutamate chain and anchored with the carboxylate group. The geometry and electronic structure of the chromophore was studied in detail with DFT. Photoelectrochemical studies revealed photosensitization of the new material towards visible light. The photoelectrodes composed of the folic acid/titanium dioxide hybrid material generated photocurrent over a 300-600-nm window. Moreover, the direction of the photocurrent could be changed from anodic to cathodic and vice versa by application of the appropriate photoelectrode potential. Photoelectrochemical and spectroscopic studies allowed the elucidation of the mechanism of photocurrent switching. Photoelectrodes composed of folate-modified titanium dioxide may serve as a simple model of optoelectronic switches and may constitute the basis for molecular photoelectronic devices. PMID:17465404

Gaweda, Sylwia; Stochel, Grazyna; Szaci?owski, Konrad

2007-05-01

132

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

PubMed

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

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

2013-10-01

133

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

Microsoft Academic Search

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

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

2010-01-01

134

Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST)  

Microsoft Academic Search

BACKGROUND: Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (?g\\/d) for adult pregnant women. The

Cathrine Hoyo; Amy P Murtha; Joellen M Schildkraut; Michele R Forman; Brian Calingaert; Wendy Demark-Wahnefried; Joanne Kurtzberg; Randy L Jirtle; Susan K Murphy

2011-01-01

135

Immobilization of folic acid on Eu3+-doped nanoporous silica spheres.  

PubMed

Folic acid (FA) was immobilized on Eu(3+)-doped nanoporous silica spheres (Eu:NPSs) through mediation of the 3-aminopropyltriethoxysilane adlayer. The ordered nanopores of Eu:NPS were preserved by the immobilization. The FA-immobilized Eu:NPSs showed the characteristic photoluminescence peak due to interactions between the FA molecules and Eu(3+) ions, and highly dispersed stability in phosphate buffered saline. PMID:21706092

Tagaya, Motohiro; Ikoma, Toshiyuki; Yoshioka, Tomohiko; Xu, Zhefeng; Tanaka, Junzo

2011-08-01

136

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

137

THE INFLUENCE OF "FOLIC ACID" ON SPONTANEOUS BREAST CANCERS IN MICE.  

PubMed

Complete regressions of spontaneous breast cancers in mice were observed in 38 among 89 animals (43 per cent.). The treatment consisted of daily intravenous injections of 5 micrograms of l. casei factor ("folic acid"). The treated animals lived longer than the controls, especially the healed mice. The incidence of the development of new tumors was decreased among the treated mice as compared with the controls. PMID:17758597

Leuchtenberger, R; Leuchtenberger, C; Laszlo, D; Lewisohn, R

1945-01-12

138

Effect of folic acid and tetrahydrofolate on tissue arsenic level in rat  

Microsoft Academic Search

Quest is still going on for a cheap, effective, and easily available remedy for chronic arsenic toxicity. This study was designed to investigate the effects of folic acid and tetrahydrofolate in lowering the arsenic burden in tissues. Rats received arsenic at 700 µg\\/day by gavage for 28 days except the control group. Arsenic accumulation was significantly lowered (p<0.05), in liver,

Mir Misbahuddin

2010-01-01

139

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

140

Short-Term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes  

Microsoft Academic Search

Background: Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes. These abnormalities might be secondary to increased plasma concentrations of homocysteine. We sought to determine whether oral folic acid supplementation, by lowering homocysteine levels, enhanced endothelial function and reduced arterial stiffness in type 2 diabetes.Methods: Twenty-six type 2 diabetic patients (age 56.5 ± 0.9 years, diabetes duration

Arduino A. Mangoni; Roy A. Sherwood; Belinda Asonganyi; Cameron G. Swift; Stephen Thomas; Stephen H. D. Jackson

2005-01-01

141

A sustained folic acid release system based on ternary magnesium\\/zinc\\/aluminum layered double hydroxides  

Microsoft Academic Search

This study first synthesized and characterized the ternary magnesium\\/zinc\\/aluminum layered double hydroxides (Mg\\/Zn\\/Al-LDHs)\\u000a intercalated with folic acid. We prepared the ternary (Mg, Zn, Al) LDH carrier by the introduction of zinc, because magnesium\\u000a and zinc are both vital minerals of human body. The nanohybrids were prepared by the method of coprecipitation and were characterized\\u000a by powdered sample X-ray diffraction (XRD),

Rong Xiao; Wenrui Wang; Longlong Pan; Rongrong Zhu; Yongchun Yu; Huiping Li; Hui Liu; Shi-Long Wang

2011-01-01

142

High folate levels in Aboriginal children after subsidised fruit and vegetables and mandatory folic acid fortification.  

PubMed

Objective: To evaluate the impact of a fruit and vegetable (F&V) subsidy program for disadvantaged Aboriginal children in Australia, implemented alongside the introduction of mandatory folic acid fortification of bread-making flour. Methods: A before-and-after evaluation was undertaken of a F&V subsidy program at three Aboriginal community-controlled health services in New South Wales. The program provided a weekly box of subsidised F&V linked to preventive health services and nutrition promotion for families. In this analysis, red blood cell (RBC) folate was assessed together with self-reported dietary intake at baseline and 12 months later in a cohort of 125 children (aged 0-17 years). Results: No children had low RBC folate at baseline or at follow-up; however, 33 children (26%) exceeded the reference range of RBC folate at baseline and 38 children (30%) exceeded the reference range at follow-up. Mean RBC folate levels increased substantially in children at follow-up (mean RBC folate z-score increased +0.55 (95%CI 0.36-0.74). Change in F&V intake (p=0.196) and mean bread intake (p=0.676) were not statistically significant predictors for change in RBC folate levels. Conclusions: RBC folate levels increased among these disadvantaged Aboriginal children following mandatory folic acid fortification and participation in a subsidised F&V program. Even before mandatory folic acid fortification, none of these children had low RBC folate. Implications: The effect on health of mandatory fortification of foods with folate is not clear, hence, ongoing population-based monitoring of folate levels to assess the impact of mandatory folic acid fortification is important. PMID:24890482

Black, Andrew P; Vally, Hassan; Morris, Peter; Daniel, Mark; Esterman, Adrian; Smith, Fiona; O'Dea, Kerin

2014-06-01

143

Antitumoral activity of PEG–gemcitabine prodrugs targeted by folic acid  

Microsoft Academic Search

Gemcitabine, 2?,2?-difluoro-2?-deoxycytidine (dFdC), is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by short plasma half-life, rapid metabolism and low selectivity towards tumor tissue. To overcome these limits, bioconjugates of gemcitabine were studied using poly(ethylene glycol) as polymeric carrier. Two types of conjugates were prepared, non-targeted and folic acid targeted conjugates. The

Gianfranco Pasut; Fabiana Canal; Lisa Dalla Via; Silvia Arpicco; Francesco M. Veronese; Oddone Schiavon

2008-01-01

144

Association of microtia with maternal obesity and periconceptional folic acid use.  

PubMed

The study objective was to examine the association of microtia with maternal intake of folic-acid-containing supplements and obesity. The study data included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Non-syndromic cases of microtia were compared to non-malformed, population-based liveborn control infants, by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included maternal race/ethnicity, education, and study site. Maternal obesity was only weakly associated with microtia. Maternal periconceptional intake of folic-acid-containing vitamin supplements reduced the risk for microtia, but only among non-obese women (OR: 0.63; 95% CI: 0.44-0.91). The reduced risk was stronger when analyses were restricted to isolated cases (OR: 0.51; 95% CI: 0.34-0.77), and it was independent of the level of maternal dietary folate intake. Adjusting for maternal race/ethnicity did not reveal alternative interpretations of this association. This analysis suggests that maternal periconceptional intake of folic-acid-containing supplements may provide protection from microtia for non-obese women. PMID:20949601

Ma, Chen; Carmichael, Suzan L; Scheuerle, Angela E; Canfield, Mark A; Shaw, Gary M

2010-11-01

145

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

146

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

PubMed Central

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

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

2013-01-01

147

Folic acid modulates eNOS activity via effects on posttranslational modifications and protein-protein interactions?  

PubMed Central

Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein–protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment.

Taylor, Sarah Y.; Dixon, Hannah M.; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

2013-01-01

148

Folic acid modulates eNOS activity via effects on posttranslational modifications and protein-protein interactions.  

PubMed

Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein-protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment. PMID:23796957

Taylor, Sarah Y; Dixon, Hannah M; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

2013-08-15

149

Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis.  

PubMed

The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with folic acid and tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 498, 655 and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis and Wnt pathways, was identified in the livers of rats treated with folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and tributyrin has stronger chemopreventive effect than each of the compounds alone. PMID:24302446

Guariento, Aline H; Furtado, Kelly S; de Conti, Aline; Campos, Adriana; Purgatto, Eduardo; Carrilho, Jéssica; Shinohara, Elvira Maria Guerra; Tryndyak, Volodymyr; Han, Tao; Fuscoe, James C; Ross, Sharon A; Beland, Frederick A; Pogribny, Igor P; Moreno, Fernando S

2014-07-01

150

Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats  

Microsoft Academic Search

This study was designed to examine the effects of supplementation with folic acid and amino acids in dams that consumed ethanol\\u000a during gestation and lactation to see whether there is an improvement in the intestinal absorption of zinc in pup rats on\\u000a the 21st day after birth. The rats were randomized into two groups: Ethanol-rats (EG) were administered ethanol during

E. Tavares; O. Carreras; A. Gómez-Tubío; D. Murillo; M. L. Murillo

2000-01-01

151

A study on gingival enlargement and folic acid levels in phenytoin-treated epileptic patients: Testing hypotheses  

PubMed Central

Background: There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the antiepileptic therapy in the prevention of antiepileptic drug-induced gingival enlargement. However, studies in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin-induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy. The statistical analysis was done using t-test and the baseline serum folate levels and the serum folate levels obtained after 6 months of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. Methods: A total of 25 patients aged between 18 and 50 years, clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was done prior to the start of and after 6 months of phenytoin therapy. Results: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin-induced gingival enlargement. Conclusions: The results of the study suggest a higher incidence of gingival enlargement in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.

Singh Nayyar, Abhishek; Khan, Mubeen; Vijayalakshmi, K. R.; Subhas, G. T.; Nataraju, B.; Anitha, M.

2013-01-01

152

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

PubMed Central

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 years 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.

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.

2012-01-01

153

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

2013-03-01

154

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

PubMed

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 >or=500 microg/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 microg/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. PMID:19022952

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

2008-12-01

155

Folic acid supplementation on homocysteine levels in children taking antiepileptic drugs: A randomized controlled trial  

PubMed Central

Objectives: To assess the level of homocysteine (tHcy) in children taking AEDs and to study whether daily oral supplementation of folic acid for 1 month will reduce the tHcy level. Materials and Methods: This was a double-blinded, randomized control trial conducted in Institute of Maternal and Child Health, Kozhikode, India. Totally 60 children were recruited and of them, 48 were enrolled. Of these children, 32 were assigned to the experimental group and 16 to the control group. Baseline data collection and tHcy estimation were done. One mg folic acid tablets were given to the experimental group and placebo tablets to the control group for 30 days. tHcy levels were re-estimated after 1 month follow-up. Statistical significance was tested by ?2 test, and paired and unpaired t-tests, as appropriate. Correlation was tested by Pearson correlation test and P value less than 0.05 was taken as the cut-off for statistical significance. Results: Baseline plasma tHcy concentrations in both groups were comparable [11.90 (6.3) and 13.02 (2.4) ?mol/l, respectively]. During the follow-up period, no increase in seizure episodes or no serious adverse reactions were noticed in either group. The reduction of tHcy in the experimental group was 1.92 ?mol/l (P = 0.04) and in the control group, there was an increase of 1.05 ?mol/l (P = 0.16). Conclusions: In children on AED treatment, folic acid supplementation may reduce tHcy level and thus reduce CVD risk.

Jeeja, Mathummal Cherumanalil; Jayakrishnan, Thayyil; Narayanan, Puthiya Veettil; Kumar, Mathur Sreedharan Vinod; Thejus, Thayyil; Anilakumari, Vadakay Purayil

2014-01-01

156

Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells  

NASA Astrophysics Data System (ADS)

A new approach towards the design of folic acid conjugated magnetic nanoparticles for enhancing their site specific intracellular uptake against a folate receptor overexpressing cancer cells is reported. Magnetite nanoparticles were prepared by coprecipitation from an Fe3+ and Fe2+ solution followed by surface modification with 2-carboxyethyl phosphonic acid to form carboxyl group terminated nanoparticles. Then folic acid and fluorescein isothiocyanate (FITC) were conjugated with carboxylic acid functionalized magnetite nanoparticles using 2,2'-(ethylenedioxy)-bis-ethylamine. These folate-conjugated nanoparticles were characterized in terms of their size by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Surface functional groups and surface composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS), respectively. Vibration sample magnetometry (VSM) measurements showed the superparamagnetic nature of the particles at room temperature. Folate-conjugated magnetic nanoparticles are noncytotoxic and receptor mediated internalization by HeLa and B16 melanoma F0 cancer cells was confirmed by flow cytometry and confocal microscopy.

Mohapatra, S.; Mallick, S. K.; Maiti, T. K.; Ghosh, S. K.; Pramanik, P.

2007-09-01

157

Biopolymer produced by fermenting the extract of soybean with folic acid and a composition containing thereof  

US Patent & Trademark Office Database

Provided are a folyl extract of fermented soybean (EFS) produced by fermenting a culture including a folic acid and soybean extract by using a microorganism, and a composition including the folyl EFS. The folyl EFS has an anti-histamine effect, an anti-allergic effect, a calcium-absorption-promotion effect, a bone-growth-promotion effect, a cell growth promotion effect, a collagen biosynthesis promotion effect, a wrinkle improvement effect, and an UV-induced cell damage inhibition effect. Accordingly, the folyl EFS can be used in a skin external application or cosmetic composition, a health supplement food composition, a feed composition, and a pharmaceutical composition.

2013-04-30

158

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

PubMed

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

Hamner, Heather C; Tinker, Sarah C

2014-04-01

159

[Radioimmunologic study of the plasma concentrations of folic acid and various antiepileptic preparations during the treatment of epileptic patients].  

PubMed

Radioimmunoassay of folic acid, phenobarbital, and difenine done in 78 epileptic patients identified the correlation between the content of these substances in the blood plasma and the side effects during antiepileptic therapy. It was established that a fall in the content of folic acid following the attack and in the interictal period is of a transitory nature, in contrast to a steady deficiency caused by anticonvulsants. A decrease in the content of folic acid to the lower limit of normal was followed by a reduced incidence of epileptic fits. On the contrary, the larger the concentrations of blood folates, the greater the risk of paroxysm recurrence. The results of the study offer the prerequisites for the prophylaxis of side effects and the effective therapy with anticonvulsant agents. PMID:6880514

Boldarov, A I; Ma?zelis, M Ia; Va?ntrub, M Ia; Zabludovski?, A L; Gvirtsman, L E

1983-01-01

160

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

Microsoft Academic Search

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

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

1998-01-01

161

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

162

Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease  

Microsoft Academic Search

Recent epidemiological and clinical data suggest that persons with low folic acid levels and elevated homocysteine levels are at increased risk of Alzheimer's disease (AD), but the underlying mechanism is unknown. We tested the hypothesis that im- paired one-carbon metabolism resulting from folic acid defi- ciency and high homocysteine levels promotes accumulation of DNA damage and sensitizes neurons to amyloid

Inna I. Kruman; T. S. Kumaravel; Althaf Lohani; Ward A. Pedersen; Roy G. Cutler; Yuri Kruman; Norman Haughey; Jaewon Lee; Michele Evans; Mark P. Mattson

2002-01-01

163

Effect of Folic Acid and Betaine Supplementation on Flow-Mediated Dilation: A Randomized, Controlled Study in Healthy Volunteers  

PubMed Central

Objectives: We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status—its main determinant—is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design: This was a randomized, placebo-controlled, double-blind, crossover study. Setting: The study was performed at Wageningen University in Wageningen, the Netherlands. Participants: Participants were 39 apparently healthy men and women, aged 50–70 y. Interventions: Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures: At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results: Folic acid supplementation lowered fasting homocysteine by 20% (?2.0 ?mol/l, 95% confidence interval [CI]: ?2.3; ?1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (?1.2 ?mol/l; ?1.6; ?0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ?0.4 FMD% (95%CI, ?1.2; 0.4) and ?0.1 FMD% (?0.9; 0.7), respectively. Conclusions: Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.

Olthof, Margreet R; Bots, Michiel L; Katan, Martijn B; Verhoef, Petra

2006-01-01

164

First report for voltammetric determination of methyldopa in the presence of folic acid and glycine.  

PubMed

In this study, a carbon paste electrode modified with TiO2 nanoparticles and ferrocene monocarboxylic acid (FM) was used to prepare a novel electrochemical sensor. The objective of this novel electrode modification was to seek new electrochemical performances for the detection of methyldopa in the presence of folic acid and glycine. The peak potentials recorded in a phosphate buffer solution (PBS) of pH7.0 were 325, 750 and 880 mV vs. Ag/AgCl/KCl (3.0M) for methyldopa, folic acid and glycine, respectively. Under the optimum pH of 7.0, the oxidation of methyldopa occurred at a potential about 160 mV less positive than that of the unmodified carbon paste electrode (CPE). The response of catalytic current with methyldopa concentration showed a linear relation in the range from 2.0×10(-7) to 1.0×10(-4)M with a detection limit of 8.0 (± 0.2)×10(-8)M. PMID:24433900

Molaakbari, Elahe; Mostafavi, Ali; Beitollahi, Hadi

2014-03-01

165

Net flux of nutrients across the rumen wall of lactating dairy cows as influenced by dietary supplements of folic acid.  

PubMed

The objective of the present study was to determine whether a dietary supplementation of folic acid, at levels used in our previous studies, would affect ruminal fermentation and the net flux of nutrients across the rumen wall of lactating dairy cows. Approximately 4 wk after calving, 5 lactating multiparous cows were surgically equipped with a ruminal cannula, an ultrasonic flow probe around the right ruminal artery, and indwelling catheters in the right ruminal vein and the ileocolic artery. Cows were fed a total mixed ration served in 7 equal meals per d (i.e., every 3.4 h). The experimental design was an unbalanced crossover arrangement with 3 periods of 4 wk each. The vitamin supplement, incorporated in equal amounts into each meal, was supplied at 0, 3, or 6 mg of folic acid per kg of BW per d. During the last week of each experimental period, blood samples were taken simultaneously from the 2 catheters every 30 min and rumen fluid was collected every 60 min during 2 consecutive meal intervals. Dietary supplementation with folic acid had no effect on milk production (27.2 +/- 1.3 kg/d) or DMI (19.9 +/- 0.7 kg/d), but milk concentrations and yields of total solids, fat, and protein increased linearly with increasing doses of folic acid ingested. Concentrations of folates in rumen fluid and arterial plasma, averaged over time, increased linearly with the dose of folic acid ingested but the net flux of folates across the rumen wall was not different from zero. Concentrations of butyrate in ruminal fluid decreased quadratically with the daily supply in folic acid. Dietary supplements of folic acid had no effect on pH and osmolality of ruminal fluid, nor on ruminal concentrations of lactate, ammonia, acetate, or propionate, total VFA, or microbial counts. The uptake of urea-N by the rumen wall tended to increase quadratically with the dose ingested but net fluxes of other nutrients were not affected by treatments. These results suggest that the effects of folic acid supplements on lactational performance cannot be explained by effects on rumen metabolism. PMID:19923614

Girard, C L; Benchaar, C; Chiquette, J; Desrochers, A

2009-12-01

166

Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks  

PubMed Central

The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’).

Bartfai, Zoltan; Banhidy, Ferenc

2011-01-01

167

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

168

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

169

Small molecule-folic acid modification on nanopatterned PDMS and investigation on its surface property.  

PubMed

Folic acid (or folate, FA) has attracted considerable attention for cancer therapy. As one small molecule, its receptor (folate receptor, FR) is significantly overexpressed on the surface of many human tumor cells compared with normal cells. In this work, physical and chemical coupled modification method, that is the combination of nanoimprinting technique and graft polymerization, was adopted to modify FA on nanopatterned polydimethylsiloxane (PDMS) surface for possible application in micro-nanofluidic cytology. The surface property of differently treated PDMS was characterized by FTIR, AFM and contact angle measurement. AO/PI double staining, cell counting and MTT method were performed to examine the potential influence of FA modified nanopatterned PDMS on human cervical carcinoma (HeLa) cell behavior. Both FA modification and nanostructure have positive effect on the growth and viability of HeLa cells. It is the first time that the small molecule-folic acid was used to immobilize on the surface of PDMS in order to improve its surface property. PMID:24627217

Hu, Yuanyuan; Ma, Binjie; Zhang, Yingying; Wang, Min

2014-06-01

170

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

171

Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.  

PubMed

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation. PMID:22617627

Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

2012-07-01

172

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

173

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

Microsoft Academic Search

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

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

2004-01-01

174

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

PubMed

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

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

2014-01-13

175

Folic Acid  

MedlinePLUS

... pregnancy, it can prevent major birth defects, including: Spina bifida (SPEYE-nuh BIF-ih-duh), which occurs when ... and other functions do not work. Children with spina bifida often have lifelong disabilities. They may also need ...

176

Association of folic acid receptor ? in maternal serum with neural tube defects.  

PubMed

Abstract Objective: To evaluate whether serum folic receptor ? levels are changed in women whose previous pregnancies were complicated with neural tube defects (NTDs). Methods: This was a case-control study that included 41 women as the control group who had previously had at least one healthy pregnancy and 37 women as the study group who had a previous pregnancy complicated with NTDs. Blood samples were obtained from all of the participants six weeks after the termination of pregnancy or delivery of a baby. Serum folate receptor ? concentrations were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: The mean concentrations of serum folate receptor ? were significantly lower in the NTD cases compared to those in the control group (p?=?0.02). There was no significant difference in mean serum folate titers between the NTD cases and the control group (p?=?0.07). Conclusion: Low serum folic acid receptor ? levels in the current study did not appear to be a regulatory marker of maternal folate homeostasis per se but rather a factor that contributed to the development of NTDs. PMID:24094304

Celik, Ebru; Karaer, Abdullah; Turkcuoglu, Ilgin; Turhan, Ugur; Gungoren, Arif; Taskapan, Cagatay; Ozyalin, Fatma; Berker, Bulent

2014-07-01

177

Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia.  

PubMed Central

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation.

Walzer, P D; Kim, C K; Foy, J M; Linke, M J; Cushion, M T

1988-01-01

178

Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia.  

PubMed

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation. PMID:3258144

Walzer, P D; Kim, C K; Foy, J M; Linke, M J; Cushion, M T

1988-01-01

179

Effect of folic acid decorated magnetic fluorescent nanoparticles on the sedimentation of starch molecules  

NASA Astrophysics Data System (ADS)

Ferrite-folic acid (FA) nanohybrids were synthesized and characterized by various analytical tools like Fourier transform infrared spectroscopy, UV-Visible spectroscopy, fluorescence spectroscopy, field emission scanning electron microscopy, X-ray diffraction analysis and vibrating sample measurement techniques. After the nanohybrid formation, both the crystallinity and the magnetization values of ferrite were disturbed due to the surface functionalization of ferrite by FA. The role of nanohybrid on the structure-property relationship of starch, particularly the sedimentation of starch under three different pHs, was evaluated. Again the magnetization value of Fe3O4-FA/starch nanocomposite system was reduced due to the encapsulation effect. The sedimentation velocity of starch under the influence of nanohybrid was enhanced in the acidic medium.

Palanikumar, S.; Kannammal, L.; Meenarathi, B.; Anbarasan, R.

2014-04-01

180

The Interactions between L-Tyrosine Based Nanoparticles Decorated with Folic Acid and Cervical Cancer Cells Under Physiological Flow  

PubMed Central

Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs).

Ditto, Andrew J.; Shah, Kush N.; Robishaw, Nikki K.; Panzner, Matthew J.; Youngs, Wiley J.; Yun, Yang H.

2012-01-01

181

No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine  

Microsoft Academic Search

A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo

Audrey Y. Jung; Yvo Smulders; Petra Verhoef; Frans J. Kok; Henk Blom; Robert M. Kok; Ellen Kampman; Jane Durga; Yiqing Song

2011-01-01

182

Registro Nazionale Malattie Rare: Malformazioni Congenite e Acido Folico (National Register of Rare Diseases: Congenital Malformation and Folic Acid).  

National Technical Information Service (NTIS)

It is estimated that in Italy at least 3% of babies are born with some congenital malformation. Scientific evidence demonstrates that the intake of folic acid by a woman prior the conception and during the early stages of pregnancy plays a role in prevent...

A. Pierini D. Taruscio F. Bianchi P. Salerno

2006-01-01

183

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

NASA Astrophysics Data System (ADS)

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

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

2011-12-01

184

Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Cancer Risk: Results from a Randomized Trial  

PubMed Central

Context Folate, vitamin B6, and vitamin B12 are thought to play an important role in cancer prevention. Objective To evaluate the effect of combined folic acid, vitamin B6, and vitamin B12 treatment on cancer risk in women at high risk for cardiovascular disease. Design, Setting, and Participants In the Women’s Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older with preexisting cardiovascular disease or 3 or more coronary risk factors were randomly assigned to receive either a daily combination of folic acid, vitamin B6, and vitamin B12 or placebo in April 1998, and treated through July 31, 2005 for 7.3 years. Intervention Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 (n=2721) or placebo (n=2721). Main Outcome Measures Confirmed newly diagnosed total invasive cancer. Results A total of 379 women developed invasive cancer (187 in the active group and 192 in the placebo group). Compared with placebo, women receiving combined folic acid, vitamin B6, and vitamin B12 had similar risk of developing total invasive cancer (101.1/10000 person-years vs 104.3/10000 person-years for the active vs placebo group; hazard ratio, 0.97; 95% confidence interval, 0.79–1.18; P=.75), breast cancer (37.8/10000 person-years vs 45.6/10000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.60–1.14; P=.24), and any cancer death (24.6/10000 person-years vs 30.1/10000 person-years; hazard ratio, 0.82; 95% confidence interval, 0.56–1.21; P=.32). Conclusions Combined folic acid, vitamin B6, and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during folic acid fortification era. Trial Registration clinicaltrials.gov Identifier: NCT00000541

Zhang, Shumin M.; Cook, Nancy R.; Albert, Christine M.; Gaziano, J. Michael; Buring, Julie E.; Manson, JoAnn E.

2008-01-01

185

Development and validation of a high performance liquid chromatography method for the simultaneous determination of aspirin and folic acid from nano-particulate systems  

PubMed Central

Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive analytical method exists to simultaneously quantify the two drugs when released from polymer-based nanoparticles. Thus, a rapid, highly sensitive method of high performance liquid chromatography (HPLC) analysis to simultaneously detect low quantities of aspirin (hydrolyzed to salicylic acid, the active moiety) and folic acid released from biodegradable polylactide-co-glycolide (PLGA) copolymer nanoparticles was developed. Analysis was done on a reversed phase C18 column using a photodiode array (PDA) detector at wavelengths of 233 nm (salicylic acid) and 277 nm (folic acid). The mobile phase consisted of acetonitrile ? 0.1% trifluoroacetic acid mixture programmed for a 30 min gradient elution analysis. In the range of 0.1 – 100 ?g/mL, the assay showed good linearity for salicylic acid (R2 = 0.9996) and folic acid (R2 = 0.9998). The method demonstrated good reproducibility, intra- and inter-day precision and accuracy (99.67, 100.1%) and low values of detection (0.03, 0.01 ?g/mL) and quantitation (0.1 and 0.05 ?g/mL) for salicylic acid and folic acid, respectively. The suitability of the method was demonstrated by simultaneously determining salicylic acid and folic acid released from PLGA nanoparticles.

Chaudhary, Abhishek; Wang, Jeffrey

2009-01-01

186

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

2013-03-01

187

Development of ?-polyoxometalate-polypyrrole-Au nanoparticles modified sensor applied for detection of folic acid.  

PubMed

In this work, electrochemically synthesized gold nanoparticles (AuNPs) and ?-polyoxometalate (?-POM) (K7PMO2W9O39·H2O) were simultaneously doped into electropolymerized polypyrrole (PPy) film using the cyclic voltammetry (CV) technique. Scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and CVs were used to characterize the composite films. The PPy-?-POM-AuNPs modified gold (Au) electrode was used to determine folic acid (FA) using square-wave voltammetry (SWV). The modified electrode exhibited excellent electrocatalytic ability to the reduction of FA at 0.3V (vs. SCE) with the electron transfer rate constant (ks) of 1.15×10(-19)s(-1). The common coexisting substances showed no interferences on the response of modified electrode to FA. The modified electrode indicated reproducible behavior and a high level stability during the experiments, making it particularly suitable for the analytical purposes. PMID:24800683

Babakhanian, Arash; Kaki, Samineh; Ahmadi, Mahtab; Ehzari, Hosna; Pashabadi, Afshin

2014-10-15

188

The folic acid absorption test compared with other laboratory tests for malabsorption.  

PubMed

In 25 patients with malabsorption, the folic acid urinary excretion (TRIFA) test was compared with the degree of steatorrhoea, the Schilling test, and the D-xylose test. No correlation was found between the faecal lipid excretion, the Schilling test, and the TRIFA test, whereas the TRIFA test did correlate fairly well with the D-xylose test. It is concluded that the TRIFA test does not replace estimations of faecal lipid excretions in the diagnosis of intestinal malabsorption. As it mainly supplies information about absorptional capacity in the upper small bowel, it is complementary to the Schilling test, which chiefly measures the absorption in the lower intestine. Finally, the TRIFA test has several advantages over the D-xylose test in practical clinical use. PMID:7234510

Elsborg, L

1981-01-01

189

Effect of folic acid supplementation on small-for-gestational-age infants born at term.  

PubMed

The effect of 250 micrograms folic acid (FA)/day or placebo given to 21 small-for-gestational-age infants born at term was studied during the first 3 months of life. The design of the study was double blind with random allocation. No randomization was performed in respect of breast-feeding or formula-feeding with a folate content of 60-70 micrograms/l. No significant differences were observed in haemoglobin concentration, haematocrit, weight and length between FA-supplemented and non-supplemented infants. A negative correlation was demonstrated between gestational age and erythrocyte folate (E-folate) concentration at 1 week. E-folate content was higher when no supplement was given in breast-fed than in formula-fed infants. PMID:2691256

Foged, N; Lillquist, K; Rolschau, J; Blaabjerg, O

1989-10-01

190

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

PubMed

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

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

2014-09-15

191

Fluorescence resonance energy transfer from tryptophan to folic acid in micellar media and deionised water.  

PubMed

The fluorescence resonance energy transfer (FRET) from tryptophan (Trp) to folic acid (FA) in aqueous sodiumdodecyl sulphate, cetyltrimethyl ammonium bromide, and Brij-35 as well as deionised water was investigated using steady state and time resolved fluorescence techniques. The data obtained from steady state fluorescence spectral studies and time resolved measurement indicated that the FRET from Trp to FA occurred most effectively in aqueous sodium dodecyl sulphate micellar solutions. The distance between Trp and FA were evaluated. Binding constant, number of binding sites and thermodynamic parameters were determined for Trp-FA interactions in deionised water. The values of the thermodynamic parameters suggest that the hydrophobic forces and hydrogen bonding are the key interacting forces between Trp-FA interaction. PMID:21288734

Mote, U S; Patil, S R; Bhosale, S H; Han, S H; Kolekar, G B

2011-04-01

192

Improved mechanical and electronic properties of co-assembled folic acid gel with aniline and polyaniline.  

PubMed

Co-assembled folic acid (F) gel with aniline (ANI) (ANI:F = 1:2, w/w) is produced at 2% (w/v) concentration in water/DMSO (1:1, v/v) mixture. The gel is rigid and on polymerization of the gel pieces in aqueous ammonium persulfate solution co-assembled folic acid - polyaniline (F-PANI) gel is formed. Both the co-assembled F-ANI and F-PANI gels have fibrillar network morphology, the fiber diameter and its degree of branching increase significantly from those of F gel. WAXS pattern indicates co-assembled structure with the F fiber at the core and ANI/PANI at its outer surface and the co-assembly is occurring in both F-ANI and F-PANI systems through noncovalent interaction of H-bonding and ? stacking processes between the components. FTIR and UV-vis spectra characterize the doped PANI formation and the MALDI mass spectrometry indicates the degree of polymerization of polyaniline in the range 24-653. The rheological experiments support the signature of gel formation in the co-assembled state and the storage (G') and loss (G?) modulii increase in the order F gel< F-ANI gel < F-PANI gel, showing the highest increase in G' ? 1100% for the F-PANI gel. The stress at break, elasticity, and stiffness also increase in the same order. The dc-conductivity of F-ANI and F-PANI xerogels is 2 and 7 orders higher than that of F xerogel. Besides, the current (I)-voltage (V) curves indicate that the F-xerogel is insulator, but F-ANI xerogel is semiconductor showing both electronic memory and rectification; on the other hand, the F-PANI xerogel exhibits a negative differential resistance (NDR) property with a NDR ratio of 3.0. PMID:24495072

Chakraborty, Priyadarshi; Bairi, Partha; Roy, Bappaditya; Nandi, Arun K

2014-03-12

193

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

PubMed

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

Rabovskaja, Viktoria; Parkinson, Bonny; Goodall, Stephen

2013-01-01

194

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

195

Effects of folic acid and folinic acid on cognitive and motor behaviors in 20-month-old rats.  

PubMed

Old rats had lower plasma concentrations of folates but not of vitamin B12 than young rats. Old rats injected with pharmacological doses of folic acid (5 mg/kg) or folinic acid (2.5 mg/kg) every 2 days for a 32-day period spontaneously alternated above chance levels at the 0-min retention interval whereas old rats injected with placebo did not. Rats injected with folinic acid that had plasma folate concentrations above the median for that group alternated at the 3-min retention interval whereas none of the other subgroups did. These results indicate that supplementation with folinic acid at pharmacological doses may decrease perseverative responding and improve spatial memory in old rats. However, neither vitamin group was improved in motor coordination, grip strength, or spatial learning in a water maze. There was no hyperactivity or loss of body weight following vitamin supplementation. PMID:8451272

Lalonde, R; Joyal, C C; Botez, M I

1993-03-01

196

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

PubMed

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

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

2014-04-01

197

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

198

Dietary Regulation of Glycolytic Enzymes. Vi. Effect of Dietary Sugars and Oral Folic Acid on Human Jejunal Pyruvate Kinase, Phosphofructokinase and Fructosediphosphatase Activities.  

National Technical Information Service (NTIS)

The effects of dietary sugars and oral folic acid on the activities of human jejunal pyruvate kinase, phosphofructokinase and fructosediphosphatase were studied in two normal volunteers and three obese patients. The activities of pyruvate kinase and phosp...

F. B. Stifel, N. S. Rosensweig, R. H. Herman

1970-01-01

199

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

Microsoft Academic Search

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

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

2006-01-01

200

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

201

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

Microsoft Academic Search

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

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

2011-01-01

202

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

Microsoft Academic Search

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

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

1999-01-01

203

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

PubMed

A novel folic acid biosensor has been fabricated using Cu doped SnO2 nanoparticles (NPs) synthesized by a simple microwave irradiation method. Powder XRD and TEM studies confirmed that both the pure and Cu doped SnO2 (Cu: 0, 10, 20wt%) crystallized in tetragonal rutile-type structure with spherical morphology. The average crystallite size of pure SnO2 was estimated to be around 16 nm. Upon doping, the crystallite sizes decreased to 9 nm and 5 nm for 10 and 20wt% Cu doped SnO2 respectively. XPS studies confirmed the electronic state of Sn and Cu to be 4+ and 2+ respectively. Cu (20wt%) doped SnO2 NPs are proved to be a good sensing element for the determination of folic acid (FA). Cu-SnO2 NPs (20wt%) modified glassy carbon electrode (GCE) exhibited the lowest detection limit of 0.024 nM over a wide folic acid concentration range of 1.0 × 10(-10) to 6.7 × 10(-5) M at physiological pH of 7.0. The fabricated sensor is highly selective towards the determination of FA even in the presence of a 100 fold excess of common interferent ascorbic acid. The sensor proved to be useful for the estimation of FA content in pharmaceutical sample with satisfactory recovery. PMID:24981704

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

2014-07-25

204

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

205

Imbalance of folic acid and vitamin B12 is associated with birth outcome: an Indian pregnant women study.  

PubMed

Background/objectives:Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid. Along with folic acid, vitamin B12 is also an important determinant of fetal growth and development. During pregnancy, the increased requirement of folic acid is met with supplementation, while vitamin B12 remains untreated and possibly deficient. The objective of our study was to study the combined effect of maternal plasma folate and vitamin B12, and their ratio on birth anthropometrics.Subjects/methods:We carried out an observational study on 49 full-term pregnant women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate, vitamin B12 and homocysteine in venous blood at 36 weeks of gestation. Neonatal anthropometrics (birth weight, length, head circumference, abdominal circumference, mid arm circumference, chest circumference, triceps skinfold and subscapular skinfold thickness) were measured within 24?h of birth.Results:Maternal plasma folate and vitamin B12 were not correlated to neonatal anthropometrics. The combined association of folate and vitamin B12 expressed as folate to vitamin B12 ratio was correlated to the neonatal anthropometrics. Imbalance in the maternal micronutrients with increasing ratio of folate to vitamin B12 was associated with an increase in plasma homocysteine (P=0.014), lowering of neonatal birth weight (P=0.009), birth length (P=0.034), head circumference (P=0.018) and chest circumference (P=0.009), while no significant association to other anthropometrics was observed.Conclusions:Supplementation of vitamin B12 in addition to supplementation of folic acid in pregnancy may be important for improving birth weight, birth length, head circumference and chest circumference. PMID:24448492

Gadgil, M; Joshi, K; Pandit, A; Otiv, S; Joshi, R; Brenna, J T; Patwardhan, B

2014-06-01

206

Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia: a randomized placebo-controlled trial  

Microsoft Academic Search

Background—Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis due to familial hypercholesterolemia (FH). Methods and Results—In a prospective, randomized, double-blind, placebo-controlled study with crossover design,

Marianne C. Verhaar; Robert M. F. Wever; John J. P. Kastelein; Douwe van Loon; S. Milstein; H. A. Koomans; T. J. Rabelink

1999-01-01

207

No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine  

PubMed Central

A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n?=?105) or placebo treatment (n?=?111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference?=?0.008, 95%CI?=??0.05,0.07, P?=?0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n?=?76; CT, n?=?70; TT, n?=?70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes. ClinicalTrials.gov NCT00110604

Jung, Audrey Y.; Smulders, Yvo; Verhoef, Petra; Kok, Frans J.; Blom, Henk; Kok, Robert M.; Kampman, Ellen; Durga, Jane

2011-01-01

208

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

209

Analytical methods for the determination of folic acid in a polymeric micellar carrier.  

PubMed

Amphiphilic copolymers have been the object of growing scientific interest due to their ability to form polymeric micelles in aqueous environments entrapping lipophilic drugs in their inner core. In this study, polyvinylalcohol substituted with oleic acid was employed as an amphiphilic micellar carrier for folic acid (FA), a model drug similar for its chemical-physical characteristics to methotrexate. In order to investigate the stability of the polymeric micelles, the drug incorporation and the kinetic aspects of drug release from these systems, selective analytical methods are required. The development of three analytical methods suitable for selectively identifying and reliably determining FA contained in the micelles and in the delivery systems is reported. UV derivative (first and second order) spectrophotometry was first applied to the aqueous solution of the FA containing micelles obtained at pH 9.0 and provided a characteristic spectral profiling with sharp peaks, related to the analyte, whose amplitude was used for quantitative application. A second approach involved a solid phase extraction (strong anion exchanger), which provided an effective clean up of the FA micelles solution, allowing accurate analysis to be performed also by a conventional spectrophotometric method. A RP-HPLC method, selectively supplying the FA separation from the micelles' components, was then used as a reference method to determine the accuracy of the spectrophotometric methods. These methods were applied to various micelle composition and to the delivery system study. PMID:12899985

Andrisano, V; Bartolini, M; Bertucci, C; Cavrini, V; Luppi, B; Cerchiara, T

2003-08-01

210

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

2013-07-01

211

Use of Folic Acid Supplements in Early Pregnancy in Relation to Maternal Plasma Levels in Week 18 of Pregnancy  

PubMed Central

We compared plasma-folate at week 18 of gestation with self-reported use of supplements containing folic acid from before pregnancy to 17 weeks gestation. Birth cohorts typically measure plasma-folate in mid-gestation, but effects of folic acid supplementation are sometimes specific to the periconceptional period. The relationship between mid-gestation plasma-folate and periconceptional supplementation is not known. The sample comprised 2911 women from The Norwegian Mother and Child Cohort Study. For women reporting continuous supplementation from gestational week -4-17 (N=238), median plasma-folate was 15.72 at week 18 (in nmol/L). This was about threefold higher than the median plasma-folate of 5.67 for women reporting no supplementation from week -4-17 (N=844), but only slightly higher than the median plasma-folate of 13.34 for all women reporting supplementation in week 13-17 (N=1158). Reported supplementation before week 8 was not associated with plasma-folate at week 18, in an analysis that adjusted for continued supplementation after week 8. Overall we found a strong and coherent relationship between self-reported folic acid use and plasma-folate at week 18. We also found that plasma-folate at week 18 did not reflect self-reported supplementation before 8 weeks. For periconceptional supplementation per se, self-report data may offer a better measure.

Roth, Christine; Monsen, Anne Lise B.; Reichborn-Kjennerud, Ted; Nilsen, Roy M.; Smith, George Davey; Stoltenberg, Camilla; Suren, Pal; Susser, Ezra; Ueland, Per Magne; Vollset, Stein Emil; Magnus, Per

2013-01-01

212

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring  

PubMed Central

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

Huot, Pedro S. P.; Dodington, David W.; Mollard, Rebecca C.; Reza-Lopez, Sandra A.; Sanchez-Hernandez, Diana; Cho, Clara E.; Kuk, Justin; Ward, Wendy E.; Anderson, G. Harvey

2013-01-01

213

Comparative effect of Ocimum sanctum, Commiphora mukul, folic acid and ramipril on lipid peroxidation in experimentally-induced hyperlipidemia.  

PubMed

Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions. PMID:21046985

Khanna, Naresh; Arora, Deepika; Halder, Sumita; Mehta, Ashish K; Garg, Gobind R; Sharma, Suman B; Mahajan, Prabha

2010-03-01

214

Iron and Folic Acid Consumption by the Ante-natal Mothers in a Rural Area of India in 2010  

PubMed Central

Background: The average rural Indian women enter her reproductive life, particularly in pregnancy, suffer from nutritional anemia due to iron deficiency. National program of India had implemented a strategy for supplementation of iron folic acid by means of iron folic acid (IFA) tablets at least 3 months during antenatal period. The study had been conducted to assess the proportion of pregnant mothers consumes the IFA tablets and the factors determine compliance. Methods: A cross-sectional, community-based study was conducted in rural area of India on 50 antenatal mothers by multistage sampling technique. The data were analyzed by using SPSS 16 (Statistical Package for the Social Sciences, ver. 16), Chicago, considering the level of significance at 95%. Results: The IFA tablet was adequately consumed by 62% mother among the study population. The consumption is more among the mother who were explained properly than those who were not explained by the health worker (?2= 4.529, P < 0.05). Conclusions: The compliance of iron folic acid tablets was still far behind to reach the National Goal though the service component are quite strong by the front line workers and health providers. An effort should be given at the level of front line health workers by training and re-training them to improve the compliance of IFA consumption.

Pal, Partha Pratim; Sharma, Shilpi; Sarkar, Tarun Kumar; Mitra, Pevel

2013-01-01

215

Folic acid conjugated ?-valerolactone-poly(ethylene glycol) based triblock copolymer as a promising carrier for targeted doxorubicin delivery.  

PubMed

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

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

2013-01-01

216

Effects of supplementary folic acid and vitamin B(12) on hepatic metabolism of dairy cows according to methionine supply.  

PubMed

The present experiment was undertaken to study the interactions between dietary supplements of rumen-protected methionine (RPM) and intramuscular injections of folic acid and vitamin B(12), given from 3 wk before calving to 16 wk of lactation, on hepatic metabolism of lactating dairy cows. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet calculated to supply Met as 1.83% of metabolizable protein, whereas the 3 other cows were fed the same diet supplemented with 18g of RPM calculated to provide Met as 2.23% of metabolizable protein. Within each level of Met, the cows received no vitamin supplement or weekly intramuscular injections of 160mg of folic acid alone or combined with 10mg of vitamin B(12). Liver biopsies were taken at 2, 4, 8, and 16 wk of lactation. Liver concentrations of folates and vitamin B(12) were increased by their respective supplements but this response to vitamin supplements was altered by methionine supply. Concentrations of total lipids and triglycerides increased in livers of cows fed RPM, whereas concentrations of cholesterol ester, cholesterol, diglycerides, phosphatidylethanolamine, and phosphatidylcholine were not affected. Folic acid, alone or combined with vitamin B(12), tended to increase the ratio of phosphatidylcholine to phosphatidylethanolamine. Gene expression of 5,10-methylene-tetrahydrofolate reductase, microsomal transfer protein, and phosphatidylethanolamine methyltransferase were higher in liver of cows fed RPM supplements. The relative mRNA abundance of 5,10-methylene-tetrahydrofolate reductase and methylmalonyl-CoA mutase were increased by the combined injections of folic acid and vitamin B(12), whereas those of methionine synthase and methionine synthase reductase were not affected by treatments. These results suggest that increasing supply of methyl groups, as preformed labile methyl groups or through methylneogenesis, affected the methylation cycle but had a limited effect on dairy cow performance. The observed effects of the combined supplement of folic acid and vitamin B(12) on lactational performance of dairy cows probably result from an improvement of energy metabolism during early lactation. PMID:20412928

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

2010-05-01

217

Structural basis for molecular recognition of folic acid by folate receptors.  

PubMed

Folate receptors (FR?, FR? and FR?) are cysteine-rich cell-surface glycoproteins that bind folate with high affinity to mediate cellular uptake of folate. Although expressed at very low levels in most tissues, folate receptors, especially FR?, are expressed at high levels in numerous cancers to meet the folate demand of rapidly dividing cells under low folate conditions. The folate dependency of many tumours has been therapeutically and diagnostically exploited by administration of anti-FR? antibodies, high-affinity antifolates, folate-based imaging agents and folate-conjugated drugs and toxins. To understand how folate binds its receptors, we determined the crystal structure of human FR? in complex with folic acid at 2.8?Å resolution. FR? has a globular structure stabilized by eight disulphide bonds and contains a deep open folate-binding pocket comprised of residues that are conserved in all receptor subtypes. The folate pteroate moiety is buried inside the receptor, whereas its glutamate moiety is solvent-exposed and sticks out of the pocket entrance, allowing it to be conjugated to drugs without adversely affecting FR? binding. The extensive interactions between the receptor and ligand readily explain the high folate-binding affinity of folate receptors and provide a template for designing more specific drugs targeting the folate receptor system. PMID:23851396

Chen, Chen; Ke, Jiyuan; Zhou, X Edward; Yi, Wei; Brunzelle, Joseph S; Li, Jun; Yong, Eu-Leong; Xu, H Eric; Melcher, Karsten

2013-08-22

218

Long-term variations of folic acid concentrations in the Northern Adriatic.  

PubMed

Folic acid (FA), which belongs to B-group vitamins has recently been recognized as possible nutrient for some phytoplankton species (a diatom Phaeodactylum tricornutum). The beneficial role of FA in human health is widely documented. In some countries food fortification with FA has already become mandatory. FA is also used under commercial name of Dosfolat for the treatment of industrial and domestic wastewaters. This is an exploratory study on seasonal and depth variability of FA concentrations in the Northern Adriatic Sea (station 101-max depth 30 m, under the Po River influence). Seawater samples were analysed in the period from February 1998 to February 2003 based on monthly determinations. Those preliminary findings showed that in the upper layer (10 m) FA concentrations were in the range from 0.1 to 28 nM. In the lower layer (20-30 m) FA concentrations were in the range from 0.1 to 12 nM. It was found that phytoplankton and microorganisms which are responsible for the production of FA in the Northern Adriatic (Station 101) were situated at the depth from 5 to 10 m. The observed water column and seasonal distributions depended on a sensitive balance between the production and the consumption of FA. PMID:15120194

Plavsi?, Marta

2004-08-01

219

Synthesis and cellular uptake of folic Acid-conjugated cellulose nanocrystals for cancer targeting.  

PubMed

Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis. PMID:24716601

Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

2014-05-12

220

Liquid chromatographic method for determining added folic acid in fortified cereal products.  

PubMed

Reversed-phase ion-pair high-performance liquid chromatography (HPLC) was coupled with detection by UV absorption (280 nm) for separation and quantitation of added folic acid (FA) in fortified cereal based foods. A simple and rapid liquid-solid extraction method, combined with enzymatic digestion, to recover FA from the sample matrices is also presented. The quantitation of added FA was achieved in products including corn (maize), wheat-, rice- and oat-based cereal breakfast foods fortified at 25% and 100% of the reference daily intake (RDI). The retention time for FA was ca. 15 min, and the detection limit was 2 ng/20 microliters injection for standard FA. When FA was added to unfortified samples of wheat flour at concentrations of 3.08 or 20.0 micrograms/g, recoveries were 93% and 96%, respectively. Comparison of HPLC results with those of a standard microbiological assay has shown quite good agreement (r = 0.998). A solid-phase extraction clean-up procedure has also been developed for use with samples fortified with low levels of FA, where interferences may otherwise hinder quantitation. PMID:9871340

Osseyi, E S; Wehling, R L; Albrecht, J A

1998-11-27

221

Synthesis of luminescent nanoporous silica spheres functionalized with folic Acid for targeting to cancer cells.  

PubMed

Luminescent europium(III)-doped nanoporous silica nanospheres (Eu:NPS) were successfully synthesized, and a folate N-hydroxysuccinimidyl ester (FA-NHS) molecule as a targeting ligand for cancer cells was immobilized on the nanosphere surfaces through mediation of the 3-aminopropyltriethoxysilane (APTES) adlayer. The ordered nanopores were preserved by the immobilization, and the specific surface area decreased only with the APTES immobilization, suggesting that the FA-NHS was predominantly immobilized on the outer surface of the nanopores. The photoluminescence of the nanospheres functionalized with folic acid (FA) exhibited a characteristic peak due to the interactions (e.g., energy transfer) between FA and Eu(3+), and further the orange luminescence could be clearly detected by fluorescence microscopy in air and water. Furthermore, the nanospheres highly dispersed in cell culture medium exhibited nontoxicity in the cellular proliferation stages of the Hela cancer cells and NIH3T3 fibroblasts and specifically bind to the Hela cells. The nanospheres after the binding and uptake also showed intense luminescence from the outer/inner cell surfaces for the culture time of 4 days. Therefore, the luminescent FA-functionalized Eu:NPS nanospheres could be used for specific targeting and imaging abilities for cancer cells. PMID:24921687

Tagaya, Motohiro; Ikoma, Toshiyuki; Xu, Zhefeng; Tanaka, Junzo

2014-07-01

222

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

223

Supranormal dietary folic acid supplementation: effects on methionine metabolism in weanling rats.  

PubMed

There are nationwide folic acid (FA) fortification programmes of staple foods established or under consideration in order to prevent neural tube defects. Universal FA fortification still remains controversial because of the concern that additional FA in the diets of population groups (e.g. children and elderly) not initially targeted for fortification may suffer adverse effects. However, dietary surveys regarding folate generally deal with adults and little is known about the consumption and long-term effects of fortified food and supplements in growing individuals. Recent reports from our laboratory show several effects of high-dose folate supplementation in rats. In the present work, we studied the effect of FA on the methionine cycle in weanling (3-week-old) male rats after 4 weeks of supplementation with 40 mg FA/kg diet v. control (1 mg FA/kg diet). FA supplementation resulted in a reduction of homocysteine and creatinine concentrations v. control group. FA supplementation did not alter S-adenosylmethionine/S-adenosylhomocysteine ratio, DNA methylation, enzymatic activities or concentrations of vitamins involved in the nutritional regulation of the methionine cycle, except for folate. FA supplementation of 40 mg/kg did not lead to hepatic or renal damage. In conclusion, there were no apparent adverse effects on one-carbon metabolism after FA supplementation in the studied conditions. PMID:17419891

Achón, M; Alonso-Aperte, E; Ubeda, N; Varela-Moreiras, G

2007-09-01

224

Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.  

PubMed

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. PMID:23955381

Joseph, Jacob; Loscalzo, Joseph

2013-08-01

225

High?dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels.  

PubMed

The aim of this study was to investigate the effect of folic acid (FA) on tetrahydrobiopterin (BH4), neopterin, nitric oxide (NO) and homocysteine (Hcy) levels in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro in the presence or absence of Hcy. The effect of various doses of FA on Hcy, BH4, neopterin and NO concentrations in HUVECs was then assessed. In the 5 and 10 nmol/l FA treatment groups, FA was found to significantly increase the levels of BH4 (10.56±3.86 and 11.23±2.1919 pmol/g vs 6.32+2.87 nmol/g; P<0.05 vs. control) and NO production (37.86±12.34 nmol/l, 38.45±11.23 nmol/l vs 26.21±9.24 nmol/l; P<0.001 vs. paired Hcy group), but reduce the levels of Hcy (132.87±29.67 and 140.87±26.76 nmol/l vs. 165.23±30.56 nmol/l; P<0.05 vs. Hcy group). No significant differences were observed in neopterin levels among the different groups of HUVECs. In conclusion, high doses of FA may be capable of protecting endothelial cells through reducing levels of Hcy and increasing BH4 and NO production. PMID:24939255

Zhang, Min; Wen, Jinlin; Wang, Xiangjiang; Xiao, Chun

2014-09-01

226

Beta-lactoglobulin/folic acid complexes: formation, characterization, and biological implication.  

PubMed

Beta-lactoglobulin (beta-LG), the major whey protein in bovine milk, binds to a wide range of compounds. Folic acid (FA) is a synthetic form of the B group vitamin known as folates, which are essential cofactors for a variety of physiological processes. The interaction of beta-LG with FA was studied using fluorescence spectroscopy to determine the FA binding constant and mode and the influence of the protein on FA photodegradation. At < or = 20 microM FA, which may be the critical self-association concentration, the binding constant and number are 2.0 (+/-0.6) x 10(6) M(-1) and 1.30 (+/-0.03) when excited at 280 nm and 4.3 (+/-2.2) x 10(5) M(-1) and 1.17 (+/-0.04) at 295 nm, as determined by protein intrinsic fluorescence. FA binds to the surface of beta-LG, possibly in the groove between the alpha-helix and the beta-barrel. Fluorescence analysis of the pterin portion of FA shows that complexation with beta-LG improves FA photostability. It is suggested that beta-LG complexes could be used as an effective carrier of FA in functional foods. PMID:20411963

Liang, Li; Subirade, Muriel

2010-05-20

227

Efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in coronary artery disease: A meta-analysis of randomized controlled trials  

PubMed Central

The aim of the present study was to conduct an updated meta-analysis of relevant randomized controlled trials (RCTs) in order to estimate the effect of folic acid supplementation on endothelial function and the concentration of plasma homocysteine in patients with coronary artery disease (CAD). An extensive search of PubMed was conducted to identify RCTs that compared folic acid with placebo therapy. The mean difference (MD) and 95% confidence interval (CI) were used as a measure of the correlation between folic acid supplementation and endothelial function/plasma homocysteine concentration. Of the 377 patients included in this analysis, 191 patients underwent folic acid supplementation and 186 individuals underwent placebo treatment. Compared with the use of a placebo, folic acid supplementation alone exhibited significant efficacy on increasing flow-mediated dilation (FMD; MD, 57.72 ?m; 95% CI, 50.14–65.31; P<0.05) and lowering the concentration of plasma homocysteine (MD, ?3.66 ?mol/l; 95% CI, ?5.44–?1.87; P<0.05; I2, 87%). There was no significant change in the response to end diastolic diameter, glyceryl-trinitrate diameter, heart rate, baseline and peak hyperemic flow and systolic and diastolic blood pressure between the folic acid and placebo groups (P>0.05). Therefore, the meta-analysis indicated that 5 mg folic acid daily supplementation for >4 weeks significantly improved FMD and lowered the concentration of plasma homocysteine in patients with CAD. However, more RCTs are required in order to confirm these observations.

YI, XIN; ZHOU, YANLI; JIANG, DINGSHENG; LI, XIAOYAN; GUO, YI; JIANG, XUEJUN

2014-01-01

228

Aqueous diastereoselective hydrogenation of folic acid to tetrahydrofolic acid in the presence of water-soluble Rh and Ir diphosphine complexes  

Microsoft Academic Search

Rhodium and iridium catalysts with chiral, water soluble diphosphine ligands, were used for the diastereoselective hydrogenation of folic acid disodium salt in water. Using a modified Rh\\/Josiphos type at 30°C, l-tetrahydrofolic acid, a relevant pharmaceutical intermediate, was obtained with a selectivity of up to 49% de; at 70°C turnover numbers of up to 2800 were achieved, albeit with lower selectivity.

Benoît Pugin; Viola Groehn; Rudolf Moser; Hans-Ulrich Blaser

2006-01-01

229

Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome.  

PubMed

Obese subjects with the metabolic syndrome (MS+) are more prone to microvascular complications than obese subjects without the metabolic syndrome (MS-). Excessive vascular nitric oxide (NO) production has been demonstrated in MS+ compared to MS-, perhaps driven by increased inflammation or oxidative stress. We tested whether in MS+, folic acid (FA) treatment could normalize NO synthase (NOS)-dependence of vascular tone in the retina and kidney. MS+ (n = 49) and MS- (n = 26) subjects were included in a randomized, double-blind, crossover trial. After 4-weeks' treatment with placebo or FA (5 mg/day), several cytokines (C-reactive protein (CRP), interleukin-1?, adiponectin), and markers of oxidative stress (glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (TAC)) were determined. NOS-dependence of retinal and renal vascular tone was assessed by retinal scanning laser Doppler flowmetry and renal clearance technique, respectively. FA had no effect on cytokine levels, but increased GSH/GSSG ratio overall (36 ± 76 vs. 102 ± 200, P = 0.04), indicative of a reduction in oxidative stress. In MS+, treatment with FA reduced NOS-dependence of retinal and renal vascular tone compared to placebo (P = 0.03 and P = 0.04, respectively). FA had no effect in MS-. After treatment with FA, NOS-dependence of retinal and renal vascular tone was similar between MS+ and MS-. Retinal and renal vascular tone in MS+ subjects is characterized by increased dependence on NOS. NOS-dependence in MS+ could be corrected by FA treatment to levels not dissimilar in MS-, and this was associated with a reduction in oxidative stress. Future trials should test whether these effects translate into a reduction of microvascular complications. PMID:20864946

Schneider, Markus P; Schlaich, Markus P; Harazny, Joanna M; Raff, Ulrike; Ritt, Martin; Ott, Christian; Schmieder, Roland E

2011-05-01

230

Does folic-acid supplementation prevent or promote colorectal cancer? Results from model-based predictions  

PubMed Central

Folate is essential for nucleotide synthesis, DNA-replication and methyl-group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid (FA) to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under FA supplementation, consistent with folate’s role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between FA’s protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation, we used a biologically-based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential impact of FA on cell proliferation and mutation rates. Conclusion: changes in colorectal cancer risk in response to FA supplementation are likely a complex function of treatment start, duration, and impact on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without FA supplementation unless supplementation is initiated early in life (before age 20). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting FA supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

Luebeck, EG; Moolgavkar, SH; Liu, AY; Boynton, A; Ulrich, CM

2010-01-01

231

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

PubMed

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

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

2012-08-01

232

Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis.  

PubMed

Acute kidney injury (AKI) is a disease with mitochondrial dysfunction and a newly established risk factor for the development of chronic kidney disease (CKD) and fibrosis. We examined mitochondrial homeostasis in the folic acid (FA)-induced AKI model that develops early fibrosis over a rapid time course. Mice given a single dose of FA had elevated serum creatinine (3-fold) and urine glucose (2.2-fold) 1 and 2 d after injection that resolved by 4d. In contrast, peroxisome proliferator gamma coactivator 1? (PGC-1?) and mitochondrial transcription factor A (TFAM), critical transcriptional regulators of mitochondrial biogenesis (MB), were down-regulated ?80% 1d after FA injection and remained depressed through 14 d. Multiple electron transport chain and ATP synthesis genes were also down-regulated from 1 to 14 d after FA, including NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUF?8), ATP synthase subunit ? (ATPS-?), and cytochrome C oxidase subunit I (COXI). Mitochondrial DNA copy number was reduced ?50% from 2 to 14 d after FA injection. Protein levels of early fibrosis markers ?-smooth muscle actin and transforming growth factor ?1 were elevated at 6 and 14 d after FA. Picrosirius red staining and collagen 1A2 (COL1A2) IHC revealed staining for mature collagen deposition at 14 d. We propose that mitochondrial dysfunction induced by AKI is a persistent cellular injury that promotes progression to fibrosis and CKD, and that this model can be used to test mitochondrial therapeutics that limit progression to fibrosis and CKD. PMID:24275386

Stallons, L Jay; Whitaker, Ryan M; Schnellmann, Rick G

2014-01-30

233

Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?  

PubMed

Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 ?g. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs. PMID:23482308

Obeid, Rima; Holzgreve, Wolfgang; Pietrzik, Klaus

2013-09-01

234

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

PubMed Central

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

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

2013-01-01

235

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

236

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

237

Squaric acid derivatives as VLA4 integrin antagonists  

Microsoft Academic Search

SAR studies aimed at improving the rate of clearance by the incorporation of a 3,4-diamino-3-cyclobutene-1,2-dione group as an amino acid isostere in a series of VLA-4 integrin antagonists are described.

John R. Porter; Sarah C. Archibald; Kirstie Childs; David Critchley; John C. Head; Janeen M. Linsley; Ted A. H. Parton; Martyn K. Robinson; Anthony Shock; Richard J. Taylor; Graham J. Warrellow; Rikki P. Alexander; Barry Langham

2002-01-01

238

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

Microsoft Academic Search

Introduction  Folate receptor (FR)-expressing macrophages have been shown to accumulate at sites of inflammation, where they promote development\\u000a of inflammatory symptoms. To target such a macrophage population, we designed and evaluated the biologic activity of EC0746,\\u000a a novel folic acid conjugate of the highly potent antifolate, aminopterin.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Using a FR-positive subclone of murine macrophage-derived RAW264.7 cells and rat thioglycollate-elicited macrophages, we

Yingjuan Lu; Torian W Stinnette; Elaine Westrick; Patrick J Klein; Mark A Gehrke; Vicky A Cross; Iontcho R Vlahov; Philip S Low; Christopher P Leamon

2011-01-01

239

Acute Effect of Folic Acid, Betaine, and Serine Supplements on Flow-Mediated Dilation after Methionine Loading: A Randomized Trial  

PubMed Central

Objectives: We investigated whether reducing post-methionine homocysteine concentrations via various treatments other than folic acid affects vascular function, as measured through flow-mediated dilation (FMD) of the brachial artery. High fasting and post-methionine homocysteine concentrations are associated with cardiovascular disease risk, but homocysteine might be a surrogate marker for low folate status. Design: This was a randomized, placebo-controlled, double-blind, crossover study. Setting: The study took place at Wageningen University in Wageningen in the Netherlands. Participants: Participants were 39 apparently healthy men and women, aged 50–70 y. Interventions: Participants ingested 10 mg of folic acid, 3 g of betaine, 5 g of serine, and placebo together with an oral methionine load. Each supplement was tested on two different days. Outcome Measures: On each of the eight treatment days, plasma homocysteine concentrations and FMD were measured before (t = 0 h, fasting) and 6 h (t = 6 h) after methionine loading. Results: The mean (± SD) fasting homocysteine concentrations averaged over the eight test days were 9.6 ± 2.1 ?mol/l. Mean fasting FMD was 3.1 ± 2.4 FMD%. A methionine load with placebo increased homocysteine concentrations by 17.2 ± 9.3 ?mol/l at 6 h after loading, similar to the increase following methionine loading with folic acid. A methionine load together with betaine and with serine increased homocysteine by 10.4 ± 2.8 ?mol/l (p < 0.001 relative to placebo) and by 12.1 ± 8.2 ?mol/l (p < 0.001 relative to placebo), respectively. Methionine loading with placebo did not affect FMD, and neither did methionine loading with folic acid, betaine, or serine; differences relative to placebo were +0.7 FMD% (95%CI, ?0.6; 1.9), +0.2 FMD% (?1.0; 1.3), and +0.3 FMD% (?0.8; 1.4), respectively. Conclusions: Experimentally induced acute changes in homocysteine concentrations did not affect FMD in healthy volunteers. This implies that potential adverse effects of high homocysteine concentrations on the cardiovascular system are not mediated through vascular function. However, homocysteine or folate may affect cardiovascular disease risk through other mechanisms.

Olthof, Margreet R; Bots, Michiel L; Katan, Martijn B; Verhoef, Petra

2006-01-01

240

Utilization of folic acid and iron supplementation services by pregnant women attending an antenatal clinic at a regional referral hospital in Kenya.  

PubMed

To determine utilization of iron and folic acid supplementation services among pregnant women in Kenya. A cross sectional study was conducted at Nyeri Hospital, a regional referral hospital in central Kenya. Women attending the antenatal clinic were selected through systematic sampling. A semi-structured questionnaire was administered to collect information on utilization of folic acid and iron supplementation services. Women who ingested folic acid or iron supplements for >4 days in a week were considered "highly compliant". The health worker in-charge of the antenatal clinic was interviewed about the frequency of supplement stock-outs during the past year. Haemoglobin concentration was measured directly from one drop of capillary blood and measured using portable HEMOCUE B-Hb photometer. Of the 381 women interviewed, only 23.6 % obtained antenatal care in the first trimester; 69.3 and 51.2 % received folic acid and iron supplements, respectively. However, only half (45-58 %) received any information about supplementation. Most women were initiated on folic acid (80.7 %) or iron (67.7 %) after 12 and 16 weeks of gestation, respectively, well after the recommended time period. However, more than 80 % of those who received folic acid and iron were highly compliant. Stock-outs were common at the facility. Of 361 women tested for Hb level, the prevalence of anaemia (Hb levels < 11 g/dl) was 7.8 %. Health workers need to better explain the importance of supplements to pregnant women. Women who come late to antenatal clinic miss opportunities to start supplementation early in pregnancy. Problems with supply chain management exacerbate the problem. PMID:22907273

Maina-Gathigi, L; Omolo, J; Wanzala, P; Lindan, C; Makokha, A

2013-09-01

241

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

242

Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation  

PubMed Central

Background A novel dual ligand–modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overcome the nonselectivity of conventional penetrating peptide-tagged nanoparticulates and to provide the advantage of selective targeting of the folic acid receptor, which is frequently overexpressed on epithelial cancer cells. Methods FP-Lipo was prepared by a sequential process of formation of a maleimide-derivatized small unilamellar vesicle, postinsertion of distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000–folate to the vesicle, and Pep-1 peptide conjugation via thiol-maleimide linkage. Conformational and physical characteristics of the FP-Lipo nanocarriers were investigated for the extent of Pep-1 peptide and folic acid on the surface, vesicle size, and zeta potential. In vitro cellular uptake behaviors of the novel carrier containing a fluorescein dextran isothiocyanate probe were examined by spectrophotometry or by confocal laser scanning microscopy. Results A novel nanocarrier bearing approximately 750 folate ligands and 100 penetrating peptides per vesicle was successfully prepared. The physical properties were as follows: 140 nm in size; 5 mV in zeta potential; less than 0.3 in polydispersity index. An in vitro cellular uptake study revealed that the FP-Lipo nanocarrier system exhibited more than twofold enhanced translocation into the folic acid receptor–positive HeLa cells compared with the single Pep-1 peptide–modified liposome. Meanwhile, its cellular association and internalization into the folic acid receptor–negative normal HaCaT cells was comparable with that of Pep-1 peptide–modified liposome. Conclusion An advanced dual ligand-modified liposome is potentially useful for the treatment of folic acid receptor–positive tumors with high translocation capability of the penetrating peptide–modified liposome.

Kang, Myung Joo; Park, Sang Han; Kang, Mean Hyung; Park, Min Jung; Choi, Young Wook

2013-01-01

243

Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid  

PubMed Central

A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.

Stupka, Elia; Clark, Adrian J. L.; Langley-Evans, Simon

2013-01-01

244

Influence of methionine supply on the response of lactational performance of dairy cows to supplementary folic acid and vitamin B12.  

PubMed

The present experiment was undertaken to determine if the effects of supplementary folic acid on lactational performance were caused by improved methylneogenesis and if the supply in vitamin B(12) could affect this metabolic pathway. In this eventuality, supplementary Met, a major source of preformed methyl groups, should reduce the requirements for these vitamins. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet estimated to supply Met as 1.83% metabolizable protein and 3 cows were fed the same diet supplemented with 18 g of rumen-protected methionine (RPM) to supply Met as 2.23% of metabolizable protein. Within each level of Met, cows received no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid alone or combined with 10 mg of vitamin B(12) from 3 wk before to 16 wk after calving. There was no treatment effect on dry matter intake during pre- and postcalving periods: 13.4 +/- 0.4 and 21.8 +/- 0.4 kg/d, respectively. Milk production was not affected by RPM supplementation. Folic acid and vitamin B(12) given together tended to increase milk production during the 16 wk of lactation. This effect was more pronounced during the first 4 wk of lactation: 37.5, 37.7, and 40.3 +/- 0.9 kg/d for cows receiving no vitamin supplement, folic acid alone, or folic acid combined with vitamin B(12), respectively. Milk fat yield was not affected by treatments. Lactose, crude protein, and total solid yields were greater, in early lactation, in cows injected with folic acid and vitamin B(12) together but this effect diminished as lactation progressed. Intramuscular injections of folic acid alone or combined with vitamin B(12) tended to decrease plasma concentrations of homocysteine from 5.51 microM with no vitamin supplement to 4.54 and 4.77 +/- 0.37 microM, respectively. Results of the present experiment suggest that the effects of the combined supplement of folic acid and vitamin B(12) on lactational performance of dairy cows were not due to an improvement in methyl groups supply, because RPM supplement, a source of preformed methyl groups, did not alter the cow responsiveness to vitamin supplements. PMID:19307650

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

2009-04-01

245

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

PubMed Central

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 to improve endothelial progenitor cell function. In this study, we investigated the gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes compared to endothelial progenitor cells from healthy subjects. Furthermore, we studied the effect of folic acid on gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes. Methods We used microarray analysis to investigate the gene expression profiles of endothelial progenitor cells from type 1 diabetes patients before (n = 11) and after a four week period of folic acid supplementation (n = 10) compared to the gene expression profiles of endothelial progenitor cells from healthy subjects (n = 11). The probability of genes being differentially expressed among the classes was computed using a random-variance t-test. A multivariate permutation test was used to identify genes that were differentially expressed among the two classes. Functional classification of differentially expressed genes was performed using the biological process ontology in the Gene Ontology database. Results Type 1 diabetes significantly modulated the expression of 1591 genes compared to healthy controls. These genes were found to be involved in processes regulating development, cell communication, cell adhesion and localization. After folic acid treatment, endothelial progenitor cell gene expression profiles from diabetic patients were similar to those from healthy controls. Genes that were normalized by folic acid played a prominent role in development, such as the transcription factors ID1 and MAFF. Few oxidative-stress related genes were affected by folic acid. Conclusion Folic acid normalizes endothelial progenitor cell gene expression profiles of patients with type 1 diabetes. Signaling pathways modulated by folic acid may be potential therapeutic targets to improve endothelial progenitor cell function.

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

2009-01-01

246

Effects of dietary supplements of folic acid and rumen-protected methionine on lactational performance and folate metabolism of dairy cows.  

PubMed

The present experiment was undertaken to determine the interactions between dietary supplements of folic acid and rumen-protected methionine on lactational performance and on indicators of folate metabolism during one lactation. Fifty-four multiparous Holstein cows were assigned to 9 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet calculated to supply methionine as 1.75% metabolizable protein, equivalent to 70% of methionine requirement, whereas the 3 other cows were fed the same diet supplemented with 18 g of a rumen-protected methionine supplement. Within each diet, the cows received 0, 3, or 6 mg/d of folic acid per kg of body weight. Rumen-protected methionine increased milk total solid concentration but not yield. Supplementary folic acid increased crude protein and casein concentrations in milk of cows fed no supplementary methionine and the effect increased as lactation progressed; it also decreased milk lactose concentration. Folic acid supplements had the opposite effects on milk crude protein, casein, and lactose concentrations in cows fed rumen-protected methionine. Milk and milk component yields and dry matter intake were unchanged. Folic acid supplementation increased serum folates and this response was greater at 8 wk of lactation. It decreased serum cysteine in cows fed rumen-protected methionine, whereas it had no effect in cows fed no supplementary methionine. The highest serum concentrations of cysteine but the lowest of vitamin B(12) were observed at 8 wk of lactation. Serum clearance of folic acid following an i.v. injection of folic acid was slower at 8 wk of lactation. During this period, the high concentrations of serum folates and cysteine, the low serum concentrations of vitamin B(12) and methionine, and the slow serum clearance of folates strongly suggest that the vitamin B(12) supply was inadequate and interfered with folate use. It could explain the limited lactational response to supplementary folic acid observed in the present experiment. PMID:15653533

Girard, C L; Lapierre, H; Matte, J J; Lobley, G E

2005-02-01

247

Imprinted polymer-carbon consolidated composite fiber sensor for substrate-selective electrochemical sensing of folic acid.  

PubMed

Molecularly imprinted polymers (MIPs) are often electrically insulating materials. Due to the presence of diffusion barrier(s) in between such MIP coating and electrode surface and the absence of a direct path for the conduction of electrons from the binding sites to the electrode, the development of electrochemical sensor is significantly restricted. The direct use of MIPs those possess intrinsic electron-transport properties, is highly limited. These problems are resolved by the design of an original, substrate-selective MIP-fiber sensor that combines conventional insulating MIP and conducting carbon powder in consolidated phase. A layer of conducting carbon particles, arranged orderly as 'carbon strip', is inducted in the polymer for direct electronic conduction. MIP-carbon composite (monolithic fiber) in this work is prepared via in situ free radical polymerization of a new monomer (2,4,6-trisacrylamido-1,3,5-triazine, TAT) and subsequent cross-linkage with ethylene glycol dimethacrylate, in the presence of carbon powder and template (folic acid), at 55 degrees C in a glass capillary. The detection of folic acid with the MIP-fiber sensor was found to be specific and quantitative (detection limit 0.20 ng mL(-1), RSD=1.3%, S/N=3), in aqueous, blood serum and pharmaceutical samples, without any problem of non-specific false-positive contribution and cross-reactivity. PMID:20227869

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

2010-05-15

248

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

PubMed Central

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

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

2014-01-01

249

Clinical study of tongue pain: Serum zinc, vitamin B12, folic acid, and copper concentrations, and systemic disease.  

PubMed

The aim of this retrospective study of patients with tongue pain who showed no improvement after initial treatment and examination was to find out if their lack of response correlated with serum concentrations of zinc, vitamin B12, folic acid, and copper, and if it was associated with coexisting systemic diseases. We studied 311 patients for whom we had data about serum concentrations of these elements, and recorded whether they had any systemic diseases and were taking medicines regularly. One patient (0.3%) had a copper concentration outside the reference range; 2 patients (0.6%) had folic acid concentrations outside the reference range. The corresponding number for vitamin B12 was 5 (2%), and for zinc 30 (10%). The systemic diseases with the highest rates were: hyperlipidaemia (n=53, 17%), gastritis or gastric ulcer (n=51, 16%), angina pectoris (n=39, 13%), diabetes mellitus (n=31, 10%), thyroid disease (n=31, 10%), mild mental disorder (n=27, 9%), hypertension (n=18, 6%), cerebral infarction (n=17, 6%), leiomyoma (n=15, 5%) and anaemia (n=15, 5%). Roughly 10% of the patients were deficient in zinc. This study suggested that the serum concentration of zinc was most important to the patients with tongue pain. Many patients had more than one systemic condition, and all were taking various drugs. PMID:19735964

Yoshida, Hiroaki; Tsuji, Kaname; Sakata, Takeichi; Nakagawa, Akihito; Morita, Shosuke

2010-09-01

250

Folate receptor imaging with 125I labeled folic acid with a whole body small animal imaging device built with plastic scintillating optical fibers  

Microsoft Academic Search

A small animal whole body imaging cylindrical device was built with plastic scintillating fibers and position sensitive photomultipliers (Hamamatsu) and digitized using flash ADCs. A co-axial brass mesh collimator (septum thickness 1 mm) was used in combination with an electronic collimation scheme to enhance spatial resolution. Imaging studies with 125I labeled folic acid were performed in mice bearing folate receptor

P. V. Kulkarni; P. P. Antich; A. Constantinescu; J. Prior; T. Nguyen; J. Fernando; J. A. Anderson; S. D. Weitman; B. A. Kamen; R. W. Parkey; R. C. Chaney; E. J. Fenyves

1995-01-01

251

Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet  

PubMed Central

Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p = 0.009), glucose intolerance (p < 0.001) and insulin resistance (p < 0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring.

Huang, Yifan; He, Yonghan; Sun, Xiaowei; He, Yujie; Li, Ying; Sun, Changhao

2014-01-01

252

Role of folic acid and its amino-derivatives in the mechanism of action of low doses of formaldehyde on organs  

Microsoft Academic Search

Experiments were carried out on 58 noninbred rats of both sexes weighing from 150 to 250 g. Before receiving formaldehyde the animals were given folic acid or aminopterin or methotrexate* by intramuscular injection in a dose of 1 mg on three consecutive days. Next, 0.1% formalin in Ringer's solution was injected in a dose of 5 ml (55 ~M formaldehyde)

T. I. Lapkina

1982-01-01

253

Recommendations on the use of folic acid supplementation to prevent the recurrence of neural tube defects. Clinical Teratology Committee, Canadian College of Medical Geneticists.  

PubMed Central

OBJECTIVE: To prevent the recurrence of neural tube defects (NTDs) in families at increased risk of having offspring with NTDs with the use of periconceptional folic acid supplementation. OPTIONS: Genetic counselling and prenatal diagnosis of NTDs. OUTCOMES: NTDs cause stillbirth, neonatal death and severe disabilities. The cost for medical care and rehabilitation in the first 10 years of life of a child with spina bifida cystica was estimated to be $42,507 in 1987. EVIDENCE: The authors reviewed the medical literature, communicated with investigators from key studies, reviewed policy recommendations from other organizations and drew on their own expertise. A recent multicentre randomized controlled trial showed that among women at high risk of having a child with an NTD those who received 4 mg/d of folic acid had 72% fewer cases of NTD-affected offspring than nonsupplemented women. Two previous intervention studies also demonstrated that folic acid supplementation was effective in reducing the rate of NTD recurrence. Several retrospective studies support this conclusion. VALUES: Recommendations are the consensus of the Clinical Teratology Committee of the Canadian College of Medical Geneticists (CCMG) and have been approved by the CCMG Board. The committee believes that primary prevention of NTDs is preferable to treatment or to prenatal detection and abortion. BENEFITS, HARMS AND COSTS: Folic acid supplementation should result in fewer NTDs among infants in Canada and ancillary savings in medical costs. The recommended dosage of folic acid is not known to be associated with adverse effects. Higher dosages of folic acid may make vitamin B12 deficiency difficult to diagnose and may alter seizure frequency in patients with epilepsy due to drug interactions with anticonvulsants. RECOMMENDATIONS: A minimum dosage of folic acid of 0.8 mg/d, not to exceed 5.0 mg/d, is recommended along with a well-balanced, nutritious diet for all women who are at increased risk of having offspring with NTDs and who are planning a pregnancy or may become pregnant. Supplementation should begin before conception and continue for at least 10 to 12 weeks of pregnancy. VALIDATION: These guidelines are similar to those of the Society of Obstetricians and Gynaecologists of Canada, the US Centers for Disease Control and Prevention and the Department of Health in Britain. SPONSORS: These guidelines were developed by the CCMG Clinical Teratology Committee and endorsed by the Board of the CCMG. No funding for the development of these guidelines was obtained from any other sources.

Van Allen, M I; Fraser, F C; Dallaire, L; Allanson, J; McLeod, D R; Andermann, E; Friedman, J M

1993-01-01

254

Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-related Macular Degeneration in a Randomized Trial of Women  

PubMed Central

Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD.

Christen, William G.; Glynn, Robert J.; Chew, Emily Y.; Albert, Christine M.; Manson, JoAnn E.

2008-01-01

255

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

256

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

257

Bioaccessibility of vitamin A, vitamin C and folic acid from dietary supplements, fortified food and infant formula.  

PubMed

In the Netherlands, vitamin intake occurs mainly via food and for some vitamins also via fortified food. In addition, some people take dietary supplements. Information on the bioavailability of vitamins is important for a good estimation of the actual exposure to vitamins. Furthermore, for a reliable intake estimation, it is important to know the accurateness of the claimed vitamin concentration on the product label. In the current study, the amount of vitamin A, vitamin C, and folic acid in different products and their maximum bioavailability (bioaccessibility) were investigated. In about half of the products, the amount of vitamins significantly deviated from the declared amounts. The vitamin bioaccessibility ranged from <1% to 100%. When assessing the dietary intake exposure of vitamins, it is important to take into account both the possible deviation from the declared level and (the variability of) the bioaccessibility of the vitamin in the products. PMID:24625000

Brandon, E F A; Bakker, M I; Kramer, E; Bouwmeester, H; Zuidema, T; Alewijn, M

2014-06-01

258

[Cytogenetic effects in peripheral blood lymphocytes in the offspring of Chernobyl nuclear power plant accident liquidators under the influence of mitomycin C in vitro and folic acid in vivo].  

PubMed

The data on cytogenetic examination concerning the offspring of the Chernobyl accident liquidators (cleanup personnel) have been obtained. It has been established that spontaneous chromosomal aberrations level before folic acid administration was 1,8 times higher than that value after its employment (4,45 to 2,42 %, p < 0,01). In lymphocyte cultures treated with mitomycin C accompanied by folic acid it was 4,5 times higher before their administration (23,95 to 5,36 %, p < 0,001). The data obtained confirm a possibility of stabilization of genetic apparatus in offspring of the Chernobyl disaster liquidators after folic acid administration. PMID:23427614

Kovaleva, V I; Bagatskaia, N V

2013-01-01

259

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

260

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

261

Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial  

PubMed Central

Summary Introduction Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent. Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient populations, but little is known about the risks of mortality and morbidity associated with supplementation. Methods We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2• 2 factorial trial in children aged 1?36 months and residing in southern Nepal. We randomly assigned children daily oral supplementation to age 36 months with: iron (12·5 mg) and folic acid (50 • g; n=8337), zinc alone (10 mg), iron, folic acid, and zinc (n=9230), or placebo (n=8683); children aged 1?11 months received half the dose. Our primary outcome measure was all-cause mortality, and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by intention to treat. This study is registered at clinicaltrials.gov, number NCT00109551. Findings The iron and folic acid-containing groups of the study were stopped early in November, 2003, on the recommendation of the data and safety monitoring board; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrolment was completed. We continued to enrol children to the placebo and zinc alone groups. 25 490 children participated and analyses are based on 29 097·3 person-years of follow-up. There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo (HR 1·03, 95% CI 0·78?1·37, and 1·00, 0·74?1·34, respectively). There were no significant differences in the attack rates for diarrhoea, dysentery, or respiratory infections between groups, although all the relative risks except one indicated modest, non-significant protective effects. Interpretation Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death, but might protect against diarrhoea, dysentery, and acute respiratory illness.

Tielsch, James M; Khatry, Subarna K; Stoltzfus, Rebecca J; Katz, Joanne; LeClerq, Steven C; Adhikari, Ramesh; Mullany, Luke C; Shresta, Shardaram; Black, Robert E

2008-01-01

262

Folic acid and protein content in maternal diet and postnatal high-fat feeding affect the tissue levels of iron, zinc, and copper in the rat.  

PubMed

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n?=?48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p?folic acid content in the maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p?folic acid supplementation resulted in a reduction in renal Cu level (p?folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation. PMID:21484405

Król, Ewelina; Krejpcio, Zbigniew; Chmurzynska, Agata

2011-12-01

263

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

264

Development of a highly sensitive and selective hyphenated technique (molecularly imprinted micro-solid phase extraction fiber–molecularly imprinted polymer fiber sensor) for ultratrace analysis of folic acid  

Microsoft Academic Search

A simple polymerization strategy is reported in this work which allows molecularly imprinted polymeric fiber (monolith) fabrication for direct use in sensing devices. This is advantageous for achieving higher degree of enrichment of target analyte (folic acid) from the complex matrices of real samples, without any surface fouling, cross-reactivity, and non-specific (false-positive) contributions. In order to measure serum folic acid

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

2010-01-01

265

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

266

Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, and N-acetylcysteine in chicken embryo model.  

PubMed

The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the risk of VPA-teratogenicity. The effect was varying. In order to promote the preventive prescription, to find out its action mechanism can be rather crucial. We used chicken embryo model to try the effect of folic acid (FA), ascorbic acid (AA), and N-acetyl cysteine (NAC). VPA at 30mM showed the higher malformation rate (66.7%) with the least mortality (22.2%). Pathological findings indicated that the cervical muscle was more susceptible to VPA injury than the ankle muscle. VPA downregulated levels of superoxide dismutase (SOD), glutathione (GSH), histone deacetylase (HDAC) and folate, and upregulated H(2)O(2) and homocysteine. FA, AA, and NAC significantly upregulated SOD, but only AA alone activated GSH. AA and NAC downregulated H(2)O(2), while FA was totally ineffective. All three nutraceutics comparably rescued HDAC with simultaneously suppressed homocysteine accumulation and folate re-elevation, although less effectively by NAC. Based on these data, we conclude VPA possesses "Multiple Point Action Mechanism". In addition to affecting the cited transcription and translation levels, we hypothesize that VPA competitively antagonize the glutamic acid to couple with pteroic acid in biosynthesis of dihydrofolic acid (DHFA). H(2)O(2) directly destroyed the NADPH reducing system at dihydrofolate reductase (DHFR) and methylene tetrahydrofolate reductase (MTHFR) levels, while completely restored by AA, an implication in preservation of intact apoenzymes. In addition, the GSH-GSSG system is sandwiched between the reducing systems NADPH/NADP and DHA-AA, its net balance is highly dependent on in situ in vivo Redox state, hence folic acid transformation is varying. To rescue the VPA-induced teratogenicity, simultaneous multiple prescriptions are suggested. PMID:22051200

Hsieh, Chiu-Lan; Wang, Hui-Er; Tsai, Wan-Jane; Peng, Chiung-Chi; Peng, Robert Y

2012-01-27

267

Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy.  

PubMed

Multifunctional nanoprobes are designed to own various functions such as tumor targeting, imaging and selective therapy, which offer great promise for the future of cancer prevention, diagnosis, imaging and treatment. Herein, silica was applied to replace cetyltrimethylammonium bromide (CTAB) molecules on the surface of gold nanorods (GNRs) by the classic Stöber method, thus eliminating their cytotoxicity and improving their biocompatibility. Folic acid molecule was covalently anchored on the surface of GNRs with silane coupling agent. The resultant folic acid-conjugated silica-modified GNRs show highly selective targeting, enhanced radiation therapy (RT) and photo-thermal therapy (PTT) effects on MGC803 gastric cancer cells, and also exhibited strong X-ray attenuation for in vivo X-ray and computed tomography (CT) imaging. In conclusion, the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for X-ray/CT imaging-guided targeting dual-mode enhanced RT and PTT. PMID:21917309

Huang, Peng; Bao, Le; Zhang, Chunlei; Lin, Jing; Luo, Teng; Yang, Dapeng; He, Meng; Li, Zhiming; Gao, Guo; Gao, Bing; Fu, Shen; Cui, Daxiang

2011-12-01

268

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

PubMed

Enrichment of eggs with folate is possible when dietary folic acid levels are increased. However, development of optimal strategies for the production of folate-enriched eggs requires knowledge as to differences due to strain of bird and a greater understanding of the factors limiting egg folate deposition. To this end, a study was designed to determine the response of two leghorn strains that differ in production performance. Hyline W36 and W98 hens (n = 6 per diet) received a barley-based ration containing 0, 2, 4, 8, 16, 32, 64, or 128 mg/kg of crystalline folic acid for 21 d. Response criteria included production parameters, measures of blood folate status, and egg folate content. Significant (P < 0.05) main effects of folate supplementation were observed for egg folate content and plasma folate, which increased, and homocysteine concentrations, which decreased with supplementation; performance, however, was not affected. The Hyline W98 strain had significantly (P < 0.05) higher total egg and yolk weights and feed consumption when compared with the W36. Significant (P < 0.05) ration x strain interactions were observed for egg and yolk weight, egg folate content, and plasma homocysteine. The higher egg mass producing strain, Hyline W98, benefited from increased folic acid through a reduction in plasma homocysteine concentrations, suggesting that this strain has a higher requirement for folate than the W36 strain. Overall, egg folate content is maximized when crystalline folic acid is supplemented to the diet at 2 mg/kg or higher. Higher levels of egg folate are not achieved due to the saturation of the precursor pool for egg folate deposition. PMID:16335121

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

2005-10-01

269

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

270

The use of imidazolium ionic liquid/copper complex as novel and green catalyst for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals.  

PubMed

A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu(2+) and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1×10(-9)-1×10(-)(6) M of folic acid with a correlation coefficient (R(2)) of 0.9991. The limit of detection of this system was found to be 1×10(-)(10) M. This method is not only simple, sensitive and low cost, but also reliable for practical applications. PMID:24322762

Azizi, Seyed Naser; Shakeri, Parmis; Chaichi, Mohammad Javad; Bekhradnia, Ahmadreza; Taghavi, Mehdi; Ghaemy, Mousa

2014-03-25

271

Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands  

Microsoft Academic Search

AIMS: To investigate the potentially protective of periconceptional folic acid use on the risk of congenital heart defects (CHDs) relative to other non-folate related malformations. METHODS AND RESULTS: We analysed data from a large regional register of birth defects (EUROCAT-Northern Netherlands), over a 10 year period (1996-2005) for a case-control study. The cases were mothers who had delivered infants with

I. M. van Beijnum; L. Kapusta; M. K. Bakker; M. den Heijer; H. J. Blom; Walle de H. E. K

2010-01-01

272

Gene-environment interactions and the risk of childhood acute lymphoblastic leukemia: exploring the role of maternal folate genes and folic Acid fortification.  

PubMed

Few studies have evaluated the interaction of folic acid fortification and folate metabolic genes on the risk of childhood acute lymphoblastic leukemia (ALL). Because folate status is influenced by both intake and genetic variation, the objective of this study was to explore maternal folate metabolic gene-folic acid fortification interactions and the risk of childhood ALL. The study population consisted of 120 ALL case-parent triads recruited from Texas Children's Cancer Center between 2003 and 2010. For this analysis, we focused on 13 maternal single nucleotide polymorphisms (SNPs) in 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Prefortification was defined as delivery before January 1997 and postfortification as delivery in or after January 1997. We used a two-step approach to evaluate gene-environment interactions. First, a case-only approach was used, as this design provides greater power in the assessment of gene-environment interactions compared to other approaches. Second, we confirmed all statistically significant interactions using a log-linear approach among case-parent triads. Only one of 13 interactions evaluated was confirmed in step 2. Specifically, mothers with the minor allele of MTR rs1804742 and who delivered during the prefortification period were at a greater risk of having a child with ALL (OR = 1.54, 95% CI: 0.82-2.88), compared to those mothers who delivered during the postfortification period (OR = 0.81, 95% CI: 0.22-2.99, P for interaction = .03). In one of the few studies to evaluate maternal folate metabolic genotype-folic acid interactions, we found limited evidence that the maternal MTR rs1804742 appeared to interact with higher folic acid levels to influence childhood ALL risk. PMID:24087922

Lupo, Philip J; Dietz, Danielle J; Kamdar, Kala Y; Scheurer, Michael E

2014-03-01

273

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

274

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients  

Microsoft Academic Search

Background: Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been\\u000a tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study,\\u000a we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral\\u000a FA supplementation on

Kostas Sombolos; Anna Papaioannou; Fotini Christidou; Taisir Natse; Gerasimos Bamichas; Lazaros Gionanlis; George Katsaris; Evagelia Progia

2006-01-01

275

Supramolecular gel from folic acid with multiple responsiveness, rapid self-recovery and orthogonal self-assemblies.  

PubMed

Through a good/poor solvent strategy, native folic acid (FA) which behaves as a super-gelator in DMSO-water system can be successfully employed to construct supramolecular gels. The system exhibited morphological evolution with the increase of FA concentration; various phases such as vesicles, fiber/vesicles, fiber/nanoparticles, nanoparticles were probed. In the self-assembly process, l-glutamic acid moiety induced the formation of helical 1-dimensional (1-D) fibers which further self-assembled into a gel. Stimuli like heat, stress, pH and light which affect the molecular structure of FA or solubility in the mixed solvents had a pronounced influence on the properties of the gels, such as mechanical properties or bulk phases. A time-dependent oscillatory stress scan indicated that the supramolecular gel had a self-healing property. Without tedious modification routes and addition of alkali metal ions, native FA which served as an efficient building block and super-gelator to build up multi-responsive and self-recovery material was investigated for the first time. PMID:24658366

Xing, Pengyao; Chu, Xiaoxiao; Ma, Mingfang; Li, Shangyang; Hao, Aiyou

2014-05-14

276

Reduction in mortality and teratogenicity following simultaneous administration of folic acid and vitamin E with antiepileptic, antihypertensive and anti-allergic drugs  

PubMed Central

Aim: The present study was designed to evaluate the teratogenic effects on breeding pattern in mice following administration of lamotrigine (LT) and levetiracetam (LV) and its combination with anti-hypertensive and anti-allergic drugs. Moreover, possibility of decrease in teratogenic effect was also evaluated upon simultaneous administration of these combinations with folic acid or vitamin E. Materials and Methods: The study was carried out on mature female mice housed in polycarbonate breeding cages. Drugs were administered continuously till the birth of neonates and pups were examined for any teratogenic potential of drugs. Results: The results of the study reveals that teratogenic effects of lamotrigine, methyldopa and loratadine (LTMLO) combination were seems to be reduced upon simultaneous administration with folic acid, while addition of vitamin E was found to be more effective in reducing the mortality rate of levetiracetam, methyldopa and loratadine combination. Conclusion: Teratogenic effects of LTMLO combination were better prevented by folic acid. However, further studies on large number of animals and humans are required before reaching to definite conclusion.

Wahid, Shahana; Khan, Rafeeq Alam; Feroz, Zeeshan

2014-01-01

277

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

278

Maternal multiple micronutrient supplementation has limited impact on micronutrient status of Bangladeshi infants compared with standard iron and folic acid supplementation.  

PubMed

Knowledge about the impact of maternal food and micronutrient supplementation on infant micronutrient status is limited. We examined the effect of maternal food and micronutrient supplementation on infant micronutrient status in the Maternal and Infant Nutrition Interventions in Matlab Trial. Pregnant women (n = 4436) were randomized to Early or Usual promotion of enrollment in a food supplementation program. In addition, they were randomly allocated to 1 of the following 3 types of daily micronutrient supplements provided from wk 14 of gestation to 3 mo postpartum: 1) folic acid and 30 mg iron (Fe30Fol); 2) folic acid and 60 mg iron; or 3) a multiple micronutrient including folic acid and 30 mg iron (MMS). At 6 mo, infant blood samples (n = 1066) were collected and analyzed for hemoglobin and plasma ferritin, zinc, retinol, vitamin B-12, and folate. The vitamin B-12 concentration differed between the micronutrient supplementation groups (P = 0.049). The prevalence of vitamin B-12 deficiency was lower in the MMS group (26.1%) than in the Fe30Fol group (36.5%) (P = 0.003). The prevalence of zinc deficiency was lower in the Usual food supplementation group (54.1%) than in the Early group (60.2%) (P = 0.046). There were no other differential effects according to food or micronutrient supplementation groups. We conclude that maternal multiple micronutrient supplementation may have a beneficial effect on vitamin B-12 status in infancy. PMID:20053938

Eneroth, Hanna; El Arifeen, Shams; Persson, Lars-Ake; Lönnerdal, Bo; Hossain, Mohammad Bakhtiar; Stephensen, Charles B; Ekström, Eva-Charlotte

2010-03-01

279

Differential usage of the transport systems for folic acid and methotrexate in normal human T-lymphocytes and leukemic cells.  

PubMed

Methotrexate (MTX) has been used as an effective anti-cancer drug for a long time. Conceptually, it is accepted that MTX and folic acid are transported by folate receptors (FRs) in cancerous cells, but the exact mechanism of MTX uptake in human leukemia is unknown. The objective of this study was to investigate different transport systems for FA and MTX, and to delineate their uptake mechanism in MOLT4, K562, Hut78 leukemia cells and normal human T cells. In MOLT4, uptake of MTX was higher than FA, similar to that of K562, Hut78 and normal T cells. In MOLT4 cells, MTX uptake was maximum at pH 7.4 whereas FA uptake was maximum at pH 4.5. Uptake of FA and MTX was significantly inhibited by anions, suggesting anion-dependent transport system. FA uptake was found to be energy dependent whereas MTX uptake was energy independent. RT-PCR and immunofluorescence results demonstrated the presence of reduced folate carrier as well as proton coupled folate transporter and absence of FR in MOLT4 and normal T cells. These data suggest the existence of two separate and independent carrier-mediated transport systems for the uptake of FA and MTX in normal and leukemic human T cells. PMID:19692428

Biswal, Bijesh Kumar; Verma, Rama Shanker

2009-11-01

280

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes.  

PubMed

The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively). PMID:24728915

Cao, Yunlei; Zhang, Zhaofeng; Zheng, Yanmin; Yuan, Wei; Wang, Jian; Liang, Hong; Chen, Jianping; Du, Jing; Shen, Yueping

2014-05-01

281

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

282

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

PubMed

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. PMID:19121630

Wu, Xiayu; Liang, Ziqing; Zou, Tianning; Wang, Xu

2009-02-13

283

[Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification].  

PubMed

This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC) and presented prevalence rates according to maternal characteristics with odds ratios (OR) and 95% confidence intervals (95%CI). Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube defects decreased by 35%, from 0.57/1,000 to 0.37/1,000 live births after fortification (OR = 0.65; 95%CI: 0.59-0.72). There was a reduction among newborns of mothers with the following characteristics: all age groups (except < 15 years), more than three years of schooling, and seven or more prenatal visits. There was a reduction over time and in most of São Paulo State, except in a few municipalities (counties) located in the western region of the State. Other factors may have contributed to the observed decline, but the results corroborate flour fortification as an important measure to prevent neural tube defects. Further research is needed to elucidate the lack of a decline in neural tube defects in the western part of São Paulo State. PMID:23370034

Fujimori, Elizabeth; Baldino, Camila Florido; Sato, Ana Paula Sayuri; Borges, Ana Luiza Vilela; Gomes, Murilo Novaes

2013-01-01

284

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

PubMed

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 [microg/kg], respectively 0 and 0 (V0), 10 and 25 (V1), and 10 and 150 (V2) in a 2 x 3 factorial arrangement. Feed conversion was lower (p = 0.05) in M than in C pigs during the growing period (0-4 weeks). Both V1 and V2 treatments increased plasma vitamin B12 (p < 0.01) and decreased plasma homocysteine (p < 0.01). Plasma 5-methyl-tetrahydrofolates were the lowest, highest and intermediate in V0, V1 and V2 pigs (p < 0.04), respectively. In V2 meat, folates were 32% higher, vitamin B12, 55% higher and homocysteine, 28% lower than in V0 (p < 0.01). Oxidative stability of the fresh meat was similar among treatments during a storage period of 42 days. Therefore, methionine supplements improved growth performance during the growing period. Vitamin supplements interacted with the methionine cycle pathway, increased vitamin content of pork meat but did not improve oxidative stability of the fresh meat during storage. PMID:18610535

Giguére, Alain; Girard, Christiane L; Matte, J Jacques

2008-06-01

285

Explaining the effects of anticipated regret messages on young women's intention to consume folic acid: a moderated-mediation model.  

PubMed

This study tests a moderated-mediation model to explain the joint effects of consideration of future consequences and exposure to health messages containing an anticipated regret component on behavioral intention to consume folic acid. In an online survey-experiment conducted in March 2011, 245 women 18-35 years of age were randomized to 1 of 3 conditions (exposure to attitude-only message/exposure to attitude-plus-anticipated-regret message/no message exposure) in a between-participants design. Results showed a positive joint effect of consideration of future consequences and exposure to an attitude-plus-anticipated-regret message on anticipated regret (B = 0.89, SE = 0.41, p < .05). Among women high in consideration of future consequences, exposure to an attitude-plus-anticipated-regret message increased anticipated regret. Likewise, another positive joint effect of consideration of future consequences and anticipated regret on behavioral intention was observed (B = 0.28, SE = 0.12, p < .05). Anticipated regret was positively related to intention among women high in consideration of future consequences. Implications are discussed. PMID:24083394

Martinez, Lourdes S

2014-01-01

286

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

287

Functional assessment of zinc nutriture using changes in plasma zinc after exercise in men supplemented with folic acid  

SciTech Connect

Recently, the authors proposed that changes in plasma zinc (Zn) and copper (Cu) content after maximal exercise could be a functional test of human trace element nutriture. To test this hypothesis, they studied the effect of folic acid (FA) supplements, previously shown to affect zinc absorption on the exercise-induced changes in plasma Zn and Cu in 7 men aged 28.6 +/- 1.2 yr (mean +/- SEM). The men were fed a constant diet with intakes of Cu (1.01 +/- 0.06 mg/d), Zn (12.7 +/- 0.3 mg/d) and FA (200 mg/d) for two 4 wk periods. This basal diet was supplemented with 400 or 800 mg/d FA and it was fed for 4 wk periods alternating with the unsupplemented diet. Pre and post-exercise hematocrit (Hct), hemoglobin (Hb), and plasma Zn and Cu were not affected by FA supplements. To correct for hemoconcentration during exercise, the van Beaumont quotient was calculated from pre and post-exercise Hct, Hb, and plasma Zn and Cu. When the basal diet was fed, the quotient for Zn was 3.4 +/- 1.4 and 2.3 +/- 1.4%, and it declined (p < 0.05) to -5.93 +/- 1.9% and -7.4 +/- 1.8% with 400 and 800 mg/d supplementation, resp. FA supplementation had no effect on the quotient for plasma Cu. These data suggest that Zn mobilization from stores during exercise is impaired with high intakes of FA.

Lukaski, H.C.; Bolonchuk, W.W.; Milne, D.B.

1986-03-05

288

Effects of folic acid on renal endothelial function in patients with diabetic nephropathy: results from a randomized trial.  

PubMed

Endothelial dysfunction has been shown to promote podocyte injury and albuminuria in diabetes, highlighting the importance of the interaction between renal endothelial cells and podocytes. Folic acid (FA) improves nitric oxide synthase (NOS) function and reduces progression of diabetic nephropathy in animal models. We tested whether high-dose FA treatment improves renal endothelial function and albuminuria in human subjects with incipient diabetic nephropathy. Following a double-blind, randomized, cross-over design, 28 patients with Type 2 diabetes and albuminuria were allocated to 4 weeks' treatment with placebo and high-dose FA (5 mg/day). Renal nitric oxide (NO) production determined as the response of renal plasma flow (RPF) to NOS inhibition with NG-monomethyl-L-arginine (L-NMMA) (4.25 mg/kg intravenously), renal oxidant stress as response of RPF to vitamin C infusion (3 mg/kg) and albuminuria were determined after each treatment phase. Neither the reduction in RPF to L-NMMA nor the increase in RPF to vitamin C infusion differed between treatment phases (?RPF to L-NMMA: -74±71 ml/min per m2 during placebo compared with -63±56 ml/min per m2 during FA, P=0.57; ?RPF to vitamin C: +93±118 ml/min per m2 compared with +94±108 ml/min per m2; P=0.70). In line with the lack of effect on the renal endothelium, albuminuria was not affected by FA treatment (110±179 mg/day during placebo compared with 87±146 mg/day during FA; P=0.12). High-dose FA treatment does not improve renal endothelial function and fails to reduce albuminuria in human subjects with diabetic nephropathy. Novel treatment options for oxidant stress and endothelial dysfunction in patients with diabetes are urgently needed. PMID:24724807

Schneider, Markus P; Schneider, Andreas; Jumar, Agnes; Kistner, Iris; Ott, Christian; Schmieder, Roland E

2014-10-01

289

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

2013-11-01

290

Predictors of preconceptional folic acid or multivitamin supplement use: a cross-sectional study of Danish pregnancy planners  

PubMed Central

Purpose Compliance with the Danish preconceptional folic acid (FA) recommendation – a daily supplement of 400 ?g – is reported to be poor. Uncertainty remains, however, about the prevalence of compliers and health-related predictors of compliance in the preconceptional period. Methods We used self-reported baseline data from 5383 women, aged 18–40 years, enrolled in an Internet-based prospective cohort study of Danish pregnancy planners during 2007–2011. We estimated the prevalence proportions of FA or multivitamin (MV) use in relation to selected sociodemographic, lifestyle, reproductive, and medical characteristics. Multivariate binomial regression was used to obtain prevalence proportion differences with 95% confidence intervals for each level of study predictors, adjusted for all other predictors. Results Overall, 7.7% of women used FA supplements, 20.4% used MV supplements, 34.0% used both, 1.5% used other single vitamins or minerals, and 36.4% did not use any dietary supplements. The prevalence of FA or MV supplement use was higher among older women, women with higher education and income, and women with healthy lifestyle factors such as being a nonsmoker, nondrinker, physically active, maintaining a normal body mass index and having regular pap smears. Greater intercourse frequency and a history of spontaneous abortion were also positively associated with FA or MV supplement use. We found no clear association between use of FA or MV supplements and a diagnosis of hypertension, diabetes, thyroid disease, pelvic inflammatory disease, or chlamydia. Conclusion A large proportion of pregnancy planners do not use FA or MV supplements. Pregnancy planners with generally risky lifestyle behaviors are less likely to comply with the FA recommendation.

Cueto, Heidi T; Riis, Anders H; Hatch, Elizabeth E; Wise, Lauren A; Rothman, Kenneth J; Mikkelsen, Ellen M

2012-01-01

291

The Solid-Phase Synthesis of PolyglutamateSS OF Folic Acid.  

National Technical Information Service (NTIS)

Details of an unambiguous chemical synthesis by which pteroyl-(gamma-L-glutamyl)n-L-glutamic acid of any desired chain length (up to n = 6) may be prepared are reported. The procedures employed are modifications of the Merrifield solid-phase peptide synth...

C. L. Krumdieck C. M. Baugh

1968-01-01

292

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

293

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 0.10 nM. 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

2013-11-01

294

Magnetic nanocarriers of doxorubicin coated with poly(ethylene glycol) and folic acid: relation between coating structure, surface properties, colloidal stability, and cancer cell targeting.  

PubMed

We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure-activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics. PMID:22172203

Kaaki, Karine; Hervé-Aubert, Katel; Chiper, Manuela; Shkilnyy, Andriy; Soucé, Martin; Benoit, Roland; Paillard, Archibald; Dubois, Pierre; Saboungi, Marie-Louise; Chourpa, Igor

2012-01-17

295

Structural elucidation of specific noncovalent association of folic acid with native cyclodextrins using an ion mobility mass spectrometry and theoretical approach.  

PubMed

The combination of ion mobility mass spectrometry studies and theoretical calculations including docking studies permitted a detailed structural description of noncovalent complexes of folic acid (FA) and native cyclodextrins (?-CD, ?-CD, and ?-CD). The mode of noncovalent association depended on the cavity size of the cyclodextrin. The structure of FA/?-CD represented the exclusion complex in which the aminobenzoic moiety and the aromatic pteridine ring of folic acid remain outside the cyclodextrin cavity, while the glutamate residue is anchored in the interior of the ?-cyclodextrin. A rotaxane-type structure was proposed for the FA/?-CD complex with the aminobenzoic part of FA being trapped in the central cavity of ?-CD. The glutamate residue and the aromatic pteridine ring interact with the primary and secondary rim hydroxyl residues, respectively, enhancing complex stability. Two possible structures of FA/?-CD were suggested, the first one being analogous to the FA/?-CD complex and the second one being more stable-in which the aromatic pteridine ring penetrates into the CD cavity while the glutamate residue with the aminobenzoic part of FA is exposed to the cone exterior of CD at its wider edge. Further insight into the association behavior of the folic acid toward cyclodextrins evaluated by thermodynamic calculations indicates that the process is highly exothermic. The complex stability increased in the order FA/?-CD < FA/?-CD < FA/?-CD. This order is consistent with the previously determined relative gas-phase stability established based on the dissociation efficiency curves of the FA/CD complexes. PMID:24712714

Zimnicka, Magdalena; Tro?, Anna; Ceborska, Magdalena; Jakubczak, Micha?; Koli?ski, Micha?; Danikiewicz, Witold

2014-05-01

296

Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12) and Omega-3 Fatty Acids  

PubMed Central

We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes.

Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana

2014-01-01

297

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

2013-12-01

298

Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo  

PubMed Central

Oral administration of a retinoic acid receptor (RAR) pan-antagonist reversibly inhibits spermatogenesis. Given the importance of RAR? in regulating spermatogenesis, we identified two RAR?-selective antagonists by transactivation and transactivation competition assays and asked whether they effectively inhibit spermatogenesis. Although these two antagonists were potent in vitro, they displayed poor in vivo activity in mice when administered orally. Testicular weights were normal and morphological analysis revealed normal spermatid alignment and sperm release. In vitro drug property analyses were performed with one of these antagonists and compared with the pan-antagonist. We showed that the discrepancies may be explained by several factors, including high plasma protein binding, faster hepatic metabolism relative to the pan-antagonist, and only moderate permeability. The conclusion of poor oral bioavailability was supported by more pronounced defects in mice when the antagonist was administered intravenously versus intraperitoneally. These results are crucial for designing new RAR?-selective antagonists for pharmaceutical application.

Chung, Sanny S. W.; Cuellar, Rebecca A. D.; Wang, Xiangyuan; Reczek, Peter R.; Georg, Gunda I.; Wolgemuth, Debra J.

2013-01-01

299

Betidamino acid scan of the GnRH antagonist acyline.  

PubMed

Strong clinical evidence suggests that GnRH antagonists will replace GnRH agonists in a number of indications because of their ability to inhibit gonadotropin secretion as long as an adequate concentration of the analogue is present in the circulation whereas superagonists will take approximately 2 weeks to desensitize the gonadotrophs. Until recently, antagonists were either too weak and/or would release histamine. Azaline B {[Ac-D2Nal1,D4Cpa2,D3Pal3, 4Aph5(atz),D4Aph6(atz),ILys8,DAla10] GnRH} and long-acting members of the azaline family {Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(X)-D4Aph(Y) -Leu-ILys-Pro-DAla-NH2}, however, appear to be promising drug candidates. Because these antagonists tend to form gels (due to the formation of beta-sheet structures) and, as a result, are not readily amenable to formulation for long-term delivery, we have investigated ways of increasing hydrophilicity while retaining high potency and lack of histamine releasing activity. Betidamino acids (a contraction of "beta" position and "amide") are N'-monoacylated (optionally, N'-monoacylated and N-mono- or N,N'-dialkylated) aminoglycine derivatives in which each N'-acyl/alkyl group may mimic naturally occurring amino acid side chains or introduce novel functionalities. We have used unresolved N alpha-Boc,N'alpha-Fmoc-aminoglycine, and N alpha-Boc,N'alpha-(CH3)Fmoc-aminoglycine as templates for the introduction of betidamino acids in acyline (Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(A c)-Leu-Ilys-Pro-DAla-NH2), a long acting member of the azaline B family, to test biocompatibility of these betide derivatives. Diastereomeric peptides could be separated using RP-HPLC in most cases. Biological results obtained in vitro (binding affinity to rat pituitary gland membranes) and in vivo (rat antiovulatory assay, AOA) indicate in most cases small differences in relative potencies (< 5-fold) between the D- and L-nonalkylated betidamino acid-containing acylines. Importantly, most betide diastereomers have high affinity for the GnRH receptor and were equipotent with acyline in the AOA. Greater differences in affinity and potency between diastereomers were observed after introduction of a methyl group on the side chain nitrogen ("beta" position) of the same analogues, with one of the diastereomer having an affinity and a potency in the AOA equivalent to that of acyline. These results suggest that chirality at the alpha-carbon coupled to side chain orientation is important for receptor recognition. The duration of action of some of the most potent analogues was also determined in the castrated male rat in order to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone release. Data suggest that introduction of a betidamino acid results in reduction of duration of action. Also, introduction of betidamino acids results in peptides with increased hydrophilicity (as determined by elution times on C18 silicas at pH 7.3) compared to that of the parent compound. N'-Methyl substitution results in parallel increase in retention times on C18 silicas as expected. PMID:9371239

Jiang, G; Miller, C; Koerber, S C; Porter, J; Craig, A G; Bhattacharjee, S; Kraft, P; Burris, T P; Campen, C A; Rivier, C L; Rivier, J E

1997-11-01

300

Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring  

PubMed Central

Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the life course may have lasting effects, with alterations in brain development resulting in changes in behavior.

Kuizon, Salomon; Buenaventura, Diego; Stapley, Nathan W.; Ruocco, Felicia; Begum, Umme; Guariglia, Sara R.; Brown, W. Ted; Junaid, Mohammed A.

2014-01-01

301

One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice  

PubMed Central

Background In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory cytokine expression and inhibits leukocyte migration. It is also a potent inhibitor of mitochondrial permeability, protecting cells from death. These properties make it a potentially valuable drug to prevent or treat AKI. It does, however, carry a significant risk of nephrotoxicity, especially with chronic use. By contrast, a single dose of CsA may be protective while limiting the risk of nephrotoxicity. Methods We conducted a controlled animal experiment in male CD-1 mice. Specifically, mice were subjected to folic acid (FA)-induced AKI and then randomly assigned to sham operation or one of three dosage of CsA treatment groups. Results Intraperitoneal injection of FA consistently induced AKI. Serum interleukin (IL)-6 and urinary neutrophil gelatinase-associated lipocalin (NGAL) rose 1 day after FA injection. Compared to sham treatment, one dose (1 and 5 mg/kg body weight) of CsA significantly reduced kidney tubular cell apoptosis, serum creatinine, blood urea, serum IL-6 and urinary NGAL 2 days after FA injection. It was also shown to block the inflammatory mediator tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression, nuclear factor kappa-B (NF?B) activation, inflammatory cell infiltration and interstitial fibrosis 14 days after treatment in a dose-dependent fashion. By contrast, a dose of 10 mg/kg body weight CsA resulted in nephrotoxicity in the setting of FA-induced AKI. Conclusions A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI.

Wen, Xiaoyan; Peng, Zhiyong; Li, Yingjian; Wang, Hongzhi; Bishop, Jeffrey V.; Chedwick, Lisa R.; Singbartl, Kai; Kellum, John A.

2012-01-01

302

Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases.  

PubMed

In order to avoid the toxicities associated with prescription drug use today, we have explored novel methods for delivering drugs selectively to pathologic cells, thereby avoiding the collateral damage that accompanies their uptake by healthy cells. In this Account, we describe our quest for the ideal targeted therapeutic agent. This effort began with a search for ligands that would bind selectively to pathologic cells, displaying no affinity for healthy cells. After identification of an optimal targeting ligand, effort was focused on construction of linkers that would carry the attached drug to pathologic cells with receptors for the selected ligand. In the case of cancer, we exploited the well-characterized up-regulation of folate receptors on malignant cells to target folate-linked pharmaceuticals to cancer tissues in vivo. Drugs that have been linked to folic acid for tumor-selective drug delivery to date include (i) protein toxins, (ii) chemotherapeutic agents, (iii) gene therapy vectors, (iv) oligonucleotides (including small interfering RNA (siRNA)), (v) radioimaging agents, (vi) magnetic resonance imaging (MRI) contrast agents, (vii) liposomes with entrapped drugs, (viii) radiotherapeutic agents, (ix) immunotherapeutic agents, and (x) enzyme constructs for prodrug therapy. Current clinical trials of four folate-linked drugs demonstrate that folate receptor-targeting holds great promise for increasing the potency while reducing toxicity of many cancer therapies. In the course of developing folate-conjugated drugs for cancer, we discovered that folate receptors are also overexpressed on activated (but not resting or quiescent) macrophages. Recognizing that activated macrophages either cause or contribute to such diseases as rheumatoid arthritis, Crohn's disease, atherosclerosis, lupus, inflammatory osteoarthritis, diabetes, ischemia reperfusion injury, glomerulonephritis, sarcoidosis, psoriasis, Sjogren's disease, and vasculitis, we initiated studies aimed at developing folate-conjugated imaging and therapeutic agents for the diagnosis and treatment of such diseases. In very brief time, significant progress has been made towards identification of clinical candidates for targeted treatment of several inflammatory and autoimmune diseases. This Account summarizes the discovery and development of a variety of folate-targeted drugs for the diagnosis and therapy of cancers and inflammatory/autoimmune diseases. PMID:17655275

Low, Philip S; Henne, Walter A; Doorneweerd, Derek D

2008-01-01

303

Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, ?-Cyclodextrin-Based Drug Complexes for Cancer Treatment  

PubMed Central

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant Ka was 1,639 M?1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated ?-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

Yin, Juan-Juan; Sharma, Sonali; Shumyak, Stepan P.; Wang, Zhi-Xin; Zhou, Zhi-Wei; Zhang, Yangde; Guo, Peixuan; Li, Chen-Zhong; Kanwar, Jagat R.; Yang, Tianxin; Mohapatra, Shyam S.; Liu, Wanqing; Duan, Wei; Wang, Jian-Cheng; Li, Qi; Zhang, Xueji; Tan, Jun; Jia, Lee; Liang, Jun; Wei, Ming Q.; Li, Xiaotian; Zhou, Shu-Feng

2013-01-01

304

Folic acid-conjugated iron oxide porous nanorods loaded with doxorubicin for targeted drug delivery.  

PubMed

Iron oxide porous nanorods (IOPNR) with lengths ranging from 40nm to 60nm and pore diameters ranging from 5nm to 10nm were prepared, and further modified with NH2-PEG-FA (FA-PEG-IOPNR) for ligand targeting and modified with NH2-PEG-OCH3 (PEG-IOPNR) as a control. Instead of chemical bonding, doxorubicin (DOX), a low water solubility anticancer drug, was loaded in the pores of the modified IOPNR because of their porous structure and high porosity. The release of DOX in acidic PBS solution (pH 5.3) was faster than that in neutral (pH 7.4) solution. The analysis results from TEM, inductively coupled plasma emission spectroscopy, confocal laser scanning microscopy, and flow cytometry analyses indicated that the presence of FA on the surface of the nanorods increase the cellular uptake of nanorods in the case of HeLa cells, a folate receptor (FR)-positive cell line. In contrast, for COS 7 cells, a FR-negative cell line, FA ligand on the surface of the nanorods showed no effect on the cellular uptake. MTT assay indicated that the cytotoxicity of DOX loaded in FA-PEG-IOPNR to HeLa cells was higher than that of DOX in PEG-IOPNR. In the case of COS 7 cells, no significant difference between the cytotoxicity of DOX loaded in FA-PEG-IOPNR and PEG-IOPNR was found. These results suggested that FA-PEG-IOPNR had the potential for target delivery of chemotherapeutic into cancer cells. PMID:24907583

Yu, Ping; Xia, Xi-Ming; Wu, Ming; Cui, Can; Zhang, Yang; Liu, Lei; Wu, Bo; Wang, Cai-Xia; Zhang, Liu-Jie; Zhou, Xiang; Zhuo, Ren-Xi; Huang, Shi-Wen

2014-08-01

305

Role of Hyperhomocysteinemia in the Regulation of Oxidative Stress and Inflammatory Responses in the Kidney: Protective Effect of Folic Acid Supplementation  

NASA Astrophysics Data System (ADS)

Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) level, is an independent risk factor for cardiovascular disease. Folic acid supplementation can effectively reduce blood Hcy levels. Recent studies have demonstrated that hyperhomocysteinemia is also associated with kidney disease. However, the underlying mechanisms remain unclear. The overall objective of the study was to investigate the biochemical and molecular mechanisms of Hcy-induced kidney injury and the effect of folic acid supplementation on Hcy-induced kidney injury. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 12 weeks. An elevation of serum total Hcy level was observed in hyperhomocysteinemic rats. Hyperhomocysteinemia-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation resulted in oxidative stress in the kidney. Reduction of oxidative stress by inhibiting superoxide anion production effectively ameliorated hyperhomocysteinemia-induced kidney injury. Inflammatory responses such as increased chemokine expression have been implicated as one of the mechanisms of kidney disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in kidney disease. Nuclear factor-kappa B (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism responsible for such an effect in rat kidneys as well as in human kidney proximal tubular cells.

Hwang, Sun-Young

306

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro.  

PubMed

A synthetic method to prepare a core-shell-structured Fe3O4@SiO2 as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe3O4@SiO2-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy. PMID:24667013

Li, Hongmei; Li, Zhen; Zhao, Jin; Tang, Baoqiang; Chen, Yanhong; Hu, Yikun; He, Zhengda; Wang, Yue

2014-01-01

307

Exp 3 H-Radioactivity Measurement in the Rat Kidney after Single Injection of Folic Acid and Continuous Infusion of exp 3 H-Thymidine. Comparison with Relevant Autoradiographic Studies.  

National Technical Information Service (NTIS)

Male Sprague-Dawley rats received a single i.v. injection of folic acid. Immediately afterwards, continuous intravenous infusion of exp 3 H-Thymidine has been started. The animals have been sacrified after 0.5 up to 10.0 days for determination of the vita...

C. Kittidesdamkerng

1979-01-01

308

Effects of intramuscular injections of vitamin B12 on lactation performance of dairy cows fed dietary supplements of folic acid and rumen-protected methionine.  

PubMed

The experiment was undertaken to determine the effects of i.m. injections of vitamin B(12) on lactational performance of primiparous dairy cows fed dietary supplements of folic acid and rumen-protected methionine from 4 to 18 wk of lactation. Fourteen primiparous Holstein cows were assigned to 7 blocks of 2 cows each, according to milk production during the third week of lactation. All cows were fed a basal diet supplemented daily with rumen-protected methionine (18 g of supplement, to bring the estimated supply of methionine to 2.2% of metabolizable protein) plus folic acid (4 mg per kg of BW). Within each block, the cows received a weekly i.m. injection (2 mL) of saline or 10 mg of vitamin B(12). Milk production was recorded daily. Milk and blood were sampled every 2 wk. Supplementary vitamin B(12) increased energy-corrected milk from 25.8 to 29.0 (SE 1.6) kg/d, as well as milk yields of solids [3.52 to 3.90 (SE 0.22) kg/d], fat [0.87 to 1.01 (SE 0.06) kg/d], and lactose [1.48 to 1.64 (SE 0.11) kg/d]. Supplementation also increased concentrations and amounts of vitamin B(12) secreted in milk but had no significant effect on dry matter intake and concentrations and amounts of folates in milk. Packed cell volume, blood hemoglobin, and serum vitamin B(12) were increased by supplementary vitamin B(12), whereas serum methylmalonic acid was decreased. Serum concentrations of sulfur amino acids were unchanged by treatment. These findings support the hypothesis that, in early lactation, supply of vitamin B(12) was not optimal and limited the lactation performance of the cows. PMID:15653534

Girard, C L; Matte, J J

2005-02-01

309

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

PubMed Central

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.

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

2013-01-01

310

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

311

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

312

Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study.  

PubMed

Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95% confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects. PMID:24092049

Rozendaal, Anna M; van Essen, Anthonie J; te Meerman, Gerard J; Bakker, Marian K; van der Biezen, Jan J; Goorhuis-Brouwer, Sieneke M; Vermeij-Keers, Christl; de Walle, Hermien E K

2013-11-01

313

Targeted Dendrimeric Anticancer Prodrug: A Methotrexate-Folic Acid-Poly(amidoamine) Conjugate and a Novel, Rapid, "One pot" Synthetic Approach  

PubMed Central

A targeted dendrimeric anticancer prodrug, a conjugate of Generation 5 (G5) polyamidoamine (PAMAM) dendrimer, folic acid (FA), and methotrexate (MTX), has been successfully synthesized by using a novel “one pot” approach which is simple, reproducible and feasible for large-scale synthesis. All dendrimer products have been characterized by 1H NMR, MALDI-TOF, GPC, and HPLC. With this new method, the ratio of FA versus MTX attached to the dendrimer can be easily tuned to achieve the desired therapeutic effect. A new analytical approach for calculating the numbers of FA and MTX attached to the dendrimer has been established. In vitro studies performed on FA receptor-expressing KB cells show that the new conjugate has a similar affinity and cytotoxic potency to G5-FA-MTX synthesized using the traditional multiple-step approach.

Zhang, Yuehua; Thomas, Thommey P.; Desai, Ankur; Zong, Hong; Leroueil, Pascale R.; Majoros, Istvan J.; Baker, James R.

2010-01-01

314

Folic acid-conjugated 4-amino-phenylboronate, a boron-containing compound designed for boron neutron capture therapy, is an unexpected agonist for human neutrophils and platelets.  

PubMed

Boron neutron capture therapy (BNCT) is an anticancer treatment based on the accumulation in the tumor cells of (10) B-containing molecules and subsequent irradiation with low-energy neutrons, which bring about the decay of (10) B to very toxic (7) Li(3+) and (4) He(2+) ions. The effectiveness of BNCT is limited by the low delivery and accumulation of the used (10) B-containing compounds. Here, we report the development of folic acid-conjugated 4-amino-phenylboronate as a novel possible compound for the selective delivery of (10) B in BNCT. An extensive analysis about its biocompatibility to mature blood cells and platelet progenitors revealed that the compound markedly supports platelet aggregation, neutrophil oxidative burst, and inhibition of megakaryocyte development, while it does not have any manifest effect on red blood cells. PMID:24666508

Achilli, Cesare; Jadhav, Sushilkumar A; Guidetti, Gianni F; Ciana, Annarita; Abbonante, Vittorio; Malara, Alessandro; Fagnoni, Maurizio; Torti, Mauro; Balduini, Alessandra; Balduini, Cesare; Minetti, Giampaolo

2014-05-01

315

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

2005-01-01

316

Completeness of reporting of setting and health worker cadre among trials on antenatal iron and folic acid supplementation in pregnancy: an assessment based on two Cochrane reviews  

PubMed Central

Background Poor reporting of medical trials has triggered the development of trial reporting standards within the scientific community. In addition to a description of the proposed intervention, adequate information about the trial setting and the group of health workers (cadre) delivering the intervention would allow a better understanding of the generalizability of the trial findings, facilitate replication of trial interventions and assist with assessment of trials for inclusion in systematic reviews. This study aims to determine the completeness of reporting for trial setting and cadre among trials included in two Cochrane reviews on iron and folic acid supplementation for women during pregnancy. Methods From the 81 trials included in the two Cochrane reviews, we extracted data on the trial setting, including the facility type and geographic location, facility descriptors (i.e. level of care) and population descriptors (i.e. socioeconomic status); and the cadre, including professional qualifications, training and supervision. Results Almost all studies reported the facility type and location (96%). However, only 68% included this information in the “methods” section of the report. Facility descriptors and population descriptors were less commonly reported (26% and 54% respectively). For 34% of the trials, we found some account of the type of health worker that delivered the intervention. Only 4% of the trials reported any training procedures. Conclusions Currently, complete reporting of setting and health worker cadre in iron and folic acid supplementation in pregnancy trials remains far from ideal, limiting assessments of the applicability of the trial findings. Trialists and journals need to ensure that this information is included in trial reports by adhering to and improving current reporting standards and by not making assumptions regarding readers’ knowledge of the context and of the intervention delivery mechanism.

2013-01-01

317

Antagonistic Effect of Fatty Acids Against Salmonella in Meat and Bone Meal  

PubMed Central

The purpose of this study was to determine whether fatty acids have an antagonistic effect on the growth and viability of Salmonella organisms. Thirty-two different lipid materials were used, utilizing a wide range of short and long free fatty acid chains expressed as per cent oleic acid.

Khan, Mahmood; Katamay, Michael

1969-01-01

318

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

319

Efficacy of Multivitamin Supplementation Containing Vitamins B 6 and B 12 and Folic Acid as Adjunctive Treatment with a Cholinesterase Inhibitor in Alzheimer's Disease: A 26Week, Randomized, Double-Blind, Placebo-Controlled Study in Taiwanese Patients  

Microsoft Academic Search

BackgroundElevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen.ObjectiveThe aim of this

Yu Sun; Chien-Jung Lu; Kuo-Liong Chien; Sien-Tsong Chen; Rong-Chi Chen

2007-01-01

320

Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug.  

PubMed

The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co-glycidyl methacrylate-co-N,N-bis(acryloyl)cystamine) microspheres were prepared by a two-stage distillation-precipitation polymerization with subsequent surface modification with FA. The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV-vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000?gmL(-1). The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release. PMID:24935187

Li, Rongrong; Feng, Fuli; Wang, Yinsong; Yang, Xiaoying; Yang, Xinlin; Yang, Victor C

2014-09-01

321

Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors  

PubMed Central

Background Folic acid (FA) is one of the B complex vitamins. It is thought that FA deficiency promotes atherosclerosis formation in arterial endothelium. FA, acting through reducing homocysteine (Hcy) levels, may contribute to decreased cholesterol (Ch) synthesis. The aim of this study was to analyze the association of low-dose folic acid supplementation with blood lipids concentrations in subjects with atherosclerosis risk factors. Material/Methods The study enrolled 124 Caucasian individuals (60 M, ages 20–39; and 64 F, ages 19–39) with atherosclerosis risk factors (family history of premature ischemic stroke, arterial hypertension, dyslipidemia, overweight and obesity, cigarette smoking, and low level of physical activity). The participants were asked to take FA at a low dose of 0.4 mg/24 h for 12 weeks. Results FA levels increased in females (6.3 vs. 12.5 ng/dL; p=0.001) and males (6.4 vs. 11.4 ng/dL; p=0.001) and Hcy levels decreased (10.6 vs. 8.3 ?mol/L; p=0.001 and 11.5 vs. 9.3; p=0.001, respectively). A significant reduction in mean concentration of total cholesterol in females (203.4 vs. 193.1 mg/dL; p=0.001) and in males (209.5 vs. 201.9; p=0.002) was observed. The low-density lipoprotein cholesterol (LDL-C) levels decreased in females and in males (107.4 vs. 99.9 mg/dL; p=0.001 and 121.5 vs. 115.1; p=0.002, respectively). The apoAI concentrations increased in smoking women and in men with BMI ?25 kg/m2 (p=0.032 and p=0.024, respectively). Conclusions Low-dose FA supplementation has a beneficial effect on blood lipids through decreasing concentrations of total cholesterol and LDL-C and increasing concentrations of apoAI.

Mierzecki, Artur; Kloda, Karolina; Bukowska, Hanna; Chelstowski, Kornel; Makarewicz-Wujec, Magdalena; Kozlowska-Wojciechowska, Malgorzata

2013-01-01

322

Antiabsence seizure activity of specific GABAB and gamma-Hydroxybutyric acid receptor antagonists.  

PubMed

Hydroxybutyric acid (GHB) is a naturally occurring compound that has the ability to induce generalized absence seizures possibly by GABAB-receptor-mediated mechanisms. The object of these experiments was to examine the effectiveness of a range of specific GABAB-receptor agonists and antagonists of varying specificity, as well as the specific GHB-receptor antagonist NCS 382, in two experimental animal models of generalized absence seizures: one in which the seizures are induced by GHB and the other in which the seizures are induced by administration of low-dose (20-mg/kg) pentylenetetrazole. All specific GABAB-receptor antagonists as well as the specific GHB-receptor antagonist produced blockade of experimental absence seizures in both models; pretreatment with GABAB-receptor agonists resulted in generalized absence status epilepticus lasting for hours. These data confirm the concept that specific GABAB-receptor antagonist activity confers antiabsence seizure activity, suggest that the same holds for specific GHB-receptor antagonists, and raise the possibility that both GHB- and GABAB-antagonist drugs have the potential to be useful therapeutic agents in generalized absence seizures. PMID:8848463

Snead, O C

1996-01-01

323

Reye-like syndrome following treatment with the pantothenic acid antagonist, calcium hopantenate.  

PubMed Central

Three senile patients developed fatal acute encephalopathy while receiving calcium hopantenate. The clinical, biochemical, and pathological picture was similar to Reye's syndrome. Calcium hopantenate is a pantothenic acid antagonist. The serum levels of calcium hopantenate were high in coma, and that of pantothenic acid examined in one patient was lowered. Evidence obtained indicated that the Reye-like syndrome might be caused by calcium hopantenate possibly due to the induction of pantothenic acid deficiency. Images

Noda, S; Umezaki, H; Yamamoto, K; Araki, T; Murakami, T; Ishii, N

1988-01-01

324

Folic acid-conjugated, SERS-labeled silver nanotriangles for multimodal detection and targeted photothermal treatment on human ovarian cancer cells.  

PubMed

The effectiveness of a therapeutic agent for cancer stands in its ability to reduce and eliminate tumors without harming the healthy tissue nearby. Nanoparticles peripherally conjugated with targeting moieties offer major improvements in therapeutics through site specificity. In this study we demonstrate this approach by targeting the folate receptor of NIH:OVCAR-3 human ovary cancer cell line. Herein we used silver nanotriangles which were biocompatibilized with chitosan (bio)polymer, labeled with para-aminothiophenol (pATP) Raman reporter molecule, and conjugated with folic acid. The nanoparticles conjugation and efficient labeling was investigated by localized surface plasmon resonance (LSPR), zeta potential, and surface-enhanced Raman scattering (SERS) measurements. Conjugated particles were proven to be highly stable in aqueous and cellular medium. The targeted uptake of conjugated nanoparticles by human ovary cancer cells was confirmed by dark field microscopy and scattering spectra of the particles inside cells. Comparative studies revealed specific internalization of the conjugated nanoparticles in comparison with similar bare nanoparticles. Moreover, the SERS identity of the particles was proven to be highly conserved inside cells. Targeted cancer cell treatment conducted by irradiating the nanoparticle-treated cells with a continuous wave-nearinfrared (cw-NIR) laser in resonance with their plasmonic band proved an efficient therapeutic response. By integrating the advantages of multimodal optical imaging and SERS detection with hyperthermia capabilities through site specificity, these nanoparticles can represent a real candidate for personalized medicine. PMID:24304361

Boca-Farcau, Sanda; Potara, Monica; Simon, Timea; Juhem, Aurelie; Baldeck, Patrice; Astilean, Simion

2014-02-01

325

Facile formation of folic acid-modified dendrimer-stabilized gold-silver alloy nanoparticles for potential cellular computed tomography imaging applications.  

PubMed

We report a facile approach to fabricating dendrimer-stabilized gold-silver alloy nanoparticles (Au-Ag alloy DSNPs) for targeted in vitro computed tomography (CT) imaging of cancer cells. In this study, folic acid (FA)-modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5·NH2-FA) were used as stabilizers to prepare Au-Ag alloy DSNPs by simultaneously reducing both gold and silver salts, followed by acetylation of the dendrimer terminal amines. The formed Au-Ag alloy DSNPs were characterized via different techniques. We show that the formed Au-Ag alloy DSNPs are spherical in shape with a relatively narrow size distribution, have good water solubility and colloidal stability, and display higher X-ray attenuation intensity than the iodine-based contrast agent of Omnipaque at the same molar concentration of the active element (i.e., Au plus Ag, or iodine). Cytotoxicity assay results show that the Au-Ag alloy DSNPs are cytocompatible in a given concentration range. Importantly, the formed Au-Ag alloy DSNPs are able to be specifically taken up by cancer cells overexpressing FA receptors and enable targeted CT imaging of the cancer cells. Given the unique structural characteristics of dendrimers and the facile synthesis of DSNPs, the developed Au-Ag alloy DSNPs may be used for various biomedical applications in sensing, diagnosis, and therapeutics. PMID:23392561

Liu, Hui; Shen, Mingwu; Zhao, Jinglong; Zhu, Jingyi; Xiao, Tingting; Cao, Xueyan; Zhang, Guixiang; Shi, Xiangyang

2013-04-01

326

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

2013-06-01

327

Polyethylenimine-Capped Silver Nanoclusters as a Fluorescence Probe for Highly Sensitive Detection of Folic Acid through a Two-Step Electron-Transfer Process.  

PubMed

A highly sensitive folic acid (FA) detection method based on the fluorescence quenching of polyethylenimine-capped silver nanoclusters (PEI-AgNCs) was put forward. In the sensing system, FA and PEI-AgNCs were brought into close proximity to each other by electrostatic interaction, and a two-step electron-transfer process, in which the electron was transferred from FA to AgNCs through PEI molecule, led to fluorescence quenching. The fluorescence quenching efficiency of PEI-AgNCs was linearly related to the concentration of FA over the range from 0.1 nM to 2.75 ?M. Good linear correlation (R(2) = 0.9981) and a detection limit of 0.032 nM were obtained under optimum conditions. Moreover, the proposed method was used for the determination of FA in real samples with satisfactory results, and those coexistent substances could not cause any significant decrease in the fluorescence intensity of AgNCs. Therefore, the proposed research system is of practical significance and application prospects. PMID:24972143

Zhang, Jian Rong; Wang, Zhong Ling; Qu, Fei; Luo, Hong Qun; Li, Nian Bing

2014-07-16

328

Facile one-pot synthesis of folic acid-modified graphene to improve the performance of graphene-based sensing strategy.  

PubMed

A convenient and environment-friendly method is reported to synthesize the reduced graphene oxide (rGO) sheets in aqueous solution using folic acid (FA) as both a reducing and stabilizing agent, to improve the performance of graphene-based sensing strategy. The as-prepared FA-rGO sheets were characterized by transmission electron microscopy (TEM), UV-vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, X-ray diffraction (XRD) and thermogravimetric analysis (TGA), which provided the clear identification of the removal of oxygen-containing functional groups from the graphene oxide (GO) to form FA-rGO sheets. Further, it was found that the obtained FA-rGO sheets exhibited better biocompatibility and could act as the more efficient energy acceptor in long range resonance energy transfer (LrRET) process than that of graphene. Additionally, the FA-rGO can also catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2, and compared with GO sheets, they exhibited the more prominent intrinsic peroxidase-like activity, thus providing the more sensitive approach for colorimetric detection of H2O2. PMID:24863796

Zhan, Lei; Zhang, Yan; Zeng, Qiao Ling; Liu, Zhong De; Huang, Cheng Zhi

2014-07-15

329

A Comparison of Two Methods Used for Measuring Antagonistic Activity of Lactic Acid Bacteria  

Microsoft Academic Search

2 Abstract: In this research, we have aimed to determine antagonistic effects of various lactic acid bacteria against Gram (+) and Gram (-) bacteria with a comparison of disc diffusion and spot-on-lawn method. In spot-on-lawn method, P. aeruginosa ATCC 27853 was the most sensitive of the tested bacteria, followed by E. coli ATCC 25927 and P. aeruginosa ATCC 10145. On

Bilge Hilal Cadirci; Sumru Citak

2005-01-01

330

Folic acid is a potent chemoattractant of free-living amoebae in a new and amazing species of protist, Vahlkampfia sp.  

PubMed

Folic acid (folate; vitamin Bc) is well recognized as essential for the proper metabolism of the essential amino acid methionine as well as for the synthesis of adenine and thymine. A folate deficiency has been Implicated in a wide variety of disorders from Alzheimer's disease to depression and neural tube defects. In the cellular slime molds, including Dictyostelium, vegetative growth-phase cells are known to chemotactically move toward folate that is secreted by bacterial food sources such as Escherichia coli. Intracellular folate signal transductlon, including G proteins, Ca(2+)channels, and the PIP3 pathway, has been reported in D. discoideum. To our surprise, the genuine chemoattractant(s) of free-living protozoan amoebae have remained to be determined, possibly because of lack of a pertinent method for assaying chemotaxis. We recently isolated a primitive free-living amoeba from the soil of Costa Rica and identified it as a new species of the genus Vahlkampfia belonging to Subclass Gymnamoebia, which includes Entamoeba and Acanthamoeba. The amoebae can grow and multiply quite rapidly, engulfing nearby bacteria such as E. coli. Importantly, we have demonstrated here using a quite simple but finely designed chemotaxis assay that the Vahlkampfia amoebae exhibit chemotaxis toward higher folate concentrations. Riboflavin and cyanocobalamin were also found to serve as positive chemoattractants. Among these chemoattractants, folate is of particular importance because its function seems to be evolutionarily conserved as a potent chemoattractant of amoeboid cells in a wide range of organisms as well as in the Protista and cellular slime molds. PMID:19341337

Maeda, Yasuo; Mayanagi, Taira; Amagai, Aiko

2009-03-01

331

Rapid Quantitation of Ascorbic and Folic Acids in SRM 3280 Multivitamin/Multielement Tablets using Flow-Injection Tandem Mass Spectrometry  

SciTech Connect

RATIONALE: Ascorbic acid (AA) and folic acid (FA) are water-soluble vitamins and are usually fortified in food and dietary supplements. For the safety of human health, proper intake of these vitamins is recommended. Improvement in the analysis time required for the quantitative determination of these vitamins in food and nutritional formulations is desired. METHODS: A simple and fast (~5 min) in-tube sample preparation was performed, independently for FA and AA, by mixing extraction solvent with a powdered sample aliquot followed by agitation, centrifugation, and filtration to recover an extract for analysis. Quantitative detection was achieved by flow-injection (1 L injection volume) electrospray ionization tandem mass spectrometry (ESI-MS/MS) in negative ion mode using the method of standard addition. RESULTS: Method of standard addition was employed for the quantitative estimation of each vitamin in a sample extract. At least 2 spiked and 1 non-spiked sample extract were injected in triplicate for each quantitative analysis. Given an injection-to-injection interval of approximately 2 min, about 18 min was required to complete the quantitative estimation of each vitamin. The concentration values obtained for the respective vitamins in the standard reference material (SRM) 3280 using this approach were within the statistical range of the certified values provided in the NIST Certificate of Analysis. The estimated limit of detections of FA and AA were 13 and 5.9 ng/g, respectively. CONCLUSIONS: Flow-injection ESI-MS/MS was successfully applied for the rapid quantitation of FA and AA in SRM 3280 multivitamin/multielement tablets.

Bhandari, Deepak [ORNL] [ORNL; Kertesz, Vilmos [ORNL] [ORNL; Van Berkel, Gary J [ORNL] [ORNL

2013-01-01

332

[Antagonistic properties of lactic acid bacteria isolated from apparently healthy and osteoporotic women].  

PubMed

Antagonistic activity of 74 cultures of lactic acid bacteria, isolated from healthy and osteoporotic women-patients aged 50-79 years, has been studied. It has been shown that the inhibitory effect of the strain studied was independent of the health of women (control group of women or patients with osteoporosis), but had strain specificity. Seventeen most active strains of lactobacilli, which showed the highest inhibitory activity against B. cereus, P. aeruginosa, P. vulgaris were selected. Only 6 strains of lactobacillus demonstrated specific antagonistic activity against the test-strains. PMID:23516836

Ohirchuk, K S; Poltavs'ka, O A; Kovalenko, N K

2013-01-01

333

A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.  

PubMed

Background Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). Patients and methods This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Results Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ?2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Conclusions Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted. PMID:24566705

Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G

2014-06-01

334

A turn-on highly selective and ultrasensitive determination of copper (II) in an aqueous medium using folic acid capped gold nanoparticles as the probe.  

PubMed

This paper describes a 'turn-on' fluorescent determination of Cu(II) in an aqueous medium using folic acid capped gold nanoparticles (FA-AuNPs) as the probe. The FA-AuNPs were synthesized by the wet chemical method and were characterized by UV-visible, fluorescence, HR-TEM, XRD, zeta potential, and DLS techniques. The FA-AuNPs show an absorption maximum at 510 nm and an emission maximum at 780 nm (?(ex): 510 nm). On adding 10 ?M Cu(II), the wine-red color of FA-AuNPs changed to purple and the absorbance at 510 nm decreased. The observed changes were ascribed to the aggregation of AuNPs. This was confirmed by DLS and HR-TEM studies. Interestingly, the emission intensity of FA-AuNPs was enhanced even in the presence of a picomolar concentration of Cu(II). Based on the enhancement of the emission intensity, the concentration of Cu(II) was determined. The FA-AuNPs showed an extreme selectivity towards the determination of 10 nM Cu(II) in the presence of 10,000-fold higher concentration of interferences except EDTA and the carboxylate anion. A good linearity was observed from 10 × 10(-9) to 1 × 10(-12) M Cu(II), and the detection limit was found to be 50 fM l(-1) (S/N = 3). The proposed method was successfully applied to determine Cu(II) in real samples. The results obtained were validated with ICP-AES. PMID:24284553

Vasimalai, N; Prabhakarn, A; John, S Abraham

2013-12-20

335

Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort.  

PubMed

DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994-1995), peri- (1996-1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability. PMID:24300587

Bae, Sajin; Ulrich, Cornelia M; Bailey, Lynn B; Malysheva, Olga; Brown, Elissa C; Maneval, David R; Neuhouser, Marian L; Cheng, Ting-Yuan David; Miller, Joshua W; Zheng, Yingye; Xiao, Liren; Hou, Lifang; Song, Xiaoling; Buck, Katharina; Beresford, Shirley Aa; Caudill, Marie A

2014-03-01

336

Effects of interaction of folic acid with uranium (VI) and basic triphenylmethane dyes on resonance Rayleigh scattering spectra and their analytical applications.  

PubMed

In pH 4.2-4.8 HAc-NaAc buffer solution, folic acid (FA) could react with uranium (VI) to form a 2:1 anionic chelate which further reacted with some basic triphenylmethane dyes (BTPMD) such as Ethyl Violet (EV), Methyl Violet (MV) and Crystal Violet (CV) to form 1:2 ion-association complexes. As a result, not only the absorption spectra were changed, but also the intensities of resonance Rayleigh scattering (RRS) were enhanced greatly and the new RRS spectra were observed. The maximum RRS wavelengths were located at 328 nm for EV system, 325 nm for MV system and 328 nm for CV system. The fading degree (DeltaA) and RRS intensities (DeltaI) of three systems were different. Under given conditions, the DeltaA and DeltaI were all directly proportional to the concentration of FA. The linear ranges and the detection limits of RRS methods were 0.0039-5.0 microg mL(-1) and 1.2 ng mL(-1) for EV system, 0.0073-4.0 microg mL(-1) and 2.2 ng mL(-1) for MV system, 0.014-3.5 microg mL(-1) and 4.7 ng mL(-1) for CV system. The RRS methods exhibited higher sensitivity, so they are more suitable for the determination of trace FA. The optimum conditions, the influencing factors and the effects of coexisting substances on the reaction were investigated. The method can be applied to the determination of FA in serum and urine samples with satisfactory results. The structure of the ternary ion-association complex and the reaction mechanism were discussed in this work. PMID:18374705

Xi, Cunxian; Liu, Zhongfang; Kong, Ling; Hu, Xiaoli; Liu, Shaopu

2008-04-14

337

A turn-on highly selective and ultrasensitive determination of copper (II) in an aqueous medium using folic acid capped gold nanoparticles as the probe  

NASA Astrophysics Data System (ADS)

This paper describes a ‘turn-on’ fluorescent determination of Cu(II) in an aqueous medium using folic acid capped gold nanoparticles (FA-AuNPs) as the probe. The FA-AuNPs were synthesized by the wet chemical method and were characterized by UV-visible, fluorescence, HR-TEM, XRD, zeta potential, and DLS techniques. The FA-AuNPs show an absorption maximum at 510 nm and an emission maximum at 780 nm (?ex: 510 nm). On adding 10 ?M Cu(II), the wine-red color of FA-AuNPs changed to purple and the absorbance at 510 nm decreased. The observed changes were ascribed to the aggregation of AuNPs. This was confirmed by DLS and HR-TEM studies. Interestingly, the emission intensity of FA-AuNPs was enhanced even in the presence of a picomolar concentration of Cu(II). Based on the enhancement of the emission intensity, the concentration of Cu(II) was determined. The FA-AuNPs showed an extreme selectivity towards the determination of 10 nM Cu(II) in the presence of 10?000-fold higher concentration of interferences except EDTA and the carboxylate anion. A good linearity was observed from 10 × 10-9 to 1 × 10-12 M Cu(II), and the detection limit was found to be 50 fM l-1 (S/N = 3). The proposed method was successfully applied to determine Cu(II) in real samples. The results obtained were validated with ICP-AES.

Vasimalai, N.; Prabhakarn, A.; John, S. Abraham

2013-12-01

338

Cobalamin and Folic Acid Status in Relation to the Etiopathogenesis of Pancytopenia in Adults at a Tertiary Care Centre in North India  

PubMed Central

Background. Pancytopenia has multiple etiologies like megaloblastic anemia, aplastic anemia, leukemia, and various infections. We investigated the clinical, etiological and hematological profile including bone marrow morphology of patients with pancytopenia in relation to their vitamin B12 and folic acid status at a tertiary care referral hospital in north India. Methods. A total of 140 consecutive patients with pancytopenia were selected from June 2007 to December 2008. Bone marrow examination and other tests were carried out as warranted, including serum cobalamin and folate assays using liquid chromatography mass spectroscopy (LC MS/MS). Results. The study population consisted of 92 males and 48 females with a mean age of 32.8 years. Megaloblastic anemia 60.7%, aplastic anemia (7.8%), and leukemia (9.2%) were common causes. Infectious causes (16.4% of all cases) included leishmaniasis, HIV–AIDS, malaria and tuberculosis. Severe cobalamin deficiency (B12 < 100?pg/mL) was seen in 81% of all patients including 91.6% of patients with MA. In contrast, only 7.14% of all pancytopenic patients were folate deficient. Folate deficiency (<5?ng/mL) was seen in just 5% MA patients. Combined cobalamin and folate deficiency was seen in 5 patients (3.51%). Conclusion. Cobalamin deficiency was found to be more common in our setting and is largely underdiagnosed in the age of folate supplementation. Infectious diseases like tuberculosis, leishmaniasis, and increasingly HIV are important and treatable causes of pancytopenia. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia.

Premkumar, M.; Gupta, N.; Singh, T.; Velpandian, T.

2012-01-01

339

Novel class of amino acid antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology, and neuroprotection  

Microsoft Academic Search

The isoxazole amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) (1), which is a highly selective agonist at the AMPA subtype of excitatory amino acid (EAA) receptors, has been used as a lead for the development of two novel EAA receptor antagonists. One of the compounds, 2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid (AMOA, 7), was synthesized via O-alkylation by ethyl chloroacetate of the amino acid protected

Povl Krogsgaard-Larsen; John W. Ferkany; Elsebet O. Nielsen; Ulf Madsen; Bjarke Ebert; Joergen S. Johansen; Nils H. Diemer; Torben Bruhn; David T. Beattie; David R. Curtis

1991-01-01

340

Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high-risk patients: The Heart Outcomes Prevention Evaluation (HOPE)-2 trial  

PubMed Central

BACKGROUND Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial – the Heart Outcomes Prevention Evaluation (HOPE)-2 study – is being conducted to evaluate this therapy in patients at high risk for CV events. OBJECTIVES To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke. METHODS A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005. RESULTS The patients’ baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention.

2006-01-01

341

Antenatal iron/folic acid supplements, but not postnatal care, prevents neonatal deaths in Indonesia: analysis of Indonesia Demographic and Health Surveys 2002/2003-2007 (a retrospective cohort study)  

PubMed Central

Objective This study aimed to assess the contribution of postnatal services to the risk of neonatal mortality, and the relative contributions of antenatal iron/folic acid supplements and postnatal care in preventing neonatal mortality in Indonesia. Design Retrospective cohort study. Setting and participants Data used in this study were the 2002–2007 Indonesia Demographic and Health Surveys, nationally representative surveys. The pooled data provided survival information of 26?591 most recent live-born infants within the 5-years prior to each interview. Primary outcomes Primary outcomes were early neonatal mortality, that is, deaths in the first week, and all neonatal mortality, that is, deaths in the first month of life. Exposures were antenatal iron/folic acid supplementation and postnatal care from days 1 to 7. Potential confounders were community, socio-economic status and birthing characteristics and perinatal healthcare. Cox regression was used to assess the association between study factors and neonatal mortality. Results Postnatal care services were not associated with newborn survival. Postnatal care on days 1–7 after birth did not reduce neonatal death (HR=1.00, 95% CI 0.55 to 1.83, p=1.00) and early postnatal care on day 1 was associated with an increased risk of early neonatal death (HR=1.27, 95% CI 0.69 to 2.32, p=0.44) possibly reflecting referral of ill newborns. Early postnatal care on day 1 was not protective for neonatal deaths on days 2–7 whether provided by doctors (HR 3.61, 95% CI 1.54 to 8.45, p<0.01), or by midwives or nurses (HR 1.38, 95% CI 0.53 to 3.57, p=0.512). In mothers who took iron/folic acid supplements during pregnancy, the risk of early neonatal death was reduced by 51% (HR=0.49, 95% CI 0.30 to 0.79, p<0.01). Conclusions We found no protective effect of postnatal care against neonatal deaths in Indonesia. However, important reductions in the risk of neonatal death were found for women who reported use of antenatal iron/folic acid supplements during pregnancy.

Titaley, Christiana Rialine; Dibley, Michael John

2012-01-01

342

Novel Cyclic Phosphinic Acids as GABAC ? Receptor Antagonists: Design, Synthesis, and Pharmacology  

PubMed Central

Understanding the role of GABAC receptors in the central nervous system is limited due to a lack of specific ligands. Novel ?-aminobutyric acid (GABA) analogues based on 3-(aminomethyl)-1-oxo-1-hydroxy-phospholane 17 and 3-(guanido)-1-oxo-1-hydroxy-phospholane 19 were investigated to obtain selective GABAC receptor antagonists. A compound of high potency (19, KB = 10 ?M) and selectivity (greater than 100 times at ?1 GABAC receptors as compared to ?1?2?2L GABAA and GABAB(1b,2) receptors) was obtained. The cyclic phosphinic acids (17 and 19) are novel lead agents for developing into more potent and selective GABAC receptor antagonists with increased lipophilicity for future in vivo studies.

2010-01-01

343

High dose folic acid pre-treatment blunts cardiac dysfunction during ischemia coupled to maintenance of high energy phosphates and reduces post-reperfusion injury  

PubMed Central

Background The B-vitamin folic acid (FA) is important to mitochondrial protein and nucleic acid synthesis, is an anti-oxidant, and enhances nitric oxide synthase activity. Here, we tested whether FA reduces myocardial ischemic dysfunction and post-reperfusion injury. Methods Wistar rats were pretreated with either FA (10mg/d) or placebo for 1-wk, and then underwent in vivo transient left coronary artery occlusion for 30min with or without 90min reperfusion (total:n=131; sub-groups used for various analyses). FA (4.5•10-6M i.c) pretreatment and global ischemia/reperfusion (30 min/30min), was also performed in vitro (n=28). Results After 30min ischemia, global function declined more in controls than FA-pretreated rats (?dP/dtmax -878±586 mmHg/s vs. placebo -1956±351 mmHg/s, p=0.03), and regional thickening was better preserved (37.3±5.3% vs. 5.1±0.6%-placebo, p=0.004). Anterior-wall perfusion fell similarly (-78.4±9.3% vs. -71.2±13.8%-placebo at 30 min); yet myocardial high energy phosphates ATP and ADP reduced by ischemia in controls were better preserved by FA-pretreatment (e.g. ATP: control: 2740±58; ischemia: 947±55; ischemia+FA: 1332±101 nmol/g, p=0.02). Basal oxypurines (xanthine, hypoxanthine, and urate) rose with FA-pretreatment, but increased less during ischemia than in controls. Ischemic superoxide generation declined (3124±280 FA vs. 5898±474 placebo, cpm/mg, p=0.001). After reperfusion, FA-treated hearts had smaller infarcts (3.8±1.2% vs 60.3±4.1%-placebo area at risk, p<0.002), less contraction band necrosis, TUNEL-positivity, superoxide, and nitric oxide synthase uncoupling. Infarct size declined similarly with 1 mg/d FA as well. Conclusion FA-pretreatment blunts myocardial dysfunction during ischemia, and ameliorates post-reperfusion injury. This is coupled to preservation of high energy phosphates, reducing subsequent ROS-generation, eNOS-uncoupling and post-reperfusion cell death.

Moens, An L.; Champion, Hunter C.; Claeys, Marc J.; Tavazzi, Barbara; Kaminki, Pawel M.; Wolin, Michael S.; Borgonjon, Dirk; Van Nassauw, Luc; Haile, Azeb; Zviman, Muz; Bedja, Djahida; Wuyts, Floris L.; Elsaesser, Rebecca S.; Cos, Paul; Gabrielson, Kathy L.; Lazzarino, Giuseppe; Paolocci, Nazareno; Timmermans, Jean-Pierre; Vrints, Christiaan J.; Kass, David A.

2008-01-01

344

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

345

Effect of the Folic Acid Analogue, Trimethoprim, on Growth, Macromolecular Synthesis, and Incorporation of Exogenous Thymine in Escherichia coli1  

PubMed Central

The effect of trimethoprim [2,4-diamino-5(2?,4?,5?trimethoxybenzyl)-pyrimidine] in the presence of thymine on Escherichia coli B temperature-sensitive and non-temperature-sensitive Thy? strains and a phosphodeoxyribomutase-negative mutant was studied. The inhibitory effect of 5 ?g of trimethoprim per ml on the growth of E. coli B was not overcome by thymine, thymidine, or thymidylate even in the presence of one-carbon metabolites and related metabolites. Deoxyribonucleic acid (DNA) and protein synthesis were more severely inhibited than ribonucleic acid (RNA) synthesis. The inhibition of DNA synthesis was partially reversed by addition of deoxyadenosine to increase the incorporation of exogenous thymine. By contrast, the inhibition of protein was not reversed even with one-carbon metabolites present, in keeping with the requirement for formylmethionyl-transfer RNAF for initiation. However, the inhibition of both DNA and protein synthesis in a phosphodeoxyribomutase-negative strain by 1 ?g of trimethoprim per ml with thymine present was partially reversed by deoxyadenosine and one-carbon metabolites, and nearly normal growth occurred. 5-Fluorodeoxyuridine added at the time of addition of trimethoprim prevented the inhibition. Sulfadiazine in the presence of thymine inhibited both Thy+ and Thy? strains whereas trimethoprim (with thymine) did not inhibit Thy? organisms. The effect of trimethoprim on the incorporation of labeled thymine into DNA was also studied. These experiments support the concept that trimethoprim in conjunction with the action of thymidylate synthetase inhibits the growth of Thy+ cells because of a depletion of tetrahydrofolate. DNA synthesis is inhibited initially by a limitation of thymine nucleotide precursor, resulting from the indirect inhibition of thymidylate synthetase and the poor incorporation of exogenous thymine.

Dale, Beverly A.; Greenberg, G. Robert

1972-01-01

346

Hereditary folate malabsorption: A positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding  

SciTech Connect

The proton-coupled folate transporter (PCFT/SLC46A1) mediates intestinal folate uptake at acidic pH. Some loss of folic acid (FA) transport mutations in PCFT from hereditary folate malabsorption (HFM) patients cluster in R113, thereby suggesting a functional role for this residue. Herein, unlike non-conservative substitutions, an R113H mutant displayed 80-fold increase in the FA transport Km while retaining parental Vmax, hence indicating a major fall in folate substrate affinity. Furthermore, consistent with the preservation of 9% of parental transport activity, R113H transfectants displayed a substantial decrease in the FA growth requirement relative to mock transfectants. Homology modeling based on the crystal structures of the Escherichia coli transporter homologues EmrD and glycerol-3-phosphate transporter revealed that the R113H rotamer properly protrudes into the cytoplasmic face of the minor cleft normally occupied by R113. These findings constitute the first demonstration that a basic amino acid at position 113 is required for folate substrate binding.

Lasry, Inbal; Berman, Bluma [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)] [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Glaser, Fabian [Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa 32000 (Israel)] [Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa 32000 (Israel); Jansen, Gerrit [Department of Rheumatology, VU University Medical Center, Amsterdam (Netherlands)] [Department of Rheumatology, VU University Medical Center, Amsterdam (Netherlands); Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)

2009-08-28

347

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands  

PubMed Central

Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161.

2014-01-01

348

Blood folate status and expression of proteins involved in immune function, inflammation, and coagulation: biochemical and proteomic changes in the plasma of humans in response to long-term synthetic folic acid supplementation.  

PubMed

We used plasma proteomics to identify human proteins responsive to folate status. Plasma was collected from subjects treated with placebo or 1.2 mg of folic acid daily for 12 weeks in a randomized controlled trial. Homocysteine and folate were measured by immunoassay and uracil misincorporation by electrophoresis. The plasma proteome was assessed by 2-D gel electrophoresis, and proteins were identified by LC MS/MS. 5-methylTHF increased 5-fold (P = 0.000003) in response to intervention. Red cell folate doubled (P = 0.013), and lymphocyte folate increased 44% (P = 0.0001). Hcy and uracil dropped 22% (P = 0.0005) and 25% (P = 0.05), respectively. ApoE A-1, alpha-1-antichymotrypsin, antithrombin, and serum amyloid P were downregulated, while albumin, IgM C, and complement C3 were upregulated (P < 0.05). More than 60 proteins were significantly associated with folate pre- and postintervention (P < 0.01). These were categorized into metabolic pathways related to complement fixation (e.g., C1, C3, C4, Factor H, Factor 1, Factor B, clusterin), coagulation (e.g., antithrombin, alpha-1-antitrypsin, kininogen) and mineral transport (e.g., transthyretin, haptoglobin, ceruloplasmin). Low folate status pre- and post-treatment were associated with lower levels of proteins involved in activation and regulation of immune function and coagulation. Supplementation with synthetic folic acid increased expression of these proteins but did not substantially disrupt the balance of these pathways. PMID:20143872

Duthie, Susan J; Horgan, Graham; de Roos, Baukje; Rucklidge, Garry; Reid, Martin; Duncan, Gary; Pirie, Lynn; Basten, Graham P; Powers, Hilary J

2010-04-01

349

Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice  

PubMed Central

Here we investigated a pharmacological approach to inhibit spermatogenesis in the mouse model by manipulating retinoid signaling using low doses of the pan-retinoic acid receptor (RAR) antagonist BMS-189453. Spermatogenesis was disrupted, with a failure of spermatid alignment and sperm release and loss of germ cells into lumen, abnormalities that resembled those in vitamin A-deficient and RAR?-knockout testes. Importantly, the induced sterility was reversible. Enhanced efficacy and a lengthened infertility period with full recovery of spermatogenesis were observed using systematically modified dosing regimens. Hematology, serum chemistry, and hormonal and pathological evaluations revealed no detectable abnormalities or adverse side effects except the distinct testicular pathology. Our results suggest that testes are exquisitely sensitive to disruption of retinoid signaling and that RAR antagonists may represent new lead molecules in developing nonsteroidal male contraceptives.

Chung, Sanny S. W.; Wang, Xiangyuan; Roberts, Shelby S.; Griffey, Stephen M.; Reczek, Peter R.

2011-01-01

350

Oncoprotein v-Myb and retinoic acid receptor alpha are mutual antagonists.  

PubMed

The process of hematopoiesis is critically dependent on correct interactions of multiple regulatory molecules and transcription factors. We have studied the interactions of the v-Myb and retinoic acid receptor proteins which have opposing effects on hematopoiesis. While v-myb acts as a transforming oncogene preventing differentiation of monoblasts to macrophages, RAR alpha functions as an anti-oncogene arresting the growth of v-myb-transformed cells and allowing their final myeloid differentiation steps to occur. We found that the retinoic acid receptor alpha inhibits v-Myb transformation by suppressing the expression of v-Myb target genes typified by the mim-1 gene. Conversely, v-Myb protein interferes with RAR alpha transactivation function as well as with retinoic acid-induced apoptosis of HL-60 cells. These results demonstrate that retinoic acid receptor and v-Myb proteins act in antagonistic ways and reciprocally modify each other's functions. PMID:9714701

Zemanová, K; Smarda, J

1998-06-01

351

Effects of excitatory amino acid antagonists on synaptic transmission in the ampullae of Lorenzini of the skate Raja clavata  

Microsoft Academic Search

1.The effects of excitatory amino acid antagonists on synaptic transmission in the ampullae of Lorenzini of the skate Raja clavata were studied.2.At concentrations of 10-3 to 10-6M, l-glutamic acid diethylester (GDEE) and l-glutamic acid dimethylester (GDME) decreased the resting afferent discharge frequency as well as the electrically evoked activities and depressed the responses to application of excitatory amino acids.3.d-a-Aminoadipic acid

G. N. Akoev; G. N. Andrianov; B. Bromm; T. Szabo

1991-01-01

352

Folic Acid Deficiency Complicating Malaria.  

National Technical Information Service (NTIS)

American marines in Vietnam were shown to have megaloblastic changes in bone marrow aspirates and an inappropriate reticulocyte response to anemia associated with malaria. Convalescence was prolonged because of delayed correction of anemia. These patients...

G. T. Strickland J. E. Kostinas

1970-01-01

353

Folic Acid Questions and Answers  

MedlinePLUS

... defects of the brain and spine ( anencephaly and spina bifida ) happen in the first few weeks of pregnancy; ... materials » Q: I already have a child with spina bifida. Should I do anything different to prepare for ...

354

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

355

In vitro and in vivo evaluation of an innocuous drug cocktail to improve the quality of folic acid targeted nuclear imaging in preclinical research.  

PubMed

Folate receptor (FR) targeting is an attractive strategy for nuclear imaging of cancer and activated macrophages through application of folic acid radioconjugates. However, significant renal accumulation of folate radioconjugates and hence exceedingly high emission of radiation from the kidneys may mask uptake of radioactivity at sites of interest such as small metastases in the abdominal region of animal models of ovarian cancer. Recently it was observed that the antifolate pemetrexed (PMX) reduces undesired renal uptake of radiofolates. A disadvantage of this strategy is the fact that pemetrexed is a chemotherapeutic agent which may have toxic side effects. The aims of this study were therefore to investigate whether the desired effect of PMX to reduce renal accumulation of folate radioconjugates would be maintained if it was applied as a cocktail together with its antidote, thymidine, and to explore whether thymidine was an effective rescue agent against PMX's related toxicity in vitro and in vivo. In vitro internalization of (67)Ga-EC0800 was investigated using FR-positive KB tumor cells and embryonic monkey MA104 kidney cells in the absence and presence of PMX alone and in combination with thymidine. Uptake of (67)Ga-EC0800 into KB cells was increased by coincubation of the cells with PMX. In contrast uptake of (67)Ga-EC0800 into MA104 cells was reduced under the same conditions. In both cell lines coincubation of thymidine did not change the results obtained with PMX. Biodistribution and SPECT/CT imaging studies of (67)Ga-EC0800 were performed with KB tumor bearing mice injected with PMX alone or with a cocktail of PMX and thymidine. The radiofolate's kidney uptake reducing effect of PMX in mice was maintained also if PMX was employed together with its antidote thymidine. The tumor uptake of (67)Ga-EC0800 remained unchanged independent of the administration of PMX or a combination of PMX and thymidine. The effect of thymidine to abrogate PMX-induced cytotoxicity was demonstrated in vitro with an MTT assay using KB and MA104 cells. Cell viability was reduced to 50% (KB cells) and 70% (MA104 cells) of untreated controls if PMX (5 ?M and 15 ?M, respectively) was coincubated. Addition of thymidine (10 ?M or 100 ?M) compensated PMX's toxic effects in a dose-dependent manner. The effect of thymidine was also investigated in non-tumor bearing mice treated with high-dosed PMX. Rescue of mice with side effects after the third and fourth cycles of PMX application (1 mg/mouse) was achieved by application of thymidine (20 mg/mouse) at five consecutive days starting the day of PMX injection. Application of PMX together with thymidine as a cocktail is effective to improve the tissue distribution of radiofolates while preventing pharmacological and potentially toxic side effects of the chemotherapeutic agent PMX. These findings open new perspectives for folate-based nuclear imaging in preclinical research potentially allowing longitudinal investigations and monitoring therapies in animal models of cancer and inflammatory diseases. PMID:23394590

Müller, Cristina; Reber, Josefine; Schlup, Claudia; Leamon, Christopher P; Schibli, Roger

2013-03-01

356

The excitatory amino acid antagonist D-CPP-ene (SDZ EAA-494) in patients with epilepsy.  

PubMed

The amino acids L-glutamate and L-aspartate have been shown to be excitatory neurotransmitters in mammalian central nervous systems. Antagonists acting selectively at excitatory amino acid receptors have shown antiepileptic properties in several animal models. We report the results of the first therapeutic trial of the competitive NMDA antagonist, D-CPP-ene (SDZ EAA-494), in eight patients with intractable complex partial seizures. All patients withdrew prematurely because of side-effects, including poor concentration (8), sedation (7), ataxia (6), depression (3), dysarthria (2), amnesia (2) and unilateral choreo-athetosis in a patient with contralateral Sturge-Weber syndrome. Seizures were unchanged in four patients and worse in three. A further patient with apparent improvement in seizures in the first week developed complex partial status epilepticus on withdrawal of DCPP-ene. EEG on treatment (5) or in the immediate post-treatment period (2) showed slowing of background activity and, in five cases, an increase in epileptiform activity. Serum concentrations of DCPP-ene were found to be unpredictable and higher than expected from pharmacokinetic data on normal subjects. There was no clear relationship between serum concentrations and the severity of side-effects. Preliminary experience with DCPP-ene in patients with refractory partial seizures is not promising. Evaluation of related compounds is warranted. PMID:8269915

Sveinbjornsdottir, S; Sander, J W; Upton, D; Thompson, P J; Patsalos, P N; Hirt, D; Emre, M; Lowe, D; Duncan, J S

1993-10-01

357

Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists  

PubMed Central

Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100??g of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not.Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching.Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin.The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats.These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent.

Hayashi, Izumi; Majima, Masataka

1999-01-01

358

Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity.  

PubMed

Bile salt export pump (BSEP) is a major bile acid transporter in the liver. Mutations in BSEP result in progressive intrahepatic cholestasis, a severe liver disease that impairs bile flow and causes irreversible liver damage. BSEP is a target for inhibition and down-regulation by drugs and abnormal bile salt metabolites, and such inhibition and down-regulation may result in bile acid retention and intrahepatic cholestasis. In this study, we quantitatively analyzed the regulation of BSEP expression by FXR ligands in primary human hepatocytes and HepG2 cells. We demonstrate that BSEP expression is dramatically regulated by ligands of the nuclear receptor farnesoid X receptor (FXR). Both the endogenous FXR agonist chenodeoxycholate (CDCA) and synthetic FXR ligand GW4064 effectively increased BSEP mRNA in both cell types. This up-regulation was readily detectable at as early as 3 h, and the ligand potency for BSEP regulation correlates with the intrinsic activity on FXR. These results suggest BSEP as a direct target of FXR and support the recent report that the BSEP promoter is transactivated by FXR. In contrast to CDCA and GW4064, lithocholate (LCA), a hydrophobic bile acid and a potent inducer of cholestasis, strongly decreased BSEP expression. Previous studies did not identify LCA as an FXR antagonist ligand in cells, but we show here that LCA is an FXR antagonist with partial agonist activity in cells. In an in vitro co-activator association assay, LCA decreased CDCA- and GW4064-induced FXR activation with an IC(50) of 1 microm. In HepG2 cells, LCA also effectively antagonized GW4064-enhanced FXR transactivation. These data suggest that the toxic and cholestatic effect of LCA in animals may result from its down-regulation of BSEP through FXR. Taken together, these observations indicate that FXR plays an important role in BSEP gene expression and that FXR ligands may be potential therapeutic drugs for intrahepatic cholestasis. PMID:12052824

Yu, Jinghua; Lo, Jane-L; Huang, Li; Zhao, Annie; Metzger, Edward; Adams, Alan; Meinke, Peter T; Wright, Samuel D; Cui, Jisong

2002-08-30

359

Bombesin receptor antagonists [corrected]. 1. Analogues with deleted, inverted or substituted amino acid residues.  

PubMed

Bombesin is a 14-residue peptide hormone which serves a variety of biological functions, including cell growth control in Swiss 3T3 cultured fibroblasts. It has been also involved in an autocrine system regulating the growth of small cell lung carcinoma. A series of bombesin analogues were developed by amino acid deletion, inversion or substitution in the carboxy-terminal region, identified by the target cell receptor. Their properties were examined for: i) competitive binding assays; ii) mitogenic induction and inhibition assays; iii) effects on early cellular events (inositol phosphates production and protein tyrosine phosphorylation). Inversion of the Trp residue, or deletion of the C-terminal tripeptide amide, induced complete loss of receptor affinity and biological effects. Deletion of the His residue, or its derivatization as His (Dnp) in conjunction with Met deletion or modification, gave rise to compounds with reduced receptor affinity and weak antagonistic properties. Other modifications in the C-terminal tripeptide affected the potency but not the biological profile of the parent peptide. These results indicate the basis for the eventual design of improved, specific bombesin receptor antagonists and stimulate further studies on their possible application in the therapy of human small cell lung cancer. PMID:1965286

De Castiglione, R; Gozzini, L; Mena, R; Brugnolotti, M; Ciomei, M; Molinari, I; Comoglio, P M; Gaudino, G

1990-12-01

360

Luteinizing hormone-releasing hormone antagonists containing very hydrophobic amino acids.  

PubMed

In a continuation of our studies on the effects of hydrophobic substitutions in analogues of luteinizing hormone-releasing hormone (LH-RH), we have synthesized LH-RH antagonists containing the very hydrophobic amino acid 3-(2-naphthyl)-D-alanine (D-Nal(2)). The D-Nal(2) substitution was found to be effective when incorporated in positions 3 and 6. The most potent analogue containing two D-Nal(2) residues was [N-Ac-Pro,D-pF-Phe,D-Nal(2)]LH-RH (ED50 = 2.2 micrograms, rat antiovulatory assay, propylene glycol-saline vehicle). This analogue also demonstrates that the N-Ac-Pro substitution is as effective as the more costly N-Ac-delta-Pro modification. Analogues containing D-Nal(2) in combination with the hydrophilic D-Arg residue in position 6 were prepared. Neither N-Ac-Pro at position 1 nor D-Nal(2) at position 3 was effective in combination with D-Arg. N-Ac-D-Nal(2) at position 1 gave a highly potent antagonist ([N-Ac-D-Nal(2),D-pF-Phe,D-Trp,D-Arg]LH-RH; ED50 = 2.4 micrograms) that exhibited a prolonged duration of action (ED50 = 9.0 micrograms, corn oil vehicle, dosing on diestrus II). PMID:6381733

Nestor, J J; Tahilramani, R; Ho, T L; McRae, G I; Vickery, B H

1984-09-01

361

TAS2R38 bitter taste genetics, dietary vitamin C, and both natural and synthetic dietary folic acid predict folate status, a key micronutrient in the pathoaetiology of adenomatous polyps.  

PubMed

Taste perception may influence dietary preferences and nutrient intakes contributing to diet-related disease susceptibility. This study examined bitter taste genetics and whether variation in the TAS2R38 gene at three polymorphic loci (A49P, V262A and I296V) could alter dietary and systemic folate levels and dietary vitamin C intake, and whether a nutrigenetic circuit existed that might link bitter taste, folate/antioxidant status and risk for a colonic adenomatous polyp. TAS2R38 diplotype predicted bitter taste (PROP) phenotype (p value <0.00001) and red cell folate status (p=0.0179) consistent with the diplotype that has the broadest range of bitter perception (AVI/PAV) also possessing the highest average red cell folate value. However, TAS2R38 diplotype did not predict dietary intake of methylfolic acid, pteroylmonoglutamic acid or total folic acid. Neither did it predict dietary intake of vitamin C. Despite this, intake of dietary folate predicts red cell folate with analysis pointing to a key nutrient-nutrient interaction between vitamin C intake and systemic folate status. Analysis of 38 patients with an adenomatous polyp and 164 controls showed that individually, dietary nutrient intake, nutrient status and taste diplotype did not influence polyp risk. However, red cell folate status (in individuals below the population median value) did interact with bitter taste diplotype (AVI/PAV) to predict polyp risk (p=0.0145). Furthermore, synthetic folic acid (below median intake) was statistically associated with adenoma occurrence (p=0.0215); individuals with adenomatous polyps had a 1.77× higher intake than controls. Additionally, stepwise regression taking account of all dietary nutrients showed a tight relationship between methylfolic acid (but not pteroylmonoglutamic acid) intake and red cell folate level in those with a low folate status and occurrence of an adenomatous polyp (p=0.0039). These findings point to a role for folate in the pathoaetiology of adenomatous polyps, with the natural and synthetic vitamers not necessarily having the same biological effect. PMID:21769326

Lucock, Mark; Ng, Xiaowei; Boyd, Lyndell; Skinner, Virginia; Wai, Ron; Tang, Sa; Naylor, Charlotte; Yates, Zoë; Choi, Jeong-Hwa; Roach, Paul; Veysey, Martin

2011-08-01

362

Design of chiral LC separations for calcium antagonists on alpha 1-acid glycoprotein and ovomucoid columns.  

PubMed

Three chiral calcium antagonist drugs, gallopamil and two dihydropyridine derivatives, have been successfully separated within short retention times using both the alpha 1-acid glycoprotein chiral stationary phase (Chiral-AGP) and the ovomucoid column (Ultron ES-OVM). Aqueous buffer at defined pH is modified by the addition of an organic component, in order to modulate the retention properties of each system. Optimization of pH and organic modifier is carried out using the modified simplex method, with Kaiser's peak separation function as a criterion. The influence of pH and percentage of organic modifier on retention, selectivity, resolution and column performance are discussed for the two dihydropyridines analysed on Chiral-AGP and Ultron ES-OVM stationary phases. A new method is proposed as a new chiral system suitability test for these protein-based phases, utilizing a racemic mixture of closely eluting verapamil enantiomers as a probe. PMID:1298397

De Lorenzi, E; Fell, A F; Caccialanza, G; Massolini, G; Kitsos, M

1992-01-01

363

Cannabinoid receptor antagonists and fatty acids alter endocannabinoid system gene expression and COX activity.  

PubMed

Cyclooxygenase (COX) possesses substrate affinity for the endocannabinoids (EC) anandamide (AEA) and 2-arachidonylglycerol (2-AG). We hypothesized that selective antagonism/activation of the cannabinoid receptors will increase COX activity and the availability of EC as substrates will lead to higher COX activity. Since the relationship between EC signaling of the endocannabinoid system (ECS) and the COX pathway in muscle has not been investigated, we examined agonist, antagonists and polyunsaturated fatty acid effects on ECS genes in myoblasts. At 50% confluency, C2C12 myoblasts were pretreated with 5 ?M of the cannabinoid receptor (CB)2 inverse agonist AM630 for 2 h and one with both AM630 and 1 ?M of the CB1 antagonist NESS0327. Cell cultures pretreated with AM630 were then administered with 25 ?M of either arachidonic acid (20:4n6), eicosapentaenoate (EPA) (20:5n3), docosahexaenoate (DHA) (22:6n3), AEA or bovine serum albumin (vehicle control) for 24 h. Quantitative polymerase chain reaction analyses were performed looking at ECS and prostaglandin genes. Total COX activity and COX-1 protein were greater in the AM630+AEA-treated cells compared to all other cell cultures. The mRNA for the AEA synthesis enzyme N-acyl phosphatidylethanolamine phospholipase D and the 2-AG synthesis enzymes diacylglycerol lipase (DAGL)? and DAGL? were higher in AM630+EPA-treated cells compared to the other groups. The mRNA levels of CB1 and CB2 were both highest in the AM630+EPA group. The mRNA for interleukin-6 and tumor necrosis factor-? was higher with AEA but lower with DHA and docosahexaenoyl ethanolamide (DHEA), supporting previous findings that the EC AEA supports activation of the COX system. These findings suggest that COX activity and protein levels are influenced by the ECS, specifically by the ligand AEA for CB1 and by inverse agonism of CB2. PMID:24854955

Kim, Jeffrey; Watkins, Bruce A

2014-08-01

364

Antagonistic effects of abscisic acid and jasmonates on salt stress-inducible transcripts in rice roots.  

PubMed Central

Abscisic acid (ABA) and jasmonates have been implicated in responses to water deficit and wounding. We compared the molecular and physiological effects of jasmonic acid (JA) (< or = 10 microM), ABA, and salt stress in roots of rice. JA markedly induced a cationic peroxidase, two novel 32- and 28-kD proteins, acidic PR-1 and PR-10 pathogenesis-related proteins, and the salt stress-responsive SalT protein in roots. Most JA-responsive proteins (JIPs) from roots also accumulated when plants were subjected to salt stress. None of the JIPs accumulated when plants were treated with ABA. JA did not induce an ABA-responsive group 3 late-embryogenesis abundant (LEA) protein. Salt stress and ABA but not JA induced oslea3 transcript accumulation. By contrast, JA, ABA, and salt stress induced transcript accumulation of salT and osdrr, which encodes a rice PR-10 protein. However, ABA also negatively affected salT transcript accumulation, whereas JA negatively affected ABA-induced oslea3 transcript levels. Endogenous root ABA and methyl jasmonate levels showed a differential increase with the dose and the duration of salt stress. The results indicate that ABA and jasmonates antagonistically regulated the expression of salt stress-inducible proteins associated with water deficit or defense responses.

Moons, A; Prinsen, E; Bauw, G; Van Montagu, M

1997-01-01

365

Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice.  

PubMed

The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions. PMID:24722818

Trevisan, Gabriela; Rossato, Mateus F; Tonello, Raquel; Hoffmeister, Carin; Klafke, Jonatas Z; Rosa, Fernanda; Pinheiro, Kelly V; Pinheiro, Francielle V; Boligon, Aline A; Athayde, Margareth L; Ferreira, Juliano

2014-07-01

366

Differential Effects of TRPV1 Antagonists in Acid-induced Excitation of Esophageal Vagal Afferent Fibers of Rats  

PubMed Central

Gastro-esophageal acid reflux can stimulate esophageal vagal sensory afferents by activating proton-sensitive ion channel transient receptor vanilloid one (TRPV1). The objective of this study was to investigate the response characteristics of vagal afferent fibers of rats to acid (0.1N HCl) and capsaicin (CAP) following esophagitis and differential effects of two classes of TRPV1 antagonists on responses of vagal afferent fibers. The chronic reflux was induced by ligating the fundus of the stomach and partial constriction of pylorus. Extracellular single fiber recordings were made from the cervical vagal afferent fibers from naïve control and fundus-ligated (FL) esophagitis rats. Innervations of fibers were identified to esophageal distension (ED) and subsequently tested to CAP and acid before and after injection of TRPV1 antagonist JYL1421 or AMG9810 (10?mol/kg, i.v.). Seventy-five vagal afferent fibers from 70 rats were identified to ED. Intra-esophageal CAP (0.1ml of 1mg/ml) excited 39.5% (17/43, 5/22 from naïve and 12/21 from FL rats) fibers. In contrast, intravenous (i.v.) injection of CAP (0.03–0.3 ?mol/kg) dose-dependently excited 72% (42/58) fibers. Responses to CAP were significantly greater for fibers from FL rats (n=32) than naïve rats (n=25). TRPV1 antagonists JYL1421 and AMG9810 (10 ?mol/kg) significantly blocked response to CAP. Intra-esophageal acid infusion stimulated 5/17 (29.4%) fibers from naïve rats and 12/28 (42%) from FL rats. Effect of acid was significantly blocked by AMG9810, but not by JYL1421. Results indicate that following esophagitis the number of fibers responsive to CAP and acid is greater than non-inflamed esophagus, which may contribute to esophageal hypersensitivity. Acid-induced excitation of vagal sensory afferents can be differentially attenuated by different classes of TRPV1 antagonists. Therefore, TRPV1 antagonists play a key role in attenuation of hypersensitivity following reflux-induced esophagitis. The use of TRPV1 antagonists could be an alternative to the traditional symptoms based treatment of chronic acid reflux and esophageal hypersensitivity.

Peles, S.; Medda, B. K.; Zhang, Zhihong; Banerjee, B.; Lehmann, A.; Shaker, R.; Sengupta, J.N.

2009-01-01

367

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

368

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  

Microsoft Academic Search

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 25,000ppm for 4 weeks in order to investigate whether male reproductive toxicity of the two chemicals might be enhanced under conditions of renal disease.

Kyoko Nabae; Yuko Doi; Satoru Takahashi; Toshio Ichihara; Chitose Toda; Koji Ueda; Yoshinori Okamoto; Nakao Kojima; Seiko Tamano; Tomoyuki Shirai

2006-01-01

369

Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound  

PubMed Central

Retinoic acid receptor alpha (RAR?) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RAR? antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure–activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR? for both compounds. Molecular modeling within the RAR? binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.

Jetson, Rachael; Malik, Neha; Luniwal, Amarjit; Chari, Venkatesh; Ratnam, Manohar; Erhardt, Paul

2013-01-01

370

Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.  

PubMed

Retinoic acid receptor alpha (RAR?) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RAR? antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure-activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR? for both compounds. Molecular modeling within the RAR? binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist. PMID:23474897

Jetson, Rachael; Malik, Neha; Luniwal, Amarjit; Chari, Venkatesh; Ratnam, Manohar; Erhardt, Paul

2013-05-01

371

Abscisic acid interacts antagonistically with classical defense pathways in rice-migratory nematode interaction.  

PubMed

Studies involving plant-nematode interactions provide an opportunity to unravel plant defense signaling in root tissues. In this study, we have characterized the roles of salicylate (SA), jasmonate (JA), ethylene (ET) and abscisic acid (ABA) in plant defense against the migratory nematode Hirschmanniella oryzae in the monocot model plant rice (Oryza sativa). Experiments with exogenous hormone applications, biosynthesis inhibition and mutant/transgenic lines were executed to test the effect on H. oryzae parasitism in rice roots. Our results demonstrate that an intact ET, JA and SA biosynthesis pathway is a prerequisite for defense against H. oryzae. By contrast, exogenous ABA treatment drastically compromised the rice defense towards this nematode. Gene expression analyses using quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrate that the disease-inducing effect of ABA is likely to be the result of an antagonistic interaction between this hormone and the SA/JA/ET-dependent basal defense system. Collectively, in rice defense against H. oryzae, at least three pathways, namely SA, JA and ET, are important, while ABA plays a negative role in defense. Our results suggest that the balance of ABA and SA/JA/ET signaling is an important determinant for the outcome of the rice-H. oryzae interaction. PMID:22985247

Nahar, Kamrun; Kyndt, Tina; Nzogela, Yasinta Beda; Gheysen, Godelieve

2012-11-01

372

Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions.  

PubMed

The plant stress hormone abscisic acid (ABA) is critical for several abiotic stress responses. ABA signaling is normally repressed by group-A protein phosphatases 2C (PP2Cs), but stress-induced ABA binds Arabidopsis PYR/PYL/RCAR (PYL) receptors, which then bind and inhibit PP2Cs. X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA's 3' ring CH that opens at the PP2C binding interface. Here, ABA analogs with sufficiently long 3' alkyl chains were predicted to traverse this tunnel and block PYL-PP2C interactions. To test this, a series of 3'-alkylsulfanyl ABAs were synthesized with different alkyl chain lengths. Physiological, biochemical and structural analyses revealed that a six-carbon alkyl substitution produced a potent ABA antagonist that was sufficiently active to block multiple stress-induced ABA responses in vivo. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class. PMID:24792952

Takeuchi, Jun; Okamoto, Masanori; Akiyama, Tomonori; Muto, Takuya; Yajima, Shunsuke; Sue, Masayuki; Seo, Mitsunori; Kanno, Yuri; Kamo, Tsunashi; Endo, Akira; Nambara, Eiji; Hirai, Nobuhiro; Ohnishi, Toshiyuki; Cutler, Sean R; Todoroki, Yasushi

2014-06-01

373

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors.  

PubMed

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 > LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions. PMID:14500756

Ohta, Hideo; Sato, Koichi; Murata, Naoya; Damirin, Alatangaole; Malchinkhuu, Enkhzol; Kon, Junko; Kimura, Takao; Tobo, Masayuki; Yamazaki, Yuji; Watanabe, Tomoko; Yagi, Mikio; Sato, Motoko; Suzuki, Rika; Murooka, Hideko; Sakai, Teruyuki; Nishitoba, Tsuyoshi; Im, Dong-Soon; Nochi, Hiromi; Tamoto, Koichi; Tomura, Hideaki; Okajima, Fumikazu

2003-10-01

374

Effects of quisqualate, N-methyl-D-aspartate, and some amino acid antagonists on synaptic transmission in ampullae of Lorenzini  

Microsoft Academic Search

The effects of quisqualic acid (QA), N-methyl-D-aspartate (NMDA), and a number of NMDA and non-NMDA receptor antagonists on background and induced activity in afferent nerve fibers were investigated in skates by means of bath application to the basal membrane of electroreceptors (ampullae of Lorenzini). Perfusion with physiological saline containing QA or NMDA (minimum concentrations required: 10-8 and 10-5 M respectively)

G. N. Akoev; Yu. N. Andrianov; B. Bromm; T. Szabo; N. O. Sherman

1989-01-01

375

Blockade of the discriminative stimulus effects of ?-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS382  

Microsoft Academic Search

The present study was designed to assess the ability of the newly synthetized, selective ?-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700

Giancarlo Colombo; Roberta Agabio; Jacques Bourguignon; Fabio Fadda; Carla Lobina; Michel Maitre; Roberta Reali; Martine Schmitt; Gian Luigi Gessa

1995-01-01

376

Synthesis and structure-activity relationships of amino acid conjugates of cholanic acid as antagonists of the EphA2 receptor.  

PubMed

The Eph-ephrin system plays a critical role in tumor growth and vascular functions during carcinogenesis. We had previously identified cholanic acid as a competitive and reversible EphA2 antagonist able to disrupt EphA2-ephrinA1 interaction and to inhibit EphA2 activation in prostate